digoxin and Heart-Failure

Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions.. To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject.. The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II-IV and at highest risk for hospitalization.. As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.

Topics: Atrial Fibrillation; Digitalis; Digoxin; Heart Failure; Humans; Randomized Controlled Trials as Topic

The study evaluates the characteristics and trends of digoxin use during outpatient visits with atrial fibrillation in the US from 2006 to 2015.We conducted a retrospective analysis of adult (age >/= 18) patient visits to office-based physicians from National Ambulatory Medical Care Survey (NAMCS) database between 2006-2015. The International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with Atrial fibrillation. Visits in which digoxin was listed as medication were analyzed with descriptive statistics. Multivariable logistic regression analysis was used to identify the predictors of usage of digoxin. Of a weighted sample of 108,113,894 patient visits, 17,617,853 (16.3%) visits included use of digoxin. Patients who used digoxin had a mean age of 75 ± 0.7 years and were predominantly Caucasian (92.56%). Among the patients who used digoxin, 24% had a diagnosis of heart failure. Multivariate analysis showed that the increased likelihood of digoxin utilization was associated with female sex (adjusted odds ratio (AOR) 1.34, 95% CI 1.05-1.71, p = .019), heart failure (aOR 1.51, 95% CI 1.05-1.17, p = .025), and usage of ³5 medications (aOR 5.32, 95% CI 3.67-7.71, p = <0.001). Among the visits with Atrial fibrillation, the percentage of visits with digoxin usage decreased from 23% in 2006 to 9% in 2013 and then again increased to 14% in 2015(P-trend <0.001). This is the first study to examine the use of digoxin in atrial fibrillation patients in a big outpatient setting. During 2006-2015, the percentage of digoxin prescriptions in atrial fibrillation patients has declined. Predictors of digoxin use in atrial fibrillation patients are female sex, congestive heart failure and higher number of concurrent medications.

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Female; Health Care Surveys; Heart Failure; Humans; Male; Retrospective Studies

One of the major indications for digoxin use is the treatment of heart failure (HF). Although the clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction (HFrEF) patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction (HFpEF) is not very clear.. The aim of this study was to show the clinical efficacy of digoxin on long-term outcomes in subjects with HFpEF.. PubMed, Embase, Scopus and Web of Science (ISI) electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".. Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treatment with digoxin was associated with a neutral effect on all-cause mortality (HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %), all-cause hospitalization (HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %), HFhospitalization (HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %), and all-cause mortality or HFhospitalization (HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %). In subgroup meta-analyses based on ejection fraction (EF), treatment with digoxin did not significantly alter these outcomes in each subset of patients.. The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including "all-cause mortality", "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Hospitalization; Humans; Prognosis; Stroke Volume; Treatment Outcome

To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial fibrillation (AF) with or without heart failure (HF).. We systematically searched MEDLINE, Embase, and Web of Science databases from inception to 19 October 2021. We included systematic reviews and meta-analyses of observational studies investigating digoxin effects on mortality of adult patients with AF and/or HF. The primary outcome was all-cause mortality; secondary outcome was cardiovascular mortality. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool and the quality of systematic reviews/meta-analyses by the A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) tool.. Eleven studies accounting for 12 meta-analyses were included with a total of 4,586,515 patients. AMSTAR2 analysis showed a high quality in 1, moderate in 5, low in 2, and critically low in 3 studies. Digoxin was associated with an increased all-cause mortality (hazard ratio [HR] 1.19, 95% confidence interval [95%CI] 1.14-1.25) with moderate certainty of evidence and with an increased cardiovascular mortality (HR 1.19, 95%CI 1.06-1.33) with moderate certainty of evidence. Subgroup analysis showed that digoxin was associated with all-cause mortality both in patients with AF alone (HR 1.23, 95%CI 1.19-1.28) and in those with AF and HF (HR 1.14, 95%CI 1.12-1.16).. Data from this umbrella review suggests that digoxin use is associated with a moderate increased risk of all-cause and cardiovascular mortality in AF patients regardless of the presence of HF.. This review was registered in PROSPERO (CRD42022325321).

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans; Systematic Reviews as Topic

Joint modelling combines two or more statistical models to reduce bias and increase efficiency. As the use of joint modelling increases it is important to understand how and why it is being applied to heart failure research.. A systematic review of major medical databases of studies which used joint modelling within heart failure alongside an exemplar; joint modelling repeat measurements of serum digoxin with all-cause mortality using data from the Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure (DIG) trial.. Overall, 28 studies were included that used joint models, 25 (89%) used data from cohort studies, the remaining 3 (11%) using data from clinical trials. 21 (75%) of the studies used biomarkers and the remaining studies used imaging parameters and functional parameters. The exemplar findings show that a per unit increase of square root serum digoxin is associated with the hazard of all-cause mortality increasing by 1.77 (1.34-2.33) times when adjusting for clinically relevant covariates.. Recently, there has been a rise in publications of joint modelling being applied to heart failure. Where appropriate, joint models should be preferred over traditional models allowing for the inclusion of repeated measures while accounting for the biological nature of biomarkers and measurement error.

Topics: Cardiotonic Agents; Cohort Studies; Digoxin; Heart Failure; Humans; Models, Statistical; Research Design

Heart failure (HF) is a common cause of morbimortality with different etiopathogenesis and prognosis between men and women. This review provides a brief overview of gender-based differences in response to pharmacological therapies of heart failure with or without reduced ejection fraction (EF). It focuses on the differences in therapy outcomes with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), angiotensin neprilysin inhibitors (ARNI), beta-adrenergic blockers, mineralocorticoid/ aldosterone receptor antagonists, diuretics, ivabradine and digoxin. The baseline data originate from randomised controlled trials (RCTs) and large registries. We conclude that current guidelines recommending similar therapeutic approaches for both men and women are appropriate, while additional consideration should be given to different approaches regarding the use of ARBs, ACEi, and digoxin. Based on the available data, the ARBs might be considered a first-line therapy of HR for women instead of ACEi. Moreover, female patients should have stricter digoxin monitoring due to higher sensitivity and increased risk of complications. Finally, women are underrepresented in current clinical trials, and therefore future trials should aim to balance the gender recruitment disparity allowing sub-group analysis and comparisons between genders to guide individualised therapeutic strategies and appropriately targeted preventative steps.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Sex Characteristics; Stroke Volume

Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19 pandemic, socioeconomic deprivation, social isolation, and reduced physical activities may induce heart failure (HF), destabilization, and cause more complications. HF appears as a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with underlying comorbidities. In reality, the expression of cardiac ACE2 is implicated as a target point for SARS-CoV-2-induced acute cardiac injury. In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF development. Hypoxic respiratory failure, as in pulmonary edema, severe acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) may affect heart hemodynamic stability due to the development of pulmonary hypertension. Indeed, Covid-19-induced HF could be through the development of cytokine storm, characterized by high proliferation pro-inflammatory cytokines. In cytokine storm-mediated cardiac dysfunction, there is a positive correlation between levels of pro-inflammatory cytokine and myocarditis-induced acute cardiac injury biomarkers. Therefore, Covid-19-induced HF is more complex and related from a molecular background in releasing pro-inflammatory cytokines to the neuro-metabolic derangements that together affect cardiomyocyte functions and development of HF. Anti-heart failure medications, mainly digoxin and carvedilol, have potent anti-SARS-CoV-2 and anti-inflammatory properties that may mitigate Covid-19 severity and development of HF. In conclusion, SARS-CoV-2 infection may lead to the development of HF due to direct acute cardiac injury or through the development of cytokine storms, which depress cardiomyocyte function and cardiac contractility. Anti-heart failure drugs, mainly digoxin and carvedilol, may attenuate severity of HF by reducing the infectivity of SARS-CoV-2 and prevent the development of cytokine storms in severely affected Covid-19 patients.

Topics: Adrenergic alpha-1 Receptor Antagonists; Anti-Arrhythmia Agents; Anti-Inflammatory Agents; Cardiotonic Agents; Carvedilol; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Digoxin; Heart Failure; Humans; SARS-CoV-2

Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for a long time, been used in heart medicine. Moreover, it has been known for decades that CGs also have great potential in cancer treatment and, thus, many clinical trials now evaluate their anticancer potential. Interestingly, heart failure and cancer are not the only conditions for which CGs could be effectively used. In recent years, the antiviral potential of CGs has been extensively studied, and with the ongoing SARS-CoV-2 pandemic, this interest in CGs has increased even more. Therefore, here, we present CGs as potent and promising antiviral compounds, which can interfere with almost any steps of the viral life cycle, except for the viral attachment to a host cell. In this review article, we summarize the reported data on this hot topic and discuss the mechanisms of antiviral action of CGs, with reference to the particular viral life cycle phase they interfere with.

Topics: Antiviral Agents; Cardiac Glycosides; COVID-19; Digitoxin; Digoxin; Drug Repositioning; Heart Failure; Humans; Neoplasms; Ouabain; Pandemics; SARS-CoV-2; Sodium-Potassium-Exchanging ATPase; Virus Internalization; Virus Replication

Since 1953, sinus tachycardia has been defined as a heart rate (HR) in sinus rhythm of >100 beats per minute (bpm). However, this number has never been formally evaluated, and no established threshold values for special groups, such as those with heart failure (HF) accompanied by a reduced ejection fraction (HFrEF). Herein, we provided evidence that lowering the HR of patients with HFrEF to <70 bpm with medications such as ivabradine improves outcomes. Numerous large-scale trials and smaller clinical studies have shown that reducing the HR in patients with HFrEF improves cardiovascular and overall outcomes. Evidence suggests that a HR of <70 bpm is appropriate for patients with HFrEF. Examination of HF registries indicates that in a large proportion of these patients the HR exceeds 80 bpm, and no consideration is given to lowering the HR, due in large part to lack of physician awareness of the benefits of a lower HR. Evidence indicates that the first-line medication for lowering HR in patients with HFrEF is ivabradine. In conclusion, the improved prognosis following appropriate HR management in patients with HFrEF suggest that the cut-off value for sinus tachycardia in these patients should be redefined as 75 bpm. Maintaining a HR of <70 bpm in patients with HFrEF is associated with improved cardiovascular and overall outcomes.

Topics: Cardiovascular Agents; Digoxin; Heart Failure; Heart Rate; Humans; Ivabradine; Stroke Volume; Tachycardia

Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digitalis; Digoxin; Exosomes; Heart Failure; Humans; Plant Extracts; Wnt Signaling Pathway

This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in paediatrics and to identify the sources of variability in its disposition. PubMed, ISI Web of Science, SCOPUS and Science Direct databases were searched from inception to January 2019. All paediatric population pharmacokinetic studies of digoxin that utilized the nonlinear mixed-effect modelling approach were incorporated in this review, and data were synthesized descriptively. After application of the inclusion-exclusion criteria 8 studies were included. Most studies described digoxin pharmacokinetics as a 1-compartment model with only 1 study describing its pharmacokinetics as 2-compartments. Age was an important predictor of clearance in studies involving neonates or infants, other predictors of clearance were weight, height, serum creatinine, coadministration of spironolactone and presence of congestive heart failure. Congestive heart failure was also associated with an increased volume of distribution in 1 study. The estimated value of apparent clearance in a typical individual standardized by mean weight ranged between 0.24 and 0.56 L/h/kg, the interindividual variability in clearance ranged between 7.0 and 35.1%. Half of the studies evaluated the performance of their developed models via external evaluation. In conclusion, substantial predictors of digoxin pharmacokinetics in the paediatric population in addition to model characteristics and evaluation techniques are presented. For clinicians, clearance could be predicted using age especially in neonates or infants, weight, height, serum creatinine, coadministration of medications and disease status. For future researchers, designing pharmacokinetic studies that allow 2-compartment modelling and linking pharmacokinetics with pharmacodynamics is recommended.

Topics: Child; Digoxin; Heart Failure; Humans; Infant; Infant, Newborn; Models, Biological; Nonlinear Dynamics; Pediatrics; Spironolactone

In 2015, 3 independent meta-analyses raised concerns about digoxin therapy being associated with an increased mortality risk in patients with atrial fibrillation (AF) and with heart failure (HF). Although several other studies have been published since then fostering these safety issues, the most recent 2016 European guidelines for AF still recommend this therapy as a class I indication. We performed an updated systematic review and random-effect meta-analysis on publications up to March 2018 reporting data on digoxin associated mortality in subjects with AF or HF. Based on the adjusted survival data of all identified 37 trials comprising a total of 825,061 patients, digoxin use was associated with an increased relative risk of all-cause mortality (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05 to 1.29, p <0.01). Treatment with digoxin was associated with an increased mortality risk in the subgroup of patients with AF (n = 627,620, HR 1.23, 95% CI, 1.17 to 1.30, p <0.01), and in the subgroup of patients with HF (n = 197,441, HR 1.11, 95% CI, 1.06 to 1.16, p<0.01). A sensitivity analysis of studies reporting data on new digoxin users (n = 41,687) demonstrated an even higher risk for all-cause mortality compared with patients not receiving cardiac glycosides (HR 1.47, 95% CI, 1.15 to 1.88, p <0.01). In conclusion, this updated meta-analysis confirms that digoxin use is associated with increased mortality in patients with AF or HF.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans; Survival Analysis

This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.. Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs.. A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF.. The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine.. These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Ivabradine; Male; Mineralocorticoid Receptor Antagonists; Mortality; Practice Guidelines as Topic; Research Design; Research Report; Sex Distribution; Sex Factors; Stroke Volume

Takotsubo cardiomyopathy (TC) is characterized by transient wall motion abnormalities most commonly involving the left ventricle (LV). Although biventricular TC had been considered uncommon condition, recently biventricular TC has been reported as a new variant observed in 19-42% of all TC presentations. Since biventricular TC has a poor prognosis as compared with isolated TC, it is important to distinguish between isolated LV TC and biventricular TC. We present a case of 70-year-old female with dyspnea persisting for 2 days. Electrocardiogram showed symmetrical T-wave inversion in leads V2-V4. Transthoracic echocardiography (TTE) revealed diffuse hypo-kinesis except for the apical inferior LV and LV ejection fraction of 32%. Hyper-kinesis of the right ventricular (RV) basal segment and dys-kinesis of the RV apical segment. 2 weeks after admission, coronary angiography showed no evidence of significant stenosis. LV ejection fraction improved to 51% and wall motion abnormalities of the RV basal and apical segments were ameliorated to normo-kinesis. Electrocardiogram revealed symmetrical and deepened T-wave inversion in leads V2-V3. The presence of a transient abnormality in biventricular wall motion beyond a single coronary artery perfusion territory with new electrocardiographic change met the diagnostic criteria of definite TC defined by Mayo Clinic criteria. 4 weeks after admission, no recurrence of wall motion abnormalities in both ventricles were found and T-wave inversion ameliorated. To our knowledge, this is the first report of biventricular TC with asymmetrical abnormities of wall motion between LV and RV.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Angiography; Digoxin; Diuretics; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Tachycardia; Takotsubo Cardiomyopathy; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Heart failure (HF) and atrial fibrillation (AF) often coexist. Subjects with permanent AF show the highest prevalence of HF. Patients with incident AF have HF in a great number of cases and, reciprocally, in patients with incident HF, an AF can be frequently found. The simultaneous presence of the two conditions is associated with mortality rates higher than those observed in individuals with only one or none of them. Interestingly, HF and AF could synergistically promote in elderly patients the development of disability and dementia. Inflammatory mechanisms coupled with changes of renin-angiotensin system, hormonal pathways and neuro-mediators could simultaneously promote left atrium remodeling and sustain both HF and AF. Beta-blockers and digoxin seem to have small therapeutic effect and limited influence on prognosis in these very complex patients. Sinus rhythm restoration could slow down the progression of disability in symptomatic subjects. Recent evidence seem to suggest that upstream therapy coupled with rehabilitation, and that AV node ablation associated with cardiac resynchronization therapy could benefit subjects with HF and AF. In conclusion, elderly patients simultaneously presenting problems of cardiac function and arrhythmia are an important challenge for geriatric medicine, and request important efforts to improve their functional profile and prognosis.

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Cardiac Rehabilitation; Cardiac Resynchronization Therapy; Digoxin; Heart Failure; Humans; Prognosis

The Digitalis Investigation Group (DIG) trial, the only large randomized trial of digoxin in heart failure, reported a neutral effect on mortality and a significant reduction in heart failure hospitalizations. Recent observational studies reported increased mortality with digoxin treatment. We present further analyses of the DIG trial displaying the inability to control bias in observational treatment comparisons despite extensive statistical adjustments.. Forty-four percent of the 6800 patients in the DIG trial had been treated with digoxin before randomization, and half of them were randomly withdrawn from digoxin treatment. We contrast the main randomization-based result of the DIG trial with the observational non-randomized comparison of patients pre-treated or not pre-treated with digoxin. Mortality [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.12-1.34; P < 0.001] and heart failure hospitalizations (HR 1.47, 95% CI 1.33-1.61; P < 0.001) were significantly higher in patients pre-treated with digoxin even after adjustment for baseline population differences. The higher risks for both outcomes in those who had previously received digoxin persisted even if they received placebo during the trial (HR 1.24, 95% CI 1.10-1.40; P < 0.001). This sharply contradicts the neutral effect on mortality and the significant reduction in heart failure hospitalizations observed in the randomized comparison.. Prescription of digoxin is an indicator of disease severity and worse prognosis, which cannot be fully accounted for by covariate adjustments in the DIG trial where patients were well-characterized. It is unlikely that weaker research approaches (observational studies of administrative data or registries) can provide more reliable estimates of the effects of cardiac glycosides.

Topics: Bias; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic

Efficacy and safety of dronedarone was shown in the ATHENA trial for paroxysmal or persistent atrial fibrillation (AF) patients. Further trials revealed safety concerns in patients with heart failure and permanent AF. This review summarizes insights from recent real-world studies and meta-analyses, including reports on efficacy, with focus on liver safety, mortality risk in patients with paroxysmal/persistent AF, and interactions of dronedarone with direct oral anticoagulants. Reports of rapidly progressing liver failure in dronedarone-prescribed patients in 2011 led to regulatory cautions about potential liver toxicity. Recent real-world evidence suggests dronedarone liver safety profile is similar to other antiarrhythmics and liver toxicity could be equally common with many Class III antiarrhythmics. Dronedarone safety concerns (increased mortality in patients with permanent AF) were raised based on randomized controlled trials (RCT) (ANDROMEDA and PALLAS), but comedication with digoxin may have increased the mortality rates in PALLAS, considering the dronedarone-digoxin pharmacokinetic (PK) interaction. Real-world data on apixaban-dronedarone interactions and edoxaban RCT observations suggest no significant safety risks for these drug combinations. Median trough plasma concentrations of dabigatran 110 mg during concomitant use with dronedarone are at acceptable levels, while PK data on the rivaroxaban-dronedarone interaction are unavailable. In RCTs and real-world studies, dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF. The concerns on liver safety must be balanced against the significant reduction in hospitalizations in patients with non-permanent AF and low risk for proarrhythmias following dronedarone treatment.

Topics: Anti-Arrhythmia Agents; Antithrombins; Atrial Fibrillation; Chemical and Drug Induced Liver Injury; Dabigatran; Digoxin; Dronedarone; Drug Interactions; Factor Xa Inhibitors; Heart Failure; Hospitalization; Humans; Mortality; Pyridines; Randomized Controlled Trials as Topic; Thiazoles

Atrial fibrillation and heart failure are commonly encountered in current clinical practice. This review aims to revisit the complex interaction of these two common situations and the best treatment whenever both occurs, especially focusing on heart failure patients undergoing cardiac resynchronization therapy (CRT).. It has been recently confirmed that in patients undergoing cardiac resynchronization therapy, 100% biventricular pacing percentage should be pursued. Large observational studies confirmed that atrioventricular junction ablation is very often the only way to gain 100% biventricular pacing in atrial fibrillation.. On the basis of the recent observational extensive data, in patients presenting intermediate or elevated atrial tachycardia-atrial fibrillation burden, atrioventricular junction ablation may represent a fundamental tool to achieve full CRT delivery, thus, conferring marked improvements in global cardiac function, and by extension, in survival. Atrial fibrillation patients should not be excluded from CRT, provided that maximal biventricular pacing is warranted.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrioventricular Node; Cardiac Resynchronization Therapy; Catheter Ablation; Digoxin; Heart Failure; Humans; Treatment Outcome

During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials.. We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence.. 28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%).. The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed.. PROSPERO CRD42016052935.

Topics: Aged; Amiodarone; Atrial Fibrillation; Atrial Flutter; Bias; Calcium Channel Blockers; Comorbidity; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Mortality; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Stroke; Treatment Outcome

Heart failure affects more than 6 million people in the United States and incurs a heavy toll in morbidity, mortality, and health care costs. It frequently coexists with other important disorders, including hypertension, coronary artery disease, diabetes, and obesity. Decades of clinical trials have shown that several medications and interventions are effective for improving outcomes; however, mortality and hospitalization rates remain high. More recently, additional medications and devices have shown promise in reducing the health burden of heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiac Rehabilitation; Cardiovascular Agents; Coronary Artery Disease; Defibrillators, Implantable; Diabetes Complications; Diagnostic Techniques, Cardiovascular; Digoxin; Diuretics; Heart Failure; Hospitalization; Humans; Hydralazine; Hypertension; Isosorbide Dinitrate; Ivabradine; Life Style; Mineralocorticoid Receptor Antagonists; Palliative Care; Primary Prevention; Referral and Consultation; Risk Factors

A number of recent observational analyses have assessed clinical outcomes associated with digoxin use in patients with atrial fibrillation. In this review, we review these data and provide suggestions on the contemporary use of digoxin in patients with atrial fibrillation as supported by the recent evidence.. Observational data from clinical trials and registries have provided variable results on the safety and efficacy of chronic digoxin use in patients with atrial fibrillation. In general, results have been consistent with an associated increase in adverse clinical outcomes with digoxin use in atrial fibrillation patients without heart failure. In atrial fibrillation patients with heart failure, while the weight of evidence suggested an associated risk with digoxin therapy, the results are inconsistent. In patients with atrial fibrillation without heart failure, digoxin should generally be avoided. In atrial fibrillation patients with heart failure, digoxin should generally be reserved for patients that do not achieve adequate rate control or are not tolerant of other rate control therapies.

Topics: Atrial Fibrillation; Digoxin; Heart Failure; Humans; Treatment Outcome

Atrial fibrillation is the most common arrhythmia of the heart with a prevalence of approximately 2% in the western world. Atrial flutter, another arrhythmia, occurs less often with an incidence of approximately 200,000 new patients per year in the USA. Patients with atrial fibrillation and atrial flutter have an increased risk of death and morbidities. In the management of atrial fibrillation and atrial flutter, it is often necessary to use medical interventions to lower the heart rate. Lowering the heart rate may theoretically prevent the development of heart failure and tachycardia-mediated cardiomyopathy. The evidence on the benefits and harms of digoxin compared with placebo or with other medical interventions is unclear. This protocol for a systematic review aims at identifying the beneficial and harmful effects of digoxin compared with placebo, no intervention, or with other medical interventions for atrial fibrillation and atrial flutter.. This protocol for a systematic review was conducted following the recommendations of Cochrane and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials comparing digoxin with placebo, no intervention, or with other medical interventions. We plan to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded on Web of Science, and BIOSIS to identify relevant trials. Any eligible trial will be assessed and classified as either at high risk of bias or low risk of bias, and our primary conclusions will be based on trials with low risk of bias. We will perform our meta-analyses of the extracted data using Review Manager 5.3 and Trial Sequential Analysis ver. 0.9.5.5 beta. For both our primary and secondary outcomes, we will create a 'Summary of Findings' table based on GRADE assessments of the quality of the evidence.. The results of this systematic review have the potential to benefit millions of patients worldwide as well as healthcare economy.. PROSPERO CRD42016052935.

Topics: Atrial Fibrillation; Atrial Flutter; Digoxin; Heart Failure; Humans; Placebos; Systematic Reviews as Topic

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Mortality

Since its isolation in the 1930s, digoxin has played a pivotal role in the treatment of cardiac conditions including heart failure and supraventricular tachyarrhythmias. The parasympathomimetic activity makes digoxin a reasonable option for controlling ventricular rate in atrial fibrillation (AF). However, the unique pharmacokinetic properties, electrolyte-dependent effects, and P-glycoprotein drug interactions influence the clinical use of digoxin. In addition, the delayed onset and narrow therapeutic index can make digoxin utilization cumbersome and often necessitates serum drug monitoring. Despite digoxin's extensive history, recent literature has cast doubt on the efficacy and safety of this medication in the population with AF. Large amounts of data suggest digoxin offers no benefit on mortality and may increase the risk of mortality though this was not consistent in all evaluations. While robust, the majority of the available studies are not randomized which limits the ability to draw firm conclusions. The potential risk of mortality must be weighed against the expected benefits of digoxin use to make individualized patient care decisions. Clinicians should refrain from utilizing digoxin monotherapy for rate control in AF when other options are viable.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans

The focus of this review is on cardiac and non-cardiac effects of digoxin, a drug used for treating the heart failure, and on link between these effects and the serum digoxin concentration (SDC) in different dosing regimens. Elderly patients are at the spotlight, as they are both at high risk and high potential benefit from digoxin therapy, explaining potential usefulness from SDC monitoring in this cohort of patients. The laboratory and clinical approaches used to prevent digitalis intoxication are reviewed, with regard to their fidelity, clinical value, and practical usefulness. The role of endogenous cardiotonic steroids, sharing structural and functional similarity to digoxin and affecting the diagnostic value of laboratory tests, is also discussed.. В обзорной статье рассмотрены основные сердечные и внесердечные эффекты дигоксина — препарата, используемого для лечения сердечной недостаточности. Оценивается их связь с сывороточной концентрацией вещества в рамках постоянного приема или насыщения препаратом, с акцентом на пожилых пациентов, у которых ввиду высокого риска и потенциальной пользы полезным представляется мониторинг сывороточной концентрации дигоксина. Рассмотрены основные подходы по лабораторному мониторингу дигоксина и клинические факторы риска передозировки сердечными гликозидами; дается оценка их точности, клинического значения и возможности применения в рутинной практике. Внимание уделено эндогенным кардиотоническим стероидам — веществам, структурно и функционально сходным с сердечными гликозидами и могущим влиять на точность лабораторной диагностики.

Topics: Aged; Cardiotonic Agents; Digoxin; Drug Monitoring; Heart Failure; Humans; Pharmacovigilance

Digoxin is one of the oldest compounds used in cardiovascular medicine. Nevertheless, its mechanism of action and most importantly its clinical utility have been the subject of an endless dispute. Positive inotropic and neurohormonal modulation properties are attributed to digoxin, and it was the mainstay of heart failure therapeutics for decades. However, since the institution of β-blockers and aldosterone antagonists as part of modern heart failure medical therapy, digoxin prescription rates have been in free fall. The fact that digoxin is still listed as a valid therapeutic option in both American and European heart failure guidelines has not altered clinicians' attitude towards the drug. Since the publication of original Digitalis Investigation Group trial data, a series of reports based predominately on observational studies and post hoc analyses have raised concerns about the clinical efficacy and long-term safety of digoxin. In the present review, we will attempt a critical appraisal of the available clinical evidence regarding the efficacy and safety of digoxin in heart failure patients with a reduced ejection fraction. The methodological issues, strengths, and limitations of individual studies will be highlighted.

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Stroke Volume

Heart failure with reduced ejection fraction (HFrEF) is a common cardiovascular condition with a significant individual and societal burden. Although it was previously known as a palliative condition, medical drug therapies that were developed in the last four decades significantly reduced morbidity and mortality of the disease. The cornerstone of HFrEF therapy remains the blockade of the renin-angiotensin-aldosterone and the β-adrenergic systems. This review aims to give an overview and update on established disease-modifying therapies in HFrEF, discuss advances and setbacks in the treatment of selected comorbidities and provide an outlook on upcoming therapies including the new concept of dual angiotensin receptor and neprilysin inhibition.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Diuretics; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Ivabradine; Mineralocorticoid Receptor Antagonists; Neprilysin; Stroke Volume; Vasodilator Agents

Outpatient management of heart failure (HF) is aimed at treating symptoms and preventing hospitalizations and readmissions. Management is initiated in a stepwise approach. Blockade of the renin-angiotensin system is a cornerstone of therapy and should be started, along with beta blockers, as soon as the diagnosis of HF is made. Other drugs, including diuretics, aldosterone antagonists, hydralazine, and nitrates, may be added based on symptoms and American College of Cardiology/American Heart Association stage. Despite a great interest in and theoretical benefit of naturoceutical products in the mitigation of oxidative stress and HF progression, none has been proven to be beneficial, and concerns exist regarding their interactions with standard HF drugs. Other nonpharmacologic interventions, including sodium restriction, regular exercise, and/or cardiac rehabilitation, should be initiated at diagnosis. HF often is progressive, and clinicians should be aware of late stage management options, including implantable devices, cardiac transplantation, and hospice care.

Topics: Adrenergic beta-Antagonists; Aged; Ambulatory Care; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Biphenyl Compounds; Cardiac Resynchronization Therapy; Cardiotonic Agents; Cardiovascular Agents; Diet, Sodium-Restricted; Digoxin; Diuretics; Drug Combinations; Exercise Therapy; Fatty Acids, Omega-3; Female; Heart Failure; Heart Transplantation; Hospice Care; Humans; Ivabradine; Mineralocorticoid Receptor Antagonists; Tetrazoles; Valsartan; Vasodilator Agents

After 230 years of use, digitalis remains an important and useful therapy for patients with atrial fibrillation, heart failure, and the 30-50 % of patients with both conditions. Although the combination of positive inotropic activity with negative chronotropic effects has been shown to reduce hospital admissions in heart failure, there is a distinct lack of robust trial data, particularly in patients with atrial fibrillation. We recently performed a comprehensive meta-analysis of all digoxin studies and demonstrated a neutral effect on mortality. This contradicts prior observational data that overlook the fact that digitalis is usually given as second-line therapy to the sickest patients. Use of these agents in clinical practice should take account of appropriate dose, serum concentration, drug interactions, and potential side effects. The aim of this review is to evaluate the evidence base for cardiac glycosides and provide a pragmatic guide to their advantages and disadvantages.

Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Conduction System; Heart Failure; Heart Rate; Heart Ventricles; Humans; Myocardial Contraction; Patient Admission; Patient Selection; Risk Factors; Treatment Outcome

There has been an increased focus on heart rate as a target in the management of cardiovascular disease and more specifically in heart failure with preserved ejection fraction in recent years with several studies showing the benefit of a lower resting heart rate on outcomes. This review paper examines the pathophysiology behind the benefits of lowering heart rate in heart failure and also the evidence for and against the pharmacological agents available to achieve this.

Topics: Adrenergic Antagonists; Amiodarone; Benzazepines; Depression, Chemical; Digoxin; Evidence-Based Medicine; Heart Failure; Heart Rate; Humans; Ivabradine

Control of the heart rate (rate control) is central to atrial fibrillation management, even for patients who ultimately require control of the rhythm. We review heart rate control in patients with atrial fibrillation, including the rationale for the intervention, patient selection, and the treatments available. The choice of rate control depends on the symptoms and clinical characteristics of the patient, but for all patients with atrial fibrillation, rate control is part of the management. Choice of drugs is patient-dependent. β blockers, alone or in combination with digoxin, or non-dihydropyridine calcium-channel blockers (not in heart failure) effectively lower the heart rate. Digoxin is least effective, but a reasonable choice for physically inactive patients aged 80 years or older, in whom other treatments are ineffective or are contraindicated, and as an additional drug to other rate-controlling drugs, especially in heart failure when instituted cautiously. Atrioventricular node ablation with pacemaker insertion for rate control should be used as an approach of last resort but is also an option early in the management of patients with atrial fibrillation treated with cardiac resynchronisation therapy. However, catheter ablation of atrial fibrillation should be considered before atrioventricular node ablation. Although rate control is a top priority and one of the first management issues for all patients with atrial fibrillation, many issues remain.

Topics: Adrenergic beta-Antagonists; Age Factors; Amiodarone; Anti-Arrhythmia Agents; Atenolol; Atrial Fibrillation; Atrioventricular Node; Bradycardia; Calcium Channel Blockers; Cardiac Resynchronization Therapy; Catheter Ablation; Digoxin; Drug Therapy, Combination; Heart Failure; Heart Rate; Humans; Pacemaker, Artificial; Patient-Centered Care; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Sotalol

An estimated 5.1 million Americans have chronic heart failure and this is expected to increase 25% by 2030. Heart failure is a clinical syndrome that evolves from either functional or structural changes to the ventricles that lead to filling or ejection abnormalities. Thus far, pharmacotherapy has been show to be beneficial in patients only with reduced ejection fraction; however, new therapies have been developed in hopes of reducing the burden of heart failure. In this review, we will discuss current pharmacotherapies recommended in American College of Cardiology/American Heart Association guidelines, the evidence behind these recommendations as well as new and emerging therapies that have been developed.

Topics: Adrenergic beta-Antagonists; American Heart Association; Amides; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Antihypertensive Agents; Atrial Natriuretic Factor; Benzazepines; Biphenyl Compounds; Calcium Channel Blockers; Cardiology; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Diuretics; Drug Combinations; Erythropoietin; Evidence-Based Medicine; Fumarates; Heart Failure; Hematinics; Humans; Hydralazine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Iron; Isosorbide Dinitrate; Ivabradine; Mineralocorticoid Receptor Antagonists; Peptide Fragments; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Societies, Medical; Stroke Volume; Tetrazoles; United States; Valsartan; Vasodilator Agents

Heart failure management is complex and constantly evolving. The American College of Cardiology and the American Heart Association (ACC/AHA) last issued evidence-based guidelines in 2013, and since then, new drugs and devices have been developed. This review presents an evidence-based approach to current heart failure management.

Topics: Adrenergic beta-Antagonists; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiac Resynchronization Therapy Devices; Defibrillators, Implantable; Digoxin; Diuretics; Drug Combinations; Evidence-Based Medicine; Exercise; Heart Failure; Heart-Assist Devices; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Systole; Tetrazoles; Valsartan

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Follow-Up Studies; Heart Failure; Humans; Male; Risk Assessment; Severity of Illness Index; Survival Analysis; Treatment Outcome

Digoxin is the oldest known treatment for heart failure (HF) and has been demonstrated to reduce admissions for worsening heart failure in a large randomized trial recruiting patients in sinus rhythm with heart failure and ejection fraction <45%. This study forms the basis for current international guidelines recommending that digoxin should be considered in patients with symptomatic HF despite optimal doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists in addition to device therapy, if indicated. However, digoxin predates mortality reducing HF therapies, and this article reviews the historical and recent data.. Multiple PubMed searches were performed including, but not limited to, the search terms "digoxin," "heart failure," "efficacy," "treatment," "side-effects," "morbidity," "mortality," and "arrythmia." Articles were excluded if not relevant, not in English or without abstract. Reference lists of relevant articles were manually searched for further references. Due to the large number of articles retrieved, a selection was reviewed based on the authors' best judgement.. Three randomized controlled trials and three large contemporary observational reports of digoxin therapy in heart failure and sinus rhythm were retrieved. Other studies were noted that included patients with heart failure and atrial fibrillation, which were also reviewed.. Definitive randomized evidence of digoxin efficacy as add-on therapy in HF is lacking because most landmark trials of modern HF disease modifying agents postdate the randomized studies of digoxin. Furthermore, questions remain regarding the optimum dose of digoxin and there are signals that digoxin may be harmful in some patients with HF. All contemporary data for digoxin in HF are derived from observational studies and the findings are conflicting. Despite two centuries of experience using cardiac glycosides to treat HF, fundamental questions regarding the efficacy and safety of digoxin in HF remain unanswered.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Digitalis; Digoxin; Heart Failure; Humans; Risk Assessment; Risk Factors; Treatment Outcome

There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation (AF) or with congestive heart failure (CHF). The aim of this meta-analysis was to provide detailed analysis of the currently available study reports. We performed a MEDLINE and a COCHRANE search (1993-2014) of the English literature dealing with the effects of digoxin on all-cause-mortality in subjects with AF or CHF. Only full-sized articles published in peer-reviewed journals were considered for this meta-analysis. A total of 19 reports were identified. Nine reports dealt with AF patients, seven with patients suffering from CHF, and three with both clinical conditions. Based on the analysis of adjusted mortality results of all 19 studies comprising 326 426 patients, digoxin use was associated with an increased relative risk of all-cause mortality [Hazard ratio (HR) 1.21, 95% confidence interval (CI), 1.07 to 1.38, P < 0.01]. Compared with subjects not receiving glycosides, digoxin was associated with a 29% increased mortality risk (HR 1.29; 95% CI, 1.21 to 1.39) in the subgroup of publications comprising 235 047 AF patients. Among 91.379 heart failure patients, digoxin-associated mortality risk increased by 14% (HR 1.14, 95% CI, 1.06 to 1.22). The present systematic review and meta-analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Epidemiologic Methods; Heart Failure; Humans

Digoxin has been a key therapeutic for heart failure and atrial tachyarrhythmias for over 200 years following Withering's groundbreaking work depicting the therapeutic benefit of the common botanical foxglove in his 1785 monograph. The use of digoxin preceded any randomised evidence or even basic understanding of its mechanism of action. Over the past two decades, there has been mounting evidence further challenging the safety and efficacy of digoxin, while multiple other therapies for both heart failure and atrial tachyarrhythmias have proven to be more effective and safe. Altogether, digoxin still has an important role in contemporary pharmacotherapeutics, though its role remains controversial and should be reserved for selective patients and clinical situations, with careful attention to serum concentrations.

Topics: Cardiotonic Agents; Digoxin; Drug Interactions; Evidence-Based Medicine; Heart Failure; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Retrospective Studies; Tachycardia; Treatment Outcome

To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods.. Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design (. CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment).. Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias.. Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling.. 52 studies were systematically reviewed, comprising 621,845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4,006,210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29,525).. Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Hospitalization; Humans; Outcome Assessment, Health Care; Treatment Outcome

For decades, digoxin has been widely used to control ventricular rate in atrial fibrillation (AF). However, it remains controversial as to whether digoxin is associated with increased mortality in AF. In this study, we searched relevant studies that were published before December 1, 2014, in PubMed, EMBASE, and the Cochrane central databases. We systematically reviewed the references and performed a meta-analysis of 8 carefully selected studies with 302,738 patients who were included for the final analysis. It was shown that digoxin use was associated with increased risk of all-cause mortality in AF overall [hazard ratio (HR) = 1.375, 95% confidence intervals (CI), 1.201-1.574, P = 0.0001]. Subgroup analysis further revealed that digoxin was associated with increased all-cause mortality in patients with AF, which was complicated by heart failure (HF) (HR = 1.201, CI, 1.074- 1.344, P = 0.001), and in those subjects without HF (HR = 1.172, CI, 1.148-1.198, P = 0.0001). Sensitivity analyses found results to be robust. Our findings indicated that digoxin use was associated with significantly increased all-cause mortality in patients with AF regardless of concomitant HF. We suggest that digoxin should not be preferentially used over other rate control medications in AF.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Data Interpretation, Statistical; Databases, Factual; Digoxin; Heart Failure; Humans; Mortality

Foetal echocardiography has progressed to be able to diagnose many forms of CHD and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. This article outlines a straightforward method for the rapid evaluation of foetus that may have congestive heart failure with or without hydrops and for the differentiation of the pre-hydropic state from normal. The presence of signs of foetal heart failure, such as cardiomegaly or valvular regurgitation, gives clues to the aetiology of hydrops. The assessment of the prognosis of hydrops foetalis can be difficult but can be aided by the use of the cardiovascular profile score. Once identified, the neurohumoral effects of foetal heart failure can be ameliorated using transplacental digoxin if the hydrops has not progressed.

Topics: Cardiomegaly; Cardiotonic Agents; Digoxin; Echocardiography, Doppler, Color; Female; Fetal Heart; Heart Failure; Humans; Hydrops Fetalis; Pregnancy; Prognosis; Ultrasonography, Prenatal

Heart failure (HF) can rightfully be called the epidemic of the 21(st) century. Historically, the only available medical treatment options for HF have been diuretics and digoxin, but the capacity of these agents to alter outcomes has been brought into question by the scrutiny of modern clinical trials. In the past 4 decades, neurohormonal blockers have been introduced into clinical practice, leading to marked reductions in morbidity and mortality in chronic HF with reduced left ventricular ejection fraction (LVEF). Despite these major advances in pharmacotherapy, our understanding of the underlying disease mechanisms of HF from epidemiological, clinical, pathophysiological, molecular, and genetic standpoints remains incomplete. This knowledge gap is particularly evident with respect to acute decompensated HF and HF with normal (preserved) LVEF. For these clinical phenotypes, no drug has been shown to reduce long-term clinical event rates substantially. Ongoing developments in the pharmacotherapy of HF are likely to challenge our current best-practice algorithms. Novel agents for HF therapy include dual-acting neurohormonal modulators, contractility-enhancing agents, vasoactive and anti-inflammatory peptides, and myocardial protectants. These novel compounds have the potential to enhance our armamentarium of HF therapeutics.

Topics: Amides; Aminobutyrates; Atrial Natriuretic Factor; Biphenyl Compounds; Digoxin; Drug Combinations; Fumarates; Heart Failure; Humans; Natriuretic Peptides; Peptide Fragments; Snake Venoms; Tetrazoles; Valsartan

Heart failure remains a major health problem in the United States, affecting 5.8 million Americans. Its prevalence continues to rise due to the improved survival of patients. Despite advances in treatment, morbidity and mortality remain very high, with a median survival of about 5 years after the first clinical symptoms. This article describes the causes, classification, and management goals of heart failure in Stages A and B.

Topics: Adrenergic beta-Antagonists; Alcohol Drinking; Angiotensin-Converting Enzyme Inhibitors; Cardiac Pacing, Artificial; Cardiotonic Agents; Cardiotoxins; Coronary Artery Disease; Defibrillators, Implantable; Diabetic Cardiomyopathies; Digoxin; Dyslipidemias; Early Diagnosis; Endocrine System Diseases; Heart Failure; HIV Infections; Humans; Hypertension; Metabolic Syndrome; Mineralocorticoid Receptor Antagonists; Renal Insufficiency, Chronic; Risk Factors; Sedentary Behavior; Sleep Apnea Syndromes; Smoking; Tachycardia

Heart failure (HF) is a syndrome characterized by upregulation of the sympathetic nervous system and abnormal responsiveness of the parasympathetic nervous system. Studies in the 1980s and 1990s demonstrated that inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors improved symptoms and mortality in HF resulting from systolic dysfunction, thus providing a framework to consider the use of β-blockers for HF therapy, contrary to the prevailing wisdom of the time. Against this backdrop, this article reviews the contemporary understanding of the sympathetic nervous system and the failing heart.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Afferent Pathways; Angiotensin Receptor Antagonists; Autonomic Nervous System Diseases; Brain; Cardiac Imaging Techniques; Cardiotonic Agents; Digoxin; Efferent Pathways; Exercise Therapy; Exercise Tolerance; Forecasting; Heart Failure; Humans; Kidney Failure, Chronic; Muscle, Skeletal; Myocardial Infarction; Norepinephrine; Oxidative Stress; Polymorphism, Genetic; Receptors, Adrenergic; Receptors, Adrenergic, beta; Reflex; Renin-Angiotensin System; Sleep Apnea, Obstructive; Sympathetic Nervous System

ACC Stage C heart failure includes those patients with prior or current symptoms of heart failure in the context of an underlying structural heart problem who are primarily managed with medical therapy. Although there is guideline-based medical therapy for those with heart failure with reduced ejection fraction (HFrEF), therapies in heart failure with preserved ejection fraction (HFpEF) have thus far proven elusive. Emerging therapies such as serelaxin are currently under investigation and may prove beneficial. The role of advanced surgical therapies, such as mechanical circulatory support, in this population is not well defined. Further investigation is warranted for these therapies in patients with Stage C heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiotonic Agents; Coronary Artery Bypass; Defibrillators, Implantable; Diet, Sodium-Restricted; Digoxin; Diuretics; Exercise Therapy; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Mitral Valve Insufficiency; Obesity; Patient Compliance; Patient Education as Topic; Sleep Apnea, Obstructive; Vasodilator Agents

Heart failure is a costly and difficult disease to treat. However, new metrics make it an imperative to keep these patients out of the hospital. Implementing and maintaining patients on successful treatment plans is difficult. A multitude of factors make transitioning care to the outpatient setting difficult. A careful and well-orchestrated team of cardiologists, general practitioners, nurses, and ancillary support staff can make an important difference to patient care. A strong body of literature supports the use of pharmacologic therapy, and evidence-based therapies can improve mortality and quality of life, and reduce hospital admissions. Adjunctive therapies can be equally important.

Topics: Adaptation, Psychological; Adrenergic beta-Antagonists; Alcohol Drinking; Ambulatory Care; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiotonic Agents; Continuity of Patient Care; Defibrillators, Implantable; Deinstitutionalization; Diet; Digoxin; Diuretics; Drug Combinations; Exercise Therapy; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Mineralocorticoid Receptor Antagonists; Palliative Care; Risk Reduction Behavior; Secondary Prevention; Self Care; Smoking Cessation; Substance-Related Disorders

Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction, augments cardiac output, and reduces pulmonary capillary wedge pressure without causing deleterious increases in heart rate or decreases in blood pressure. Moreover, it is also a neurohormonal modulator at low doses. In the pivotal DIG (Digitalis Investigation Group) trial, digoxin therapy was shown to reduce all-cause and HF-specific hospitalizations but had no effect on survival. With the discovery of neurohormonal blockers capable of reducing mortality in HF with reduced ejection fraction, the results of the DIG trial were viewed as neutral, and the use of digoxin declined precipitously. Although modern drug and device-based therapies have dramatically improved the survival of ambulatory patients with HF, outcomes for patients with worsening chronic HF, defined as deteriorating signs and symptoms on standard therapy often leading to unscheduled clinic or emergency department visits or hospitalization, have largely remained unchanged over the past 2 decades. The available data suggest that a therapeutic trial of digoxin may be appropriate in patients with worsening chronic heart failure who remain symptomatic.

Topics: Animals; Cardiotonic Agents; Chronic Disease; Digoxin; Heart Failure; Hospitalization; Humans; Treatment Outcome

Heart failure with preserved ejection fraction (HFpEF) is now recognized as a major and growing public health problem worldwide. Yet significant uncertainties still surround its pathophysiology and treatment, leaving clinicians in a dilemma regarding its optimal management. Whether HFpEF and heart failure with reduced ejection fraction (HFrEF) are two distinct entities or two ends of a common spectrum remains a matter of debate. In particular, the lack of benefit observed with renin-angiotensin system blockers has raised questions regarding our understanding of the pathophysiology of HFpEF. New paradigms including a prominent role of co-morbidities, inflammation, endothelial dysfunction, and pro-hypertrophic signalling pathways have been proposed. Recent proof-of-concept trials using a phosphodiesterase inhibitor, a mineralocorticoid receptor antagonist, an angiotensin receptor/neprilysin inhibitor, a soluble guanylate cyclase stimulator, or a sino atria, if current blocker provide important insight for the development of novel therapeutic strategies in HFpEF.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Clinical Trials as Topic; Diagnosis, Differential; Digoxin; Female; Heart Failure; Humans; Male; Stroke Volume

African Americans are disproportionately affected by heart failure, with a high prevalence at an early age. Hypertension, diabetes, obesity, and chronic kidney disease are all common in African Americans and all predispose to heart failure. Neurohormonal imbalances, endothelial dysfunction, genetic polymorphisms, and socioeconomic factors also contribute. In general, the same evidence-based treatment guidelines that apply to white patients with heart failure also apply to African Americans. However, the combination of hydralazine and isosorbide dinitrate is advised specifically for African Americans.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black or African American; Cardiotonic Agents; Defibrillators, Implantable; Digoxin; Drug Combinations; Health Status Disparities; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Hydralazine; Hypertension; Incidence; Isosorbide Dinitrate; Mineralocorticoid Receptor Antagonists; Prevalence; Quality of Health Care; Socioeconomic Factors; Vasodilator Agents

There is no robust evidence that any treatment can modify the natural history of patients with heart failure and preserved left ventricular ejection fraction (HFpEF), although most agree that diuretics can control congestion and improve symptoms. HFpEF is often complicated by systemic and pulmonary hypertension, atrial fibrillation, obesity, chronic lung and kidney disease, lack of physical fitness, and old age that can complicate both diagnosis and management. Further trials should phenotype patients precisely and create better definitions of HFpEF based on biomarkers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Piperazines; Prognosis; Purines; Randomized Controlled Trials as Topic; Reference Values; Risk Assessment; Sildenafil Citrate; Stroke Volume; Sulfonamides; Survival Analysis; Syndrome; Treatment Outcome; Ventricular Function, Left

Cardiomyopathy during pregnancy is uncommon but potentially catastrophic to maternal health, accounting for up to 11% of maternal deaths. Peripartum cardiomyopathy is diagnosed in women without a history of heart disease 1 month before delivery or within 5 months postpartum. About half of all women will have full myocardial recovery within 6 months of diagnosis, but complications such as severe heart failure or death are not rare. African-American women have higher rates of diagnosis and adverse events. Women with preexisting cardiomyopathy, such as dilated or hypertrophic cardiomyopathy, followed closely during pregnancy often tolerate pregnancy and delivery. Risk factors for adverse outcomes include functional status at baseline, severity of systolic dysfunction or outflow tract gradient, or history of prior cardiac event, such as arrhythmia or stroke. The level of brain natriuretic peptide (BNP) can be used to risk stratify women for adverse events. Pregnant women with cardiomyopathy should be followed closely by a multidisciplinary team comprised of nurses, obstetricians, neonatologists, cardiologists, anesthesiologists, and cardiac surgeons.

Topics: Adrenergic beta-Antagonists; Adult; Anesthesia, Obstetrical; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiomyopathies; Contraindications; Digoxin; Diuretics; Female; Heart Failure; Humans; Incidence; Infant, Newborn; Maternal Age; Maternal Mortality; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, High-Risk; Prognosis; Risk Factors; Spironolactone; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiac Resynchronization Therapy; Defibrillators, Implantable; Digoxin; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Ventricular Dysfunction

Digoxin is one of the oldest of drugs acting on the heart and still one of the most frequently used. While in atrial fibrillation digoxin continues to have a valid role in the control of ventricular rate when added to beta-blockers and calcium antagonists, digoxin for heart failure is no longer a supportable option in view of the negative recent meta-analysis.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digitalis; Digoxin; Heart Failure; Humans; Plant Preparations

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiovascular Agents; Chronic Disease; Digoxin; Drug Combinations; Heart Failure; Heart Failure, Systolic; Humans; Hydralazine; Isosorbide Dinitrate; Ivabradine; Mineralocorticoid Receptor Antagonists

Heart failure is a common disorder associated with high morbidity and mortality as well as increasing socio-economic costs. General practitioners take care of most of the affected patients. Knowledge on pathophysiology and modern treatment concepts are decisive for rational decision making. Patient management focuses on longer survival and higher quality of life. Major goals include reductions in unnecessary hospital admissions as well as appropriate and timely involvement of heart failure specialists.. Die Herzinsuffizienz ist häufig und verursacht hohe sozial-ökonomische Kosten. Der Hausarzt ist der erste Ansprechpartner für die meisten Patienten. Um effizient abzuklären und sinnvolle Therapieentscheidungen zu treffen, ist die Kenntnis der zugrundeliegenden Ursachen und der medikamentösen wie nicht-medikamentösen Behandlungsoptionen zentral. Ziele sind längeres Überleben und bessere Lebensqualität. Entscheidend ist einerseits die Vermeidung unnötiger Hospitalisationen, andererseits gilt es zum richtigen Zeitpunkt die notwendigen Spezialisten zu involvieren.. L'insuffisance cardiaque est non seulement associée à une haute mortalité et morbidité, mais elle est aussi liée à de grandes dépenses socio-économiques. La plupart des patients atteints de cette maladie sont traités par le médecin généraliste. Il est donc important de comprendre la pathophysiologie et les nouvelles stratégies de traitement. Le but doit être d'augmenter la survie et la qualité de vie. Il faut donc d'un coté reduire les hospitalisations superflues et d'un autre coté consulter à temps les specialistes.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Evidence-Based Medicine; Heart Failure; Hemodynamics; Humans; Ivabradine; Mineralocorticoid Receptor Antagonists; Patient Readmission; Quality of Life; Survival Rate; Ventricular Dysfunction, Left

Digoxin has been used for hundreds of years to aid rate control in atrial fibrillation and as a positive inotrope in heart failure. Our familiarity with digoxin has allowed it to become easily prescribed even though there are data suggesting that use of digoxin may in fact result in increased mortality and pro-arrhythmia. Within this review we explain some of the outcome data associated with digoxin use to determine if it is time to take the gloves off and examine if we should still be using this drug in the 21st century.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Risk Assessment

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

The individual patient responses to chronic heart failure (HF) pharmacotherapies are highly variable. This variability cannot be entirely explained by clinical characteristics, and genetic variation may play a role. Therefore, this review will summarize the background pharmacogenetic literature for major HF pharmacotherapy classes (ie, β-blockers, angiotensin-converting enzyme inhibitors, digoxin, and loop diuretics), evaluate recent advances in the HF pharmacogenetic literature in the context of previous findings, and discuss the challenges and conclusions for HF pharmacogenetic data and its clinical application.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Heart Failure; Humans; Pharmacogenetics; Precision Medicine; Sodium Potassium Chloride Symporter Inhibitors

Atrial fibrillation (AF) is a prevalent condition particularly amongst the elderly, which contributes to both morbidity and mortality. The burden of disease has lead to significant increases in health care utilization and cost in recent years. Treatment of Atrial fibrillation consists of either a rate or rhythm control strategy. Rhythm control is achieved using medical management and/or catheter ablation. In spite of major strides in catheter ablation, this procedure remains a second line treatment of AF. Anti-arrhythmic medications represent the main treatment modality for the maintenance of sinus rhythm. Amiodarone has been used for decades because of its efficacy and lack of pro-arrhythmia despite numerous extracardiac side effects. Novel agents such as Dronedarone were designed to emulate Amiodarone without the extra-cardiac side effects. Unfortunately recent trials have raised concerns for the safety of this medication in certain patients. Other agents such as Vernakalant and Ranolazine are in development that promise to be more atrial selective in their action, thereby potentially avoiding pro-arrhythmia and heart failure side effects. It remains to be seen however if one or more of these agents achieves the required high efficacy and safety threshold. This review summarizes the main anti-arrhythmic clinical trials, early phase trials involving novel agents and examines the conflicting data relating to Dronedarone.

Topics: Acetanilides; Amiodarone; Anisoles; Anti-Arrhythmia Agents; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Dronedarone; Forecasting; Heart Failure; Humans; Phenethylamines; Piperazines; Pyrrolidines; Ranolazine; Sulfonamides; Technology, Pharmaceutical; Ventricular Dysfunction, Left

Digoxin is highly potent and efficacious for treatment of heart failure (HF) and/or atrial fibrillation (AF) yet compliance is often poor.. To examine prevalence rates of non-compliance with digoxin; variations between clinical settings, types of non-compliance and methods of detection; and potential factors influencing non-compliance with digoxin.. This was a systematic review and meta-analysis of prospective observational studies of non-compliance with digoxin in patients with HF and/or AF, published in English. The studies were identified through these bibliographic databases: MEDLINE, EMBASE, CINAHL, IPA and Cochrane CENTRAL. Subgroup analysis examined the influence of clinical settings, types of non-compliance and methods of detection.. Ten studies met the inclusion criteria, comprising 1841 patients with HF and/or AF. The corresponding prevalence rates of non-compliance for outpatients, after hospital discharge and inpatients were 43.1% (interquartile range [IQR] 29-48%), 25% (95% confidence interval [CI] 12-37%) and 4.5%, respectively. In patients with HF and AF co-morbidities, the prevalence rate of non-compliance with digoxin was 38.7% (IQR 27-46%); the corresponding prevalence rates of overdosing and underdosing were 33.04% (IQR 22-49%) and 33.8% (95% CI 25-42%), respectively. Rates varied depending on the methods of detecting non-compliance. Regularity of prescribed dose, diuretic use, coronary artery bypass, implantable cardioverter-defibrillator, number of office visits and pill boxes demonstrated strong associations with non-compliance with digoxin.. Non-compliance with digoxin is prevalent among patients with HF and/or AF. A better understanding of the factors influencing compliance and improved intervention strategies are necessary to increase digoxin compliance.

Topics: Ambulatory Care; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Chi-Square Distribution; Comorbidity; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Inpatients; Male; Medication Adherence; Risk Factors; Treatment Outcome

The indications for digoxin are currently limited to rare cases of heart failure and/or atrial fibrillation. Its use should be even more rare in geriatrics its pharmacological characteristics, associated with age-related changes and comorbidities, particularly increase the risk of digoxin poisoning in the elderly. However, at least a third of aged patients suffering from heart failure and/or atrial fibrillation is treated by digitalis. Digoxin intoxication can provoke gastrointestinal troubles, neurological disturbances and, above all, cardiac conduction impairment and dysrythmias, which explain its severity and high mortality rate. Presently, first-line therapy is the administration of digoxin specific antibodies. Poor prognosis factors, frequently found in digoxin intoxications in the elderly, have been established for guiding the prescription of antibodies and their dosage. It is important for geriatricians to be able to recognize poisoning signs and the conditions in which an antidote treatment is necessary. This will permit a more effective management of the case, with the support of a poison control center and possible referral of the patient to an intensive care unit.

Topics: Aged; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Intensive Care Units; Poison Control Centers; Prognosis; Treatment Outcome

Drug therapies for patients with acute heart failure syndromes (AHFS) are reviewed, including clinical practice guideline recommendations for the treatment of hospitalized patients with heart failure (HF).. AHFS may be defined as new-onset, gradual, or rapidly worsening HF signs and symptoms that require urgent therapy. Clinical practice guidelines from the American College of Cardiology Foundation-American Heart Association, Heart Failure Society of America, and European Society of Cardiology offer recommendations for the management of AHFS, addressing the role of diuretics, vasodilators, and inotropes. The guidelines emphasize the utility of vasodilators for patients with signs and symptoms of pulmonary congestion, including pulmonary edema or severe hypertension or both, who have not responded to diuretics. The early initiation of vasoactive medications, including diuretics and vasodilators, has been linked to improved outcomes in some reports. Conversely, the use of inotropes is de-emphasized, particularly as part of the routine management of these patients. Newer agents, including vasopressin antagonists, have also been approved recently but are not addressed by the clinical practice guidelines. The guidelines address the importance of initiating and optimizing evidence-based oral medications for long-term use, including angiotensin-converting-enzyme (ACE) inhibitors, angiotensin-receptor blockers, β-blockers, and aldosterone antagonists, during the patient's hospital stay in an effort to address long-term outcomes.. Drug therapy of AHFS may include diuretics, vasodilators, morphine, ACE inhibitors, digoxin, inotropes, and vasopressin antagonists. Clinical practice guidelines for patients with AHFS provide a useful mechanism to incorporate available evidence and standards of practice into patient care.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Dobutamine; Heart Failure; Humans; Milrinone; Morphine; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Practice Guidelines as Topic; Vasodilator Agents

Based on multiple randomized controlled trials performed in the last 20 years, drugs form the basis of treatment for heart failure with reduced ejection fraction (HFREF). Despite solid evidence for their efficacy and safety and publication of detailed national and international guidelines many patients with HFREF remain, who are not at all or only insufficiently treated. Treatment goals include reduction of mortality and hospitalizations, improvement of symptoms and exercise tolerance as well as prevention of disease progression. ACE-inhibitors and beta-adrenergic receptor blockers exert beneficial effects on all treatment goals and are therefore indicated in all patients with HFREF if tolerated. Diuretics allow control of fluid retention and maintenance of "euvolemia". Low-dose spironolactone can be considered in persistent moderate to severe (NYHA 3 - 4) HFREF despite treatment. Angiotensin receptor blockers are indicated for ACE-inhibitor intolerance or in addition to ACE-inhibitors and beta-adrenergic receptor blockers in case of persistent symptoms. Triple combination of ACE-inhibitors, angiotensin receptor blockers and aldosterone antagonists should be avoided in view of the substantial risk of hyperkalemia. In current praxis digoxin is mainly used as an adjunctive agent for rate control of atrial fibrillation in combination with beta-adrenergic receptor blockers. Titration and maintenance of heart failure treatment requires continuous control of clinical parameters, renal function and electrolytes. It is recommended to use drugs and dosest hat have been shown to be effective in clinial trials. Despite the fact that heart failure is mainly a disease of the elderly, this population is underrepresented in clinical trials. The risk of side effects and drug-drug interactions is increased in elderly patients because of physiologic changes with age and frequent comorbidities with resultant polypharmacy.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Cardiac Output, Low; Chronic Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists

The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection fraction (HFREF). Studies of the various drugs given for HFNEF have revealed conflicting results. The aim of this systematic review was to determine whether there is any benefit with pharmacotherapy in HFNEF in terms of cardiac outcomes.. Electronic and printed sources were searched until August 2010 for randomized controlled clinical trials (RCTs) comparing drug therapy with placebo in HFNEF. Weighted mean difference and pooled odds ratio (OR) with 95% confidence intervals were calculated.. A total of six RCTs including 8410 patients with a mean follow-up period of 21 months were included in the analysis. Although there were no significant differences in all cause mortality between the two groups (pooled OR 0.95, 95% CI 0.79, 1.13, P= 0.55), the subgroup analysis revealed a slight but non significant advantage with the β-adrenoceptor blocker group. There was no significant difference between the two groups in terms of cardiovascular mortality, hospitalization, worsening heart failure, ejection fraction, E : A ratio, deceleration time and E : E' ratio.. There was no significant benefit of pharmacotherapy in HFNEF. This might have been because of a lack of stringent inclusion criteria for patients in the trials and lower power of the studies. Hence trials with well defined inclusion criteria, better power, longer follow-up periods and with echocardiographic parameters as endpoints are required to shed further light on this topic.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Digoxin; Drug Therapy; Heart Failure; Humans; Randomized Controlled Trials as Topic; Stroke Volume

There is a significant amount of diversity among heart failure (HF) patients. Contemporary HF regimens often do not take into consideration many of the factors that might influence an individual's response to treatment. Clinical recommendations based on trial data derived from mainly younger Caucasian male study populations have, in most cases, been applied equally to women and African-Americans. Subgroup analyses of randomized HF trials and results of retrospective cohort studies have been used for customizing HF regimens in women and African-Americans. Pharmacogenetics is an emerging strategy for personalizing HF therapy. Genetic biomarkers may play an important role in predicting a patient's response to treatment and in predicting those at risk of toxicity. HF pharmacotherapy has improved over the last two decades; however, substantial work remains in order to personalize HF management and maximize the benefit of pharmacologic interventions, while limiting adverse events.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Black or African American; Digoxin; Female; Genetic Markers; Heart Failure; Humans; Incidence; Isosorbide Dinitrate; Male; Precision Medicine; Sex Factors; United States; White People

Digoxin is the oldest cardiac medication used in contemporary medicine. With a complex pharmacokinetic profile and narrow therapeutic index, its use in managing patients with atrial arrhythmias or heart failure can present a challenge to today's clinicians. Digoxin dosing based on patient-specific factors such as age, lean body weight, and renal function will allow practitioners to minimize drug toxicity while maintaining clinical efficacy. The ability to recognize digoxin overdose, which can manifest in both the acute and chronic settings, helps guide the appropriate dosing of digoxin immune globulins to reverse toxicity. Understanding this unique medication is essential for clinicians to ensure digoxin is used safely and effectively in practice.

Topics: Atrial Fibrillation; Cardiotonic Agents; Clinical Protocols; Digoxin; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Heart Rate; Humans; Immunoglobulin Fab Fragments; Myocardial Contraction

Topics: Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Digoxin; Diuretics; Dyspnea; Echocardiography; Edema; Exercise Tolerance; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Patient Education as Topic; Referral and Consultation; Terminal Care; Ventricular Dysfunction, Left

The management of heart failure in children is becoming a specialized discipline within pediatric cardiology. Unlike the treatment of heart failure in adults, for which an extensive body of literature supports current treatment regimens, management of heart failure in children is largely guided by extrapolation from adult studies and expert opinion. This review focuses on the current state-of-the-art with respect to the outpatient management of heart failure in children.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiotonic Agents; Child; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Diuretics; Heart Defects, Congenital; Heart Failure; Humans

Fetal echocardiography has progressed to be able to diagnose many forms of congenital heart disease (CHD) and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. Fetal echocardiography is for pregnancies at risk of structural, functional, and rhythm-related fetal heart disease. Routine obstetrical ultrasound screening is critical in the prenatal detection of fetal heart disease/CHD. With or without CHD, fetal heart dysfunction defined as inadequate tissue perfusion may occur. Perinatal problems other than CHD can also be assessed, such as the effects of noncardiac malformations that affect hemodynamics, that is, twin-twin transfusion. Cardiac rhythm can affect cardiac function and outcome, and prenatal diagnosis can be lifesaving. A tool for the assessment of cardiac function is the Cardiovascular Profile Score that combines ultrasonic markers of fetal cardiovascular unwellness based on univariate parameters, which have been correlated with perinatal mortality. This "heart failure score" could potentially be used in much the same way as and in combination with the biophysical profile score. This study will present a summary of fetal Doppler and its place in the diagnosis and assessment of prognosis of fetal heart failure.

Topics: Cardiotonic Agents; Digoxin; Echocardiography, Doppler; Echocardiography, Doppler, Color; Equipment Safety; Female; Fetal Diseases; Heart Failure; Heart Rate, Fetal; Humans; Hydrops Fetalis; Pregnancy; Severity of Illness Index

Digoxin has been reported to improve symptoms and reduce hospitalization in patients with heart failure as well as to control rapid ventricular rate in patients with atrial fibrillation. Both of these are high-prevalence diseases in the elderly, and yet studies have indicated that digoxin may not be used appropriately in this population. Clinical trials evaluating digoxin use specifically in the elderly are scarce.. This article discusses the evidence on the therapeutic use of digoxin in the elderly and the changes in the pharmacokinetics of digoxin with aging to provide recommendations about the appropriate use of this drug in this population.. Peer-reviewed clinical trials, review articles, and relevant treatment guidelines limited to those evaluating patients aged >65 years were identified from MEDLINE and the Current Contents database (both from 1966 to May 1, 2010) using the search terms digoxin, pharmacokinetics, heart failure, and atrial fibrillation. Citations from available articles were also reviewed for additional references.. One pharmacokinetic study, 8 clinical trials, and 2 guidelines were identified as relevant to digoxin use specifically in the elderly. In an elderly population (aged ≥65 years; n = 7) compared with a younger population (aged <65 years; n = 6), the elderly had a significant increase in digoxin t(1/2) (mean [SD]: oral dosing, 69.6 [13.1] vs 36.8 [4.5] hours; N dosing, 68.8 [12.3] vs 38.2 [3.5] hours; both, P < 0.05) and a decrease in total-body clearance (0.8 [0.2] vs 1.7 [0.2] mL/min/kg; P < 0.05). The use of digoxin in heart failure has been found to reduce the risk of hospitalization (risk ratio = 0.72; 95% CI, 0.66-0.79; P < 0.001). This beneficial effect of digoxin was found to be not significantly different across age groups in those aged >18 years. In terms of atrial fibrillation, the ability of digoxin to control the ventricular rate is believed to be caused by its vagotonic effect on the atrioventricular node. Therefore, digoxin is recommended for ventricular rate control only in patients with heart failure or sedentary lifestyle (ie, low sympathetic tone), or in those who cannot tolerate other rate-control agents. Because the prevalence of heart failure is high among the elderly (15.2 per 1000 population at age 65-74 years, 31.7 per 1000 population at age 75-84 years, and 65.2 per 1000 population at age ≥85 years), many of whom have a relatively sedentary lifestyle, digoxin may be an appropriate agent for ventricular rate control in the elderly.. The elderly population appears to gain comparable benefits as does a younger population from the use of digoxin for heart failure management in terms of symptom improvement and reduction of hospitalization. In atrial fibrillation, digoxin does not control the ventricular rate as efficaciously during exercise and in high adrenergic states as do R-blockers and calcium channel blockers. The elderly have reduced elimination of digoxin, so if digoxin is to be used, the dosing strategy must be conservative and therapeutic monitoring is needed. Further clinical studies are needed to confirm the pharmacokinetic parameters of digoxin in elderly patients with heart failure and/or atrial fibrillation.

Topics: Aged; Aged, 80 and over; Aging; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

The present review will examine the prognostic importance of atrial fibrillation and heart failure, explore the different therapeutic options for treating atrial fibrillation and present the results of the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial.. The Atrial Fibrillation and Congestive Heart Failure trial was a randomized trial involving patients with both atrial fibrillation and heart failure. The trial was designed to compare the maintenance of sinus rhythm with the control of ventricular rate in patients with left ventricular dysfunction, heart failure and a history of atrial fibrillation. There was no significant difference in the rate of death from cardiovascular causes in the rhythm-control group as compared with the rate-control strategy. In addition, there was no significant difference in any of the secondary outcomes including death from any cause, worsening heart failure or stroke. The rate-control strategy eliminated the need for repeated cardioversion and reduced rates of hospitalization.. The results of the Atrial Fibrillation and Congestive Heart Failure trial indicate that a routine strategy of rhythm control does not reduce rate of death and suggest that rate control should be considered a primary approach for patients with atrial fibrillation and heart failure.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Catheter Ablation; Comorbidity; Digoxin; Heart Failure; Heart Rate; Humans; Randomized Controlled Trials as Topic; Tachycardia

The pharmacologic management of acute heart failure syndromes (AHFS) has changed little over the past 15 years. Traditional therapies, such as nitrates and loop diuretics, remain the mainstay of therapy, with inotropes reserved for patients who present in shock or an advanced low-output state. We review the use of these therapies in AHFS with added insights from recent clinical trials and registry data.

Topics: Acute Disease; Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Diuretics; Dobutamine; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Milrinone; Mineralocorticoid Receptor Antagonists; Morphine; Nitroprusside; Practice Guidelines as Topic; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Survival Analysis; Syndrome; Treatment Outcome

Digitalis preparations have been used for centuries. Digoxin is an agent that is readily available, can be administered acutely and long-term, intravenously or orally, is safe and may be beneficial in both acute and chronic heart failure (HF). It may be an ideal drug for the treatment of acute heart failure syndromes and warrants further investigation in large clinical trials. The role of digoxin in acute and chronic HF was discussed at the 2008 European Society of Cardiology Working Group on Acute Cardiac Care Meeting held in Versailles, France from 25-28 October 2008. This report represents a summary of the presentation at this meeting.

Topics: Acute Disease; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Stroke Volume; Treatment Outcome

Heart failure affects 5 million Americans, and nearly 50% of these are women. Sex differences have been noted regarding the underlying etiology, pathophysiology, and prognosis. Women are less likely to have coronary artery disease and more likely than men to have hypertension and valvular disease as the underlying etiology. They often present at an older age with better systolic function than men. For both sexes, there is significant morbidity, but age-adjusted data reveal that women have a better survival. Despite these known sex differences, medical management recommendations are the same for women and men, because prospective sex-specific clinical trials have not been performed. However, our review raises some concerns that women might respond differently to therapy.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiac Pacing, Artificial; Digoxin; Female; Heart Failure; Heart-Assist Devices; Humans; Hydralazine; Isosorbide Dinitrate; Male; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Platelet Aggregation Inhibitors; Risk Factors; Sex Factors; Women's Health

Heart failure is a syndrome characterized initially by left ventricular dysfunction that triggers countermeasures aimed to restore cardiac output. These responses are compensatory at first but eventually become part of the disease process itself leading to further worsening cardiac function. Among these responses is the activation of the sympathetic nervous system (SNS) that provides inotropic support to the failing heart increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure, but eventually accelerates disease progression affecting survival. Activation of SNS has been attributed to withdrawal of normal restraining influences and enhancement of excitatory inputs including changes in: 1) peripheral baroreceptor and chemoreceptor reflexes; 2) chemical mediators that control sympathetic outflow; and 3) central integratory sites. The interface between the sympathetic fibers and the cardiovascular system is formed by the adrenergic receptors (ARs). Dysregulation of cardiac beta(1)-AR signaling and transduction are key features of heart failure progression. In contrast, cardiac beta(2)-ARs and alpha(1)-ARs may function in a compensatory fashion to maintain cardiac inotropy. Adrenergic receptor polymorphisms may have an impact on the adaptive mechanisms, susceptibilities, and pharmacological responses of SNS. The beta-AR blockers and the inhibitors of the renin-angiotensin-aldosterone axis form the mainstay of current medical management of chronic heart failure. Conversely, central sympatholytics have proved harmful, whereas sympathomimetic inotropes are still used in selected patients with hemodynamic instability. This review summarizes the changes in SNS in heart failure and examines how modulation of SNS activity may affect morbidity and mortality from this syndrome.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Cardiotonic Agents; Digoxin; Exercise Tolerance; Heart Failure; Hemodynamics; Humans; Parasympathetic Nervous System; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Receptors, Adrenergic; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, beta-2; Renin-Angiotensin System; Sympathetic Nervous System; Sympatholytics; Sympathomimetics

Treatment with inotropic agents is one of the most controversial topics in heart failure. Initial enthusiasm, based on strong pathophysiological rationale and apparent empirical efficacy, has been progressively limited by results of controlled trials and registries showing poorer outcomes of the patients on inotropic therapy. The use of these agents remains, however, potentially indicated in a significant proportion of patients with low cardiac output, peripheral hypoperfusion and end-organ dysfunction caused by heart failure. Limitations of inotropic therapy seem to be mainly related to their mechanisms of action entailing arrhythmogenesis, peripheral vasodilation, myocardial ischemia and damage, and possibly due to their use in patients without a clear indication, rather than to the general principle of inotropic therapy itself. This review will discuss the characteristics of the patients with a potential indication for inotropic therapy, the main data from registries and controlled trials, the mechanism of the untoward effects of these agents on outcomes and, lastly, perspectives with new agents with novel mechanisms of action.

Topics: Acute Disease; Cardiotonic Agents; Digoxin; Dobutamine; Etiocholanolone; Exercise Test; Heart Failure; Hemodynamics; Hospitals, Group Practice; Humans; Hydrazones; Prognosis; Pyrazines; Pyridazines; Quinolines; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Simendan; Treatment Outcome; Urea; Vasodilator Agents

Digoxin is an important therapeutic agent for the treatment of congestive cardiac failure. In spite of its narrow therapeutic index, digoxin has been used extensively by the medical community and, lately, the use of digoxin as a mechanistic probe for p-glycoprotein transporter activity has increased. This review describes recent trends in the bioanalysis of digoxin, where scores of liquid chromatographic-mass spectrometric assays have been successfully employed to measure digoxin in preclinical, clinical and mechanistic studies. It provides various considerations such as internal standard selection, extraction schemes, matrix effect, selectivity evaluation and optimization of mass spectral conditions, for example, to enable the development of sound bioanalytical methods for digoxin. Some recent updates with regard to clinical pharmacology, absorption and disposition aspects of digoxin have been included. Overall, liquid chromatographic-mass spectrometric assays represent an important tool for many future preclinical, clinical and mechanistic probe studies that would probe digoxin with or without other coadministered substrates.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiotonic Agents; Chromatography, High Pressure Liquid; Chromatography, Liquid; Clinical Trials as Topic; Digoxin; Drug Interactions; Female; Heart Failure; Humans; Male; Mass Spectrometry; Radioimmunoassay; Tandem Mass Spectrometry

Heart failure is a major public health problem. Heart failure with preserved systolic function (HF-PSF) is a common form, which is difficult to diagnose. Results of recent studies show that HF-PSF has a poor prognosis, with an annual survival rate similar to that of heart failure with left ventricular systolic dysfunction. Despite these findings, the therapeutic management of HF-PSF is not clearly defined. We will discuss in this review of the literature the current therapeutic management of HF-PSF, including the role of precipitating factors such as hypertension, myocardial ischaemia and supraventricular arrhythmias, and the main results of epidemiological registries and randomized controlled clinical trials in this disease. Only four large therapeutic trials have assessed the impact of different classes of drugs (digoxin, angiotensin II converting enzyme inhibitors, angiotensin II receptors type I blockers and beta-blockers) on morbidity and mortality in HF-PSF. Results of these trials are disappointing. Apart from the beta-blockers, the other three classes of drugs did not show benefit on the outcome of the disease. Moreover, the results of the beta-blocker trial are controversial as a mixed population of heart failure with and without preserved systolic function was studied. Finally, the current therapeutic management of patients with HF-PSF is still based on our pathophysiological knowledge: education, low salt diet, diuretics, slowing heart rate and controlling triggering factors. Other large randomized controlled multicenter trials, which may help us in the understanding of HF-PSP and its therapeutic management, are ongoing.

Topics: Adrenergic beta-Antagonists; Adult; Aged, 80 and over; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Benzopyrans; Blood Pressure; Cardiotonic Agents; Digoxin; Ethanolamines; Heart Failure; Heart Rate; Humans; Hypertension; Myocardial Ischemia; Nebivolol; Perindopril; Randomized Controlled Trials as Topic; Registries; Renal Artery Obstruction; Systole; Treatment Outcome

For more than 200 years digitalis has been considered of paramount importance in the treatment of heart failure and atrial fibrillation. The IN-CHF Italian registry shows that prescriptions were reduced from 63.3% in the period 1995-1999 to 40% in the period 2000-2005, a very different trend compared to prescriptions of angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, and beta-blockers. The commercial value of digitalis is much lower than other drugs and it does not seem to be of interest for the pharmaceutical companies. Unfortunately, this is a logical trend in the business world. For many years the major indications of digitalis have been heart failure and atrial fibrillation. The most important study on efficacy of digitalis in the treatment of heart failure was the DIG trial (1997), which showed no difference in mortality when compared to placebo but significant beneficial effects in reducing hospital admission rates. Many post-hoc researches evaluated blood levels of digitalis and proved beneficial effects also on mortality when digoxinemia values were 0.5-0.9 ng/ml. In conclusion, digitalis should still be considered effective for the treatment of heart failure; therefore prescription modality as well as the range of normal values of digoxinemia should be updated.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digitalis Glycosides; Digoxin; Drug Prescriptions; Female; Follow-Up Studies; Heart Failure; Humans; Male; Multicenter Studies as Topic; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Time Factors

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Treatment Outcome

Topics: Cardiotonic Agents; Decision Making; Digoxin; Heart Failure; Humans; Treatment Outcome

Heart failure caused by systolic dysfunction affects more than 5 million adults in the United States and is a common source of outpatient visits to primary care physicians. Mortality rates are high, yet a number of pharmacologic interventions may improve outcomes. Other interventions, including patient education, counseling, and regular self-monitoring, are critical, but are beyond the scope of this article. Angiotensin-converting enzyme inhibitors and beta blockers reduce mortality and should be administered to all patients unless contraindicated. Diuretics are indicated for symptomatic patients as needed for volume overload. Aldosterone antagonists and direct-acting vasodilators, such as isosorbide dinitrate and hydralazine, may improve mortality in selected patients. Angiotensin receptor blockers can be used as an alternative therapy for patients intolerant of angiotensin-converting enzyme inhibitors and in some patients who are persistently symptomatic. Digoxin may improve symptoms and is helpful for persons with concomitant atrial fibrillation, but it does not reduce cardiovascular or all-cause mortality. Serum digoxin levels should not exceed 1.0 ng per mL (1.3 nmol per L), especially in women.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Heart Failure; Humans; Hydrazines; Isosorbide Dinitrate; Severity of Illness Index; Systole; Vasodilator Agents

Chronic heart failure (CHF) is common, and increases in incidence and prevalence with age. There are compelling data demonstrating reduced mortality and hospitalizations with adrenergic blockade in older patients with CHF. Despite this, many older patients remain undertreated. The aim of the present article is to review the potential mechanisms of the benefits of adrenergic blockade in CHF and the clinical data available from the large randomized studies, focusing particularly on older patients.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Carbazoles; Carvedilol; Chronic Disease; Comorbidity; Digoxin; Heart Failure; Humans; Propanolamines; Ventricular Dysfunction, Left; Ventricular Remodeling

Heart failure management is complex and costly. Genetic variations that alter drug absorption, metabolism, and receptor-ligand interactions have the potential to modify drug response and safety. Evidence shows that genetic factors interact with numerous heart failure medications, including vasodilators, beta blockers, and angiotensin-converting enzyme inhibitors. Technologic advances will soon allow population-based genome-wide genetic testing at a reasonable cost. Understanding the genetic factors that influence drug response in heart failure will allow physicians to personalize therapies and optimize response while minimizing serious adverse events.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Biomarkers, Pharmacological; Digoxin; Heart Failure; Humans; Pharmacogenetics; Polymorphism, Genetic; Toxicogenetics

Diastolic heart failure is a common form of congestive heart failure that is responsible for significant morbidity and mortality. In contrast to heart failure caused by systolic left ventricular dysfunction, diastolic heart failure is harder to diagnose and less likely to be accepted as a diagnosis. In addition, treatment strategies are much less defined than those for heart failure caused by systolic dysfunction.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output; Cardiotonic Agents; Diastole; Digoxin; Diuretics; Drug Therapy, Combination; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Prognosis; Risk Assessment; Severity of Illness Index; Stroke Volume; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left

Congestive heart failure (CHF) is an increasingly common medical condition and the fastest growing cardiovascular diagnosis in North America. Over one-third of patients with heart failure also have renal insufficiency. It has been shown that renal insufficiency confers worsened outcomes to patients with heart failure. However, a majority of the larger and therapy-defining heart failure medication and device trials exclude patients with advanced renal dysfunction. These studies also infrequently perform subgroup analyses based on the degree of renal dysfunction. The lack of information on heart failure patients who have renal insufficiency likely contributes to their being prescribed mortality and morbidity reducing medications and receiving diagnostic and therapeutic procedures at lower rates than heart failure patients with normal renal function. Inclusion of patients with renal insufficiency in heart failure studies and published guidelines for medication, device, and interventional therapies would likely improve patient outcomes.

Topics: Acute Disease; Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiac Catheterization; Cardiac Pacing, Artificial; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Milrinone; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Treatment Outcome; Ultrafiltration

Acute decompensated heart failure is the most common cause for hospitalization among patients over 65 years of age. It may result from new onset of ventricular dysfunction or, more typically, exacerbation of chronic heart failure symptoms. In-hospital mortality remains high for both systolic and diastolic forms of the disease. Therapy is largely empirical as few randomized, controlled trials have focused on this population and consensus practice guidelines are just beginning to be formulated. Treatment should be focused upon correction of volume overload, identifying potential precipitating causes, and optimizing vasodilator and beta-adrenergic blocker therapy. The majority of patients (>90%) will improve without the use of positive inotropic agents, which should be reserved for patients with refractory hypotension, cardiogenic shock, end-organ dysfunction, or failure to respond to conventional oral and/or intravenous diuretics and vasodilators. The role of aldosterone antagonists, biventricular pacing, and novel pharmacological agents including vasopressin antagonists, endothelin blockers, and calcium-sensitizing agents is also reviewed.

Topics: Adrenergic beta-Antagonists; Blood Pressure; Digoxin; Diuretics; Endothelins; Heart Failure; Heart Rate; Humans; Mineralocorticoid Receptor Antagonists; Prognosis; Vasodilator Agents

Over the past 2 decades, investigators have learned more about the pathophysiologic changes that occur in systolic and diastolic dysfunction. Ironically, in some cases, the biologic pathways that have protected the heart during acute dysfunction are the same pathways that cause progressive deleterious effects with chronic activation. In particular, it is the activation of the neurohormonal system that has a significant impact on disease progression. As a result, the neurohormonal system has provided a key target for pharmacologic therapy in patients with heart failure secondary to systolic dysfunction. These targets include the renin-angiotensin-aldosterone system as well as the sympathetic nervous system. Neurohormonal manipulation, however, is often ineffective in the pharmacologic therapy of patients with endstage heart failure, therefore other treatment strategies - including the use of inotropic agents to improve pump function and diuretics to control fluid balance are needed.

Topics: Adrenergic alpha-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Vasodilator Agents

The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chronic heart failure has enabled targeted therapy to be introduced with consequent improvement in symptoms, reduction in hospitalisation and lower mortality.

Topics: Adolescent; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Child; Child, Preschool; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Heart Transplantation; Humans; Male; Myocardial Contraction; Phosphodiesterase Inhibitors; Stem Cell Transplantation

Anti-neurohormonal pharmacological agents successfully tested in randomized controlled trials over the last two decades - firstly angiotensin-converting enzyme inhibitors (ACE-I), then beta-blockers (BB) and more recently aldosterone receptor-antagonists (ARA) and angiotensin II receptor blockers (ARB) - have significantly contributed to increase the chance of favorable outcomes in patients with chronic heart failure. An ACE-I and a BB, usually combined with diuretics and often with digoxin, continue to represent the cornerstones for the treatment of heart failure; moreover, most patients who are taking these drugs are now expected to receive as add-on therapies also an ARA and/or an ARB. However, as the number of available drugs increases coupled with the hope of greater clinical benefits, these more complicated pharmacological options are destined to generate even more controversy. Now, much debate is over to which triple (ACE-I + BB + ARA or ARB) and quadruple (ACE-I + BB + ARA + ARB) therapies may be offered. Current guidelines do not fully address the aim of providing straightforward guidance about what should be the third drug of the triple therapy and as to whether or not quadruple therapy may have any role in the present-day heart failure management. Adapting any pharmacological strategy--based upon both scientific evidence and clinical reasoning--to the specific profile of the individual patient can be helpful to circumvent uncertainties and errors in daily practice of medicine and make the best use of currently available drugs.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Evidence-Based Medicine; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Treatment Outcome

Congestive heart failure is a growing public health problem worldwide, particularly in the elderly population, in whom it has a substantial impact on quality of life and survival. Despite the fact that heart failure is the most common reason for hospitalisation over the age of 65 years, most clinical trials have excluded the elderly population. This is unfortunate because it may not be generally assumed that elderly patients are similar to younger ones. Nonspecific symptoms and co-morbidities in the elderly may make diagnosis of heart failure difficult. In addition, physiology changes with age, polypharmacy complicates therapy and the aim of therapy may change in the presence of co-morbidities such as cancer or dementia. Furthermore, drug interactions and adverse effects are frequent in heart failure in general, but increase significantly with age. Nevertheless, there is little evidence that treatment of heart failure should be fundamentally different in elderly patients compared with younger patients, although careful monitoring of medical therapy is of particular importance in elderly heart failure patients. Therefore, general guidelines on diagnosis and therapy of heart failure also apply to elderly patients, but therapy may need to be adjusted to cater for individual needs, potential interactions and altered elimination of drugs. This article summarises the evidence available for treatment in elderly patients with heart failure, discusses potential differences in elderly subjects compared with their younger counterparts and provides recommendations for clinical practice.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Aging; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure; Humans; Incidence; Mineralocorticoid Receptor Antagonists; Prevalence; Vasodilator Agents

Cardiac insufficiency is a disease of old age. Analyses of subgroups have showed that old patients benefit to a particular extent from therapeutic measures the effectiveness of which has been confirmed in numerous studies. In the light of this knowledge, it is all the more difficult to understand why this group of patients are still not receiving effective treatment. In this area, there is an urgent need for improvement. Also difficult to understand is the fact that the guidelines for the treatment of chronic cardiac failure issued by the German Cardiology Society pay so little attention to cardiovascular research of cardiac insufficiency in old age, and thus bear indirect responsibility for the less than optimal treatment of this condition, which can be so severe in the old patient. These guidelines should contain a section on the peculiarities of cardiac insufficiency in high old age.

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Clinical Trials as Topic; Diagnosis, Differential; Diastole; Digitoxin; Digoxin; Diuretics; Drug Therapy, Combination; Echocardiography, Doppler; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Practice Guidelines as Topic; Prevalence; Prognosis; Risk Factors

Topics: Atrial Fibrillation; Cardiovascular Diseases; Digoxin; Disease Management; Heart Failure; Humans

beta-Blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aldosterone receptor antagonists, and digoxin are the most common drug classes used to treat chronic heart failure. We examine current clinical trial evidence concerning heart-failure management in the elderly.. beta-Blockers provide significant mortality benefit to elderly heart-failure patients and are remarkably well tolerated. Angiotensin-converting-enzyme inhibitors improve mortality and morbidity in systolic heart failure. However, the risk/benefit relationship of angiotensin-converting-enzyme therapy in the elderly has not been adequately determined. Angiotensin II receptor blockers improve morbidity in elderly and non-elderly chronic heart-failure patients; however, data are limited regarding mortality in these patients. Aldosterone receptor antagonists provide significant mortality benefit to elderly chronic heart-failure patients. Digoxin is beneficial as an additive therapy in the treatment of systolic heart failure regardless of advanced age.. Agents that provide substantive clinical benefit overall also appear to do so in the elderly, based on subgroup analysis of major trials. There have been very few prospective, placebo-controlled trials specifically in elderly heart-failure patients. Elderly heart-failure patients generally tolerate standard chronic heart-failure therapies well. Standard chronic heart-failure therapies should not be withheld from elderly patients based on concerns regarding efficacy or fear of medication intolerance.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 2 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Drug Tolerance; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome

Heart failure (HF) affects approximately 5 million persons in the United States; more than 550,000 new cases of HF are reported each year. Prevalence of HF with a normal left ejection fraction increases with age and is higher in older women than older men. Both underlying and precipitating causes of HF should be treated when possible. Hypertension, especially isolated systolic hypertension, should be treated with diuretics, ACE inhibitors, and beta blockers. Myocardial ischemia should be treated with nitrates and beta blockers. Anemia should be treated, as should hyperthyroidism, hypothyroidism, and obstructive sleep apnea. Use of inappropriate drugs, such as nonsteroidal anti-inflammatory drugs, should be avoided. Coronary revascularization should be performed in selected individuals.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Calcium Channel Blockers; Cardiotonic Agents; Comorbidity; Digoxin; Diuretics; Exercise; Heart Failure; Humans; Hypertension; Myocardial Revascularization; Stroke Volume; Ventricular Function, Left

Unlike heart failure with a low ejection fraction, there is no evidence-based treatment for heart failure with preserved ejection fraction which improves clinical outcomes. Indeed, the only evidence for any treatment effect comes from small studies with verapamil where this drug increased exercise capacity and reduced a heart failure score. Large trials are presently underway which are examining the effect of treatment with an ACE inhibitor, ARB and aldosterone antagonist in patients with heart failure and preserved ejection fraction.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Diastole; Digoxin; Heart Failure; Humans; Stroke Volume

Digoxin has been the cornerstone of the treatment of heart failure for more than 2 centuries. Now that newer therapies have been introduced that reduce the mortality rate in heart failure and recent trials have failed to prove the same for digoxin, its use has significantly decreased. But a careful review of the multiple pharmacologic actions of digoxin and closer analysis of the results of recent trials suggest that digoxin may in fact continue to be an effective treatment for heart failure.

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Topics: Age Distribution; Age Factors; Aged; Aged, 80 and over; Cardiotonic Agents; Diastole; Digoxin; Drug Administration Schedule; Drug Monitoring; Evidence-Based Medicine; Female; Geriatrics; Heart Failure; Humans; Male; Nursing Homes; Patient Selection; Practice Guidelines as Topic; Practice Patterns, Physicians'; Safety; Sex Characteristics; Systole; Treatment Outcome; United States

Topics: Age Factors; Aged; Cardiotonic Agents; Digoxin; Drug Utilization Review; Evidence-Based Medicine; Geriatrics; Heart Failure; Humans; Nursing Homes; Patient Selection; Practice Patterns, Physicians'; Treatment Outcome

Heart failure due to systolic dysfunction is a clinical syndrome that is characterized by the appearance of the signs or symptoms of heart failure in the presence of structural heart disease that has led to decreased left ventricular contractility. Current clinical practice guidelines emphasize the importance of diagnosing and treating left ventricular dysfunction in patients without symptoms of heart disease. It is essential that currently available scientific findings are taken into account when treating all patients seen with this condition, from dietary advice to use of the most sophisticated devices. We do not know the precise treatment responses of patient belonging to subgroups that were underrepresented in large clinical trials. The present article, written after the recent publication of European and American clinical practice guidelines, provides a summary of recommended medical treatment for patients with heart failure due to systolic dysfunction.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Systole; Ventricular Dysfunction, Left

At present in Europe number of deaths due to diseases of cardiovascular system in women has exceeded number of deaths in men. It has been established that process of cardiac remodeling proceeds differently in women and men. This determines different prognosis of the course of chronic heart failure. So after acute myocardial infarction in women more often develops chronic heart failure with preserved systolic left ventricular function while in men prevails chronic heart failure with systolic dysfunction. Substantial differences exist in efficacy of pharmacotherapy: for instance thrombolysis in women is less effective than in men, women are less sensitive to angiotensin converting enzyme inhibitors, administration of digoxin, some antiarrhythmic drugs cause complications in women more often than in men.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Benzopyrans; Calcium Channel Blockers; Chronic Disease; Digoxin; Electrocardiography; Ethanolamines; Female; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Nebivolol; Sex Factors

The main aims of the treatment of chronic heart failure are to improve and to maintain the quality of life, to increase duration of life, to decrease mortality, to prevent diseases leading to the heart failure development, and to prevent the progression of heart failure. Diuretics are the drugs of first choice for the treatment of congestive heart failure. They can improve the quality of patient's life quite quickly. Noncompliance to methodological diuretic use can cause a serious damage such as metabolic disorders, arrhythmias, and even sudden death. Loop diuretics are the drugs of choice. Resistance to diuretics occurs in 10-20% of the cases during the course of treatment; therefore, drug combination as well as dose modification is required. Diuretics are not recommended to use alone for a symptomatic relief. They are prescribed in combination with beta-blockers, angiotensin-converting-enzyme inhibitors, and/or angiotensin receptor blockers for a continuous pathogenetic therapy of congestive heart failure. Digoxin in combination with diuretics is the drug of choice for treatment of heart failure when tachyarrhythmia or severe systolic left ventricular dysfunction appears or it is impossible to administer beta-blockers. In this article, the guidelines of European Society of Cardiology and also American College of Cardiology and American Heart Association for the symptomatic management of congestive heart failure, updated in 2005, are reviewed.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiotonic Agents; Digoxin; Disease Progression; Diuretics; Drug Resistance; Drug Therapy, Combination; Heart Failure; Humans; Patient Compliance; Practice Guidelines as Topic; Quality of Life

Heart failure (HF) is a prevalent and morbid chronic disease that patients experience in stages. Progression through the stages of HF can be slowed with optimal medical therapy. Although HF remains a clinical diagnosis made at the bedside, measurement of serum brain natriuretic peptide (BNP) can help in the diagnosis when there is uncertainty. The initial workup for patients with newly diagnosed HF is directed at identifying the underlying cause of left ventricular dysfunction. An assessment of hemodynamic status, determined by a careful physical examination, can be used to direct therapy. Angiotensin-converting enzyme inhibitors (ACEIs) and beta blockers remain the two most important therapies for patients with chronic HF. Aldosterone antagonists improve mortality but require close monitoring for severe hyperkalemia. Angiotensin-receptor blockers (ARBs) are excellent alternatives to ACEIs for ACEI-intolerant patients. Digoxin, a second line agent in HF, improves symptoms without mortality benefit. Successful management of HF requires aggressive management of comorbid conditions and careful follow up to slow disease progression, optimize functional status, and improve longevity.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Natriuretic Peptide, Brain

In The Netherlands, the incidence and prevalence of heart failure are rising as is the case in most other European countries. Overall, there are 200,000 patients with heart failure in The Netherlands and around 25,000 hospitalisations annually with a discharge diagnosis of heart failure. Most of these patients are managed in primary care, often together with a cardiologist. There is an active guideline program in different professional organisations (e.g. general practitioners, cardiologists) and in 2002 a collaborative multidisciplinary guideline for management of chronic heart failure was developed. However, there is clearly room for improvement in the adherence to these guidelines both with regard to the diagnosis and the treatment of HF patients. For example, ACE-I and beta-blockers are still under-prescribed. In particular, the more severely ill patients seem to be under treated. At present, general practitioners and cardiologists differ in their views on heart failure, resulting in differences in diagnosis and management. In addition to the multidisciplinary guidelines, several other initiatives have been developed to improve outcomes in these patients, such as rapid access clinics and outpatient heart failure clinics.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiology; Digoxin; Diuretics; Family Practice; Heart Failure; Humans; Incidence; Netherlands; Practice Guidelines as Topic; Prevalence; Spironolactone

Heart failure is a leading cause of morbidity and mortality. It affects over 5 million patients annually. There are an estimated 400,000-700,000 new cases diagnosed each year. The management of heart failure has changed significantly over the last decade. This review focuses on the pharmacologic management of systolic heart failure, and provides current recommendations for the practicing acute care provider.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Digoxin; Diuretics; Emergency Medicine; Heart Failure; Humans; Practice Guidelines as Topic; Treatment Outcome; Vasodilator Agents

In patients with heart failure and atrial fibrillation cardiac glycosides, generally in combination with beta-blockers, are indicated to control ventricular rate. In systolic heart failure and sinus rhythm, however, the use of digitalis continues to be debated. There are special concerns that cardiac glycosides might lead to an increased mortality rate in women. Retrospective analyses, however, do not indicate any sex-based differences in the effectiveness of cardiac glycosides. Beneficial effects of cardiac glycosides in heart failure seem to be related to the attenuation of sympathetic activation and neurohumoral alterations, which is already obtained at low digoxin serum concentrations, while high serum levels are associated with increased mortality. Therefore, in patients with sinus rhythm who remain symptomatic under an optimized therapy with ACE inhibitors, beta-blockers and diuretics in addition to digitalis should be considered regardless of the gender. However, target serum digoxin concentrations should be low in a range of 0.5 to 0.8 ng/ml.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Risk Factors; Sex Factors; Survival Analysis; Sympathetic Nervous System; Treatment Outcome

Arrange for echocardiography or radionuclide angiography within 72 hours of a heart failure exacerbation. An ejection fraction >50% in the presence of signs and symptoms of heart failure makes the diagnosis of diastolic heart failure probable. To treat associated hypertension, use angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, or diuretics to achieve a blood pressure goal of <130/80 mm Hg. When using beta-blockers to control heart rate, titrate doses more aggressively than would be done for systolic failure, to reach a goal of 60 to 70 bpm. Use ACE inhibitors/ARBs to decrease hospitalizations, decrease symptoms, and prevent left ventricular remodeling.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Calcium Channel Blockers; Comorbidity; Diastole; Digoxin; Diuretics; Echocardiography; Family Practice; Female; Heart Failure; Humans; Hypertension; Male; Practice Guidelines as Topic; Prevalence; Prognosis; Risk Factors; United States

Topics: Anti-Arrhythmia Agents; Digoxin; Evidence-Based Medicine; Heart Failure; Heart Rate; Humans; Practice Guidelines as Topic; Survival Analysis; Treatment Outcome

In a series of papers the authors analyze literature data on the use of cardiac glycosides for long term treatment of chronic heart failure. Part 1 is devoted to clinical pharmacology of glycosides with special emphasis on digoxin. In low doses digoxin produces no substantial effect on contractility of left ventricular myocardium but can cause worsening of its diastolic function. Favorable action of digoxin on clinical course and outcomes of chronic heart failure is most probably related to modulation of neuro-humoral systems. Data on factors influencing sensitivity to glycosides in various categories of patients with heart failure, their interaction with other drugs, and contraindications for digoxin are also presented.

Topics: Cardiac Glycosides; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Treatment Outcome

beta-Blockers are currently being evaluated more intensively to define their role in clinical use as antiarrhythmic agents. beta-Adrenergic blockade has been studied in relation to atrial fibrillation, ventricular arrhythmias, and sudden death; however, it is apparent from a number of studies that not all beta-blockers are equally effective. Randomized clinical trial data, both in heart failure and post-myocardial infarction (MI) patients, have shown differences in mortality benefits in addition to a variable effect on arrhythmias and sudden death. Carvedilol, a third-generation beta-blocker with proven clinical benefit in the management of heart failure and post-MI patients, has properties that may make it an effective antiarrhythmic agent. This paper reviews the current clinical arrhythmia data available for carvedilol from large-scale clinical trials and small studies. The trial evidence demonstrates that carvedilol therapy can be an effective adjunctive rate-control therapy in patients with atrial fibrillation, prevent mortality in patients with heart failure or post-MI with left ventricular dysfunction, with or without atrial fibrillation, and reduce its onset and the incidence of ventricular arrhythmia and sudden death.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Carbazoles; Carvedilol; Death, Sudden, Cardiac; Digoxin; Heart Failure; Humans; Metoprolol; Myocardial Infarction; Propanolamines; Randomized Controlled Trials as Topic

Several treatment strategies exist for patients hospitalized with acute heart failure syndromes (AHFS). These therapies traditionally focus on improving hemodynamics and relieving congestion. This review focuses on noninodilator therapies, including diuretics, nitrovasodilators (nitroprusside and nitroglycerin), vasodilators (nesiritide), digoxin, and intravenous angiotensin-converting enzyme inhibitors. These agents are used based on their associated symptomatic improvements alone. In the hospitalized setting, none of these agents have demonstrated benefits on long-term outcomes. Future work in AHFS should strive to understand the influence of conventional and new pharmacologic therapies on the underlying pathophysiology of AHFS, the processes that lead to myocardial injury and progressive heart failure, and measurable clinical outcomes.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Heart Failure; Humans; Natriuretic Peptide, Brain; Nitroglycerin; Nitroprusside; Severity of Illness Index; Syndrome; Vasodilator Agents

Chronic heart failure (HF) is an increasingly common cardiovascular disorder. The goal of health-care providers is to optimize quality of life in this population, including sexual health. Up to 75% of patients with HF report erectile dysfunction (ED). As HF is a condition with distinct physiologic sequelae, some unique organic and psychological factors contributing to ED in this patient population have been identified, along with risk factors common to the development of coronary artery disease, HF and ED. This review describes contributing factors to ED in the setting of HF and highlights treatment considerations for this distinct patient population.

Topics: Adrenergic beta-Antagonists; Angioplasty, Balloon; Depression; Digoxin; Diuretics; Endothelium, Vascular; Erectile Dysfunction; Exercise; Heart Failure; Humans; Male; Piperazines; Purines; Sexual Behavior; Sildenafil Citrate; Sulfones

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Comorbidity; Digoxin; Disease Progression; Diuretics; Drug Monitoring; Geriatric Nursing; Heart Failure; Humans; Nursing Homes; Osteoarthritis; Patient Selection; Pulmonary Disease, Chronic Obstructive

This review summarizes the current status of randomized trials of digitalis in treating patients with congestive heart failure who are in sinus rhythm. Methods and results Randomized double-blind placebo-controlled trials of 20 or more adult patients followed for 7 weeks or more were selected. We identified 13 trials that met the inclusion criteria, comprising a total of 7896 patients. Of this number, 7755 patients contributed to information on mortality, 7262 to information on hospitalization for worsening heart failure, and 1096 to information on clinical status. Patients treated with digitalis compared with placebo had an odds ratio and confidence intervals for mortality of 0.98 (0.89, 1.09), for hospitalization of 0.68 (0.61, 0.75), and for a lesser degree of deterioration in clinical status of 0.31 (0.21, 0.43).. The literature indicates that the drug has no effect on long-term mortality, but reduces the incidence of hospitalization, and has a positive effect on the clinical status of symptomatic patients. The drug has beneficial effects in patients who remain symptomatic despite being appropriately treated with diuretics and angiotensin-converting enzyme inhibitors. However the effects of coadministration with beta-blockers, spironolactone, and valsartan remain uncertain.

Topics: Adult; Digitalis Glycosides; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Research Design

Atrial fibrillation affects approximately 2 million people in the United States and is a common comorbidity among patients with heart failure. Clinical studies indicate that the benefits of the beta-blocker carvedilol in patients with heart failure extend to patients with heart failure complicated by atrial fibrillation. The results of the Carvedilol in Atrial Fibrillation Evaluation (CAFE) trial provide support that carvedilol has incremental benefit when added to digoxin for the management of atrial fibrillation in patients with heart failure. Additional recent studies suggest that carvedilol may be useful in managing postsurgical atrial fibrillation and also may prevent recurrence of atrial fibrillation among patients who undergo cardioversion.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Carbazoles; Carvedilol; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Propanolamines; Randomized Controlled Trials as Topic; Ventricular Remodeling

Topics: Animals; Autonomic Nervous System; Baroreflex; Cardiotonic Agents; Cardiovascular Agents; Clinical Trials as Topic; Digitalis Glycosides; Digoxin; Diuresis; Drug Interactions; Heart Failure; Heart Rate; Humans; Phytotherapy; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Vascular Resistance; Vasodilator Agents

Topics: Aged; Atrial Fibrillation; Biological Availability; Calcium Signaling; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Drug Interactions; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Parasympathetic Nervous System; Parasympathomimetics; Randomized Controlled Trials as Topic; Sodium-Potassium-Exchanging ATPase

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Practice Guidelines as Topic

Diastolic heart failure (DHF) is characterized by the clinical presentation of heart failure in the setting of preserved left ventricular systolic function and evidence of diastolic dysfunction. It is estimated to be present in at least one-third of patients, who represent the signs and symptoms of heart failure, and is especially prevalent among the elderly population. Despite an increasing understanding of the pathophysiology of this disease and the improvement of diagnostic and prognostic assessment, the management of DHF remains to be established. Medical therapy consists of the cautious use of diuretics, and some studies suggested the beneficial role of beta-blockers and calcium antagonists. The rationale of current therapy is largely dependent on understanding the pathophysiology of DHF and observations from clinical trials that included relatively small numbers of patients. Large, multicenter, randomized, controlled studies are needed to define the role of various therapeutic agents in DHF, and whether the prognosis of the disease will be altered. The SWEDIC trial observed that carvedilol treatment in patients with DHF was associated with an improvement in diastolic indices measured by Doppler echocardiography. The CHARM-Preserved trial reported a non-significant reduction of cardiovascular death or admission for heart failure. Other studies which are underway include PEP-CHF and the Hong Kong Diastolic Heart Failure study. They will play a pivotal role in ascertaining the therapeutic efficacy of various agents and will help experts to set up treatment guidelines for this common condition.

Topics: Adrenergic beta-Antagonists; Animals; Calcium Channel Blockers; Diastole; Digoxin; Diuretics; Echocardiography, Doppler; Heart Failure; Humans; Renin-Angiotensin System

Optimal outpatient treatment of systolic heart failure has three goals that should be pursued simultaneously: (1) control of risk factors for the development and progression of heart failure, (2) treatment of heart failure, and (3) education of patients. Control of risk factors includes treating hypertension, diabetes, and coronary artery disease, and eliminating the use of alcohol and tobacco. All patients with heart failure should be taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker. In the absence of contraindications, an ACE inhibitor is preferred. In most patients, physicians should consider adding a beta blocker to ACE-inhibitor therapy. In patients with severe heart failure, spironolactone is a useful addition to baseline drug therapy, as is carvedilol (substitute carvedilol if patient is already taking a beta blocker). Patients with stable heart failure should be encouraged to begin and maintain a regular aerobic exercise program. Digoxin therapy may reduce the likelihood of hospitalization but does not reduce mortality. It must be monitored closely, with a target dosage level of 0.5 to 1.1 ng per mL. Symptoms may be controlled with the use of diuretics and restricted dietary sodium. Finally, patient education, with the patient's active participation in the care, is a key strategy in the management of heart failure. Periodic follow-up between scheduled office visits, which is essential in the long-term management of heart failure, may include telephone calls from the office nurse, maintenance of a daily symptom and weight diary, and participation in a disease-management program.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Decision Trees; Digoxin; Family Practice; Heart Failure; Humans; Practice Guidelines as Topic

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Aspirin; Calcium Channel Blockers; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Spironolactone; Warfarin

The general profile of women with cardiac failure differs from that of the male population, especially with respect to aetiology and prognosis. Women are often older, have preserved systolic function more often and a higher incidence of risk factors such as hypertension and diabetes. Moreover, global mortality is lower in women. From the therapeutic point of view, women with symptomatic left ventricular dysfunction probably benefit from ACE inhibitors but those with asymptomatic dysfunction have no reduction in mortality with this class of drugs. In addition, treatment with ACE inhibitors is usually interrupted in women because of a higher incidence of secondary effects. The poorer tolerance could be explained by the profile of women with cardiac failure. The large scale multicentre trials with betablockers included very few women. In MERIT-HF, in which there was a large number of women (23%), the female subgroup was the only one in which a benefit in mortality was not demonstrated. However, a retrospective analysis of the data of this subgroup plus a meta-analysis of all trials with betablockers does show improved mortality with this class of drugs in women. In a retrospective study of the DIG study, there seems to be a difference in the effects of digoxin between men and women; the prescription of digoxin is associated with a higher overall mortality in women. Finally, women seem to require diuretics more often than do men. There are many explanations for the differences observed in therapeutic responses between men and women. The role of sex hormones is often evoked, although it has never been clinically proved. The treatment of heart failure in women should take clinical and biological factors specific to women into account and may explain the relative inefficacy of certain forms of treatment.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Sex Factors

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Aspirin; Calcium Channel Blockers; Cardiotonic Agents; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Spironolactone; Warfarin

Congestive heart failure represents a growing health issue with significant morbidity, expense, and mortality. Unfortunately, despite heart failure affecting men and women equally, women historically have represented a minority in heart failure trials. Despite this disparity, treatment decisions rely heavily on these trials. Women with heart failure often have different clinical features than men, such as age of onset and comorbidities. Compared with men, women also demonstrate differences in remodeling and the response to injury, such as volume or pressure overload and myocardial infarction. We are only beginning to understand the clinical implications of these gender differences and their impact on pharmacologic treatments. After discussing these differences, a review of the agents useful in systolic failure is made, including angiotensin-converting enzyme inhibitors, b-blockers, digoxin, and aldosterone inhibition. Treatment of diastolic heart failure with empiric guidelines follows.

Topics: Adrenergic beta-Antagonists; Age of Onset; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Digoxin; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Prognosis; Sex Factors; Women's Health

Pharmacologic clinical trials in heart failure (HF) have provided substantial advances in effective treatment of this condition, moving us from our focus on short-term symptom relief to an expectation of substantial improvement in long-term clinical outcomes for our patients. Based on an appreciation of the importance of neurohormonal activation in the pathophysiology of HF, clinical trials have demonstrated the value of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in impeding the progression of HF and in reducing morbidity and mortality for patients with this condition. Clinical trials have further demonstrated the benefits of digoxin in improving symptoms and reducing hospitalization frequency, as well as in aldosterone blockade, at least in patients with severe symptoms. Given the ethical imperative to treat with ACE inhibitors, the angiotensin receptor antagonists have been difficult to study; nevertheless, their value is becoming increasingly clear, particularly for patients intolerant of ACE inhibitors. Trials with several classes of newer agents-cytokine antagonists, endothelin receptor blockers, and vasopeptidase inhibitors-have recently yielded disappointing results. Early results with vasopressin receptor antagonists provide some promise of long-term benefit. Clinical trials have provided significant treatment advances; ongoing and future trials will demonstrate the degree to which we can improve on what we have achieved to date with pharmacologic treatments.

Topics: Adrenergic beta-Antagonists; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antidiuretic Hormone Receptor Antagonists; Cardiotonic Agents; Cardiovascular Agents; Clinical Trials as Topic; Cytokines; Digoxin; Disease Progression; Drugs, Investigational; Endothelin Receptor Antagonists; Heart Failure; Humans; Risk; Survival Analysis; Treatment Failure; Treatment Outcome

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Electrophysiology; Heart Conduction System; Heart Failure; Humans; Neurotransmitter Agents; Randomized Controlled Trials as Topic; Treatment Outcome

The specific binding of digitalis glycosides to the Na,K-ATPase is used as a tool for Na,K-ATPase quantification with high accuracy and precision. In myocardial biopsies from patients with heart failure, total Na,K-ATPase concentration is decreased, and the decrease in Na,K-ATPase concentration correlates with a decrease in heart function. During digitalization, a fraction of remaining pumps are occupied by digoxin. No evidence for an endogenous digitalis-like factor of any clinical importance was obtained. It is recommended that digoxin be administered to heart failure patients who still have dyspnea after institution of mortality-reducing therapy.

Topics: Cardiotonic Agents; Digoxin; Heart; Heart Failure; Humans; Myocardium; Sodium-Potassium-Exchanging ATPase

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Female; Heart Conduction System; Heart Failure; Humans; Male; North America; Ventricular Dysfunction, Left; Women's Health

Digoxin therapy has no effect on mortality in heart failure. Digoxin may be useful for maintaining clinical stability and exercise capacity in patients with symptomatic heart failure. Digoxin appears to be of most benefit in patients with severe heart failure, cardiomegaly and a third heart sound. Digoxin should be used as a second-line drug after diuretics, angiotensin-converting enzyme inhibitors and beta-blockers in patients with congestive heart failure who are in sinus rhythm. Digoxin should be used as a first-line drug in patients with congestive heart failure who are in atrial fibrillation. ARRHYTHMIAS: Digoxin has a limited, but useful, role, either alone or in combination with other agents such as beta-blockers, diltiazem or verapamil, in achieving satisfactory resting ventricular rate control in patients with chronic atrial fibrillation. In patients who lead a predominantly sedentary lifestyle (perhaps particularly in those who are elderly), digoxin alone may be the agent of choice.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans

Congestive heart failure (CHF) is a serious clinical syndrome associated with increased morbidity, mortality, and health-related expenditure. In the United States, the incidence and prevalence of CHF have been shown to increase with age, particularly among the elderly (age >/=65 years). In addition, more elderly persons are living in or will be living in nursing homes. Given these trends, it is important to consider the quality of care, including pharmacologic treatment, received by elderly nursing home residents with a diagnosis of CHE There is currently a lack of clinical trial data on the pharmacologic treatment of CHF among elderly nursing home residents and, therefore, no standard of care. In lieu of clinical trial data, empiric studies based on nursing home populations may be useful.. This article reviews empiric studies concerning the pharmacologic treatment of CHF in elderly nursing home residents.. Empiric studies on the use of angiotensin-converting enzyme (ACE) inhibitors, digoxin, and diuretics in elderly nursing home residents with a diagnosis of CHF were identified through searches of MEDLINE, Cochrane Trials, and International Pharmaceutical Abstracts using the terms elderly, nursing home, geriatric, and heart failure. The search was limited to the past 11 years (1991-2002) to identify current patterns of treatment in the population of interest. Additional studies were identified through a manual search of the reference lists of the retrieved articles.. Thirteen empiric studies were identified: 9 examined ACE-inhibitor use, 4 digoxin use, and 7 diuretic use. The findings of these studies indicated that ACE inhibitors are underused, are often prescribed at clinically inefficient doses, and are used more often in "young" elderly nursing home residents (age 65-74 years). Among patients who received a prescription for digoxin, many did not have an appropriate indication (eg, no documented atrial fibrillation, normal sinus rhythm). Similarly, diuretics were found to be inappropriately prescribed to elderly nursing home residents for the treatment of CHF.. Based on the available empiric studies, elderly nursing home residents with a diagnosis of CHF do not appear to receive adequate treatment with ACE inhibitors, digoxin, or diuretics based on the recommendations of clinical or als or clinical guidelines. However, the clinical trials and clinical guidelines target the general elderly population and thus may not be applicable to elderly nursing home residents. Future research should explore factors influencing the pharmacologic treatment of CHF in elderly nursing home residents, and trials of new pharmacologic treatments for CHF should include elderly nursing home residents.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Drug Utilization; Heart Failure; Humans; Nursing Homes

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Aspirin; Calcium Channel Blockers; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Warfarin

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a frequently prescribed group of highly effective drugs of which the most well-known side effect is gastrointestinal peptic ulcer. However, NSAIDs have additional renal, cardiovascular, hematological, dermatological, and neurological side effects. Although the spectrum of side effects is slightly different between the conventional NSAIDs and the recently developed cyclooxygenase 2 (COX-2) inhibitors, their overall spectrum is quite similar. Aim of this review is to summarize the current knowledge about NSAIDs and their effects on patients with cardio- or cerebrovascular disorders. NSAIDs interact with many drugs which are used in patients with cardio- or cerebrovascular disorders: They attenuate the effects of diuretics, betablockers, ACE inhibitors and AT-2 blockers, thus leading to uncontrolled hypertension or aggravation of heart failure. They increase digoxin levels, potentiate the effect of oral anticoagulants and interact with platelet inhibitors, thus leading to a higher bleeding risk. There are indications that NSAIDs may induce hypertension in normotensives and that COX-2 inhibitors may lead to an increased rate of myocardial infarction and strokes. Based on these data it is recommended that NSAIDs should be avoided in patients with cardio- or cerebrovascular disorders and alternative pharmaceutical, physical or surgical therapy should be applied. If NSAIDs are inevitable, their side effects should be well monitored; they should be prescribed with caution when given in combination with diuretics, betablockers, ACE inhibitors, AT-2 blockers, digitalis, oral anticoagulants and platelet inhibitors. COX- 2 inhibitors should be avoided in patients with known coronary or cerebrovascular disorders. In patients with uncontrolled hypertension or worsening of heart failure, unreported NSAID-use should be considered. Generally, there is a need to develop further analgetic drugs without the described side effects for patients with cardio- and cerebrovascular disorders.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Cerebrovascular Disorders; Digoxin; Diuretics; Drug Interactions; Heart Failure; Humans; Hypertension; Myocardial Infarction; Pain

As patients age, congestive heart failure becomes an increasingly important problem and accounts for up to 20% of hospital admissions for patients over 65 years. With technological improvements in the treatment of coronary artery disease, improved survival after myocardial infarction, and better hypertension therapy, patients are living longer, thus the need for successful management of older patients with chronic heart failure. The elderly, especially minorities, tend to be under-represented in congestive heart failure trials. This article will focus on the care of the geriatric patient with congestive heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Aging; Angiotensin-Converting Enzyme Inhibitors; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Terminal Care

Heart failure is increasing in incidence and prevalence and is predominantly a condition of the elderly, which confers significant morbidity and mortality risks and places an enormous economic burden on the health care system and society. A reduction in hospitalizations and improvement of quality of life are the primary goals in the management of heart failure. Evidence-based medicine provides clinicians with the best armamentarium to provide high quality and cost-effective care to patients diagnosed with this chronic, progressive, and debilitating condition. A multidisciplinary approach to care can be instrumental in the management of these complex patients. Further studies are warranted in elderly patients to provide the evidence for optimal therapies in this frail population.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Drug Interactions; Echocardiography; Heart Failure; Humans; Long-Term Care; Receptors, Angiotensin; Spironolactone

Chronic heart failure is widely recognised as a common and escalating problem that causes major disability and often shortens life. Diuretics and digoxin have formed the mainstay of treatment for many years. Clinical trials have demonstrated that angiotensin converting enzymes and beta-blockers, in selected patients, improve symptoms and reduce mortality. Angiotensin-II antagonists and spironolactone may also have a role in certain individuals. Newer pharmacological approaches to the management of this complex disease are being developed, but await full evaluation.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Spironolactone; Vasodilator Agents

Diastolic heart failure is predominantly a disease of the elderly: at the age of 70 years, almost half of all patients with heart failure have diastolic heart failure. Hypertension and obesity are common underlying disorders in patients with diastolic heart failure. Patients with diastolic heart failure have an equal, or only slightly better, prognosis in terms of mortality compared to patients with systolic heart failure. Echocardiography can distinguish diastolic heart failure from systolic heart failure. Patients with heart failure and a normal ejection fraction almost certainly have a diastolic dysfunction. There is a lack of reliable data about the optimal medicinal treatment strategy for patients with diastolic heart failure. Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and (non-dihydropyridine) calcium antagonists have therapeutic potential. Digoxin may be contraindicated.

Topics: Adrenergic beta-Antagonists; Age Factors; Angiotensin-Converting Enzyme Inhibitors; Diastole; Digoxin; Echocardiography; Heart Failure; Humans; Hypertension; Obesity; Prognosis

Digoxin is an agent with a long history of use in the management of heart failure; its benefits have just been quantified in recent years. It has long been known that digoxin provides a small amount of inotropic augmentation; however, it is now realized that digoxin also modulates the neurohormonal activation that occurs in heart failure. Although long-term therapy with digoxin does not decrease mortality, it does provide clinical benefit in terms of improved exercise tolerance and decreased hospitalizations across all severities of heart failure. Serum concentrations of digoxin associated with clinical benefits are lower than previously recognized (0.8-1.0 ng/mL). Digoxin toxicity can be easily avoided by maintaining these relatively low serum concentrations, avoiding and aggressively treating hypokalemia, and being mindful of poor renal function and drug interactions that may result in digoxin accumulation.

Topics: Cardiotonic Agents; Digoxin; Drug Interactions; Drug Monitoring; Exercise Tolerance; Heart Failure; Hospitalization; Humans; Neurotransmitter Agents; Sodium-Potassium-Exchanging ATPase; Treatment Outcome

Topics: Acute Disease; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Electric Countershock; Heart Failure; Humans; Quinidine; Randomized Controlled Trials as Topic; Sotalol; Sympatholytics; Time Factors; Vasodilator Agents

Foxglove and its constituents therapeutic agent digitalis have been used for centuries for the treatment of heart failure. All digitalis-like cardiotonic steroids enhance heart contraction through a mechanism involving the inhibition of the Na(+),K(+)- ATPase. Recently, Rathore and colleagues reported that sex-based differences may exist in the efficacy of digoxin for the treatment of heart failure. The authors of the study found that female patients exhibited increased risk of death associated with digoxin therapy, whereas male patients appeared to have no increased risk of death related to digoxin therapy. Blaustein and colleagues delve into the report and discuss possible explanations for these findings, suggest alternative ones, and advocate for enrolling greater numbers of women in clinical studies.

Topics: Animals; Clinical Trials as Topic; Digitalis; Digitalis Glycosides; Digoxin; Female; Heart Failure; Hormone Replacement Therapy; Humans; Male; Ouabain; Sex Factors; Sodium-Potassium-Exchanging ATPase

The roles of the renin-angiotensin system and the sympathetic nervous system in the pathogenesis and progression of heart failure are well established. Angiotensin-converting enzyme (ACE) inhibitors and ss-adrenergic-receptor antagonists have been shown to slow down and, in many cases, reverse the process of cardiac remodeling, thus leading to improved cardiac function and clinical outcomes in patients with heart failure. Standard treatment for heart failure consists of a diuretic, an ACE inhibitor (or angiotensin-receptor blocker if the ACE inhibitor is not well tolerated), a ss-blocker, and low-dose digoxin (if needed). Numerous clinical trials have demonstrated reductions in morbidity and mortality with this combination of medications. However, the majority of patients included in these clinical trials had New York Heart Association (NYHA) functional class II or III heart failure. Because few patients with NYHA class IV heart failure have been evaluated in clinical trials, the treatment approach in this patient population is less well defined. The purpose of this article is to review the results of clinical trials with ss-blockers that included patients with severe heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Renin-Angiotensin System; Sympathetic Nervous System

Serum digoxin concentrations (SDC) have been used clinically since the early 1970s. Whereas the therapeutic range for SDC is frequently cited as either 0.8 to 2.0 ng/mL or 0.5 to 2.0 ng/mL, studies over the past decade suggest an upper limit of 1.0 ng/mL for treating heart failure. The same upper limit for SDC is suggested for patients with heart failure and atrial fibrillation with rapid ventricular response. Reducing the upper limit of the therapeutic range to 1.0 ng/mL on computerized and paper laboratory report forms may guide clinicians to avoid unnecessarily high SDC, thus minimizing risk of digoxin toxicity without sacrificing therapeutic benefit for heart failure.

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Evidence-Based Medicine; Forms and Records Control; Heart Failure; Humans; Laboratories; Laboratories, Hospital; United States

Congestive heart failure may be deemed the epidemic of cardiology in the 21st century in the industrialized part of the world. Although new therapies improving morbidity and mortality from chronic heart failure have emerged it is likely that there is a growing role for digoxin. Thus, digoxin treatment is known to control symptoms of congestive heart failure when added to standard therapy. In this setting, we review the prevailing knowledge of the Na,K-ATPase, the cellular receptor for the inotropic action of digitalis glycosides, in relation to the hemodynamic effect of digoxin. It is concluded that if improvement of hemodynamics is needed in congestive heart failure, this knowledge should be taken into account and in many cases digoxin should be added to standard therapy. Digoxin is still the only safe inotropic drug for oral use that improves hemodynamics. Digoxin should be used to heart failure patients in sinus rhythm when they after institution of mortality reducing treatment still have heart failure symptoms, and to patients intolerant to heart failure mortality reducing drugs. Digoxin should probably in heart failure patients with sinus rhythm be given in the lowest possible dose that relieves symptoms sufficiently.

Topics: Aged; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Hemodynamics; Humans; Myocardium; Sodium-Potassium-Exchanging ATPase

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Combined Modality Therapy; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Patient Care Team; Randomized Controlled Trials as Topic; Spironolactone; Survival Rate; Treatment Outcome

Topics: Cardiac Glycosides; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Dobutamine; Heart Failure; Humans; Multicenter Studies as Topic; Odds Ratio; Risk; Severity of Illness Index; Treatment Failure; Treatment Outcome

Over the last two decades the incidence of congestive heart failure (CHF) has increased with aging of the population and in spite of the decline in age-adjusted mortality rates due to coronary heart disease. Its management has seen substantial progress, embodied in the introduction of ACE inhibitors, initially as part of triple therapy in which they complemented diuretics and digoxin, and latterly as first-line therapy. The current consensus on treatment of CHF has been based on the multiple clinical studies performed with ACE inhibitors in which these agents have been shown to prevent a new cardiovascular accident and/or progression to more severe CHF in an increasingly wide range of patients with symptomatic CHF or post-infarction left ventricular dysfunction (ejection fraction

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Diuretics; Drug Therapy, Combination; Evidence-Based Medicine; Heart Failure; Humans; Quality of Life; Vasodilator Agents

Chronic heart failure (CHF) is increasing in prevalence worldwide, particularly in the elderly. Accordingly, this epidemic is likely to translate into a major increase in healthcare costs. Systolic heart failure is the most common cause of CHF presentations. Although the causes vary, the most common single aetiological factor is ischaemic heart disease, which accounts for approximately 50% of heart failure presentations. Research into CHF pharmacotherapy has been copious, with the focus principally centred on systolic heart failure. The evidence base for pharmacotherapy in CHF is amongst the largest currently in clinical medicine. There have been multiple trials establishing the mortality and morbidity benefits of pharmacotherapy. Amongst these, large scale trials of angiotensin-converting enzyme inhibitors, beta-blockers and spironolactone have provided a sound basis for evidence-based treatment approaches to the CHF patient. Recently research interest has increased in biomedical engineering with studies being performed in biventricular pacing and mechanical hearts. Early data with biventricular pacing or cardiac resynchronisation therapy is encouraging. Diastolic heart failure alone accounts for at least 20 - 40% of CHF presentations and whilst it may occur in isolation, is most commonly seen in association with systolic heart failure. In this study, we present a broad overview of the current therapeutic modalities for the management of CHF, with particular emphasis on pharmacotherapy.

Topics: Adrenergic beta-Antagonists; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Pacemaker, Artificial; Spironolactone; Vasodilator Agents

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Combined Modality Therapy; Defibrillators, Implantable; Digoxin; Exercise; Heart Failure; Humans; Spironolactone

Congestive heart failure (CHF) due to progressive systolic dysfunction has become a modern-day epidemic. Despite the increased incidence and prevalence, significant progress has been made in the past 10 to 15 years in the treatment of CHF at all stages. The current outlook for patients with newly diagnosed, mild heart failure is encouraging. It should be noted, however, that most of the morbidity and health care expenditure is incurred by a minority of patients diagnosed with CHF who are in the advanced stages of their disease. The thrust of this article will be to provide practical advice beyond current guidelines on the management of advanced CHF.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Hemofiltration; Humans; Hypolipidemic Agents; Infusions, Intravenous; Monitoring, Physiologic; Referral and Consultation; Self Care

The management of chronic heart failure in elderly patients is often complicated by the presence of multiple comorbid conditions, polypharmacy, psychosocial and financial concerns, and difficulties with adherence to complex medication and dietary regimens. In addition, few patients over 80 years of age have been enrolled in clinical trials, so that the efficacy of current heart failure therapies remains uncertain in this age group. Taken together, these factors contribute to the persistently high hospitalization and mortality rates as well as the poor quality of life associated with chronic heart failure in the elderly. In this article, nonpharmacologic aspects of care and the pharmacotherapy of systolic heart failure in elderly patients are reviewed. Optimal management requires a systematic approach comprising 5 key elements: coordination of care across disciplines, patient and caregiver education, enhancement of self-management skills, effective followup, and the judicious use of medications. However, it must be recognized that even with "best practice" interventions, the prognosis for established heart failure remains poor. Future research must therefore be directed at developing more effective strategies for the prevention of heart failure in our aging population.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Patient Education as Topic; Self Care

Heart failure is a major and increasing cause of death and disability and accounts for significant resource use. In the United States alone, the prevalence is 4.6 million, with an incidence rate of 550,000 new cases a year and approximately 957,000 hospitalizations a year.. Methods of evaluating cost and outcome and of comparing cost with outcome are reviewed. Economic and cost-effectiveness studies in heart failure research, especially those related to clinical trials, are reviewed in the therapeutic areas of digoxin, angiotension-converting enzyme inhibition, beta blockers, disease management, and transplantation.. In an era in which economic constraints on medical resource use limit the ability to give all services to all patients, economic studies can help guide more rational decision making. Economic studies in heart failure can be expected to improve and so help society to make better, more informed choices.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cost-Benefit Analysis; Costs and Cost Analysis; Decision Trees; Digoxin; Heart Failure; Humans; Outcome Assessment, Health Care; Quality-Adjusted Life Years

Finding the optimal combination of drugs in the correct dosages, which requires careful monitoring over time, is key to slowing the disease process and prolonging life. For most patients, treating heart failure involves correcting underlying left ventricular dysfunction, thereby slowing the remodeling process.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Digoxin; Disease Progression; Diuretics; Drug Evaluation; Drug Therapy, Combination; Heart Failure; Humans

Mortality outcomes in clinical trials have become the foundation for the evidence-based management of patients with systolic heart failure. This review was intended to give the clinician a better understanding of newer pharmacological strategies in this patient population.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone; Survival Analysis

Underlying causes and precipitating causes of congestive heart failure (CHF) should be treated when possible. Older persons with CHF and normal left ventricular (LV) ejection fraction should have maintenance of sinus rhythm, treatment of hypertension and myocardial ischemia, slowing of the ventricular rate below 90 beats/minute, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers as tolerated. Angiotensin-converting enzyme (ACE) inhibitors should be administered if CHF persists despite diuretics and beta blockers. If persons are unable to tolerate ACE inhibitors because of cough, rash, or altered taste sensation, angiotensin II type 1 receptor antagonists should be given. If CHF persists despite diuretics, beta blockers, and ACE inhibitors or the person is unable to tolerate beta blockers, ACE inhibitors, and angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine should be administered. Calcium channel blockers should be used if CHF persists despite administration of diuretics and the person is unable to tolerate beta blockers, ACE inhibitors, angiotensin II type 1 receptor antagonists, and isosorbide dinitrate plus hydralazine. Digoxin, beta blockers, verapamil, and diltiazem may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with CHF in sinus rhythm with normal LV ejection fraction.

Topics: Adrenergic beta-Antagonists; Aged; Aging; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Clinical Trials as Topic; Diagnosis, Differential; Diastole; Digoxin; Diuretics; Female; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Prevalence; Prognosis; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Stroke Volume; Ventricular Dysfunction, Left

Recommendations for the treatment of heart failure were carried out by a systematic review of the available evidence of the different pharmacologic treatments.. The review focused on the treatment of chronic and systolic heart failure. All the studies published in english about the pharmacologic treatment of heart failure where identified. The evidence of every pharmacologic treatment was classified according to: a) efficacy variables (reduction of mortality and hospitalizations, improvement of functional class, ejection fraction and exercise tolerance), and b) the level of quality of the evidence according to an evaluation scale. The evidence was also reviewed for the comparisons and the combinations of the pharmacologic treatments, as well as for the toxicity and costs of treatments.. The recommendations were defined according to the NYHA functional class and were classified in the A, B and C categories according to the level of quality of the available evidence. The evidence on mortality was considered the most important. First line drugs, the alternatives and other possible treatments were take into account.. There is enough evidence based on information about some variables such as reduction of mortality or hospitalizations to carry out treatment recommendations in all stages of heart failure. This point out the interest ant the priority of used them in the evaluation and improvement of the results of heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Calcium Channel Blockers; Cardiotonic Agents; Cost-Benefit Analysis; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure; Humans; Spironolactone; Vasodilator Agents

Topics: Amiodarone; Anti-Arrhythmia Agents; Clinical Trials as Topic; Death, Sudden; Digoxin; Evidence-Based Medicine; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Peptidyl-Dipeptidase A; Ventricular Dysfunction, Left

Treatment strategies for chronic heart failure in children have generally been extrapolated from studies in adults with heart failure. This presentation reviews the existing knowledge and recommendations regarding the treatment of chronic heart failure in adults and the information that is available in children. Medications currently recommended for use in adults include diuretics, digoxin, angiotensin-converting enzyme inhibitors, and beta-blockers. These recommendations are based on results from large, randomized, multicenter trials. Anecdotal evidence suggests similar beneficial effects of these medications in children. The fact that the etiologies, pathophysiology, and physiologic consequences of heart failure in children often differ greatly from those in adults, however, justifies the development of prospective, randomized trials to evaluate these medications specifically in children. Findings from these types of studies will provide critical information for developing guidelines for the appropriate treatment of children with chronic heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Child; Chronic Disease; Digoxin; Diuretics; Heart Failure; Humans

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Age Factors; Angiotensin-Converting Enzyme Inhibitors; Child; Child, Preschool; Clinical Trials as Topic; Digoxin; Diuretics; Ethics, Medical; Female; Heart Defects, Congenital; Heart Failure; Humans; Infant; Male; Patient Selection; Pediatrics

Endoxin is a factor with a digitalis-like biological activity. It is a Na+ pump inhibitor and may be an endogenous medium of digitalis receptor. There are abnormal plasma levels of endoxin in some pathophysiologic states such as hypertension, acute myocardial infarction, arrhythmia, heart failure, etc. Some studies have demonstrated that the abnormal endoxin levels may be implicated in pathogenesis of these diseases or pathophysiologic process involved. Therefore, to clarify the effects of endoxin has much significance in understanding pathogenesis, prevention and treatment of hypertension and other cardiovascular diseases.

Topics: Animals; Cardenolides; Cardiomegaly; Cardiovascular System; Diabetes Mellitus; Digoxin; Enzyme Inhibitors; Heart Diseases; Heart Failure; Humans; Hypertension; Myocardial Infarction; Pulmonary Heart Disease; Saponins; Sodium-Potassium-Exchanging ATPase

Ischaemic heart disease is probably the most important cause of heart failure. All patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with heart failure due to ischaemic heart disease may also, theoretically, benefit from treatments designed to relieve ischaemia and prevent coronary occlusion and from revascularisation. However, there is little evidence to show that effective treatments, such as angiotensin converting enzyme (ACE) inhibitors and beta-blockers, exert different effects in patients with heart failure with or without coronary disease. Moreover, there is no evidence that treatment directed specifically at myocardial ischaemia, whether or not symptomatic, or coronary disease alters outcome in patients with heart failure. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion appear ineffective or harmful in patients with heart failure. There is no evidence, yet, that revascularisation improves prognosis in patients with heart failure, even in patients who are demonstrated to have extensive myocardial hibernation. On current evidence, revascularisation should be reserved for the relief of angina. Large-scale, randomised controlled trials are currently underway investigating the role of specific treatments targeted at coronary syndromes in patients who have heart failure. The CHRISTMAS study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The WATCH study is comparing the efficacy of aspirin, clopidogrel and warfarin. The HEART-UK study is assessing the effect of revascularisation on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are currently assessing the safety and efficacy of statin therapy in patients with heart failure. Only when the results of these and other studies are known will it be possible to come to firm conclusions about whether patients with heart failure and coronary disease should be treated differently from other patients with heart failure due to left ventricular systolic dysfunction.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Hypolipidemic Agents; Myocardial Ischemia; Myocardial Revascularization; Nitrates; Patient Selection; Smoking Cessation; Spironolactone; Thrombolytic Therapy

To systematically review the management of atrial fibrillation (AF) in patients with heart failure.. Studies investigating the management of AF in patients with heart failure published between 1967 to 1998 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers.. Eight studies pertaining to acute and twenty-four pertaining to chronic AF were identified. For patients with acute AF ventricular rate control, anticoagulation and treatment of heart failure should be pursued simultaneously before cardioversion is attempted. Digoxin is relatively ineffective at controlling ventricular response and for cardioversion. Intravenous diltiazem is rapidly effective in controlling ventricular rate and limited evidence suggests it is safe. Amiodarone controls ventricular rate rapidly and increases the rate of cardioversion. There are insufficient data to conclude that immediate anti-coagulation, trans-oesophageal echocardiography to exclude atrial thrombi followed by immediate cardioversion is an appropriate strategy. Patients with chronic AF should be anti-coagulated unless contra-indications exist. It is not clear whether the preferred strategy should be cardioversion and maintenance of sinus rhythm with amiodarone or ventricular rate control of AF combined with anticoagulation to improve outcome including symptoms, morbidity and survival. Electrical cardioversion has a high initial success rate but there is also a high risk of early relapse. Amiodarone currently appears the most effective and safest therapy for maintaining sinus rhythm post-cardioversion. Digoxin is fairly ineffective at controlling ventricular rate during exercise. Addition of a beta-blocker reduces ventricular rate and improves symptoms. Whether digoxin is required in addition to beta-blockade for the control of AF in this setting is currently under investigation. If pharmacological therapy is ineffective or not tolerated then atrio-ventricular node ablation and permanent pacemaker implantation should be considered.. There is a paucity of controlled clinical trial data for the management of AF among patients with heart failure. The interaction between AF and heart failure means that neither can be treated optimally without treating both. Presently treatment should be on a case by case basis.

Topics: Acute Disease; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Diltiazem; Electric Countershock; Heart Failure; Humans; Retrospective Studies

Heart failure is becoming the most prevalent cardiovascular disorder in the older population, in part as a consequence of the declining fatality rate of hypertension, myocardial infarction and ictus, resulting in progressive increment of older subjects at increased risk of developing heart failure. In this review the principal aspects of congestive heart failure in the elderly are described, underlining the necessity of distinguish the "normal" ageing process from the many noxae that cause this disease. Moreover a discussion is given about the peculiarity of the physiopathology and symptomatology of heart failure in the aged patients, with particular emphasis to the diastolic ventricular dysfunction that is very frequent in these patients, posing complex problems of diagnosis and therapy.

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Calcium Channel Blockers; Cardiotonic Agents; Clinical Trials as Topic; Diastole; Digoxin; Diuretics; Drug Interactions; Echocardiography; Electrocardiography; Fibrinolytic Agents; Heart Failure; Humans; Platelet Aggregation Inhibitors; Radiography, Thoracic; Systole; Ventricular Dysfunction

Congestive heart failure is a progressive disease with significant morbidity and mortality. Despite advances in the prevention and treatment of cardiovascular diseases, the incidence and prevalence of congestive heart failure have increased in recent years. Contributing factors include increased survival in patients with coronary artery disease (especially myocardial infarction), an aging population and significant advances in the control of other potentially lethal diseases. New and existing agents, including angiotensin-converting enzyme inhibitors, beta blockers and, more recently, spironolactone, are being used increasingly to prolong life in patients with heart failure. Although digoxin has been used to treat heart failure for more than 200 years, its role in patients with congestive heart failure and sinus rhythm is still debatable. Over the past decade, digoxin has received renewed attention because of recognition of its neurohormonal effect and the successful use of lower dosages. In recent trials, digoxin has been shown to reduce morbidity associated with congestive heart failure but to have no demonstrable effect on survival. The goal of digoxin therapy in patients with congestive heart failure is to improve quality of life by reducing symptoms and preventing hospitalizations.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Drug Interactions; Drug Therapy, Combination; Heart Failure; Humans; Multicenter Studies as Topic; Ventricular Dysfunction, Left; Ventricular Function, Left

Although medical therapy, particularly with angiotensin-converting enzyme (ACE) inhibitors, has been demonstrated to prolong life in patients with chronic heart failure, the effect of standard medical therapy on sudden unexpected death in patients with heart failure is less well understood. Recent clinical trials have provided new insights into this growing problem. The impact of modern medical therapy for heart failure, including ACE inhibitors, beta-adrenergic antagonists, digoxin, calcium channel antagonists, and antiarrhythmic interventions will be discussed.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Cardiotonic Agents; Death, Sudden, Cardiac; Digoxin; Female; Heart Failure; Humans; Male; Randomized Controlled Trials as Topic

Topics: Animals; Cardiotonic Agents; Cat Diseases; Cats; Digoxin; Dog Diseases; Dogs; Heart Failure; Humans

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Prognosis

The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. beta-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents--all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Digoxin; Diuretics; Forecasting; Heart Failure; Humans

Congestive heart failure (CHF) is a disease with high mortality rates and increasing prevalence in the United States. As our understanding of the pathophysiologic characteristics of this disease has progressed, so has our pharmacologic approach to treatment. Digoxin was the first documented drug used in the treatment of CHF, and since that time, the efficacy of its use has been the source of great controversy. A more recent treatment option is the use of angiotensin-converting enzyme (ACE) inhibitors, the first drug class shown to increase survival rates in CHF. Although controversy remains, ACE inhibitors appear to be gaining favor over digoxin in the pharmacologic approach to treatment. This article provides a pathophysiologic review of CHF as it is understood today, the rationale behind the use of digoxin and ACE inhibitors, and a challenge for the future in the pharmacotherapy of CHF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Disease Progression; Forecasting; Heart Failure; Hemodynamics; Humans; Patient Selection; Prevalence; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Cardiotonic Agents; Diagnosis, Differential; Digoxin; Diuretics; Heart Failure; Humans; Prognosis; Risk Factors; Vasodilator Agents

Cardiovascular disease is ubiquitous within the elderly population and requires treatment with multiple types of medications. As with any cardiovascular pharmaceutical regimen, the risk versus the benefit of each medication must be strongly considered. This is particularly true where, for various reasons, adverse effects are more often prevalent and pronounced. Over the years, it has been documented that digoxin is a frequently prescribed medication in elderly populations. Although this drug can be beneficial when used in the appropriate setting, recent data would suggest that inappropriate administration of digoxin is common and not without potentially serious consequences. Currently, the use of digoxin can be advocated to control heart failure in atrial fibrillation and when added to ACE inhibitors and diuretics in those patients with symptomatic heart failure related to systolic left ventricular dysfunction. It is likely that the excessive use of digoxin in elderly populations as discussed in this review is perhaps based on the prevalence of diastolic heart failure in the elderly as well as other co-morbid conditions that may mimic heart failure signs and symptoms. Since the elderly appear to be at high risk for digoxin toxicity, the inappropriate use of this medication to treat these conditions could result in significant and unnecessary morbidity. It is proposed that echocardiography should be performed in most elderly patients when congestive heart failure is suspected. This simple diagnostic tool, along with a careful history and medical examination, would hopefully prevent the misinterpretation of confusing clinical findings and would help to identify the patients with normal systolic function or valvular disease such as critical aortic stenosis, where digoxin treatment would not be warranted. If it is necessary to administer digoxin, then the likelihood of significant toxicity can be greatly reduced by using an algorithm to calculate the appropriate dosage, which takes into consideration the patient's gender, bodyweight and creatinine clearance. Although it is probable that the indications for digoxin use to treat congestive heart failure will continue to evolve, at the present time most would recommend using this agent in symptomatic heart failure related to a reduction in left ventricular systolic function or when associated with atrial fibrillation.

Topics: Aged; Cardiotonic Agents; Contraindications; Digoxin; Drug Utilization; Geriatric Assessment; Heart Failure; Humans; Randomized Controlled Trials as Topic

Heart failure is a major and still growing medical and epidemiological problem, but in the last 10-20 years great progress has been made in its treatment. Alleviating symptoms is not (any longer) the only aim of the treatment; improving the life expectation or reducing the mortality has become a different, at least as important aim. Left ventricular dysfunction, even if asymptomatic, should be regarded, just as hypertension and hypercholesterolaemia, as a risk factor for which efficacious treatment is available and which consequently should be treated. A problem in this respect is that the effect of treatment of asymptomatic left ventricular dysfunction and of mild forms of heart failure is difficult to measure. Beta-blocking agents have proved to be the greatest gain in the treatment of heart failure in recent years, in addition to ACE inhibitors, diuretics and digoxin. These preparations should be prescribed with caution and due consideration. However, their favourable influence is such that use on a much larger scale than currently appears to be justified.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Heart Failure; Humans; Netherlands; Practice Guidelines as Topic; Prognosis; Risk Factors; Survival Rate; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Digoxin; Diuretics; Heart Failure; Humans; Middle Aged; Myocardial Infarction; Prognosis

Over the past 200 years, digoxin has been commonly used to treat patients with congestive heart failure. Clinical trials have demonstrated the benefits of the use of digoxin on exercise tolerance, ejection fraction, and neurohormone production. The Digoxin Investigators Group trial has recently provided strong evidence for the long-term benefits of digoxin on morbidity for patients with heart failure. This article will review the evidence of the benefits of digoxin and its current role in the treatment of patients with congestive heart failure.

Topics: Cardiotonic Agents; Digitalis; Digoxin; Exercise Tolerance; Heart Failure; Humans; Myocardial Contraction; Plants, Medicinal; Plants, Toxic; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome

Since its introduction in 1785, digitalis has been the cornerstone in the treatment of heart failure, although there during the last 20 years have been an increasing number of critical voices questioning its use in patients with sinus rhythm. In 1997 the Digitalis Investigation Group published the so far largest randomized trial on the use of digoxin in patients with heart failure (DIG-trial). All the included patients had sinus rhythm, and all received an ACE-inhibitor. Digoxin had no effect on mortality, but caused a decrease in hospitalizations. Based on the DIG-study, several minor clinical trials and two large withdrawal studies (RADIANCE and PROVED) it now seems clear that digoxin still has a role in the management of heart failure, not only in patients with atrial fibrillation, but also in patients with sinus rhythm.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Cardiotonic Agents; Controlled Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Randomized Controlled Trials as Topic

Clinical studies have solidified the utility of digoxin in patients with left ventricular dysfunction and normal sinus rhythm. No definitive data have been published to clarify the range of serum digoxin concentrations associated with clinical benefit. The traditional therapeutic range of 0.8-2.0 ng/ml was developed originally to classify digoxin toxicity, not efficacy. In addition, this reference range was used before publication of the Digitalis Investigators Group trial. Clinical and neurohormonal studies have attempted to characterize serum concentrations that are associated with clinical efficacy.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Hemodynamics; Hormones; Humans; Nervous System

Digoxin, which has a very narrow therapeutic window, is one of the most commonly prescribed drugs in the treatment of congestive heart failure. In some cases of atrial fibrillation digoxin is used in combination with verapamil. Verapamil can increase the plasma concentration of digoxin up to 60-90%. So far the precise mechanism of this pharmacokinetic drug-drug interaction is not known. Many studies suggest that verapamil reduces the renal clearance of digoxin. The energy-dependent membrane-bound transport enzyme, P-glycoprotein, may also be involved. Reports from oncology research show that verapamil can interact with P-glycoprotein as a modulator. Also taking into account that digoxin, like many anticancer drugs, is a substrate for P-glycoprotein, it is likely that P-glycoprotein modulation accounts for the digoxin-verapamil interaction. Current knowledge suggest that the non-competitive digoxin-verapamil interaction is due to inhibition of P-glycoprotein activity by verapamil resulting in a decreased renal tubular elimination of digoxin.

Topics: Animals; Anti-Arrhythmia Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiotonic Agents; Digoxin; Drug Interactions; Drug Resistance, Multiple; Heart Failure; Humans; Verapamil

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Digitalis; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Plants, Medicinal; Plants, Toxic; Randomized Controlled Trials as Topic; Time Factors

Combination therapy with a diuretic, digoxin, ACE inhibitor, and beta-blocker can help patients with heart failure caused by severe systolic dysfunction feel better and live longer. Especially with ACE inhibitors and beta-blockers, the key to success is starting at low doses and titrating carefully to proven target doses. The demanding complexity of the four-drug regimen is well worth the results.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Disease Progression; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Prognosis; Quality of Life; Survival Rate

Neurohumoral activation refers to increased activity of the sympathetic nervous system, renin-angiotensin system, vasopressin and atrial natriuretic peptide. It is now known that neurohumoral activation contributes to the transition from ventricular dysfunction to clinical heart failure, and is an independent predictor of poor prognosis in heart failure. Although the treatment of heart failure has traditionally focused on drugs to improve ventricular function, there is increasing evidence that therapeutic modulation of neurohumoral activation is a key to successful treatment of heart failure. For example, there is mounting evidence that angiotensin converting enzyme inhibitors (the unquestioned cornerstone for treatment of heart failure), beta receptor blockers, digitalis, and endurance exercise training exert their benefit in heart failure in large part through neurohumoral modulation. This observation--discussed in this brief review--highlights the concept that compensatory neurohumoral activation to decreased cardiac function may itself contribute to the development of heart failure and its poor prognosis.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Digoxin; Exercise Therapy; Heart Failure; Humans; Myocardial Infarction; Neurotransmitter Agents; Sympathetic Nervous System; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Vasodilator Agents

The use of digitalis in congestive heart failure with normal sinus rhythm is still debated. While older uncontrolled, withdrawal studies from 1969 to 1983 provided incomplete data, with poorly documented clinical status and poor haemodynamic and exercise data, some patients did improve clinically when digitalis treatment was utilised. Randomised, double-blind, placebo-controlled trials from 1977 to 1991 were of better quality but still short in duration, with small sample sizes and still with incomplete haemodynamic and exercise data. In 1993, the Prospective Randomised Study of Ventricular Failure and Efficacy of Digoxin (PROVED) and Randomised Assessment of Digoxin on Inhibitors of the Angiotensin-Converting Enzyme (RADIANCE) study, followed in 1997 by the Digitalis Investigation Group (DIG) trial, documented that digoxin prevents clinical deterioration and hospitalisations, and improves exercise tolerance and left ventricular function, but has no effect on survival. A substudy of the DIG trial showed no detrimental effect of digoxin on survival in patients with ejection fraction (EF) of > 45%, i.e. left ventricular (LV) diastolic dysfunction. Therefore, digoxin appears to be the first inotrope with no detrimental effect on survival in heart failure. In addition, the neurohormonal effect of digoxin has been documented, and is possibly present with dosages even lower than 0.25 mg. Finally, it has been determined that patients with only mild heart failure do obtain documented benefit from administration of this drug.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Heart Failure; Hemodynamics; Humans; Multicenter Studies as Topic; Myocardial Contraction; Randomized Controlled Trials as Topic

Topics: Anti-Arrhythmia Agents; Digoxin; Heart Failure; Humans; Sodium-Potassium-Exchanging ATPase; Sympathetic Nervous System

To review therapies for treating patients with heart failure (HF).. Recommendations in this paper are mainly based on the results of randomized controlled trials. To a lesser extent, data from smaller, more physiologic studies are included. Where appropriate, recommendations are based on the results of a consensus conference.. Although pharmacologic therapy is the main strategy for treating HF patients, general measures, such as counseling and advice about regular physical activity, are an important component of management. Use of angiotensin-converting enzyme inhibitors (ACE-I) is central to treating HF patients, because these agents decrease mortality and morbidity significantly. Digoxin does not reduce mortality but does reduce morbidity. Angiotensin II antagonists, although found to provide clinical benefit equal to ACE-I, have not been found as yet to have similar effects on mortality and morbidity. Diuretics and nitrates are useful for treating these patients' symptoms. Calcium channel blockers should generally be avoided.. Angiotensin-converting enzyme inhibitors are the therapy of choice for HF patients and should be used in all cases unless there are contraindications or clear evidence of intolerance. All other therapies are used mainly for symptom relief.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Controlled Clinical Trials as Topic; Digoxin; Diuretics; Exercise; Heart Failure; Humans; Outpatients; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Vasodilator Agents

The recently reported Digitalis Investigation Group (DIG) study has shown that digoxin has no demonstrable effect on survival in heart failure, but may be useful to ameliorate morbidity. The question may be raised whether digoxin is useful for symptomatic improvement in patients with mild or moderate heart failure. A major difficulty in answering this question is the lack of appropriate clinical measures of heart failure that allow a categorization such as mild, moderate and severe heart failure. However, data in several clinical trials permit an approach to this issue in an approximate way. For instance, the DIG study itself indicated that the beneficial clinical effect of digoxin was also apparent in pre-defined subgroups which corresponded to less severe forms of heart failure. The problem with the DIG study in this respect was the lack of direct measures of clinical improvement and the use of what might be taken as surrogates for these; however, it can probably be assumed that digoxin had a beneficial symptomatic effect even in patients with milder forms of heart failure. Direct clinical measures of clinical result were used in the Randomized Assessment of the effect of Digoxin on Inhibitors of ACE Study and the Prospective Randomized Study on Ventricular Failure and the Efficacy of Digoxin. Some inconsistencies between the clinical results of these trials may be explained partly on the basis of sample size, although on the whole the results point to a definite clinical improvement of patients on digoxin therapy, even when heart failure was considered to be mild on the basis of several measurements. Admittedly, the size of the effect of digoxin therapy in these patients may be quite modest. Although some concerns over safety may remain after the DIG trial, it can generally be accepted that digoxin is an effective drug for symptomatic improvement in patients with mild or moderate heart failure. The small size of this effect, however, indicates that the decision to use the drug may well be left to the discretion of the attending physician.

Topics: Clinical Trials as Topic; Digoxin; Heart Failure; Hospitalization; Humans; Quality of Life

The goals of therapy for congestive heart failure (CHF) are to improve quality of life and to prolong it. Improvement in patients with CHF can only be realized, however, if a multidisciplinary healthcare team can provide effective management in both the inpatient and outpatient settings. Inhibition of compensatory mechanisms that perpetuate CHF is the first step in achieving treatment goals. Combination therapy with diuretics, digoxin (Lanoxicaps, Lanoxin), and vasodilators is used for patients with symptomatic heart failure and volume overload. Because angiotensin-converting enzyme inhibitors improve survival rates more than other vasodilators, they are preferred in patients with systolic dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Diuretics; Drug Resistance; Heart Failure; Humans

Improvement of symptoms, increase in exercise capacity and prevention of disease progression are the aims of drug therapy in patients with congestive heart failure. At present only the ACE inhibitors are able to achieve all therapeutic targets and should therefore be regarded as drugs of first choice in systolic dysfunction. Diuretics are also necessary in most patients since they rapidly reduce pulmonary congestion and peripheral oedema, but have no documented beneficial long term effects on the course of CHF. Digoxin remains a useful drug to treat symptomatic patients who do not respond adequately to the combination of ACE inhibitors and diuretics, as well as in patients with atrial fibrillation. However, a reduction of mortality by digitalis glycosides cannot be expected. A new trend in the treatment of CHF is the utilisation of beta blockers. These drugs showed positive effects in chronic CHF in several studies, particularly in patients with dilated cardiomyopathy. Newer drugs such as carvedilol, seem to improve the symptoms and reduce complications even in CHF due to coronary artery disease. The role of beta blockers in the routine management of patients with heart failure requires further evaluation.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Prognosis; Systole

It has for years been a matter of debate whether digoxin may/should be used in chronic heart failure with sinus rhythm. Interest in digoxin was renewed when it was found that the substance had a vagotonic as well as a sympatholytic effect in heart failure patients. A recent clinical trial led to the conclusion that although digoxin had no effect on the mortality among heart failure patients, it did lead to a reduction of the number of hospital admissions, particularly because of heart failure (indicating reduced morbidity and deceleration of the progression of the disease). Many heart failure patients continue to have symptoms in spite of treatment with diuretics and ACE inhibitors. As only few alternatives are available, many physicians in the near future will go on using digoxin in these patients- and as the recent study shows, rightly so.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

Even at rest, blood pressure and heart fluctuate continuously around their mean values. Considerable interest has recently focused on the assessment of spontaneous in fluctuations in heart rate and blood pressure, i.e., heart rate and blood pressure variability, using time or frequency domain indexes. Heart rate variability has been extensively studied in cardiovascular disease and has emerged as a valuable parameter for detecting abnormalities in autonomic cardiovascular control, evaluating the prognosis and assessing the impact of drug therapy on the autonomic nervous system in patients with myocardial infarction, congestive heart failure or a heart transplant. In contrast, until the recent development of noninvasive methods for continuous blood pressure recording, blood pressure variability received little attention, and this parameter remains to be evaluated in cardiovascular disease.

Topics: Adrenergic beta-Antagonists; Animals; Autonomic Nervous System; Blood Pressure; Cardiotonic Agents; Digoxin; Dogs; Heart Failure; Heart Rate; Heart Transplantation; Humans; Myocardial Infarction; Signal Processing, Computer-Assisted; Vagus Nerve

Digitalis has been widely used in the treatment of cardiac disease for more than 200 years. The present article reviews the current role of digitalis in the management of heart failure and atrial fibrillation (AF) in light of recent study findings. Generally, first-line therapy for the management of heart failure due to systolic dysfunction should include an ACE inhibitor and a diuretic. In patients who remain symptomatic despite the use of these drugs, the addition of digoxin should be considered. Because digoxin has been shown to reduce the number of hospital admissions attributable to worsening heart failure, more liberal use of digoxin in the management of heart failure may be justified. Digoxin may be adequate as monotherapy for ventricular rate control in patients with chronic AF, particularly in sedentary and elderly patients. A beta-blocker or calcium antagonist (either alone or in combination with digoxin) is indicated when digoxin is ineffective for ventricular rate control. Digoxin is ineffective in restoring sinus rhythm, preventing paroxysms or controlling rate in paroxysmal AF. The elderly are at an increased risk of digoxin toxicity. Low dosages of digoxin appear to be effective in the treatment of heart failure due to systolic dysfunction and may reduce the incidence of digitalis toxicity in these patients. In elderly patients with AF and inadequate rate control who are receiving digitalis monotherapy, adding another atrioventricular nodal blocking drug may be more appropriate than increasing the digoxin dose, in order to avoid toxic digoxin levels.

Topics: Aged; Aging; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Dosage Forms; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Heart Failure; Heart Rate; Humans; Myocardial Contraction; Randomized Controlled Trials as Topic

Despite advances in medical treatment, the annual mortality associated with severe heart failure remains over 40%, and even in mild heart failure the associated mortality is 40% over 4 years. Once it has been demonstrated that the morbidity and mortality to heart failure can be adequately addressed by combinations of drug therapy, then it is logical to attempt to strip out redundant components of these therapeutic regimes. In the meantime, however, combination therapy is required to counter many of the pathophysiological facets of the heart failure syndrome, including fluid retention, neuroendocrine activation, progressive ventricular dysfunction, and sudden cardiac death. Diuretics and ACE inhibitors are well-established drug treatments. Digoxin appears to lessen the rate of progression of heart failure without altering survival. New evidence suggests that beta-blockers may be useful additions to the heart failure therapeutic armamentarium, although whether all beta-blockers are equally effective remains to be established.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Carbazoles; Carvedilol; Chronic Disease; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Propanolamines; Vasodilator Agents

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic

The benefit of digoxin in chronic heart failure has been debated fervently for decades. In the 1970s, the use of digoxin was challenged due to the high incidences of digitalis toxicity and the lack of data on the effects of digoxin in patients with chronic heart failure. In the 1980s, interest in digoxin was renewed after several trials with oral inotropic agents demonstrated increased mortality. Recently, several trials have studied the hemodynamic, neurohormonal, and clinical effects of digoxin, providing further insights into the possible mechanisms for its beneficial effects in patients with chronic heart failure. In an effort to find new pharmacologic therapies for the treatment of this patient population, studies of newer oral inotropic agents such as vesnarinone, pimobendan, and ibopamine have been disappointing. This paper reviews data published or presented in 1995 and 1996 examining the effects of digoxin and other oral inotropic agents in patients with chronic heart failure.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Heart Failure; Hemodynamics; Humans; Survival Rate

Over 400,000 people in the United States are diagnosed with congestive heart failure (CHF) annually. The 3 major causes of acute cardiac hospitalizations in the United States--CHF, unstable angina, and acute myocardial infarction--all reflect a failure to prevent progression of established cardiovascular disease. More effective treatment strategies for CHF should be directed at preventing rehospitalization through modification of cardiac risk factors. Several large clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors, while considered preferred therapy, are routinely underutilized by all healthcare practitioners. Digoxin has also been shown in several clinical trials to reduce the need for rehospitalization in CHF patients. Finally, patients' quality of life and the morbidity associated with CHF can be reduced through well-structured disease management programs in conjunction with ACE inhibitor and digoxin therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Disease Progression; Heart Failure; Hospitalization; Humans; Survival Analysis; United States

Sudden cardiac death (SCD) may occur in as many as 40% of all patients who suffer from heart failure. This review describes the scope of the problem, risk factors for SCD, the effect of medications used in heart failure on SCD and the potential effect of the implantable cardioverter-defibrillator in primary prevention.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Calcium Channel Blockers; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Diuretics; Heart Failure; Humans; Risk Factors

It is 10 years since the CONSENSUS I study showed that ACE inhibitors improved mortality in heart failure. This finding has been confirmed in numerous trials, for example SOLVD, SAVE. Indeed, in the intervening 10 years, many other potential therapies have been examined in mortality trials, but so far no other therapy has had as good effect on mortality as ACE inhibitors. The other therapies which have been examined are digoxin, amlodipine, beta-blockers, amiodarone, etc. Despite ACE inhibitors being a very effective therapy for heart failure, there is still remarkable under-use of them in clinical practice. The reason for this needs to be explained further, but fear of hypothermia and renal dysfunction appear to be major factors.

Topics: Adrenergic beta-Antagonists; Amiodarone; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Blood Pressure; Clinical Trials as Topic; Digoxin; Diuretics; Heart Failure; Humans; Hydralazine; Treatment Outcome; Vasodilator Agents

Short-term goals of heart failure management are directed toward relieving symptoms such as shortness of breath, decreased exercise tolerance, and lower-extremity edema and improving functional capacity and quality of life. Long-term goals include decreasing mortality and slowing or reversing the underlying cardiac structural abnormalities of heart failure. Improvement in symptomatic endpoints (e.g., exercise tolerance) does not necessarily correlate with endpoints for improved survival (e.g., left ventricular ejection fraction). It is therefore important to evaluate the effects of drugs on these distinct endpoints separately. Symptoms of heart failure are commonly managed with the use of diuretics, vasodilators, and positive inotropes or digoxin. Ideally, therapy should consist of a diuretic plus vasodilator (e.g., angiotensin-converting enzyme [ACE] inhibitor or isosorbide dinitrate plus hydralazine), with or without digoxin. Prevention of further left ventricular dysfunction can be accomplished by inhibiting neurohormonal processes and ventricular remodeling that occur in heart failure using ACE inhibitors, nitrates and hydralazine, or beta blockers. Significant therapeutic advances have been made with respect to symptom relief, hospitalizations, and mortality reduction in patients with congestive heart failure. Despite these advances, patient morbidity and mortality remain high and underscore the necessity for optimal use of existing therapies along with research directed at achieving further improvements in both quality of life and life expectancy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Myocardium; Vasodilator Agents

Atrial fibrillation represents a common and challenging arrhythmia. A rational approach to management of the individual case depends on careful assessment of the temporal of the arrhythmia, any associated cardiovascular disease, and any particular features suggesting the advisability or risks of any particular treatment regimen. The nature of an arrhythmia and of individual patient factors change over time, requiring a flexible approach to long-term treatment that may be defined only after months or years. While new treatment options such as catheter ablation techniques and implantable atrial defibrillators are being tested, old therapies (e.g., low-dose amiodarone) are undergoing reappraisal. Increasing recognition of the dangers of antiarrhythmic therapy used to maintain sinus rhythm is focusing attention on nonpharmacologic methods. All patients with persistent atrial fibrillation merit serious consideration for direct current cardioversion before accepting that atrial fibrillation is permanent, and many patients may benefit from more than one attempt to restore and maintain sinus rhythm.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Calcium Channel Blockers; Catheter Ablation; Digoxin; Electric Countershock; Flecainide; Heart Failure; Heart Rate; Heart Ventricles; Humans; Quinidine; Sinoatrial Node; Thromboembolism; Time Factors

Congestive heart failure is a frequent disorder with an estimated prevalence of 0.4-2% in the general population. Despite recent advances in our understanding of the pathophysiology of this disorder and new developments in its treatment, the prognosis of heart failure remains poor. All patients with heart failure should undergo diagnostic evaluation to determine the type of cardiac dysfunction, establish its etiology and orient treatment. Angiotensin converting enzyme (ACE) inhibitors, diuretics and digoxin are the standard therapy for chronic congestive heart failure caused by systolic dysfunction. ACE inhibitors are indicated in all stages of heart failure, even in asymptomatic patients. Diuretics should be added in the presence of fluid retention. Digoxin remains an important component in the management of refractory symptoms and atrial fibrillation. Symptomatic improvement and reduced morbidity have been shown with all these drugs. However, improved survival has been documented for ACE inhibitors only. Currently, numerous drugs with different mechanisms of action are being evaluated in ongoing clinical trials. Promising results have been published, mainly with beta-receptor blockers and newer positive inotropic substances. Rapidly growing evidence from basic research will advance our understanding of heart failure and hopefully pave the way for new preventive and therapeutic strategies in the near future.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Diuretics; Heart Failure; Hemodynamics; Humans; Vasodilator Agents

Congestive heart failure (CHF) continues to be a lethal end stage of cardiovascular diseases caused by hypertension, coronary heart disease, valve deformity, diabetes and cardiomyopathy. Current therapy for CHF can maintain function, improve quality of life, and prolong survival. Diuretics, angiotensin-converting enzyme inhibitors (ACE), and digoxin remain in standards of therapy. Diuretics remains an important component of the symptomatic management of patients with CHF, but severely II patients may require additional agents. One option frequently used in patients who exhibit resistance to loop diuretics is infusion of low-dose dopamine. Combination diuretics may effectively increase urine output, with the addition of thiazide or spironolactone. Documentation of the clinical benefit of ACE inhibitors represents the most important advance in therapeutics for CHF in the last decade. ACE inhibitors improves left ventricular function, and survival and unless contraindicated, patients with left ventricular systolic dysfunction should receive high dose ACE inhibitor with diuretic if there is peripheral oedema. For patients who cannot take an ACE inhibitor the combination of hydralazine and nitrates may offer some prognostic benefit. Digoxin has been the traditional first drug of choice for CHF, but with protracted controversy about its efficacy and safety. It is hope that new agents as vesnarione, and ibopamine may improve contractility without having adverse consequences. Acceptance of beta-blockade as a potentially beneficial therapeutic intervention increase in the past year. This year, improved diastolic function and afterload reduction were reported with beta-blockade. Amiodarone unlike other antiarrhythmic drugs does not seem depress left ventricular function, and may be the best drug in patients with CHF and symptomatic arrhythmias. The correct role of anticoagulation in patients with CHF remains controversial. Although the benefits of anticoagulation for the treatment of most patients with atrial fibrillation are increasingly accepted, it has not been shown to improve outcome in patients with CHF in normal sinus rhythm.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Digoxin; Diuretics; Dopamine; Drug Resistance; Heart Failure; Humans; Myocardial Contraction; Quality of Life; Treatment Outcome

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Child; Child, Preschool; Digoxin; Forecasting; Heart Defects, Congenital; Heart Failure; Humans; Infant

Digoxin has been a controversial drug since its introduction >200 years ago. Although its efficacy in patients with heart failure and atrial fibrillation is clear, its value in patients with heart failure and sinus rhythm has often been questioned. In the 1980s, reports of some large-scale trials indicated that digoxin, with or without vasodilators or angiotensin-converting enzyme inhibitors, reduced signs and symptoms of congestive heart failure and improved exercise tolerance. This beneficial influence was mainly found in patients with more advanced heart failure and dilated ventricles, whereas the effect in those with mild disease appeared to be less pronounced. In the last few years, new data have shown that digoxin may also have clinical value in mild heart failure, either when used in combination with other drugs or when administered alone. As neurohumoral activation has increasingly been recognized to be a contributing factor in the disease progression of chronic heart failure, the modulating effects of digoxin on neurohumoral and autonomic status have received more attention. Also, there is evidence that relatively low doses of digoxin may be at least as effective as higher doses and have a lower incidence of side effects. Further, the recognition that the use of digoxin too early after myocardial infarction may be harmful and the development of other drugs, in particular angiotensin-converting enzyme inhibitors, have obviously changed the place of digoxin in the treatment of chronic heart failure. The large-scale survival trial by the Digitalis Investigators Group (DIG), whose preliminary results have recently been presented, has shown that although digoxin has a neutral effect on total mortality during long-term treatment, it reduces the number of hospital admissions and deaths due to worsening heart failure. The potentially new features of the old drug digoxin are discussed in this review.

Topics: Anti-Arrhythmia Agents; Cardiac Output, Low; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Although heart failure secondary to left ventricular systolic dysfunction remains a serious disease with high morbidity and mortality, pharmacologic intervention has been shown to be associated with improved survival and a decreased number of hospitalizations. Primary-care providers must be aware of the potential benefits of recent therapeutic advances and current treatment recommendations for patients with heart failure to receive optimal care. Important aspects of nonpharmacologic care are dietary restrictions, exercise training, and through patient education and counseling. Pharmacologic therapy includes diuretics, angiotensin-converting enzyme inhibitors (ACE) and other vasodilating agents, and digoxin. ACE inhibitors are currently recommended for all patients with left ventricular dysfunction in whom use of these agents is not contraindicated. The mortality and morbidity from heart failure even with ACE inhibitors remain high, however. Promising clinical findings with such investigational agents as vesnarinone and pimobendan and the new-generation beta-blocker carvedilol suggest future new treatments to further improve the prognosis of these patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Exercise; Heart Failure; Humans; Patient Education as Topic; Systole; Ventricular Dysfunction, Left

Topics: Anti-Arrhythmia Agents; Baroreflex; Cardiotonic Agents; Digoxin; Heart Failure; Heart Rate; Humans; Neurosecretory Systems; Sympathetic Nervous System

Heart failure is common in the elderly and is associated with a significant morbidity and mortality. It accounts for about 5% of adult medical admissions and the expenditure of 1% of the total National Health Service budget. Clinical presentation in old age may be with the classical symptoms of heart failure but often, due to multiple pathology and low functional ability, presentation is atypical. Both nonspecific symptoms and signs of heart failure, are often a delayed presentation in this population, make diagnosis difficult. Treatment of the failing heart in an older person is similar to the young however, diligence is required when prescribing due to age-related pharmacokinetic changes and co-existent morbidity. This may result in polypharmacy and an increase in drug interactions which themselves may have deleterious consequences. However, knowledge of the aetiology of heart failure in old age and the possible atypical presentation as well as available treatments, will result in better management and improved quality of life and reduced mortality in the elderly heart failure population.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Female; Heart Failure; Humans; Hydralazine; Isosorbide; Male; Middle Aged; Prognosis; Vasodilator Agents

Topics: Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Heart Failure; Humans; Risk Assessment

The prognosis in patients with heart failure (HF) is poor. The angiotensin converting enzyme (ACE) inhibitors are among the most promising of current options, with benefits not only in terms of haemodynamic and clinical improvement but also in mortality. Data are reviewed comparing the once-daily ACE inhibitor lisinopril with captopril or enalapril in patients already receiving digoxin and/or diuretics for heart failure. Data are also reviewed which compare lisinopril with digoxin in patients already receiving diuretics alone for heart failure. Lisinopril is more effective than placebo and at least as effective as captopril or enalapril in these comparative studies on the basis of haemodynamics, exercise test results and clinical signs and symptoms of heart failure. Lisinopril may also be a suitable alternative, as well as being an adjunct, to digoxin in patients already receiving diuretics alone. Lisinopril is usually well tolerated in patients with heart failure. The mechanism of benefit of ACE inhibitors in heart failure is not clear, but apart from blockade of the renin-angiotensin-aldosterone system (RAAS), may also involve modulation of sympathetic stimulation, cardioreparation and regulation of potassium balance. The new ATLAS study (Assessment of Treatment with Lisinopril And Survival) is being conducted to address the question of whether ACE inhibitors in general practice should be given at the current low doses, or at the higher doses used in large survival studies.

Topics: Captopril; Clinical Trials as Topic; Digoxin; Enalapril; Exercise Test; Heart Failure; Hemodynamics; Humans; Lisinopril; Quality of Life

Over the past 25 years, a great deal has been learned about the pathophysiology and management of heart failure--a major health problem whose prevalence and incidence have not declined, unlike other cardiovascular disorders. Several of these lessons are reviewed herein. However, despite these advances, important issues remain to challenge both the practicing physician and the research scientist.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiotonic Agents; Digoxin; Diuretics; Heart; Heart Failure; Heart Transplantation; Humans; Kidney; Myocardium; Peptidyl-Dipeptidase A; Renin-Angiotensin System; Vasodilator Agents

Angiotensin-converting enzyme (ACE) inhibition therapy has now become firmly ensconced in the modern therapeutic approach to all stages of congestive heart failure (CHF), including the early presymptomatic phase. Although its benefit is abundantly proven as add-on therapy in established CHF, after digitalis and diuretics, smaller and shorter studies have shown that, as second-line therapy and combined with diuretics, it may be preferable to digoxin with an undoubted benefit in postinfarction failure. As first-line therapy in early presymptomatic CHF, the evidence is also good, based on the prevention arm of the Studies of Left Ventricular Dysfunction (SOLVD), albeit in predominantly postinfarction patients, and on the Survival and Ventricular Enlargement (SAVE) study on postinfarction patients. ACE inhibitors given prophylactically or therapeutically helped to prevent clinical heart failure in the SOLVD and SAVE studies. These data suggest a role for ACE inhibitors as effective first-line monotherapy in early heart failure, acting on left ventricular function to avoid or lessen unfavorable remodeling. There are some contraindications or cautions for the use of ACE inhibitors in CHF, such as preexisting hypotension, high-renin states such as bilateral renal artery stenosis with hypertensive heart failure, aortic stenosis combined with CHF, overdiuresis with excess sodium depletion, and significant preexisting renal failure. ACE inhibition therapy may have deleterious effects on renal function in heart failure, for example, by decreasing the glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Vasodilator Agents

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Defibrillators, Implantable; Digoxin; Diuretics; Female; Heart Conduction System; Heart Failure; Humans; Male; Prognosis; Vasodilator Agents

Congestive heart failure is characterized by contractile dysfunction and frequent complex ventricular ectopy. Despite advances in therapy, mortality from heart failure is substantial, estimated at 10-80 percent per year, and sudden death is common. Magnesium is the second most common intracellular cation, strongly influences cardiac cell membrane function, and is an important catalyst of many enzymatic reactions in the myocyte. Epidemiological studies have implicated magnesium deficit in the genesis of sudden death. Patients with congestive heart failure are predisposed to magnesium deficit for many reasons, including neurohormonal activation, poor gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in these patients and has been linked to an increased frequency of complex ventricular ectopy. Several early, uncontrolled studies have suggested a beneficial effect of magnesium administration on ventricular arrhythmias in patients with congestive heart failure. Two recent randomized, double blind, placebo-controlled trials have shown that both intravenous and oral administration of magnesium chloride results in a significant reduction in the frequency and complexity of ventricular arrhythmias in patients with congestive heart failure. Magnesium administration is well tolerated and serious adverse effects are rare. The potential mechanisms of the antiarrhythmic action of magnesium and limitations of the available data are discussed. The evidence reviewed suggests that serum magnesium concentrations should be monitored and corrected in patients with congestive heart failure. Ventricular arrhythmias may respond to acute intravenous magnesium administration, which should be considered as early therapy. Further study is needed to define magnesium dose and the effect of concomitant potassium administration. A prospective clinical trial is warranted to determine the chronic effects of magnesium administration in patients with heart failure.

Topics: Absorption; Aged; Anti-Arrhythmia Agents; Death, Sudden; Digoxin; Diuretics; Heart Failure; Humans; Kidney Tubules; Magnesium; Magnesium Deficiency; Middle Aged; Prognosis; Ventricular Fibrillation

Topics: Adrenergic beta-Antagonists; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Catheter Ablation; Cerebrovascular Disorders; Defibrillators, Implantable; Digoxin; Electrophysiology; Heart; Heart Failure; Humans

The introduction of new drugs, and a re-evaluation of older drugs, have radically changed the pharmacological management of heart failure. Angiotensin converting enzyme (ACE) inhibitors, digitalis, diuretics and the combination of nitrates and hydralazine are now used. The first Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS I) and the second Vasodilator therapy in Heart Failure Trial (V-HeFT II) have demonstrated that patients with severe or advanced heart failure should be treated with ACE inhibitors, digitalis and diuretics (other vasodilators can be used if ACE inhibitors are contraindicated) to improve symptoms and duration of life. The Studies Of Left Ventricular Dysfunction (SOLVD) and the Munich Heart Failure trial have shown that patients with mild heart failure should be treated with ACE inhibitors. However, data from several large clinical registries suggest that only 40% of patients with heart failure are being given ACE inhibitors perhaps through fear of serious renal damage or hypotension; these fears are unfounded. Patients with anterior myocardial infarcts and reduced left ventricular function also benefit from ACE inhibitors. The fourth International Study of Infarct Survival (ISIS 4) and results from the Gruppo Italiano per Io Studio della Sopravvivenza nell'Infarto miocardico 3 (GISSI 3) have indicated that patients with acute myocardial infarction benefit from early ACE inhibitor therapy and that survival is increased. Heart failure treatment can be optimized by establishing a disease etiology and stressing the need to restrict dietary sodium. ACE inhibitors should be used for depressed left systolic ventricular function, including patients in New York Heart Association class I heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Calcium Channel Blockers; Captopril; Clinical Trials as Topic; Contraindications; Digitalis; Digoxin; Diuretics; Enalapril; Heart Failure; Humans; Hydralazine; Lisinopril; Nitrates; Plants, Medicinal; Plants, Toxic; Randomized Controlled Trials as Topic; Stroke Volume

Digoxin and other low doses of drugs that have inotropic properties may have an important role to play in the therapy of patients with chronic heart failure. There is convincing evidence that digoxin is effective in relieving the signs and symptoms of heart failure due to systolic dysfunction. While earlier results with some of the other agents have been disappointing, recent data suggest that a reevaluation of these agents is necessary. There is now compelling evidence that lower doses of these agents may be clinically useful without necessarily having any significant hemodynamic effects. The recent experience with vesnarinone is especially promising in showing that therapy with these agents may improve survival in addition to improving clinical status. It is becoming recognized that hemodynamic activity should not necessarily be a prerequisite for clinical utility for those agents. The neuroendocrine and electrophysiologic effects of many of these agents, including digitalis, remain incompletely characterized and may play an important role in their therapeutic benefit. It appears that certain drugs that have inotropic properties may be effective only when their inotropic effects are not readily demonstrated. Further research into the appropriate mechanisms of action and proper dosing of these drugs may lead to a renewed interest in the use of positive inotropes for chronic heart failure.

Topics: Adrenergic beta-Agonists; Cardiotonic Agents; Digoxin; Double-Blind Method; Drug Evaluation; Electrophysiology; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Neurosecretory Systems; Phosphodiesterase Inhibitors; Pyrazines; Quinolines

This review of the pharmacologic treatment of heart failure due to left ventricular systolic dysfunction summarizes the recommendations of the expert panel for the Agency for Health Care Policy and Research Heart Failure Guideline. It provides specific advice to help guide practitioners through clinical decision making.. Data were obtained from English-language studies and referenced in MEDLINE or EMBASE between 1966 and 1993. We used the search terms heart failure, congestive; congestive heart failure; heart failure; cardiac failure; and dilated cardiomyopathy in conjunction with terms for the specific treatments. Where data were lacking, we relied on opinions of panel members and peer reviewers.. Only large prospective trials were used to estimate treatment efficacy. Smaller trials, case series, and case reports were reviewed for the incidence of adverse effects.. Randomized clinical trials were reviewed for inclusion and exclusion criteria, patient outcomes, adverse effects, and eight categories of study quality using a defined list of study flaws.. Angiotensin-converting enzyme (ACE) inhibitors should be given to all patients unless specific contraindications exist. Diuretics should be used judiciously early in treatment to prevent excessive diuresis that could prevent titration of ACE inhibitors to target doses. Digoxin has not been shown to affect the natural history of heart failure and should be reserved for patients who remain symptomatic after treatment with ACE inhibitors and diuretics. Isosorbide dinitrate and hydralazine hydrochloride should be tried in patients who cannot tolerate ACE inhibitors or who have refractory symptoms.

Topics: Angiotensin-Converting Enzyme Inhibitors; Decision Support Techniques; Digoxin; Diuretics; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; United States; United States Agency for Healthcare Research and Quality; Ventricular Dysfunction, Left

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Calcium Channel Blockers; Digoxin; Diuretics; Heart Failure; Humans; Vasodilator Agents

Topics: Digoxin; Heart Failure; Humans; Myocardial Contraction; Stimulation, Chemical

During 1993 the indications for the use of angiotensin-converting enzyme (ACE) inhibitors were expanded to include patients with left ventricular dysfunction and acute myocardial infarction. The role and use of ACE inhibitors in patients with chronic systolic ventricular dysfunction, established in earlier trials, has been further clarified. Increasing attention is being focused on ACE inhibitors, specifically the mechanisms by which they improve mortality, their side effects, and the possibility of further increasing their use by avoiding renal dysfunction and first-dose hypotension. Although most of the interest has centered on ACE inhibitors, the importance of diuretics and their use in combination with ACE inhibitors is being clarified. Most important has been the demonstration over the past year of the effectiveness of digoxin in preventing cardiac deterioration in patients with systolic left ventricular dysfunction and sinus rhythm. The increased understanding of the renin-angiotensin-aldosterone system, its modification by ACE inhibitors, and the interaction of ACE inhibition with other drugs provides the basis for a further improvement in morbidity and mortality in patients with heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Clinical Trials as Topic; Digoxin; Diuretics; Heart Failure; Hemodynamics; Humans

In the last 15 years several double-blind, placebo-controlled clinical trials have unequivocally shown that digitalis decreases symptoms of cardiac failure, results in a reduction in the need for hospitalization for treatment of congestive heart failure, and improves cardiac function. The major unresolved question concerning digitalis use is its safety. There are experimental data and clinical evidence that digitalis use may be associated with an increased mortality, particularly in the first year or two after an acute myocardial infarction. This increased mortality appears to be present even after adjustment for predictor covariants. This conclusion depends on the ability of statistical methods to account for differences in comorbidity. Since the question of digitalis safety remains after myocardial infarction, the physician should carefully examine the indications for administration of digitalis. More than the usual surveillance is required during chronic digitalis administration.

Topics: Cardiac Output, Low; Digoxin; Double-Blind Method; Heart; Heart Failure; Humans; Randomized Controlled Trials as Topic

The natural history of patients with heart failure has changed relatively little until recently. Several large randomized trials have however recently changed our approach to the patient with symptomatic as well as asymptomatic left ventricular dysfunction. Although the effect of digoxin on survival is still uncertain there is still good evidence from the Radiance study in which patients were randomly withdrawn from digoxin that patients who remain on digoxin have a significant improvement in exercise tolerance and well being. The Consensus trial in patients with class IV heart failure suggested that ACE inhibitors were effective in improving survival. This therapy has not however been widely adapted in patients with mild to moderate heart failure. The recent randomized SOLVD treatment trial in conjunction with the VHEFT II study clearly shows that ACE inhibitors should be the basis for therapy along with a diuretic and digoxin if necessary in all patients with symptomatic left ventricular dysfunction unless contraindicated or not tolerated. There is also evidence from the SOLVD prevention trial that ACE inhibitors can prevent the development of manifest heart failure and hospitalization for heart failure in patients with asymptomatic left ventricular dysfunction. The importance of ACE inhibitors in patients with asymptomatic left ventricular dysfunction is confirmed by data from the SAVE trial which examine both symptomatic and asymptomatic patients with left ventricular dysfunction 3-16 days post infarction. Of interest in both the SOLVD treatment and prevention trials as well as the SAVE trial was the finding that ACE inhibitors reduced the incidence of recurrent ischemic events.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Agonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Ventricular Function, Left

Ten to 15 years ago, the thrust of research in the treatment of congestive heart failure centered around finding new inotropic agents. While initially useful, these agents given chronically actually accelerated left ventricular failure and were associated with excess mortality. Recently, it has been learned that altering the body's response to heart failure is more beneficial compared to attempts to stimulate left ventricular inotropic function. Such altering of the neurohumoral responses to heart failure has been associated with improvements in both morbidity and mortality.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Heart Failure; Humans; Phosphodiesterase Inhibitors; Vasodilator Agents

Ventricular failure is accompanied by a series of neurohormonal responses that result in vasoconstriction. Vasoconstriction develops and is mediated by norepinephrine, angiotensin II, and vasopressin. Vasoconstriction maintains blood pressure but contributes to deterioration in ventricular function. Baroreceptor dysfunction contributes to the syndrome by failing to ameliorate the sympathetic overstimulation. Drug therapy has historically included positive inotropes until recent data suggested that these drugs contributed to worsened survival. The role of digitalis glycosides in patients with ventricular failure who are in normal sinus rhythm remains a subject of scrutiny. Thus far, no long-term oral positive inotrope has replaced digoxin. Vasodilator therapy and interference with the neurohormonal response have become the major approaches to pharmacologic management of ventricular failure. Angiotensin-converting enzyme inhibitors have shown convincingly that they improve survival, slow the course of disease progression, and block the neurohormonal response to ventricular failure. New treatments for ventricular failure must be directed at long-term gain rather than short-term hemodynamic results.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Constriction, Pathologic; Digoxin; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Norepinephrine; Survival Rate; Vasodilator Agents; Vasopressins

Topics: Calcium; Digoxin; Heart Failure; Humans; Myocardial Contraction; Myocardium; Sodium-Potassium-Exchanging ATPase

The article reviews recent discoveries about the pathophysiology of chronic heart failure, especially where new insights have led to new treatment strategies, with particular emphasis on the use of angiotensin converting enzyme inhibitors. Indications for referral of patients with chronic heart failure to hospital for further investigation or treatment are also given. It is concluded that ACE-inhibitors represent a new era in the treatment of chronic heart failure in patients with isolated or for the main part systolic left ventricle dysfunction, and that ACE-inhibitor treatment must be regarded as a first line drug in this condition, along with diuretics and perhaps digoxin. Patients in NYHA class IIIb-IV should be referred to a specialist or hospital with regard to supplemental cardiological investigations and initiation of ACE-inhibitor treatment, if such treatment has not already ben started. Patients with slight to moderate heart failure (NYHA class II-IIIa) should be referred as well, unless it is known that the cause of heart failure is an ischaemic heart condition that does not require operation. In the latter case, after the relevant investigations have been conducted, ACE-inhibitor treatment can usually be started in a general practice setting, bearing the usual safety regulations and contraindications in mind.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Contraindications; Digoxin; Diuretics; Heart Failure; Humans; Middle Aged; Vasodilator Agents

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Neurosecretory Systems; Survival Rate; Vasodilator Agents

Digitalis glycosides are the first-choice drugs in the treatment of the patients with congestive heart failure and atrial fibrillation. Recently, it has been shown that digitalis glycosides have potentially beneficial neurohumoral modulating effects by decreasing excessive neurohumoral responses directly or by improving baroreflex mechanisms in congestive heart failure. Accordingly, there are many investigators who believe that digitalis glycosides are neurohormonal modulating agents in heart failure. There may be a dissociation between hemodynamic and neurohormonal effects in response to digitalis glycosides. The activation of the neurohormonal system may be present in patients with asymptomatic left ventricular dysfunction. Digitalis glycosides may therefore be used, not only to improve symptomatic congestive heart failure, but also to protect against the progressive deterioration of asymptomatic cardiac dysfunction.

Topics: Atrial Natriuretic Factor; Digitalis; Digoxin; Heart Failure; Humans; Norepinephrine; Plants, Medicinal; Plants, Toxic; Renin

Although supported by 2 centuries of anecdotal clinical evidence, the safety and efficacy of the cardiac glycosides for the treatment of congestive heart failure due to systolic ventricular dysfunction had never been rigorously examined by prospective clinical trials until the past decade. A reevaluation of the appropriate role of these drugs in modern cardiovascular pharmacology was prompted by the introduction in the 1970s of new classes of drugs for the treatment of congestive heart failure and supraventricular arrhythmias. Concurrently, several reports appeared, questioning the routine prescription of digoxin for the treatment of heart failure, particularly in patients in sinus rhythm. The majority of clinical trials published since 1980, most of which examined patients with New York Heart Association class II and III congestive heart failure, indicate that digoxin with or without concomitant administration of a vasodilator lessens symptoms and reduces the morbidity associated with congestive heart failure, particularly in patients with more advanced symptoms and ventricular dysfunction. The data on efficacy are less clear in support of the routine prescription of digoxin in the treatment of mild (class I and II) congestive heart failure. Although most recent trials attest to the relative safety and efficacy of digoxin in patients with congestive heart failure whose serum levels are maintained between 1 and 2 ng/ml, there is no conclusive evidence as yet that cardiac glycosides improve survival, as has been documented for vasodilators and, in particular, angiotensin-converting enzyme inhibitors. The National Institutes of Health-sponsored Digitalis Investigators Group (DIG) trial now underway should provide an answer to this question within the next few years.

Topics: Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

The pathophysiology of the serious and disabling problem of heart failure has been confirmed to involve activation of multiple neuroendocrine systems, especially the sympathetic system and renin angiotensin aldosterone system. The results of several large scale clinical trials demonstrate that reduction in morbidity and mortality are possible with currently available drugs. The benefits for the patient can be maximised by early intervention, especially by the family physician as opposed to interventions applied late, which often yield minimal benefit.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Heart Failure; Humans

In recent years, thanks to a better understanding of the pathophysiology of congestive heart failure and progress made in the pharmacology of cardiovascular drugs, new therapeutics have been advocated in the treatment of congestive heart failure. Among them, converting enzyme inhibitors are the most useful. However, the classical association of digoxin-furosemide and general measures remains a very effective first-choice treatment in most cases. Only in particular situations, such as cardiomyopathy and decompensated atrio-ventricular insufficiency, should priority be given to converting enzyme inhibitors. Phosphodiesterase inhibitors are essentially used within the context of post-cardiac surgery intensive care. Beta-blockers which have been recently proposed for treatment of adult patients must not be used, as there is still no data available on their effectiveness and tolerance in pediatric patients.

Topics: Age Factors; Angiotensin-Converting Enzyme Inhibitors; Captopril; Child; Child, Preschool; Digoxin; Dihydralazine; Dopamine; Female; Furosemide; Heart Defects, Congenital; Heart Failure; Humans; Infant; Infant, Newborn; Male

Angiotensin converting enzyme (ACE) inhibition and digoxin may be used in the management of heart failure. Digoxin increases myocardial contractility in vitro, and has a modest but durable beneficial effect in congestive heart failure due to impaired left ventricular systolic function. ACE inhibitors have clear beneficial effects in all grades of heart failure and, in addition, modify the natural history and reduce mortality. Comparative studies in mild to moderate heart failure reveal a tendency towards greater benefits and tolerability of ACE inhibitors over digoxin. ACE inhibition is indicated, in conjunction with diuretic therapy, for all grades of heart failure. Digoxin is best reserved for patients with atrial fibrillation and a rapid ventricular response, and for those whose heart failure is not controlled with an ACE inhibitor plus a diuretic. In patients with heart failure following myocardial infarction, digoxin is of modest benefit. Digoxin should be administered slowly and carefully to avoid acute vasoconstriction and toxicity. Provisional data suggest ACE inhibitors are also beneficial in these patients. However, the results of clinical trials presently in progress are required to clarify their role following myocardial infarction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Digoxin; Heart Failure; Humans

Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Interactions; Heart Failure; Humans

The high prevalence and poor prognosis of heart failure are a major concern. Hospitalization for heart failure accounts for a major proportion of health-care expenditure. A number of large clinical trials have been initiated to assess therapeutic strategies to improve prognosis for patients with this condition. Results from one of the largest and most recently completed of such studies, the Studies of Left Ventricular Dysfunction (SOLVD) trial, demonstrate that addition of the long-acting angiotensin-converting enzyme (ACE) inhibitor, enalapril to conventional therapy with diuretics and digoxin is associated with reduced rates of mortality and hospitalization for heart failure. Activation of the renin-angiotensin-aldosterone system (RAAS) appears to play an important role in the pathogenesis of this condition. The effects of treatment with this ACE inhibitor may be related to the degree of RAAS suppression it affords.

Topics: Digoxin; Diuretics; Drug Therapy, Combination; Enalapril; Heart Failure; Hospitalization; Humans; Prevalence; Prognosis; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Vasodilator Agents

Topics: Age Factors; Cardiomyopathies; Digoxin; Heart Failure; Oxygen Inhalation Therapy

Digitalis should be used for slowing a rapid ventricular rate in atrial fibrillation or atrial flutter unassociated with the preexcitation syndrome. Digitalis may be used to convert paroxysmal supraventricular tachycardia to sinus rhythm. Patients with the tachycardia-bradycardia syndrome should receive maintenance doses of digitalis after pacemaker implantation. Digitalis should not be used for treating CHF with normal LV systolic function unless a supraventricular tachyarrhythmia is present. Conflicting studies have been reported as to the efficacy of digoxin in the treatment of patients with CHF in sinus rhythm. Digoxin may be used for treating CHF with abnormal LV systolic function which does not respond to diuretics and ACE inhibitors or in patients unable to tolerate ACE inhibitor or other vasodilator therapy. Digitalis has a low toxic-therapeutic ratio, especially in elderly persons. Digoxin-specific Fab antibody fragments may be used for treating digitalis toxicity refractory to conventional measures with a treatment response in at least 90% of patients with advanced and potentially life-threatening digitalis toxicity.

Topics: Clinical Trials as Topic; Digitalis; Digoxin; Female; Heart Failure; Humans; Male; Plants, Medicinal; Plants, Toxic; Tachycardia, Supraventricular

Although digitalis preparations have been in use for greater than 200 years, it is only within the last 2 decades that the central hemodynamic and neurohumoral effects occurring over several hours following intravenous administration of digoxin have been investigated in patients with congestive heart failure (CHF). Although digoxin has been shown to stimulate myocardial contractility in tissue preparations, its positive inotropic activity does not consistently translate into improvements in hemodynamic measurements in humans. Digoxin given intravenously results in increased cardiac index and decreased heart rate, left ventricular filling pressure, and right atrial pressure, as well as in acute attenuation of neurohumoral abnormalities, in patients with chronic CHF who have abnormal baseline hemodynamic measurements. Unlike other drugs with positive inotropic activity, however, digoxin does not influence hemodynamics in normal volunteers or in CHF patients in whom hemodynamics have been normalized with other therapies. These differing effects may be related to the drug's diverse peripheral vascular effects in CHF patients in whom vasodilation may occur in comparison with those that occur in normal subjects in whom the peripheral vasoconstrictor effects may prevent the inotropic effects of the drug from being translated into an increase in cardiac output. The hemodynamic effects of digoxin in patients with chronic CHF due primarily to diastolic dysfunction have not been fully investigated. Intravenous digoxin produces hemodynamic effects in patients with CHF associated with acute myocardial infarction, but these changes are small compared with those resulting from the administration of dobutamine. Digoxin does not appear to influence hemodynamic measurements in patients with right ventricular dysfunction unless concomitant left ventricular failure is present. In patients with chronic left ventricular dysfunction, the hemodynamic effects of intravenous digoxin and vasodilators are enhanced when these agents are given in combination.

Topics: Cardiotonic Agents; Digoxin; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Myocardial Infarction; Vasodilator Agents; Ventricular Function, Right

Despite recent advances in the treatment of congestive heart failure (CHF), many patients continue to present with symptoms refractory to digoxin, diuretic, and vasodilatory therapy. Since it is unlikely that this population will decrease in the near future, practical approaches to management of refractory CHF are reviewed. Refractory CHF here is defined as New York Heart Association (NYHA) functional class III-IV heart failure, despite maximal drug therapy. Before such a diagnosis is made, the patient should be treated with digoxin, diuretics, and a vasodilator. Approach to therapy requires assessment of changing clinical status and pathophysiology, optimizing oral drug treatment, and providing temporary parenteral support when indicated. Specific attention should be given to factors that influence the optimal response to each of these 3 treatment classes. A theoretical, but unproven, concept suggests that combined vasodilatory therapy may be appropriate as long as excessive hypotension is avoided. In the course of management, a decision is required as to whether further optimization of therapy can be achieved on an outpatient basis. Hospital-based intravenous inotropic support given for 2-4 days will often provide the opportunity to restructure patient therapy.

Topics: Administration, Oral; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Infusions, Intravenous; Vasodilator Agents

Although digitalis glycosides were introduced in the treatment of cardiac maladies greater than 200 years ago, controversy persists regarding the precise role of digoxin in any multidrug approach to the treatment of congestive heart failure (CHF). Despite its widespread use for more than 2 centuries, only recently have double-blind, randomized, placebo-controlled trials of digoxin therapy been conducted in patients with moderate CHF and sinus rhythm. These trials demonstrate that digoxin is superior to placebo in improving left ventricular (LV) ejection fraction, increasing exercise capacity, and preventing CHF worsening. Digoxin produces benefits similar to those seen with angiotensin converting enzyme (ACE) inhibitors with regard to clinical compensation and improvement in LV function. However, improved survival is demonstrated only in response to ACE inhibitors. The recently completed RADIANCE study addresses the value of combining digoxin with ACE inhibitor therapy in patients with mild-to-moderate CHF. Because increased mortality has been reported with the newer oral inotropic agents, it currently appears that digoxin is the only oral inotropic agent useful in clinical practice in the treatment of CHF. However, the effects of digoxin on mortality in patients with CHF remain unknown. In the large, double-blind, randomized trial conducted by the National Heart, Lung, and Blood Institute, the effects of digoxin on mortality in patients with CHF and already being treated with ACE inhibitors are currently being evaluated. Presently, based on the results of placebo-controlled studies, it appears that digoxin, alone or in combination with ACE inhibitors, is beneficial in patients with any signs or symptoms of CHF due to systolic LV dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Therapy, Combination; Exercise; Heart Failure; Humans; Randomized Controlled Trials as Topic; Ventricular Function, Left

The development of the radioimmunoassay for digoxin by Smith and coworkers in 1969 was a landmark in digitalis therapy. Since then, the complex pharmacokinetics of digoxin have been defined. As a result, the incidence of digitalis toxicity has markedly decreased. To use the digoxin assay properly, however, the relation of this pharmacokinetic parameter to digoxin pharmacodynamics must be known and the limitations of the assay itself understood. Systolic time intervals (STI) are uniquely useful to quantitate the inotropic effect of digitalis preparations. This technique can demonstrate the onset and magnitude of the inotropic effect for both oral and intravenous digitalis administration. By defining the mathematical relation between STI and simultaneous serum digoxin concentrations following intravenous administration of 1 mg digoxin, computer simulations can be made of the effect of dosing changes on blood and tissue concentrations. The serum digoxin assay has technical problems relating to quality control, interference by metabolites, and cross-reactions with endogenous digitalis-like substances. Further, a standard time for measurement following dosing has not been established. Physical activity can significantly after the serum digoxin concentrations by increasing skeletal muscle binding. Numerous drugs can interfere with digoxin absorption or elimination. Using the serum digoxin assay is the only way to assess these interactions. Computer surveillance (ideally with physician or pharmacist interaction) has been used to monitor digitalis but has not yet gained widespread acceptance. This is clearly a method in need of further testing.

Topics: Digoxin; Drug Monitoring; Heart Failure; Humans; Poisoning; Radioimmunoassay

Recent studies have more clearly defined the role of drug therapy in patients with chronic congestive heart failure (CHF). Treatment of patients with asymptomatic left ventricular dysfunction (New York Heart Association [NYHA] class I) cannot be recommended at this time. The benefit of prophylactic treatment with angiotensin-converting enzyme inhibitors (ACEIs) or vasodilators in patients at high risk for developing symptomatic CHF is currently being evaluated. Treatment of patients with symptomatic CHF (NYHA class II-IV) should be initiated with a combination of a diuretic, digoxin, and an ACEI. This combination has been shown to reduce the mortality rate in patients with NYHA class II-IV CHF. Patients who remain symptomatic despite treatment with this combination may benefit from the addition of the direct-acting, nonspecific vasodilators--hydralazine and a nitrate. The addition of the nonspecific vasodilators to an ACEI has not been tested in controlled trials. In patients who remain symptomatic despite treatment with diuretics, digoxin, ACEIs, and nonspecific vasodilators, treatment options are not clear. The use of beta-agonists, phosphodiesterase inhibitors, and intermittent fixed-dose, fixed-interval dobutamine should be avoided as these agents are associated with a high mortality rate. Heart transplantation should be considered early in the course of CHF to allow for preservation of other vital organ systems. Unfortunately, heart transplantation is available to only a very small minority of potential transplant candidates.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Dobutamine; Drug Therapy, Combination; Heart Failure; Humans; Phosphodiesterase Inhibitors; Receptors, Adrenergic, beta

Heart failure commonly occurs in the elderly age group. Treatment mainly centres on the use of digoxin and diuretics. In intractable heart failure other agents ie inotropic agents and vasodilators may be considered. Routine maintenance on diuretic and digoxin should not be encouraged. A conscious effort to tail off these medication is needed.

Topics: Aged; Algorithms; Digoxin; Diuretics; Heart Failure; Humans; Middle Aged; Vasodilator Agents

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Heart Failure; Humans; Infant, Newborn; Survival Rate; Ventricular Function, Left

Topics: Digitalis Glycosides; Digoxin; Drug Evaluation; Drug Monitoring; Heart Failure; Hemodynamics; Humans

Topics: Digoxin; Heart Failure; History, 16th Century; History, 20th Century; History, Medieval; Humans; Meta-Analysis as Topic

Topics: Atrial Natriuretic Factor; Digoxin; Heart Failure; Humans; Myocardial Contraction; Neurosecretory Systems; Norepinephrine; Reflex; Renin; Ventricular Function, Left

The clinical literature on the subject of inotropic therapy of heart failure, particularly use of digitalis glycosides, is full of contradictions. Most of this disparity can be accounted for if not reconciled by taking the methodology of the clinical trials into consideration. Because drug interventions may produce subtle effects requiring a subjective determination, the questions being asked in these studies cannot be answered without removing as many sources of bias as possible from the patient management and data analysis. If a study has not been adequately randomized, double-blinded, and placebo-controlled, the clinical findings will be inconclusive at best. Systolic myocardial dysfunction plays a pivotal role in the pathogenesis of CHF in many patients and is a prerequisite for the use of cardiotonic drugs. Although the clinical signs of heart failure may be relieved initially by diuretics and vasodilators, compensation may require the addition of a positive inotrope, particularly in advanced cases. In veterinary medicine, the choice of positive inotrope is limited to digoxin, digitoxin, dobutamine, or amrinone. Digoxin possesses superior pharmacokinetics and is the cardiac glycoside of choice for use in the dog. Dobutamine and amrinone are more potent inotropes, but since they must be administered by continuous intravenous infusion, their use is limited to critical care therapy. At the present time, only digoxin can be administered orally for sustained long-term maintenance therapy. Milrinone, a more potent derivative of amrinone, also offers this option, but it has not been available since its brief trial debut as an investigational drug. None of the nonglycoside alternatives couples the benefits of positive inotropic and negative chronotropic effects. Consequently, digoxin remains the mainstay for chronic inotropic support of the heart. Atrial fibrillation with a rapid ventricular response rate is the prime indication for digoxin. In the last few years, evidence from methodologically sound clinical trials on humans has also restored faith in the efficacy of digoxin for treating heart failure in patients with normal sinus rhythm. From these studies, the profile of a digitalis responsive heart failure patient has emerged. Digoxin is most likely to be efficacious when heart failure is associated with chronic, severe ventricular systolic dysfunction, which has resulted in ventricular dilatation. The most reliable clinical marker is the presence of a t

Topics: Animals; Cardiotonic Agents; Catecholamines; Digitoxin; Digoxin; Dog Diseases; Dogs; Heart Failure; Humans; Phosphodiesterase Inhibitors

To reappraise the effectiveness of digoxin for the treatment of congestive heart failure (CHF) in patients with sinus rhythm in light of data from recently published randomized controlled trials and to quantitatively assess its usefulness.. Computerized searches of the MEDLINE database were performed, and the reference list of each retrieved article was reviewed.. Review of more than 360 citations and the reference lists of 19 review articles and 61 potentially relevant articles revealed seven double-blind randomized controlled trials that were included in this overview.. Study quality was assessed and descriptive information concerning the study populations, the specific interventions, and clinically relevant outcome measurements was extracted.. The common odds ratio for CHF deterioration while receiving digoxin versus placebo was 0.28, with a 95% confidence interval of 0.16 to 0.49. Predictors of digoxin benefit included presence of a third heart sound and the severity and duration of CHF.. Data from seven trials of high methodologic quality suggest that, on average, one out of nine patients with CHF and sinus rhythm derive a clinically important benefit from digoxin (with a 95% confidence interval of 1/33 to 1/5).

Topics: Digoxin; Double-Blind Method; Heart Failure; Heart Rate; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic

We report on a 33-year-old para II who was admitted to our hospital in her 29th gestational week with extensive fetal hydrops. Examinations showed a fetal supraventricular tachycardia with biventrical cardiac insufficiency. Digoxin was given both to the mother and to the fetus. At first, this treatment seemed to have no effect. Over a period of several weeks, however, oral therapy with digoxin and verapamil resulted in a stabilized fetal heart rate (175-180 beats/min). Signs of fetal cardiac insufficiency disappeared almost completely. In the 39th week the child was born spontaneously. Clinical examination revealed only a slight cardiac insufficiency. New possibilities of intrauterine therapy are discussed in the light of this case and other reports in the literature.

Topics: Adult; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Heart Rate, Fetal; Humans; Hydrops Fetalis; Infant, Newborn; Pregnancy; Pregnancy Trimester, Third; Tachycardia, Supraventricular; Verapamil

The objectives of treatment for patients with chronic heart failure are the prevention of the initial occurrence, the alleviation of signs and symptoms, the delay of the progression of damage to heart muscle and the reduction of the mortality rate. Many drugs are used in severe heart failure. Current controversy is concerned with which drugs to use in patients with mild heart failure or with left ventricular dysfunction. There is a trend towards the earlier introduction of an angiotensin-converting enzyme inhibitor combined with a diuretic.

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Heart Failure; Humans

From the discussion of these questions, several conclusions seem firm, whereas other issues await resolution. Patients with severe CHF should be treated with diuretics, digoxin, and an ACE inhibitor. In mild and moderate CHF, a diuretic should be combined with either digoxin or an ACE inhibitor--usually the latter. However, most of these patients would benefit from receiving all three drugs. Patients with asymptomatic left ventricular systolic dysfunction are at jeopardy for progressive deterioration. Angiotensin converting enzyme inhibitors and, possibly, direct vasodilators may prevent progression. In initiating vasodilator therapy, ACE inhibitors usually should be the agent of choice. Exceptions may be patients with ongoing ischemia in whom nitrates are an appropriate alternative and those who are poor candidates because of hypotension, renal insufficiency, or hyperkalemia.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Digoxin; Diuretics; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Stroke Volume; Vasodilator Agents

"The addition of angiotensin converting enzyme inhibitors to digoxin and diuretics is effective in improving and prolonging the lives of patients with severe heart failure. Our next goal is to prevent the progression of heart failure in patients with asymptomatic left ventricular dysfunction."

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans

Angiotensin converting enzyme inhibitors are now firmly established in the treatment of patients with chronic heart failure (CHF). Their beneficial acute and chronic hemodynamic effects are not associated with reflex tachycardia or drug tolerance. Angiotensin converting enzyme inhibitors produce symptomatic improvement and improve exercise capacity in all grades of heart failure. They also improve the prognosis of patients with severe heart failure. Quinapril is a recently introduced, nonsulfhydryl ACE inhibitor, whose intermediate half-life makes it well-suited for the treatment of patients with CHF. The acute and chronic hemodynamic effects of quinapril are similar to those of other ACE inhibitors. In a large, multicenter, randomized, placebo-controlled study of 225 patients with mild to moderate CHF, 10 to 40 mg/day quinapril significantly improved clinical status and exercise capacity in a dose-related manner. The incidence of side effects did not differ significantly from that of placebo. The initial studies with quinapril are promising and warrant further clinical investigation of this compound.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Output; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Isoquinolines; Physical Exertion; Quinapril; Tetrahydroisoquinolines; Vascular Resistance

The place of digoxin in the pediatric cardiologist's armamentarium remains uncertain. As an antiarrhythmic, its use in the Wolff-Parkinson-White syndrome is obsolete, but it remains useful in the treatment of the chronic atrial fibrillation seen in some patients postoperatively and in children with dilated cardiomyopathy. The efficacy of digoxin in heart failure is unproven. There is some evidence of improvement in non invasive left ventricular contractile indices in neonates and infants, but it is unclear whether this is associated with sustained clinical improvement. There is even less evidence of its effectiveness in the older child. Whilst the measurement of any effect will undoubtedly be difficult, the time has come for double-blind, placebo-controlled trials in selected groups of patients. These should be designed not only to test the notion that digoxin does not improve ventricular function, but also to embrace the possibility that its administration may result in clinical improvement over and above that following diuretics alone. An absence of proof of efficacy must be distinguished from no efficacy--more data are needed.

Topics: Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Heart Defects, Congenital; Heart Failure; Humans; Infant

Topics: Captopril; Digoxin; Heart Failure; Humans

Taking a careful look at each of the outcomes measured in randomized, controlled trials of digoxin suggest that discrepancies in results may be more apparent than real. Digoxin does work, but clinically important benefit is restricted to a relatively small proportion of congestive heart failure (CHF) patients. The play of chance, the dose of digoxin used, and the severity of heart failure in patients enrolled in the studies are other factors that may explain the variability in results that were observed. A systematic examination of the sort undertaken here is likely to help resolve apparent difference in outcomes of clinical trials of new (and old) therapies in CHF patients.

Topics: Digoxin; Heart Failure; Humans; Randomized Controlled Trials as Topic

Controversy continues concerning the use of digoxin as a positive inotropic agent in the treatment of heart failure in patients in sinus rhythm. Digoxin is properly used to control the heart rate in patients in atrial fibrillation. The findings from 14 uncontrolled and 6 controlled clinical trials have been examined. Digoxin does exert a small chronic positive inotropic effect. Although some individual patients, particularly those with fluid overload, appear to benefit from digoxin, controlled clinical trials in patients, most of whom have been treated with diuretics, have failed to demonstrate an increase of exercise capacity. No mortality trial has been attempted. Digoxin has the potential to be harmful in patients with ischemic heart disease. Alternative and safer therapies have been shown to be equal or superior to digoxin.

Topics: Digoxin; Heart Failure; History, 18th Century; History, 19th Century; History, 20th Century; Humans

Due to the narrow therapeutic-to-toxic ratio of digoxin, numerous studies have been done to assess the optimal digoxin level in patients with congestive heart failure. A digoxin level of 0.7-1.5 ng/mL (or 0.9-2.0 nMol/L) is generally considered optimal, but even at these levels toxicity may occur in certain clinical situations such as severe pulmonary disease or when electrolyte or metabolic disturbances are present. The optimal daily maintenance dose of digoxin depends on the preparation given and can be calculated by the equation of Jelliffe, which is largely based on the creatinine clearance of the patient. The daily digoxin dose must also be adjusted to take into consideration disease processes or concomitant drug therapy that can alter the volume of distribution, the biotransformation, or the excretion of the drug.

Topics: Digoxin; Heart Failure; Humans

Topics: Arrhythmia, Sinus; Blood Circulation; Cardiac Glycosides; Digoxin; Heart Failure; Humans; Myocardial Contraction; Propanolamines; Xamoterol

The effects of enalapril were evaluated in a double-blind, controlled study during 8 weeks, in patients with stable, congestive chronic cardiac insufficiency (functional classification II and III of the NYHA), in sinus rhythm, treated with digitalis and diuretics. 20 patients were randomly divided in two groups: one group continuing the digoxin (group A: 10 patients) and one group where enalapril was substituted for digoxin (group B: 10 patients). Patients from group B presented less clinical aggravation during the study. The left ventricular stroke volume (SV) is significantly decreased in group B at rest (0.21 +/- 0.06 at 50; 0.18 +/- 0.04 at 54; p less than 0.05), while it remained stable during stress. No variations of the SVs were noted at rest and during stress in group A. Considering its favorable clinical effects and after evaluation of its longterm side effects, enalapril may be an acceptable alternative to digitalis in cardiac insufficiency with sinus rhythm, except in patients for whom a drop in the systemic blood pressure or an increased kaliemia or creatininemia, could be potentially harmful.

Topics: Digoxin; Double-Blind Method; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Physical Exertion; Radionuclide Angiography; Random Allocation; Rest; Stroke Volume

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Heart Failure; Humans

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Heart Failure; Humans; Vasodilator Agents

Topics: Adrenergic beta-Antagonists; Atrial Natriuretic Factor; Calcium Channel Blockers; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Vasodilator Agents

The evidence suggests that digitalis glycosides do indeed improve ventricular performance through a sustained but moderate positive inotropic effect. This effect is more marked in failing than in nonfailing myocardium. The clinical studies suggest a moderate salutary effect in patients with chronic CHF who are in sinus rhythm. The drug can be given safely to patients with CAD and in combination with other medications when the physician is aware of those factors leading to increased sensitivity to digitalis.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Myocardial Contraction; Time Factors; Vasodilator Agents

Topics: Animals; Atrial Fibrillation; Digitalis Glycosides; Digoxin; Heart Failure; Hemodynamics; Humans; Myocardial Infarction

Over 200 years age, William Withering described the advantages which might be gained by the considered use of extracts of the foxglove, digitalis purpurea, in patients with congestive heart failure, particularly if the rhythm was irregular. In the subsequent years many patients undoubtedly benefited from the use of this drug. The introduction of diuretics in the present century provided an alternative, more effective and safer treatment for heart failure. More recently, angiotensin-converting enzyme inhibitors have become available. The use of digoxin in the treatment of heart failure is now indicated almost solely for the control of a fast heart rate in patients with atrial fibrillation.

Topics: Digoxin; Heart Failure; Humans

There are no uniform diagnostic criteria for congestive heart failure. To determine the pattern of diagnostic criteria used, reports of 51 randomized, double-blind, placebo-controlled, clinical drug trials published between 1977 and 1985 were reviewed. Only 23 (45%) of the trials specified objective diagnostic criteria beyond treatment history, clinical diagnosis, or functional class. Of these, there were two trials each for digoxin, hydralazine, amrinone, and metoprolol; for each pair, only one study showed therapy beneficial. Of the amrinone pair, the positive study required a lower ejection fraction (less than 30% compared with less than 45%) and selected patients with more clinical severity. Conversely, for metoprolol, the positive study specified a higher ejection fraction (less than 49% compared with less than 35%) and selected patients with clinically milder disease, suggesting that conflicting results may relate to differences in study population. Many studies of congestive heart failure are done without explicit diagnostic criteria. Criteria lack uniformity, and such discrepancies may explain conflicting results.

Topics: Amrinone; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Hydralazine; Metoprolol; Research Design

Topics: Digitalis; Digoxin; Diuretics; Heart Failure; Humans; Plants, Medicinal; Plants, Toxic; Vasodilator Agents

The value of digoxin in the patient in normal sinus rhythm with chronic congestive heart failure continues to be controversial. Although many patients taking digoxin have no clinical deterioration after its discontinuance, there is a subgroup of patients (up to 30% of the total group) who demonstrate clinical deterioration on digoxin withdrawal. Patients with an S3 gallop and an enlarged left ventricle are especially likely to benefit from digoxin therapy. Furthermore, there is good evidence in patients with congestive heart failure that there is a persistent, chronic, positive inotropic effect with digoxin. Since digitalis is the only presently available, chronic, oral positive inotropic drug capable of increasing stroke volume at any given filling pressure, it should be used in patients with congestive heart failure.

Topics: Digitalis Glycosides; Digoxin; Diuretics; Heart Failure; Heart Rate; Humans; Myocardial Contraction; Physical Exertion; Substance Withdrawal Syndrome

Despite continuous controversy associated with a variety of aspects of the pharmacology of the cardiac glycosides, it appears that these agents will continue to be widely used in the future. Current methods for the measurement of digoxin are unreliable and allow measurement of both cardioinactive metabolites of digoxin and endogenous digoxin-like substances. As a result, the therapeutic monitoring of digoxin concentrations should, for the most part, be limited to an assessment of patient compliance and confirmation of a clinical impression of drug toxicity.

Topics: Animals; Blood Proteins; Cardenolides; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Immunoassay; Monitoring, Physiologic; Saponins

Topics: Anti-Arrhythmia Agents; Calcium Channel Blockers; Digoxin; Diuretics; Drug Interactions; Heart Failure; Humans

The epidemiology and etiology, pathophysiology, diagnosis, and treatment of congestive heart failure (CHF) are reviewed. CHF affects as many as 4 million Americans and is one of the most prevalent causes of death in hospitalized patients. Major risk factors for developing CHF include advanced age, male sex, hypertension, coronary artery disease, smoking, hypercholesterolemia, diabetes mellitus, and rheumatic heart disease. Heart failure results from decreased intrinsic myocardial contractility caused by one or more of three changes: (1) altered adrenergic nervous system function, (2) impaired delivery of calcium to contractile elements in the heart, and (3) reduced myosin-ATPase activity in the myocardium. The disease is progressive, and no intervention has yet been found to stop it effectively. CHF is diagnosed based on subjective signs and symptoms and objective assessment using auscultation, ECG, chest roentgenogram, laboratory tests, and noninvasive and invasive tests. Treatment of CHF begins with restriction of physical activity and sodium intake. Pharmacologic interventions start with either digitalis glycosides or thiazide diuretics; both may be used concomitantly as the disease progresses. Current studies are focusing on the use of angiotensin-converting enzyme inhibitors as first-line agents for CHF. When CHF worsens, loop diuretics are substituted for or added to the thiazide diuretics, and vasodilators are added to reduce the workload on the heart. Other inotropic agents, including the new bipyridine derivatives, may also be used. In patients not responding to these and other aggressive therapeutic interventions, cardiac transplantation is the only option. Despite advances in management of CHF, little improvement in overall survival has been demonstrated, and no intervention has stopped or reversed the progression of CHF.

Topics: Adrenergic beta-Agonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Output; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Myocardial Contraction; Oxygen Consumption; Risk; Vasodilator Agents

Positive inotropic agents are used to improve the impaired cardiac contractility that characterizes chronic heart failure. Digitalis is the traditional drug given for this purpose. However, there is controversy about the effectiveness of digitalis in chronic heart failure. Analysis of the available data indicates the efficacy of digoxin in mild heart failure (i.e., New York Heart Association functional classes I and II) and the relative lack of efficacy in advanced heart failure (i.e., NYHA functional class IV). Further, digoxin can be stopped in a substantial number of patients without recurrence of congestive heart failure. In selected patients whose condition no longer responds to digoxin, the long-term administration of dobutamine may be an effective alternative approach.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiac Glycosides; Cardiotonic Agents; Digitalis Glycosides; Digoxin; Dobutamine; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Infusions, Parenteral; Middle Aged; Myocardial Contraction; Random Allocation; Risk; Sodium-Potassium-Exchanging ATPase; Stroke Volume

Topics: Digitalis Glycosides; Digoxin; Heart Failure; History, 20th Century; Humans

Angiotensin converting enzyme inhibitors can be recommended in the treatment of severe cardiac failure (New York Heart Association Functional Class III or VI) where they are probably superior to other vasodilators. Their use should be considered when routine therapy with diuretics and digoxin has failed to ameliorate symptoms. Whether they can be recommended also for mild heart failure and whether the benefits outweigh any risks associated with long-term blockade of the renin-angiotensin system are questions that remain to be answered. Their use in hypertension and early in acute myocardial infarction might prevent the development of heart failure, but appropriate studies in man are awaited.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Digoxin; Diuretics; Dogs; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Kidney; Renin-Angiotensin System; Risk

Digitalis glycosides continue to place high on the list of prescribed drugs. Digoxin is 8th on prescriptions written in the United States in 1980, digitoxin 16th, and digitalis leaf 23rd. There is little doubt that most physicians continue to believe these drugs are useful. The application of more definite indications, smaller doses, and the recognition of the role of pharmacokinetics and drug interactions make use of the glycosides more challenging than ever before in 1985.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Age Factors; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Biological Availability; Bretylium Tosylate; Deslanoside; Digitalis Glycosides; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Heart Failure; Humans; Injections, Intramuscular; Injections, Intravenous; Intestinal Absorption; Kidney Failure, Chronic; Lidocaine; Metabolic Clearance Rate; Myocardial Infarction; Obesity; Phenytoin; Potassium; Pulmonary Heart Disease; Thyroid Diseases

This review mainly summarizes selected aspects of the present knowledge of drug elimination kinetics independent of developmental changes, with special attention given to clinical situations. The effects of different disease states, drug interactions, changes in urinary pH, induction of microsomal enzymes, competition for renal excretory mechanisms, possible enterohepatic recirculation, binding of drugs to tissues, effects of a drug on another drug's metabolizing organ, and dose-dependent elimination, on increase or decrease of drug elimination rates in children, have been presented. Based on the available data it seems that one may postulate the following conclusions: (1) that the distribution factors as well as changes in drug elimination capacities seem to play a role, perhaps with differing relative importance, during each of the maturational periods; (2) that the physicochemical properties of a drug and its dosage, as well as changes in the volume of distribution in children, in the course of certain disease states may have a significant effect on kinetics of drug disposition in the body; (3) that systemic clearance, a model independent parameter, rather than elimination half-life, a hybrid pharmacokinetic parameter, more accurately reflects elimination of some drugs from the body; (4) that each drug and every clinical situation may require the evaluation of the direct effect on pharmacokinetic processes, since general principles may not always apply; (5) that drug disposition studies should also be performed, if possible, on patients under actual clinical situations and receiving the usual therapeutic regime, and (6) that the half-life of colistin is independent of postnatal age which should serve as a warning not to generalize about drug excretion in the young infant.

Topics: Adult; Anti-Bacterial Agents; Brain Injuries; Child; Child, Preschool; Colistin; Cystic Fibrosis; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Female; Half-Life; Heart Failure; Humans; Hydrogen-Ion Concentration; Hypothermia, Induced; Infant; Infant, Newborn; Kidney; Kinetics; Liver; Nephrotic Syndrome; Nutrition Disorders; Pharmaceutical Preparations; Phenobarbital; Reye Syndrome; Serum Albumin; Urine

Since the initial introduction of digitalis 200 years ago by Withering, its low therapeutic ratio has limited the use of this agent. The utility of digitalis in patients with congestive heart failure and a recent myocardial infarction has been questioned recently. Findings of rigorously controlled clinical studies suggest a small but definite hemodynamic and clinical improvement in patients administered digitalis. Congestive heart failure can be effectively treated without cardiac glycosides. However, when used judiciously, digitalis provides an additional agent in our therapeutic armamentarium. The inotropic, dormotropic, and vagomimetic properties are uniquely suited for the patient with supraventricular arrhythmias and compromised left ventricular function.

Topics: Digitalis Glycosides; Digoxin; Heart Failure; Humans; Myocardial Contraction; Myocardial Infarction

Topics: Acute Disease; Blood Pressure; Cardiac Complexes, Premature; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Dobutamine; Heart Failure; Hemodynamics; Humans; Isoproterenol; Myocardial Infarction

Use of digitalis for the treatment of patients with congestive heart failure and sinus rhythm remains controversial. To ascertain the proper therapeutic role of digitalis, we have critically appraised the published clinical evidence of digitalis efficacy using standardized methodologic criteria. A search of the English literature from 1960 to 1982 identified 736 articles, of which 16 specifically addressed the clinical evaluation of digitalis therapy for patients with congestive heart failure and sinus rhythm. Only two double-blind, placebo-controlled trials provided clinically useful information. One study showed that digoxin therapy could be withdrawn successfully in elderly patients with stable congestive heart failure. The other showed that patients with chronic heart failure and an S3 gallop benefited from digoxin therapy.

Topics: Clinical Trials as Topic; Digitalis; Digitalis Glycosides; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Plants, Medicinal; Plants, Toxic; Pulmonary Heart Disease; Research Design

Topics: Adolescent; Captopril; Cardiomyopathies; Child; Digoxin; Dobutamine; Dopamine; Echocardiography; Electrocardiography; Endocarditis, Bacterial; Furosemide; Heart; Heart Defects, Congenital; Heart Diseases; Heart Failure; Humans; Hydralazine; Isoproterenol; Nitroprusside; Physical Examination; Radionuclide Imaging; Rheumatic Heart Disease

Topics: Arrhythmias, Cardiac; Blood Pressure; Creatine Kinase; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Heart Failure; Humans; Myocardial Contraction; Myocardial Infarction; Oxygen Consumption

The clinical and laboratory findings in and the treatment of congestive heart failure, supraventricular tachycardia, pericardial disease, and hypoxemic spells are discussed.

Topics: Child; Child, Preschool; Digoxin; Emergencies; Heart Diseases; Heart Failure; Humans; Hypoxia; Infant; Infant, Newborn; Pericarditis; Tachycardia, Paroxysmal

Topics: Action Potentials; Administration, Oral; Atrial Fibrillation; Atrioventricular Node; Autonomic Nervous System; Digitalis Glycosides; Digoxin; Drug Interactions; Exercise Test; Heart Failure; Verapamil; Wolff-Parkinson-White Syndrome

Topics: Catecholamines; Digoxin; Dobutamine; Dopamine; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Myocardial Infarction; Nitroprusside; Oxygen Consumption

Topics: Adult; Aged; Biological Availability; Blood Proteins; Digitalis Glycosides; Digitoxin; Digoxin; Female; Heart Failure; Humans; Intestinal Absorption; Kidney; Kinetics; Male; Middle Aged; Protein Binding

The current extensive use of digoxin in elderly patients with left ventricular failure and sinus rhythm may not be clinically justifiable; in a significant proportion of these patients the frequency of digitalis toxicity may outweight the therapeutic benefits of the drug. When digoxin is used in elderly patients, the specific geriatric pharmacology of the drug must be considered. Clinical benefit should be documented before proceeding to long-term maintenance therapy. In selected elderly patients, withdrawal of digoxin with careful follow-up may be a worthwhile procedure. Studies are needed comparing the relative benefits and toxicities of digoxin versus diuretics in the management of heart failure in the elderly.

Topics: Adult; Age Factors; Aged; Atrial Fibrillation; Digoxin; Diuretics; Drug Interactions; Half-Life; Heart Conduction System; Heart Failure; Heart Ventricles; Humans; Middle Aged; Monitoring, Physiologic; Patient Compliance; Quinidine

Topics: Acute Kidney Injury; Airway Obstruction; Anemia, Hemolytic; Arteriovenous Fistula; Asphyxia Neonatorum; Cardiac Output; Digoxin; Ductus Arteriosus, Patent; Female; Heart Failure; Humans; Hyperthyroidism; Hypoglycemia; Infant; Infant, Newborn; Isoproterenol; Medical History Taking; Pregnancy; Pulmonary Edema; Pulmonary Valve; Sepsis; Streptococcal Infections; Tachycardia, Paroxysmal; Tricuspid Valve Insufficiency

Topics: Digoxin; Echocardiography; Electrocardiography; Heart Failure; Humans; Plethysmography, Impedance; Propranolol; Pulmonary Circulation; Renin-Angiotensin System; Sympathetic Nervous System; Vasodilator Agents

Recent intoxication studies during digitalis therapy have shown that digoxin and digitoxin produce different pharmakokinetic results. The main difference is in the elimination pathways of the two substances. Whereas digoxin is almost exclusively excreted by the kidneys, digitoxin may be excreted both by the kidneys and by the intestine via the bile. New dosage guidelines have resulted from these studies. The problems of adjustment by means of instrumental parameters are presented and the need for individual dosage on the least effective dose principle is discussed.

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Dosage Forms; Dose-Response Relationship, Drug; Heart Failure; Humans; Kidney; Liver

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure; Humans; Radioimmunoassay

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Failure, Chronic

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure; Humans; Intestinal Absorption

Topics: Arrhythmias, Cardiac; Delirium; Depression; Digitalis Glycosides; Digitoxin; Digoxin; Hallucinations; Heart Failure; Humans; Vision Disorders

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic; Poisoning; Vision Disorders

Topics: Animals; Cardiomyopathies; Cat Diseases; Cats; Diet, Sodium-Restricted; Digoxin; Electrocardiography; Furosemide; Heart Diseases; Heart Failure; Lidocaine; Propranolol; Thromboembolism

Topics: Arrhythmias, Cardiac; Body Fluids; Digoxin; Heart Failure; Humans; Methods

Topics: Aldosterone; Animals; Blood Volume; Cardiac Output; Diet, Sodium-Restricted; Digitalis Glycosides; Digoxin; Diuretics; Dog Diseases; Dogs; Edema; Extracellular Space; Heart Failure; Infusions, Parenteral; Kidney; Ouabain; Thirst

Topics: Animals; Body Weight; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic; Liver Diseases; Myocardial Contraction; Protein Binding; Structure-Activity Relationship; Thyroid Diseases; Tissue Distribution

Topics: Acid-Base Imbalance; Aged; Atropine; Cardiac Complexes, Premature; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Heart Block; Heart Failure; Heart Ventricles; Humans; Kidney Failure, Chronic; Phenytoin; Potassium; Tachycardia

Topics: Angina Pectoris; Arrhythmias, Cardiac; Biological Availability; Cardiac Glycosides; Central Nervous System Diseases; Digitoxin; Digoxin; Endocrine System Diseases; Gastrointestinal Diseases; Heart Failure; Humans; Hypersensitivity; Hypertension; Intestinal Absorption; Myocardial Infarction; Preoperative Care

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Heart Failure; Humans; Hyperthyroidism; Hypothyroidism; Intestinal Absorption; Kidney Failure, Chronic; Molecular Conformation; Obesity

Topics: Benzothiadiazines; Diagnosis, Differential; Digoxin; Diuretics; Heart Failure; Humans; Hyponatremia; Lung Diseases; Sodium Chloride Symporter Inhibitors; Vascular Resistance; Vasodilator Agents

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Diuretics; Dogs; Haplorhini; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Potassium

Cardiovascular diseases and their treatment in the aged are discussed under the headings of ischemic heart disease, hypertension, cardiac failure (with special reference to the use of diuretics and digoxin), infective carditis and thyroid disorders. Advanced age modifies the approach to treatment; the choice of drugs and the dosage must be adjusted accordingly. Possible drug interactions should also be considered. A rehabilitation program is of great benefit for many elderly cardiac patients. It should be planned individually and involve psychologic and environmental factors as well as medical therapy. After successful treatment of the acute episode, even the aged patient can undertake rewarding activities in his remaining lifetime.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Bacterial Agents; Arrhythmias, Cardiac; Benzothiadiazines; Cardiac Rehabilitation; Cardiac Surgical Procedures; Cardiovascular Diseases; Coronary Disease; Delayed-Action Preparations; Digoxin; Diuretics; Endocarditis; Female; Heart Failure; Humans; Hypertension; Hypertension, Malignant; Hyperthyroidism; Hypothyroidism; Isosorbide Dinitrate; Male; Methyldopa; Middle Aged; Nitroglycerin; Sodium Chloride Symporter Inhibitors

The pharmacokinetics of the cardiac glycofides have been elucidated as a result of the development of assays of sufficient sensitivity to measure the concentration of digitalis compounds in biological fluids. Digoxin can accumulate in the body without the administration of a loading dose, and a steady state blood concentration will be reached in 5 to 7 days. Digitoxin requires 35 days to accumulate to a plateau. If a loading dose of digoxin is used, it should be approximately three times the estimated daily maintenance dose. Factors that determine the selection of the appropriate maintenance dose of digoxin include renal function and lean body mass. Digitoxin is less dependent on renal function for its elimination than is digoxin. Knowledge of the pharmacokinetics of digitalis preparations is useful in determining how to change from one cardiac glycoside to another, each with different half-lives. One should wait 3 days before starting digoxin therapy when changing from maintenance digitoxin to digoxin (assuming normal renal function). The pharmacokinetics of changing from ouabain to digoxin without loss of digitalis effect are described. The metabolism of the commonly used digitalis preparations are summarized.

Topics: Atrial Fibrillation; Creatinine; Delayed-Action Preparations; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Feces; Half-Life; Heart Failure; Humans; Kidney; Kinetics; Ouabain; Time Factors

Topics: Administration, Oral; Aged; Digitalis Glycosides; Digitoxin; Digoxin; Feces; Heart Atria; Heart Failure; Humans; Injections, Intramuscular; Injections, Intravenous; Intestinal Absorption; Kidney Diseases; Liver Diseases; Malabsorption Syndromes; Obesity; Tachycardia; Thyroid Diseases; Tritium; Water-Electrolyte Balance

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Drug Therapy; England; Heart Failure; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Intestinal Absorption; Molecular Conformation; Protein Binding

Topics: Acute Disease; Aminophylline; Assisted Circulation; Cardiac Glycosides; Digoxin; Diuretics; Electric Countershock; Heart; Heart Diseases; Heart Failure; Humans; Morphine; Ouabain; Oxygen Inhalation Therapy; Phentolamine; Pulmonary Edema; Tachycardia; Vasodilator Agents

Topics: Age Factors; Arrhythmias, Cardiac; Child; Child, Preschool; Chlorothiazide; Diet, Sodium-Restricted; Digitalis Glycosides; Digoxin; Diuretics; Ethacrynic Acid; Furosemide; Heart Block; Heart Defects, Congenital; Heart Failure; Heart Septal Defects, Ventricular; Humans; Infant; Infant, Newborn; Organomercury Compounds; Pacemaker, Artificial; Phenytoin; Procainamide; Propranolol; Quinidine; Tetralogy of Fallot; Transposition of Great Vessels

Topics: Age Factors; Creatinine; Diet; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Heart Failure; Humans; Hypercalcemia; Hypokalemia; Kidney; Kinetics; Liver; Magnesium; Ouabain; Plants, Medicinal; Plants, Toxic; Rest; Thyroid Gland; Time Factors

Topics: Adenosine Triphosphatases; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart; Heart Failure; Heart Rate; Humans; Kidney Diseases; Kinetics; Lanatosides; Lidocaine; Myocardium; Pacemaker, Artificial; Phenytoin; Potassium; Procainamide; Propranolol; Quinidine; Thyroid Diseases

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Coronary Disease; Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure; Humans; Tachycardia, Paroxysmal

Topics: Cardiac Output; Catecholamines; Digitalis Glycosides; Digitoxin; Digoxin; Dopamine; Glucagon; Heart; Heart Failure; Humans; Isoproterenol; Myocardial Infarction; Norepinephrine

Topics: Arrhythmias, Cardiac; Bradycardia; Cardiac Complexes, Premature; Child; Child, Preschool; Deafness; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Failure; Heart Ventricles; Humans; Infant; Infant, Newborn; Lidocaine; Male; Propranolol; Tachycardia; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

Topics: Arrhythmias, Cardiac; Creatinine; Digitoxin; Digoxin; Heart Failure; Humans; Intestinal Absorption; Protein Binding; Time Factors

Topics: Absorption; Aldosterone; Animals; Cardiac Glycosides; Digitalis Glycosides; Digoxin; Diuresis; Diuretics; Dogs; Heart Failure; Humans; Kidney; Kidney Tubules; Lanatosides; Natriuresis; Plants, Medicinal; Strophanthins

Topics: Age Factors; Arrhythmias, Cardiac; Calcium; Child; Coronary Care Units; Digitalis Glycosides; Digoxin; Electric Countershock; Electrocardiography; Endocrine System Diseases; Heart Diseases; Heart Failure; Heart Rate; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Liver Diseases; Lung Diseases; Magnesium; Obesity; Ouabain; Poisoning; Potassium; Psychophysiologic Disorders; Pulmonary Heart Disease; Thyroid Diseases; Time Factors

Topics: Arrhythmias, Cardiac; Digoxin; Gastrointestinal Diseases; Heart Failure; Humans; Injections; Tablets

Topics: Acid-Base Equilibrium; Acidosis; Angiocardiography; Blood Gas Analysis; Blood Pressure; Bradycardia; Cardiac Catheterization; Cardiac Output; Child; Child, Preschool; Cineangiography; Cyanosis; Digoxin; Diuretics; Dyspnea; Electrocardiography; Heart Auscultation; Heart Block; Heart Defects, Congenital; Heart Failure; Heart Rate; Humans; Infant; Infant, Newborn; Oxygen Inhalation Therapy; Pulse; Referral and Consultation; Tachycardia; Vectorcardiography

Topics: Atrial Fibrillation; Atrial Flutter; Cardiac Surgical Procedures; Digitalis; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Block; Heart Failure; Humans; Isoproterenol; Lanatosides; Mitral Valve Stenosis; Pacemaker, Artificial; Tachycardia; Thoracic Surgery; Toxicology; Ventricular Fibrillation

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensins; Desoxycorticosterone; Digoxin; Dogs; Heart Failure; Hyperaldosteronism; Hypertension; Hypertension, Renal; Kidney; Liver Cirrhosis; Metabolism; Nephrosis; Physiology; Renin; Research; Sodium

In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared with placebo reduced the risk of heart failure events or cardiovascular death in patients with heart failure with reduced ejection fraction. We explored the influence of atrial fibrillation or flutter (AFF) on the effectiveness of omecamtiv mecarbil.. GALACTIC-HF enrolled patients with New York Heart Association (NYHA) Class II-IV heart failure, left ventricular ejection fraction ≤35%, and elevated natriuretic peptides. We assessed whether the presence or absence of AFF, a pre-specified subgroup, modified the treatment effect for the primary and secondary outcomes, and additionally explored effect modification in patients who were or were not receiving digoxin. Patients with AFF (n = 2245, 27%) were older, more likely to be randomized as an inpatient, less likely to have a history of ischaemic aetiology or myocardial infarction, had a worse NYHA class, worse quality of life, lower estimated glomerular filtration rate, and higher N-terminal pro-B-type natriuretic peptide. The treatment effect of omecamtiv mecarbil was modified by baseline AFF (interaction P = 0.012), with patients without AFF at baseline deriving greater benefit. The worsening of the treatment effect by baseline AFF was significantly more pronounced in digoxin users than in non-users (interaction P = 0.007); there was minimal evidence of effect modification in those patients not using digoxin (P = 0.47) or in digoxin users not in AFF.. Patients in AFF at baseline were less likely to benefit from omecamtiv mecarbil than patients without AFF, although the attenuation of the treatment effect was disproportionally concentrated in patients with AFF who were also receiving digoxin.Clinical Trial Registration: NCT02929329.

Topics: Atrial Fibrillation; Atrial Flutter; Digoxin; Heart Failure; Humans; Quality of Life; Stroke Volume; Urea; Ventricular Function, Left

There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure.. To compare low-dose digoxin with bisoprolol (a β-blocker).. Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019.. Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d).. The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting.. Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group.. Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points.. ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.

Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Quality of Life; Single-Blind Method; Stroke Volume

Anemia aggravates the disease course and the survival rate of chronic heart failure (CHF) patients. The purpose of the study was to investigate the level of erythropoietin (EPO) in CHF patients with anemic syndrome, with the aim to more accurately assess the severity of the disease and its treatment, depending on the anemia degree.. Patients with ischemic CHF of I-IV functional class (FC) with and without anemia were examined (total number of patients=208, patients with anemia=174). The EPO was determined using the enzyme-linked immunosorbent assay. Before treatment, the patients underwent the following medical therapy: angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, long-acting nitrates, diuretics, digoxin, and beta-blockers at individual doses. Depending on the plasma EPO level, the CHF patients with anemia were divided into four randomized groups in terms of treatment.. Normal erythropoietinemia was found in 36.2% of the CHF patients with anemic syndrome (I-III FC), hypoerythropoietinemia in 44.8% (III-IV FC), and hypererythropoietinemia in 18.96% (III-V FC). The EPO level in the blood plasma of the patients with I-II FC CHF with hypoerythropoietinemia, who were treated with methoxy polyethylene glycol-epoetin β (MEB), increased by 2.2 times. Combination therapy with disease-modifying drugs and MEB led to a significant increase in the plasma EPO level in the CHF patients with hypoerythropoietinemia.. It was shown that the EPO level in patients with CHF and anemia did not always drop. Hypererythropoietinemia in patients with CHF and anemia leads to an unfavorable treatment prediction. This necessitates the investigation of the EPO level in all patients with CHF before and after treatment, with the aim of correcting the anemic syndrome. The research showed that the combined therapy of patients with CHF and anemia using MEB medication and iron with regard to the EPO level in the blood plasma improved their overall physical condition, reduced heart failure symptoms and hospitalization frequency, and demonstrated a clear tendency to reduce the general mortality rate.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Anemia; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Erythropoietin; Female; Heart Failure; Humans; Male; Middle Aged; Nitrates; Severity of Illness Index

To evaluate the effects of digoxin in patients with the newly described phenotype of heart failure (HF) and mid-range ejection fraction (HFmrEF), attributed to mild left ventricular systolic dysfunction.. We carried out a retrospective analysis of the Digitalis Investigation Group (DIG) trial which had 7788 patients available for analysis with a left ventricular ejection fraction (LVEF) ranging between 3% and 85%. We compared the effect of digoxin to placebo in three mutually exclusive groups of patients defined by LVEF category: <40% (HF with reduced LVEF, HFrEF, n = 5874), 40-49% (HFmrEF, n = 1195) and ≥50% (HF with preserved LVEF, HFpEF, n = 719). The primary outcome was the composite of cardiovascular death or HF hospitalisation. Patients with HFmrEF resembled patients with HFrEF, more than those with HFpEF, with respect to age, sex and aetiology but were more like HFpEF patients with respect to blood pressure and the prevalence of hypertension. Event rates in patients with HFmrEF were similar to those in HFpEF and much lower than in HFrEF. Digoxin reduced the primary endpoint in patients with HFrEF, mainly due to reduced HF hospitalisation: the digoxin/placebo hazard ratio (HR) for HF hospitalisation was 0.71 [95% confidence interval (CI) 0.65-0.77]. The digoxin/placebo HR for HF hospitalisation in patients with HFmrEF was 0.80 (95% CI 0.63-1.03) and 0.85 (95% CI 0.62-1.17) in those with HFpEF. The digoxin/placebo HR for the composite of HF death or HF hospitalisation was 0.74 (95% CI 0.68-0.81) in HFrEF, 0.83 (95% CI 0.66-1.05) in HFmrEF and 0.88 (95% CI 0.65-1.19) in HFpEF.. In this study, event rates in patients with HFmrEF were closer to those in HFpEF than HFrEF. Digoxin had most effect on HF hospitalisation in patients with HFrEF, an intermediate effect in HFmrEF, and the smallest effect in HFpEF.

Topics: Aged; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Digoxin is widely used in patients with atrial fibrillation (AF).. The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration.. The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.. At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users.. In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations ≥1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Correlation of Data; Death, Sudden; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Risk Assessment; Risk Factors

Digoxin use has been associated with a lower risk of 30-day all-cause admission and readmission in patients with heart failure and reduced ejection fraction (HFrEF).. Digoxin use will be associated with improved outcomes in patients with HFrEF receiving β-blockers.. Of the 3076 hospitalized Medicare beneficiaries with HFrEF (EF <45%), 1046 received a discharge prescription for β-blockers, of which 634 were not on digoxin. Of the 634, 204 received a new discharge prescription for digoxin. Propensity scores for digoxin use, estimated for each of the 634 patients, were used to assemble a matched cohort of 167 pairs of patients receiving and not receiving digoxin, balanced on 30 baseline characteristics. Matched patients (n = 334) had a mean age of 74 years and were 46% female and 30% African American.. 30-day all-cause readmission occurred in 15% and 27% of those receiving and not receiving digoxin, respectively (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.31-0.83, P = 0.007). This beneficial association persisted during 4 years of follow-up (HR: 0.72, 95% CI: 0.57-0.92, P = 0.008). Digoxin use was also associated with a lower risk of the combined endpoint of all-cause readmission or all-cause mortality at 30 days (HR: 0.54, 95% CI: 0.34-0.86, P = 0.009) and at 4 years (HR: 0.76, 95% CI: 0.61-0.96, P = 0.020).. In hospitalized patients with HFrEF receiving β-blockers, digoxin use was associated with a lower risk of 30-day all-cause readmission but not mortality, which persisted during longer follow-up.

Topics: Adrenergic beta-Antagonists; Aged; Alabama; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Echocardiography; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Hospital Mortality; Humans; Male; Patient Readmission; Propensity Score; Retrospective Studies; Survival Rate; Time Factors; Ventricular Function, Left

Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF).. HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters.. The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO. Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is required to clarify the role of digoxin in contemporary clinical practice including its effects on functional capacity, quality of life, and long-term outcomes.

Topics: Canada; Cardiotonic Agents; Cause of Death; Digoxin; Dose-Response Relationship, Drug; Exercise; Exercise Therapy; Female; Follow-Up Studies; France; Health Status; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Outpatients; Retrospective Studies; Stroke Volume; Time Factors; Treatment Outcome; United States

Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being.. The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF.. Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice.. The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF.. East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications.. Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results.

Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Digoxin; Female; Heart Failure; Heart Rate; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Research Design; Stroke; Time; United Kingdom

Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated according to diabetes status.. We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Mortality from all-cause, cardiovascular (CV) causes and heart failure (HF), along with HF hospitalisation and suspected digoxin toxicity were analyzed according to diabetes status and randomised treatment assignment.. Of the 6800 patients, those with diabetes (n=1933) were older, more often women, had worse clinical status and more co-morbidity than those without diabetes. All-cause and CV mortality were higher in patients with diabetes than in those without and digoxin did not reduce mortality in either sub-group. The rate of HF hospitalization (per 100 person-years) in patients with diabetes was higher than in those without and was reduced by digoxin in both patient groups: diabetes - placebo 20.5 and digoxin 16.0 (HR 0.79, 95% CI: 0.68-0.91); no diabetes - placebo 12.7 and digoxin 8.7 (HR 0.69, 0.62-0.77); interaction p=0.14. Suspected digoxin toxicity in patients randomised to digoxin was more common among patients with diabetes than without (6.5% versus 5.8%), as was hospitalisation for digoxin toxicity (1.4% versus 0.8%).. Added to an ACE inhibitor, digoxin reduced HF hospitalisation in HF-REF patients with and without diabetes without a substantial risk of toxicity.

Topics: Aged; Cardiotonic Agents; Diabetes Mellitus; Digitalis; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hyperkalemia; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke Volume; Treatment Outcome

Although inappropriate use of digoxin has been described in various populations, a real-world evaluation of patterns of digoxin prescription has not been well studied in patients with atrial fibrillation (AF). The aim of this study was to identify prevalence, indications and appropriateness of digoxin use in the general population of patients with non-valvular AF (NVAF) in Turkey.. We included and classified patients from the RAMSES (ReAl-life Multicentre Survey Evaluating Stroke prevention strategies in Turkey) study, a prospective registry including 6273 patients with NVAF, on the basis of digoxin use. After excluding the data of 73 patients whose medical history about digoxin use or left ventricle function was absent, 6200 patients were included for the final analysis. Digoxin use was considered inappropriate if patients did not have left ventricular systolic dysfunction or symptomatic heart failure (HF).. Digoxin was used in 1274 (20·5%) patients. Patients treated with digoxin were older (71·4 ± 9·8 years vs. 69·2 ± 10·9 years, P < 0·001), more likely to be female (58·8% vs. 55·9%, P = 0·019) and had more common comorbidities such as HF (40·2% vs. 17·4%), diabetes (26·4% vs. 21·1%), coronary artery disease (35·3 vs. 27·6%) and persistent/permanent AF (93·4% vs. 78·4%; P < 0·001 for each comparison). Of the 1274 patients, the indication of digoxin use was considered inappropriate in 762 (59·8%).. Our findings show that nearly one-fifth of the patients with NVAF were on digoxin therapy and nearly 60% of these patients were receiving digoxin with inappropriate indications in a real-world setting.

Topics: Aged; Atrial Fibrillation; Comorbidity; Digoxin; Female; Heart Failure; Heart Ventricles; Humans; Male; Prospective Studies; Stroke; Turkey

We sought to determine the relationship between changes in natriuretic peptides and symptoms as a consequence of introducing beta-blocker therapy, in patients with chronic heart failure (CHF) and persistent atrial fibrillation (AF).. In a randomised, double-blind, placebo-controlled study involving 47 patients with CHF and persistent AF (mean age 68 years and 62% men), we analysed the individual change (Δ) in B-type natriuretic peptide (BNP) level to the introduction of carvedilol (titrated to a target dose of 25 mg twice daily, group A) or placebo (group B) in addition to background treatment with digoxin. Symptoms score, 6-min walk distance, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), heart rate (24-hour ECG) and BNP were measured at baseline and at 4 months.. LVEF (Δ median +5 vs. +0.4, p = 0.048), symptoms score (Δ median -4 vs. 0, p = 0.04), NYHA class (Δ median -33% vs. +3% in NYHA class 3-4, p = 0.046) and heart rate [Δ median 24-hour ventricular rate (VR) -19 vs. -2, p < 0.0001] improved with combination therapy of digoxin and carvedilol compared to digoxin alone, but BNP (Δ median +28 vs. -6 , p = 0.11) trended in the opposite direction. There was no relationship between the degree of symptomatic improvement or VR control and BNP response.. After the introduction of carvedilol, clinical outcome appears unrelated to BNP changes in patients with CHF and AF. Changes in BNP cannot be used as a marker of clinical response in terms of symptoms or cardiac function in this setting.

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Biomarkers; Carbazoles; Carvedilol; Case-Control Studies; Digoxin; Double-Blind Method; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Propanolamines; Treatment Outcome; Ventricular Function, Left

Digoxin is widely used for rate control of atrial fibrillation. However, recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation. Moreover, the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined.. All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during follow-up (n = 803), randomly assigned to losartan or atenolol-based treatment, in post-hoc analysis of a substudy of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial. During 4.7 ± 1.1 years of mean follow-up, 167 patients died (17.8%) and 372 (39.7%) were treated with digoxin. In univariate Cox analyses, in-treatment digoxin use, entered as a time-varying covariate, was associated with a 61% higher risk of dying (hazard ratio 1.61, 95% confidence interval 1.18-2.19, P = 0.003). After adjusting for other univariate predictors of death in this population, including age, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse pressure, and Sokolow-Lyon voltage treated as time-varying covariates, digoxin use was no longer a significant predictor of mortality (hazard ratio 1.04, 95% confidence interval 0.73-1.48, P = 0.839).. In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population. These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies.. .

Topics: Aged; Anti-Arrhythmia Agents; Antihypertensive Agents; Atenolol; Atrial Fibrillation; Blood Pressure; Digoxin; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Lipoproteins, HDL; Losartan; Male; Middle Aged; Risk

Digoxin's pharmacological, hemodynamic, and electrophysiological properties are well understood. However, in modern heart failure (HF) treatment, its effect has yet to be fully investigated.. The aim of the present study was to determine the effects of digoxin on outcomes in patients with mild HF implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D) device.. We investigated the effect of digoxin treatment on the end points of HF/death, HF alone, death alone, and ventricular tachycardia or ventricular fibrillation (VT/VF) in 1820 patients with mild HF (New York Heart Association class I and II), prolonged QRS duration (≥130 ms), and reduced left ventricular ejection fraction (≤30%) enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy trial. Multivariate Cox proportional hazards regression models were used to determine the effect of time-dependent digoxin usage on the end points.. Digoxin therapy was not associated with an increased or decreased risk of HF/death (hazard ratio [HR] 1.07; 95% confidence interval [CI] 0.86-1.33; P = .0.56), HF alone (HR 1.1.04; 95% CI 0.82-1.32; P = .76), or death alone (HR 0.93; 95% CI 0.67-1.32; P = .71). However, digoxin was associated with a significant 41% increased risk of VT/VF (HR 1.41; 95% CI 1.14-1.75; P = .002), which was driven by a significantly increased risk of VT/VF with heart rate ≥200 beats/min (HR 1.65; 95% CI 1.27-2.15; P ≤ .001), whereas no increased risk of VT/VF with heart rate <200 beats/min was evident (HR 1.20; 95% CI 0.92-1.57; P = .19). No significant differences in digoxin's effect on any of the end points were found between patients with ICD and patients with CRT-D (interaction P > .5).. The use of digoxin in patients with mild HF implanted with an ICD or CRT-D device was not associated with reductions in HF/death events. However, digoxin therapy was associated with an increased risk of high-rate VT/VF (≥200 beats/min).

Topics: Canada; Cardiac Resynchronization Therapy; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Europe; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Incidence; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Survival Rate; Tachycardia, Ventricular; Time Factors; United States

Previous studies on digoxin use in patients with atrial fibrillation (AF) and the risk of all-cause mortality found conflicting results. We conducted a population-based, retrospective, cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec province, Canada, from 1998 to 2012. The AF cohort was grouped into patients with and without heart failure (HF) and into digoxin and no-digoxin users according to the first prescription filled for digoxin within 30 days after AF hospital discharge. We derived propensity score-matched digoxin and no-digoxin treatment groups for the groups of patients with and without HF, respectively, and conducted multivariable Cox proportional hazards regression analyses to determine association between digoxin use and all-cause mortality. The AF propensity score-matched cohorts of patients with and without HF were well balanced on baseline characteristics. In the propensity score-matched HF group, digoxin use was associated with a 14% greater risk of all-cause mortality (adjusted hazard ratio 1.14, 95% confidence interval 1.10 to 1.17). In the propensity score-matched no-HF group, digoxin use was associated with a 17% greater risk of all-cause mortality (adjusted hazard ratio 1.17, 95% confidence interval 1.14 to 1.19). In conclusion, our retrospective analyses found that digoxin use was associated with a greater risk for all-cause mortality in patients aged ≥65 years with AF regardless of concomitant HF. Large, multicenter, randomized controlled trials or prospective cohort studies are required to clarify this issue.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failure; Humans; Male; Population Surveillance; Prognosis; Propensity Score; Prospective Studies; Quebec; Risk Assessment; Risk Factors; Survival Rate

To compare the frequency of achieving a therapeutic serum digoxin concentration (SDC), defined as 0.5-0.9 ng/ml, by using a simplified nomogram to individualize digoxin dosing with standard dosing practices in patients with heart failure, and to characterize the relationship between genetic polymorphisms of the ABCB1 gene and SDC.. Prospective study with a historical control group.. Outpatient care center of an urban academic medical center.. A total of 131 adults with heart failure due to left ventricular dysfunction who were treated with digoxin.. Digoxin doses were determined either by the dosing nomogram (65 patients) or standard care (SC; 66 patients) by using historical controls who were randomly selected from a list of SDCs obtained from laboratory records and who had their digoxin doses determined by standard dosing practices.. The primary end point was the proportion of patients achieving a steady-state SDC of 0.5-0.9 ng/ml; secondary end points were mean SDC and proportion of patients achieving a steady-state SDC lower than 1.0 ng/ml. Postdistributive steady-state SDCs were measured 2-4 weeks after digoxin dosage adjustment or initiation. Therapeutic SDCs were achieved with similar frequency in both groups (38.7% in the nomogram group vs 34.5% in the SC group, p=0.65); however, more patients in the nomogram group had SDCs lower than 1.0 ng/ml than in the SC group (85.0% vs 44.9%, p<0.001). Mean daily digoxin doses were lower in the nomogram group (149 ± 67 μg vs 177 ± 74 μg, p=0.02), resulting in lower mean SDCs compared with those in the SC group (0.52 ± 0.30 ng/ml vs 1.12 ± 0.58 ng/ml, p<0.001). Patients in the pharmacogenetic substudy provided blood samples for genotyping of three common ABCB1 single nucleotide polymorphisms: C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642). SDCs were not significantly associated with ABCB1 genotypes.. Our simplified digoxin dosing nomogram resulted in lower SDCs compared with standard dosing practices but achieved therapeutic SDCs with similar frequency. A greater proportion of patients dosed according to our nomogram had SDCs lower than 1.0 ng/ml, consistent with consensus guidelines. Genetic polymorphisms of the ABCB1 gene were not associated with SDC.

Topics: Academic Medical Centers; Aged; Amino Acid Substitution; ATP Binding Cassette Transporter, Subfamily B; Cardiotonic Agents; Chicago; Digoxin; Dose-Response Relationship, Drug; Drug Monitoring; Female; Gene Frequency; Genetic Association Studies; Heart Failure; Historically Controlled Study; Humans; Male; Middle Aged; Nomograms; Outpatient Clinics, Hospital; Polymorphism, Single Nucleotide; Precision Medicine; Ventricular Dysfunction, Left

Elevated serum digoxin concentration can cause toxicity, including death. Dronedarone increases digoxin concentration by P-glycoprotein interaction. In Permanent Atrial Fibrillation Outcome Study Using Dronedarone On Top Of Standard Therapy Trial (PALLAS), dronedarone was associated with both increased cardiovascular death and heart failure in patients with permanent atrial fibrillation. The present analysis examines whether the dronedarone-digoxin interaction might explain these adverse outcomes.. Subgroup analysis was performed to compare outcomes of patients on digoxin at baseline or not. In PALLAS, 1619 patients were randomized to dronedarone and 1617 to placebo, of whom 544 (33.6%) and 526 (32.5%) were receiving digoxin, respectively. Median (Q1,Q3) digoxin serum concentration on day 7 was 1.1 (0.7,1.5) ng/mL on dronedarone and 0.7 (0.5,1.1) ng/mL on placebo (P<0.001). Among patients on digoxin, there were 15 (8.6%/year) cardiovascular deaths on dronedarone and 2 (1.2%/year) on placebo (adjusted hazard ratio, 7.31; 95% confidence interval, 1.66-32.20; P=0.009). Among patients not on digoxin, there were 6 cardiovascular deaths on dronedarone (1.7%/year) and 8 on placebo (2.2%/year; adjusted hazard ratio, 0.67; 95% confidence interval, 0.23-1.95; P=0.46; interaction P value 0.01). In patients on digoxin, there were 11 arrhythmic deaths on dronedarone and none on placebo; and in patients not on digoxin, there were 2 arrhythmic deaths on dronedarone and 4 on placebo (P value for interaction 0.002). There was no interaction between baseline digoxin use and the adverse effect of dronedarone on heart failure events.. In PALLAS, there was a strong effect of concurrent digoxin use on the adverse effect of dronedarone on cardiovascular death, but not on occurrence of heart failure.. http://www.clinicaltrials.gov. Unique identifier: NCT01151137.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Cause of Death; Digoxin; Double-Blind Method; Dronedarone; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Electrocardiography; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Proportional Hazards Models; Risk Factors; Time Factors; Treatment Outcome

Digoxin is recommended for long-term rate control in paroxysmal, persistent, and permanent atrial fibrillation (AF). While some analyses suggest an association of digoxin with a higher mortality in AF, the intrinsic nature of this association has not been examined in propensity-matched cohorts, which is the objective of the current study.. In Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), 4060 patients with paroxysmal and persistent AF were randomized to rate (n = 2027) vs. rhythm (n = 2033) control strategies. Of these, 1377 received digoxin as initial therapy and 1329 received no digoxin at baseline. Propensity scores for digoxin use were estimated for each of these 2706 patients and used to assemble a cohort of 878 pairs of patients receiving and not receiving digoxin, who were balanced on 59 baseline characteristics. Matched patients had a mean age of 70 years, 40% were women, and 11% non-white. During the 3.4 years of the mean follow-up, all-cause mortality occurred in 14 and 13% of matched patients receiving and not receiving digoxin, respectively [hazard ratio (HR) associated with digoxin use: 1.06; 95% confidence interval (CI): 0.83-1.37; P = 0.640]. Among matched patients, digoxin had no association with all-cause hospitalization (HR: 0.96; 95% CI: 0.85-1.09; P = 0.510) or incident non-fatal cardiac arrhythmias (HR: 0.90; 95% CI: 0.37-2.23; P = 0.827). Digoxin had no multivariable-adjusted or propensity score-adjusted associations with these outcomes in the pre-match cohort.. In patients with paroxysmal and persistent AF, we found no evidence of increased mortality or hospitalization in those taking digoxin as baseline initial therapy.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Digoxin; Female; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Propensity Score; Treatment Outcome

Digitalis glycosides are known to improve the hemodynamic and neurohormonal perturbations that contribute to heart failure (HF)-induced renal dysfunction (RD). The objective of this study was to determine if randomization to digoxin is associated with improvement in renal function (IRF) and to evaluate if patients with digoxin-induced IRF have improved clinical outcomes.. Patients in the Digitalis Investigation Group (DIG) dataset with protocol-driven 1-year serum creatinine levels (performed in a central laboratory; n = 980) were studied. IRF was defined as a postrandomization ≥20% increase in estimated glomerular filtration rate (eGFR). IRF occurred in 15.5% of the population (mean improvement in eGFR 34.5 ± 15.4%) and was more common in patients randomized to digoxin (adjusted odds ratio 1.6; P = .02). In patients without IRF, digoxin was not associated with reduced death or hospitalization (adjusted hazard ratio [HR] 0.96, 95% CI 0.8-1.2; P = .67). However, in the group with IRF, digoxin was associated with substantially improved hospitalization-free survival (adjusted HR 0.49, 95% CI 0.3-0.8; P = .006; P interaction = .026).. In this subset of the DIG trial, digoxin was associated with long-term improvement in kidney function and, in patients demonstrating this favorable renal response, reduction in death or hospitalization. Additional research is necessary to confirm these hypothesis-generating findings.

Topics: Cardio-Renal Syndrome; Cardiotonic Agents; Creatinine; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Male; Middle Aged

The aim of this study was to investigate the influences of Simvastatin (Zocor) on nitric oxide (NO), calcitonin gene related peptide (CGRP) and endothelin (ET) in blood plasma of patients with coronary heart disease (CHD) complicated with congestive heart failure (CHF).. 80 cases of patients with CHD complicated with CHF were randomly divided into two groups: the conventional treatment (control) group (Digoxin, Dihydrochlorothiazide, Isosorbide dinitrate) containing 40 cases and the conventional treatment and Simvastatin (combination) combination group containing 40 cases. In addition, there were 40 healthy persons in the normal group. Greiss method was used for NO detection, and immunoradiometry method was used to detect CGRP and ET levels in blood before and after treatment.. NO and CGRP levels in blood of patients with CHD complicated with CHF was apparently lower than those of the normal group, and there were significant differences (p < 0.01). Also, ET was significantly higher than that of the normal group (p < 0.01). After treatment, all indicators were significantly improved (p < 0.01). Also, the improvement of the conventional treatment plus Simvastatin group was more significant. Compared with the conventional treatment group after treatment, there was a significant difference (p < 0.05).. The combination of conventional treatment and Simvastatin could significantly improve metabolic disturbances of NO, CGRP and ET of patients with CHD complicated with CHF.

Topics: Adult; Aged; Calcitonin Gene-Related Peptide; Coronary Disease; Digoxin; Drug Therapy, Combination; Endothelins; Endothelium, Vascular; Female; Heart Failure; Humans; Hydrochlorothiazide; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isosorbide Dinitrate; Male; Middle Aged; Nitric Oxide; Simvastatin

Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF.. The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19-1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06-1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12-2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05-1.79, P = 0.019 and EHR 1.41, 95% CI 1.09-1.84, P = 0.010, respectively). There was no significant digoxin-gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality.. Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Digoxin; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Proportional Hazards Models

The aim of this study was to investigate the effects of acute pharmacological treatment on the plasma levels of l-arginine, asymmetrical dimethylarginine (ADMA), and symmetrical dimethylarginine (SDMA). We also investigated the related effects on endothelial nitric oxide synthase (eNOS) expression and activity and cytochrome c oxidase activity in the primary blood mononuclear cells (PBMCs) isolated from patients with acute congestive heart failure (ACHF). Compared to pre-treatment values, ADMA, SDMA, and l-arginine plasma levels were significantly higher after pharmacological treatment (ADMA, 0.82 versus 0.43 µM; SDMA, 1.52 versus 1.12 µM; l-arginine, 1.78 versus 1.29 µM; p < 0.01. In addition, the levels of eNOS expression and activity were decreased after pharmacological treatment, while cytochrome c oxidase activity resulted in higher O2-production. In the PBMCs isolated from patients with acute congestive heart failure (ACHF) and impaired renal function, higher SDMA and ADMA levels were more evident after therapy, as were reduced expression and activity of eNOS. Increased O2- produced after treatment may be involved in impaired recovery of cardiac function associated with higher plasma levels of SDMA.

Topics: Adult; Aged; Alanine Transaminase; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arginine; Aspartate Aminotransferases; Blotting, Western; Chromatography, High Pressure Liquid; Digoxin; Diuretics; Echocardiography; Electron Transport Complex IV; Female; Heart Failure; Humans; Kidney Function Tests; Leukocytes, Mononuclear; Male; Middle Aged; Nitric Oxide Synthase Type III; Oxygen

In the Digitalis Investigation Group (DIG) trial, digoxin reduced mortality or hospitalization due to heart failure (HF) in several pre-specified high-risk subgroups of HF patients, but data on protocol-specified 2-year outcomes were not presented. In the current study, we examined the effect of digoxin on HF death or HF hospitalization and all-cause death or all-cause hospitalization in high-risk subgroups during the protocol-specified 2 years of post-randomization follow-up.. In the DIG trial, 6800 ambulatory patients with chronic HF, normal sinus rhythm, and LVEF ≤45% (mean age 64 years, 26% women, 17% non-whites) were randomized to receive digoxin or placebo. The three high-risk groups were defined as NYHA class III-IV symptoms (n = 2223), LVEF <25% (n = 2256), and cardiothoracic ratio (CTR) >55% (n = 2345). In all three high-risk subgroups, compared with patients in the placebo group, those in the digoxin group had a significant reduction in the risk of the 2-year composite endpoint of HF mortality or HF hospitalization: NYHA III-IV [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.57-0.75; P < 0.001], LVEF <25% (HR 0.61; 95% CI 0.53-0.71; P < 0.001), and CTR >55% (HR 0.65; 95% CI 0.57-0.75; P < 0.001). Digoxin-associated HRs (95% CI) for 2-year all-cause mortality or all-cause hospitalization for subgroups with NYHA III-IV, LVEF <25%, and CTR >55% were 0.88 (0.80-0.97; P = 0.012), 0.84 (0.76-0.93; P = 0.001), and 0.85 (0.77-0.94; P = 0.002), respectively.. Digoxin improves outcomes in chronic HF patients with NYHA class III-IV, LVEF <25%, or CTR >55%, and should be considered in these patients.

Topics: Administration, Oral; Aged; Cardiotonic Agents; Digoxin; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Risk Factors; Treatment Outcome

Monocytes play a critical role in the pathophysiology of heart failure (HF), but few studies have evaluated the prognostic implications of an increased monocyte count in patients with HF and reduced ejection fraction (EF). The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) examined the effects of tolvaptan in patients with worsening HF and EF ≤40%. This post hoc analysis evaluated the primary end points of all-cause mortality and cardiovascular mortality or HF hospitalization in 3,717 patients. At baseline, 265 (7.1%) had an increased monocyte count defined by ≥800/μl. Patients with increased monocyte count tended to have an increased EF and were less likely to have a history of diabetes mellitus, hypercholesterolemia, or coronary revascularization but were more likely to have higher HF functional class and to be taking HF therapies such as diuretics, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and digoxin (p <0.05 for all comparisons). At median follow-up of 9.9 months, increased monocyte count was predictive of all-cause mortality (hazard ratio 1.27, 95% confidence interval 1.003 to 1.60, p = 0.047) but was not associated with cardiovascular mortality or HF hospitalization (hazard ratio 1.06, 95% confidence interval 0.87 to 1.30, p = 0.55). Similar results were seen when monocyte count was analyzed as a continuous variable. However, after adjustment for baseline clinical risk factors, monocyte count was not predictive of either primary end point. In conclusion, increased monocyte count occurs in a minority of patients hospitalized with HF and is associated with poor postdischarge prognosis. However, it does not contribute prognostic value above other more traditional risk factors.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cardiotonic Agents; Digoxin; Double-Blind Method; Follow-Up Studies; Heart Failure; Hospital Mortality; Humans; Inpatients; Kaplan-Meier Estimate; Leukocyte Count; Monocytes; Prognosis; Prospective Studies; Stroke Volume; Survival Rate; Tolvaptan

Digoxin has been shown to reduce heart failure (HF) hospitalizations with no overall effect on mortality in HF patients. We used cluster analysis to delineate the clinical characteristics of HF patients in whom digoxin therapy was associated with improved or worsened clinical outcomes.. The Digitalis Investigation Group (DIG) database was partitioned into 20 clusters. Multivariate Cox regression analyses was used, to identify clusters in which digoxin was associated with either an increase (Mortality(dig)HR>1), decrease (Mortality(dig)HR<1), or no association with all cause mortality (Mortality(dig)HR-NS); and separately, with an increase (HFA(dig)HR>1), decrease (HFA(dig)HR<1), or no association (HFA(dig)HR-NS) with HF admissions (HFA).. We identified 938 patients in the Mortality(dig)HR>1 group, 6818 patients in the Mortality(dig)HR-NS group, and none in Mortality(dig)HR<1 group. The Mortality(dig)HR>1 group had a higher prevalence of females, diabetes mellitus, hypertension, higher age, systolic blood pressure (SBP), heart rate and ejection fraction (EF), compared to the Mortality(dig)HR-NS group. Similarly, 6325 patients clustered in the HFA(dig)HR<1 group, 1431 patients in the HFA(dig)HR-NS group, and none in the HFA(dig)HR>1 group. The HFA(dig)HR-NS group had a higher prevalence of females and hypertension, higher SBP, body mass index and EF; and lower prevalence of peripheral edema and third heart sound, compared with the HFA(dig)HR<1 group.. Thus, the baseline characteristics of patients who did not have reduction in HF hospitalization or who had increased mortality were very similar and included females with hypertension, higher EF and higher SBP. Thus, use of digoxin in patients with this profile may need to be avoided.

Topics: Aged; Cluster Analysis; Databases, Factual; Digoxin; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Risk Factors; Sex Factors; Treatment Outcome

After the publication of DIG trial, the therapeutic target of serum digoxin concentration (SDC) for the treatment of heart failure (HF) has been lowered (0.40-1.00 ng/ml). However, the majority of equations to calculate digoxin dosages were developed for higher SDCs. Recently, a new equation was validated in Asian population for low SDCs by Konishi et al., but results in Caucasians are unknown.. This study was aimed to test the Konishi equation in Caucasians specifically targeting low SDCs. Furthermore, the Konishi equation was compared with other frequently used equations.. This was a prospective, multicenter study.. Clinically indicated digoxin was given in 40 HF patients. The dosage was calculated with the Konishi equation. The SDC was measured at 1 and 6 months after starting digoxin. Adherence to digoxin was monitored with a specific questionnaire.. After exclusion of patients admitting poor adherence, we found a reasonable correlation between predicted and measured SDC (r=0.48; P<0.01) by the Konishi equation. Excluding patients with poor adherence and relevant worsening of renal function, the measured SDC (n=54 measurements) was within the pre-defined therapeutic range in 95% of the cases. The mean, maximal and minimal measured SDC were 0.69±0.19, 1.00 and 0.32 ng/ml, respectively. The correlation was weaker for the Jelliffe, the Koup and Jusko, and the Bauman equations.. This study supports the clinical validity of the Konishi equation for calculating individual digoxin dosage in Caucasians, targeting SDCs according to current HF guidelines.

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Male; Medication Adherence; Middle Aged; Prospective Studies; Regression Analysis; Treatment Outcome; White People

Fimasartan (BR-A-657) is an angiotensin II receptor antagonist, recently approved as an antihypertensive agent.. This study aimed to investigate whether administration of fimasartan has an effect on the steady-state pharmacokinetics of digoxin.. An open-label, two-period, two-treatment, single-sequence, crossover study was conducted in 14 healthy male volunteers. On the first day of each 7-day treatment period, subjects received a loading dose of digoxin 0.5 mg, either alone or together with fimasartan 240 mg in the morning, followed by an additional dose of digoxin 0.25 mg after 6 h. On the subsequent 6 days, digoxin 0.25 mg, either alone or with fimasartan 240 mg was administered once daily. Serial blood samples for pharmacokinetics were collected up to 24 h after the last administration in each period.. The geometric mean ratio and 90% confidence intervals (CI) for the Cmax,ss and AUCτ,ss of digoxin (with/without fimasartan) were 1.307 (1.123 - 1.520) and 1.087 (1.015 - 1.165), respectively. Study medications were well-tolerated without serious adverse events or clinically meaningful changes.. Coadministration of fimasartan with digoxin does not result in clinically significant changes of digoxin pharmacokinetics at steady-state in healthy subjects.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Area Under Curve; Arrhythmias, Cardiac; Biphenyl Compounds; Cardiotonic Agents; Cross-Over Studies; Digoxin; Female; Heart Failure; Humans; Male; Pyrimidines; Tetrazoles; Young Adult

Inappropriate doses and high serum concentrations of digoxin are highly prevalent in patients with renal impairment, and the drug dosage adjustment according to the glomerular filtration rate (GFR) is recommended. The aim of our study was to evaluate the dependence degree of digoxin total clearance (CL) on GFR, and the diagnostic efficiency of a predictive model for serum digoxin steady-state concentrations (Css) from estimated GFR by Cockcroft-Gault formula.. In 400 outpatients treated orally with digoxin, serum Css were determined (fluorescence polarization immunoassay from Abbott Laboratories), and total CL was calculated. The prediction of Css was carried out using a hyperbolic model developed by Konishi et al in Japan (J Clin Pharm Ther 2002;27:257), and the constants of the equation were modified for a Caucasian population.. Only 26% of the digoxin CL interindividual variability may be explained by differences in GFR, and this fact is a serious limitation for the derived predictive models. A 65% diagnostic efficiency was obtained for original and modified hyperbolic models in the correct classification of predicted Css as subtherapeutic, therapeutic or supratherapeutic with respect to obtained Css concentrations.. The diagnostic efficiency obtained in the prediction of serum digoxin concentrations from estimated GFR values is unacceptable for the drug dosage adjustment in clinical practice.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Drug Monitoring; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Models, Biological; Osmolar Concentration; Reproducibility of Results; Sensitivity and Specificity; White People; Young Adult

Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation.. We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death.. After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02).. Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Cardiovascular Diseases; Chronic Disease; Digoxin; Double-Blind Method; Dronedarone; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Heart Rate; Hospitalization; Humans; Male; Risk Factors; Stroke

To assess adherence to medical treatment in patients with heart failure (HF) using a specific questionnaire and measurement of the serum concentration of digoxin.. Forty patients with symptomatic HF and a clinical indication for digoxin were included in this pilot study. The assessment of adherence to the medical regime was based on two different methods: (i) the CARDIA-Questionnaire and (ii) the measurement of serum digoxin concentration (SDC) at 1 and 6 months. All patients were placed on digoxin treatment (target SDC 0.6-0.8 ng/mL) at baseline. Poor adherence was defined if the patient self-reported taking < or =75% of the prescribed HF medication or had an SDC < 0.4 ng/mL (subtherapeutic range) at the follow-up visits. During the entire follow-up, the proportion of patients with poor adherence was 15% as assessed by the questionnaire, 20% as assessed by the SDC, and 25% if both methods were combined.. Although HF is a symptomatic disease, the proportion of patients with poor adherence to the medical regime in our study was high (up to 25%). The objective methodology based on the measurement of the SDC identified a higher number of patients with poor adherence when compared with the CARDIA-Questionnaire.

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Health Behavior; Heart Failure; Humans; Male; Medication Adherence; Pilot Projects; Prospective Studies; Psychometrics; Risk Factors; Surveys and Questionnaires; Switzerland

For out-of-hospital cardiac arrest (OHCA) to be predicted and prevented, it is imperative the healthcare system has access to those vulnerable before the event occurs. We aimed to determine the extent of contact to the healthcare system before OHCA.. All patients in Denmark with a registered OHCA June 1, 2001-December 31, 2005 were matched on age and sex with 10 random controls from the entire Danish population. We estimated the association with OHCA by conditional logistic regression analyses, and we determined the proportion of patients in contact with the healthcare system before OHCA from hospital admissions or claimed prescriptions.. We identified 12,089 patients with an OHCA. Of these, 62% (7548) and 85% (10,312) were in contact with the healthcare system up to 30 days and 1 year before OHCA, respectively. Association with OHCA up to 30 days before the event pertained to myocardial infarction (odds ratio (OR)=6.4, 95% confidence interval (CI): 4.7-8.6)); heart failure (OR=5.1, CI: 4.1-6.3); ischemic heart disease (OR=1.9, CI: 1.6-2.4); and cardiac dysrhythmia (OR=1.8, CI: 1.4-2.2). Concomitant pharmacotherapy up to 30 days before OHCA with the strongest association was: corticosteroids (systemic) (OR=2.7, CI: 2.5-3.0), bronchial dilators (OR=2.5, CI: 2.3-2.7), anti-psychotic medication (OR=2.1, CI: 1.9-2.3), and digoxin (OR=2.1, CI: 2.0-2.3). Similar results were found for associations up to 1 year before OHCA.. Contrary to general belief, the majority of OHCA patients are in contact with the healthcare system shortly before OHCA.

Topics: Adrenal Cortex Hormones; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Bronchodilator Agents; Denmark; Digoxin; Female; Health Behavior; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Out-of-Hospital Cardiac Arrest; Patient Admission; Regression Analysis

The purpose of this study was to assess whether management of heart failure (HF) guided by an individualized N-terminal pro-B-type natriuretic peptide (NT-proBNP) target would lead to improved outcome compared with HF management guided by clinical assessment alone.. Natriuretic peptides may be attractive biomarkers to guide management of heart failure (HF) and help select patients in need of more aggressive therapy. The PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study is, to our knowledge, the first large, prospective randomized study to address whether management of HF guided by an individualized target NT-proBNP level improves outcome.. A total of 345 patients hospitalized for decompensated, symptomatic HF with elevated NT-proBNP levels at admission were included. After discharge, patients were randomized to either clinically-guided outpatient management (n = 171), or management guided by an individually set NT-proBNP (n = 174) defined by the lowest level at discharge or 2 weeks thereafter. The primary end point was defined as number of days alive outside the hospital after index admission.. HF management guided by this individualized NT-proBNP target increased the use of HF medication (p = 0.006), and 64% of HF-related events were preceded by an increase in NT-proBNP. Nevertheless, HF management guided by this individualized NT-proBNP target did not significantly improve the primary end point (685 vs. 664 days, p = 0.49), nor did it significantly improve any of the secondary end points. In the NT-proBNP-guided group mortality was lower, as 46 patients died (26.5%) versus 57 (33.3%) in the clinically-guided group, but this was not statistically significant (p = 0.206).. Serial NT-proBNP measurement and targeting to an individual NT-proBNP value did result in advanced detection of HF-related events and importantly influenced HF-therapy, but failed to provide significant clinical improvement in terms of mortality and morbidity. (Effect of NT-proBNP Guided Treatment of Chronic Heart Failure [PRIMA]; NCT00149422).

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Biomarkers, Pharmacological; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Post hoc analyses of the Digitalis Investigation Group (DIG) trial indicate that digoxin at low (0.5 to 0.9 ng/ml) serum digoxin concentration (SDC) reduces mortality, which is eliminated at higher (>or=1 ng/ml) SDC, and that low-dose digoxin (

Topics: Aged; Canada; Cardiotonic Agents; Cause of Death; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Survival Rate; Time Factors; Treatment Outcome; United States

It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy.. To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy.. Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008.. Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy).. Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires.. Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction). Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment.. isrctn.org Identifier: ISRCTN43596477.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cardiovascular Agents; Digoxin; Disease-Free Survival; Diuretics; Female; Germany; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Nitrates; Odds Ratio; Peptide Fragments; Proportional Hazards Models; Quality of Life; Severity of Illness Index; Stroke Volume; Surveys and Questionnaires; Switzerland; Treatment Outcome

Atrial fibrillation (AF) and heart failure (HF) often coexist. The aim was to investigate whether restoring sinus rhythm (SR) could improve cardiac function, symptoms, exercise capacity and quality of life (QoL) in patients with chronic heart failure.. Patients with HF and persistent AF receiving guideline-recommended treatments, including anticoagulants, were eligible for the study. Patients were randomised to either rhythm (treated with amiodarone for at least 3 months prior to attempting biphasic external cardioversion and continued amiodarone long-term if SR was restored) or rate control. Anticoagulants were continued throughout the study regardless of rhythm, unless contraindications developed. Both groups were treated with beta blockers and/or digoxin to reduce the heart rate to <80 bpm at rest and <110 bpm after walking. Symptoms, walk distance (6-minute corridor walk test, 6MWT), QoL and cardiac function were assessed at baseline and 1 year.. 61 patients with HF and persistent AF (median duration 14 months (IQR 5 to 32)) were randomly assigned to a rate or rhythm control strategy. Of patients assigned to rhythm control (n = 30), 66% were in SR at 1 year, and 90% of those assigned to rate control (n = 31) achieved the heart rate target. At 1 year, NYHA class (p = 0.424) and 6MWT distance (p = 0.342) were similar between groups but patients assigned to rhythm control had improved LV function (p = 0.014), NT-proBNP concentration (p = 0.046) and QoL (p = 0.019) compared with those assigned to rate control. Greatest improvement was seen in patients in whom SR was maintained.. Restoring SR in patients with AF and heart failure may improve QoL and LV function when compared with a strategy of rate control.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Biomarkers; Combined Modality Therapy; Digoxin; Drug Therapy, Combination; Electric Countershock; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Treatment Outcome; Ventricular Function, Left

Levosimendan is a calcium-sensitizing drug for the treatment of heart failure. The aim of this exploratory study was to assess the hemodynamic and pharmacokinetic interactions between digoxin and oral levosimendan as well as the proarrhythmic potential of this combination in patients with chronic heart failure.. Male or female patients (n = 24) with chronic heart failure of NYHA Classes II-III.. A randomized, placebo-controlled, double-blind, parallel-group trial. After a 1-week digoxin-free washout period, the patients were randomized to receive either digoxin and levosimendan (digoxin + levosimendan), or digoxin and placebo (digoxin) orally for 14 +/- 2 days. The levosimendan dose was 1 mg 3 times daily, and the digoxin dose was 0.125-0.25 mg once daily. Systolic time intervals, electrocardiography (ECG), magneto-cardiography (MCG) and 24-h ambulatory ECG were performed at baseline and at the end of each treatment period. Pharmacokinetic variables of levosimendan and digoxin were calculated in both treatment periods. Steady-state concentrations of the active metabolites OR-1855 and OR-1896 were determined at baseline at Visit 2.. There tended to be a greater shortening of QS2i (suggesting trend to positive inotropy) in the digoxin + levosimendan group (-14ms) compared with the digoxin group (-5ms), although the difference was not statistically significant (p=0.359). However, the change from baseline in QS2i after digoxin + levosimendan was of statistically borderline significance (p=0.05). The change from baseline in the digoxin group was not statistically significant. ECG and MCG repolarization measures and occurrence of nonsustained ventricular tachycardia showed no substantial differences. After 2 weeks of digoxin + levosimendan treatment, mean area under the curve (AUC) of levosimendan increased approximately by 49% (p<0.01). The maximum plasma concentration (Cmax) of levosimendan increased from 17 to 23 ng/ml. The mean concentrations of the metabolites OR-1855 and OR-1896 in plasma were 4.3 and 8.3 ng/ml, respectively.. The addition of oral levosimendan to digoxin therapy produced only a modest statistically nonsignificant additive inotropic effect. In contrast to the earlier data with intravenous levosimendan, the results indicate a pharmacokinetic interaction between levosimendan and digoxin. Data obtained from repolarization analyses and ambulatory ECG did not indicate any possible proarrhythmic effects of the combination.

Topics: Acetamides; Administration, Oral; Aged; Area Under Curve; Cardiotonic Agents; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Magnetocardiography; Male; Middle Aged; Pyridazines; Simendan

In the Digitalis Investigation Group trial, digoxin-associated decrease in the combined end point of heart failure (HF) hospitalization or HF mortality was significant in systolic but not in diastolic HF. To assess whether this apparent disparity could be explained by differences in baseline characteristics and sample size, we used propensity score matching to assemble a cohort of 916 pairs of patients with systolic and diastolic HF who were balanced in all measured baseline covariates. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of the effect of digoxin on outcomes separately in systolic and diastolic HF, at 2 years (protocol prespecified), and at the end of 3.2 years of median follow-up. HF hospitalization or HF mortality occurred in 28% and 32% of patients with systolic HF (HR digoxin vs placebo 0.85, 95% CI 0.67 to 1.08, p = 0.188) and 20% and 25% in those with diastolic HF (HR 0.79, 95% CI 0.60 to 1.03, p = 0.085) receiving digoxin and placebo, respectively. At 2 years, HRs for this combined end point were similar for systolic HF (0.72, 95% CI 0.55 to 0.95, p = 0.022) and diastolic HF (0.69, 95% CI 0.50 to 0.95, p = 0.025). Digoxin also decreased 2-year HF hospitalization in systolic HF (HR 0.73, 95% CI 0.54 to 0.97, p = 0.033) and diastolic HF (HR 0.64, 95% CI 0.45 to 0.90, p = 0.010). In conclusion, as in patients with systolic HF, digoxin was equally effective in those with diastolic HF, who constitute half of all patients with HF, yet have few evidence-based therapeutic options.

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Outcome Assessment, Health Care; Proportional Hazards Models

Recent studies suggest that cardiac myocyte apoptosis contributes to the progress of CHF (congestive heart failure). In the present study, we tested the hypothesis that metoprolol in conjunction with the standard treatment regime for CHF [an ACE (angiotensin-converting enzyme) inhibitor, diuretics and digoxin] may significantly reduce the plasma concentrations of the apoptotic mediators sFas (soluble Fas) and sFasL (soluble Fas ligand) in patients with CHF. An ELISA was used to determine the plasma concentrations of sFas and sFasL in 106 patients with stable CHF at recruitment. Echocardiography was performed at baseline and after 1 year of treatment with metoprolol in conjunction with the standard treatment regime for CHF (i.e. an ACE inhibitor, diuretics and digoxin). The dose of metoprolol was doubled on a biweekly basis up to 50 mg twice a day or maintained at the maximum tolerated dose. Data after 1 year were available for 92 patients and were analysed. The plasma concentrations of sFas and sFasL in patients with CHF decreased significantly (P<0.01) after 1 year of treatment with metoprolol in conjunction with the standard treatment regime compared with at baseline (5.4+/-0.2 compared with 3.2+/-0.1 ng/ml respectively for sFas, and 52.1+/-2.3 compared with 26.7+/-1.0 pg/ml respectively for sFasL). Compared with baseline, after 1 year of treatment with metoprolol in conjunction with the standard treatment regime there were significant improvements in LV (left ventricular) ejection fraction (from 32.6+/-0.9 to 51.5+/-0.8%; P<0.01), LV end-diastolic dimension (from 69.8+/-0.6 to 57.7+/-0.3 mm; P<0.01), LV end-systolic dimension (from 53.9+/-0.6 to 40.5+/-0.5 mm; P<0.01), LV end-diastolic volume (from 254.7+/-5.0 to 164.1+/-2.2 ml; P<0.01) and LV end-systolic volume (from 142.0+/-4.2 to 72.2+/-2.0 ml; P<0.01). In addition, the distance walked in a 6-min walk test increased markedly (P<0.01) from 260.3+/-5.2 m at baseline to 440.9+/-5.7 m after 1 year of treatment. In conclusion, we have demonstrated that metoprolol in conjunction with an ACE inhibitor, diuretics and digoxin in patients with CHF can lead to a reverse in LV remodelling potentially through its anti-apoptotic effects.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Apoptosis; Biomarkers; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Exercise Test; Fas Ligand Protein; fas Receptor; Female; Heart Failure; Humans; Male; Metoprolol; Middle Aged; Prospective Studies; Severity of Illness Index; Ultrasonography; Ventricular Function, Left

To evaluate the effect of Xuezhikang (XZK) on cardiac function and serum C-reactive protein (CRP) in patients with chronic heart failure (CHF).. Sixty-eight CHF patients were randomly assigned to two groups, the control group (30 cases) treated with angiotensin converting enzyme inhibitor, beta-receptor inhibitor, digoxin and diuretic, and the treated group (38 cases) with the above treatment plus XZK for six months. The changes of cardiac function and serum CRP level were measured by echocardiography and enzyme-linked immunosorbent assay (ELISA) respectively before and after treatment.. Compared with those before treatment, the NYHA cardiac function grade, the left ventricular dimension end diastole (LVDd), and the left ventricular dimension end systole (LVDs) decreased significantly (P < 0.05), and the ejection fraction (EF) and E/A ratio increased significantly in both groups after treatment (P < 0.05) , however, the decrement or increment was more significant in the treated group than that in the control group respectively (P < 0.05); the serum CRP level decreased significantly in the treated group after treatment and showed a level obviously lower than that in the control group (P < 0.05), which changed insignificantly after treatment.. Xuezhikang could improve cardiac function and decrease serum CRP level at the same time.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; C-Reactive Protein; Cholesterol; Digoxin; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Lipoproteins; Male; Middle Aged; Phytotherapy; Ventricular Function, Left

Discontinuation of digoxin is associated with worsening heart failure (HF) symptoms. However, the long-term effects of discontinuation of digoxin therapy on mortality and morbidity in HF have not been well studied. Of the 7,788 participants in the Digoxin Investigation Group trial, 3,365 received digoxin before randomization. During the trial, digoxin was continued in 1,666 patients and discontinued in 1,699 patients. Using multivariable Cox regression analyses, we first determined the effect of discontinuation of digoxin on mortality and hospitalization during 39.7 months of median follow-up. Of the 1,666 patients continued on digoxin, 457 had low (0.5 to 0.9 ng/ml) and 340 had high (>or=1.0 ng/ml) serum digoxin concentrations (SDC) after 1 month of therapy and of the 1,699 patients whose digoxin was discontinued, 1,674 were alive at 1 month. We examined the effects of continuation of digoxin at low or high SDC. Compared with continuation of long-term digoxin therapy, discontinuation of digoxin was associated with a significant increase in all-cause hospitalization (adjusted hazard ratio [AHR] 1.18, 95% confidence interval [CI] 1.09 to 1.28, p <0.0001) and HF hospitalization (AHR 1.35, 95% CI 1.20 to 1.51, p <0.0001), but had no effect on all-cause mortality (AHR 1.06, 95% CI 0.95 to 1.19, p = 0.272). In contrast, continuation of digoxin at low SDC was associated with a reduction in all-cause mortality (AHR 0.75, 95% CI 0.63 to 0.90, p = 0.002), all-cause hospitalization (AHR 0.80, 95% CI 0.70 to 0.91, p = 0.001), and hospitalization for HF (AHR 0.60, 95% CI 0.50 to 0.73, p <0.0001). In conclusion, continuation of long-term digoxin therapy at low SDC was associated with reduction in mortality and hospitalization in ambulatory patients with chronic HF receiving background therapy with angiotensin-converting enzyme inhibitors and diuretics.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Regression Analysis; Substance Withdrawal Syndrome

To determine the effects of digoxin on all-cause mortality and heart failure (HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration (SDC).. This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial (n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5-0.9 ng/mL was associated with lower mortality [29 vs. 33% placebo; adjusted hazard ratio (AHR), 0.77; 95% confidence interval (CI), 0.67-0.89], all-cause hospitalizations (64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78-0.92) and HF hospitalizations (23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54-0.72). SDC> or =1.0 ng/mL was associated with lower HF hospitalizations (29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59-0.79), without any effect on mortality. SDC 0.5-0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex (P=0.917).. Digoxin at SDC 0.5-0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Digoxin; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged

The activity of the human cytochrome P450 and P-glycoprotein (P-gp) changes according to gender. The present study evaluated the effect of gender on the influence of carvedilol on serum digoxin levels in patients with heart failure.. Twenty-four patients (12 female and 12 male) with New York Heart Association class II-III heart failure were included in the study. Patients were taking oral digoxin (0.0625-0.25 mg, once a day) and were administered oral carvedilol (6.25 mg, two times daily) for 7 days.. In the male group, carvedilol led to statistically significant increases in the area under the concentration time curve to 16 h (AUC(0-16h)) and the peak concentration (C(max)) for digoxin, with no change in time to peak (t(max))(AUC(0-16h)= 24.1+/-9.2 ng.h/ml vs. 15.4+/-5.8 ng.h/ml, p<0.001, C(max)=2.2+/-1.0 ng/ml vs. 1.6+/-0.6 ng/ml, p<0.01, t(max)=2.4+/-2.2 h vs. 2.1+/-1.0 h, p>0.05). In the female group, carvedilol administration did not cause statistically significant change in the AUC(0-16h), C(max), or t(max) for digoxin (p>0.05). In the male group, carvedilol resulted in a significant increase in the AUC(0-16h) and C(max) for digoxin compared with the female group (AUC(0-16h)=24.1+/- 9.2ng.h/ml vs. 17.0+/-6.8 ng.h/ml, C(max)=2.2+/-1.0 ng/ml vs. 1.5+/-0.6 ng/ml, p<0.05, respectively).. Men seem to have a higher activity relative to women for the drug efflux transporter P-gp. Our results suggest that carvedilol will cause drug interaction with digoxin following the inhibition of P-gp-mediated transcellular transport of digoxin in males.

Topics: Aged; Antihypertensive Agents; Area Under Curve; Carbazoles; Cardiotonic Agents; Carvedilol; Digoxin; Drug Interactions; Female; Heart Failure; Humans; Male; Propanolamines; Sex Characteristics; Time Factors

To observe the effects of conventional therapy combined with Kanlijian (KLJ) on exercise tolerance, quality of life and frequency of heart failure aggravation in patients with chronic heart failure (CHF).. Sixty CHF patients differentiated as sufferring from the syndrome of Xin-Shen Yang deficiency were included in the study and randomly assigned at the ratio of 2:1 into the KLJ group (n = 39) and the control group (n = 21). All the patients were treated with conventional therapy of Western medicine, but to those in the KLJ group, KLJ was medicated additionally one dose daily with 24 wks as one therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM syndrome were observed after treatment. The indexes, including 6-minute walking distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade, hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before and after treatment were recorded and compared. Also the frequency of re-admission due to aggravation of heart failure in one year's time were observed.. (1) The efficacy on TCM syndrome, improvement on scores of TCM syndrome, therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior to those in the control group. (2) Hemodynamic indexes after treatment, left ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two groups had no significant difference, while left ventricular ejection fraction (LVEF) was increased significantly in the KLJ group, but with no obvious change in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in the KLJ group was significantly higher than that in the control group. (4) The 1-year frequency of re-admission significantly decreased in the KLJ group.. The adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function, reduce the dosage of diuretic and digoxin needed, and decrease the re-admission frequency due to aggravation of heart failure.

Topics: Digoxin; Diuretics; Drugs, Chinese Herbal; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Quality of Life; Stroke Volume

To compare the clinical effect of three TCM therapeutic methods, Yiqi (YQ, supplementing Qi), Huoxue (HX, activating blood circulation) and Yiqi Huoxue (YQHX) method on congestive heart failure and heart function.. Eighty patients were divided into 3 groups randomly, they were treated by conventional therapy and with the additional TCM drugs for YQHX to group A (n = 36), drugs for YQ to group B (n = 24), and drugs for HX to group C (n = 20). After 2 weeks' treatment, clinical effect was observed and cardiac function was detected and compared.. The total effective rate was 91.7% in group A, which was superior to that in group B (66.7%) and group C (65.0%) respectively. Cardiac function was improved remarkably after treatment in all groups, the optimal effect was shown in group A.. All the 3 methods could improve clinical symptoms and cardiac function in patients with congestive heart failure, among which YQHX method has the optimal effect.

Topics: Aged; Astragalus Plant; Astragalus propinquus; Coronary Disease; Digoxin; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Phytotherapy; Salvia miltiorrhiza; Stroke Volume

About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published.. Ambulatory chronic heart failure patients (n = 988) with normal sinus rhythm and ejection fraction > 45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n = 492) or placebo (n = 496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07; P = 0.136) experienced the primary combined outcome of heart failure hospitalization or heart failure mortality. Digoxin had no effect on all-cause or cause-specific mortality or on all-cause or cardiovascular hospitalization. Use of digoxin was associated with a trend toward a reduction in hospitalizations resulting from worsening heart failure (HR, 0.79; 95% CI, 0.59 to 1.04; P = 0.094) but also a trend toward an increase in hospitalizations for unstable angina (HR, 1.37; 95% CI, 0.99 to 1.91; P = 0.061).. In ambulatory patients with chronic mild to moderate diastolic heart failure and normal sinus rhythm receiving angiotensin-converting enzyme inhibitor and diuretics, digoxin had no effect on natural history end points such as mortality and all-cause or cardiovascular hospitalizations.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiotonic Agents; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Morbidity; Sinoatrial Node; Stroke Volume; Survival Rate; Treatment Outcome

Gentamicin is frequently used to treat infectious diseases in patients receiving digitalis therapy. The aim of this study is to evaluate the effect of gentamicin on serum digoxin level.. Twenty-four diabetic patients and patients with congestive heart failure and twelve normal healthy volunteers were enrolled in this study. The patients received digoxin treatment 0.25 mg/day. Gentamicin in a dose of 80 mg i.m. twice a day for 7 days was prescribed for these patients to treat chest infection. Serum digoxin and creatinine levels were determined before and after gentamicin administration.. Gentamicin induced a significant increase in serum digoxin level of diabetic patients and patients with congestive heart failure. Serum creatinine level increased significantly before and after i.m. injection of gentamicin.. The present study indicated that increase serum digoxin level when combined with gentamicin should be considered a risk factor for digitalis toxicity.

Topics: Adult; Anti-Bacterial Agents; Cardiotonic Agents; Creatinine; Diabetes Mellitus, Type 2; Digoxin; Drug Interactions; Gentamicins; Heart Failure; Humans; Male; Middle Aged

The Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial was an investigator-initiated study to evaluate if predischarge carvedilol initiation in stabilized patients hospitalized for heart failure (HF) increased the number of patients treated with beta-blockade at 60 days after randomization without increasing side effects or length of hospital stay.. Beta-blockers are underused in HF. Predischarge initiation may improve the use of evidence-based beta-blockade.. The IMPACT-HF was a prospective, randomized open-label trial conducted in 363 patients hospitalized for HF. Patients were randomized to carvedilol initiation pre-hospital discharge or to postdischarge initiation (>2 weeks) of beta-blockade at the physicians' discretion. The primary end point of the study was the number of patients treated with beta-blockade at 60 days after randomization. Secondary end points included the number of patients discontinuing beta-blockade, median dose achieved, and a composite of death, rehospitalization, unscheduled visit for HF, or > or =50% increase in oral diuretic, new oral diuretic, or any intravenous therapy with diuretics, inotropes, or other vasoactive agents.. At 60 days 165 patients (91.2%) randomized to predischarge carvedilol initiation were treated with a beta-blocker, compared with 130 patients (73.4%) randomized to initiation postdischarge (p < 0.0001). Predischarge initiation was not associated with an increased risk of serious adverse events. The median length of stay was five days in both groups.. Predischarge initiation of carvedilol in stabilized patients hospitalized for HF improved the use of beta-blockade at 60 days without increasing side effects or length of stay. Predischarge initiation may be one approach to improve beta-blocker use in this population.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Carbazoles; Carvedilol; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Patient Discharge; Propanolamines; Prospective Studies; Treatment Outcome; United States

Renal dysfunction is a common complication for patients with heart failure, but its association with clinical outcomes has not been fully characterized. We evaluated the association of glomerular filtration rate (GFR) with heart failure survival and the effect of digoxin on heart failure outcomes across GFR strata. A secondary analysis from the Digitalis Intervention Group trial was conducted of 6800 outpatients with systolic heart failure. Renal function was categorized as estimated GFR (expressed in ml/min per 1.73 m(2)). All-cause mortality (mean, 3 yr) was inversely proportional to GFR (GFR >60, 31% mortality; GFR 30 to 60, 46% mortality; GFR <30, 62% mortality; P < 0.001). Among patients with a GFR <50, lower GFR were associated with greater adjusted mortality risk (GFR <30: hazard ratio [HR], 2.06, 95% confidence interval [CI], 1.69 to 2.51; GFR 30 to 40: HR, 1.42, 95% CI, 1.22 to 1.67; GFR 40 to 50: HR, 1.22, 95% CI, 1.07 to 1.39; GFR 50 to 60: HR, 1.00, referent). In contrast, participants with GFR 60 to 70 had similar risk (HR, 1.00; 95% CI, 0.88 to 1.14) compared with GFR 50 to 60, and those with GFR >70 had a slightly lower mortality hazard (0.89; 95% CI, 0.78 to 1.00). Linear spline analyses confirmed that GFR = 50 was the appropriate risk threshold; above 50, GFR had no association with mortality, whereas below 50, mortality risk increased sharply with declining GFR (spline coefficient, P < 0.0001). Digoxin efficacy did not differ by level of GFR (P = 0.19 for interaction). Renal dysfunction is strongly associated with mortality in stable outpatients with heart failure, notably in patients with estimated GFR <50 ml/min per 1.73 m(2). The effect of digoxin did not differ by level of renal function.

Topics: Aged; Cardiotonic Agents; Cohort Studies; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Renal Insufficiency; Risk Factors; Survival Analysis

The aim of the present study is to show a better short-term (2 weeks) clinical improvement in patients with heart failure (HF) who are receiving angiotensin converting enzyme inhibitors (ACEIs) (with or without digoxin) when compared to the standard therapy excluding ACEIs.. The study was conducted in Al-Gamhuria Teaching Hospital, Aden, Yemen, from January to July 2003. In this study, 78 patients with HF were enrolled into 3 therapeutic groups (ACEIs alone, ACEI and digoxin and digoxin alone) and their responses within 2 weeks were recorded. Exclusion criteria were as follows: thyroid disorders, gastrointestinal disturbances (diarrhea, malabsorption), electrolyte unbalanced (unless corrected) and insufficient data. Serum creatinine was measured at the beginning and after 10 days. In addition, the patients' body weight and age were recorded. Criteria for a complete improvement within 2 weeks were the occurrence of the following: 1) The relief of pulmonary congestion, 2) Decrement in heart rate to less than 74 +/- 5, 3) Disappearance of the lower limb edema, and 5) Recorded positive electroencephalogram change. Partial amelioration was recognized if only 2 or 3 of the preceding criteria were observed.. Nine patients received digoxin alone, while 40 patients were treated with ACEIs and digoxin. Treatment with ACEIs without digoxin was observed in 29 patients. The discrepancy between the number of patients was necessitated by the need of patients with HF. This last category of treatment regimen produced better clinical improvement (complete with 10.1%, partial with 24.3%) compared to the digoxin group without ACEI (complete 2.5% or partial 5.1%). Nevertheless, the addition of digoxin to an ACEI increased this ratio (17.8% for complete and 28.2% for partial improvement). A 49.3% increase in serum creatinine was observed after 10 days in 25 HF patients, who were randomly selected and followed up (the baseline concentration was 99.75 +/- 9.9 umol/L, while the level after 10 days was 148.97 +/- 19.8 umol/L, p=0.005).. We confirmed that short-term use of ACEI regimens has a superior effect on the therapy of HF (34.4% complete and partial response) as compared to the therapy of not using ACEI (7.6% had a complete and partial response). The combination of ACEI and digoxin has resulted in the best outcome (46% had a complete and partial response). However, we also noticed a significant rise in serum creatinine by 49% concomitant with the use of ACEI (the baseline concentration was 99.75 +/- 9.9 um/L, while the level after 10 days was 148.97 +/- 19.8 umol/L, p=0.005).

Topics: Administration, Oral; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cross-Sectional Studies; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Probability; Prognosis; Risk Assessment; Severity of Illness Index; Survival Rate; Treatment Outcome; Yemen

A comparative randomized clinical study was conducted to evaluate the diagnostic and prognostic value of the activation of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-2, IL-6, IL-8)] and the increased production of autoimmune complexes in the pathogenesis of chronic heart failure (CHF) in patients with coronary heart disease (CHD). The study included 47 patients with CHD who had a more than 6-month history of Q-forming myocardial infarction. The patients were randomized into 3 groups: 1) 21 patients with NYHA Functional Class (FC) II heart failure (HF); 2) 16 patients with FC III HF; and 3) 10 with FC IV HF. Basic therapy involved angiotensin-converting enzyme (ACE) inhibitors, nitrates, diuretics, beta-adrenoblockers; 27.6% received digoxin, disaggregatory agents. A study protocol involved the estimation of the parameters of EchCG, paired bicycle ergometric tests, 6-min walking test, ECG daily monitoring, the levels of proinflammatory cytokines in the serum and IgG autoantibodies to cardiolipin. The findings suggest that with the higher expression of autoimmune complexes, the activation of cytokines (primarily TNF-alpha, IL-1alpha, IL-2) plays an important role in the pathogenesis of CHF in patients with postinfarct cardiac dysfunction: the high activation of cytokines and the elevated level of autoimmune complexes are associated with moderate or severe NYHA FC II-IV HF, depressed left ventricular contractility (ejection fraction, 23-38%), low exercise tolerance, and cardiac remodeling.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antigen-Antibody Complex; Coronary Disease; Cytokines; Digoxin; Diuretics; Heart Failure; Humans; Middle Aged; Myocardial Infarction; Nitrates; Platelet Aggregation Inhibitors; Stroke Volume

To evaluate the magnitude and dose-relatedness of the effect of clarithromycin on the pharmacokinetics of digoxin, and to compare the effects of clarithromycin with those of P-glycoprotein inhibitors.. Eight Japanese inpatients with congestive heart failure participated in this study. Each patient received oral digoxin therapy for at least 7 days and were coadministered oral clarithromycin to prevent or treat pneumonia. To evaluate the effects of clarithromycin on the pharmacokinetics of digoxin, digoxin concentrations were compared before and after coadministration of clarithromycin.. Digoxin concentrations were higher after coadministration of clarithromycin in all patients (before, 0.838 +/- 0.329 ng/mL; after, 1.36 +/- 0.619 ng/mL); (p < 0.005). A significant correlation was observed between the dose of clarithromycin and the percentage of increase in the digoxin concentration.. Digoxin concentrations increased during concomitant administration of clarithromycin, and this effect was dose-dependent on clarithromycin. The percentage increase in digoxin concentrations after the usual oral dose of clarithromycin (400 mg/d) is approximately 70%. Therefore, digoxin concentrations must be monitored carefully after coadministration of clarithromycin, and the doses of digoxin may need readjustment in patients who are concomitantly receiving clarithromycin.

Topics: Adult; Aged; Aged, 80 and over; ATP Binding Cassette Transporter, Subfamily B; Clarithromycin; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Failure; Humans; Male; Middle Aged

The Digitalis Investigation Group (DIG) trial reported that digoxin provided no overall mortality benefit and only a modest reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function. The clinical outcomes associated with digoxin therapy at different serum concentrations in the DIG trial have not been assessed.. To assess variations in serum digoxin concentration (SDC) and their association with mortality and hospitalization in patients with heart failure.. Post hoc analysis of the randomized, double-blinded, placebo-controlled DIG trial, conducted from August 1991 to December 1995, with the main analysis restricted to men with a left ventricular ejection fraction of 45% or less (n = 3782). Patients randomly assigned to receive digoxin were divided into 3 groups based on SDC at 1 month (0.5-0.8 ng/mL, n = 572; 0.9-1.1 ng/mL, n = 322; and > or =1.2 ng/mL, n = 277) and compared with patients randomly assigned to receive placebo (n = 2611).. All-cause mortality at a mean follow-up of 37 months.. Higher SDCs were associated with increased crude all-cause mortality rates (0.5-0.8 ng/mL, 29.9%; 0.9-1.1 ng/mL, 38.8%; and > or =1.2 ng/mL, 48.0%; P =.006 for trend). Patients with SDCs of 0.5 to 0.8 ng/mL had a 6.3% (95% confidence interval [CI], 2.1%-10.5%) lower mortality rate compared with patients receiving placebo. Digoxin was not associated with a reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL (2.6% increase; 95% CI, - 3.0% to 8.3%), whereas patients with SDCs of 1.2 ng/mL and higher had an 11.8% (95% CI, 5.7%-18.0%) higher absolute mortality rate than patients receiving placebo. The association between SDC and mortality persisted after multivariable adjustment (SDC 0.5-0.8 ng/mL hazard ratio [HR] 0.80, 95% CI, 0.68-0.94; SDC 0.9-1.1 ng/mL HR 0.89, 95% CI, 0.74-1.08; SDC > or =1.2 ng/mL HR 1.16, 95% CI, 0.96-1.39; and HR of 1.00 [referent] for placebo).. Our findings demonstrate that higher SDCs were associated with increased mortality and suggest that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL.

Topics: Cardiotonic Agents; Data Interpretation, Statistical; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left

The Digitalis Investigation Group (DIG) trial was a randomized double-blind placebo-controlled study that examined the effect of digoxin on mortality in 7,788 patients with heart failure and sinus rhythm. A prespecified substudy evaluated the effect of digoxin therapy on health-related quality of life (HQOL) in a subset of these patients.. Patients in the DIG trial had clinical heart failure and were randomized to either digoxin or placebo in addition to their baseline diuretic and angiotensin-converting enzyme therapy (n = 7,788). The patients in this substudy had HQOL measured using a self-administered questionnaire employing scales that measured general health, physical functioning, depression, anger, anxiety, life satisfaction, and disease specific measures. A subjective assessment by the investigator and a 6-minute walk test evaluated functional status. HQOL was measured at baseline and at the 4- and 12-month follow-up visits.. The baseline characteristics of the patients in the quality of life substudy (n = 589) were comparable to the remaining patients in the study (n = 7,199) by age and other clinical measures, including history of prior myocardial infarction or etiology of heart failure; heart failure was of shorter duration and the ejection fraction was slightly better than in the main trial. Within the substudy, patients receiving digoxin (n = 298) or placebo (n = 291) were also similar in baseline characteristics. There was no statistically significant difference in any HQOL measure between the digoxin and the placebo groups at baseline. At the 4-month visit, only perceived health was improved in the digoxin group. At 12 months, there was no statistically significant difference in perceived health, physical functioning, Minnesota Living with Heart Failure, depression, anxiety, anger, Ladder of Life, or the 6-minute walk between the digoxin and placebo groups.. In this subset of the DIG population, digoxin therapy had no effect on the HQOL in patients with heart failure in sinus rhythm.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Digoxin; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; North America; Predictive Value of Tests; Quality of Life; Regression Analysis; Reproducibility of Results; Severity of Illness Index; Stroke Volume; Surveys and Questionnaires; Time Factors; Treatment Outcome

Cardiac remodelling is now recognised as an important aspect of cardiovascular disease progression and is, therefore, emerging as a therapeutic target in cardiac failure due to different etiologies. Little is known about the influence of different therapies for cardiac failure on the remodelling seen in infants with congenital cardiac disease.. During follow-up of a prospective and randomized trial, we investigated therapeutic effects on neurohormonal activation, ventricular function, and myocardial gene expression. We compared the data from 8 infants with severe congestive heart failure due to left-to-right shunts, who received digoxin and diuretics alone, to 9 infants who received additional treatment with propranolol.. In these infants, beta-adrenergic blockade significantly reduced highly elevated levels of renin, from 284 +/- 319 microU/ml compared to 1061 +/- 769 microU/ml. Systolic ventricular function was normal in both groups, but diastolic ventricular function was improved in those receiving propranolol, indicated by significantly lower left atrial pressures, lower end-diastolic pressures, and less pronounced ventricular hypertrophy, the latter estimated by lower ratios of myocardial wall to ventricular cavity areas on average of 42%. Further hemodynamic parameters showed no significant differences between the groups, except for the lower heart rate in infants treated with propranolol. In those treated with digoxin and diuretics, there was a significant downregulation of beta2-receptor and angiotensin-2 receptor genes, and up-regulation of endothelin A receptor and connective tissue growth factor genes, that were partially prevented by additional treatment with propranolol.. Beta-blockade is a new therapeutic approach for congestive heart failure in infants with congenital cardiac disease, producing with significant benefits on neurohormonal activation, diastolic ventricular function, and cardiac remodelling.

Topics: Adrenergic beta-Antagonists; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Defects, Congenital; Heart Failure; Heart Function Tests; Hemodynamics; Humans; Infant; Male; Probability; Prognosis; Propranolol; Prospective Studies; Reference Values; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Survival Rate; Treatment Outcome; Ventricular Remodeling

Multidisciplinary care (MDC) of heart failure (HF) can significantly reduce rates of unplanned hospitalisation, the major cost component of HF care.. This prospective, randomised, controlled study examines the cost-benefits of MDC of HF in the setting of optimal medical care.. 98 NYHA class IV HF patients (mean age 70.8+/-10.5 years) were randomised to MDC (n=51) or routine care (RC; n=47) of HF. A direct intervention cost was calculated from contact time (scheduled and unscheduled) spent by the MDC team. Unplanned hospitalisation costs for HF were calculated at a daily rate of 242. Outcomes were determined in monetary terms, i.e. the cost of the service per hospitalisation prevented and net costs/savings at 3 months.. The direct intervention cost of the MDC team was 5860, with an average cost per patient of 113 (95% Cl: 97-128). At 3 months, there were a total of 12 unplanned HF readmissions in the RC group (25.5% rate, 195 days) compared to 2 in the MDC group (3.9% rate, 17 days). The number needed to treat to prevent one hospitalisation for HF was 6 over 3 months. The cost of the service per hospitalisation prevented was 586. The intervention produced a net cost saving of 37,216 for 51 patients treated over 3 months. Sensitivity analyses using 50% variation in costs and lower relative risk reductions confirmed the cost-benefits of the intervention.. MDC of HF remains cost-beneficial when combined with optimal, medical care. The significant clinical and cost-benefits suggest that this intensive approach to MDC and medical management should become the standard of care for HF.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cost-Benefit Analysis; Decision Making; Digoxin; Diuretics; Dose-Response Relationship, Drug; Female; Furosemide; Health Care Costs; Heart Failure; Hospitalization; Humans; Ireland; Length of Stay; Male; Middle Aged; Perindopril; Prospective Studies; Time Factors; Ventricular Dysfunction, Left

To investigate the effect of Shengmai Injection (SMI) on serum concentration and pharmacokinetic parameters of digoxin in patients with congestive heart failure.. Forty in-patients with congestive heart failure were selected and randomly divided into 4 groups, the three treated groups I, II and III treated with digoxin combined with 20 ml, 40 ml and 60 ml of SMI respectively, and the control group, 10 patients in each group. The serum concentration of digoxin at different time points was determined with radioimmunoassay and the pharmacokinetical parameters were calculated with 3P97 pharmacokinetic software.. The serum concentration of digoxin in the treated group I was significantly lower than that in the control group (P < 0.05), with the pharmacokinetical parameters, including the elimination half-life time (T1/2), elimination rate constant (Ke), apparent volume of distribution (Vd), plasma clearance (CL) and area under curve (AUC), significantly different to those in the control group (P < 0.05 or P < 0.01). But the serum concentration of digoxin with its pharmacokinetical parameters in the other two treated groups were not different significantly to those in the control group respectively (P > 0.05).. SMI could influence the metabolism of digoxin in patients with congestive heart failure. This study has provided an important reference for safe and rational combined use of digoxin and SMI in clinical practice.

Topics: Adult; Aged; Coronary Disease; Digoxin; Drug Combinations; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Phytotherapy

The aim of this study was to characterize the population pharmacokinetics of levosimendan in patients with heart failure (NYHA grades III and IV) and its relationship to demographic factors, disease severity and concomitant use of digoxin and beta-blocking agents.. Data from two efficacy studies with levosimendan administered by intravenous infusion were combined (190 patients in total). The data were analysed using a nonlinear mixed-effects modelling approach as implemented in the NONMEM program. The model development was done in three sequential steps. First the best structural model was determined (e.g. a one-, two- or three-compartment pharmacokinetic model). This was followed by the identification and incorporation of important covariates into the model. Lastly the stochastic part of the model was refined.. A two-compartment model best described levosimendan pharmacokinetics. Clearance and the central volume of distribution were found to increase linearly with bodyweight. No other covariates, including concomitant use of digoxin and beta-blocking agents, influenced the pharmacokinetics. In the final model, a 76-kg patient was estimated to have a clearance +/- s.e. of 13.3 +/- 0.4 l h-1 and a central volume of distribution of 16.8 +/- 0.79 l. The interindividual variability was estimated to be 39% and 60% for clearance and central volume of distribution, respectively. Weight changed clearance by 1.5% [95% confidence interval (CI) 0.9%, 2.1%] and the central volume of distribution by 0.9% (95% CI 0.5%, 1.3%) per kg.. The population pharmacokinetics parameters of levosimendan in this patient group were comparable to those obtained by traditional methods in healthy volunteers and patients with mild heart failure. Bodyweight influenced the clearance and the central volume of distribution, which in practice is accounted for by weight adjusting doses. None of the other covariates, including digoxin and beta-blocking agents, significantly influenced the pharmacokinetics of levosimendan.

Topics: Adrenergic beta-Antagonists; Cardiotonic Agents; Digoxin; Double-Blind Method; Heart Failure; Humans; Hydrazones; Infusions, Intravenous; Pyridazines; Simendan

This study examined the relative merits of digoxin, carvedilol, and their combination for the management of patients with atrial fibrillation (AF) and heart failure (HF).. In patients with AF and HF, both digoxin and beta-blockers reduce the ventricular rate, and both may improve symptoms, but only beta-blockers have been shown to improve prognosis. If combined therapy is not superior to beta-blockers alone, treatment of patients with HF and AF could be simplified by stopping digoxin.. We enrolled 47 patients (29 males; mean age 68 years) with persistent AF and HF (mean left ventricular ejection fraction [LVEF] 24%) in a randomized, double-blinded, placebo-controlled study. In the first phase of the study, digoxin was compared with the combination of digoxin and carvedilol (four months). In the second phase, digoxin was withdrawn in a double-blinded manner in the carvedilol-treated arm, thus allowing a comparison between digoxin and carvedilol (six months). Investigations were undertaken at baseline and at the end of each phase.. Compared with digoxin alone, combination therapy lowered the ventricular rate on 24-h ambulatory electrocardiographic monitoring (p < 0.0001) and during submaximal exercise (p < 0.05), whereas LVEF (p < 0.05) and symptom score (p < 0.05) improved. In phase 2, there was no significant difference between digoxin alone and carvedilol alone in any variable. The mean ventricular rate rose and LVEF fell when patients switched from combination therapy to carvedilol alone. Six-minute walk distance was not significantly influenced by any therapy.. The combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cyclohexane Monoterpenes; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Humans; Male; Monoterpenes

To investigate the clinical effect of manshuailing oral liquid on patients with congestive heart failure of type heart and kidney Yang deficiency.. 90 patients of heart failure were randomly divided into 2 groups. 45 cases in the routine treatment group (RT) received general therapy including diuretics and digitalis, and 45 cases in the Chinese herb medicine group (CH) were treated basically with the above medicine, with additional manshuailing oral liquid. The clinical effect was summarized 6 weeks after treatment.. Total effect rate was 82.2% and 62.2% in CH and RTgroup respectively. Compared with pretreatment, heart function including stroke volume (SV), stroke volume index (SVI), cardiac index (CI), shorten rate of left ventricular short axe (deltaD%), distance of inter-ventricular septal to mitral valve (EPSS) were all improved significantly in both groups (P < 0.05 or P < 0.01), and with even better effects in the CH group than the RT group (P < 0.05 or P < 0.01), except the SV.. Manshuailing oral liquid can alleviate clinical symptom, decreased EPSS, increase deltaD% and improve heart function.

Topics: Administration, Oral; Adult; Aged; Cardiotonic Agents; Combined Modality Therapy; Diagnosis, Differential; Digoxin; Drug Combinations; Drugs, Chinese Herbal; Female; Heart Failure; Heart Function Tests; Humans; Hydrochlorothiazide; Isosorbide Dinitrate; Male; Medicine, Chinese Traditional; Middle Aged; Phytotherapy; Plants, Medicinal; Sodium Chloride Symporter Inhibitors; Vasodilator Agents; Yang Deficiency

We evaluated whether spironolactone would improve cardiac sympathetic nerve activity and symptoms in patients with congestive heart failure (CHF).. Thirty patients with CHF (left ventricular ejection fraction [LVEF] < 40%; mean, 30% +/- 9%) were treated with an angiotensin-converting enzyme inhibitor, a loop diuretic, and, in most cases, digoxin. Fifteen patients (group A) were assigned to additionally receive spironolactone (12.5-50 mg/day), and the remaining 15 patients (group B) continued their current regimen. Patients were studied before and 6 mo after treatment. The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-meta-iodobenzylguanidine (MIBG) images. LVEF was determined by echocardiography, and New York Heart Association (NYHA) functional class was estimated.. Before treatment, LVEF, TDS, H/M ratio, WR, and NYHA functional class were similar in both groups. With treatment, LVEF did not significantly improve in either group. However, after treatment in group A, TDS decreased from 37 +/- 9 to 25 +/- 13 (P = 0.0001), H/M ratio increased from 1.62 +/- 0.20 to 1.83 +/- 0.27 (P < 0.0001), and WR decreased from 51 +/- 9 to 40 +/- 15 (P < 0.001). In group B, these parameters did not significantly change. NYHA functional class improved in both groups (in group A, from 3.3 +/- 0.5 to 1.7 +/- 0.5 [P < 0.0001]; in group B, from 3.3 +/- 0.5 to 2.4 +/- 0.6 [P = 0.01]); this was a significantly greater improvement in group A than in group B (P < 0.01).. Spironolactone improves cardiac sympathetic nerve activity and symptoms in patients with CHF.

Topics: 3-Iodobenzylguanidine; Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Drug Therapy, Combination; Female; Heart; Heart Failure; Humans; Iodine Radioisotopes; Male; Radionuclide Imaging; Radiopharmaceuticals; Spironolactone; Stroke Volume; Sympathetic Nervous System

Analysis of heart rate variability (HRV) provides a noninvasive index of autonomic nervous system activity. HRV has shown to be reduced in congestive heart failure and in children with congenital heart disease (CHD). Beta-blockers improve HRV in adults with congestive heart failure, but this improvement remains to be demonstrated in children.. HRV was analysed in 14 infants with severe heart failure due to CHD who received a 'standard' therapy with digoxin and diuretics ('Digoxin/Diuretics' group) and in 9 of these patients with an additional propranolol therapy ('Propranolol' group) 17 days later on average and compared with HRV of 70 healthy infants ('Healthy Control').. Comparing the 'Digoxin/Diuretics' group versus 'Healthy Control', we found significantly reduced HRV in the time domain and the frequency domain, that could be abolished in the 'Propranolol' group. None of the HRV parameter were significantly related to age or any hemodynamic parameter but inversely related to ejection fractions within the normal range (pNN50: r= -0.58, p=0.004; rMSSD: r= -0.42; p=0.049). HRV measurements (SDNN, r= -0.48) and plasma norepinephrine levels (r=0.7) were significantly related to clinical symptoms of heart failure, measured by the Ross Score.. HRV represents a noninvasive parameter that is reduced in infants with congenital heart disease depending on the severity of heart failure but not on hemodynamic disturbances. Propranolol but not digoxin therapy effectively reduced the supposed autonomic imbalance in infants with severe heart failure due to CHD.

Topics: Adult; Anti-Arrhythmia Agents; Digoxin; Heart Defects, Congenital; Heart Failure; Heart Rate; Hemodynamics; Humans; Infant; Neurotransmitter Agents; Propranolol

The Digitalis Investigation Group trial reported that treatment with digoxin did not decrease overall mortality among patients with heart failure and depressed left ventricular systolic function, although it did reduce hospitalizations slightly. Even though the epidemiologic features, causes, and prognosis of heart failure vary between men and women, sex-based differences in the effect of digoxin were not evaluated.. We conducted a post hoc subgroup analysis to assess whether there were sex-based differences in the effect of digoxin therapy among the 6800 patients in the Digitalis Investigation Group study. The presence of an interaction between sex and digoxin therapy with respect to the primary end point of death from any cause was evaluated with the use of Mantel-Haenszel tests of heterogeneity and a multivariable Cox proportional-hazards model, adjusted for demographic and clinical variables.. There was an absolute difference of 5.8 percent (95 percent confidence interval, 0.5 to 11.1) between men and women in the effect of digoxin on the rate of death from any cause (P=0.034 for the interaction). Specifically, women who were randomly assigned to digoxin had a higher rate of death than women who were randomly assigned to placebo (33.1 percent vs. 28.9 percent; absolute difference, 4.2 percent, 95 percent confidence interval, -0.5 to 8.8). In contrast, the rate of death was similar among men randomly assigned to digoxin and men randomly assigned to placebo (35.2 percent vs. 36.9 percent; absolute difference, -1.6 percent; 95 percent confidence interval, -4.2 to 1.0). In the multivariable analysis, digoxin was associated with a significantly higher risk of death among women (adjusted hazard ratio for the comparison with placebo, 1.23; 95 percent confidence interval, 1.02 to 1.47), but it had no significant effect among men (adjusted hazard ratio, 0.93; 95 percent confidence interval, 0.85 to 1.02; P=0.014 for the interaction).. The effect of digoxin therapy differs between men and women. Digoxin therapy is associated with an increased risk of death from any cause among women, but not men, with heart failure and depressed left ventricular systolic function.

Topics: Aged; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Survival Analysis; Ventricular Dysfunction, Left

To determine plasma levels of N-terminal pro-brain natriuretic peptide (N-BNP) in control children to establish a normal age-dependent range from the neonatal period to adulthood. In addition, plasma concentrations of N-BNP were measured in children with congestive heart failure (CHF) and correlated with ejection fraction and clinical symptoms of heart failure.. For establishing a normal age-dependent range of plasma N-BNP, venous blood samples were taken in 133 control patients from the neonatal period to adulthood (10 days-32 years) and in 31 children with CHF. Plasma N-BNP levels were determined by an enzyme immunoassay. In children (1 month-14 years) with CHF, plasma N-BNP levels were correlated to ejection fraction measured by echocardiography and clinical symptoms of heart failure using the Ross Score.. N-BNP levels in control children, adolescents, and adults did not show a significant age-related difference. In control children, the normal range was established between 150 (10th percentile) and 430 fmol/mL (90th percentile). Mean plasma N-BNP in control children was 311 fmol/mL (range: 74-654 fmol/mL). In 31 children with CHF, the plasma N-BNP levels were significantly higher (mean: 846; range: 219-2718) than in control children. N-BNP levels showed a negative correlation with the ejection fraction (r = -0.53) and a positive correlation with the clinical heart failure score (r = 0.74).. Plasma N-BNP levels reflect the severity of symptoms of heart failure and the impairment of cardiac function in children with CHF. In the future, determination of plasma N-BNP levels may be used as a helpful adjunct to monitor the effect of various treatments for CHF in children.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Child; Child, Preschool; Digoxin; Diuretics; Echocardiography; Heart Failure; Humans; Infant; Infant, Newborn; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Reference Values; Severity of Illness Index; Stroke Volume

Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure.. To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing.. The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial.. A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias.. All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients.. Composite end point of time to death or first hospitalization for congestive heart failure.. One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming.. For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Pacemaker, Artificial; Single-Blind Method; Survival Analysis; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Warfarin

Topics: Adult; Aged; Digoxin; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Male; Middle Aged; Phytotherapy

Neurohormonal activation in children with heart failure due to congenital heart disease leads to downregulation of myocardial beta-receptors that may influence the postoperative course after cardiothoracic surgery.. Myocardial biopsies of 26 children (aged 14+/-4 months) were obtained from the right atrium during cardiac surgery. Patients were allocated to either of two groups based on the duration of their intensive care unit stay: group 1 comprised those who stayed less than 7 days (n = 17), whereas group 2 comprised those who stayed more than 7 days, plus 3 infants who died during the early postoperative course (n = 9). For beta1- and beta2-mRNA quantitation, real-time polymerase chain reaction with fluorescence-labeled products was used.. Values for myocardial beta1-receptor gene expression were twice as high in group 1 children compared with group 2 (beta1-receptor 0.12+/-0.07 versus 0.06+/-0.03, p = 0.0016; beta2-receptor 0.12+/-0.07 versus 0.06+/-0.03, p = 0.0071). Beta-receptor gene expression in 16 children who received standard treatment for heart failure averaged lower than in the 10 children who received additional propranolol.. Beta-receptor downregulation due to congestive heart failure has an impact on the postoperative course in children with congenital disease and depends on heart failure therapy.

Topics: Biopsy; Child, Preschool; Digoxin; Diuretics; Down-Regulation; Drug Therapy, Combination; Female; Heart Defects, Congenital; Heart Failure; Hospital Mortality; Humans; Infant; Length of Stay; Male; Myocardium; Postoperative Complications; Propranolol; Prospective Studies; Receptors, Adrenergic, beta; Risk Factors

We sought to determine whether there was a relationship between serum digoxin concentration (SDC), including SDCs typically regarded as low, and clinical efficacy related to digoxin in patients with symptomatic left ventricular dysfunction.. Digitalis glycosides have been used for 200 years in the treatment of heart failure (HF), but the SDC required for optimal clinical efficacy and acceptable toxicity remains controversial.. This relationship was investigated by utilizing data from two randomized, double-blinded, placebo-controlled, digoxin-withdrawal trials: the Prospective Randomized study Of Ventricular failure and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin on Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Major end points were worsening HF, change in left ventricular ejection fraction and treadmill time after randomization. The primary analysis investigated the relationship between SDC at randomization and these end points. A secondary categorical analysis compared these end points in patients who discontinued digoxin versus patients who continued digoxin and had low (0.5 to 0.9 ng/ml), moderate (0.9 to 1.2 ng/ml) or high (>1.2 ng/ml) SDCs at randomization.. Multiple regression analysis failed to find a relationship between randomization SDC, considered as a continuous variable, and any study end point (all p > 0.236). Multivariable Cox analysis found that the risk of worsening HF was significantly less (all p < 0.02) for patients in any category of SDC who continued digoxin, as compared with patients withdrawn from digoxin. Specifically, patients in the low SDC category were significantly less likely than placebo patients to experience worsening HF during follow-up (p = 0.018).. The beneficial effects of digoxin on common clinical end points in patients with HF were similar, regardless of SDC.

Topics: Aged; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Endpoint Determination; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

To evaluate the effect of an arteriolar dilator (diltiazem hydrochloride) versus a venodilator (isosorbide dinitrate) on digoxin kinetics and to estimate the efficacy and tolerability of these vasodilators when combined with digoxin for 10 days therapy in patients with congestive heart failure secondary to ischemic heart disease.. A double blind randomized cross over study was carried out to investigate the effect of an arteriolar dilator (diltiazem hydrochloride 180 mg/day orally) versus a venodilator (isosorbide dinitrate 30 mg/day orally) on digoxin kinetics (0.25 mg/day orally), after 10 days therapy in patients with heart failure due to ischemic heart disease. Also, the effect of these drugs on blood pressure, heart rate, renal functions and serum electrolytes, and their efficacy and tolerability in combination with digoxin were studied. This study was carried out in the Department of Medicine, Main Alexandria University Hospital, Alexandria, Egypt, during the period May 1999 through to May 2000.. Diltiazem caused a significant increase in digoxin maximum serum concentration without significant change in time to reach maximum concentration and the apparent volume of distribution. The total digoxin clearance was significantly reduced and the elimination half life was prolonged. Subsequently the area under time-concentration curve and the steady-state digoxin level were increased, but were still within therapeutic margin. On the other hand isosorbide dinitrate significantly increased digoxin maximum serum concentration but without change in the other digoxin pharmacokinetic parameters. Isosorbide dinitrate, but not diltiazem, caused significant reduction in supine and standing blood pressure, while both drugs did not significantly alter pulse rate, renal functions, serum sodium potassium and electrocardiographic pattern.. Patients who received diltiazem displayed a mean 51% increase in the area under the plasma concentration-time curve, 50% increase in mean steady state serum digoxin concentration, and 37% increase in peak serum digoxin concentration. While patients who received isosorbide dinitrate showed only a 15% increase in digoxin maximum serum concentration and no statistically significant change in mean steady state digoxin concentration or area under the plasma concentration-time curve. The elimination half life during the diltiazem phase was prolonged by 29% while there was no significant change with isosorbide dinitrate. Netiher diltiazem or isosorbide dinitrate significantly altered the time to reach maximum serum digoxin concentration. The addition of a vasodilator such as, diltiazem or isosorbid dinitrate to digoxin could significantly improve the symptoms and signs of heart failure compared to digoxin alone. They were well tolerated and without fear of electrolyte imbalance which potentiate digoxin toxicity.

Topics: Analysis of Variance; Digoxin; Diltiazem; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Electrolytes; Enzyme Inhibitors; Female; Half-Life; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Male; Middle Aged; Myocardial Ischemia; Vasodilator Agents

Intrinsic changes in skeletal muscle are being increasingly suspected as part of the underlying cause of exercise intolerance in patients with chronic heart failure (CHF). The objective of the present study was to determine whether differences existed between CHF patients and age-matched healthy controls in the concentration of skeletal muscle Na(+)-K(+)-ATPase (adenosine triphosphatase), a cation pump that functions to restore Na(+)-K(+) gradients and protect membrane excitability. Moreover, given the potency for physical activity in altering long-term regulation of the pump, an additional objective was to examine the role of activity level in pump expression in CHF patients. Na(+)-K(+)-ATPase concentration (pmol/g wet wt) determined in the vastus lateralis muscle of 27 CHF males (ejection fraction, 23 +/- 1.6%), using the vanadate facilitated [(3)H] ouabain binding technique, was not different (264 +/- 10) from 10 sedentary controls (268 +/- 19,P > 0.05). Similarly, no differences (P > 0.05) could be found between female patients (228 +/- 16, n = 7) and controls (243 +/- 13, n = 9). Differences between untrained control (294 +/- 20, n = 7), chronically active (251 +/- 20, n = 9), and trained (252 +/- 16, n = 6) CHF groups in Na(+)-K(+) pump expression were also insignificant. This study indicates that long-term regulation of Na(+)-K(+)-ATPase concentration is not altered in moderate CHF patients, regardless of the history of regular activity. However, the positive correlations (P < 0.05) that were observed between peak aerobic power (VO(2) peak) and Na(+)-K(+)-ATPase (r = 0.422) and VO(2) peak and maximal citrate synthase activity (r = 0.404) suggests a role for the skeletal muscle in explaining exercise intolerance in CHF patients.

Topics: Binding, Competitive; Chronic Disease; Citrate (si)-Synthase; Digoxin; Exercise; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Muscle, Skeletal; Oxidation-Reduction; Sex Factors; Sodium-Potassium-Exchanging ATPase; Stroke Volume

Infants with congenital heart disease and left-to-right shunts may develop significant clinical symptoms of congestive heart failure in spite of therapy with digoxin and diuretics. We investigated the effects of beta-blockade in infants with severe heart failure.. We performed a prospective, randomized, open monocenter trial in infants treated with digoxin and diuretics (n=10) in comparison to 10 infants receiving additional beta-blocker therapy. After 17 days on average beta-blocker treated infants (propranolol:1,6 mg/kg/day) improved significantly with respect to Ross heart failure score (3.3+/-2.3 vs. 8.3+/-1.9, P=0.002), lower renin levels (338+/-236 vs. 704+/-490 microU/l, P=0.008) and lower mean heart rates in Holter ECG (118+/-10 vs. 142+/-11 beats/min, P<0.001). While digoxin and diuretic treated infants had unchanged mean heart rate (149+/-8 vs. 148+/-10 beats/min), less decrease of symptoms (Ross Score: 8.5+/-1.7 vs. 6.8+/-2.3, P=0.02) but a significant increase of renin levels (139+/-102 vs. 938+/-607 microU/l, P=0.001).. Additional propranolol treatment but not digoxin and diuretics alone can effectively reduce clinical symptoms of heart failure in infants with congenital heart disease, who suffer from increased neurohormonal activation.

Topics: Adrenergic beta-Antagonists; Cardiotonic Agents; Digoxin; Diuretics; Heart Defects, Congenital; Heart Failure; Heart Rate; Heart Septal Defects; Hemodynamics; Hormones; Humans; Infant; Infant, Newborn; Propranolol; Prospective Studies; Severity of Illness Index; Statistics, Nonparametric

This study was designed to determine the effect of increasing age on mortality, hospitalizations and digoxin side effects in patients with heart failure (HF), and to determine whether the effect of digoxin on clinical outcomes varies as a function of age.. The incidence and prevalence of HF increase with advancing age, but there are limited data on the clinical course and response to specific therapeutic interventions in elderly patients with HF.. The Digitalis Investigation Group (DIG) study was a prospective, randomized clinical trial involving 7,788 patients with HF randomized to digoxin or placebo and followed for an average of 37 months. In the present analysis, patients were stratified into five age categories: <50 years (n = 841), 50 to 59 years (n = 1,545), 60 to 69 years (n = 2,885), 70 to 79 years (n = 2,092) and > or =80 years (n = 425). Interactions between age and the following clinical outcomes were examined: total mortality, all-cause hospitalizations, HF hospitalizations, the composite of HF death or HF hospitalization, hospitalization for suspected digoxin toxicity and withdrawal from therapy because of side effects.. Increasing age was an independent risk factor for total mortality, all-cause hospitalization, HF hospitalization, HF death or hospital admission, hospitalization for suspected digoxin toxicity and withdrawal from digoxin therapy (all p < 0.001). However, there were no significant interactions between age and digoxin treatment with respect to any of the major clinical end points.. Increasing age is associated with progressively worse clinical outcomes in patients with HF. However, the beneficial effects of digoxin in reducing all-cause admissions, HF admissions, and HF death or hospitalization are independent of age. Thus, digoxin remains a useful agent for the adjunctive treatment of HF due to impaired left ventricular systolic function in patients of all ages.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Survival Analysis

Previous studies in patients with congestive heart failure (CHF) have revealed abnormalities of cellular volume that might have an impact on the dysregulation of peripheral vascular resistance. Human mononuclear leukocytes (HML) represent a model for the study of cellular volume regulation. We investigated the impact of enalapril and carvedilol on HML volume and on the activity of the Na+/H+ exchanger in 26 patients with CHF and 20 volunteers. Over a period of 4 weeks, 18 patients received enalapril in addition to the previous therapy while 8 patients additionally received carvedilol. HML diameters and the activity of the Na+/H+ exchanger were measured by a Coulter Counter. Both patient groups showed abnormally increased initial volumes of HML compared to the volunteer group at baseline. Four weeks of therapy with enalapril in addition to therapy with diuretics and digoxin did not result in a statistically significant reduction of lymphocyte volume, whereas add-on therapy with carvedilol to therapy with ACE inhibitors, diuretics and digoxin reduced the volume significantly. Alterations could not be found in the activity of the Na+/H+ exchanger in either patient group compared to volunteers. Supplementary drug therapy with carvedilol in patients with CHF leads to a reduction of the increased lymphocytic volume, possibly reflecting the beneficial effect of beta-blockade.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Carvedilol; Cell Size; Digoxin; Diuretics; Drug Interactions; Enalapril; Female; Heart Failure; Humans; Leukocytes, Mononuclear; Lymphocytes; Male; Middle Aged; Propanolamines; Sodium-Hydrogen Exchangers; Treatment Outcome

The aim of the study was to investigate the effect of chronic digoxin treatment on circadian blood pressure profile in normotensive patients with mild congestive heart failure.. In a randomized double-blind, placebo-controlled cross-over protocol, 12 normotensive patients with mild congestive heart failure took digoxin or placebo for a total of 7 days. Automatic 24-h ambulatory blood pressure measurements were carried out at day 7, of either digoxin or placebo.. Diastolic blood pressure significantly decreased and systolic blood pressure significantly increased during overnight sleep in the digoxin phase compared to placebo. Digoxin had no effect on either systolic or diastolic blood pressure during daytime. Heart rate decreased in the overnight sleeping phase but did not differ significantly between placebo and digoxin phase.. Digoxin significantly decreases diastolic blood pressure during overnight sleep in patients with congestive heart failure. This effect is likely to be caused by reduction of sympathetic activity or increase of parasympathetic activity. Increase of systolic blood pressure during sleep is probably caused by the positive inotropic effect of the drug.

Topics: Aged; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiotonic Agents; Circadian Rhythm; Diastole; Digoxin; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Placebos; Systole

The predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for congestive heart failure (CHF), the use of angiotensin-converting-enzyme (ACE) inhibitors in this population, and the ability of a pharmacist outreach program to address underutilization of ACE inhibitors were studied. All physicians and owner-managers of community pharmacies on Newfoundland's Avalon Peninsula were asked to participate in the study. Pharmacists who agreed to participate were asked to list patients of the participating physicians with prescriptions for (1) furosemide and digoxin with and without an ACE inhibitor or angiotensin II-receptor inhibitor and (2) an ACE inhibitor. Physicians were visited by a pharmacist and asked whether each of their patients receiving digoxin and furosemide was being treated for CHF and to identify further cases of CHF among their patients receiving an ACE inhibitor. Intervention-group physicians received academic detailing on the use and dosage of ACE inhibitors and angiotensin II-receptor inhibitors for CHF. Both groups were reinterviewed after three months to establish what if any changes in therapy had occurred for each patient discussed during the first visit. The positive predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for CHF was 94%. Seventy-six percent of patients identified by physicians as CHF patients who were taking digoxin and furosemide were treated with an ACE inhibitor. Thirty-six percent of patients treated with an ACE inhibitor for CHF received the targeted dosage. Four physicians stated that the outreach visit influenced their prescribing, but there was no significant difference in ACE inhibitor prescribing between the intervention and control groups. A pharmacist outreach program involving the use of prescription records and academic detailing did not affect prescribing or dosages of ACE inhibitors but demonstrated value as a quality assurance tool.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Community Pharmacy Services; Community-Institutional Relations; Digoxin; Diuretics; Drug Prescriptions; Drug Therapy, Combination; Furosemide; Heart Failure; Humans; Interviews as Topic; Newfoundland and Labrador; Practice Patterns, Physicians'; Predictive Value of Tests; Records

There is currently no objective practical guide to intensity of drug treatment for individuals with heart failure. We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide (N-BNP) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen.. 69 patients with impaired systolic function (left-ventricular ejection fraction <40%) and symptomatic heart failure (New York Heart Association class II-IV) were randomised to receive treatment guided by either plasma N-BNP concentration (BNP group) or standardised clinical assessment (clinical group).. During follow-up (minimum 6-months, median 9.5 months), there were fewer total cardiovascular events (death, hospital admission, or heart failure decompensation) in the BNP group than in the clinical group (19 vs 54, p=0.02). At 6 months, 27% of patients in the BNP group and 53% in the clinical group had experienced a first cardiovascular event (p=0.034). Changes in left-ventricular function, quality of life, renal function, and adverse events were similar in both groups.. N-BNP-guided treatment of heart failure reduced total cardiovascular events, and delayed time to first event compared with intensive clinically guided treatment.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Digoxin; Diuretics; Double-Blind Method; Female; Follow-Up Studies; Furosemide; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Time Factors; Vasodilator Agents; Ventricular Dysfunction, Left

The incidence, predictive factors, morbidity, and mortality associated with the development of supraventricular tachyarrhythmias (SVTs) in patients with congestive heart failure (CHF) are poorly defined.. In the Digitalis Investigation Group trial, patients with CHF who were in sinus rhythm were randomly assigned to digoxin (n = 3,889) or placebo (n = 3,899) and followed up for a mean of 37 months. Baseline factors that predicted the occurrence of SVT and the effects of SVT on total mortality, stroke, and hospitalization for worsening CHF were determined.. Eight hundred sixty-six patients (11.1%) had SVT during the study period. Older age (odds ratio [OR], 1.029 for each year increase in age; p = 0.0001), male sex (OR, 1.270; p = 0.0075), increasing duration of CHF (OR, 1.003 for each month increase in duration of CHF; p = 0.0021), and a cardiothoracic ratio of > 0.50 (OR, 1.403; p = 0.0001) predicted an increased risk of experiencing SVT. Left ventricular ejection fraction, New York Heart Association functional class, and treatment with digoxin vs placebo were not related to the occurrence of SVT. After adjustment for other risk factors, development of SVT predicted a greater risk of subsequent total mortality (risk ratio [RR] = 2.451; p = 0.0001), stroke (RR = 2.352; p = 0.0001), and hospitalization for worsening CHF (RR = 3. 004; p = 0.0001).. In CHF patients in sinus rhythm, older age, male sex, longer duration of CHF, and increased cardiothoracic ratio predict an increased risk for experiencing SVT. Development of SVT is a strong independent predictor of mortality, stroke, and hospitalization for CHF in this population. Prevention of SVT may prolong survival and reduce morbidity in CHF patients.

Topics: Age Factors; Aged; Cardiotonic Agents; Digoxin; Double-Blind Method; Female; Heart Failure; Heart Rate; Humans; Incidence; Male; Middle Aged; Odds Ratio; Prognosis; Sex Factors; Stroke; Stroke Volume; Survival Rate; Tachycardia, Supraventricular

We examined clinical outcomes associated with non-randomised digoxin therapy in a postmyocardial infarction population with clinical heart failure (AIRE study). Our results raise concern about the safety of digoxin in this population.

Topics: Adult; Cardiotonic Agents; Digoxin; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Product Surveillance, Postmarketing; Tachycardia, Ventricular; Treatment Outcome

There is not much evidence about the usefulness of digoxin or enalapril in the treatment of heart failure due to mitral insufficiency.. To compare digoxin and enalapril in the treatment of heart failure due to mitral insufficiency.. Patients with mitral insufficiency, in sinus rhythm, with a heart failure grade II or III and with echocardiographic left ventricular dilatation were eligible for the study. They received sequentially, during 12 weeks each, digoxin 0.25 mg/day or enalapril in doses up to 20 mg/day, with a washout in-between period of 2 weeks. The order of the sequence was determined randomly. At the start and end of treatment, functional class according to NYHA and maximal exercise tolerance in the treadmill were assessed and a color Doppler echocardiogram was done to measure ventricular dimensions, function and degree of mitral insufficiency.. Nine patients on enalapril and 12 on digoxin improved their functional capacity. Digoxin improved exercise time in 76 +/- 168 sec (p = 0.022), whereas this change was not significant with enalapril (38 +/- 158 sec; p = 0.2). With enalapril treatment, ventricular diastolic dimension decreased from 59.3 +/- 8.1 to 58 +/- 9.3 mm and the area of mitral insufficiency decreased from 8.1 +/- 3.5 to 6.6 +/- 3.1 cm2. Digoxin did not induce any significant echocardiographic change.. In these patients, digoxin and enalapril improved functional class. Digoxin improved exercise time and enalapril reduced ventricular dimensions and mitral insufficiency.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Double-Blind Method; Enalapril; Exercise Tolerance; Female; Heart Failure; Heart Ventricles; Humans; Male; Mitral Valve Insufficiency

In our country, patients with congestive heart failure who are treated chronically with digoxin are usually advised by their physicians to stop taking the medication two days a week. This is probably aimed at decreasing digitalis toxicity. Based on digoxin pharmacokinetics we assumed that the drug plasmatic level should diminish by 40 to 50%, below the therapeutic concentration of 0.8 to 2 milligrams, after two days of suspension. The objectives of this study were: a) to analyze the reduction of the plasmatic concentration of digoxin after a two day interruption of treatment, b) to compare the plasmatic levels of the drug between patients who received continuous and discontinuous treatment. A prospective, randomized and simple blind trial was designed. A total of 36 patients with congestive heart failure and systolic dysfunction with atrial fibrillation or sinus rythm were included. Group 1 (19 patients) received continuous treatment and Group 2 (17 patients) took the drug from Monday to Friday. In the continuous treatment group there was no significant difference between the Monday (1.06 +/- 0.55 milligrams) and the Friday (1.1 +/- 0.57 milligrams) digoxin concentrations. In the discontinuous treatment group the Monday digoxin concentration (0.611 +/- 0.396 milligrams) was lower than the Friday one (1.04 +/- 0.58 milligrams). The difference was statistically significant with a p = 0.000002. In conclusion, the two days a week suspension schedule reduces the plasmatic concentration of digoxin to subtherapeutic levels while the continuous regime maintains stable concentrations within the therapeutic range. Adjusting the dose to the creatinine clearance, average concentrations of 1 milligram are obtained. These results suggest that digitalis intoxication could be prevented by adjusting the dose according to renal function rather than interrupting the treatment as it is usually done in our country.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

We sought to study the efficacy of "triple" therapy with digoxin, diuretic and angiotensin-converting enzyme inhibitor (ACEI) compared to other combinations of these drugs in patients with symptomatic left ventricular systolic dysfunction.. Controversy continues concerning the role of combining digoxin with diuretic and ACEI in the initial management of patients with heart failure.. The study utilized data from two studies of digoxin efficacy: Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Worsening heart failure defined as augmentation of heart failure therapy or an emergency room visit or hospitalization for increased heart failure was the main outcome measure.. A total of 266 patients comprising the four treatment groups of the combined PROVED (diuretic alone or digoxin and diuretic) and RADIANCE (ACEI and diuretic, or digoxin, diuretic and ACEI) trials were analyzed. Worsening heart failure occurred in only 4 of the 85 patients who continued digoxin, diuretic and ACEI therapy (4.7%) compared to 18 of the 42 patients (19%) on digoxin and diuretic therapy (p=0.009), to 23 of the 93 patients (25%) on ACEI and diuretic therapy (p=0.001) and to 18 of the 46 patients (39%) on diuretic alone (p < 0.001). Life table and multivariate analysis also demonstrated that worsening heart failure was least likely in patients treated with triple therapy (p < 0.01 vs. all other groups).. Pending definitive, prospective clinical trials, our results argue for triple therapy as the initial management of patients with symptomatic heart failure due to systolic dysfunction.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Ventricular Function, Left

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome

To test the long-term effect of enalapril maleate treatment on progression of clinical signs of heart disease in dogs with moderate or severe naturally acquired heart failure associated with chronic degenerative mitral valvular disease (mitral regurgitation [MR]) or dilated cardiomyopathy (DCM).. Prospective multicenter study.. 110 dogs enrolled at 15 locations in the United States.. All dogs enrolled in this study were maintained on their randomly allocated treatment regimen until death, treatment failure (deterioration of condition requiring additional medication), or termination of the study. All dogs entered in the study received standard heart failure treatment (furosemide with or without digoxin). Statistical analysis (log-rank test) was performed to compare the distribution of number of days in the study between dogs that received placebo tablets and dogs that received enalapril tablets.. When dogs with MR and DCM were grouped together, mean number of days until treatment failure was significantly different between those receiving enalapril and those given placebo tablets (157.5 and 77.0 days, respectively). For dogs with MR, mean number of days until treatment failure was significantly different between those receiving enalapril and placebo tablets (159.5 and 86.6 days, respectively). Mean number of days until treatment failure among dogs with DCM receiving enalapril and placebo tablets was 142.8 and 56.5, respectively.. Use of enalapril in combination with standard treatment (diuretics with or without digoxin) appears to be beneficial over an extended period, compared with standard treatment alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cardiotonic Agents; Death, Sudden, Cardiac; Digoxin; Disease Progression; Diuretics; Dog Diseases; Dogs; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Male; Mitral Valve Insufficiency; Prospective Studies; Uremia

Increased mortality in digoxin-treated subjects has been demonstrated in patients with recent myocardial infarction. Those with congestive heart failure (CHF) due to causes other than myocardial infarction seem to be free from this effect. No information is currently available concerning mortality in elderly people who are frequently prescribed digitalis even in the absence of CHF. The aim of this study was to investigate whether subjects improperly receiving digoxin were worse off than those not receiving this drug. This analysis is a part of CASTEL, a population-based prospective study that has enrolled a cohort of 2,254 subjects aged > or = 65 years. CHF was diagnosed in 187 subjects and atrial fibrillation (AF) in 90. The remaining 1,977 were free from CHF and in sinus rhythm, but 447 were treated with digitalis. Cumulative mortality and morbid events by digitalis treatment were calculated in all these categories. Among subjects free from CHF and AF (improper use), all-cause and cardiovascular mortality was significantly higher among those taking digitalis than in those who did not. Non-fatal events including CHF were also more apparent in the former than in the latter. Cox analysis confirmed digitalis as a predictor of mortality in these subjects. No effect of digitalis on survival was found in patients with CHF or AF (proper use). In elderly subjects without atrial fibrillation or CHF, the use of digitalis worsens morbidity and mortality.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cohort Studies; Digoxin; Heart Conduction System; Heart Failure; Humans; Male; Morbidity; Multivariate Analysis; Prospective Studies

It has been proposed that worsening of heart failure with dihydropyridines, such as nicardipine, is related to the activation of the neuroendocrine system. To test this, we evaluated 20 patients with severe heart failure (mean age, 55 +/- 13 years; New York Heart Association functional class III; left ventricular ejection fraction, 18% +/- 8% on maintenance therapy with captopril, digoxin, and diuretics) who were randomized to nicardipine (60 or 90 mg/d) or placebo during a 4-month double-blind protocol. The following measurements were obtained at baseline, monthly, and at 4 months or last follow-up visit: rest and exercise radionuclide ventriculography, maximal treadmill time, 6-minute walking test distance, serum norepinephrine and aldosterone concentrations, and plasma renin activity. During the follow-up period, worsening of heart failure occurred in 6 patients in the nicardipine group and in 2 patients in the placebo group (p = 0.06). The maximal treadmill time for a 6-minute walking distance and exercise radionuclide ejection fraction at the last follow-up visit did not change in patients who did not deteriorate with heart failure in the placebo or nicardipine groups as compared with baseline values. In this study group of patients with severe heart failure receiving therapy with digoxin, captopril, and diuretics, nicardipine was associated with worsening heart failure without an apparent activation of the neurohormones. However, because of the small number of patients and a significant number of patients who deteriorated during the follow-up period, no definitive conclusions can be made.

Topics: Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Captopril; Cardiotonic Agents; Digoxin; Disease Progression; Diuretics; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Neurosecretory Systems; Nicardipine; Norepinephrine; Renin; Severity of Illness Index; Stroke Volume; Treatment Outcome

To find the safe and effective treatment and drugs for congestive heart failure (CHF).. Ninety CHF patients whose heart function belong to III-IV grade were randomly divided into 3 groups: Group A was treated with Qiangxinling liquid extract (QXLLE); Group B with QXLLE plus small dose of digoxin and Group C with digoxin alone.. The total effective rate on heart function of Group A was 86.7%, Group B 93.3% and Group C 83.3%, the effect of Group B was better than that of the other two groups (P < 0.05, P < 0.01). The digoxin withdrawing and reducing rate in Group B was higher than that in Group C (86.7% vs 50.0%, P < 0.05). The left ventricular systolic function, including stroke volume, cardiac output, ejection fraction of the 3 groups were improved after treatment, among them the effect of Group B was the best (P < 0.01). Moreover, improvement in ventricular diastolic function was shown in Group A and B, including the maximum blood flow of the late and the early diastolic stage as well as the ratio of them (P < 0.05, P < 0.01). The plasma renin activity, angiotensin II and atrial natriuretic peptide of Group A and B were also lowered after treatment and were significantly different to those of the Group C (P < 0.01).. QXLLE could improve the heart function, clinical symptoms and neuro-endocrinal indexes of CHF patients and reduce the side effects of digoxin.

Topics: Adult; Aged; Cardiac Output; Digoxin; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Male; Middle Aged; Stroke Volume

The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial. We studied the effect of digoxin on mortality and hospitalization in a randomized, double-blind clinical trial.. In the main trial, patients with a left ventricular ejection fraction of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and angiotensin-converting-enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average follow-up, 37 months). In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo.. In the main trial, mortality was unaffected. There were 1181 deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence interval, 0.91 to 1.07; P=0.80). In the digoxin group, there was a trend toward a decrease in the risk of death attributed to worsening heart failure (risk ratio, 0.88; 95 percent confidence interval, 0.77 to 1.01; P=0.06). There were 6 percent fewer hospitalizations overall in that group than in the placebo group, and fewer patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7 percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79; P<0.001). In the ancillary trial, the findings regarding the primary combined outcome of death or hospitalization due to worsening heart failure were consistent with the results of the main trial.. Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.

Topics: Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Stroke Volume; Treatment Outcome

Long-term beta-adrenergic blockade does not appear to be associated with drug-induced training in patients with congestive heart failure (CHF); whether exercise training can increase peak aerobic capacity in patients with CHF who are treated with beta-adrenergic blockers is currently unknown.. We studied 23 patients with CHF who were treated with carvedilol or propranolol in addition to ACE inhibitors, furosemide, and digoxin. Of the patients treated with carvedilol, 8 underwent exercise training and 8 remained sedentary. All 7 patients treated with propranolol underwent exercise training. Peak oxygen consumption (mL.kg-1.min-1) was serially measured in trained and sedentary patients. Peak reactive hyperemia (mL.min-1.100 mL-1) was determined in the calf and forearm immediately before and after 12 weeks of training. The peak oxygen consumption of trained patients treated with either carvedilol or propranolol increased from 12.9 +/- 1.4 to 16.0 +/- 1.6 (P < .001) and 12.4 +/- 1.0 to 15.7 +/- 0.9 (P < .001) mL.kg-1.min-1, respectively, whereas it did not change in the sedentary patients. Peak reactive hyperemia increased significantly in the calves but not the forearms of trained patients.. Long-term, nonselective beta-adrenergic blockade with carvedilol or propranolol does not prevent patients with CHF from deriving systemic and regional benefits from physical training.

Topics: Adaptation, Physiological; Adrenergic beta-Antagonists; Aerobiosis; Aged; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Cardiotonic Agents; Carvedilol; Digoxin; Diuretics; Drug Therapy, Combination; Exercise Therapy; Female; Forearm; Furosemide; Heart; Heart Failure; Humans; Hyperemia; Leg; Male; Middle Aged; Oxygen Consumption; Propanolamines; Propranolol; Receptors, Adrenergic, beta

Topics: Canada; Cardiotonic Agents; Digoxin; Double-Blind Method; Heart Failure; Hospitalization; Humans; United States

This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.

Topics: Aged; Angiography; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiac Output; Cardiotonic Agents; Cause of Death; Digoxin; Diuretics; Epoprostenol; Exercise Tolerance; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Proportional Hazards Models; Pulmonary Wedge Pressure; Quality of Life; Risk Factors; Stroke Volume; Survival Rate; Vascular Resistance; Ventricular Dysfunction, Left; Walking

Topics: Adult; Aged; Digoxin; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Survival Rate

This was a double-blind, placebo-controlled, crossover study designed to determine the influence of digitalis treatment on left ventricular (LV) response to physical exercise in patients with congestive heart failure (CHF). In 10 patients with CHF (ejection fraction 29 +/- 2%), LV function was assessed during upright bicycle exercise using an ambulatory radionuclide detector for continuous noninvasive monitoring of cardiac function. Exercise was performed during control conditions and after a 3-week treatment with digoxin (0.25 mg/day orally) or placebo. Ten normal volunteers matched for sex and age constituted the control group. In normals, exercise ejection fraction and end-diastolic volume increased (both p <0.001), while end-systolic volume decreased progressively (p <0.001). In control conditions, patients with CHF had a sharp increase in heart rate during exercise, while ejection fraction did not change; both end-diastolic and end-systolic volumes increased significantly (both p <0.001) during exercise. During digoxin treatment, heart rate response to exercise recorded in patients with CHF was comparable to that recorded in normal subjects. In addition, a significant increase in ejection fraction during exercise was detected (P <0.001), and the increase in end-systolic volume was significantly smaller than that observed in control conditions (p <0.05). When patients received placebo, the responses of LV function to exercise were comparable to those observed in control conditions. These findings demonstrate that digitalis has a favorable influence on LV functional adaptation to exercise in CHF.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cross-Over Studies; Digoxin; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Heart Failure; Humans; Male; Middle Aged; Reference Values; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Therapy with angiotensin-converting enzyme inhibitors and nonselective vasodilators (hydralazine and isosorbide dinitrate) has become accepted treatment in patients with symptomatic, chronic congestive heart failure (CHF), and has been demonstrated in large clinical trials to ameliorate symptoms, improve exercise performance, and reduce cardiac mortality. Nevertheless, the management of patients with CHF remains a therapeutic challenge. The second Vasodilator-Heart Failure Trial (V-HeFT II) showed that the average 2-year mortality with enalapril (18%) was significantly lower than that with hydralazine-isosorbide dinitrate (25%) but, somewhat surprisingly, the nonspecific vasodilators produced significantly more improvement in exercise performance and left ventricular function. Such data suggest that improvement in symptoms, hemodynamics, and survival may not be afforded by the use of a single class of vasodilator therapy, but might be optimized by the combined use of different agents. This report describes the rationale and design of V-HeFT III, a multicenter, prospective, randomized, double-blind, placebo-controlled trial comparing the effects of chronic oral extended-release felodipine (felodipine ER) 2.5 to 5 mg twice daily, when added to a stable regimen of enalapril and loop diuretics, with or without digoxin, on exercise performance, morbidity, and mortality in patients with New York Heart Association functional class II to III CHF followed for a minimum of 12 weeks. Felodipine is a second-generation dihydropyridine calcium antagonist with a high degree of vascular selectivity which, in the doses used in this study, exerts its systemic arterial effect by decreasing peripheral vascular resistance without producing negative inotropic effects. The results of V-HeFT III may shed important light on the role of additive vasodilator therapy in the management of patients with CHF.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Exercise Test; Felodipine; Heart Failure; Hemodynamics; Humans; Prospective Studies; Quality of Life; Research Design; Treatment Outcome; Vasodilator Agents

To evaluate the efficacy and safety of the second generation dihydropyridine calcium channel blocker lacidipine in patients with heart failure.. Placebo controlled, parallel group, double blind study over 8 weeks.. General community hospital in Breda, The Netherlands.. A random sample was studied of 25 outpatients with symptoms of mild to moderate heart failure, despite treatment with diuretics, digoxin, and angiotensin converting enzyme inhibitors. Their mean age was 65 years, with mean left ventricular ejection fraction of 0.24 and a peak oxygen consumption of 14.4 ml/min/kg. Two patients dropped out on lacidipine, one patient on placebo.. Treatment with lacidipine 4 mg once daily or placebo for eight weeks.. Cardiopulmonary exercise testing, invasive haemodynamics, and plasma neurohormones.. Treatment with lacidipine 4 mg once daily, as compared to placebo treatment, significantly improved peak oxygen consumption (P < 0.02), cardiac index (P < 0.01), and stroke volume (P < 0.03) paralleled by a decrease in systemic vascular resistance (P < 0.03) and arteriovenous oxygen content difference (P < 0.01). Plasma noradrenaline, plasma renin activity, and aldosterone values did not differ between lacidipine and placebo.. This second generation dihydropyridine may be of value as an adjunct to standard treatment in congestive heart failure patients.

Topics: Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Digoxin; Dihydropyridines; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Prospective Studies; Renin; Stroke Volume; Vascular Resistance

The influence of epoprostenol on the pharmacokinetics of drugs administered concurrently to patients with congestive heart failure (CHF) receiving epoprostenol was evaluated as a secondary objective of a Phase II pilot study. A total of 278 blood samples were collected from 30 patients with end-stage CHF receiving conventional therapy alone or conventional therapy plus epoprostenol. Estimates of oral clearance (Cl), volume of distribution, and absorption rate constant of digoxin were generated from plasma digoxin concentrations using nonlinear mixed effects modeling, and the effect of epoprostenol on Cl of digoxin was evaluated by univariate analysis. Additional factors that were evaluated by univariate analysis included age, obesity, time since study entry, cardiac output, concomitant use of angiotensin-converting enzyme (ACE) inhibitor, concomitant dobutamine, and estimated creatinine clearance. Backward elimination was used to arrive at a final model that included concomitant epoprostenol as a covariate. The final model revealed an approximate 15% decrease in Cl of digoxin in response to short-term administration of epoprostenol that was no longer apparent by the end of the 12-week treatment phase. Simulations revealed that this effect, although statistically significant, would not be clinically significant in most patients; however, the potential exists for short-term elevation of digoxin concentrations in response to concurrent administration of epoprostenol.

Topics: Adult; Cardiotonic Agents; Digoxin; Epoprostenol; Heart Failure; Humans; Metabolic Clearance Rate; Nonlinear Dynamics; Pilot Projects; Platelet Aggregation Inhibitors

This article provides a detailed overview of the rationale for key aspects of the protocol of the Digitalis Investigation Group (DIG) trial. It also highlights unusual aspects of the study implementation and the baseline characteristics. The DIG trial is a large, simple, international placebo-controlled trial whose primary objective is to determine the effect of digoxin on all cause mortality in patients with clinical heart failure who are in sinus rhythm and whose ejection fraction is < or = 0.45. An ancillary study examines the effect in those with an ejection fraction > 0.45. Key aspects of the trial include the simplicity of the design, broad eligibility criteria, essential data collection, and inclusion of various types of centers. A total of 302 centers in the United States and Canada enrolled 7788 patients between February 1991 and September 1993. Follow-up continued until December 1995 with the results available in Spring 1996.

Topics: Aged; Digitalis Glycosides; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Multicenter Studies as Topic; Patient Selection; Randomized Controlled Trials as Topic; Treatment Outcome

Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are based primarily on studies with unmatched control groups, suboptimal blood sampling, and in patients not receiving angiotensin-converting enzyme (ACE) inhibitors. These agents increase renal blood flow, which theoretically may offset alterations in drug disposition in patients with CHF. The pharmacokinetics of procainamide in patients with chronic CHF and in matched controls were compared. A single intravenous dose of 750 mg of procainamide was administered to 9 patients with chronic New York Heart Association (NYHA) class II or III CHF (mean +/- SD left ventricular ejection fraction 22 +/- 9%) receiving medical therapy and 7 control subjects matched for age and gender. Blood and urine samples were collected at intervals over a period of 48 and 72 hours, respectively. Patients with CHF and control subjects were demographically similar, with the exception of concomitant medications, including ACE inhibitors (8/9 versus 1/7, respectively). There were no significant differences between patients with CHF and control subjects in mean +/- SD peak serum concentrations (Cmax), area under the serum concentration-time curve (AUC0-infinity), total clearance, renal clearance, half-life (t1/2), or volume of distribution (Vd) of procainamide. Similarly, there were no significant differences between patients with CHF and control subjects in the mean +/- SD Cmax, AUC0-infinity, renal clearance, or t1/2 of N-acetylprocainamide (NAPA). Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Procainamide

This study was designed to determine whether decreases in the circadian variability of arterial blood pressure and heart rate measured in ambulatory patients would correlate with neurohumoral indices of the severity of congestive heart failure not the result of systemic arterial hypertension, and whether treatment with angiotensin-converting enzyme (ACE) inhibitors would restore a more normal pattern. The study also examined the ability of ambulatory blood pressure monitoring to discern pharmacodynamic patterns in patients with congestive heart failure, which is associated with decreased variability in circadian variations in blood pressure and heart rate among hospitalized patients. Increased plasma norepinephrine, renin activity, and atrial natriuretic peptide (ANP) have a positive correlation with worsening clinical status. ACE inhibitors have been found to be beneficial in the treatment of congestive heart failure. Ambulatory 24-h blood pressure and neurohumoral measurements were recorded in 30 patients with congestive heart failure (class II-IV, New York Heart Association) before treatment with lisinopril or captopril and repeated after 6 weeks of treatment. Fourier analysis was used as a curve-smoothing technique to compare the pharmacodynamics of the two ACE inhibitors. The absolute amplitude of systolic blood pressure correlated inversely with plasma norepinephrine and ANP (p = 0.004) but not with renin activity. Mean 24-h systemic arterial blood pressure did not decrease significantly after treatment with ACE inhibitors. An increase in absolute amplitude of systolic blood pressure correlated inversely with baseline amplitude (p < 0.00001). Inspection of the Fourier-smoothed curves demonstrated differences in the circadian effect of lisinopril and captopril on systolic blood pressure and rate-pressure product. Ambulatory 24-h blood pressure monitoring may prove useful in the assessment of the severity and treatment of congestive heart failure.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Captopril; Circadian Rhythm; Digoxin; Diuretics; Double-Blind Method; Female; Heart Failure; Heart Rate; Humans; Lisinopril; Male; Middle Aged; Norepinephrine

Forty-five patients with class IV cardiac function were divided into three groups: group I (digoxin group), group II (Red Ginseng group) and group III (Red Ginseng plus digoxin group). Each group consisted of 15 cases. After treatment, the improvement of the hemodynamical and biochemical indexes of group II and group III were greater than those of group I, and group III was the most significant amongst all. The results suggested that Red Ginseng and digoxin had synergism for treatment of congestive heart failure, and Red Ginseng was an effective and safe adjuvant without any side effects.

Topics: Adult; Aged; Digoxin; Drug Synergism; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Panax; Plants, Medicinal

This study assessed the effects of digoxin and ibopamine on variables of heart rate variability in relation to neurohormonal activation.. Analysis of heart rate variability can be used to study the autonomic dysfunction that characterizes chronic heart failure. In the Dutch Ibopamine Multicenter Trial, patients with heart failure were found to have increased neurohormonal activation with placebo therapy but not with digoxin and ibopamine therapy.. We studied 59 patients with mild to moderate heart failure (mean [+/- SEM] age 60 +/- 1 years, mean ejection fraction 0.30 +/- 0.01). Patients were randomized to double-blind treatment with digoxin (0.25 mg [n = 22]), ibopamine (100 mg three times a day [n = 19]) or placebo (n = 18); background therapy consisted of furosemide (up to 80 mg).. After 3 months, plasma norepinephrine levels had increased with placebo, whereas they decreased with digoxin (+31 vs. -60 pg/ml, respectively, p < 0.01). With ibopamine, nonsignificant decrease was observed (-27 pg/ml, p = 0.10). All variables of heart rate variability showed a deterioration in the placebo group. With digoxin, the percent differences between successive RR intervals > 50 ms (pNN50) increased (+ 1.7 +/- 0.9%, p < 0.01), along with absolute and normalized high frequency power (+ 40 +/- 33 ms2, p < 0.05 and + 2.4 +/- 1.7%, p < 0.01, respectively). These changes were observed during daytime hours only and were most pronounced in patients with the most impaired baseline heart rate variability. With ibopamine, nonsignificant trends similar to the changes with digoxin were observed.. In patients with early stages of heart failure, digoxin may prevent a progressive deterioration in heart rate variability, whereas ibopamine does not show statistically significant effects. The changes in heart rate variability with digoxin parallel an observed decrease in neurohormonal activation. Digoxin apparently enhances cardiac vagal tone in the setting of neuroendocrine activation.

Topics: Aldosterone; Cardiotonic Agents; Deoxyepinephrine; Digoxin; Diuretics; Dopamine Agonists; Double-Blind Method; Electrocardiography, Ambulatory; Female; Furosemide; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Norepinephrine; Renin; Time Factors

Twelve patients with refractory chronic congestive heart failure (Class IV NYHA), related to idiopathic dilated cardiomyopathy (10 patients); previous myocardial infarction (one patient) and peripartum cardiomyopathy (one patient), received Terminalia Arjuna, an Indian medicinal plant, as bark extract (500 mg 8-hourly) or matching placebo for 2 weeks each, separated by 2 weeks washout period, in a double blind cross over design as an adjuvent to maximally tolerable conventional therapy (Phase I). The clinical, laboratory and echocardiographic evaluation was carried out at baseline and at the end of Terminalia Arjuna and placebo therapy and results were compared. Terminalia Arjuna, compared to placebo, was associated with improvement in symptoms and signs of heart failure, improvement in NYHA Class (Class III vs. Class IV), decrease in echo-left ventricular enddiastolic (125.28 +/- 27.91 vs. 134.56 +/- 29.71 ml/m2; P < 0.005) and endsystolic volume (81.06 +/- 24.60 vs. 94.10 +/- 26.42 ml/m2; P < 0.005) indices, increase in left ventricular stroke volume index (44.21 +/- 11.92 vs. 40.45 +/- 11.56 ml/m2; P < 0.05) and increase in left ventricular ejection fractions (35.33 +/- 7.85 vs. 30.24 +/- 7.13%; P < 0.005). On long term evaluation in an open design (Phase II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Cardiomyopathy, Dilated; Chemotherapy, Adjuvant; Chronic Disease; Coronary Disease; Cross-Over Studies; Digoxin; Double-Blind Method; Female; Furosemide; Heart Failure; Heart Function Tests; Humans; Hypertension; India; Male; Middle Aged; Plants, Medicinal; Quality of Life; Spironolactone; Treatment Outcome; Ventricular Function, Left; Weight Loss

Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied.. We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20 +/- 0.07 to 0.39 +/- 0.11 mg/day corresponding to an increase in the serum digoxin concentration from 0.67 +/- 0.22 to 1.22 +/- 0.35 ng/mL. Radionuclide and echocardiographic left ventricular ejection fraction; maximal treadmill time; heart failure score; serum concentrations of norepinephrine, aldosterone, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity were obtained before and after the increase in digoxin dose. Subsequently, 9 patients were randomized to receive digoxin and 9 to receive placebo and radionuclide ejection fraction measured after 12 weeks. With the higher dose of digoxin compared with the lower dose, there was a significant increase in radionuclide ejection fraction from 23.7 +/- 9.6% to 27.1 +/- 11.8% (P = .007). No significant changes were noted in heart failure score; exercise tolerance; serum concentrations of norepinephrine, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, there was a significant decrease in ejection fraction (from 29.4 +/- 10.4% to 23.7 +/- 8.9%) in the placebo group but not in patients who continued to receive digoxin (P = .002).. The increase in maintenance digoxin dose, while maintaining serum concentrations within therapeutic range, resulted in a significant increase in left ventricular ejection fraction that was not associated with significant changes in heart failure score, exercise tolerance, and neurohumoral profile.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Cardiotonic Agents; Digoxin; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Renin; Single-Blind Method; Stroke Volume; Vasopressins; Ventricular Function, Left

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14% +/- 5%, New York Heart Association Class II/III/IV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirty-seven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninety-nine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE1 for pre- and afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 +/- 9 months; patients who underwent staged therapy for 9 +/- 5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alprostadil; Angiotensin-Converting Enzyme Inhibitors; Death, Sudden, Cardiac; Digoxin; Dobutamine; Female; Follow-Up Studies; Furosemide; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Life Tables; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome

To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs.. 252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks.. Patients aged 18-75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks.. Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered.. Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure.

Topics: Administration, Oral; Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Felodipine; Female; Heart Failure; Humans; Male; Middle Aged

This study was conducted to determine the effect of long-term digoxin therapy on autonomic function in patients with mild to moderate chronic heart failure.. Chronic heart failure is characterized by increased sympathetic activity and decreased parasympathetic activity. Intravenous digitalis has been found to reduce sympathetic activity immediately in these patients, but whether short-term neurohormonal effects are sustained during long-term oral therapy has not been assessed.. We determined sympathetic activity in 26 patients with heart failure by measuring plasma norepinephrine levels and parasympathetic activity from variables of heart period variability derived from 24-h ambulatory electrocardiographic Holter recordings obtained before and after 4 to 8 weeks of digoxin therapy.. After digoxin therapy, plasma norepinephrine decreased significantly from a mean +/- SEM of 552 +/- 80 to 390 +/- 37 ng/ml. In addition, the RR interval increased significantly from 719 +/- 19 to 771 +/- 20 ms. High frequency power increased from 84 +/- 24 to 212 +/- 72 ms2, and the root mean square of successive differences in RR interval increased from 20.3 +/- 1.8 to 27.0 +/- 3.4 ms, indicating a substantial increase in parasympathetic activity. Low frequency power, an index of baroreflex activity, was also significantly increased (239 +/- 80 to 483 +/- 144 ms2) by digoxin therapy.. These results indicate 1) that long-term therapy with digoxin acts to ameliorate the autonomic dysfunction of patients with heart failure, and 2) that the short-term neurohormonal effects of digoxin are sustained during prolonged treatment with the drug.

Topics: Autonomic Nervous System; Digoxin; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Parasympathetic Nervous System; Signal Processing, Computer-Assisted; Time Factors

An evaluation was made of the performance of the Sheiner, Koup, Dobbs and Paulson methods for predicting total body clearance of digoxin in 59 patients with and without congestive heart failure (CHF). The predicted clearances were then used to predict the steady-state serum concentrations of digoxin. Actual serum concentrations were measured at steady state following single oral daily doses of digoxin for at least 1 month. Predictive performance was determined for each method by calculating the mean prediction error (ME) and the mean squared prediction error (MSE). Ninety-five per cent confidence intervals and correlation coefficients were also calculated. The prediction bias and precision of the methods were compared statistically by calculating the 95% confidence intervals of the delta ME and delta MSE. For patients with CHF, the Sheiner method was the least biased and the most precise for predicting observed serum levels. For patients without CHF, no significant difference between the Sheiner and Koup methods, and between the Dobbs and Paulson methods were seen, although the former two methods were less biased and more precise than the latter two. The Sheiner method was used as the basis for evaluating the performance of the three other methods in predicting digoxin clearance from patients with and without CHF. This revealed that the Koup, Dobbs and Paulson methods tended to overpredict clearances in patients with CHF; on the other hand, for patients without CHF, the Koup method was the least biased and the most precise of the three methods.

Topics: Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Female; Fluorescence Polarization; Heart Failure; Humans; Male; Middle Aged; Observer Variation; Predictive Value of Tests

In this study 24-h Holter electrocardiographic recordings were used to measure the effects of an angiotensin converting enzyme inhibitor, enalapril given for 4 weeks, on the frequency of cardiac arrhythmias in 24 patients (14 patients had enalapril, 30 patients had placebo) with congestive heart failure (New York Heart Association Functional Class 3) receiving maintenance therapy with digoxin and furosemide. Although the placebo group had no change in the frequence of arrhythmias, enalapril-treated patients showed significant decrease in the frequency of premature ventricular complexes couplet, bigemine VPS and ventricular tachycardia. Moreover, it was observed that six cases of atrial fibrillation returned to sinus rhythm. During enalapril treatment, some patients experienced increased serum potassium levels, but there was no change in serum digoxin levels. We also observed echocardiographic improvement in left ventricular function as well as clinical symptoms of congestive heart failure. Finally we observed that there was an antiarrhythmic effect of enalapril in congestive heart failure. We thought that the antiarrhythmic effect of enalapril in congestive heart failure was probably due to hemodynamic improvement.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Placebos; Potassium; Tachycardia, Ventricular; Ventricular Function, Left

Due to differences in treatment effect in studies on the effectiveness of digoxin in patients with congestive heart failure in sinus rhythm, a cross-over placebo-controlled, randomized double blind clinical trial was performed. Thirty one patients, without previous treatment with digoxin, in New York Heart Association (NYHA) functional class II to IV, with a dilated left ventricle and/or ventricular systolic dysfunction were included. Patients received digoxin, adjusted for blood levels, or placebo, during an 8 week period, prior to crossing over to the other treatment for another 8 weeks. The order of treatments was randomly allocated. Outcome measurement were performed at the end of each 8 week period. Digoxin, compared with placebo, improved NYHA class, 6.9% vs 41.4% (p = 0.013) and increased the treadmill exercise time, 406 +/- 204 s vs 484 +/- 185 s (p = 0.003). During the digoxin treatment the left ventricular and systolic diameter was reduced from 52.9 +/- 8.9 to 50.1 +/- 9.7 mm (p = 0.016) and the shortening fraction increased from 21.4 +/- 8.3 to 24.8 +/- 8.1% (p = 0.009). No significant difference was observed in the left ventricular end diastolic diameter (LVED) of the left ventricle and in a estimation of quality of life. In conclusion, digoxin treatment produced a significant improvement in functional capacity, exercise time, and left ventricular performance.

Topics: Adult; Digoxin; Double-Blind Method; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Sinoatrial Node

In order to compare the acute hemodynamic effects of digoxin (0.01 mg/kg) and enoximone (1 mg/kg), a phosphodiesterase inhibitor inotropic agent, in severe chronic congestive heart failure, 8 patients (male, mean age 56.7 years, sinus rhythm) were investigated with a randomized cross-over study. Peak effect of enoximone (30 min) in comparison to that of digoxin (90 min) resulted in a similar reduction of left-ventricular filling pressure (-27 vs. -28%) and mean pulmonary artery pressure (-23 vs. -24%). Pulmonary (-39 vs. -16%; p < 0.01) and systemic vascular resistance (-27 vs. -4%; p < 0.001) were significantly lowered by enoximone. Cardiac index (+30 vs. +6%; p < 0.001) and heart rate (+11 vs. -3%; p < 0.05) were increased significantly more by enoximone than by digoxin. Since enoximone resulted in an enhancement of cardiac performance greater than that produced by digoxin, enoximone could be a useful and powerful substitute for digoxin in the acute therapy of severe chronic congestive heart failure with sinus rhythm.

Topics: Adult; Aged; Chronic Disease; Coronary Disease; Cross-Over Studies; Digoxin; Enoximone; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Severity of Illness Index; Ventricular Function, Left

Digoxin and other low doses of drugs that have inotropic properties may have an important role to play in the therapy of patients with chronic heart failure. There is convincing evidence that digoxin is effective in relieving the signs and symptoms of heart failure due to systolic dysfunction. While earlier results with some of the other agents have been disappointing, recent data suggest that a reevaluation of these agents is necessary. There is now compelling evidence that lower doses of these agents may be clinically useful without necessarily having any significant hemodynamic effects. The recent experience with vesnarinone is especially promising in showing that therapy with these agents may improve survival in addition to improving clinical status. It is becoming recognized that hemodynamic activity should not necessarily be a prerequisite for clinical utility for those agents. The neuroendocrine and electrophysiologic effects of many of these agents, including digitalis, remain incompletely characterized and may play an important role in their therapeutic benefit. It appears that certain drugs that have inotropic properties may be effective only when their inotropic effects are not readily demonstrated. Further research into the appropriate mechanisms of action and proper dosing of these drugs may lead to a renewed interest in the use of positive inotropes for chronic heart failure.

Topics: Adrenergic beta-Agonists; Cardiotonic Agents; Digoxin; Double-Blind Method; Drug Evaluation; Electrophysiology; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Neurosecretory Systems; Phosphodiesterase Inhibitors; Pyrazines; Quinolines

To compare the effects of a multimodal nonpharmacologic intervention to digoxin and to placebo in patients with congestive heart failure receiving background therapy with angiotensin-converting enzyme inhibitors.. Randomized, parallel assignment to three treatment groups of 20 patients with congestive heart failure (New York Heart Association Class II and III).. Nonpharmacologic treatment program included the following: (1) graduated exercise training, three to five times per week; (2) structured cognitive therapy and stress management; and (3) dietary intervention aimed at salt reduction and weight reduction in the overweight. Digoxin was titrated to achieve a blood level between 0.8 and 2.0 ng/ml. Placebo and digoxin were administered in a randomized, double-blind fashion.. Echocardiographic ejection fraction improved (p < 0.05) in the digitalis group (change = +4.4 +/- 6.5) compared with both placebo (change = -3.2 +/- 3.9) and nonpharmacologic therapy (change = -3.2 +/- 3.9). The nonpharmacologic treatment program was well tolerated by all patients and resulted in significant improvement (p < 0.05) in exercise tolerance (digoxin = +51 +/- 50 s, placebo = +91 +/- 76, nonpharmacologic therapy = +182 +/- 139), as well as Beck Depression Inventory score (digoxin = +1.2 +/- 4.4, placebo = +2.0 +/- 4.2, nonpharmacologic therapy = -5.0 +/- 4.2), Hamilton Scale scores of anxiety (digoxin = +3.0 +/- 6.8, placebo = +6.0 +/- 2.6, nondrug therapy = -5.2 +/- 5.4), and depression (digoxin = +1.0 +/- 4.9, placebo = +5.0 +/- 5.0, nonpharmacologic therapy = -6.6 +/- 10.1). In addition, weight loss was significantly greater with nonpharmacologic therapy (digoxin = +0.32 +/- 1.76 kg; placebo = -1.35 +/- 1.44 kg; nonpharmacologic therapy = -4.37 +/- 4.50 kg) compared with both digoxin and placebo.. Nonpharmacologic therapy improved functional capacity, body weight, and mood state in patients with congestive heart failure. In contrast, digoxin improved ejection fraction without corresponding changes in exercise tolerance or quality of life.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cognitive Behavioral Therapy; Combined Modality Therapy; Diet, Reducing; Diet, Sodium-Restricted; Digoxin; Double-Blind Method; Emotions; Exercise Therapy; Female; Heart Failure; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales

An enzyme-linked immunosorbent assay is described for the measurement of ouabain in human plasma. This assay is specific for ouabain, strophanthidin, and ouabagenin, with other steroids, including digoxin and vasopressor hormones, exhibiting negligible cross-reactivity. Assay sensitivity was 0.06 nmol/L if 1 mL plasma was extracted and less than 0.005 nmol/L when 20 mL plasma was analyzed. Extracted plasma samples showed ouabainlike immunoreactivity that diluted in parallel with the ouabain standard curve. Repeated extraction and assay of single plasma samples, however, did not produce consistent results in the assay. Increased specificity was obtained by high-performance liquid chromatography of sample extracts before assay. When high-performance liquid chromatographic profiles of plasma spiked with ouabain standard or following bolus intravenous injections of ouabain into normal human volunteers were compared with profiles of unspiked plasma, there was no support for the immunoreactive material in the latter samples being ouabain. We propose that if ouabain is present in the human circulation, its concentration is less than 0.005 nmol/L.

Topics: Animals; Antibodies; Antibody Specificity; Chromatography, High Pressure Liquid; Cross Reactions; Digoxin; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Heart Failure; Humans; Kidney Failure, Chronic; Ouabain; Pre-Eclampsia; Pregnancy; Rabbits; Sensitivity and Specificity; Steroids; Strophanthidin; Vasopressins

K-strophanthin or digoxin were added to diuretics (all cases) and vasodilators (most cases) for treating advanced congestive heart failure in 22 patients with dilated cardiomyopathy and sinus rhythm. K-strophanthin (0.125 mg intravenously) or digoxin (0.25 mg orally) were administered daily in two 3-month periods, during which vasodilators and diuretics were kept constant and patients received one of the two digitalis preparations in a double-blind fashion, crossing over to the alternative preparation in the next period. Blindness was assured throughout the trial with a daily intravenous injection of 10 ml normal saline solution either containing K-strophanthin or not, and with daily oral administration of either placebo or active digoxin. At the end of the run-in period, 15 days after starting active preparations, and thereafter every month for the next 6 months, we evaluated left ventricular pump function at rest and patients' functional performance by a cardiopulmonary exercise test. At Day 15, cardiac index and ejection fraction at rest, compared with run-in, were significantly raised with both glycosides; during exercise while on K-strophanthin, peak oxygen consumption was augmented by 1.4 ml/min/kg (p < 0.01) and oxygen consumption at anaerobic threshold by 2.2 ml/min/kg (p < 0.01); corresponding variations on digoxin (-0.1 and +0.3, respectively) were not significant versus run-in. These patterns were duplicated at repeated tests during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anaerobic Threshold; Analysis of Variance; Cardiomyopathy, Dilated; Digoxin; Double-Blind Method; Drug Administration Schedule; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Stroke Volume; Strophanthins; Ventricular Function, Left

This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo.. Ibopamine and digoxin are drugs that exert hemodynamic and neurohumoral effects. Because there is accumulating evidence that progression of disease in chronic heart failure is related not only to hemodynamic but also to neurohumoral factors, both drugs might be expected to have a favorable long-term effect.. We studied 161 patients with mild to moderate chronic heart failure (80% in New York Heart Association functional class II and 20% in class III), who were treated with ibopamine (n = 53), digoxin (n = 55) or placebo (n = 53) for 6 months. Background therapy consisted of furosemide (0 to 80 mg); all other drugs for heart failure were excluded. Clinical assessments were made at baseline and after 1, 3 and 6 months.. Of the 161 patients, 128 (80%) completed the study. Compared with placebo, digoxin but not ibopamine significantly increased exercise time after 6 months (p = 0.008 by intention to treat analysis). Ibopamine was only effective in patients with relatively preserved left ventricular function, as it significantly increased exercise time in this subgroup (for patients with a left ventricular ejection fraction > 0.30; p = 0.018 vs. placebo). No patient receiving digoxin withdrew from the study because of progression of heart failure, compared with six patients receiving ibopamine and two receiving placebo. At 6 months, plasma norepinephrine was decreased with digoxin and ibopamine therapy (-106 and -13 pg/ml, respectively) but increased with placebo administration (+62 pg/ml) (both p < 0.05 vs. placebo). Plasma aldosterone was unaffected, but renin was decreased by both agents after 6 months (p < 0.05 vs. placebo). Total mortality and ambulatory arrhythmias were not significantly affected by the two drugs.. Ibopamine and digoxin both inhibit neurohumoral activation in patients with mild to moderate chronic heart failure. However, the clinical effects of these drugs are different and appear to be related to the degree of left ventricular dysfunction.

Topics: Adolescent; Adult; Aged; Aldosterone; Cardiotonic Agents; Deoxyepinephrine; Digoxin; Dopamine Agents; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Netherlands; Norepinephrine; Prospective Studies; Renin; Severity of Illness Index

We conducted a prospective, double-blind, placebo-controlled multicenter trial in order to evaluate the long-term effects of captopril (50 mg/day), digoxin (0.25 mg/day) and placebo on quality of life, cardiovascular events, clinical symptoms and exercise tolerance in patients with documented myocardial infarction, resulting in regional wall motion abnormalities, and with mild heart failure (NYHA class II to III without treatment) and exercise not limited by angina. 222 patients were studied, 63 were randomized to captopril, 66 to digoxin, 67 to placebo. Follow-up was conducted for two years. Base line characteristics in the three treatment groups were similar. After one year of therapy, digoxin had significantly improved general well-being (p < 0.01 vs captopril), symptom score (p < 0.05 vs captopril and placebo), and vitality (p < 0.05 vs captopril). Digoxin improved NYHA class in 45% as compared to placebo (28%, p < 0.05). Worsening of angina was more frequent with captopril as compared to digoxin (p < 0.05). However, cardiovascular events during follow-up were lower in the captopril group as compared to placebo and digoxin (p < 0.01 captopril vs placebo). No differences between groups were observed in baseline and follow-up exercise tolerance between the three groups. Dizziness during upright tilt and cough were more frequent with captopril as compared to digoxin or placebo. After two years of follow-up (captopril n = 32, digoxin n = 29, placebo n = 27) general well-being was improved with both digoxin and captopril (p < 0.004 and p < 0.03 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angina Pectoris; Captopril; Coronary Disease; Digoxin; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Nitroglycerin; Prospective Studies; Quality of Life; Survival Rate

Twelve patients with dilating cardiomyopathy complicated heart failure were divided randomly into auriculo-acupuncture group (n = 7) and controls (n = 5). Left cardiac function and plasma levels of PRA, ALD, EDLS, ANF were measured. Results showed that CO, CI, ANF, EDLS, ALD were decreased in test group (P < 0.05), which indicated that auriculo-acupuncture plus needle-embedding in Heart acupoint could improve the left cardiac function in patients with dilating cardiomyopathy complicated heart failure and that the function of acupoints is distinctly different from that of non-point.

Topics: Acupuncture Points; Acupuncture Therapy; Adult; Atrial Natriuretic Factor; Blood Proteins; Cardenolides; Cardiac Output; Cardiomyopathy, Dilated; Digoxin; Ear, External; Female; Heart Failure; Humans; Male; Random Allocation; Saponins; Ventricular Function, Left

Angiotensin converting enzyme inhibitors, diuretics, and digoxin are each effective in treating congestive heart failure, but many patients remain symptom-limited on all three medications. This trial was designed to determine whether the addition of oral flosequinan, a new direct-acting arterial and venous vasodilator with possible dose-dependent positive inotropic effects, improves exercise tolerance and quality of life in such patients.. In a randomized, double-blind multicenter trial, 322 patients with predominantly New York Heart Association class II or III congestive heart failure and left ventricular ejection fractions of 35% or less, who were stabilized on a diuretic, angiotensin converting enzyme inhibitor, and digoxin, were treated with 100 mg flosequinan once daily, 75 mg flosequinan twice daily, or matching placebo. Efficacy was evaluated with serial measurements of treadmill exercise time, responses to the Minnesota Living With Heart Failure Questionnaire (LWHF), and clinical assessments during a baseline phase and a 16-week treatment period. After 16 weeks, 100 mg flosequinan once daily produced a significant increment in median exercise time (64 seconds at 16 weeks) compared with placebo (5 seconds), whereas the higher-dose flosequinan group did not show a statistically significant increase. Flosequinan (100 mg once daily) also improved the overall LWHF score significantly compared with placebo; both active therapies decreased the physical component, but 75 mg flosequinan twice daily was associated with a trend toward worsening of the emotional component. Most clinical assessments tended to improve on active therapy.. These results indicate that additional symptomatic benefit can be attained by adding flosequinan to a therapeutic regimen already including a converting enzyme inhibitor. Because in the future most patients will fall into this category, flosequinan is a potential adjunctive agent in the management of severe congestive heart failure. However, because recent evidence indicates that the flosequinan dose studied in the present trial has an adverse effect on survival, the benefit-to-risk ratio must be assessed in individual patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Diuretics; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Quality of Life; Quinolines; Vasodilator Agents

Because of conflicting results from studies examining the initial treatment of patients with chronic left heart failure (CHF) and sinus rhythm, the clinical efficacy and safety of digoxin and a diuretic were compared in a multicenter, randomised, open twelve-week study. 47 patients with CHF (NYHA II and III) were treated either with digoxin or a combination of hydrochlorothiazide and triamterene. Three patients from the diuretic group and four from the digoxin group required premature termination of study periods because of increasing symptoms of CHF. Both regimens decreased significantly a heart failure score and increased distinctly the symptom-limited exercise tolerance, but results did not differ between the groups. Echocardiographic parameters, ejection fraction and radionuclide indices of diastolic function estimated by gated blood pool scan did not change with either treatment. It was concluded that digoxin or the diuretic therapy alone was effective in ameliorating the clinical signs of CHF. Due to missing differences in the clinical efficacy of both drugs an individual and not schematic treatment regimen of CHF is warranted.

Topics: Aged; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Hydrochlorothiazide; Male; Middle Aged; Prospective Studies; Triamterene; Ventricular Function, Left

The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure.. Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy.. Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin.. Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016).. These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Topics: Body Weight; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Stroke Volume; Substance Withdrawal Syndrome; Time Factors; Treatment Failure; Ventricular Function, Left

34 patients with ventricular dysfunction (18 in NYHA class II and 16 in NYHA class III heart failure) whose clinical status was stabilized by diuretics and systemic vasodilators, entered a randomized trial to compare the effects of short-term oral digoxin and active placebo on left ventricular diastolic function, non invasively evaluated by echo-Doppler transmitral left ventricular filling flow. At baseline patients were subdivided by reversal--the ratio of peak early (E) and late (A) transmitral filling velocities--E/A < 1 (group I) or normal--E/A > or = 1 (group II) echo-Doppler E/A ratio; group II exhibited a shorter deceleration time (125 +/- 20 ms vs 198 +/- 38 ms, p > 0.05) and isovolumic relaxation time (64 +/- 15 ms vs 93 +/- 10 ms; p < 0.05) as well as a higher peak E velocity (85 +/- 28 cm/s vs 54 +/- 20 cm/s; p < 0.05), ("restrictive" left ventricular filling pattern). After 4 weeks, no changes in all echo-Doppler parameters were noted in group I in response to either oral digoxin or active placebo. Clinical amelioration (defined as reduction by at least one functional class) was observed in 3 patients after digoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Animals; Diastole; Digoxin; Double-Blind Method; Echocardiography, Doppler; Female; Guinea Pigs; Heart Failure; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Ventricular Function, Left

Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice.. We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks. Otherwise, their medical therapy for heart failure was not changed.. Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 patients who continued to receive digoxin (P < 0.001). The relative risk of worsening heart failure in the placebo group as compared with the digoxin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All measures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.033 for maximal exercise tolerance, P = 0.01 for submaximal exercise endurance, and P = 0.019 for New York Heart Association class). In addition, the patients switched from digoxin to placebo had lower quality-of-life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P < 0.001).. These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaired systolic function who have remained clinically stable while receiving digoxin and angiotensin-converting-enzyme inhibitors.

Topics: Captopril; Confidence Intervals; Digoxin; Double-Blind Method; Drug Therapy, Combination; Enalapril; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Physical Endurance; Systole

The haemodynamic effects of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, were studied in patients in New York Heart Association functional class II and III. Twenty-one clinically stable patients with coronary artery disease or cardiomyopathy completed a randomized double-blind treatment period of 2 months with either 15 mg zofenopril once daily or placebo. Regular therapy with digoxin and diuretic drugs was continued. Left ventricular volumes were measured by radionuclide angiography at rest and during submaximal bicycle exercise. Zofenopril significantly increased mean stroke volume at rest from 59 to 67 ml (48 vs 48 ml in the control group, 95% confidence interval of the difference 1 to 16 ml) and left ventricular ejection fraction at rest from 39 to 43% (30 vs 30% in the control group, 95% confidence interval of the difference 1 to 8%). No significant changes occurred in heart rate, cardiac output, and blood pressure at rest, and zofenopril did not result in haemodynamic alterations during exercise. Thus, 15 mg of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, administered once daily to patients with moderate heart failure increases left ventricular function at rest, but not during exercise.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Digoxin; Double-Blind Method; Drug Administration Schedule; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged

Lisinopril 5-20 mg once daily was compared with digoxin 0.125-0.375 mg once daily in a double-blind, randomized, parallel-group study involving 217 patients with mild-to-moderate heart failure (New York Heart Association [NYHA] grades II-III) who were maintained on optimized diuretic therapy. After 6 weeks of treatment, digoxin and lisinopril had increased exercise duration by 18 seconds (p = 0.015) and 32 seconds (p = 0.0007), respectively, versus the baseline run-in period. The difference between treatments was not statistically significant (p = 0.1343). After 12 weeks, digoxin and lisinopril had increased exercise duration by 29 seconds and 51 seconds, respectively. The effect of digoxin compared with the baseline value was not significant but that for lisinopril was (p = 0.0027). The difference between treatments approached statistical significance (p = 0.0813). There was no difference between lisinopril and digoxin with regard to their effects on the frequency of ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Blood pressures were not significantly different between treatments, although both systolic and diastolic blood pressure were consistently lower in the lisinopril group throughout randomized treatment. The proportions of patients demonstrating an improvement in NYHA grading were similar for both lisinopril and digoxin. Both treatments had similar effects on the symptoms of heart failure. Both drugs appeared to be equally well tolerated with a similar frequency of adverse events reported for both drugs (30% for lisinopril vs 29% for digoxin). Withdrawals from treatment were of a similar frequency for both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Dipeptides; Diuretics; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Physical Exertion; Placebos

The prognosis of heart failure patients is poor and as many as half of the deaths are sudden and thereby presumably attributable to arrhythmias. In the present study the effect of traditional therapy of mild heart failure with digoxin on arrhythmias was compared with the effect of xamoterol, a cardioselective beta 1 partial agonist, which has in addition beta-blocking properties at higher levels of sympathetic tone. Fifteen patients (NYHA class II-III) were included in the study. After a two-week baseline period they were randomized to digoxin or xamoterol for four weeks followed by a two-week washout and another four weeks of crossover therapy. Heart rate, blood pressure, and the number of complex ventricular premature beats remained essentially unchanged with digoxin. With xamoterol heart rate increased from 86 to 93 (ns) but was significantly higher during the night in comparison with digoxin. The number of ventricular premature beats decreased from 186 +/- 317 to 110 +/- 137 and increased to 130 +/- 175 after treatment. The number of runs decreased from 11 +/- 35 to 2.7 +/- 5 and increased to 5.6 +/- 9 after therapy. In conclusion, no significant effect of digoxin or xamoterol on ventricular arrhythmias was found. However, xamoterol showed a tendency to reduce simple and complex ventricular arrhythmias in patients with mild to moderate heart failure.

Topics: Adrenergic beta-Agonists; Analysis of Variance; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Male; Middle Aged; Propanolamines; Time Factors; Xamoterol

The effects of four inotropic agents with differing ancillary properties [a cardiac glycoside (digoxin), a combined alpha- and beta-adrenergic agonist (dobutamine), a beta-adrenergic agonist (prenalterol), and a phosphodiesterase inhibitor (amrinone)] alone and with subsequent addition of isosorbide dinitrate were compared in 48 consecutive acute myocardial infarction patients with radiographic and haemodynamic (pulmonary artery occluded pressure greater than 18 mm Hg) left ventricular failure. All agents with the exception of dobutamine reduced the elevated left heart filling pressure; only digoxin and dobutamine augmented the cardiac stroke volume index. All drugs except digoxin reduced the SVRI; an arteriolar constrictor response was evident 60 min after digoxin and a tachycardia resulted after combined alpha- and beta- and beta-adrenergic stimulations (dobutamine and prenalterol, respectively). The addition of isosorbide dinitrate reversed the inotrope-induced elevations of systemic arterial pressure and resulted in additional reductions in left heart filling pressure. These data suggest that, in the absence of substantial venodilator properties in an inotropic compound, reduction in elevated left heart filling pressure is not achieved with inotropic therapy alone in acute left ventricular failure and combining a venodilator may be haemodynamically advantageous.

Topics: Adult; Aged; Amrinone; Cardiotonic Agents; Digoxin; Dobutamine; Heart Failure; Humans; Isosorbide Dinitrate; Male; Middle Aged; Prenalterol; Prospective Studies; Single-Blind Method; Vasodilation

We evaluated the efficacy of K-strophanthidin and digoxin in 20 patients with stable, severe congestive heart failure. In this aim, we studied the left ventricular pump function at rest and following manipulation of the cardiac load (cold pressor test and nitroprusside infusion), the exercise performance (cardiopulmonary exercise test), and the level of circulating norepinephrine. The study was double-blind and cross-over and comprehended 4 periods of 1-week each during which patients received in random order: placebo (oral+intravenous), K-strophanthidin (intravenous + oral placebo), digoxin (oral+intravenous placebo and, in 8 patients, intravenous + oral placebo). The efficacy of the various compounds was tested at the end of each period 1 and 10 hours after drug dosing. Comparable results were obtained by the 2 sets of measurements. Both digoxin and K-strophanthidin showed a positive inotropic effect. This is shown by an upward shift of the ejection fraction/end-systolic stress. In spite of this, only K-strophanthidin significantly increased exercise performance: tolerance time (+153 s), peak oxygen consumption (+1.2 ml/kg/min) and oxygen consumption at anaerobic threshold (+2.3 ml/kg/min). Norepinephrine plasma level at rest was significantly lowered only by K-strophanthidin. Results were comparable when digoxin was given intravenously. We conclude that both glycosides elicit an increase of the inotropic cardiac state but only K-strophanthidin improves exercise performance.

Topics: Administration, Oral; Adult; Aged; Cardiac Output; Cardiomyopathy, Dilated; Chronic Disease; Digoxin; Double-Blind Method; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Strophanthidin

In 61 patients with NYHA IV class chronic congestive heart failure, treated in succession with digoxin (D) and furosemide (F) for two weeks, with D+F and isosorbide dinitrate (S) or nifedipine (N) for two weeks, with D+F+S or N without C for two weeks, clinical status, chest X-ray picture and two dimensional echocardiography were evaluated at the end of each stage of the treatment. There were analyzed heart rate (HR), arterial systolic (Ps) and diastolic (Pd) blood pressure, body weight (Mc), 24-hour urinary output (Dd), cardio-thoracic index (CTI), cardiac volume index (CVI) and dimensions of the left ventricle: systolic (LVIDs), and diastolic (LVIDd). The mean daily doses of the drugs were as follows: D-0.290 +/- 0.108 mg, F-13.0 +/- 4.1 mg, S-44.5 +/- 9.8 mg, N-42.0 +/- 12.2 mg, and C-75.1 +/- 24.4 mg. The treatment with vasodilators (Vd) induced decreases in Mc, CVI, LVIIDs and LVIDd in comparison with the treatment with D and F. The largest lowerings in HR, Ps, Pd and Mc were observed during the treatment with D and F. The most beneficial effects with regard to CVI, LVIDs and LVIDd were obtained during four-week treatment with captopril.

Topics: Adult; Aged; Captopril; Digoxin; Drug Administration Schedule; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Male; Middle Aged; Nifedipine; Time Factors; Vasodilator Agents

Indolidan (IN) experimentally inhibits type IV phosphodiesterase. It was administered to twelve patients (age 64 +/- 15 years) with New York Heart Association (NYHA) class 2-3 congestive heart failure in which digoxin and diuretic therapy were continued. IN was administered i.v. at 1,180 +/- 340 micrograms (15 micrograms/kg) over two hours. After 24 hours, IN was given p.o. at 231 +/- 44 micrograms. The time course effect of IN i.v. revealed an increase in cardiac index and a decrease in pulmonary capillary wedge pressure and blood pressure. Daily oral administration of IN or placebo was carried out for up to 3 months. There were no significant hemodynamic changes of chronically administered IN. The maximum oxygen uptake increased in placebo relative to IN therapy. IN tended to be arrhythmogenic as evidenced by a general increased frequency of ventricular premature contractions of both single and paired type. Therefore, IN had some hemodynamic efficacy on acute i.v. and p.o. administration but not during chronic therapy, and there was negative safety features of arrhythmias.

Topics: Administration, Oral; Aged; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Exercise Tolerance; Heart Failure; Hemodynamics; Humans; Indoles; Injections, Intravenous; Middle Aged; Oxindoles; Oxygen Consumption; Pyridazines

Electrolyte abnormalities are a frequent and potentially hazardous complication in the treatment of patients with congestive heart failure. Medical treatment with diuretics and/or digitalis, as well as neurohumoral activation most likely initiated by the compromised cardiac function, contributes to this alteration. The addition of potassium- and magnesium-sparing diuretics (triamterence, amiloride) to therapy with frusemide or hydrochlorothiazide is of possible value in preventing intracellular electrolyte abnormalities.

Topics: Aged; Aged, 80 and over; Digoxin; Double-Blind Method; Drug Therapy, Combination; Erythrocytes; Furosemide; Heart Failure; Humans; Hydrochlorothiazide; Intracellular Fluid; Lymphocytes; Magnesium; Middle Aged; Potassium; Triamterene

The efficacy and safety of ramipril were compared with that of digoxin in a prospective, randomized, double-blind, crossover study of 35 patients with congestive heart failure (CHF), New York Heart Association (NYHA) grades II to IV, stabilized on diuretic maintenance therapy. Major assessments were conducted at baseline and at the end of each 10-week treatment period: primary efficacy variables were total exercise duration (modified Bruce, treadmill), NYHA grade, and clinical signs and symptoms (by visual analogue score) of heart failure. Twenty-seven patients completed the study. There were two deaths (one on each study drug) and six patient withdrawals (one on ramipril and five on digoxin). Although the NYHA grade was significantly better on ramipril than on digoxin, there were no other important differences in the relief of either signs or symptoms of heart failure. A significant order effect was observed with the exercise testing data and therefore only data in the first active treatment period were analyzed; no significant differences were noted. There were fewer reports of adverse effects, and no clinically significant episodes of hyperkalemia or renal impairment on ramipril. We conclude that ramipril seems to be better tolerated and marginally more effective than digoxin in the management of patients with moderate to severe chronic CHF, stabilized on maintenance diuretic therapy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Bridged Bicyclo Compounds; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Prospective Studies; Ramipril

In 25 patients whose chronic congestive heart failure (CHF) had recently worsened to New York Heart Association class IV, pimobendan (5 to 20 mg/day) was added to maximum conventional therapy consisting of digoxin, diuretics, angiotensin-converting enzyme inhibitors, coumadin derivatives to prevent thromboembolic complications, and amiodarone to suppress serious ventricular rhythm disturbances. CHF was fatal in less than 1 month in five patients (two had shown some initial improvement). The other 20 had sustained improvement by at least one functional class, interrupted by episodes of CHF that usually responded to intravenous therapy. Median survival was 12 months (range 10 days to greater than 3 years); five patients died suddenly, 12 died of intractable CHF, and two died of other causes. Six patients were alive 3 years after the onset of treatment with pimobendan. Add-on therapy with pimobendan produced a sustained improvement in many patients with severe CHF that was no longer responding to a combination of digoxin, diuretics, and angiotensin-converting enzyme inhibitors.

Topics: Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Pyridazines; Survival Analysis; Vasodilator Agents

The study was designed to evaluate the safety of ibopamine (3,4-diisobutyryl ester of N-methyldopamine. SB(-)-505. Inopamil; CAS 66195-31-1) for the chronic treatment of congestive heart failure. It was conducted as a comparative cohort survey, versus digitalis. A third cohort was made with patients who received both drugs in association. Any differences between cohorts at baseline were dealt with by identifying explanatory variables with linear discriminant analysis and by performing multivariate statistical analysis by Cox's proportional hazard model. During 16 months, 3.330 patients were enrolled and then followed-up for a median time of 1 year. Baseline characteristics are reported as well as follow-up results on mortality, disease progression, anginal episodes, arrhythmias, need for cointervention and other undesired on-therapy events. Results pointing to efficacy are consistent with the favourable results from controlled randomized double blind medium--long term clinical trials. In addition, data from the present study do indeed provide strong evidence on the safety of long-term treatment with ibopamine. At variance with inotropic agents ibopamine did not increase mortality. The results rather suggest that long-term treatment with ibopamine affords an increase in survival and a delay in the progression of the disease, without adverse effects on cardiac rhythm and myocardial oxygen balance, and with a general improvement in the patients' quality of life.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Blood Pressure; Cardiotonic Agents; Deoxyepinephrine; Digoxin; Drug Prescriptions; Drug Therapy, Combination; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Product Surveillance, Postmarketing; Prognosis; Risk Factors

Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated. At rest there were no significant differences in the right-sided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiloride; Chronic Disease; Digoxin; Diuretics; Double-Blind Method; Drug Therapy, Combination; Exercise; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Rest

A large-scale, prospective, 8-week, office-based study was conducted to evaluate the effects of adding captopril to a therapeutic regimen of diuretic and digoxin or diuretic alone in the management of patients with mild to moderate congestive heart failure (CHF). A total of 2218 primary care physicians evaluated 6669 patients over the study period for efficacy parameters, which included changes in a modified New York Heart Association (NYHA) functional classification, symptomatology, and daily activity levels. Overall, 63.8% of evaluated patients improved with regard to functional ability, with 19% improving two or more modified NYHA classes. Symptoms of CHF, including dyspnea on exertion, fatigue, and orthopnea and signs, including rales and peripheral edema, were reduced in 86% of these patients: 41.5% demonstrated mild improvement; 30.0%, moderate improvement; and 14.5%, marked improvement. Three parameters, with which patients reported having difficulty at study entry, were assessed serially to evaluate changes in functional capacity; 78.5% of patients reported an increased walking distance, 72.3% had increased capacity for climbing stairs, and 60.2% had improved capacity for individual recreational activities. Adverse experiences were reported in 18.1% of all patients; 4.9% of patients withdrew from the study because of an adverse effect. Combination therapy with captopril and diuretic for CHF was shown to be safe and effective regardless of patient age (less than 70 years vs. greater than or equal to 70 years), duration of heart failure (less than 1 year vs. greater than 1 year), presence of digoxin treatment, or the dosing schedule employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Activities of Daily Living; Aged; Captopril; Digoxin; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Office Visits; Physicians, Family; Prospective Studies; Walking

The effect of digoxin on contractility and symptoms in infants with a large ventricular septal defect (VSD) is controversial. Nineteen infants with symptoms of congestive heart failure due to a VSD were studied with load-independent indexes during 4 study periods: (1) before any medication; (2) while on chronic diuretics; (3) while on both diuretics and digoxin; and (4) while on diuretics alone, to determine if digoxin: (a) increases "contractility" when added to diuretic therapy; and (b) improves symptoms. Symptoms, signs (heart and respiratory rates, and weight gain), shortening fraction, preload (left ventricular end-diastolic dimension), afterload (left ventricular end-systolic wall stress) and contractility were measured at each period. The difference between the measured and predicted velocities of circumferential fiber shortening for the measured left ventricular end-systolic wall stress served as an index of contractility. Eighteen infants also underwent catheterization. Mean pulmonary-to-systemic blood flow ratio was 3:1. When digoxin was added to diuretics, contractility index was significantly greater than in control subjects (0.13 +/- 0.15 vs 0.0 +/- 0.12 circ/s, p = 0.04). When patients were again on diuretics alone (after discontinuation of digoxin), contractility index was no longer different. Symptoms and signs were not significantly improved by either diuretics or digoxin. It is concluded that in infants with a large left-to-right VSD shunt and receiving digoxin and diuretics, contractility index was significantly greater than in control subjects. However, neither diuretics alone nor in combination with digoxin improved symptoms significantly.

Topics: Digoxin; Diuretics; Drug Therapy, Combination; Echocardiography; Heart Failure; Heart Septal Defects, Ventricular; Humans; Infant; Myocardial Contraction

Patients with New York Heart Association functional class II or III heart failure stabilized on furosemide therapy were entered into a randomized controlled trial comparing enalapril (n = 72) and digoxin (n = 73). End points were clinical outcome, treadmill exercise capacity and echocardiographic left ventricular dimensions. Improvement in clinical outcome was defined as a reduction of at least one functional class or withdrawal because of an adverse clinical event. After 4 weeks, 13 patients receiving enalapril showed improvement, 55 had no change and 9 manifested deterioration compared with 7, 49 and 17, respectively, in the digoxin group (p less than 0.01). After 14 weeks, 13 patients receiving enalapril showed improvement, 50 had no change and 9 manifested deterioration, compared with 14, 37 and 22, respectively, in the digoxin group (p less than 0.025). More patients in the digoxin group were withdrawn because of an adverse clinical event (p less than 0.05). Exercise time and percent fractional shortening improved in both groups (p less than 0.001 and less than 0.05, respectively), with no significant difference between groups (p greater than 0.50). Both rate-pressure product and subjectively evaluated exertion during submaximal exercise were reduced only in the enalapril group. Although the majority of patients in both groups did well, those receiving enalapril experienced fewer adverse clinical events and had less fatigue during submaximal exercise.

Topics: Adult; Aged; Canada; Digoxin; Double-Blind Method; Drug Monitoring; Echocardiography; Enalapril; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Treatment Outcome

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Chronic Disease; Coronary Disease; Digoxin; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Pulmonary Gas Exchange; Stroke Volume; Vasodilator Agents; Ventricular Function, Left

In a randomized single-blind cross-over trial, the efficacy of digoxin, angiotensin-converting enzyme (ACE) inhibition by quinapril, and their combination on exercise tolerance, heart size (echocardiography), and neurohumoral systems was investigated in 19 outpatients with congestive heart failure (CHF) New York Heart Association functional class II and sinus rhythm. Baseline therapy consisted of 25 mg hydrochlorothiazide and remained unchanged. After treatment with quinapril, exercise tolerance significantly increased (606 vs. 644 s, 2 p less than 0.03) and left ventricular end-diastolic dimension (63 vs. 58 mm, 2 p less than 0.03), mean arterial blood pressure (MABP, 100 vs. 92 mm Hg, 2 p less than 0.03) and plasma norepinephrine (NE) levels (378 vs. 323 pg/ml, 2 p less than 0.03) were significantly reduced. Digoxin increased resting systolic blood pressure (SBP 133 vs. 142 mm Hg, 2 p less than 0.03). Combined administration of both drugs significantly increased fractional shortening (24 vs. 28%, 2 p less than 0.03), reflecting the positive inotropic action of digoxin in combination with afterload reduction. However, there was no further increase in exercise tolerance. Our data suggest that early administration of ACE inhibitors may be beneficial in patients with mild CHF and sinus rhythm, although the magnitude of improvement was less substantial than that reported for patients with more severe CHF.

Topics: Adult; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Hydrochlorothiazide; Isoquinolines; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Quinapril; Randomized Controlled Trials as Topic; Renin; Single-Blind Method; Tetrahydroisoquinolines

"In the realm of congestive heart failure, we've made tremendous diagnostic and therapeutic strides--yet so many crucial questions remain unanswered. An educational meeting such as this can help us share what we know and progress to new awareness."

Topics: Adrenergic beta-Antagonists; Atrial Natriuretic Factor; Clinical Trials as Topic; Digoxin; Enalapril; Heart Failure; Humans; Multicenter Studies as Topic

In a double-blind study comparing two active treatments (digoxin and xamoterol) and placebo in patients with heart failure, improvements in exercise capacity and quality of life were observed in all three groups, with no significant differences. The substantial benefits seen in the placebo group were probably the result of increased attention from the medical and research staff and suggest the therapeutic value of special heart failure clinics. The relationship between exercise and symptomatic/functional status has been unclear. We developed quantitative measures of quality-of-life variables and examined their relationship with exercise capacity. There were significant relationships between change in exercise duration and changes in breathlessness, tiredness, chest pain, walking difficulty, rate of walking, difficulty with daily tasks, speed of daily tasks, mood, and sleeping. This study confirms the validity of measuring change in exercise capacity and demonstrates that specific measurements of quality of life make an important contribution to the evaluation of the treatment of heart failure.

Topics: Adult; Aged; Digoxin; Exercise; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Multicenter Studies as Topic; Propanolamines; Quality of Life; Randomized Controlled Trials as Topic; Xamoterol

To reappraise the effectiveness of digoxin for the treatment of congestive heart failure (CHF) in patients with sinus rhythm in light of data from recently published randomized controlled trials and to quantitatively assess its usefulness.. Computerized searches of the MEDLINE database were performed, and the reference list of each retrieved article was reviewed.. Review of more than 360 citations and the reference lists of 19 review articles and 61 potentially relevant articles revealed seven double-blind randomized controlled trials that were included in this overview.. Study quality was assessed and descriptive information concerning the study populations, the specific interventions, and clinically relevant outcome measurements was extracted.. The common odds ratio for CHF deterioration while receiving digoxin versus placebo was 0.28, with a 95% confidence interval of 0.16 to 0.49. Predictors of digoxin benefit included presence of a third heart sound and the severity and duration of CHF.. Data from seven trials of high methodologic quality suggest that, on average, one out of nine patients with CHF and sinus rhythm derive a clinically important benefit from digoxin (with a 95% confidence interval of 1/33 to 1/5).

Topics: Digoxin; Double-Blind Method; Heart Failure; Heart Rate; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic

We tried to assess the value of both ventricular function changes and its correlation with maximal exercise capacity in patients with chronic heart failure. For this purpose, a double blind crossover study was designed, and the change in the exercise tolerance and both ventricular ejection fraction were evaluated. When compared with digoxin treatment (p less than 0.01) and with a control-period (p less than 0.001), the captopril increases total exercise time significantly. The response of right ventricular ejection fraction was similar. The changes in right ventricular ejection fraction, but not those of left ventricular ejection fraction, correlated with the variations of exercise time (r = 0.67). These facts suggest that right ventricular function is an important determinant of exercise capacity in patients with chronic heart failure and that its behaviour explain, in part, the response to captopril treatment.

Topics: Adult; Captopril; Chronic Disease; Digoxin; Double-Blind Method; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Random Allocation; Stroke Volume; Time Factors

In 50 patients with chronic congestive heart failure (CCHF, III or IV class), aged 62.8 +/- 9.1 years, who were treated with digoxin (Dx) and furosemide (F) (investigation A), continuous 24-hour ecg registration was performed according to Holter. Next, this treatment was extended by two-week administration of nifedipine (N) or isosorbide dinitrate (S) (investigation B), followed by one-month addition of captopril (Cp) (investigation C). During the last two weeks Dx, F, N or Dx, F, S were administered with Cp being withdrawn (investigation D). At the end of each stage of the treatment ecg registration was repeated according to Holter. At the same time, during the investigation A there were performed determinations of blood serum sodium, potassium and digoxin concentrations, two-dimensional echocardiography and evaluation of submaximal exercise tolerance. In 96 per cent of patients with CCHF, treated with Dx and F, cardiac rhythm disturbances were found. In 53.3 per cent life-threatening ventricular arrhythmias occurred, including unstable ventricular tachycardia in 11.1 per cent of patients. Addition of N or S to the classical treatment did not decrease either patient number or amounts of cardiac rhythm disturbances in individual classes according to Lown. Also Cp did not affect numbers of patients with cardiac rhythm disturbances, but it decreased numbers of patients with life-threatening ventricular arrhythmias from 53.3 per cent to 28.9 per cent (from 24/45 to 13/45). At the same time, Cp significantly decreased numbers of ventricular arrhythmias in class 3 and 4a (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Captopril; Cardiac Output; Coronary Disease; Digoxin; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Furosemide; Heart Block; Heart Failure; Heart Valve Diseases; Heart Ventricles; Humans; Isosorbide; Male; Middle Aged; Nifedipine; Tachycardia; Vasodilator Agents

In a randomized placebo-controlled double-blind trial of 230 congestive heart failure patients, four treatments were evaluated for efficacy, with exercise tolerance time (ETT) as the primary outcome. Various two-sample tests were applied to the analysis of ETT data. It is shown in this paper that the conventional two-sample tests (t and rank-sum) are insensitive to situations where the effect of the experimental therapy is not consistent across a patient population. Tests recommended by O'Brien are more appropriate for these data. It is also shown that the application of the O'Brien tests led to the identification of sub-groups where the observed effect of the experimental therapy was most pronounced.

Topics: Adult; Data Interpretation, Statistical; Digoxin; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Milrinone; Pyridones; Randomized Controlled Trials as Topic; Statistics as Topic; Vasodilator Agents

"The addition of angiotensin converting enzyme inhibitors to digoxin and diuretics is effective in improving and prolonging the lives of patients with severe heart failure. Our next goal is to prevent the progression of heart failure in patients with asymptomatic left ventricular dysfunction."

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans

The effect of digoxin in the treatment of decompensated chronic cor pulmonale was investigated in a randomized double-blind, cross-over, placebo-controlled trial. A total of 34 successive patients with evident right heart failure were included in the study. The mean maintenance daily dose of digoxin was 0.30 +/- 0.03 mg with the mean serum level of 1.7 +/- 0.7 nmol/L. The severity of heart failure was assessed according to a clinicoradiographic scoring system (Heart Failure Score). The heart failure worsened during the placebo-period in eight (23.5%) patients (four with atrial fibrillation, two with a third heart sound (S3), one with a cardiothoracic ratio of more than 0.5 and one with sinus rhythm). By regression analysis, the heart failure significantly worsened only in the subgroup of patients with atrial fibrillation. Digoxin was successfully (without worsening of the heart failure) discontinued in 26 (76.5%) patients. No significant improvement was observed in the patients with S3 gallop. It was concluded that digoxin had no beneficial effect in chronic cor pulmonale patients with heart failure, except in those with atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Digoxin; Double-Blind Method; Drug Administration Schedule; Female; Heart Failure; Humans; Male; Middle Aged; Pulmonary Heart Disease; Time Factors

Angiotensin converting enzyme inhibitors are now firmly established in the treatment of patients with chronic heart failure (CHF). Their beneficial acute and chronic hemodynamic effects are not associated with reflex tachycardia or drug tolerance. Angiotensin converting enzyme inhibitors produce symptomatic improvement and improve exercise capacity in all grades of heart failure. They also improve the prognosis of patients with severe heart failure. Quinapril is a recently introduced, nonsulfhydryl ACE inhibitor, whose intermediate half-life makes it well-suited for the treatment of patients with CHF. The acute and chronic hemodynamic effects of quinapril are similar to those of other ACE inhibitors. In a large, multicenter, randomized, placebo-controlled study of 225 patients with mild to moderate CHF, 10 to 40 mg/day quinapril significantly improved clinical status and exercise capacity in a dose-related manner. The incidence of side effects did not differ significantly from that of placebo. The initial studies with quinapril are promising and warrant further clinical investigation of this compound.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Output; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Hemodynamics; Humans; Isoquinolines; Physical Exertion; Quinapril; Tetrahydroisoquinolines; Vascular Resistance

We describe a randomized double-blind 4-week study on the efficacy of monotherapy with ibopamine 200 mg b.i.d. in comparison to placebo and open titrated digoxin in patients with mild congestive heart failure NYHA class I and II. A total of 60 patients (22 males and 38 females) were evaluated for body weight, signs and symptoms score and the need for additional diuretic treatment for adequate symptom control. Mean decreases in body weight in the ibopamine group exceeded mean decreases in body weight in the placebo group (3.03 kg). The signs and symptoms score was improved in 7 out of 20 patients in the placebo group, in all patients treated with ibopamine and in 21 of 22 patients of the digoxin subgroup while the patient-questionnaire score improved in 23.5% (placebo), 100% (ibopamine) and 81.2% (digoxin) of the cases, respectively. There were no treatment failures in the ibopamine and digoxin group. However, 8 of 20 patients receiving placebo had need of additional diuretic therapy. No adverse drug reactions were reported in the ibopamine-treated patients. We conclude that ibopamine monotherapy over 4 weeks has favourable effects on body weight and signs and symptoms of mild congestive heart failure without exerting major side effects. The efficacy is comparable to digoxin therapy.

Topics: Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Deoxyepinephrine; Digoxin; Double-Blind Method; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Vasodilator Agents

The appearance of impaired left ventricular diastolic function in chronic ischemic heart disease often precedes systolic dysfunction. Myocardial ischemia and increased calcium loading have been implicated in the genesis of increased left ventricular stiffness. We have assessed the effects of long-term therapy with different classes of calcium channel-blocking drugs on left ventricular peak filling rate in patients with chronic stable angina and congestive heart failure secondary to ischemic heart disease. Therapeutic effects of nicardipine (30 mg t.i.d.), nisoldipine (10 mg b.i.d.), and verapamil (120 mg t.i.d.) (4 weeks) have been assessed on radionuclide left ventricular diastolic filling parameters in patients with chronic stable angina using placebo-controlled studies. All three drugs significantly improved exercise capacity as compared with placebo. Verapamil produced significant improvements in peak filling rate (p less than 0.005), time to peak filling rate (p less than 0.01), and first one-third filling fraction (p less than 0.005), whereas nicardipine only improved peak filling rate (p less than 0.005); neither drug altered the mean ejection fraction (n = 20). Nisoldipine did not significantly alter diastolic filling parameters or ejection fraction (n = 10). Nisoldipine and digoxin were also assessed in congestive heart failure (New York Heart Association [NYHA] classes II and III) associated with ischemic heart disease (n = 26) (open parallel design). Neither produced significant alterations in peak filling rate and ejection fraction after 3 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angina Pectoris; Calcium Channel Blockers; Cardiac Output; Digoxin; Exercise Test; Heart Failure; Humans; Middle Aged; Myocardial Contraction; Radionuclide Ventriculography; Randomized Controlled Trials as Topic; Stroke Volume; Time Factors

Ibopamine, a dopamine derivative suitable for oral administration, is reported to improve cardiac function in patients with chronic heart failure. In order to evaluate the inotropic effect of ibopamine and to compare it with that of digoxin, we studied 10 patients with chronic heart failure (NYHA II-III). All patients were in sinus rhythm. After a washout period of 5 days, when the patients received a constant diuretic dosage and a placebo, ibopamine 100 mg t.i.d. or digoxin 0.25 mg o.d. was randomly given double-blind. The active treatment was continued for a 10-day period, and was followed by a second washout period of 5 days. Subsequently, the patients received digoxin if previously on ibopamine or ibopamine if previously on digoxin for 10 days. Diuretic was continued at the same dosage throughout the study. At the end of the two washout periods, all patients performed a static (hand grip) and a dynamic exercise (bicycle ergometer). Both ibopamine and digoxin improved cardiac response to both types of exercise compared to the washout periods. In particular, PEP/LVET decreased (p less than 0.001 for both drugs) and O2 consumption improved (from 586 +/- 48 to 716 +/- 35 ml/min for ibopamine and from 585 +/- 38 to 713 +/- 52 ml/min for digoxin). No difference was noted between the two drugs in the improvement of exercise tolerance. No side effects were noted with the two drugs. These data indicate that ibopamine could be a valid alternative to digoxin in heart failure patients in sinus rhythm when given for 10 days. More data are needed to evaluate the long-term efficacy of ibopamine.

Topics: Adult; Aged; Cardiotonic Agents; Chronic Disease; Deoxyepinephrine; Digoxin; Dopamine; Double-Blind Method; Drug Evaluation; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Physical Endurance; Random Allocation; Vasodilator Agents

Topics: Captopril; Digoxin; Heart Failure; Humans

A multicenter, randomized, double-blind, parallel-group trial was conducted to compare the effects of enalapril and digoxin on clinical signs and symptoms, as well as exercise capacity, in 142 patients with congestive heart failure classified as mild to severe (New York Heart Association functional classes II to IV). The patients received optimal treatment with digitalis and diuretics for 2 to 4 weeks. Thereafter, they were randomly assigned to receive either enalapril plus diuretics (n = 72) or digoxin plus diuretics (n = 70). After 8 weeks of treatment, a significant improvement in classification was observed in 22 of 63 patients (35%) in the enalapril group and in 17 of 61 (28%) in the digoxin group (difference not significant [NS]). Similarly, duration of exercise increased in both groups (p less than 0.005; p = NS between groups). Blood pressures decreased in the enalapril group (from 129 +/- 19/80 +/- 10 to 121 +/- 20/78 +/- 11 mm Hg; p less than 0.001), but not in the digoxin group (from 134 +/- 19/82 +/- 12 to 138 +/- 19/85 +/- 10 mm Hg; NS). Serum creatinine and electrolytes did not exhibit any significant change from baseline values, except for serum potassium, which increased slightly in the enalapril group (from 4.24 +/- 0.48 to 4.43 +/- 0.49 mmol/liter; p less than 0.05) and decreased slightly in the digoxin group (from 4.28 +/- 0.47 to 4.18 +/- 0.40 mmol/liter; p less than 0.05). Adverse events were reported in 13 patients (5 withdrawals) in the enalapril group and in 7 patients (2 withdrawals) in the digoxin group (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Clinical Trials as Topic; Digoxin; Double-Blind Method; Enalapril; Exercise Test; Heart Failure; Humans; Middle Aged; Multicenter Studies as Topic; Placebos; Random Allocation

The effects of enalapril were evaluated in a double-blind, controlled study during 8 weeks, in patients with stable, congestive chronic cardiac insufficiency (functional classification II and III of the NYHA), in sinus rhythm, treated with digitalis and diuretics. 20 patients were randomly divided in two groups: one group continuing the digoxin (group A: 10 patients) and one group where enalapril was substituted for digoxin (group B: 10 patients). Patients from group B presented less clinical aggravation during the study. The left ventricular stroke volume (SV) is significantly decreased in group B at rest (0.21 +/- 0.06 at 50; 0.18 +/- 0.04 at 54; p less than 0.05), while it remained stable during stress. No variations of the SVs were noted at rest and during stress in group A. Considering its favorable clinical effects and after evaluation of its longterm side effects, enalapril may be an acceptable alternative to digitalis in cardiac insufficiency with sinus rhythm, except in patients for whom a drop in the systemic blood pressure or an increased kaliemia or creatininemia, could be potentially harmful.

Topics: Digoxin; Double-Blind Method; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Physical Exertion; Radionuclide Angiography; Random Allocation; Rest; Stroke Volume

Xamoterol is a partial beta 1 adrenoceptor agonist with positive inotropic properties. Treatment with xamoterol and digoxin was compared in 19 patients with cardiac failure (NYHA class II-III). The study consisted of a short-term and a long-term phase. The former was a randomized, double-blind, crossover study with 6-week treatment periods. In the 15 patients who completed this phase, there was no significant difference between exercise duration on digoxin and on xamoterol. Exercise duration increased on digoxin by 27% and on xamoterol by 17% relative to baseline. Comparing digoxin and xamoterol, maximum exercise heart rate (p less than 0.001), blood pressure (p less than 0.01), and the pressure-rate product during maximum exercise were significantly lower on xamoterol treatment. The systolic time interval was shorter on digoxin than on xamoterol (p less than 0.001). No changes occurred in the echocardiographic parameters. After the short-term study, 13 patients were followed 3-6 months on the drug to which they had responded best (digoxin 7, xamoterol 6). The results of the short-term study were maintained during this period. In conclusion, we found that xamoterol may be an alternative to digoxin in patients with mild to moderate heart failure.

Topics: Adrenergic beta-Agonists; Adult; Aged; Digoxin; Double-Blind Method; Echocardiography; Electrocardiography; Exercise Test; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Propanolamines; Xamoterol

We randomly assigned 230 patients in sinus rhythm with moderately severe heart failure to treatment with digoxin, milrinone, both, or placebo. The effects of each were compared during a 12-week, double-blind trial. Treatment with milrinone or digoxin significantly increased treadmill exercise time as compared with placebo (by 82 and 64 seconds respectively; 95 percent confidence limits, 44 and 123, and 30 and 100). Both treatments reduced the frequency of decompensation from heart failure, from 47 percent with placebo to 34 percent with milrinone (P less than 0.05; 95 percent confidence limits, 22 and 46) and 15 percent with digoxin (P less than 0.01; 95 percent confidence limits, 7 and 26). However, the clinical condition of 20 percent of the patients taking milrinone deteriorated within two weeks after treatment was begun, as compared with only 3 percent of those taking digoxin (P less than 0.05). The left ventricular ejection fraction at rest was not significantly changed by milrinone (+0.2 percent; 95 percent confidence limits, -1.5 and 1.9), but it was increased by digoxin (+1.7 percent; P less than 0.01; 95 percent confidence limits, -0.03 and 3.4) and decreased by placebo (-2.0 percent; 95 percent confidence limits, -3.8 and -0.1). Three-month survival was related inversely to the base-line ejection fraction. Analysis of mortality from all causes according to the intention to treat suggested an adverse effect of milrinone (P = 0.064). After adjustment for an excess of patients with lower ejection fractions randomly assigned to receive milrinone, this trend was not significant (P = 0.26). Increased ventricular arrhythmias occurred more frequently in patients who received milrinone than in those who did not (18 vs. 4 percent; P less than 0.03). We conclude that milrinone significantly increased exercise tolerance and reduced the frequency of worsened heart failure. However, in the population of patients studied, milrinone or the combination of milrinone and digoxin offered no advantage over digoxin alone. Furthermore, our data suggest that milrinone may aggravate ventricular arrhythmias.

Topics: Administration, Oral; Cardiotonic Agents; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Milrinone; Pyridones; Random Allocation; Stroke Volume; Vasodilator Agents

In a randomized and double-blind study of 116 patients with chronic heart failure (NYHA classes II or III) the effectiveness of captopril + hydrochlorothiazide (HCT) (group 1) and of digoxin + HCT (group 2) were compared. Treatment was effected for a 12-month period with a combination of 50 mg captopril (twice 25 mg daily, oral) and HCT, or 0.2 mg digoxin (twice 0.1 mg daily, oral) and HCT. In a pretreatment phase over 3-4 weeks the patients of group 1 were given an average HCT dose of 37.7 mg daily, whereas those of group 2 received 34.9 mg per day. At the end of the 12-month treatment period the patients in the captopril/HCT group had improved significantly more--by the criteria of echocardiographic intracardiac diameters, exercise tolerance and NYHA class--than those in the digoxin/HCT group. Change by a mean of one NYHA class had occurred in 61 patients (51.8%) of group 1 and in 47 (40.7%) of group 2 (P les than 0.01). These findings suggest that treatment of patients with mild to moderately severe chronic heart failure in sinus rhythm best be initiated with an angiotensin-converting enzyme inhibitor together with a diuretic rather than a digitalis-diuretic combination.

Topics: Blood Pressure; Captopril; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Female; Heart Failure; Humans; Hydrochlorothiazide; Male; Middle Aged; Stroke Volume

The interaction between felodipine and digoxin was studied after a single oral dose and at steady state in 14 patients with congestive heart failure. Felodipine (10 mg) was randomly given as an extended release (FER) tablet in a double-blind, placebo-controlled, cross-over fashion. In addition, felodipine (10 mg) was given openly as a plain tablet, following the double-blind period. Each period lasted for 7 d. Felodipine ER did not alter the pharmacokinetics of digoxin when given as a single dose or at steady state compared with placebo. At steady state the felodipine plain tablet resulted in an 11% increase (P less than 0.05) in peak plasma concentrations of digoxin. Systolic time intervals as noninvasively measured haemodynamic parameters were not significantly altered following the felodipine ER period, while the felodipine plain tablet significantly decreased the pre-ejection/left ventricular ejection time ratio compared to placebo.

Topics: Aged; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Felodipine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Nitrendipine; Random Allocation

1. The efficacy of captopril and isosorbide dinitrate (ISDN) as adjunctive therapy to digoxin and diuretics in mild heart failure was compared in a double-blind study. 2. Twenty-one patients were randomly allocated to captopril (twice or three times daily) or ISDN. Eighteen patients completed a protocol of placebo run-in, dose titration and maintenance treatment for 3 months. 3. Symptom-limited exercise tolerance, ejection fraction and radionuclide indices of diastolic function estimated by gated blood pool scan did not change with either treatment. 4. Captopril improved functional class (Canadian Cardiovascular Society) and reduced requirements for increased diuretic dosage at both 1 and 3 months of maintenance treatment. Patients treated with ISDN required increased diuretic and did not improve their functional class. Differences between the treatments were significant only for diuretic dosage requirements. 5. We conclude that adjunctive therapy of mild heart failure with captopril administered twice daily provides a diuretic-sparing effect and may improve functional class during 3 months of maintenance treatment.

Topics: Blood Pressure; Captopril; Digoxin; Diuretics; Exercise Test; Heart Failure; Humans; Isosorbide Dinitrate; Male; Middle Aged; Renin; Time Factors

The two agents beta-methyldigoxin (medixin), a Soviet medilazide, and bemecor (digicor), a foreign analogue (LEK, Yugoslavia) were comparatively evaluated. An equal high (85%) clinical efficacy of the drugs was found in 81 patients with varying stages of heart failure. A positive therapeutic effect was accompanied by lower heart rate, higher diuresis and natri-and kaliuresis, decreased systolic and diastolic pressures in the pulmonary artery. The incidence of adverse reactions and the causes of their occurrence are analyzed.

Topics: Adult; Aged; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Medigoxin; Middle Aged; Myocardial Contraction; USSR; Yugoslavia

18 patients with II NYHA class chronic congestive heart failure (CCHF) had been given nifedipine (Cordipin) 54.4 +/- 12.0 mg (day) for 6 weeks (group I). In 25 patients with III--IV NYHA class CCHF after 2-week optimal improvement of a clinical state with digoxine (D) and furosemide (F), nifedipine (N) had been added for 2 weeks/mean daily dose -- 40.8 +/- 12.8 mg (group II). Estimation of a left ventricular function using 2-DE and a submaximal effort tolerance as well as clinical examinations were carried out initially, after 2 and 6 weeks in group I, whereas in group II post D, F 2-week therapy and after next 2 weeks of combined D, F, N treatment. Nifedipine significantly increased ejection fraction from 44.2 +/- 13.0% to 49.0 +/- +/- 12.6% and decreased myocardial oxygen demand factor from 23.36 +/- 9.81 to 21.08 +/- 7.55 X 10(3) (p less than 0.05). Nonsignificant but marked increase of diuresis, cardiac and stroke indices as well as body weight loss were observed. Nifedipine addition to D and F neither improved nor deteriorated examined parameters in patients with III-IV NYHA class CCHF. Nifedipine did not also improve the submaximal exercise tolerance in both groups.

Topics: Adult; Aged; Chronic Disease; Clinical Trials as Topic; Digoxin; Diuresis; Female; Furosemide; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Nifedipine; Time Factors

The substitution of digoxin with ibopamine, a new inotropic and vasodilating agent, was evaluated in a multicenter study in 58 patients with mild-to-moderate congestive heart failure, stabilized on diuretics, and digoxin therapy. The study was a parallel, double-blind, randomized trial of four weeks duration in which half of the group continued the pre-study medication (diuretics and digoxin) and half of the group was treated with diuretics and ibopamine (100 mg, three times a day). At baseline evaluation, the two groups were similar for age, sex, underlying cardiac disease, duration of congestive heart failure, symptom score, cardiothoracic ratio, echocardiographic parameters of left ventricular function and exercise tolerance as measured by bicycle ergometry. After four weeks, no clinical deterioration was found in the patients treated with ibopamine in any measured parameter. There were two deaths during the study: a sudden death and one following an acute myocardial infarction. Both patients were on digoxin. This study suggests that in patients with mild-to-moderate congestive heart failure, ibopamine therapy may effectively and safely substitute digoxin therapy for up to four weeks, representing an option for patients requiring inotropic support but are at risk for potential digoxin toxicity.

Topics: Adult; Aged; Arrhythmias, Cardiac; Deoxyepinephrine; Digoxin; Dopamine; Echocardiography; Exercise Test; Female; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged

Sixteen patients in heart failure and sinus rhythm were, after a four-week treatment-free period, randomly assigned to receive, for four to six weeks, either a diuretic combination (hydrochlorothiazide + triamterene) or a digitalis glycoside. Subsequently the treatment was exchanged between the two groups. Without treatment nine patients were in stage II (New York Heart Association classification), seven in stage III. Pulmonary wedge pressure at rest was 27 +/- 14, on exercise 32 +/- 8 mm Hg, cardiac output 5.3 +/- 1.0 at rest and 7.8 +/- 2.3 l/min on exercise. Digitalis glycosides improved symptoms by one stage in three of 16 patients. All objective measures showed slight but not significant improvement. Diuretic treatment improved symptoms in five patients, while heart size and echocardiographically measured ventricular volume decreased slightly. Cardiac output decreased at rest, but not significantly, and on exercise not at all. Pulmonary arterial pressure (21 +/- 9 mm Hg), pulmonary wedge pressure (13 +/- 7 mm Hg) and pulmonary artery pressure on exercise (39 +/- 11 mm Hg) were significantly lower on diuretics than without treatment. The results support the primary use of diuretics in the treatment of chronic heart failure.

Topics: Aged; Chronic Disease; Digitalis Glycosides; Digitoxin; Digoxin; Drug Combinations; Drug Evaluation; Female; Heart Failure; Hemodynamics; Humans; Hydrochlorothiazide; Male; Middle Aged; Time Factors; Triamterene

This article reports the results of a multicenter international study of the use of lisinopril in patients with congestive heart failure also receiving digoxin, diuretics, or both. Two thirds of the 130 subjects enrolled in the study received lisinopril and one third received placebo. Lisinopril treatment led to a significant improvement in both bicycle and treadmill exercise tolerance, New York Heart Association classification status, cardiac function assessed noninvasively, and symptomatology. There was no age differentiation; the same improvement was achieved in the 35 patients over 65 years old as in the younger patients. There was a mild decrease in both systolic and diastolic blood pressure in patients receiving lisinopril, peaking at seven hours. These changes, however, were not significantly different from those seen with placebo. Apart from one patient in whom hypotension developed followed by reversible renal failure, there were no serious adverse effects, and the incidence of sudden death and biochemical abnormalities was no different from that seen with placebo. This study confirms that this agent is an effective, safe, well-tolerated agent in the treatment of congestive cardiac failure and is equally applicable to younger and older patients.

Topics: Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Digoxin; Diuretics; Double-Blind Method; Enalapril; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Lisinopril; Male; Middle Aged; Placebos; Random Allocation

433 patients aged 29-80 with mild to moderate heart failure entered a multicentre double-blind randomised between-patient comparison of xamoterol 200 mg twice daily, digoxin 0.125 mg twice daily, and placebo. Patients were assessed at baseline and after three months. Of 349 who completed the double-blind phase, 300 had valid exercise tests. Compared with placebo, xamoterol significantly increased exercise duration and work done on a bicycle ergometer and improved breathlessness and tiredness during daily life as assessed by visual analogue scale and by Likert scale. Digoxin showed no statistically significant advantage over placebo on any of the measures except the Likert scale. Exercise performance and work done were significantly higher with xamoterol than with digoxin.

Topics: Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Digoxin; Double-Blind Method; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Propanolamines; Random Allocation; Xamoterol

The evidence suggests that digitalis glycosides do indeed improve ventricular performance through a sustained but moderate positive inotropic effect. This effect is more marked in failing than in nonfailing myocardium. The clinical studies suggest a moderate salutary effect in patients with chronic CHF who are in sinus rhythm. The drug can be given safely to patients with CAD and in combination with other medications when the physician is aware of those factors leading to increased sensitivity to digitalis.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Myocardial Contraction; Time Factors; Vasodilator Agents

A randomized, crossover, single-blind study compared the efficacy and dosing accuracy of digoxin and digitoxin in 15 ambulatory patients wth congestive heart failure. Loading doses and maintenance doses were calculated according to published equations that adjust for sex, height, and lean body weight (for digitoxin), plus estimated creatinine clearance (for digoxin). At each 2-week visit, serum drug concentrations were measured and compliance with the prescribed regimen was assessed by tablet count. At the end of each study period, a congestive heart failure (CHF) score was determined in a blinded fashion by the same physician. Patient compliance was unusually high (greater than or equal to 80%) at every visit. Therapeutic concentrations were achieved with digoxin and digitoxin in 5 and 14 patients, respectively (p less than 0.05). During digitoxin therapy, CHF scores were lower than pretreatment values (p less than 0.05). The difference between CHF scores during the digoxin and digitoxin periods did not achieve significance (0.05 less than p less than 0.06). Therapeutic serum concentrations can be achieved more easily and frequently with digitoxin than digoxin without compromising the patient's CHF status.

Topics: Adult; Aged; Clinical Trials as Topic; Digitoxin; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Random Allocation

A possible interaction between felodipine and digoxin was studied in 23 patients with congestive heart failure before and after 8 weeks treatment with both drugs. A modest, non-significant increase in serum digoxin level 2 h postdose (+15%) was found in the felodipine group (n = 11) compared to placebo (n = 12), with no change in the trough and 6 h postdose levels. There was a bimodal distribution of the observed changes in serum digoxin level 2 h postdose: a significant increase (p less than 0.001) was observed only in patients with a high plasma felodipine level, which may have been caused by changes in the absorption rate in those patients. Changes in the elimination of digoxin after felodipine therapy appeared unlikely, since the trough and 6 h post-dose levels were unchanged. Analysis of the clinical characteristics, haemodynamics and laboratory values revealed no significant differences between the subgroups. The observed increase in serum digoxin warrants monitoring the trough and peak levels digoxin in patients with congestive heart failure who are also being treated with felodipine.

Topics: Aged; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Felodipine; Female; Heart Failure; Humans; Male; Middle Aged; Nitrendipine; Prospective Studies

Because of conflicting results from studies examining the usefulness of digoxin in congestive heart failure (CHF) patients in sinus rhythm, a cross-over trial was conducted in which 20 patients received 7 weeks of digoxin titrated to a level of 1.54 to 2.56 nmol/liter and 7 weeks of matched placebo. The order of treatments was determined by random allocation and patients, clinicians and research staff were blind to allocation. In patients with deteriorating condition, the treatment period was terminated and outcome measures were obtained. If deterioration occurred during the first period, the patient was crossed over without the code being broken. Seven patients required premature termination of study periods because of increasing symptoms of CHF. All 7 were taking placebo at the time (p = 0.016). Small differences in dyspnea (p = 0.044), walking test score (p = 0.055), clinical assessment of CHF (p = 0.036) and ejection fraction (p = 0.004) favored the digoxin treatment group. Patients with more severe CHF were more likely to benefit from digoxin administration. It was concluded that oral digoxin, in doses titrated to produce a serum level of 1.54 to 2.56 nmol/liter, improved quality of life and functional exercise capacity in some patients with CHF in sinus rhythm.

Topics: Aged; Clinical Trials as Topic; Digoxin; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Random Allocation

This study evaluates the effects of a standardized meal on cardiovascular hemodynamics in 12 patients with New York Heart Association Class III congestive heart failure. This was done as part of a larger study in which an orally active dopaminergic agonist was given on two mornings, once with a standardized breakfast and once fasting, and one morning a placebo was given with the breakfast. The order of days was randomized. Hemodynamic data were obtained over 8 h each day. There were significant changes in several hemodynamic variables after the placebo-food regimen lasting up to 1.5 h: cardiac index rose from 1.8 +/- 0.4 to 2.2 +/- 0.5 L/min.m2 at 30 min (p less than .001) and to 2.0 +/- 0.5 L/min.m2 at one hour (p less than .05); stroke volume index rose from 20 +/- 7 to 24 +/- 7 ml/min at 30 min (p less than .05) and to 23 +/- 7 ml/min at one hour (p less than .05); systemic vascular resistance fell from 1890 +/- 685 to 1534 +/- 497 dyne.sec/cm5 at 30 min (p less than .001) and to 1668 +/- 524 dyne.sec/cm5 at one hour (p less than .05). Mixed venous oxygen saturation was measured continuously in seven patients and rose significantly at one and 1.5 h. We conclude that food ingestion can have a significant effect on cardiovascular hemodynamics and that this effect should be considered when therapeutic effects are to be guided by invasive hemodynamic monitoring in this population.

Topics: Adult; Aged; Digoxin; Eating; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Random Allocation

The effects on cardiac function of captopril (CPT) and digoxin (D) were compared in a study of 16 patients with chronic heart failure due to ischemic heart disease (15) and to congestive cardiomyopathy (1) (New York Heart Association class II n.13 and class III n.3). All patients were normotensive and in sinus rhythm. CPT 25 mg every 8 hours (t.i.d.) or D 0.25 mg once daily was given in a single-blind crossover design: A placebo (PLC) t.i.d. was given for 5 to 10 days, then CPT or D, according to a random sequence, replaced three or one of the PLC tablets; after one month, CPT and D were switched to PLC for 5 to 10 days; subsequently, the PLC tablets were replaced by CPT in the patients who previously received D and vice versa, and both treatments were again continued for one month. PLC, CPT, and D tablets were all identical. Diuretics once daily were given throughout the study. Plasma renin activity (PRA), plasma aldosterone (ALDO), plasma noradrenaline (NA), and adrenaline (A) were determined at the end of the two PLC periods and the two active treatments. A hand grip and a bicycle exercise were performed at the end of the two PLC periods and the two active treatments. No difference was noted between the PLC periods. PRA increased with CPT and did not change with D. ALDO was decreased by both CPT and D. NA and A were similarly decreased by both drugs, both supine and standing.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Captopril; Clinical Trials as Topic; Digoxin; Epinephrine; Heart Failure; Humans; Isometric Contraction; Middle Aged; Norepinephrine; Osmolar Concentration; Renin

Topics: Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Monitoring, Physiologic

Topics: Adult; Aged; Biological Availability; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Medigoxin; Middle Aged; Monitoring, Physiologic

Some calcium antagonist drugs used in hypertension and cardiac diseases have been shown to increase plasma digoxin levels mainly as a result of reduced renal clearance. Felodipine is a new dihydropyridine calcium antagonist drug with cardiovascular effects, whose pharmacokinetics and effects on plasma digoxin levels have been studied in patients with left ventricular failure. 12 patients (11 men) on long term digoxin therapy were given 2.5 or 5 mg felodipine bid for 7 days followed by 1 week on 10mg bid. Plasma levels of digoxin and felodipine were measured before dosage and 30, 60 and 90 minutes and 2, 3, 4, 6, 8, 10 and 24 hours after the first dose and after 1 week of therapy (steady state). The area under plasma concentration versus time curve was calculated after the first dose and in steady state both for digoxin and felodipine. The absorption characteristics Cmax and Tmax were calculated both for felodipine and digoxin on the different felodipine doses. There was a linear relationship between dose and plasma level of felodipine. Plasma half-life in the 4- to 10-hour period of felodipine was 5.5 hours after a 10mg single dose, and 12 hours after 10mg bid. Felodipine 2.5mg, 5mg and 10mg all transiently increased peak plasma digoxin concentrations (by about 40%) at 1 hour after intake. Urinary excretion of digoxin during the day was unchanged, but impaired renal clearance may account for the transient increase in digoxin plasma level after felodipine.

Topics: Aged; Antihypertensive Agents; Digoxin; Felodipine; Female; Heart Failure; Humans; Male; Middle Aged; Nitrendipine

The potential for pharmacokinetic drug interaction between ethmozine (moricizine HCl), a phenothiazine class I antiarrhythmic investigational drug, and digoxin was evaluated in 13 cardiac patients with normal renal function. Antiarrhythmic therapy was initiated in patients with potentially lethal (nonlife-threatening) ventricular arrhythmias (greater than 30 ventricular ectopic beats [VEB]/hr) who were receiving maintenance digoxin therapy for congestive heart failure and/or atrial fibrillation. Serum digoxin concentrations of patients were measured frequently by radioimmunoassay and plasma ethmozine concentrations by high-performance liquid chromatographic methods. Patients entered a short-term (4 weeks) single-blind, placebo controlled ethmozine protocol with an option to receive long-term (1 to 6 months) open-label maintenance ethmozine therapy. Ambulatory ECGs (48 hour) used to assess antiarrhythmic efficacy of ethmozine during each week of the short-term protocol showed that 77% of patients demonstrated greater than 90% mean hourly frequency suppression of all forms of ventricular ectopy. Serum digoxin concentrations during short-term ethmozine dosing showed a nonsignificant (p greater than 0.05) increase of 10% to 15% (mean 0.91 ng/ml to 1.13 ng/ml). The short-term protocol serum digoxin levels correlated closely with serum digoxin concentrations during placebo therapy (1st week, r = 0.90; 2nd week, r = 0.87). Serum digoxin concentrations were not significantly different (p greater than 0.05) from placebo values at the end of 1, 3, and 6 months of maintenance ethmozine therapy. Thus, we conclude that ethmozine administered in an antiarrhythmic efficacious dosage (10 mg/kg/day) showed no important clinical or statistically significant change in serum digoxin concentrations of cardiac patients with normal renal function.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Complexes, Premature; Clinical Trials as Topic; Digoxin; Drug Interactions; Female; Heart Failure; Humans; Kinetics; Male; Middle Aged; Moricizine; Phenothiazines

To evaluate the concept that long duration of action is an advantageous property of angiotensin-converting enzyme inhibitors in the treatment of severe heart failure, we randomly assigned 42 patients to therapy with either a short-acting inhibitor (captopril, 150 mg daily) or a long-acting inhibitor (enalapril, 40 mg daily) for one to three months while concomitant therapy with digoxin and diuretics was kept constant. The treatment groups had similar hemodynamic and clinical characteristics at base-line evaluation and similar initial responses to converting-enzyme inhibition. During long-term therapy, captopril and enalapril produced similar decreases in systemic blood pressure, but the hypotensive effects of enalapril were more prolonged and persistent than those of captopril. Consequently, although the patients in both groups improved hemodynamically and clinically during the study, serious symptomatic hypotension (syncope and near syncope) was seen primarily among those treated with enalapril. Sustained hypotension also probably accounted for the decline in creatinine clearance (P less than 0.05) and the notable retention of potassium (P less than 0.05) observed in the patients treated with enalapril but not in those treated with captopril. We conclude that when large, fixed doses of converting-enzyme inhibitors are used in the treatment of patients with severe chronic heart failure, long-acting agents may produce prolonged hypotensive effects that may compromise cerebral and renal function, and thus they may have disadvantages in such cases, as compared with short-acting agents.

Topics: Adult; Aged; Blood Pressure; Captopril; Chronic Disease; Clinical Trials as Topic; Creatinine; Digoxin; Diuretics; Drug Therapy, Combination; Electrolytes; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Random Allocation

The effect of captopril as long-term treatment in 20 patients with congestive heart failure has been studied in a double-blind trial. Captopril caused a significant increase in serum digoxin levels. No patients developed evidence of digoxin toxicity. Serum and total body potassium rose and the frequency of ventricular arrhythmias showed a modest decline. Creatinine clearance and radioisotopically measured glomerular filtration rate fell, but there was a poor relationship between these and the increase in serum digoxin. In a further open study on 12 patients, creatinine, urea, and digoxin clearance were significantly reduced by captopril. However, digoxin clearance declined more than creatinine clearance (89 +/- 25 mumol/L to 69 +/- 22 mumol/L and 81 +/- 14 mumol/L to 72 +/- 19 mumol/L, respectively, p less than 0.05 for the difference). Fractional excretion of urea and digoxin filtered at the glomerulus declined, indicating greater tubular reabsorption or reduced tubular secretion of these compounds. Captopril causes an increase in serum digoxin by reducing renal clearance of the drug.

Topics: Captopril; Clinical Trials as Topic; Creatinine; Digoxin; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Tubules; Male; Middle Aged; Potassium; Urea; Urodynamics

In a placebo controlled double-blind study including 10 patients with heart failure the nisoldipine/digoxin interaction was studied. Nisoldipine was shown to elevate digoxin plasma concentrations significantly by about 15% (trough levels). During chronic combination therapy with nisoldipine trough levels and plasma concentrations 4 h after the morning dose of digoxin were 1.35 +/- 0.14 and 1.92 +/- 0.16 ng ml-1 respectively, whereas they averaged to 1.16 +/- 0.14 and 1.52 +/- 0.16 ng ml-1 with digoxin and placebo (P less than 0.05; mean +/- s.e. mean). Systolic time intervals were significantly altered by nisoldipine co-administration compared with digoxin plus placebo. In certain patients the elevation of digoxin plasma levels due to nisoldipine co-administration could be of clinical relevance.

Topics: Adult; Aged; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Double-Blind Method; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Nifedipine; Nisoldipine; Pulse

Captopril 25 mg every 8 hours for 1 month appeared to improve dynamic effort tolerance and cardiac function under the stress of isometric exercise in patients with chronic heart failure, functional class II-III NYHA. The improvement was comparable to that obtained in the same subjects with digoxin 0.25 mg once a day given for a similar period of 1 month. Therefore, captopril with its lower toxicity and wider therapeutic range, might be considered as a valid alternative to digoxin for treatment of patients in sinus rhythm with mild to moderate heart failure.

Topics: Adult; Aged; Blood Pressure; Captopril; Chronic Disease; Digoxin; Heart Failure; Humans; Isometric Contraction; Middle Aged; Physical Exertion; Random Allocation

In 15 patients with moderate congestive heart failure not completely controlled on digoxin (0.25 mg o.d.) and frusemide (25 mg o.d.), we compared the addition of captopril (12.5 to 50 mg b.i.d.) with increasing doses of frusemide (25 to 100 mg o.d.), in a randomized double-blind, double-dummy, comparative trial. Thirteen patients completed the 3 months study: two dropped-out in the frusemide group. Statistically significant clinical improvement occurred in both treatment groups. Exercise tolerance also significantly improved in both groups in a parallel fashion. Echocardiographic cardiac function data showed a significantly better pattern of changes in the captopril group. The addition of low doses of captopril to basal therapy seems to be as effective as the addition of high doses of frusemide in uncontrolled moderate congestive heart failure. This approach with captopril also appears to be more physiological and safe.

Topics: Aged; Captopril; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Random Allocation; Time Factors

This study compares the effects of digoxin, placebo and ibopamine (SB-7505), the orally active 3,4-diisobutyryl ester of N-methyl-dopamine, on exercise tolerance and cardiac rhythm of 14 patients whose left ventricular heart failure (end-diastolic pressure, 26.3 +/- 5.9 mmHg; ejection fraction, 0.42 +/- 0.10%) depended on a previous myocardial infarction. Patients were admitted to the study while on chronic oral digoxin treatment (serum levels between 1.1 and 1.9 ng/ml). Placebo instead of digoxin was given for the following month. Thereafter ibopamine 50 mg t.i.d. for one month was given. A sequence of one-month treatments with digoxin, placebo and ibopamine was repeated, then ibopamine was administered continuously for the next two months. The concurrent treatment (diuretics in all patients, nitroderivates in twelve, calcium antagonists in two) remained unchanged during the observation period. Symptoms-limited exercise tests and 24-h Holter recordings were obtained at admission, at the end of each one-month treatment and at the end of the observation period. Two patients developed unstable angina without increase of serum creatine phosphokinase while on ibopamine and were withdrawn. Out of the 12 patients that concluded the trial, one required supplementary doses of diuretic at the end of the second period on placebo. The results obtained during the trial suggest that: a) therapeutic plasma levels of digoxin have no deleterious effect on cardiac rhythm nor significantly increase exercise tolerance as compared with placebo; b) diuretics and nitrates appear to sustain the clinical stability of these patients as a group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Deoxyepinephrine; Digoxin; Dopamine; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Physical Exertion

Twenty-four-hour Holter electrocardiographic recordings were used to measure the effects of a converting-enzyme inhibitor, enalapril, given for 12 weeks, on the frequency of cardiac arrhythmias in 10 patients with congestive heart failure (New York Heart Association functional class II to III) receiving maintenance therapy with digoxin and furosemide. Nine patients were given placebo, and both study groups were conducted in a double-blind, parallel manner. The placebo group had no change in the frequency of arrhythmias, whereas enalapril-treated patients showed a significant decrease in the frequency of premature ventricular complexes, ventricular couplets and ventricular tachycardia. A minor, nonsignificant reduction in atrial premature complexes was seen in patients who received enalapril. Compared with placebo patients, those who received enalapril had an increase in plasma potassium levels of 0.33 mmol/liter, a decrease in plasma digoxin, and decreases in pulmonary artery wedge, mean pulmonary artery and right atrial pressures. However, none of these indexes were correlated with the concomitant decline in cardiac arrhythmias. It is concluded that enalapril reduces the frequency of ventricular arrhythmias in congestive heart failure, although the underlying mechanisms are not known.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Dipeptides; Electrocardiography; Enalapril; Female; Furosemide; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Pulmonary Wedge Pressure

Topics: Aged; Benzazepines; Bradycardia; Clinical Trials as Topic; Coronary Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Placebos

Prenalterol (P), a partial adrenergic agonist with functional beta 1-specificity, has been shown to have inotropic effects when given orally and thus represents a potential substitute or adjunct to conventional digitalis therapy (D) in the long-term management of congestive cardiomyopathy (COCM). A direct comparison between both drugs has not been reported. In a blind controlled trial, 15 patients with COCM (NYHA II-III) with sinus rhythm and a left ventricular ejection fraction (LV-EF) of 34.5 +/- 2.6% received consecutively D (0.25-0.5 mg/d), placebo (PLAC), P (slow releases = SR) (80 mg/d SR) and both drugs combined in respective doses. After 4 weeks of therapy with each drug, effects were assessed by gated blood pool scintigraphy at rest (R) and during graded bicycle exercise (EX), systolic time intervals (STI), Holter monitoring and a clinical score. Plasma levels of both drugs and of catecholamines and lactate were also determined. Compared to PLAC, LV-EF was not significantly altered by D at R (34.5 +/- 2.6 vs. 31.9 +/- 2.3%, p = ns), but a shortening of the QS2-interval could be demonstrated (533 +/- 7 vs. 550 +/- 6 msec, p less than 0.05). In contrast, during EX an improvement of LV-EF was observed (34.5 +/- 3 vs. 31.3 +/- 2.8%, p less than 0.05). P alone showed no significant alterations in LV-EF and STI, along with a lack of symptomatic improvement. The addition of D (D + P) resulted in improved left ventricular performance both at R (LV-EF 37.9 +/- 3.3 vs. 31.9 +/- 2.3%, p less than 0.01, QS2 530 +/- 8 vs. 550 +/- 6 msec, p less than 0.01) and during EX (LV-EF 35.3 +/- 2.5 vs. 31.1 +/- 2.8%). Values between D and D + P were not significantly different. No drug or combination improved maximal working capacity.. Beneficial effects of chronic treatment with D could be demonstrated in patients with COCM, particularly during EX. Further studies are needed to determine why the acute effects of P are not fully sustained during long-term therapy.

Topics: Adult; Cardiac Output; Cardiac Volume; Cardiomyopathy, Dilated; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Heart Failure; Humans; Lactates; Lactic Acid; Long-Term Care; Male; Middle Aged; Myocardial Contraction; Norepinephrine; Practolol; Prenalterol

Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced (11.7 +/- 6.3[SD] vs 17.1 +/- 3.1 U at baseline; p less than .05). Hemodynamics were similar at baseline and remained unchanged during placebo treatment. Mean left ventricular ejection fraction rose from 29.6 +/- 17.7% to 42.7 +/- 22.3% (p less than .05) after 3 months of minoxidil treatment (this result was influenced largely by responses in two patients), and remained unchanged (at 25.1 +/- 16.6%) after 3 months of placebo. Exercise duration and maximal oxygen uptake during exercise were unchanged during minoxidil or placebo treatment. Total clinical events, including increased need for diuretics, angina, ventricular arrhythmias, worsening heart failure, and death were all more frequent during minoxidil vs placebo administration (21 vs seven total events; p less than .01). Thus, despite improving hemodynamics and left ventricular function, long-term minoxidil administration was associated with a poorer clinical course in patients with chronic left ventricular failure. Furthermore, this experience demonstrates that improvement of left ventricular function alone cannot be reliably interpreted as proof of clinical efficacy of therapeutic interventions in patients with heart failure.

Topics: Aged; Blood Pressure; Cardiac Output; Clinical Trials as Topic; Digoxin; Diuretics; Double-Blind Method; Heart Failure; Heart Rate; Hemodynamics; Humans; Middle Aged; Minoxidil; Physical Exertion; Pyrimidines; Random Allocation; Stroke Volume; Time Factors; Vascular Resistance

Topics: Administration, Oral; Aged; Alprenolol; Arrhythmias, Cardiac; Blood Pressure; Clinical Trials as Topic; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Middle Aged; Myocardial Infarction; Random Allocation; Time Factors

Use of digitalis for the treatment of patients with congestive heart failure and sinus rhythm remains controversial. To ascertain the proper therapeutic role of digitalis, we have critically appraised the published clinical evidence of digitalis efficacy using standardized methodologic criteria. A search of the English literature from 1960 to 1982 identified 736 articles, of which 16 specifically addressed the clinical evaluation of digitalis therapy for patients with congestive heart failure and sinus rhythm. Only two double-blind, placebo-controlled trials provided clinically useful information. One study showed that digoxin therapy could be withdrawn successfully in elderly patients with stable congestive heart failure. The other showed that patients with chronic heart failure and an S3 gallop benefited from digoxin therapy.

Topics: Clinical Trials as Topic; Digitalis; Digitalis Glycosides; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Plants, Medicinal; Plants, Toxic; Pulmonary Heart Disease; Research Design

Topics: Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digoxin; Heart Failure; Heart Rate; Hemodynamics; Humans; Hypertension; Long-Term Care; Myocardial Contraction; Substance Withdrawal Syndrome

Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7 +/- 7.7 vs 35.4 +/- 3.2 pg/ml) nor estradiol (35.8 +/- 6.4 vs 32.2 +/- 3.9 pg/ml) nor testosterone (6.32 +/- 0.74 vs 6.45 +/- 0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55 +/0- 0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147 +/- 24 vs 142 +/- 19 pg/ml) and free estradiol (657 +/- 77 vs 615 +/- 78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128 +/- 18 to 389 +/- 18 ng/ml) and testosterone (from 5.96 +/- 0.90 to 10.33 +/- 1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150-210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took beta-methyldigoxin (n = 8), beta-acetyldigoxin (n = 20) and digitoxin (n = 7) from 1 to 9 (mean: 1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Cortex Hormones; Adult; Digitalis; Digoxin; Gonadal Steroid Hormones; Gynecomastia; Heart Failure; Hemodynamics; Humans; Male; Plants, Medicinal; Plants, Toxic; Sex Factors

The evaluation of the long-term treatment of heart failure is complicated by many biological, clinical and technical problems. Chronic heart failure results from a variety of causes, each resulting in fundamentally different histopathological profiles. Once established chronic heart failure is unremitting, but the speed of progression of the haemodynamic derangement varies widely between different individuals. Moreover, the extent of the haemodynamic disorder correlates poorly with the severity of symptoms. The metabolism of drugs and the response of the damaged myocardium to these drugs is often quite different in the patient with heart failure than in the normal subject. Finally chronic heart failure is a terminal condition of relatively short duration so that clinical trials designed to test the efficacy of a drug treatment will fail if they are continued for more than a brief period, as all patients will die. It is against this complex biological background that the long-term clinical efficacy of diuretics and digitalis in the treatment of chronic heart failure must be evaluated.

Topics: Administration, Oral; Chronic Disease; Clinical Trials as Topic; Digoxin; Diuretics; Drug Interactions; Drug Therapy, Combination; Drug Tolerance; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Prognosis; Substance Withdrawal Syndrome

The effects of oral digoxin and placebo in 41 geriatric in-patients were compared using a randomized, double-blind, cross-over method. The patients were in sinus rhythm or had atrial fibrillation. The observation period was two months on digoxin or placebo. Patients with symptoms of cardiac failure at rest or during light physical activity, X-ray signs of pulmonary congestion, proven need of digoxin therapy following earlier withdrawal, atrial fibrillation with a ventricular rate greater than 95 beats/min and patients in whom digitalis intoxication was suspected were excluded from the study. Five (14%) of 37 patients deteriorated during the placebo phase. Four of these developed rapid atrial fibrillation and one patient developed sinus tachycardia and symptoms of heart failure.

Topics: Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Double-Blind Method; Female; Heart Failure; Homes for the Aged; Humans; Male; Middle Aged; Random Allocation

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the severity of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P less than 0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound.

Topics: Adult; Aged; Cardiac Catheterization; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Evaluation; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Placebos; Random Allocation

Topics: Clinical Trials as Topic; Digoxin; Female; Heart Failure; Humans; Male

To assess the efficacy of digitalis in patients with chronic clinically compensated congestive heart failure and normal sinus rhythm, we performed a double-blind crossover study with digoxin and placebo in 30 consecutive outpatients fulfilling these criteria; serum digoxin levels, clinical symptoms and signs, and objective indexes of cardiac function were monitored. No patient's clinical condition deteriorated during three months of placebo administration. Discontinuation of digoxin resulted in a small increase in echocardiographically determined resting left ventricular end-diastolic dimension (1.8 +/- 0.6 mm, p less than 0.001) and a similar decrease in velocity of circumferential fiber shortening (-0.08 +/- 0.04 circ/sec, p less than 0.05) from the corresponding values of 55.8 +/- 2.3 mm and 0.90 +/- 0.08 circ/sec during digitalis therapy. Resting left ventricular ejection time and pre-ejection period were prolonged by digoxin withdrawal. Maximal exercise capacity was unchanged. No clinical exacerbation of heart failure attributable to digitalis withdrawal occurred over a follow-up period averaging 19 months. The results indicate that long-term digoxin therapy has only a minor effect on cardiac performance that is without apparent clinical importance in a representative population of ambulatory patients treated with cardiac glycosides.

Topics: Adult; Aged; Blood Pressure; Cardiac Volume; Clinical Trials as Topic; Digoxin; Double-Blind Method; Echocardiography; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Stroke Volume

Topics: Adolescent; Adult; Coronary Disease; Digoxin; Female; Heart Aneurysm; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Nitroglycerin; Propranolol; Radionuclide Imaging; Technetium; Theophylline; Verapamil

The efficacy of treatment with spironolactone for congestive heart failure secondary to congenital heart disease was studied in 21 infants under 1 year of age. All received digoxin and chlorothiazide. In addition, group A (n = 10) was given supplements of potassium and group B (n = 11) received spironolactone. Daily clinical observations of vital signs, weight, hepatomegaly, and vomiting were recorded. Paired t test analysis showed significant reduction in liver size and weight (P less than 0.01) and respiratory rate (P less than 0.05) in group B, and less significant decreases in group A. The incidence of vomiting was slightly lower in group B. We conclude that the addition of spironolactone hastens and enhances the response to standard treatment with digoxin and chlorothiazide in infants with congestive heart failure.

Topics: Chlorothiazide; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Female; Heart Defects, Congenital; Heart Failure; Humans; Infant; Male; Potassium; Random Allocation; Spironolactone

To clarify the controversy regarding the benefits of long-term oral digoxin in the treatment of heart failure, we evaluated hemodynamics at rest and during exercise in nine patients in sinus rhythm with symptomatic heart failure. Patients were studied during long-term digoxin therapy, after withdrawal of the drug, and six hours after readministration. Upon withdrawal of digoxin, pulmonary capillary-wedge pressure increased from 21 +/- 8 to 29 +/- 10 mm Hg, and cardiac index decreased from 2.4 +/- 0.7 to 2.1 +/- 0.6 liters per minute per square meter of body-surface area, suggesting a deterioration in left ventricular function. In addition, heart rate tended to increase and stroke-work index, stroke-volume index, and radioangiographic ejection fraction decreased. Acute readministration restored the hemodynamic values to those observed during long-term digoxin therapy. The improvement in hemodynamics during long-term digoxin administration was also observed during exercise. This improvement demonstrated the value of long-term oral digoxin therapy in congestive heart failure.

Topics: Administration, Oral; Adult; Aged; Chronic Disease; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Long-Term Care; Male; Middle Aged; Stroke Volume

The efficacy on congestive heart failure of metildigoxin (beta-methyldigoxin, MD), a derivative of digoxin (DX), which had a good absorption rate from digestive tract, was examined in a double blind study using a gorup comparison method. After achieving digitalization with oral MD or intravenous deslanoside in the non-blind manner, maintenance treatment was initiated and the effects of orally administered MD and DX were compared. MD was administered in 44 cases, DX in 42. The usefulness of the drug was evaluated after 2 weeks, taking into account the condition of the patient and the case of administration. No significant difference was observed between the usefulness of MD and that of DX. The use of digitalis differs according to the preparation involved. In the double blind study on MD and DX, the way in which digitalis was used may have inclined towards the way in which DX, which is more familiar to us, is used. Therefore, even if MD were superior to DX in usefulness, it would be difficult to obtain a result which proved this. Taking these points into consideration, it is concluded that MD is practically useful in clinical medicine.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Digitalis Glycosides; Digoxin; Double-Blind Method; Female; Heart Failure; Hemodynamics; Humans; Intestinal Absorption; Male; Medigoxin; Middle Aged

Topics: Clinical Trials as Topic; Coronary Disease; Digoxin; Double-Blind Method; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Penbutolol; Propanolamines; Propranolol

Topics: Acetyldigoxins; Aged; Clinical Trials as Topic; Digoxin; Dihydroergotoxine; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Neurocognitive Disorders; Random Allocation

The serum digoxin levels of 23 patients were measured by radio immune assay. The patients were divided into 2 groups receiving either 0,5 mg digoxin b.i.d. or 0,25 mg digoxin b.i.d. orally after having been changed from a maintenance dose of 0,2 mg beta-methyl-digoxin b.i.d. The applicated digoxin was the preparation Lenoxin. The question was whether typical or reduced maintenance doses of digoxin in the new preparation reached therapeutic digoxin serum levels in the absence of renal insufficiency.. 1. The maintenance dose of 0,2 mg beta-methyl-digoxin produced stable serum digoxin levels within non-toxic range in all patients; 2. the dosage of 0,5 mg digoxin (group 1) induced accumulation to toxic levels (2,14 mg/ml). A change to 0,25 mg digoxin led to therapeutical serum levels; 3. when using the dosage of 0,25 mg digoxin from the onset of the test (group 2) accumulation was avoided and normal serum digoxin levels were observed during the test period.

Topics: Administration, Oral; Aged; Digoxin; Female; Heart Failure; Humans; Male; Medigoxin; Middle Aged

Discontinuation of digoxin in 56 patients with sinus rhythm who had been taking it for a long time did not produce clinical deterioration in 33 of 34 patients whose pre-withdrawal steady-state plasma-digoxin concentration was less than 0.8 ng/ml; fast atrial fibrillation developed in the other patient. 22 patients had plasma-digoxin levels between 0.8 and 2.0 ng/ml before withdrawal--of these, 7 deteriorated without digoxin (5 had atrial fibrillation, which was associated with congestive heart-failure, measurement of the pre-injection period/left-ventricular ejection time (P.E.P./L.V.E.T.) ratio suggested that digoxin did exert a sustained positive inotropic effect. Thus, successful discontinuation of digoxin was possible in 86% of the total group and was more likely when the plasma-digoxin concentration was below 0.8 ng/ml. Unexpected atrial fibrillation was the commonest development inthe 8 patients in whom digoxin withdrawal was unsuccessful.

Topics: Adult; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Stimulation, Chemical; Substance Withdrawal Syndrome; Tachycardia

In a controlled double-blind trial in 80 patients with cerebrovascular and cardiac insufficiency the differentiated effect of a combination therapy with cardiac glycosides and Hydergin were studied both with regard to parameters of cerebral organic and cardiac performance. Two randomized collectives of patients with an average age of 63 years were compared with each other for this purpose. They received either acetyldigoxin (0.4 mg/day) alone or in combination with Hydergin (3 mg/day). Duration of treatment was 8 weeks altogether. The single treatment with the cardiac glycoside alone does not lead to a satisfactory improvement in the symptoms of cerebral attacks. The results presented of this study support the necessity in these patients of an internist basic therapy in combination with a preparation like Hydergin acting favorably on cerebral metabolism.

Topics: Acetyldigoxins; Cerebrovascular Disorders; Digoxin; Dihydroergotoxine; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged

The absorption of digoxin has been investigated in 8 patients before and after successful treatment of severe right heart failure. 3H-digoxin 0.1 mg as a solution, and un-labelled digoxin 0.25 mg as a tablet, were given to fasted patients. Blood samples were taken at various time intervals up to 120 hours and urine was collected over the same period. The concentrations of labelled digoxin in plasma and urine were measured in a liquid scintillation counter, unlabelled digoxin was estimated by radioimmunoassay, and various pharmacokinetic parameters were calculated. There was no significant difference in the plasma concentration curves in severe right heart failure and after its successful treatment, nor did any of the calculated pharmacokinetic parameters change significantly. Therefore, inhibition of the absorption of digoxin appears unlikely. In an additional study to estimate absolute bioavailability two different groups of patients in severe right heart failure were given 3H-digoxin 0.1 mg or unlabelled digoxin 0.25 mg i.v. and the pharmacokinetic parameters were compared with those from the previous study. The bioavailability of the 3H-digoxin solution and of the digoxin tablet were in the same range as values previously published for healthy volunteers, and patients both with and without cardiac failure.

Topics: Biological Availability; Clinical Trials as Topic; Digoxin; Half-Life; Heart Failure; Humans; Intestinal Absorption; Kinetics; Time Factors

Topics: Adolescent; Adult; Blood Pressure; Cardiac Glycosides; Coronary Disease; Digoxin; Female; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Placebos; Pulmonary Artery; Time Factors

A study was undertaken to (1) develop an individualized audiovisual patient education program about digoxin and congestive heart failure, and (2) ascertain whether a patient who received the education program from a pharmacist would demonstrate a significantly greater gain in knowledge about digoxin and congestive heart failure than a traditionally-educated patient. The education program consisted of a slide/tape audiovisual presentation which was reinforced by the pharmacist presenting the program at the patient's bedside. Each patient was randomly assigned to either the study group or control group of patients. A 27-question pretest was given to both the control and study groups of patients to determine their baseline knowledge of congestive heart failure and digoxin therapy. Only the study group of patients received the individualized education program. All patients were then given a posttest to determine the degree of learning that took place during their hospital stay. The patients who received the individualized digoxin education program from a pharmacist demonstrated a significantly greater gain in knowledge about digoxin and congestive heart failure than traditionally-educated patients. It is suggested that hospital pharmacists should deliver an individualized education program to patients taking digoxin during their hospital stay.

Topics: Audiovisual Aids; Digoxin; Educational Measurement; Evaluation Studies as Topic; Heart Failure; Humans; Patient Education as Topic; Pharmacists

Topics: Biological Availability; Clinical Trials as Topic; Digoxin; Drug Combinations; Heart Failure; Humans; Verapamil

The need for maintenance digoxin treatment was assessed in a double-blind, variable-dose, crossover comparison with placebo. Forty-six outpatients who had been prescribed the drug for heart failure were studied; 33 were in sinus rhythm and the remainder in atrial fibrillation. Mean serum digoxin concentrations in those with sinus rhythm averaged 1-33 nmol/l, but a lower concentration, averaging 0-97 nmol/l, was accepted in those with atrial fibrillation as six of them developed bradycardia. Sixteen of the 46 patients deteriorated on placebo, and eight completely recovered when digoxin was reintroduced; in the remainder additional diuretics were required temporarily. Spirometric values deteriorated on changing to placebo whether or not the patient showed clinical evidence of recurrence of heart failure. In a separate study of nine patients who showed no clinical evidence of deterioration on placebo, reintroduction of digoxin caused a shortening of left ventricular ejection time, which persisted for at least a month. This suggests that the inotropic response to digoxin is sustained during maintenance treatment.

Topics: Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Placebos; Respiration

Topics: Clinical Trials as Topic; Digoxin; Heart Failure; Humans

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Digoxin; Dihydroergotoxine; Drug Combinations; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Pyridines; Pyrithioxin

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Digoxin; Drug Combinations; Female; Heart Failure; Humans; Male; Middle Aged; Nicotinic Acids

Segontin-Digoxin and digoxin were tested in a cross-over double blind trial in 30 patients with coronary heart disease and concomitant organic insufficiency in a cardiological specialist practice. As far as the coronary symptoms were concerned, treatment with Segontin-Digoxin was clearly superior to digoxin therapy alone. With regard to the elimination or improvement of signs of myocardial insufficiency, no difference could be established between the two preparations. A distinct lowering of heart rate and blood pressure, especially in hypertensives, was observed with Segontin-Digoxin therapy compared with digoxin alone.

Topics: Adult; Aged; Blood Pressure; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Combinations; Drug Evaluation; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Placebos; Prenylamine; Tranquilizing Agents

Patients with acute myocardial infarction were allocated to two groups according to a double blind-system of radomization. The patients (n = 18) in one of the groups received digoxin intravenously as an injection of 0.01 mg. per kilogram of body weight during 10 minutes. The patients in the other group (n = 15) received saline and served as controls. A continuous ECG record was obtained from each patient during 1 hour preceding the administration of digoxin or saline and was continued for 3 hours following the injection. No antiarrhythmic treatment was given during the time of the study. Based on the continuous ECG, calculations were made of the relative incidence of patients with different types of ventricular tachyarrhythmias during the period of observation as well as the percentage of arrhythmia-containing 1 minute intervals observed during this period. There was no statistical difference between the incidence of ventricular tachyarrhythmias in the two groups in the 1 hour period preceding drug injection. The administration of digoxin and saline did not change the incidence of ventricular tachyarrhythmias and there was also no statistically significant difference between the two groups as regards the incidence of patients showing different types of ventricular tachyarrhythmias during the 3 hour period following drug administration, Considering the 1-minute intervals, those without any ventricular premature contractions were less in the digoxin group (92 per cent) than in the saline group (88 per cent; p less than 0.001). Serum levels of digoxin at the end of the observation period were well above what is considered the minimum therapeutic level and in three patients the level approached or reached the toxic range. In these three patients there was still no increased incidence of ventricular tachyarrhythmias. It is concluded that patients with acute myocardial infarction complicated by incipient left ventricular failure do not show an increased sensitivity to an ordinary dose of digoxin as measured by the occurrence of ventricular tachyarrhythmia.

Topics: Acute Disease; Adult; Aged; Blood Pressure; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Infusions, Parenteral; Male; Middle Aged; Myocardial Infarction; Tachycardia

Topics: Azepines; Clinical Trials as Topic; Coronary Disease; Digoxin; Dilazep; Drug Combinations; Heart Failure; Humans

The task of this study was to examine the feasibility of applying echocardiography in determining alterations of left ventricular performance during administration of vasoactive drugs. Patients suffering from congestive heart failure were treated with Digitalis, other patients with normal hearts were subjected to infusion therapy of Isoproterenol, Propranolol, Verapamil and Calcium chloride. A new concept for interpretation of function curves relating the velocity of circumferential fiber shortening (VCF) and time was introduced to establish the inotropic, bathmotropic and chronotropic effects of vasoactive drugs to the myocardium. It can be concluded that echocardiography is a feasible tool in determining changes of left ventricular dynamics during administration of vasoactive drugs, in indicating the individual dosage of a vasoactive drug in each patient and the follow-up the course of the therapeutic success.

Topics: Digoxin; Echocardiography; Heart; Heart Failure; Heart Ventricles; Humans; Isoproterenol; Propranolol; Proscillaridin; Verapamil

The additive natriuretic effect of a single dose of bendroflumethiazide, 5 mg., has been studied in patients with advanced congestive heart failure in long-term treatment with bumetanide, 4 mg., daily. Three permutation trial tests were performed including six patients each. In the first trial, the response to supplementary bendroflumethiazide, 5 mg., was definitely superior to that of additional bumetanide, 4 mg., in terms of renal output of sodium, chloride, potassium, water, and osmolar clearance. In the second trial, a similar pattern was found in patients receiving a combination of bumetanide, 4 mg., and spironolactone, 100 mg., daily. The third trial compared the effects of bendroflumethiazide, 5 mg., plus bumetanide, 4 mg.; of bendroflumethiazide, 5 mg.; and of bumetanide, 4 mg. In terms of natriuresis and chloruresis, the response to the combination of two drugs was significantly larger than the sum of the effects of other treatments. It is concluded that the combined effects of the drugs represent a supra-additive effect addition for sodium and chloride. A tentative explanation of the mechanism of interaction in terms of inhibition of renal tubular supplementary spironolactone, involve a tendency to development of hypokalemia, hypochloremia, and alkalosis, it is recommended that supplementary use of bendroflumethiazide in this setting is combined with the administration of potassium chloride or potassium-saving diuretics.

Topics: Adult; Bendroflumethiazide; Benzoates; Butylamines; Chlorides; Clinical Trials as Topic; Coronary Disease; Creatine; Digoxin; Diuretics; Drug Synergism; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Natriuresis; Nephrons; Placebos; Potassium; Potassium Chloride; Sodium; Spironolactone; Sulfonamides

Clinical open trials of beta-methyldigoxin were carried out in 15 institutions in order to examine the effect, usefulness and ease of its oral administration. In the case of oral digitalization with 0.2 mg, 3 times daily, an effect was obtained in all of 13 cases of congestive heart failure accompanied by atrial fibrillation or flutter. The average time and dose required for digitalization were about 50 hours and 1.27 mg respectively. In 9 of the 13 cases, the effect was achieved within 48 hours. The average maintenance does of beta-methyldigoxin in 102 cases of congestive heart failure with atrial fibrillation was 0.177 mg per day. About 75% of the cases were maintained with 0.15 to 0.2 mg. This range of dose of beta-methyldigoxin was much smaller than that of digoxin in our series. This can be ascribed to a higher absorption rate of beta-methyldigoxin from the digestive tract. Studies on the cases in which patients previously treated with other glycosides were switched over to beta-methyldigoxin revealed that 1 mg of beta-methyldigoxin is equivalent to 1.8 mg of digoxin or to 0.59 mg of digitoxin. The usefulness and ease of beta-methyldigoxin in maintenance was evaluated as being somewhat superior to other cardiac glycosides, according to the global judgement of the physicians. The observed side effects were similar to those of other glycosides in frequency and character.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Lanatosides; Male; Middle Aged; Proscillaridin

We have measured the plasma concentrations in sick neonates and infants being administered digoxin by a safer regimen. In the presence of normal renal function the plasma concentrations appear to be satisfactory.

Topics: Administration, Oral; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Injections, Intramuscular

Topics: Clinical Trials as Topic; Digoxin; Drug Evaluation; Female; Heart Failure; Humans; Lanatosides; Male

The bioavalability of digoxin tablets and solution has been studied during maintenance therapy in a cross over study. Each preparation was given over a period of at least 7 days to patients with compensated congestive heart failure. Urine concentrations and plasma levels were analysed for digitoxin. There was no significant difference between the two preparations. Determination of steady state serum concentrations and urinary excretion during maintenance therapy as an index of bioavalability are more cumbersome than a single dose study. From a pharmacokinetic point of view however, analyses of steady-state conditions are preferable to a single dose study. In addition, steady state of drug input and output resembles the usual digitalis therapy.

Topics: Administration, Oral; Adult; Aged; Biological Availability; Biopharmaceutics; Creatinine; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Solutions; Tablets; Urea

Haemodynamic changes after intravenous administration of 0.4 mg beta-methyldigoxin or 0.4 mg digoxin daily were measured on the first to fourth day in 42 patients in heart failure after onset of transmural myocardial infarction. Regular reduction in filling pressure and increased stroke volume while arterial blood pressure remained unaltered pointed to improved contractility. Digitalization in the first few days after infarction achieved sustained tendency towards improved haemodynamics. It is concluded that early digitalization is indicated in patients with acute myocardial infarction if there are signs of heart failure.

Topics: Adult; Aged; Blood Pressure; Cardiac Output; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Time Factors

Topics: Adult; Benzoates; Cardiovascular System; Clinical Trials as Topic; Digoxin; Drug Combinations; Drug Evaluation; Heart Failure; Humans; Male; Middle Aged; Morpholines; Tranquilizing Agents; Verapamil

Topics: Administration, Oral; Adult; Aged; Biological Availability; Blood Urea Nitrogen; Clinical Trials as Topic; Creatinine; Digoxin; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Iodine Radioisotopes; Male; Middle Aged; Radioimmunoassay; Solubility; Tablets; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Creatinine; Digitalis; Digoxin; Dyspnea; Edema; Female; Heart Failure; Humans; Male; Middle Aged; New York; Phytotherapy; Placebos; Plants, Medicinal; Plants, Toxic; Respiratory Insufficiency; Skilled Nursing Facilities; Time Factors

Topics: Adult; Aged; Clinical Trials as Topic; Digoxin; Evaluation Studies as Topic; Heart Failure; Hemodynamics; Humans; Middle Aged

Topics: Adult; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Coronary Disease; Digoxin; Evaluation Studies as Topic; Heart Diseases; Heart Failure; Humans; Middle Aged; Time Factors

Topics: Adult; Aged; Clinical Trials as Topic; Digoxin; Drug Combinations; Drug Evaluation; Feeding and Eating Disorders; Female; Headache; Heart Failure; Humans; Male; Middle Aged; Nausea; Vertigo; Vision Disorders; Vomiting

A comparative study was performed of the absorption, the plasma level at equilibrium, and the urinary excretion of digoxin using two types of Lanoxin tablets, those produced before and after the 1972 alteration of the tablet manufacture.After a single dose the absorption rate of the new tablets was about twice as great as the old, both in young subjects and in the elderly patients. There were no significant differences in the plasma levels of digoxin for the two tablets 15 hours after the last administration in patients on an equal maintenance dose. The urinary excretion of digoxin increased about 40% when the "old" Lanoxin was replaced by the "new." In elderly patients a daily dose of 0.125 mg twice daily of the new tablets should be sufficient to reach the therapeutic range. Young people need a higher dosage. If the kidney function is reduced by as much as 50% the dose should be reduced.

Topics: Adult; Age Factors; Aged; Digoxin; Drug Compounding; Heart Failure; Humans; Intestinal Absorption; Middle Aged; Tablets; Time Factors

Topics: Adult; Aged; Body Height; Body Weight; Computers; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Kidney Function Tests; Male; Middle Aged; Prospective Studies

Topics: Administration, Oral; Adult; Aged; Clinical Trials as Topic; Digoxin; Drug Tolerance; Female; Heart Failure; Humans; Intestinal Absorption; Male; Middle Aged

Topics: Aged; Central Venous Pressure; Digoxin; Dye Dilution Technique; Electrocardiography; Heart Failure; Humans; Injections, Intravenous; Middle Aged

Topics: Administration, Oral; Adult; Aged; Digoxin; Female; Heart Failure; Humans; Injections, Intravenous; Intestinal Absorption; Male; Middle Aged; Time Factors

Topics: Administration, Oral; Blood Pressure; Cardiac Glycosides; Cardiac Volume; Chromium Isotopes; Digitalis Glycosides; Digoxin; Female; Heart; Heart Failure; Heart Function Tests; Heart Rate; Hemodynamics; Humans; Hypertension; Lanatosides; Male; Middle Aged; Strophanthins; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Heart Failure; Humans; Methods; Phenytoin

Topics: Digitoxin; Digoxin; Female; Heart Failure; Humans; Injections, Intravenous; Intestinal Absorption

Topics: Digoxin; Heart Failure; Humans; Kinetics; Lanatosides; Tritium

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Berlin; Digoxin; Heart Block; Heart Failure; Humans; Myocardial Infarction; Myocardium; Oxygen Consumption; Tachycardia; Ventricular Fibrillation

Topics: Clinical Trials as Topic; Coronary Disease; Digitoxin; Digoxin; Electrocardiography; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Strophanthins

Topics: Adult; Aged; Animals; Cats; Coronary Disease; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Rats

Topics: Adult; Aged; Clinical Trials as Topic; Digitalis Glycosides; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

Despite being the oldest therapy for heart failure, the use of digoxin is still controversial due to the narrow margin of safety. In Indonesia, digoxin is still considered one of the treatments for heart failure. However, analysis of intoxication has never been reported. This study aims to analyze the occurrence of digoxin intoxication, rate of rehospitalization and one-year survival in heart failure patients under digoxin treatment.. A cross section-observational study was conducted at Harapan Kita National Cardiovascular Centre from January 2017 to December 2018 on heart failure patients who received digoxin therapy and had data on serum digoxin level. Intoxication was defined as the presence of specific ECG alteration(s), at least one extra-cardiac symptom(s) and further classified as definite (serum digoxin >2 ng/mL), probable (serum digoxin 0.91-1.99 ng/mL), or possible (serum digoxin 0.5-0.9 ng/mL). Risk factors of intoxication were analyzed by Chi-square test, and one-year survival was analyzed with Kaplan Meyer method.. 54 of 195 patients (27.69%) were classified as having intoxication, consisting of 32 (16.41%) definite, 19 (9.74%) probable, and 3 (1.54%) possible. Renal insufficiency was revealed as a significant influencing factor of digoxin intoxication with RR 2.48 (CI 1.13-5.464, p=0.016). Overall one-year survival of patients receiving digoxin was 259 days in the intoxication group and 307 days in the non-intoxication group. One-year rehospitalization was 11.8% in patients who received digoxin and 29.2% in those without digoxin (p=0.085).. The proportion of digoxin intoxication in heart failure patients was 27.69%. Renal insufficiency was revealed as a significant influencing factor of intoxication. There was a tendency of reduced hospitalization in those who received digoxin.

Topics: Digoxin; Disease Progression; Heart Failure; Humans; Indonesia; Patient Readmission; Renal Insufficiency

The cardiac glycoside (CG) digoxin is a generic drug approved for the treatment of heart failure and supraventricular arrhythmias. Over the past few decades, substantial strides have been made toward repurposing digoxin to treat various noncardiac diseases. Here, we evaluate recent insights into basic and clinical work related to noncardiac use of digoxin.

Topics: Cardiac Glycosides; Digoxin; Heart Failure; Humans; Ouabain; Sodium-Potassium-Exchanging ATPase

Background Digoxin acutely increases cardiac output in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, the effects of chronic digoxin use in PAH are unclear. Methods and Results Data from the Minnesota Pulmonary Hypertension Repository were used. The primary analysis used likelihood of digoxin prescription. The primary end point was a composite of all-cause mortality or heart failure (HF) hospitalization. Secondary end points included all-cause mortality, HF hospitalization, and transplant-free survival. Multivariable Cox proportional hazards analyses determined the hazard ratios (HR) and 95% CIs for the primary and secondary end points. Among 205 patients with PAH in the repository, 32.7% (n=67) were on digoxin. Digoxin was more often prescribed to patients with severe PAH and right ventricular failure. After propensity score-matching, 49 patients were digoxin users, and 70 patients were nonusers; of these 31 (63.3%) in the digoxin group and 41 (58.6%) in nondigoxin group met the primary end point during a median follow-up time of 2.1 (0.6-5.0) years. Digoxin users had a higher combined all-cause mortality or HF hospitalization (HR, 1.82 [95% CI, 1.11-2.99]), all-cause mortality (HR, 1.92 [95% CI, 1.06-3.49]), HF hospitalization (HR, 1.89 [95% CI, 1.07-3.35]), and worse transplant-free survival (HR, 2.00 [95% CI, 1.12-3.58]) even after adjusting for patient characteristics and severity of PAH and right ventricular failure. Conclusions In this retrospective, nonrandomized cohort, digoxin treatment was associated with greater all-cause mortality and HF hospitalization, even after multivariate correction. Future randomized controlled trials should assess the safety and efficacy of chronic digoxin use in PAH.

Topics: Digoxin; Familial Primary Pulmonary Hypertension; Heart Failure; Hospitalization; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Retrospective Studies; Treatment Outcome

Digoxin toxicity (plasma digoxin concentration ≥0.9 ng/mL) is associated with worsening heart failure (HF). Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions. The present study aimed to construct a flowchart using DT analysis that can be used by medical staff to predict digoxin toxicity. We conducted a multicenter retrospective study involving 333 adult patients with HF who received oral digoxin treatment. In this study, we employed a chi-squared automatic interaction detection algorithm to construct DT models. The dependent variable was set as the plasma digoxin concentration (≥ 0.9 ng/mL) in the trough during the steady state, and factors with p < 0.2 in the univariate analysis were set as the explanatory variables. Multivariate logistic regression analysis was conducted to validate the DT model. The accuracy and misclassification rates of the model were evaluated. In the DT analysis, patients with creatinine clearance <32 mL/min, daily digoxin dose ≥1.6 µg/kg, and left ventricular ejection fraction ≥50% showed a high incidence of digoxin toxicity (91.8%; 45/49). Multivariate logistic regression analysis revealed that creatinine clearance <32 mL/min and daily digoxin dose ≥1.6 µg/kg were independent risk factors. The accuracy and misclassification rates of the DT model were 88.2 and 46.2 ± 2.7%, respectively. Although the flowchart created in this study needs further validation, it is straightforward and potentially useful for medical staff in determining the initial dose of digoxin in patients with HF.

Topics: Adult; Cardiotonic Agents; Creatinine; Digoxin; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Humans; Machine Learning; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Common chronic heart failure (CHF) is characterized by impaired ventricular filling and/or ejection function, which leads to insatiable cardiac output and increased incidence. The decline in cardiac systolic function is a key factor in the pathogenesis of CHF. Systolic function is simply the filling of oxygenated blood in the left ventricle, followed by the blood being pumped throughout the body during a heartbeat. A weak heart and the inability of the left ventricle to contract appropriately as the heart beats indicate poor systolic function. Many traditional herbs have been suggested to strengthen the systolic function of the heart in patients. However, stable and efficient experimental methods for screening compounds that enhance myocardial contractility are still lacking in the process of ethnic medicine research. Here, taking digoxin as an example, a systematic and standardized protocol is provided for screening compounds that enhance myocardial contractility by using isolated right atria from guinea pigs. The results showed that digoxin could markedly enhance the contractility of the right atrium. This systematic and standardized protocol is intended to serve as a methodological reference for screening the active ingredients of ethnic medicines in the treatment of CHF.

Topics: Animals; Digoxin; Guinea Pigs; Heart Atria; Heart Failure; Heart Ventricles; Systole

Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have been conflicting. This study assessed the association between digoxin use and all-cause mortality using comprehensive health data of patients treated for acute coronary syndrome (ACS). This was a retrospective analysis of 8,388 consecutive ACS patients treated in Tays Heart Hospital between 2007 and 2017, with a follow-up until the end of 2018. The adjusted Cox regression model was used to analyze the association between digoxin treatment and all-cause mortality with and without the inverse probability of treatment weighting (IPTW) method. IPTW was applied to estimate the residual confounding by the treatment selection. Clinical phenotype data were collected from various sources, including a prospectively updated online database maintained by physicians. The median follow-up time was 6.0 years (interquartile range 3.5 to 9.0 years). During the follow-up, 30.8% (n = 2,580) of the patients died. Altogether, 4.0% (n = 333) of the patients were treated with digoxin during hospitalization. In the Cox regression model, digoxin associated with increased mortality (age- and sex-adjusted hazard ratio [HR] 1.76 [1.51 to 2.05], p <0.001 and in the full risk factor-adjusted HR 1.23 [1.04 to 1.45], p = 0.016). The IPTW Cox analysis average treatment effect HR was 1.71 (1.12 to 2.62, p = 0.013), standardized average treatment effect HR was 1.35 (0.96 to 1.90, p = 0.082), and treatment effect among the treated HR was 1.32 (1.09 to 1.59, p = 0.004). In conclusion, digoxin treatment during ACS associates with increased mortality, despite adjusting for other risk factors and after accounting for factors explaining the residual confounding by selection bias.

Topics: Acute Coronary Syndrome; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans; Retrospective Studies

This study aimed to investigate the effect of digoxin on mortality and rehospitalization in heart failure with reduced ejection fraction (HFrEF) patients. Heart failure is a clinical syndrome that requires frequent rehospitalization and has a high mortality. This study aimed to investigate the effect of digoxin on mortality and rehospitalization in patients with heart failure with reduced ejection fraction.. The study included 326 patients with HFrEF that were hospitalized for decompensation between September 2014 and January 2016. The patients were divided into two groups: digoxin users and a control group. The study's endpoints were cardiovascular death and rehospitalization after 24-month long-term follow-ups.. Rehospitalization was lower in patients taking digoxin (25% vs. 47%, p = 0.001). The mean age of patients taking digoxin (n: 78) was 63.7 ± 12.4 years, among which 64% were males. The mean age of the control group was 65.4 ± 11.8 years, among which 74% were males. However, there was no difference in mortality between the two groups (34% vs. 45%, p = 0.10). While Kaplan-Meier curves revealed no significant differences between mortality rates in the groups (log-rank p = 0.508), a statistical difference was found between the groups in rehospitalization rates (log-rank p =  0.013). A multiple linear regression analysis revealed that smoking (HR: 1.97, CI: 1.24-3.11, p = 0.004), systolic blood pressure (HR: 0.983, CI: 0.974-0.992, p < 0.001), atrial fibrillation (HR: 2.09, CI: 1.17-3.72, p = 0.012), C-reactive protein (CRP) (HR: 1.009, CI: 1.003-1.015, p = 0.004), beta-blockers (HR: 0.891, CI: 0.799-0.972, p = 0.009), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (HR: 0.778, CI: 0.641-0.956, p < 0.001), mineralocorticoid receptor antagonists (HR: 0.41, CI:0.26-0.65, p < 0.001), and digoxin use (HR: 0.59, CI: 0.43-0.80, p = 0.001) are independent predictors of rehospitalization in patients with HFrEF.. Our results show that digoxin use does not affect mortality in HFrEF patients. However, rehospitalization decreased in patients taking digoxin in HFrEF.

Topics: Aged; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Prognosis; Stroke Volume

To analyze the factors related to inadequate chronic treatment with digoxin and whether the inadequacy of treatment has an impact on short-term outcome.. Patients diagnosed with AHF who were in chronic treatment with digoxin, were selected. Digoxin treatment was classified as adequate or inadequate. We investigated factors associated to inadequacy and whether such inadequacy was associated with in-hospital and 30-day mortality, prolonged hospital stay (>7 days) and combined adverse event (re-consultation to the ED or hospitalization for AHF or death from any cause) during the 30 days after discharge.. We analyzed 2,366 patients on chronic digoxin treatment (median age = 83 years, women = 61%), which was considered adequate in 1,373 cases (58.0%) and inadequate in 993 (42.0%). The inadequacy was associated with older age, less comorbidity, less treatment with beta-blockers and renin-angiotensin inhibitors, better ventricular function, and worse Barthel index. In-hospital and 30-day mortality was higher in patients with inadequate digoxin treatment (9.9% versus 7.6%, p = 0.05; and 12.6% versus 9.1%, p < 0.001, respectively). No differences were recorded in prolonged stay (35.7% versus 33.8%) or post-discharge adverse events (32.9% versus 31.8%). In the model adjusted for baseline and decompensation episode differences, inadequate treatment with digoxin was not significantly associated with any outcome, with an odds ratio of 1.31 (95%CI = 0.85-2.03) for in-hospital mortality; 1.29 (0.74-2.25) for 30-day mortality; 1.07 (0.82-1.40) for prolonged stay; and 0.88 (0.65-1.19) for post-discharge adverse event.. There is a profile of patients with AHF who inadequately receive digoxin, although this inadequateness for chronic digitalis treatment was not associated with short-term adverse outcomes.

Topics: Acute Disease; Aftercare; Aged, 80 and over; Digoxin; Emergency Service, Hospital; Female; Heart Failure; Humans; Patient Discharge; Prognosis

Prognosis of fetuses with hydrops and tachyarrhythmia has been portrayed as poor in most published reports. This might lead to biased counselling, unnecessary caesarean section, preterm delivery, and even termination of pregnancy.. To evaluate contemporary fetal and postnatal outcomes of hydropic fetuses with fetal tachyarrhythmia when it is treated effectively and monitored systematically.. This is a retrospective review of a single centre experience at the University Hospital of Wales over a 20-year period. All fetuses received high doses of flecainide and digoxin combination treatment. Tachycardia response rate, time to arrhythmia and hydrops resolution, fetal and postnatal morbidity, and mortality rates were analysed.. Twenty fetuses were diagnosed with hydrops fetalis and received treatment. The mechanism of fetal tachyarrhythmia was supraventricular tachycardia in thirteen and atrial flutter in eight cases. Among the 20 fetuses treated, the overall tachycardia response rate was 90% (18/20) with the restoration of sinus rhythm in 85% (17/20) of the cases. The median time to restore sinus rhythm or to rate control of the arrhythmia was 1.5 days (range 12 hours to 13 days). Hydrops resolved in 17 of the 20 fetuses, with a median time of 12 days (range 3-21 days). Four fetuses went into spontaneous preterm birth and one fetus was delivered early due to worsening hydrops. No significant neurological morbidity was observed in surviving neonates and infants on clinical examination. There was one postnatal death due to respiratory complications of prematurity in the non-responsive supraventricular tachycardia case.. High-dose flecainide and digoxin combination offers effective treatment strategy in fetuses with hydrops and tachyarrhythmia with favourable outcomes. This study may guide more realistic counselling for pregnancies complicated by tachyarrhythmia and hydrops.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cesarean Section; Digoxin; Female; Fetal Diseases; Flecainide; Heart Failure; Humans; Hydrops Fetalis; Infant, Newborn; Pregnancy; Premature Birth; Retrospective Studies; Tachycardia; Tachycardia, Supraventricular

In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by doxorubicin. Adult rats were distributed into four experimental groups. Each group was challenged with a single intraperitoneal application of doxorubicin at a dose of 12 mg/kg. Then, they were treated with saline solution and the glycosides oleandrin, ouabain, and digoxin at a dose of 50 µg/kg, for 7 days. They underwent echocardiography, electrocardiography, hematologic, biochemical tests, and microscopic evaluation of the heart. All animals presented congestive heart failure, which was verified by a reduction in the ejection fraction. Oleandrin and digoxin were able to significantly reduce (p < 0.05) the eccentric remodeling caused by doxorubicin. Oleandrin and digoxin were significantly lower (p < 0.05) than the control group in maintaining systolic volume and left ventricular volume in diastole. Other parameters evaluated did not show significant statistical differences. All animals showed an increase in erythrocyte count, and an increase in the duration of the QRS complex on the ECG and myocardial necrosis at the histopathological analysis. It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin.

Topics: Animals; Cardenolides; Cardiac Glycosides; Cardiotonic Agents; Cardiotoxicity; Digoxin; Disease Models, Animal; Doxorubicin; Heart Failure; Ouabain; Rats, Wistar; Recovery of Function; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling

Digoxin (DG) use in patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm remains controversial. We aimed to assess the prognostic effect of DG in patients in sinus rhythm submitted to cardiac resynchronization therapy (CRT). Retrospective study including 297 consecutive patients in sinus rhythm, with advanced HFrEF submitted to CRT. Patients were divided into 2 groups: with DG and without DG (NDG). During a mean follow-up of 4.9 ± 3.4 years, we evaluated the effect of DG on the composite end point defined as cardiovascular hospitalization, progression to heart transplantation, and all-cause mortality. Previous to CRT, 104 patients (35%) chronically underwent DG and 193 patients (65%) underwent NDG treatment. The 2 groups did not differ significantly regarding HF functional class, HF etiology, QRS, and baseline left ventricular ejection fraction. The proportion of responders to CRT was similar in both groups (54% in DG vs. 56% in NDG; P = 0.78). During the long-term follow-up period, the primary end point occurred in a higher proportion in DG patients (67 vs. 48%; P = 0.002). After adjustment for potential confounders, DG use remained as an independent predictor of the composite end point of CV hospitalization, heart transplantation, and all-cause mortality [hazards ratio = 1.58; confidence interval, 95 (1.01-2.46); P = 0.045]. In conclusion, in patients in sinus rhythm with HFrEF submitted to CRT, DG use was associated with CV hospitalization, progression to heart transplant, and all-cause mortality.

Topics: Aged; Cardiac Resynchronization Therapy; Cardiotonic Agents; Cause of Death; Digoxin; Disease Progression; Female; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Patient Admission; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Heart Rate; Humans

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Heart Rate; Humans

Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF.. Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable.. The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Topics: Atrial Fibrillation; Digoxin; Heart Failure; Humans; Registries; Stroke Volume; Sweden

Prior studies have reported conflicting results on digoxin's impact on clinical outcomes and quality of life, and there are limited data from Asia. The aim of this study is to evaluate the use of digoxin and its impact on clinical outcomes and quality of life in a high-risk cohort of elderly Chinese atrial fibrillation (AF) patients.. The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry is a prospective, multicentre nationwide study conducted from October 2014 to December 2018. Endpoints of interest were the composite outcome of all-cause death/any thromboembolism (TE), all-cause death, cardiovascular death, sudden cardiac death, and TE events, as well as the quality of life. The eligible cohort for this analysis included 6391 individuals, of whom 751 (11.8%) patients were treated with digoxin. On multivariate analysis, the use of digoxin was associated with a higher odds ratio (OR) of composite outcome [OR: 1.71; 95% confidence interval (CI): 1.32-2.22], all-cause death (OR: 1.62; 95% CI: 1.23-2.14), and any TE (OR: 1.78; 95% CI: 1.08-2.95). Results were consistent in a subgroup of patients with diagnosed heart failure (HF) and patients with permanent AF. The use of digoxin was associated with worse health-related quality of life (mean EQ index: 0.76 ± 0.19 vs. 0.84 ± 0.18; P < 0.001).. In this nationwide cohort study, digoxin use was associated with an overall higher risk of the composite outcome of all-cause death/any TE, all-cause death, and any TE, regardless of HF diagnosis. Patients treated with digoxin had a worse health-related quality of life.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; China; Cohort Studies; Digoxin; Heart Failure; Humans; Prospective Studies; Quality of Life; Registries; Venous Thromboembolism

Topics: Diabetes Mellitus, Type 2; Digoxin; Glucosides; Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left

Topics: Benzhydryl Compounds; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Glucosides; Heart Failure; Humans

Digoxin is used for rate control in atrial fibrillation (AF), but evidence for its efficacy and safety after myocardial infarction (MI) is scarce and mixed. We studied post-MI digoxin use effects on AF patient outcomes in a nationwide registry follow-up study in Finland. Digoxin was used by 18.6% of AF patients after MI, with a decreasing usage trend during 2004-2014. Baseline differences in digoxin users (n = 881) and controls (n = 3898) were balanced with inverse probability of treatment weight adjustment. The median follow-up was 7.4 years. Patients using digoxin after MI had a higher cumulative all-cause mortality (77.4% vs. 72.3%; hazard ratio [HR]: 1.19; confidence interval [CI]: 1.07-1.32; p = 0.001) during a 10-year follow-up. Mortality differences were detected in a subgroup analysis of patients without baseline heart failure (HF) (HR: 1.23; p = 0.019) but not in patients with baseline HF (HR: 1.05; p = 0.413). Cumulative incidences of HF hospitalizations, stroke and new MI were similar between digoxin group and controls. In conclusion, digoxin use after MI is associated with increased mortality but not with HF hospitalizations, new MI or stroke in AF patients. Increased mortality was detected in patients without baseline HF. Results suggest caution with digoxin after MI in AF patients, especially in the absence of HF.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Follow-Up Studies; Heart Failure; Humans; Myocardial Infarction; Risk Factors; Stroke

Digoxin is a cardiac glycoside, derived from the plant Digitalis purpurea. For many years digitalis has been widely used in the treatment of heart failure (HF), owing to its cardiotonic and neurohormonal effects and atrial fibrillation (AF), due to its parasympathomimetic effect on the AV node.. The aim of this paper is to evaluate the available evidence on the safety and efficacy of digoxin in patients with HF and AF, by reviewing the pertinent literature.. We conducted a PubMed/MEDLINE and SCOPUS search to evaluate the currently available evidence on the administration of digoxin and its association with all-cause mortality risk in patients with AF and HF.. Several observational analyses of clinical trials and meta-analyses have shown conflicting results on the safety and efficacy of digoxin administration in patients with AF and HF. According to these results, digoxin should be avoided in patients without HF, as it is associated with worse outcomes. On the other hand, in patients with AF and HF digoxin should be used with caution.. The impact of digoxin on all-cause mortality and adverse effects in these patients remains unclear based on the current evidence. More trials at low risk of bias evaluating the effects of digoxin are needed.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Topics: Atrial Fibrillation; Digoxin; Heart Failure; Humans; Urea

Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other pharmacologic and device therapies, digoxin retains a role in select patients unable to tolerate or refractory to standard therapies. Contemporary utilization of and costs related to digoxin in the United States of America (USA) remain uncharacterized. The objective of this study was to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017.. We utilized the Medical Expenditure Panel Survey to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. The Medical Expenditure Panel Survey is an overlapping panel survey that interviews households in the USA to ascertain their healthcare utilization and expenditures. Complex sampling procedures allow for nationally representative estimates of utilization and expenditures. We report the number of digoxin users and expenditures across key subgroups in 2-year increments from 2010 to 2017.. The number of digoxin users in the USA declined by 47% from 766 users per 100,000 adults in 2010-11 to 402 users per 100,000 adults in 2016-17. While digoxin use declined among women and self-identified White adults, adults living at or below the federal poverty level and those who self-identified as Asian or Hispanic represent an increasing proportion of overall digoxin users. While nationwide digoxin expenditures declined by 26% from 2010-11 to 2012-13, they peaked at $260.3 million in 2014-15 and remained elevated at $188.7 million in 2016-17.. Despite a nationwide trend towards declining use, digoxin remains prevalent amongst people of Asian and Hispanic descent in the USA. After a spike in cost in 2013, digoxin prices have yet to return to pre-spike levels. The role of digoxin in contemporary heart failure and arrhythmia management will continue to evolve as additional randomized and observational analyses become available.

Topics: Adult; Digoxin; Female; Health Expenditures; Heart Failure; Humans; Patient Acceptance of Health Care; Surveys and Questionnaires; United States

We aimed to assess the impact of digoxin use following left ventricular assist device (LVAD) implantation on clinical outcomes.. Patients implanted with continuous flow LVADs at a single academic medical center and survived to initial hospital discharge were included in the analysis (. Digoxin use was associated with reduction in GIB events, but not in RVF or mortality. Further studies are needed to confirm these findings and to investigate optimal timing and patient population.

Topics: Adult; Aged; Digoxin; Female; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Hemoglobins; Humans; Male; Middle Aged; Neprilysin; Potassium; Receptors, Angiotensin; Retrospective Studies; Risk Factors

Topics: Digoxin; Heart Failure; Humans; Tachycardia

P-glycoprotein (P-gp) is one of the most intensely studied transporters owing to its broad tissue distribution and substrate specificity. Existing research suggests that the risk of systemic exposure to dabigatran etexilate (DABE) and digoxin, two P-gp probe substrates in vivo, has significantly increased in elderly patients. We applied a model-based quantitative pharmacological approach to assess aging-related P-gp changes in the Chinese old-elderly population.. Population pharmacokinetic (PopPK) modeling was first performed using clinical pharmacokinetic data to explore the effect of age on the pharmacokinetic characteristics of dabigatran (DAB, the active principle of DABE) and digoxin in elderly Chinese patients. Corresponding physiologically based pharmacokinetic (PBPK) models were established to further explain the elevated systemic exposure to these two drugs. Eventually, standard dosing regimens of DABE and digoxin were assessed in Chinese old-elderly patients with chronic heart failure (CHF) with different stages of renal impairment.. PopPK analysis suggested that age as a covariate had an additional effect on the apparent clearance of these two drugs after correcting for creatinine clearance. PBPK simulation results suggested that disease-specific pathophysiological changes could explain DAB exposure in the young elderly. In the elderly population, 17.1% of elevated DAB exposure remained unexplained, and 25.5% of the reduced P-gp function associated with aging was ultimately obtained using sensitivity analysis. This value was further validated using digoxin data obtained by PBPK modeling. The simulation results suggest that CHF patients with advanced age and moderate-to-severe renal impairment require heightened vigilance for elevated exposure risk during the use of DABE and digoxin.. Aging might be a significant risk factor for elevated systemic exposure to DAB and digoxin by reducing P-gp-mediated efflux in the Chinese old elderly population.

Topics: Adult; Age Factors; Aged; Aging; ATP Binding Cassette Transporter, Subfamily B, Member 1; Computer Simulation; Dabigatran; Digoxin; East Asian People; Heart Failure; Humans; Middle Aged

The management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort.. We conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD).. The all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09-1.46,. Digoxin should be prescribed with caution to patients with CRS.

Topics: Cardio-Renal Syndrome; Coronary Artery Disease; Digoxin; Heart Failure; Hospitalization; Humans; Kidney Failure, Chronic

Heart failure is one of the common cardiovascular diseases, and digoxin is required in the list of drug treatments. Considering the positive effect of this drug on heart failure, unfortunately, its therapeutic and toxic serum levels are different and very close to each other in different people. This study aimed to investigate the digoxin serum level in heart failure patients. For this purpose, we examined 32 patients with heart failure and digoxin users in this cross-sectional descriptive study. Some important factors involved in determining digoxin toxicity, such as age, gender, creatinine, creatinine clearance, cardiac output, urea, potassium, calcium, and digoxin levels, were measured. Statistical analysis showed that digoxin serum level increases with age (p<0.01). The increase in digoxin serum level was related to urea, creatinine, and potassium serum levels (p<0.01). In general, it seems that to prevent the increase of digoxin serum level and poisoning with it, it is necessary to continuously control the serum level of this drug in the form of serum measurement or according to its clearance.

Topics: Creatinine; Cross-Sectional Studies; Digoxin; Heart Failure; Humans; Potassium; Urea

This study aimed to investigate the possible use of Procyanidin extracted from Crataegus azarolus in the treatment of induced heart failure in rats. Thirty-six male rats were randomly assigned to three groups; the first two groups had six rats each, and the third group included four subgroups (each with six rats). The first group was regarded as the control group, while the second group (normal rats) received oral Procyanidin 30mg/kg/day for 14 days. The rest of the experimental groups were all injected intraperitoneally with 5mg/kg/day for seven days to induce heart failure. The first subgroup (IIIa) served as a positive control, and the other subgroups (IIIb, c, and d) received oral Procyanidin 30mg/kg/day, spironolactone 20mg/kg/day, and digoxin 7Mcg/kg/day, respectively, for 14 days. Heart failure induction in rats significantly increased levels of cardiac biomarkers, including NT-proBNP, BNP, ALP, MMP9, CPK, systolic, and diastolic blood pressure. The normal rats that received only Procyanidin experienced a significant decrease in the ALP level. Moreover, Procyanidin, accompanied by spironolactone and digoxin, significantly decreased NT-proBNP, BNP, ALP, and diastolic BP in rats with heart failure. Procyanidin extracted from C. azarolus significantly decreased cardiac biomarkers in rats with iso-induced HF. The final results demonstrated similar effects with both spironolactone and digoxin in induced heart failure in rats, revealing the possibility of using Procyanidin in the HF treatment.

Topics: Animals; Biomarkers; Crataegus; Digoxin; Heart Failure; Male; Natriuretic Peptide, Brain; Peptide Fragments; Proanthocyanidins; Rats; Spironolactone

The use of digitalis has been plagued by controversy since its initial use. We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACSs) complicated by heart failure (HF) accounting for sex difference and prior heart diseases.. Of the 25 187 patients presenting with acute HF (Killip class ≥2) in the International Survey of Acute Coronary Syndromes Archives (NCT04008173) registry, 4722 (18.7%) received digoxin on hospital admission. The main outcome measure was all-cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models. Women who received digoxin had a higher rate of death than women who did not receive it [33.8% vs. 29.2%; relative risk (RR) ratio: 1.24; 95% confidence interval (CI): 1.12-1.37]. Similar odds for mortality with digoxin were observed in men (28.5% vs. 24.9%; RR ratio: 1.20; 95% CI: 1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratio: 1.26; 95% CI: 1.10-1.45 in women and RR ratio: 1.21; 95% CI: 1.06-1.39 in men) and those in sinus rhythm at admission (RR ratio: 1.34; 95% CI: 1.15-1.54 in women and RR ratio: 1.26; 95% CI: 1.10-1.45 in men).. Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS.

Topics: Acute Coronary Syndrome; Clinical Studies as Topic; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Registries

To determine the prognosis of Takayasu arteritis (TA) patients with moderate-to-severe aortic regurgitation treated with surgical vs conservative treatment and to identify independent prognostic factors of long-term outcomes.. Between January 2002 and January 2017, 101 consecutive TA patients with moderate-to-severe aortic regurgitation treated with either surgical (n = 38) or conservative (n = 63) treatments were investigated in this retrospective observational case-control study. The primary end point was all-cause mortality, and the secondary end point comprised the combined end points of death, non-fatal stroke and cardiac events (non-fatal myocardial infarction and congestive heart failure). Propensity score matching was used to reduce the bias of baseline risk factors.. The unadjusted all-cause 10-year mortality in the conservative group was increased compared with the surgical group (28.2% vs 7.4%; log-rank P = 0.036), and the combined end points showed the same trend (52.1% vs 25.3%; log-rank P = 0.005). After an adjustment of baseline risk factors, the conservative treatment was associated with reduced survival rates of both all-cause mortality [hazard ratio (HR): 8.243; 95% CI: 1.069, 63.552; P = 0.007] and combined end points (HR: 6.341; 95% CI: 1.469, 27.375; P = 0.002). Conservative treatment (HR: 3.838, 95% CI: 1.333, 11.053; P = 0.013) and left ventricular end-diastolic diameter (HR: 1.036, 95% CI: 1.001, 1.071; P = 0.042) were risk factors for increased combined end points.. Surgical treatment improves the outcomes of patients with moderate-to-severe aortic regurgitation due to TA. The dilated left ventricle indicated a worse prognosis.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aorta; Aortic Valve Insufficiency; Calcium Channel Blockers; Cardiotonic Agents; Case-Control Studies; Cause of Death; Conservative Treatment; Digoxin; Female; Glucocorticoids; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Prednisone; Propensity Score; Retrospective Studies; Severity of Illness Index; Stroke; Takayasu Arteritis; Treatment Outcome

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Digoxin; Heart Failure; Humans

Topics: Creatinine; Digoxin; Genotype; Heart Failure; Humans; Organic Anion Transporters; Spironolactone

Medicinal preparations currently used for the treatment of patients with chronic cardiac failure involve those that reduce the heart load (vasodilators, diuretics, beta-blockers, and angiotensin- converting enzyme (ACE) inhibitors). Cardiotonic drugs with the cAMP-dependent mechanism are unsuitable for long-term administration due to the intensification of metabolic processes and an increase in the oxygen demand of the myocardium and all tissues of the body. For many years, digoxin has remained the only preparation enhancing the efficiency of myocardial performance. The detection of digoxin and ouabain in intact animals has initiated a search for other compounds with cardiotonic activity. The review summarizes current data on the effect exerted on the heart performance by endogenous compounds, from simple, such as NO and CO, to steroids, fatty acids, polypeptides, and proteins. Controversial questions and problems with the introduction of scientific achievements into clinical practice are discussed. The results obtained by the authors and their colleagues after many years of studies on the cardiotropic properties of serum lipoproteins are also reported. The experimentally established cardiotonic activity of apoprotein A-1, which is accompanied by a decrease in the relative consumption of oxygen, maybe of great interest.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans

Assess the association between digoxin use and gastrointestinal bleeding (GIB) in a multicenter continuous flow left ventricular assist device (LVAD) cohort.. Patients implanted with continuous flow LVADs with data on GIB and digoxin use from two centers were included in the analysis (n = 649). GIB events were captured up to 2 years of follow-up. Digoxin use was defined as digoxin prescribed at discharge or within the first 3 months after LVAD implantation. A negative binomial regression model was performed to determine the association between digoxin use and number of GIB events over the follow-up period.. Mean age of the cohort was 57 years (±14) and 45% (293/649) were bridge to transplant (BTT). Digoxin was prescribed in 33% of patients. Digoxin use was associated with an unadjusted 32% reduction in the incidence of rate of all cause GIB (IRR 0.68, 95% CI 0.46-0.99, p = 0.049). After adjusting for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, renal function, and implanting center there was still a 34% reduction in the incidence rate (IRR 0.67, 95% CI 0.45-0.99, p = 0.048). When limiting the analysis to those with likely arteriovenous malformation associated GIB, the association strengthened (unadjusted: IRR 0.48, 95 % CI 0.26-0.89, p = 0.02, adjusted: IRR 0.47, 95 % CI 0.25-0.9, p = 0.022).. In this multicenter study, inclusive of contemporary devices, digoxin use was associated with reduced GIB events. Prospective data will be required to confirm this association.

Topics: Digoxin; Enzyme Inhibitors; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Registries; Retrospective Studies; United States

Guanxin Shutong (GXST) capsule is a renowned traditional Chinese medicine widely used for the treatment of cardiovascular diseases in the clinic. However, no pharmacological experimental studies of GXST has been reported on the treatment of pressure overload-induced heart failure. This study aimed to investigate the effects of GXST capsule on ameliorating myocardial fibrosis conditions in pressure overload-induced heart failure rats.. Rats were randomly divided into 6 groups: Normal group, Model group, GXST-treated group at a dose of 0.5 g/kg, 1 g/kg, 2 g/kg, respectively, and digoxin positive control group at a dose of 1 mg/kg. After 4 weeks of administration, cardiac function was evaluated by echocardiography. Cardiac injury and fibrotic conditions were evaluated by H&E staining, Masson staining, and Sirius Red staining. Myocardial fibrosis was evaluated by immunohistochemistry staining and Western blot.. GXST significantly inhibited cardiac fibrosis, reduced the excessive deposition of collagen, and finally improved cardiac function. GXST reversed ventricular remodeling might be through the TGF-β/Smad3 pathway.. GXST capsule demonstrated a strong anti-fibrosis effect in heart failure rats by inhibiting the TGF-β/Smad3 signaling pathway.

Topics: Animals; Aorta, Thoracic; Capsules; Cardiomyopathies; Collagen; Constriction; Digoxin; Disease Models, Animal; Drugs, Chinese Herbal; Echocardiography; Fibrosis; Heart Failure; Ligation; Male; Medicine, Chinese Traditional; Myofibroblasts; Rats, Sprague-Dawley; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta; Ventricular Remodeling

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Heart Rate; Humans

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Disease; Digoxin; Heart Failure; Humans; Middle Aged; Prospective Studies; Risk Factors

Although the efficacy and safety of existing therapies of heart failure (HF) have been demonstrated in clinical trials, little is known about the treatment patterns in clinical practice, especially in France.. To describe the treatment initiation patterns and the subsequent treatment changes among HF patients, in the first year following an incident hospitalization for HF, in a French real-world setting.. A cohort of patients aged ≥ 40 years, with an incident hospitalization for HF between 01/01/2008 and 31/12/2013, was identified in the 1/97th permanent random sample of the French nationwide claims database and followed 1 year. HF drug exposure-beta blockers (BB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), aldosterone antagonists (AA), diuretics, digoxin, or ivabradine-was assessed quarterly using a Proportion of Days Covered ≥ 66% (≥ 60 days out of the 90 days of the quarter), by considering HF drugs individually or in combination. Drug changes were assessed between each quarter.. Between 2008 and 2013, 7387 patients were included. Their mean age was 77.7 years (± 12.0 years) and 51.6% were women. During the follow-up, 24.4% died, 20% were not exposed to any HF treatment, 48.3 to 43.2% had diuretics, one third had BB or ACEI, 9% had ARB or AA, 6% had digoxin, and 2% had ivabradine. The main change occurred between the first and the second quarter for 53.1% of the initially untreated patients.. This study provides valuable information on treatment patterns after an initial hospitalization for HF.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Clinical Protocols; Cohort Studies; Digoxin; Diuretics; Drug Substitution; Female; France; Heart Failure; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Time Factors

The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline-recommended treatments in the real world in China.. Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN-HF) were enrolled to assess the all-cause mortality, HF mortality, all-cause re-hospitalization, and HF re-hospitalization associated with digoxin use. Eight hundred eighty-two eligible HFrEF patients in the CN-HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow-up of 28.6 months. Kaplan-Meier survival analysis showed that the all-cause mortality (P < 0.001) and all-cause re-hospitalization (P = 0.020) were significantly higher in digoxin group than non-digoxin group, while HF mortality (P = 0.232) and HF re-hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional-hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all-cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27-2.44; P = 0.001] and all-cause re-hospitalization (HR 1.27; 95% CI 1.03-1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all-cause mortality irrespective of rhythm or in combination with other guideline-recommended therapies.. Digoxin use is independently associated with increased risk of all-cause mortality and all-cause re-hospitalization in HFrEF patients.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; China; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Treatment Outcome; Ventricular Function, Left

European guidelines for heart failure (HF) have continuously incorporated new evidence since the first publication in 1995. We aimed to explore time trends in utilisation of pharmacological treatment for HF and dispensing of recommended dosages among patients with a first-time diagnosis of HF. We performed a historical cohort study of patients with a first-time HF diagnosis from 1997 to 2015, identified in the Danish National Patient Registry. Dispensed pharmacological treatment included angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor blockers (MRAs), digoxin and diuretics. Furthermore, we estimated the proportion of patients receiving the recommended target dosages 1 year after the diagnosis. The utilisation increased and correlated with publication of landmark studies, and among patients diagnosed in 2015, approximately two of three received ACEI/ARB and beta-blocker, respectively. Less than half of the patients redeeming prescriptions for ACEIs, ARBs, beta-blockers or MRAs received the recommended target dosages. The utilisation of pharmacological therapy for HF appears to be correlated with the publications of landmark Phase III clinical trials. However, a high proportion of patients do not receive the recommended target dosages. Despite improvements over time, a substantial gap appears to remain between guideline recommendations and pharmacological therapy in routine care.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Denmark; Digoxin; Diuretics; Drug Therapy; Female; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists

Digoxin is a commonly prescribed drug in the management of heart failure and atrial fibrillation. Despite its widespread use, most clinicians have little experience with recognising clinical signs and symptoms that might suggest a potentially lethal drug toxicity. We herein describe two cases with specific reference to the electrocardiographic changes induced by digoxin and discuss the predisposing factors for toxicity, recognition of possible toxicity and treatment approaches.

Topics: Aged; Anti-Arrhythmia Agents; Digoxin; Electrocardiography; Female; Heart Failure; Humans

This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk. Thus, physicians should be aware of this association and accordingly estimate the risks and benefits of digoxin use. Nevertheless, some patient variables, such as body mass index and obesity, were unavailable in this study. The findings in this study should be elucidated carefully because the potential effects of these factors could not be considered.

Topics: Administrative Claims, Healthcare; Aged; Aged, 80 and over; Atrial Fibrillation; Digoxin; Drug Prescriptions; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Middle Aged; Prevalence; Psoriasis; Risk Factors; Taiwan

Digoxin reduces the risk of heart failure hospitalization in patients with heart failure with reduced ejection fraction. Less is known about this association in patients with heart failure with preserved ejection fraction (HFpEF), the examination of which was the objective of the current study.. In the Medicare-linked OPTIMIZE-HF registry, 7374 patients hospitalized for HF had ejection fraction ≥50% and were not receiving digoxin prior to admission. Of these, 5675 had a heart rate ≥50 beats per minute, an estimated glomerular filtration rate ≥30 mL/min/1.73 m. Among the 1026 matched patients with HFpEF, 30-day heart failure readmission occurred in 6% and 9% of patients initiated and not initiated on digoxin, respectively (HR 0.70; 95% CI, 0.45-1.10; P = .124). HRs (95% CIs) for 30-day all-cause readmission and all-cause mortality associated with digoxin initiation were 0.95 (0.73-1.23; P = .689) and 0.93 (0.55-1.56; P = .773), respectively. Digoxin initiation had no association with 6-year outcomes.. Digoxin initiation prior to hospital discharge was not associated with 30-day or 6-year outcomes in older hospitalized patients with HFpEF.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiotonic Agents; Cause of Death; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mineralocorticoid Receptor Antagonists; Mortality; Patient Readmission; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Warfarin

Recent publications have raised serious concerns regarding the safety of digoxin for atrial fibrillation (AF). However, the subgroup of patients with reduced ejection fraction and AF have been speculated to derive clinical benefit from digoxin. We aimed to assess the impact of digoxin on mortality and cardiovascular hospitalizations in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial since all AF-CHF patients had an ejection fraction ≤35% and AF.. Using marginal structural modeling, a contemporary statistical method that overcomes limitations of traditional modeling techniques and reduces bias, we assessed the impact of digoxin on the pre-specified primary and secondary outcomes of the AF-CHF trial, i.e., all-cause, cardiac and arrhythmic death as well as cardiovascular hospitalization. Among 1376 patients, 869 (65%) were on digoxin at one-year follow-up. Over a mean (SD) follow-up of 37 (19) months (maximum 74 months), 445 (32%) patients died, 357 (26%) from cardiovascular causes and 159 (12%) from arrhythmic death. Digoxin was significantly associated with all-cause, cardiac, and arrhythmic death, with estimated hazard ratios (HR) of 1.39 (95% confidence interval [CI] 1.11-1.73, P = 0.004), 1.44 (95% CI 1.13-1.82, P = 0.003), and 2.03 (95% CI 1.63-2.54, P < 0.0001), respectively. Digoxin was not associated with cardiovascular hospitalizations [HR 1.12 (95% CI 0.91-1.37), P = 0.29].. Digoxin is associated with increased all-cause mortality among patients with combined heart failure with reduced ejection fraction and AF, which is predominantly driven by arrhythmic deaths. In contrast, cardiovascular hospitalizations were not impacted by digoxin.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Hospitalization; Humans; Stroke Volume

Digoxin is a cardiac glycoside, used to control rapid ventricular rates in atrial fibrillation and to reduce the hospitalizations due to heart failure. Digoxin has a narrow therapeutic range. So, in the treatment of older patients (≥ 65 years), it is important to set the optimal dose of digoxin to prevent toxicity and therapeutic drug monitoring of digoxin trough plasmatic concentration (C0) may be useful.. To assess measured C0, to evaluate age influence on digoxin pharmacokinetic parameters and to report adverse events in patients administered digoxin.. It consisted in a retrospective study. We included all the patients addressed to the department of clinical pharmacology for digoxin C0 measurement by an automated fluorescence polarization immunoassay. Therapeutic ranges of digoxin C0 were: 1 to 2.5 ng.mL-1 in children, 0.8 to 2 ng.mL-1 in adults and 0.5 to 0.9 ng.mL-1 in older adults (≥ 65 years) in atrial fibrillation and heart failure.. We collected 183 samples from 132 patients. Sex ratio M/W was 0.47. Mean age was 60 years and 57% of patients were older adults. Mean dose of digoxin was 0.3 mg.day-1. In older adults, 45% were administered daily doses over 0.125 mg.day-1. Mean digoxin C0 was 1.6 ng.mL-1. There was more supra-therapeutic C0 in older adults than younger ones (p<0.0001).There was no correlation between C0 and daily dose of digoxin. Adverse events, mainly cardiac and digestive, were reported in 47 patients (36%), among this population 47% were older adults.. TDM is useful to prevent toxicity, mainly in older adults where diagnosis may be difficult to establish.

Topics: Adolescent; Adult; Age Factors; Age of Onset; Aged; Aged, 80 and over; Atrial Fibrillation; Child; Child, Preschool; Digoxin; Dose-Response Relationship, Drug; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Male; Middle Aged; Retrospective Studies; Young Adult

Digoxin reduces the risk of heart failure hospitalization but has no effect on mortality in patients with heart failure without atrial fibrillation in the randomized controlled trial setting. Observational studies of digoxin use in patients with atrial fibrillation have suggested a higher risk for poor outcomes. Less is known about this association in patients with heart failure and atrial fibrillation, the examination of which was the objective of the current study.. We conducted an observational propensity score-matched study of predischarge digoxin initiation in 1768 hospitalized patients with heart failure and atrial fibrillation in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, balanced on 56 baseline characteristics (mean age, 79 years; 55% women; 7% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated for the 884 patients initiated on digoxin compared with 884 not initiated on digoxin.. HRs (95% CIs) for 30-day, 2-year, and 4-year all-cause mortality were 0.80 (0.55-1.18; P = .261), 0.94 (0.87-1.16; P = .936), and 1.01 (0.90-1.14; P = .729), respectively. Respective HRs (95% CIs) for heart failure readmission were 0.67 (0.49-0.92; P = .014), 0.81 (0.69-0.94; P = .005), and 0.85 (0.74-0.97; P = .022), and those for all-cause readmission were 0.78 (0.64-0.96; P = .016), 0.90 (0.81-1.00; P = .057), and 0.91 (0.83-1.01; P = .603). These associations were homogeneous between patients with left ventricular ejection fraction ≤45% vs >45%.. Among hospitalized older patients with heart failure (HFrEF and HFpEF) and atrial fibrillation, initiation of digoxin was associated with a lower risk of heart failure readmission but had no association with mortality.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Retrospective Studies; Treatment Outcome

This study aimed to utilize a population pharmacokinetic method to obtain information about the influence of covariates on the in vivo behavior of digoxin in patients with cardiac insufficiency.. A total of 228 therapeutic drug monitoring concentrations were retrospectively collected from 176 inpatients. The patients were randomly divided into a modeling group (n = 126) and a validation group (n = 50). The first-order absorption one-compartment model was used to develop a population pharmacokinetic model from a nonlinear mixed effects modeling approach. Sixteen single nucleotide polymorphisms involved in the pharmacokinetic variables of digoxin were identified by using the MassARRAY system. Various demographic parameters, biochemical test values, concomitant medications, and genetic variants were investigated.. The typical population value of digoxin CL/F was 5.06 L/h, and the volume of distribution was 211.82 L. The drug CL/F was significantly related to serum creatinine, in a combination of spironolactone and SLCO4C1 genotypes of 2 variants (rs3114660 and rs3114661). Results of model evaluation and internal/external validation indicated a stable and precise performance of the final model.. For the first time, 2 single nucleotide polymorphisms (rs3114660 and rs3114661) in SLCO4C1 were found to significantly affect the elimination of digoxin in vivo. The final population model may be useful for the individualized dosing of digoxin for patients with cardiac insufficiency.

Topics: Adult; Aged; Aged, 80 and over; Creatinine; Digoxin; Drug Monitoring; Female; Genotype; Heart Failure; Humans; Male; Middle Aged; Models, Biological; Organic Anion Transporters; Retrospective Studies; Spironolactone; Young Adult

Despite limited options for rate control of atrial fibrillation and for low-output heart failure seen in cardiac amyloidosis (CA), digoxin use is discouraged due to a reported increased risk of sensitivity and toxicity. We present our experience with digoxin use in patients with CA and report the event rate of suspected digoxin-related arrhythmias and toxicity. This is a retrospective study of patients with CA seen at our institution between November 1995 and October 2018. Patients were screened for a history of ≥7 days of continuous digoxin use and stratified based on amyloid precursor protein-transthyretin (ATTR) and immunoglobulin light chain (AL). Medical records were used to identify suspected digoxin-related arrhythmias and toxicity events. Digoxin was used in 69 patients (42 ATTR, 27 AL) for a median duration of 6 months (IQR, 1 to 16). Indication for use was rate control in 64% of patients and symptomatic heart failure management in 36%. Suspected digoxin-related arrhythmias and toxicity events occurred in 12% of patients. No deaths were attributed to digoxin use or toxicity, but 11 patients died while on digoxin-most due to progressive heart failure in the setting of CA. In conclusion, digoxin may be a therapeutic option for rate and symptom control for some patients with AL-CA and ATTR-CA. Rigorous patient selection is recommended, and patients should be closely monitored during digoxin administration.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Retrospective Studies

Clinical experience with landiolol use in patients with atrial fibrillation (AF) and a severely depressed left ventricular (LV) function is limited. We compared the efficacy and safety of landiolol with that of digoxin as an intravenous drug in controlling the heart rate (HR) during AF associated with a very low LV ejection fraction (LVEF).We retrospectively analyzed 53 patients treated with landiolol (n = 34) or digoxin (n = 19) for AF tachycardias with an LVEF ≤ 25. The landiolol dose was adjusted between 0.5 and 10 μg/kg/minute according to the patient's condition. The response to treatment was defined as a decrease in the HR of ≤ 110/minute, and that decreased by ≥ 20% from baseline.There were no significant differences between the two groups regarding the clinical characteristics. The responder rate to landiolol at 24 hours was significantly higher than that to digoxin (71.0% versus 41.2%; odds ratio: 4.65, 95% confidence interval: 1.47-31.0, P = 0.048). The percent decrease in the HR from baseline at 1, 2, 12, and 24 hours was greater in the landiolol group than in the digoxin group (P < 0.01, P = 0.071, P = 0.036, and P = 0.016, respectively). The systolic blood pressure (SBP) from baseline within 24 hours after administering landiolol was significantly reduced, whereas digoxin did not decrease the SBP over time. Hypotension (< 80 mmHg) occurred in two patients in the landiolol group and 0 in the digoxin group (P = 0.53).Landiolol could be more effective in controlling the AF HR than digoxin even in patients with severely depressed LV function. However, careful hemodynamic monitoring is necessary when administering landiolol.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Morpholines; Retrospective Studies; Severity of Illness Index; Stroke Volume; Tachycardia; Treatment Outcome; Urea; Ventricular Dysfunction, Left

Recently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC-guided.. To assess the impact of SDC-guided digoxin therapy on mortality in HFrEF patients.. Data of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC-guided (target SDC: 0.5-0.9 ng/mL). All-cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM).. After 7.1 ± 4.7 years follow-up period (FUP) all-cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity-adjusted HR = 1.430; 95% CI = 1.134-1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all-cause mortality (HR = 1.750; 95% CI = 1.257-2.436, P = .001 and HR = 1.687; 95% CI = 1.153-2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827-1.570, P = .426), compared to digoxin nonusers.. According to our propensity-matched analysis, SDC-guided digoxin therapy was associated with increased all-cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring.

Topics: Cardiotonic Agents; Digoxin; Female; Follow-Up Studies; Heart Failure; Humans; Hungary; Male; Middle Aged; Propensity Score; Retrospective Studies; Stroke Volume; Survival Rate; Time Factors; Treatment Outcome

While clinical experience with left ventricular assist devices (LVAD) continues to grow and evolve, little is known regarding the ongoing use of certain medications in this population. We sought to evaluate the utility of digoxin in LVAD recipients and its association with outcomes.. A total of 505 patients who underwent continuous-flow LVAD implantation at 5 centers from 2007-2015 were included. Patients were divided into 4 groups: not on digoxin at any time (ND; n = 257), received digoxin pre implant (PreD; n = 144), received digoxin pre and post implant (ContD; n = 55), and received digoxin only post implant (PostD; n = 49). Survival and all-cause readmission were compared between the 4 groups.. There was no difference in survival at 1 year nor at 3 years between groups (ND = 88%, 66%, respectively; PreD = 85%, 66%; ContD = 86%, 57%; PostD = 90%, 51%; p = 0.7). Readmission per 100 days also was not different between groups (ND = 0.5, PreD = 0.6, ContD = 0.5, PostD = 0.7; p = 0.1).. In this large, multicenter cohort, use of digoxin was not associated with any significant benefit in regard to mortality or hospitalization in patients supported with a continuous-flow LVAD. Importantly, its discontinuation post implant did not worsen all-cause hospitalization or survival.

Topics: Aged; Digoxin; Female; Heart Failure; Heart-Assist Devices; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Stroke Volume; Ventricular Dysfunction, Left

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans

Mutlu M, Aslan Y, Kader Ş, Aktürk-Acar F, Dilber E. Clinical signs and symptoms of toxic serum digoxin levels in neonates. Turk J Pediatr 2019; 61: 244-249. Digoxin is widely used in the treatment of congestive heart failure and some arrhythmias. Digoxin toxicity may occur easily because digoxin has a narrow therapeutic index. This retrospective study was conducted to evaluate the clinical signs and symptoms of toxic serum digoxin levels in neonates. Medical reports of the neonates who had serum digoxin concentrations > 2 nanogram/milliliter (ng/ml) were reviewed in terms of patient demographics, serum digoxin concentrations, signs and symptoms of digoxin toxicity, serum digoxin and electrolyte levels, renal function tests, electrocardiograms, echocardiography, and treatments applied. Digoxin toxic levels were identified in the 13 neonates. Of the 13 neonates with digoxin toxic level, 9 (69%) were term and 8 (62%) were female. Twenty-three percent (3/13) of newborn infants were symptomatic. Symptomatic patients had statistically significantly higher serum digoxin levels, at 7.76±2.76 (5.4-10.8) ng/ml, than asymptomatic patients, at 3.31±1.09 (2.02-4.95) (p=0.036). Symptoms related to toxic digoxin levels were observed in the three neonates with plasma digoxin levels > 5 ng/ml. Gastrointestinal and central nervous system symptoms were the major clinic findings. Despite high digoxin levels, no digoxin-related arrhythmia was observed on electrocardiography, other than sinus bradycardia. Two premature neonates were treated with digoxin-specific antibody Fab fragments (DigiFab®) and hypokalemia developed in both of them. Our data suggests that symptoms related with digoxin toxic levels were observed in neonates with plasma digoxin levels > 5 ng/ml. Serum digoxin levels should be measured in case of signs and symptoms of digoxin toxicity or risk factors for such toxicity.

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Immunoassay; Infant, Newborn; Male; Retrospective Studies; Risk Factors

Digitalis has been used for over 200 years to treat patients with heart failure, and evidence supports its use to improve clinical symptoms and quality of life, but not survival. The objective of this retrospective study was to evaluate the effects of digitalis on readmission and mortality in patients with heart failure with reduced ejection fraction (HFrEF) who were receiving current guideline recommended medical therapy.. We reviewed medical record data from a retrospective cohort study of 1047 patients admitted to the hospital from 2005 to 2014 with decompensated HFrEF. 244 received digitalis, at some point during patient trajectory, and 803 never received digitalis. The primary outcomes of interest were the length of stay in hospital, readmission rates after discharge at 1, 6, 12, and 24 months and the overall mortality rate, at the same time points.. We studied the effects of digitalis after adjusting for age, sex, race, potentially confounding comorbidities, and prescription medications. Digitalis treatment is associated with decreases in EF in patients with HFrEF (OR = -2.83, P < 0.001) and was associated with an increased readmission rate for any reason after discharge from the hospital at 6, 12, and 24 months, 53%, 34%, and 35%, respectively. No statistically significant difference was found between patients who received digitalis and those who did not (referent group) for the length of hospital stay and overall mortality rate.. Digitalis use is associated with increased re-admission rates for any reason following discharge from the hospital at 6, 12, and 24 months.

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Patient Discharge; Patient Readmission; Quality of Life; Retrospective Studies; Stroke Volume; Survival Rate; United States

Digoxin is widely used in patients with rheumatic heart disease (RHD) despite a lack of data on its impact on clinical outcomes. We aimed to determine the association of digoxin use on clinical outcomes in patients with RHD.. We performed a retrospective analysis of the association of digoxin use with mortality at 2 years in a large RHD registry. Secondary outcomes were recurrent heart failure (HF) and hospitalisation for any cause. We assessed associations using multivariable logistic regression in the entire cohort and in subgroups of patients with atrial fibrillation (AF) and HF. We also estimated average treatment effects from propensity-adjusted analyses using inverse probability treatment weighting.. Information on digoxin use at baseline was available for 98.7% (3298/3343) of patients. In the overall population, digoxin was significantly associated with mortality (OR 1.63, 95% CI 1.30 to 2.04, p<0.0001) and recurrent HF (OR 1.48, 95% CI 1.07 to 2.04, p=0.019). On propensity-weighted analyses, this effect was markedly attenuated (OR 1.05, 95% CI 1.01 to 1.09, p=0.005). Patients in sinus rhythm without HF had a higher propensity-adjusted odds of death with digoxin use (OR 1.06, 95% CI 1.01 to 1.12, p=0.015), but those with both AF and HF had lower mortality (OR 0.88, 95% CI 0.80 to 0.98, p=0.019).. Digoxin use is associated with higher mortality in patients with RHD, but this is greatly attenuated on propensity adjustment, indicating the presence of substantial treatment bias. The adjusted estimates may therefore not be reliable, and large randomised trials are needed to determine the true effect of digoxin in patients with RHD.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Female; Global Health; Heart Failure; Humans; Male; Middle Aged; Mortality; Outcome Assessment, Health Care; Propensity Score; Registries; Rheumatic Heart Disease

Due to the narrow therapeutic range of digoxin, determining serum/plasma digoxin concentrations is critical for assessing patients with congestive heart failure, atrial fibrillation, and certain types of arrhythmias. However, digoxin quantification by competitive immunoassays is susceptible to interferences that may alter the accuracy of its measurement in patient plasma. This study aimed to characterize the extent of bilirubin interference in three commonly used digoxin immunoassays.. Digoxin concentrations were compared using the Beckman Coulter® Unicel DxI 800, the Vitros® 4600, and the Roche Cobas® 8000 in neat or digoxin-spiked icteric and non-icetric plasma samples. A mixing study was performed to demonstrate how digoxin quantification is affected by bilirubin. An equation was derived that predicts the response of the DxI 800, given known bilirubin and digoxin concentrations.. The DxI reported detectable concentrations of digoxin in high bilirubin samples with no added digoxin, while the Vitros® 4600 and Cobas® 8000 gave virtually undetectable results. Spiking digoxin into samples with elevated bilirubin concentrations resulted in a higher percent recovery for the DxI 800 when compared to the other two platforms. The mixing study also revealed an increase in the percent recovery in the DxI 800, while the Vitros® 4600 and Cobas® 8000 were comparable to the expected concentration of digoxin.. The DxI 800 is most prone to interference by bilirubin, while the Vitros® 4600 and Cobas® 8000 are relatively unaffected. Icteric samples should be interpreted with caution if digoxin quantification is needed, especially on the DxI 800 assay.

Topics: Arrhythmias, Cardiac; Bilirubin; Digoxin; Drug Monitoring; Heart Failure; Humans; Immunoassay

The value of digoxin in heart failure (HF) remains controversial, particularly in patients with preserved ejection fraction (HFpEF). This study evaluated the 1-year risk of events after digoxin treatment for acute heart failure (AHF) in patients >70 years old with HFpEF.. 1833 patients were included in this analysis (mean age, 82 years). The main endpoints were all-cause death and the composite of death and/or HF re-admission within 1 year. Cox regression analysis was used to evaluate the association between digoxin treatment and prognosis.. 401 patients received digoxin treatment; of these, 86% had atrial fibrillation. The mean baseline heart rate was 86 ± 22 bpm. At the 1-year follow-up, 375 patients (20.5%) died and 684 (37.3%) presented composite endpoints. Patients treated with digoxin showed higher rates of death (3.21 vs. 2.44 per 10 person-years, p = .019) and composite endpoint (6.72 vs. 5.18 per 10 person-years, p = .003). After multivariate adjustment, digoxin treatment remained associated with increased risks of death (HR = 1.46, 95% CI: 1.16-1.85, p = .001) and the composite endpoint (HR = 1.35, 95% CI: 1.13-1.61, p = .001). A distinctive prognostic effect of digoxin was found across the heart rate continuum; the risks for both endpoints were higher at lower heart rates and neutral at higher heart rates (p of the interactions = 0.007 and 0.03, respectively).. In older patients with HFpEF discharged after AHF, digoxin treatment was associated with increased mortality and/or re-admission, particularly in patients with lower heart rates.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Cause of Death; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Multivariate Analysis; Patient Discharge; Patient Readmission; Prognosis; Proportional Hazards Models; Prospective Studies; Registries; Risk Factors; Spain; Stroke Volume

Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world.. We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan.. Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.

Topics: Adrenergic beta-Antagonists; Age Distribution; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Asia; Asia, Eastern; Asia, Southeastern; Asia, Western; Cardiac Resynchronization Therapy Devices; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Disease Management; Diuretics; Europe; Europe, Eastern; Female; Heart Failure; Heart-Assist Devices; Hospitalization; Humans; Latin America; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; North America; Pacemaker, Artificial; Practice Patterns, Physicians'; Stroke Volume; Treatment Outcome

Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A influence trough SDC in Chinese heart failure patients and to make clinical recommendations.Chinese patients (n = 104) diagnosed with heart failure under long-term digoxin therapy (0.125 mg daily) were enrolled in this study. Blood samples were collected for the analysis of trough SDC (immunofluorescence) and the polymorphisms of OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A (PCR-RFLP and Sanger sequencing).Patients with glomerular filtration rate (GFR) under 30 mL/min had significantly higher trough SDC (1.20 ± 0.50 ng/mL) than recommended trough SDC for heart failure patients. Trough SDC was not significantly influenced by mutations of OATP1B1 388A>G (P = .890), 521T>C (P = .054), and OATP1B3 699G>A (P = .854). Patients with OATP1B1 521T>C mutant-type carrier had slightly higher trough SDC (0.98 ± 0.53 ng/mL) than those with wild-type carrier (0.74 ± 0.40 ng/mL) when they have repaired renal function.Heart failure patients with severe renal dysfunction (GFR<60 mL/min) and/or OATP1B1 521T>C mutant-type carriers are recommended a smaller dosage of digoxin and strict therapeutic drug monitoring.

Topics: Aged; Cardiotonic Agents; China; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Humans; Liver-Specific Organic Anion Transporter 1; Male; Middle Aged; Mutation; Polymorphism, Genetic; Prospective Studies; Solute Carrier Organic Anion Transporter Family Member 1B3

Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes.. To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM]).. The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018.. One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed.. Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals.. The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of β blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9).. Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM.. ClinicalTrials.gov Identifier: NCT01090362.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Diseases; Cohort Studies; Digoxin; Female; Guideline Adherence; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mortality; Myocardial Ischemia; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Proportional Hazards Models; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke; Stroke Volume

Digoxin is widely used in patients with atrial fibrillation (AF), but its association with adverse outcomes remains controversial.. We aimed to assess the association between digoxin and adverse outcomes in Chinese patients with AF.. We used data from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study involving 31 hospitals. In total, 10,472 eligible patients with AF, enrolled from August 2011 to December 2016, were included in this study. The association between digoxin use and all-cause mortality, cardiovascular death, and cardiovascular hospitalization were investigated using Cox proportional hazards models.. In total, 1152 (11%) patients were treated with digoxin at baseline. Patients receiving digoxin were older (mean age 69.7 vs. 66.5 years) and had a higher heart rate (92.4 vs. 79.7 beats/min). A higher proportion of patients receiving digoxin therapy had a history of heart failure (62.5 vs. 15.6%), diabetes mellitus (34.4 vs. 24.4%), and persistent AF (67.9 vs. 38.4%). Digoxin use was independently associated with increased all-cause mortality (adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI) 1.02-1.43; p = 0.031), cardiovascular death (aHR 1.25; 95% CI 1.01-1.55; p = 0.043), and cardiovascular hospitalization (aHR 1.21; 95% CI 1.05-1.39; p = 0.007). The associations were also homogeneous across various subgroups except in patients with and without renal dysfunction (p value for interaction = 0.029).. In this Chinese AF cohort, for patients who had not undergone ablation, digoxin use was associated with a significant increase in adverse outcomes. Although residual confounders may exist, and serum concentrations of digoxin were unavailable, digoxin should be used with caution in clinical practice, and its effects need to be critically evaluated in randomized trials.. URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Heart Rate; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Socioeconomic Factors

Over the past 2 decades, guidelines for digoxin use have changed significantly. However, little is known about the national-level trends of digoxin use, hospitalizations for toxicity, and subsequent outcomes over this time period.. To describe digoxin prescription trends, we conducted a population-level, cohort study using data from IQVIA, Inc.'s National Prescription Audit (2007-2014) for patients aged ≥65 years. Further, in a national cohort of Medicare fee-for-service beneficiaries aged ≥65 years in the United States, we assessed temporal trends of hospitalizations associated with digoxin toxicity and the outcomes of these hospitalizations between 1999 and 2013.. From 2007 through 2014, the number of digoxin prescriptions dispensed decreased by 46.4%; from 8,099,856 to 4,343,735. From 1999 through 2013, the rate of hospitalizations with a principal or secondary diagnosis of digoxin toxicity decreased from 15 to 2 per 100,000 person-years among Medicare fee-for-service beneficiaries. In-hospital and 30-day mortality rates associated with hospitalization for digoxin toxicity decreased significantly among Medicare fee-for-service beneficiaries; from 6.0% (95% confidence interval [CI], 5.2-6.8) to 3.7% (95% CI, 2.2-5.7) and from 14.0% (95% CI, 13.0-15.2) to 10.1% (95% CI, 7.6-13.0), respectively. Rates of 30-day readmission for digoxin toxicity decreased from 23.5% (95% CI, 22.1-24.9) in 1999 to 21.7% (95% CI, 18.0-25.4) in 2013 (P < .05).. While digoxin prescriptions have decreased, it is still widely prescribed. However, the rate of hospitalizations for digoxin toxicity and adverse outcomes associated with these hospitalizations have decreased. These findings reflect the changing clinical practice of digoxin use, aligned with the changes in clinical guidelines.

Topics: Aged; Aged, 80 and over; Cohort Studies; Digoxin; Female; Heart Failure; Humans; Male; Practice Patterns, Physicians'; Retrospective Studies; United States

This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum.. Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials.. In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females.. Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF.. Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

Topics: Adrenergic beta-Antagonists; Age Distribution; Aged; Aged, 80 and over; Cardiac Resynchronization Therapy; Cardiotonic Agents; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hypertension; Kidney Diseases; Logistic Models; Male; Middle Aged; Mortality; Myocardial Ischemia; Phenotype; Prognosis; Proportional Hazards Models; Registries; Severity of Illness Index; Sex Factors; Stroke Volume; Sweden

Heart failure is a leading cause for hospital readmission. Digoxin use may lower this risk in patients with heart failure with reduced ejection fraction (HFrEF), but data on contemporary patients receiving other evidence-based therapies are lacking.. Among the 3062 matched patients, digoxin use was associated with a significantly lower risk of heart failure readmission at 30 days (HR, 0.74; 95% CI, 0.59-0.93), 1 year (HR, 0.81; 95% CI, 0.72-0.92), and 6 years (HR, 0.90; 95% CI 0.81-0.99). The association with all-cause readmission was significant at 1 and 6 years but not 30 days. There was no association with mortality. Similar associations were observed among the 2850 matched patients without bradycardia or renal insufficiency.. Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, digoxin use is associated with a lower risk of hospital readmission but not all-cause mortality.

Topics: Aged; Cardiotonic Agents; Cause of Death; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Medicare; Patient Readmission; Propensity Score; Stroke Volume; United States

This analysis was designed to investigate the relationship between drug application and mortality rate in Chinese older coronary artery disease (CAD)/chronic heart failure (CHF) patients with and without low glomerular filtration rate (GFR).. All 1050 Chinese hospitalized patients with diagnosed CAD were included in this analysis, and Cox Regression was used to analyze the relationship between drug application and mortality rate after multivariate adjustment. Low GFR was defined as GFR < 60 ml/min/1.73m. There were 372 patients (35.4%) with low GFR in patients with CAD (1050 patients), and 168 patients (51.4%) in patients with CHF (327 patients). In CAD patients without low GFR, clopidogrel [P = 0.028, odds ratio (OR): 0.620, 95% confidence interval (CI): 0.404-0.951] rather than aspirin (P = 0.173) was significantly associated with lower mortality rate. Statins (P < 0.001, OR: 0.287, 95% CI: 0.180-0.456) were significantly associated with lower mortality rate. In CAD patients with low GFR, aspirin, clopidogrel and statins had no significant relationship with mortality rate (P > 0.05 for all). In CHF patients without low GFR, statins were significantly associated with lower mortality rate (P < 0.001, OR: 0.220, 95% CI: 0.098-0.490). In CHF patients with low GFR, statins had no significant relationship with mortality rate (P > 0.05 for all).. Clopidogrel but not aspirin was beneficial in Chinese older CAD patients without low GFR rather than those with low GFR, and statins benefited for Chinese older CAD/CHF patients without low GFR rather than those with low GFR. These discoveries might offer some help for the therapy of Chinese older patients with cardiovascular/renal diseases.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Asian People; Aspirin; Calcium Channel Blockers; Clopidogrel; Coronary Artery Disease; Digoxin; Drug Utilization; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Nitrates

The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented.. The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists.. Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled.. Four-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778).. Among hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes.

Topics: Aged; Cardiotonic Agents; Cause of Death; Digoxin; Female; Heart Failure; Humans; Male; Outpatients; Patient Readmission; Propensity Score; Registries; Retrospective Studies; Risk Factors; Stroke Volume; Survival Rate; Treatment Outcome; United States; Withholding Treatment

Topics: Cardiotonic Agents; Digitalis; Digoxin; Heart Failure; Humans; Stroke Volume

Recently, digoxin use has been found to associate with higher mortality. Yet, potential mechanisms by which digoxin use increases mortality remain unclear. Increased arrhythmogenicity from digoxin use is one possibility. Thus, we aimed to evaluate the relation between digoxin and shock events in patients with implantable cardioverter defibrillators (ICDs).. We performed a retrospective chart review of all patients with ICDs and at least 1 device interrogation at our institution between January 1, 2012, and January 1, 2015. We aimed to cover 1 year of interrogation period. Patients with heart failure, atrial fibrillation, or both were included in the analysis. Patients were divided into 2 groups based on digoxin use, defined as use of digoxin for any period of time during ICD interrogation period. Incidence of ICD shock events and electrical storms and hospitalizations were compared between the 2 groups.. The study included 202 patients. Of those, 55 patients were on digoxin and 147 were not on digoxin. Patients on digoxin were more likely to receive ICD shocks (odds ratio [OR] = 2.5, 95% confidence interval [95% CI] = 1.01-6.18, P = .04) and have increased risk of electrical storms ( P = .02). Moreover, total hospitalizations were higher in digoxin users ( P = .02). Multivariate logistic regression analysis also showed that digoxin use was an independent predictor of shock events (OR = 4.07, 95% CI = 1.43-11.58, P = .009).. Digoxin is associated with increased shock events and electrical storms in patients with ICDs; however, large randomized controlled studies are needed to confirm our findings.

Topics: Aged; Cardiotonic Agents; Defibrillators, Implantable; Digoxin; Electric Countershock; Electric Injuries; Female; Heart Failure; Humans; Male; Middle Aged; Prosthesis Failure; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Rate control is now a front-line therapy in the management of atrial fibrillation (AF). However, the survival benefits of different rate-control medications remain controversial, so we assessed the efficacy of rate-control medications in AF patients with concomitant heart failure (HF).Methods and Results:From January 2002 to December 2008, a total of 7,034 AF patients with a single type of rate-control drug or without rate-control treatment were enrolled from the Korea National Health Insurance Service database. The death rates over a mean follow-up of 4.5±1.2 years were 12.6% (580 of 4,593) and 29.0% (709 of 2,441) in non-HF and HF patients, respectively. Among the total subjects, the risk of death was lower in patients receiving β-blockers (adjusted hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.64-0.88) and calcium-channel blockers (adjusted HR 0.74, 95% CI 0.55-0.98) compared with those who did not receive rate-control medications. In patients without HF, use of rate-control medications did not affect the risk of death. In patients with HF, β-blockers significantly decreased the mortality risk (adjusted HR 0.63, 95% CI 0.50-0.79), whereas use of calcium-channel blockers or digoxin was not associated with death. The results were observed consistently among the cohorts after propensity matching.. Use of β-blockers was associated with a reduced mortality rate for AF patient with HF but not for those without HF. These findings should be examined in a large randomized trial.

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Calcium Channel Blockers; Case-Control Studies; Cohort Studies; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Mortality; Propensity Score; Registries; Republic of Korea

Measurement of serum digoxin concentrations before steady-state is reached results in a falsely low concentration, and may affect treatment safety. We evaluated the proportion of serum digoxin measurements performed before steady-state is reached and the reasons for inappropriate sampling in hospitalized patients.. Electronic medical records of patients hospitalized between January 2011 and December 2015 treated with oral digoxin, that had more than one digoxin measurement were included. Serum digoxin measurements performed before achievement of pharmacological steady state were considered as inappropriate. The chi-square and chi-square for trend tests were used to analyse the relationship between inappropriate measurements and age, gender, diagnosis, inpatient service, serum digoxin, potassium and creatinine concentrations.. We evaluated 2065 hospital admissions for 1621 patients and 11,407 digoxin measurements. The time between consecutive measurements was 1.9 ± 2.4 days and 97% of all measurements were classified as inappropriate. There was no releationship between patient age, gender, serum creatinine concentration and inappropriate measurement. As opposed to expected, inappropriate digoxin measurement was higher when potassium concentrations were within the normal range (P = 0.025). Share of inappropriate determinations of digoxin was higher when concentrations > 2.6 nmol/L were recorded (P < 0.05). These measurements were requested most often in coronary care unit and cardiology department.. In our study, inappropriate serum digoxin measurement was found to be very high although only one of the appropriateness criteria was evaluated. The findings reveal the need for some strategies to prevent inappropriate measurements and reduce costs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Creatinine; Digoxin; Drug Monitoring; Female; Heart Failure; Hospitalization; Humans; Immunoassay; Male; Middle Aged; Retrospective Studies; Young Adult

Digoxin has been shown to reduce heart failure hospitalizations with a neutral effect on mortality. It is unknown whether there is heterogeneity of treatment effect for digitalis therapy according to predicted risk of heart failure hospitalization.. We conducted a post hoc analysis of the Digitalis Investigator Group (DIG) studies, randomized controlled trials of digoxin vs placebo in participants with heart failure and left ventricular ejection fraction ≤45% (main DIG study, n = 6800) or >45% (ancillary DIG study, n = 988). Using a previously derived multistate model to risk-stratify DIG study participants, we determined the differential treatment effect on hospitalization and mortality outcomes. There was a 13% absolute reduction in the risk of any heart failure hospitalizations (39% vs 52%; odds ratio 0.58; 95% confidence interval 0.47-0.71) in the digoxin vs placebo arms in the highest-risk quartile, compared with a 3% absolute risk reduction for any heart failure hospitalization (17% vs 20%; odds ratio 0.84; 95% confidence interval, 0.66-1.08) in the lowest-risk quartile. There were 12 fewer total all-cause hospitalizations per 100 person-years in the highest-risk quartile compared with an increase of 8 hospitalizations per 100 person-years in the lowest-risk quartile. There was neutral effect of digoxin on mortality in all risk quartiles and no interaction between baseline risk and the effect of digoxin on mortality (P = .94).. Participants in the DIG study at higher risk of hospitalization as identified by a multistate model were considerably more likely to benefit from digoxin therapy to reduce heart failure hospitalization.

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Risk Factors; Treatment Outcome

Digoxin is commonly prescribed for heart failure patients with reduced ejection fraction (HFrEF) and patients with atrial fibrillation (AF). Due to digoxin's narrow therapeutic range, monitoring the serum digoxin concentration (SDC) is important. However, the SDC measurement is not widely available. Equations using clinical parameters can be employed to estimate the SDC but have never been studied in the Thai population. Therefore, we conducted this study to evaluate the correlation between the measured SDC and predicted digoxin level using 2 commonly used equations: the Konishi equation and the Koup and Jusko equation.. This report describes prospective, cross-sectional study conducted at Chiang Mai University. One hundred and fourteen patients were recruited in the study. All of the patients were diagnosed as having HFrEF, AF or both and had been receiving digoxin for at least 4 weeks. The SDC of each patient was measured at steady state and assigned to one of 3 groups according to the classifications of the Digitalis Investigation Group (DIG) trial: in the therapeutic range, over the therapeutic range and in the suboptimal range.. There were significant correlations between the measured and predicted SDCs using both the Konishi equation and the Koup and Jusko equation, which had correlation coefficients (R) of 0.69 and 0.31 (P < .05 for both), respectively. The percentages of patients with measured SDCs in the therapeutic range, over the therapeutic range and in the suboptimal range were 27.2%, 9.6% and 63.2%, respectively. The sensitivity and specificity of the Konishi equation in predicting SDCs in the over the therapeutic range were 72.73% (95% Confidence interval (CI): 39.03%-93.98%) and 80.58% (95% CI: 71.62%-87.72%), respectively. Of the 5 patients (4.4%) who were rehospitalized, 2 patients (0.01%) were readmitted due to acute decompensated heart failure (ADHF). One of the patients had an SDC that was over the therapeutic range. None of the readmitted patients had ventricular arrhythmia.. The Konishi equation yielded better predictions of the SDC, especially in the subgroup of HFrEF patients. Furthermore, the prediction of SDCs in the over the therapeutic range using this equation was superior to that of the Koup and Jusko equation. With further validation in a larger population, this equation should facilitate the detection of patients who are over the therapeutic range in clinical practice.

Topics: Aged; Atrial Fibrillation; Cardiotonic Agents; Cross-Sectional Studies; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Models, Theoretical; Patient Readmission; Prospective Studies; Sensitivity and Specificity; Stroke Volume; Thailand

Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1-2ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood.. The presented research was based on a retrospective analysis including 2149 patients treated with digoxin and hospitalized between 1980 and 2000. Was used for the determination of SCD automatic analyzer TDX ABBOTT GmbH - fluorescence polarization immunoassay (FPIA), with therapeutic range for digoxin of 0.8-2.0ng/ml.. Average SCD result in the study population was located within the therapeutic range and amounted 1.06ng/ml (55.7% of patients). Statistically significant differences in digoxin level were observed depending on the way of medicine administration (p=0.000001) and the daily amount (p=0.001). Moreover, statistically significant differences in digoxin level were observed depending on sex (p=0.00002).. An elevated level of digoxin was observed in the case of patients who received the medication both orally and intravenously, together with an increase in the daily amount of digoxin doses. It was confirmed that an elevated digoxin level occurs in the course of treatment in the case of women.

Topics: Administration, Intravenous; Administration, Oral; Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Drug Administration Schedule; Drug Monitoring; Female; Heart Failure; Humans; Male; Middle Aged; Poland; Retrospective Studies; Risk Factors; Sex Factors; Time Factors; Treatment Outcome

Digoxin is used in the treatment of atrial fibrillation (AF) and heart failure (HF). It was reported to increase the risk of death in HF. Studies on digoxin are based mainly on patients treated some years ago, before the era of common b-blocker use.. This study aims to show the influence of digoxin in a modern cohort of HF patients on top of the contemporary guideline-directed treatment.. This study retrospectively analyses the Polish part of the European Society of Cardiology Heart Failure Long-Term Registry. It includes 912 patients treated for HF between February 2012 and January 2013, and followed until May 2014. At baseline, 19.1% took digoxin, 89.6% angiotensin convertase enzyme inhibitors or angiotensin receptor blockers, 91.9% b-blockers, and 69.4% mineralocorticoid receptor antagonists.. Digoxin is associated with increased risk of death after adjustment for significant covariates in patients who have HF with reduced ejection fraction (HFrEF) but no AF history (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.23-5.19; p = 0.011), and it does not influence significantly the risk of hospitalisation (adjusted HR 1.46, 95% CI 1.05-1.72; p = 0.11). Digoxin use shows no significant association with the risk of death or hospitalisation in patients with AF and HFrEF or HF with preserved ejection fraction (HFpEF). Patients on digoxin present a significantly worse clinical status with lower left ventricular ejection fraction and higher New York Heart Association class, and fewer of them received the guideline-directed treatment.. Digoxin is associated with increased risk of death in HFrEF patients without AF history receiving the guideline- -directed treatment. Digoxin seems to be employed in patients with worse clinical status, which may at least partially explain its association with increased risk of death.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Middle Aged; Poland; Registries; Retrospective Studies; Treatment Outcome

Digoxin is considered contraindicated in light-chain (AL) amyloidosis, given reports of increased toxicity published 30-50 years ago. We sought to determine the frequency of digoxin toxicity in patients with AL.. We identified 107 patients with AL amyloidosis who received digoxin between 2000 and 2015.. Digoxin may be cautiously utilized in AL amyloidosis patients. We suggest its use in lower doses and frequent drug concentration monitoring along with close monitoring of electrolytes and renal function. Nonetheless, toxicity at low serum concentration cannot be excluded due to potential for toxic concentration at the tissue level and should be taken under consideration when prescribing digoxin for these patients. Studies with higher-level evidence are needed to confirm these findings.

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Retrospective Studies

Whether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data.. MSM is a newer statistical approach, which estimates causal association in the absence of randomization. MSM more effectively accounts for time-varying treatment and mitigates potential biases, in contrast to the two statistical approaches used in prior analyses of the AFFIRM data.. Among 4,060 patients in AFFIRM, 660 (16.3%) died during follow-up. Digoxin was associated with significantly higher mortality in the full cohort (estimated hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11-1.60, P  =  0.002) and in 3,121 patients without HF (HR 1.36, 95% CI 1.07-1.72, P  =  0.011). There was a trend toward higher mortality with digoxin in 939 patients with HF (HR 1.29, 95% CI 0.96-1.72, P  =  0.090). Associations were nonsignificant in 463 patients with HF and left ventricular ejection fraction (EF) ≥40% and in 155 patients with EF ≤30%.. Digoxin is associated with significantly increased mortality among AFFIRM patients collectively, as determined by MSM statistical methodology. However, the impact of digoxin among AFFIRM patients with coexisting HF is inconclusive.

Topics: Aged; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Models, Statistical; Randomized Controlled Trials as Topic; Ventricular Dysfunction, Left

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Stroke Volume; Ventricular Function, Left

Topics: Acute Kidney Injury; Aged, 80 and over; Atrial Fibrillation; Confusion; Delirium; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Lung Diseases; Medically Uninsured; Nausea; Poisoning; Radiography, Thoracic; Vomiting

The impact of atrial fibrillation (AF) on mortality of patients with heart failure (HF) has been established. Nevertheless, the effect of some factors in mortality, such as digoxin or diuretic use, remains controversial. This study aims at assessing mortality in community-dwelling patients with stable HF related to AF and determines the relation of these drugs with prognosis.. Community-based cohort study of HF patients diagnosed between January 2010 and December 2014 attended at any one of the 279 primary healthcare centres of the Catalan Institute of Health (Spain). Follow-up ended on December 31, 2015, and the main outcome was mortality for all causes. The effect of clinical and demographic characteristics on survival was assessed by Cox proportional hazards model.. A total of 13 334 HF patients were included. Mean age was 78.7 years (SD 10.1), and 36.8% had AF. Mean follow-up was 26.9 months (SD 14.0). At the end of the study, 25.8% patients had died, and mortality was higher when AF was present (28.8% vs 24.1%, P < 0.001, respectively). Multivariate model confirmed the higher risk of death for AF patients (HR 1.10 95%, CI 1.02-1.19). Digoxin and diuretics were not associated with higher mortality in AF patients (HR 1.04 95% CI 0.92-1.18 and HR 1.04 95% CI 0.85-1.26, respectively).. An excess of mortality in HF patients with AF was found in a large retrospective community-based cohort. Digoxin and diuretics did not affect mortality in HF patients with AF.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Retrospective Studies; Risk Factors

Resting heart rate (HR) reduction with ivabradine (IVA) improves outcomes of patients with heart failure and reduced ejection fraction (HFrEF). Nevertheless, the best option to slow HR in patients with HFrEF treated with beta-blockers and a HR >70 bpm is unsettled.. To evaluate whether, in patients with HFrEF, commencing therapy with digoxin (CT-DIG) is associated to a worse prognosis than commencing treatment with ivabradine (CT-IVA).. Observational study over 10 years on 2364 patients with HFrEF in sinus rhythm and a HR >70 bpm. Main outcomes were mortality, hospitalisations and visits. We analyse the independent relationship of CT-DIG or CT-IVA with the prognosis, stratifying patients for cardiovascular comorbidity, and for other potential confounders (378 patients who CT-DIG vs another 355 patients who CT-IVA vs another 1631 patients non-exposed to IVA or DIG).. During a median follow-up of 57.5 months, 1751 patients (74.1%) died, and 2151 (91.0%) were hospitalised for HF. CT-DIG or CT-IVA was associated with a lower all-cause mortality (DIG: HR = 0.86 [95% CI, 0.82-0.90], and IVA: HR = 0.88 [0.83-0.93]), cardiovascular mortality (DIG: HR = 0.84 [0.80-0.89] and IVA: HR = 0.83 [0.78-0.89]), hospitalisation (DIG: HR = 0.86 [0.83-0.89] and IVA: HR = 0.87 [0.83-0.91]) and 30-day readmission (DIG: HR = 0.84 [0.79-0.90] and IVA: HR = 0.88 [0.79-0.95]), after adjustment for cardiovascular comorbidity, and other potential confounders. These associations with the prognosis of HFrEF did not differ between patients who CT-DIG and those who CT-IVA.. Commencing therapy with digoxin or with ivabradine is associated with an improved prognosis of patients with HFrEF.

Topics: Adrenergic beta-Antagonists; Aged; Cardiotonic Agents; Cardiovascular Agents; Cohort Studies; Comorbidity; Digoxin; Female; Heart Failure; Hospitalization; Humans; Ivabradine; Male; Patient Readmission; Prognosis; Stroke Volume; Treatment Outcome

Autoantibody against M2-muscarinic acetylcholine receptor (anti-M2AChR) has a biological effect similar to a vagus agonist. Digoxin has a function of vagus nervous system stimulation. We hypothesized that anti-M2AChR is highly correlated with digoxin in patients with chronic heart failure (CHF).. Synthetic M2AChR peptides served as the target antigen in an ELISA were used to screen the sera of 80 CHF patients, who were separated into a negative (-) or positive (+) anti-M2AChR group according to their anti-M2AChR reactivity. Echocardiography and serum digoxin concentration (SDC) were performed at baseline and after 1 year of digoxin in combination with the standard treatment regime. The end-point events were compared over 1 year of follow-up.. Seventy-two CHF patients completed the final data analysis, including 32 (+)anti-M2AChR and 40 (-)anti-M2AChR patients. The resting heart rate of the positive group was higher than that of the negative group at baseline (p < 0.05; 89.0 ± 1.6 vs. 83.8 ± 1.1 bpm). Both groups showed improvement in the left ventricular end-diastolic and end-systolic dimensions and ejection fraction with digoxin in combination with the standard treatment regime for 1 year (all p < 0.01). However, the 32 patients with (-)anti-M2AChR had greater improvements than the 40 patients with (+)anti-M2AChR, and this was accompanied by a marked decrease of rehospitalization (all p < 0.01) but not of cardiovascular mortality after 1 year. The SDC of patients with (-)anti-M2AChR was significantly lower than that of patients with (+)anti-M2AChR (p < 0.05; 0.63 ± 0.05 vs.1.16 ± 0.06 ng/mL) and had a positive correlation with anti-M2AChR (r = 0.81, p < 0.001).. These results suggested that anti-M2AChR could be a useful biomarker of vagus nerve overactivation and is associated with a poor response to digoxin treatment in CHF patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Autoantibodies; Biomarkers; Cardiotonic Agents; China; Digoxin; Enzyme-Linked Immunosorbent Assay; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Prospective Studies; Receptor, Muscarinic M2; Ventricular Function, Left; Young Adult

Gastrointestinal bleeding (GIB) is one of the principal adverse events affecting patients with continuous-flow left ventricular assist devices (CF-LVADs). Despite the early recognition that GIB is commonly because of gastrointestinal angiodysplasia (GIAD), the exact pathophysiology of this process remains elusive. It has been postulated that the abnormal hemodynamic profile in CF-LVAD patients may activate the angiogenesis signaling cascade via the HIF (hypoxia-inducible factor)-1α/angiopoietin-2 pathway leading to formation of GIADs. Digoxin is a potent inhibitor of HIF-1α synthesis, and we hypothesized that its use reduces the incidence of GIAD and GIB in patients with CF-LVAD.. Charts of all adult patients implanted with CF-LVAD between February 2006 and February 2017 were reviewed with particular emphasis on occurrence and cause of GIB. Fifty-four of 199 patients (27%) experienced a GIB. Overall frequency of GIB was lower in the 64 patients receiving digoxin compared with the 135 patients not receiving digoxin (16% versus 33%, P=0.01). Multivariable-adjusted Cox regression analysis confirmed that digoxin use was independently associated with a reduced risk for overall GIB (hazard ratio, 0.49; 95% CI, 0.24-0.98; P=0.045). GIBs were then categorized as non-GIAD, GIAD, or likely GIAD. Although the incidence of non-GIAD was similar in both groups (11% versus 7%, P=0.41), the frequency of GIAD/likely GIAD bleeding was significantly reduced in the digoxin group (5% versus 25%, P=0.0003). Multivariable-adjusted analysis confirmed that digoxin use was independently associated with a reduced risk for GIAD/likely GIAD bleeding (hazard ratio, 0.18; 95% CI, 0.06-0.6; P=0.005). However, digoxin use was not associated with reduced risk for non-GIAD GIB (hazard ratio, 1.54; 95% CI, 0.58-4.08; P=0.39).. Use of digoxin was associated with a significant reduction in GIAD-related GIB in patients with CF-LVAD.

Topics: Adult; Aged; Angiodysplasia; Cardiotonic Agents; Digoxin; Female; Gastrointestinal Hemorrhage; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Prosthesis Design; Protective Factors; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Ventricular Function, Left

Despite major advances in atrial fibrillation (AF) catheter ablation, rate control remains the most widely used management strategy for AF in the general population. In addition to its use as a primary approach to control symptoms and prevent complications of AF, rate control is often a necessary complement to rhythm-control strategies, especially with antiarrhythmic drugs. The value of rate-control therapy is supported by several large randomized clinical trials showing no difference in major cardiovascular outcomes between rate-control and rhythm-control strategies with currently available therapeutic approaches (antiarrhythmic drugs and/or catheter ablation). Despite its extensive use, the rational basis for rate-control therapy is underemphasized in clinical teaching and practice. In this article, we aim to provide evidence-based thoughts on important practical aspects of rate-control therapy in AF by reviewing 5 clinically relevant issues. We (1) highlight the pharmacological differences between the mechanisms of action of β-blockers and Ca

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiac Resynchronization Therapy; Digoxin; Exercise Tolerance; Heart Failure; Heart Rate; Humans; Practice Guidelines as Topic; Stroke Volume

Digoxin is commonly prescribed to elderly patients with heart failure and atrial fibrillation, and macrolide antibiotics markedly increase the risk of digoxin toxicity.. The aim was to determine whether, in older patients receiving digoxin, macrolide antibiotics are associated with sudden death.. We used a population-based, nested, case-control design from January 1, 1994 to December 31, 2012 in a cohort of Ontario residents aged 66 years or older prescribed digoxin. The primary outcome was the risk of sudden death within 14 days of exposure to one of three antibiotics (erythromycin, clarithromycin, or azithromycin), relative to cefuroxime.. Among 39,072 Ontarians who died suddenly while receiving digoxin, 586 died within 14 days of receiving a study antibiotic. Relative to cefuroxime, we found no statistically significant increase in the risk of sudden death following treatment with erythromycin [adjusted odds ratio (aOR) 0.98; 95% confidence interval (CI) 0.65-1.48], clarithromycin (aOR 1.25; 95% CI 0.94-1.65), or azithromycin (aOR 1.07; 95% CI 0.75-1.53).. This finding reinforces the cardiovascular safety of macrolide antibiotics in a high-risk population.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Atrial Fibrillation; Azithromycin; Cardiotonic Agents; Case-Control Studies; Cefuroxime; Clarithromycin; Death, Sudden; Digoxin; Drug Interactions; Erythromycin; Female; Heart Failure; Humans; Macrolides; Male; Ontario; Risk Factors

Topics: Aged, 80 and over; Anti-Arrhythmia Agents; Antihypertensive Agents; Atorvastatin; Atrial Fibrillation; Bone Density Conservation Agents; Deprescriptions; Digoxin; Diltiazem; Diuretics; Drug Overdose; Factor Xa Inhibitors; Female; Furosemide; Heart Failure; Histamine H1 Antagonists, Non-Sedating; Histamine H2 Antagonists; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ibandronic Acid; Lisinopril; Loratadine; Metoprolol; Polypharmacy; Pyrazoles; Pyridones; Ranitidine; Syncope

Topics: Adrenergic beta-Antagonists; Cardiovascular Agents; Carvedilol; Digoxin; Disease Progression; Heart Failure; Humans; Infant, Newborn

Heart failure (HF) is the leading cause of death in the world and digoxin remains one of the oldest therapies for HF. However, its safety and efficacy have been controversial since its initial use and there is uncertainty about its long-term efficacy and safety. Recently, the repositioning of cardiac glycosides is to function in anti-tumor activity via multiple working pathways. It is interesting to compare the potential effects of digoxin in clinical patients and cell lines. First, we analyze patient information retrieved from the National Health Insurance Research database of Taiwan between January 1, 2000 and December 31, 2000. This retrospective study included a study cohort (1,219 patients) and a comparison cohort. Our analytical data suggested that patients taking digoxin are at an increased risk of cancers, including breast, liver, and lung cancers, during the 10-year follow-up period. In contrast to the anti-tumor function of digoxin, we further examined the potential pathway of digoxin via the cell-based strategy using several breast cancer cell lines, including MCF-7, BT-474, MAD-MB-231, and ZR-75-1. Digoxin consistently exerted its cytotoxicity to these four cell lines with various range of concentration. However, the proliferation of ZR-75-1 cells was the only cell lines induced by digoxin and the others were dramatically suppressed by digoxin. The responsiveness of SRSF3 to digoxin might be involved with cell-type differences. In summary, we combined a cohort study for digoxin treatment for HF patients with a cell-based strategy that addresses the translation issue, which revealed the complexity of personalized medicine.

Topics: Adult; Aged; Cell Survival; Comorbidity; Digoxin; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Precision Medicine; Risk; Socioeconomic Factors

Recently published analysis of contemporary atrial fibrillation (AF) cohorts showed an association between digoxin and increased mortality and hospitalizations; however, other studies have demonstrated conflicting results. Many AF cohort studies did not or were unable to examine racial differences. Our goal was to examine risk factors for hospitalizations and mortality with digoxin use in a diverse real-world AF patient population and evaluate racial differences.. Our study demonstrates an overall increased risk of hospitalizations and mortality with digoxin use but no racial/ethnic differences in outcomes were observed. Further studies including minority populations are needed to critically evaluate these associations.

Topics: Administrative Claims, Healthcare; Adolescent; Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Black or African American; Chi-Square Distribution; Digoxin; Disease Progression; Drug Utilization Review; Female; Heart Failure; Hospitalization; Humans; Incidence; Kaplan-Meier Estimate; Male; Medicaid; Middle Aged; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States; White People; Young Adult

Digoxin use has been shown to be associated with a lower risk of 30-day all-cause hospital readmissions in older patients with heart failure (HF). In the current study, we examined this association among long-term care (LTC) residents hospitalized for HF.. Of the 8049 Medicare beneficiaries discharged alive after hospitalization for HF from 106 Alabama hospitals, 545 (7%) were LTC residents, of which 227 (42%) received discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 545 patients, were used to assemble a matched cohort of 158 pairs of patients receiving and not receiving digoxin who were balanced on 29 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin among matched patients were estimated using Cox regression models.. Matched patients (n = 316) had a mean age of 83 years, 74% were women, and 18% African American. Thirty-day all-cause readmission occurred in 21% and 20% of patients receiving and not receiving digoxin, respectively (HR, 1.02; 95% CI, 0.63-1.66). Digoxin had no association with all-cause mortality (HR, 0.90; 95% CI, 0.48-1.70), HF readmission (HR, 0.90; 95% CI, 0.38-2.12), or a combined endpoint of all-cause readmission or all-cause mortality (HR, 0.97; 95% CI, 0.65-1.45) at 30 days. These associations remained unchanged at 1 year postdischarge.. The lack of an association between digoxin and 30-day all-cause readmission in older nursing home residents hospitalized for HF is intriguing and needs to be interpreted with caution given the small sample size.

Topics: Aged; Aged, 80 and over; Alabama; Anti-Arrhythmia Agents; Digoxin; Female; Heart Failure; Homes for the Aged; Hospitalization; Humans; Long-Term Care; Male; Patient Readmission; Propensity Score

The aim of this study was to evaluate factors of digoxin use and its relation to mortality in ED patients with atrial fibrillation (AF).. The Chinese AF registry enrolled 2016 AF patients from 20 representative EDs, and the period of study was one year. Predictors of digoxin use and its relation to mortality were assessed by logistic and Cox regression analyses.. Digoxin was assigned in 609 patients (30.6%), and younger age, lower body mass index values, and existence of permanent AF, heart failure (HF), chronic obstructive pulmonary disease, and valvular heart disease were identified to be factors associated with digoxin use. During the follow-up, compared to patients without digoxin therapy, digoxin-treated patients had significantly higher risk of all-cause death (17.2% vs. 13.0%, P=0.012) and cardiovascular death (15.1% vs. 6.7%, P<0.001), but similar risk of sudden cardiac death (1.1% vs. 0.7%, P=0.341). However, after adjustment for related covariates, digoxin use was no longer notably associated with increased all-cause mortality (hazards ratio [HR] 0.973, 95% confidence interval [CI] 0.718-1.318) and cardiovascular death (HR 1.313, 95% CI 0.905-1.906). Besides, neutral associations of digoxin treatment to mortality were obtained in relevant subgroups, with no interactions observed between digoxin and gender, HF, valvular heart disease, or concomitant warfarin treatment in mortality risk.. In ED patients with AF, digoxin was more frequently assigned to vulnerable patients with concomitant HF or valvular heart disease, and digoxin use was not related to a significantly increased risk of mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Anti-Arrhythmia Agents; Atrial Fibrillation; Body Mass Index; Cardiovascular Diseases; Cause of Death; China; Comorbidity; Death, Sudden, Cardiac; Digoxin; Emergency Service, Hospital; Female; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Mortality; Proportional Hazards Models; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Registries; Risk Factors

The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment.. Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected.. 624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven't analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin. Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing.. A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed.. Introducción: La concentración sérica de digoxina (CSD) debe situarse entre 0,8 y 2 ng/ml. El objetivo es valuar el seguimiento farmacocinético de las CSD que se realiza desde Atención Primaria (AP) en pacientes con tratamiento crónico.Métodos: Estudio trasversal observacional retrospectivo de pacientes en tratamiento crónico con digoxina que pertenecen al departamento de un Hospital General Universitario. Se recogen datos de edad, sexo, diagnóstico, número de determinaciones séricas de digoxina realizadas, fecha y origen de la solicitud de monitorización, resultado analítico y valoración farmacocinética. (Infradosificación, normodosificación o supradosificación).Resultados: 624 pacientes están en tratamiento crónico con digoxina: 68% mujeres, edad media 78,4 (39-98) años. 308 (49,4%) pacientes no tienen realizada ninguna determinación analítica de CSD (Grupo 1), 183 (29,3%) pacientes tienen CSD realizadas de manera esporádica con solicitud tramitada desde Atención Especializada (Grupo 2) y 133 (21,3%) pacientes tienen CSD realizadas de manera periódica con solicitud cursada por médicos de AP, con un promedio de 2,42 monitorizaciones por paciente y año (Grupo 3). Estos son los que tienen un seguimiento farmacocinético del tratamiento crónico con digoxina.Del Grupo 2,2(13,6%) entran por el Servicio de Urgencias por presentar intoxicación digitálica con CSD>2 ng/ml, y 39 (21,3%) pacientes por baja dosificación con CSD<0,5ng/ml. Del Grupo 3,4 (3%) presentan intoxicación digitálica y 5 (3,8%) infradosificación.Conclusiones: Una pequeña parte de los pacientes que se encuentran en tratamiento crónico con digoxina están en seguimiento farmacocinético. Se observa una reducción de las complicaciones derivadas de CSD inapropiadas con respecto a los que no están en seguimiento farmacocinético.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Chronic Disease; Cross-Sectional Studies; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Male; Middle Aged; Primary Health Care; Retrospective Studies

Background Digoxin is a cardiac glycoside that is recommended by clinical practice guidelines to be used in patients with heart failure with reduced ejection fraction (HFrEF) who still have persistent symptoms despite optimal medical therapy. However, this recommendation is based on limited and old trial data. Moreover, pharmacoepidemiologic studies are important in determining the prevalence of digoxin use and factors influencing this. Objective This study aimed to determine the prevalence and the predictors of digoxin utilization among patients with HFrEF with or without atrial fibrillation (AF) in Qatar. Setting Heart Hospital, a specialized tertiary care center in Qatar. Methods A retrospective observational study was conducted using Cerner electronic medical records. Subjects included 736 patients admitted between January 1, 2013 and December 31, 2014 with the diagnosis of HFrEF with or without AF. Two groups of patients were studied: digoxin users and digoxin non-users at index hospitalization until discharge. Univariate and multivariate binary logistic regression analyses were conducted to determine the predictors of digoxin prescription. Data analyses were performed using IBM SPSS

Topics: Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Drug Utilization; Female; Forecasting; Heart Failure; Humans; Male; Middle Aged; Prevalence; Qatar; Retrospective Studies; Stroke Volume; Tertiary Care Centers

Mitochondrial activity is essential for cardiac and skeletal muscle. The relationship between mitochondrial dysfunction and different cardiovascular conditions has been well described. Pharmacological treatment for heart failure involves different drugs as: angiotensin-converting enzyme inhibitors, B-adrenergic blockers, digitalis glycosides and diuretics. The clinical benefit from medication is clear, however, the role of this drugs in mitochondrial metabolisms is not well understood.. The objective of our study was to analyze structural and functional characteristics of cardiac and skeletal muscle mitochondria in mice treated with drugs normally used for heart failure and compare it to a control group. Methods: Twenty-five Albino Mice divided in five groups were treated with heart failure medication during 30 days (group I to IV). 30 days after treatment they were sacrificed, heart and skeletal muscle were analyzed and compared with a control group (V). Results: Enzymatic activity was slightly increased in groups treated with heart failure medication compared to control group (p>0.05). Mitochondrial morphology was significantly altered in groups treated compared to control group, in addition, mitochondrial area was significantly increased in the treated groups, in both cardiac and skeletal muscle. Conclusions: We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology.. Twenty-five Albino Mice divided in five groups were treated with heart failure medication during 30 days (group I to IV). 30 days after treatment they were sacrificed, heart and skeletal muscle were analyzed and compared with a control group (V). Results: Enzymatic activity was slightly increased in groups treated with heart failure medication compared to control group (p>0.05). Mitochondrial morphology was significantly altered in groups treated compared to control group, in addition, mitochondrial area was significantly increased in the treated groups, in both cardiac and skeletal muscle. Conclusions: We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology.. Enzymatic activity was slightly increased in groups treated with heart failure medication compared to control group (p>0.05). Mitochondrial morphology was significantly altered in groups treated compared to control group, in addition, mitochondrial area was significantly increased in the treated groups, in both cardiac and skeletal muscle. Conclusions: We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology.. We concluded that heart failure medication could produce modifications in mitochondrial function; we believe that mitochondria maintains the enzymatic activity by increasing size and modifying morphology.. la actividad mitocondrial es esencial para el músculo cardíaco y esquelético. La relación entre la disfunción mitocondrial y diferentes condiciones cardiovasculares ha sido bien descrita. El tratamiento farmacológico de la insuficiencia cardíaca implica diferentes medicamentos como: inhibidores de la enzima convertidora de la angiotensina, bloqueadores B-adrenérgicos, glucósidos digitálicos y diuréticos. Los beneficios clínicos del tratamiento son claros, sin embargo, el papel de estos fármacos en el metabolismo mitocondrial no esta bien establecido.Objetivo del estudio: El objetivo de nuestro estudio fue analizar las características estructurales y funcionales de las mitocondrias del músculo cardíaco y esquelético en ratones tratados con fármacos habitualmente utilizados para la insuficiencia cardíaca y compararlo con un grupo control.Métodos: Veinticinco ratones albinos divididos en cinco grupos fueron tratados con la medicación para insuficiencia cardíaca durante 30 días (grupo I a IV). 30 días después del tratamiento se sacrificaron, el corazón y el músculo esquelético se analizaron y se compararon con un grupo control (V).Resultados: La actividad enzimática se incrementó ligeramente en los grupos tratados con medicamentos insuficiencia cardiaca en comparación con el grupo control (p> 0,05). morfología mitocondrial se modificó significativamente en los grupos tratados en comparación con el grupo control, además, el área mitocondrial fue significativamente mayor en los grupos tratados, tanto en el músculo cardíaco y estriado.Conclusiones: Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología.. El objetivo de nuestro estudio fue analizar las características estructurales y funcionales de las mitocondrias del músculo cardíaco y esquelético en ratones tratados con fármacos habitualmente utilizados para la insuficiencia cardíaca y compararlo con un grupo control.. Veinticinco ratones albinos divididos en cinco grupos fueron tratados con la medicación para insuficiencia cardíaca durante 30 días (grupo I a IV). 30 días después del tratamiento se sacrificaron, el corazón y el músculo esquelético se analizaron y se compararon con un grupo control (V).Resultados: La actividad enzimática se incrementó ligeramente en los grupos tratados con medicamentos insuficiencia cardiaca en comparación con el grupo control (p> 0,05). morfología mitocondrial se modificó significativamente en los grupos tratados en comparación con el grupo control, además, el área mitocondrial fue significativamente mayor en los grupos tratados, tanto en el músculo cardíaco y estriado.Conclusiones: Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología.. La actividad enzimática se incrementó ligeramente en los grupos tratados con medicamentos insuficiencia cardiaca en comparación con el grupo control (p> 0,05). morfología mitocondrial se modificó significativamente en los grupos tratados en comparación con el grupo control, además, el área mitocondrial fue significativamente mayor en los grupos tratados, tanto en el músculo cardíaco y estriado.Conclusiones: Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología.. Concluimos que la medicación insuficiencia cardíaca podría producir modificaciones en la función mitocondrial; creemos que las mitocondrias pueden mantener la actividad enzimática mediante el aumento de tamaño y modificación de la morfología.

Topics: Animals; Antihypertensive Agents; Atenolol; Cardiotonic Agents; Digoxin; Disease Models, Animal; Diuretics; Electrocardiography; Enalapril; Female; Furosemide; Heart Failure; Isosorbide Dinitrate; Male; Mice; Mitochondria, Heart; Spironolactone

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cardiotonic Agents; Child, Preschool; Digoxin; Female; Fever; Heart Failure; Humans; Myocarditis; Rheumatic Fever

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Glycosides; Clinical Trials as Topic; Digoxin; Drug Prescriptions; Heart Failure; Humans; Publication Bias; Retrospective Studies; Risk Assessment; Selection Bias

Topics: Digoxin; Heart Failure; Humans

Various properties of digoxin have been exploited for decades, amongst which are its positive inotropy used in the treatment of heart failure, and its vagotonic effect used to slow ventricular response to atrial fibrillation. Pharmacologic properties of digoxin are however characterised by a narrow therapeutic interval, and recent observational studies suggest a potential association with increased mortality in patients with atrial fibrillation. As a result and because of available alternative therapeutic strategies, current guidelines do not recommend digoxin as first line treatment of atrial fibrillation. Digoxin may be considered in patients with heart failure and atrial fibrillation with rapid ventricular response when other therapeutic options cannot be pursued.. Depuis de nombreuses années, la digoxine est utilisée dans le traitement de l’insuffisance cardiaque en raison de son inotropisme positif, et pour contrôler la réponse ventriculaire en présence de fibrillation auriculaire (FA) via ses propriétés vagotoniques. Caractérisée par une marge thérapeutique étroite, des études observationnelles récentes suggèrent que la digoxine pourrait être associée à une surmortalité chez les patients avec FA. Pour ces raisons, et du fait de nombreuses alternatives thérapeutiques, la digoxine n’est actuellement plus recommandée en première intention lors de FA. Elle peut être envisagée chez les patients présentant une insuffisance cardiaque et une FA à réponse ventriculaire rapide lorsque des traitements alternatifs ne peuvent être poursuivis.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans; Practice Guidelines as Topic

The treatment of elderly multimorbid patients according to clinical guidelines often results in polypharmacy. An individual risk assessment is required to consider the possibility of deprescribing especially potentially inappropriate medication in the elderly. This exemplary case report describes a medication review of a patient with multiple chronic cardiovascular diseases taking into account the impact on renal function.

Topics: Aged, 80 and over; Atrial Fibrillation; Carbazoles; Carvedilol; Diclofenac; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Myocardial Infarction; Potassium; Potentially Inappropriate Medication List; Propanolamines; Ramipril; Risk Factors; Spironolactone

Serum digoxin levels have limited utility for determining digoxin toxicity in adults. Paediatric data assessing the utility of monitoring serum digoxin concentration are scarce. We sought to determine whether serum digoxin concentrations are associated with signs and symptoms of digoxin toxicity in children.. We carried out a retrospective review of patients 2 ng/ml).. There were 87 patients who met study criteria (male 46%, mean age 8.4 years). CHD was present in 67.8% and electrocardiograms were performed in 72.4% of the patients. The most common indication for digoxin toxicity was heart failure symptoms (61.5%). Toxic serum digoxin concentrations were present in 6.9% of patients (mean 2.6 ng/ml). Symptoms associated with digoxin toxicity occurred in 48.4%, with nausea/vomiting as the most common symptom (36.4%), followed by tachycardia (29.5%). Compared with those without toxic serum digoxin concentrations, significantly more patients with toxic serum digoxin concentrations were female (p=0.02). The presence of electrocardiogram abnormalities and/or signs and symptoms of digoxin toxicity was not significantly different between patients with and without serum digoxin concentrations (p>0.05).. Serum digoxin concentrations in children are not strongly associated with signs and symptoms of digoxin toxicity.

Topics: Adolescent; Age Factors; Arrhythmias, Cardiac; Cardiovascular Agents; Child; Child, Preschool; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Infant; Male; Nausea; Retrospective Studies; Texas; Vomiting

The use of digoxin in patients having atrial fibrillation (AF) with or without heart failure (HF) is not without controversy. The aim of this study was to examine the impact of digoxin therapy on mortality stratified by HF.. Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department of 23 hospitals in 6 countries in the Middle East. Patients were recruited between October 2009 and June 2010 and followed up for 1 year after enrollment. Analyses were performed using univariate and multivariate statistical techniques.. The study included a total of 1962 patients with AF, with an overall mean age of 56 ± 16 years, and 52% (n = 1026) were males. At hospital discharge, digoxin was prescribed in 36% (n = 709) of the patients, whereas HF was present in 27% (n = 528) of the cohort. A total of 225 (12.1%) patients died during the 12-month follow-up period after discharge (5.3% [n = 104] were lost to follow-up). Patients with HF were consistently associated with higher mortality at 1 month (5.1% vs 2.1%; P < .001), 6 months (17.2% vs 5.0%; P < 0.001), and 12 months (24.3% vs 7.6%; P < .001) when compared to those without HF. When stratified by HF, digoxin therapy was associated with significantly higher mortality in those without HF at 6 months (8.7% vs 3.7%; adjusted odds ratio (aOR), 5.07; P < .001) and 12 months (12.3% vs 6.0%; aOR, 4.22; P < .001) but not in those with HF (6 months: 18.6% vs 14.7%; aOR, 1.62; P = .177 and 12 months: 25.4% vs 22.4%; aOR, 1.37; P = .317).. In patients with AF and HF, digoxin did not offer any survival advantages. However, in those without HF, digoxin therapy was, in fact, associated with significantly higher long-term mortality.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Middle East; Patient Selection; Prospective Studies; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Pregnancy increases stress on the circulation of parturient with mitral stenosis secondary to rheumatic heart disease and increases the risk of peripartum heart failure, especially during delivery. This study investigated the epidural anesthesia management for cesarean section in pregnant women with rheumatic heart disease and mitral stenosis.. 48 parturients with rheumatic heart disease and mitral stenosis that had cesarean section deliveries with epidural anesthesia in the Union Hospital, Fujian Medical University (Fuzhou, China) from Jan 2002 to Dec 2012 were retrospectively analyzed. Heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), central venous pressure (CVP), fluid intake volume and fluid output volume (blood loss + urine volume) were analyzed.. Medication included digitalis drugs for heart failure or potential heart failure, digoxin and furosemide for chronic congestive heart failure and beta blockers for arrhythmia. Frequent premature ventricular contractions were treated with lidocaine and propafenone. Dexamethasone was administered when heart failure occurred during less than 37 weeks gestation. HR, SAP, DAP, MAP and CVP were significantly increased at the time of delivery. The fluid intake volume was more elevated in the NYHA III-IV group of parturients than the NYHA I-II group, while fluid output volume was less. All parturients survived.. Epidural anesthesia was applied successfully for cesarean sections for parturients with rheumatic heart disease and mitral stenosis.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Anti-Arrhythmia Agents; Cesarean Section; China; Digoxin; Diuretics; Female; Furosemide; Gestational Age; Heart Failure; Humans; Mitral Valve Stenosis; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnant Women; Retrospective Studies; Rheumatic Heart Disease; Young Adult

Topics: Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male

Topics: Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male

The aim of this study was to assess temporal trends and factors associated with digoxin use at discharge among patients admitted with heart failure (HF).. Digoxin has class IIa recommendations for treating HF with reduced ejection fraction (HFrEF) in the United States. Digoxin use, temporal trends, and clinical characteristics of HF patients in current clinical practice in the United States have not been well studied.. An observational analysis of 255,901 patients hospitalized with HF (117,761 with HFrEF and 138,140 with preserved EF [HFpEF]) from 398 hospitals participating in the Get With The Guidelines-HF registry between January 2005 and June 2014 was conducted to assess the temporal trends and factors associated with digoxin use.. Among 117,761 HFrEF patients, only 19.7% received digoxin at discharge. Digoxin prescriptions decreased from 33.1% in 2005 to 10.7% in 2014 (ptrend < 0.0001). Factors associated with digoxin use in HFrEF included atrial fibrillation (AF) (odds ratio [OR]: 2.14; 95% confidence intervals [CI]: 2.02 to 2.28), history of implantable cardioverter defibrillator use (OR: 1.39; 95% CI: 1.32 to 1.46), chronic obstructive pulmonary disease (OR: 1.13, 95% CI: 1.08 to 1.18), diabetes mellitus (OR: 1.10, 95% CI: 1.06 to 1.14), younger age (OR: 0.96, 95% CI: 0.95 to 0.97), lower blood pressure (OR: 0.96, 95% CI: 0.96 to 0.97), and having no history of renal insufficiency (OR: 0.91, 95% CI: 0.85 to 0.97). Use of digoxin in patients with HFpEF (n = 138,140) without AF was 9.8% in 2005, which decreased to 2.2% in 2014 (ptrend < 0.0001).. One in 5 HFrEF patients received digoxin at discharge, with a significant downward temporal trend in use over the study period. Use of digoxin in HFpEF patients without AF was very low and decreased over the study period.

Topics: Age Factors; Aged; American Heart Association; Atrial Fibrillation; Blood Pressure; Cardiotonic Agents; Comorbidity; Defibrillators, Implantable; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Practice Patterns, Physicians'; Pulmonary Disease, Chronic Obstructive; Registries; Renal Insufficiency; Stroke Volume; United States

This study was developed to determine contemporary management of digoxin toxicity and clinical outcomes.. Although the use of digoxin in heart failure management has declined, toxicity remains a prevalent complication.. The Premier Perspective Comparative Hospital Database (Premier Inc., Charlotte, North Carolina) was used to retrospectively identify patients diagnosed with digoxin toxicity and/or who received digoxin immune fab (DIF) over a 5-year period (2007 to 2011). DIF was evaluated using treatment date, number of vials administered, and total cost. Clinical outcomes included length of stay (total hospitalization; days after DIF), cost of hospitalization, and in-hospital mortality. Exploratory multivariate analyses were conducted to determine predictors of DIF and effect on length of stay, adjusting for patient characteristics and selection bias.. Digoxin toxicity diagnosis without DIF treatment accounted for 19,543 cases; 5,004 patients received DIF of whom 3086 had a diagnosis of toxicity. Most patients were >65 years old (88%). The predictors of DIF use were urgent/emergent admission, hyperkalemia, arrhythmia associated with digoxin toxicity, acute renal failure, or suicidal intent (odds ratios 1.7, 2.4, 3.6, 2.1, and 3.7, respectively; p < 0.0001 for all). The majority (78%) of DIF was administered on days 1 and 2 of the hospitalization; 10% received treatment after day 7. Digoxin was used after DIF administration in 14% of cases. Among patients who received DIF within 2 days of admission, there was no difference for in-hospital mortality or length of stay compared with patients not receiving DIF.. Digoxin toxicity diagnoses are clustered in the elderly. One-fifth of cases receive treatment with DIF, most within 2 days of admission. Opportunities exist for improved diagnosis and post-DIF management. Prospective data may be required to assess the impact of DIF on length of stay.

Topics: Aged; Aged, 80 and over; Antidotes; Cardiotonic Agents; Databases, Factual; Digoxin; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Immunoglobulin Fab Fragments; Linear Models; Male; Middle Aged; Retrospective Studies

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Heart Failure; Humans

In a woman with rheumatic heart disease, atrial flutter with a rapid ventricular response, and congestive heart failure, treatment with digoxin slows conduction in the atrioventricular node and thus allows atrioventricular conduction to occur by way of a previously unrecognized accessory pathway.

Topics: Anti-Arrhythmia Agents; Atrial Flutter; Atrioventricular Node; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Middle Aged; Rheumatic Heart Disease; Tachycardia, Ventricular

Many of the studies associating digoxin use with increased mortality were conducted before beta-blockers became a standard therapy for heart failure (HF) patients. Our goal was to determine the effect of beta-blockers on the prognosis of patients hospitalized for decompensated HF who receive digoxin therapy at discharge.. We analyzed 2402 patients admitted with a primary diagnosis of decompensated HF during the prospective National Heart Failure Survey in Israel. Multivariate modeling was used to determine the effect of beta-blockers and digoxin on 1- and 10-year survival.. Patients discharged on digoxin and beta-blockers (DIG+/BB+) had a lower 1-year mortality rate than those discharged on digoxin alone (DIG+/BB-), (31% vs. 44%; p<0.001). Digoxin administration was associated with an increase in adjusted 1-year (Hazard ratio [HR] 1.28; 95% confidence interval (CI) 1.08-1.50) and 10-year mortality risk (HR 1.27; CI 1.16-1.42), whereas beta-blocker administration was associated with a decrease in adjusted 1-year (HR 0.76; CI 0.68-0.87) and 10-year mortality risk (HR 0.83; CI 0.77-0.89; all p<0.001). In comparison to a DIG-/BB+ group serving as a reference, multivariate adjusted HR for DIG+/BB+ and DIG+/BB- groups were 1.36 (CI 1.03-1.91; p<0.001) and 2.01 (CI 1.59-2.85; p<0.001) at 1-year, and 1.04 (CI 0.84-1.28; p>0.1) and 1.37 (CI 1.17-1.76; p<0.001) at 10years.. In patients hospitalized with decompensated HF, digoxin administration at discharge is associated with increased 1- and 10-year mortality risk. However, the simultaneous use of beta-blockers and digoxin is associated with lower 1- and 10-year mortality risk when compared to use of digoxin alone.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Female; Heart Failure; Hospitalization; Humans; Israel; Male; Middle Aged; Prognosis; Proportional Hazards Models; Prospective Studies; Survival Analysis; Treatment Outcome

Digoxin is widely used as symptomatic treatment in heart failure (HF), but the role in contemporary treatment of HF with sinus rhythm (SR) is debatable. We investigated the risk of death and hospital readmission, according to digoxin use, in a nationwide cohort of digoxin-naïve patients with HF and SR.. From Danish nationwide registries, digoxin-naïve HF patients from 1996 to 2012 were identified. Patients with cardiac dysrhythmias or use of warfarin were excluded. Digoxin users and non-users were compared in propensity matched cox regression models with respect to primary outcomes of all-cause mortality and HF readmission.. The study population comprised 5327 digoxin users and 10,654 matched non-users with a median age of 77. During follow-up 10,643 (66.6%) patients died and 7584 (47.5%) patients were readmitted due to HF. Use of digoxin was associated with increased risk of death (hazard ratio (HR): 1.19, 95%-CI: 1.15-1.24) and increased risk of HF readmission (HR: 1.19, 95%-CI: 1.13-1.25). Cumulative incidences of readmission, considering death as a competing risk was 50% for digoxin users and 47% for non-users. The associations applied regardless of concomitant HF treatment. In an exploratory analysis considering patients with previous digoxin use, no effect on mortality (HR: 1.00, 95%-CI: 0.94-1.06), nor on HF readmission (HR: 1.00, 95%-CI: 0.93-1.09) was observed.. In chronic HF with SR, digoxin was associated with a slightly increased risk of death and was not associated with decreased HF readmission rates.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Cardiotonic Agents; Cohort Studies; Denmark; Digoxin; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Male; Mortality; Patient Readmission; Propensity Score; Registries; Risk Factors

Placental P-glycoprotein (P-gp) plays a significant role in controlling transplacental digoxin transfer rate. Investigations on P-gp regulation in placenta of women with different pregnant pathological states are of great significance to individualized transplacental digoxin treatment for fetal heart failure (FHF). This study aimed to explore the effect of 17α-ethynylestradiol induced intrahepatic cholestasis of pregnancy (ICP) on placental P-gp in mice.. ICP model in mice was induced by subcutaneous injection of 17α-ethynylestradiol dissolved in propylene glycol once daily from E12.5 to E16.5. Maternal plasma ALT, AST, TB, DBIL, γ-GT, LDH, ALP and TBA concentrations were measured. HE staining was applied for observation of maternal liver cells degeneration, necrosis and intrahepatic cholestasis. Placental Abcb1a/Abcb1b/HIF-1α mRNA and P-gp/HIF-1α protein expression were determined by real-time quantitative PCR and western-blot. Maternal plasma and fetal-unit digoxin concentrations were detected by a commercial kit assay.. The ICP group showed higher levels of maternal plasma ALT, AST, TB, DBIL, γ-GT, LDH, ALP and TBA concentrations, reduction in fetal survival rates, lower placental and fetal weights, and typical liver cells degeneration, necrosis and intrahepatic cholestasis. The placental Abcb1a mRNA and P-gp expression of ICP group were significantly elevated, while transplacental digoxin transfer rates were significantly decreased. Both placental HIF-1α mRNA and protein expression was significantly elevated in the ICP group, and there was a positive correlation between Abcb1a mRNA and HIF-1α mRNA.. 17α-ethynylestradiol induced ICP could up-regulate placental P-gp expression and reduce transplacental digoxin transfer rate in mice, which might be partly associated with higher expression of HIF-1α.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cholestasis, Intrahepatic; Digoxin; Ethinyl Estradiol; Female; Heart Failure; Mice; Placenta; Pregnancy; Pregnancy Complications

Topics: Digoxin; Heart Failure; Humans

Many patients with heart failure and reduced EF remain at high risk for hospitalization despite evidence-based therapy. Digoxin may decrease hospitalization; however, uncertainty persists concerning its proper administration and effect on mortality. This study investigated whether using dose response concepts to re-evaluate the relationship between serum digoxin concentration and key mortality outcomes in patients with reduced EF in the Digitalis Investigation Group trial would help clarify efficacy and safety.. Multivariable Cox proportional hazards modelling and propensity score adjustment assessed the relationship between serum digoxin concentration (≥0.5 ng/mL) as a continuous variable and mortality outcomes. In patients treated with digoxin, a significant linear association was found between serum concentration and all-cause mortality [adjusted hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.14-1.38, P < 0.001 per 0.5 ng/mL increase in serum concentration]. Based on this relationship, a bidirectional association was found between digoxin therapy and all-cause mortality when compared with placebo. The lowest serum concentrations (0.5-0.7 ng/mL) were associated with the lowest risk of all-cause mortality (adjusted HR 0.77, 95% CI 0.67-0.89, P < 0.001) while high serum concentrations (1.6-2.0 ng/mL) were associated with increased mortality (adjusted HR 1.33, 95% CI 1.12-1.58, P = 0.001). Consistent with this finding, lower serum concentrations (0.5-0.7 ng/mL) were associated with reduced death from worsening heart failure and a neutral effect on cardiovascular death not due to worsening heart failure.. These findings favour targeting serum concentrations from 0.5 to 0.7 ng/mL when dosing digoxin in patients with heart failure and reduced EF.

Topics: Aged; Cardiotonic Agents; Cause of Death; Digoxin; Dose-Response Relationship, Drug; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Mortality; Multivariate Analysis; Propensity Score; Proportional Hazards Models; Stroke Volume; Treatment Outcome

This study aimed to evaluate the clinical and epidemiologic profile of congestive heart failure at the principal free-care hospital in Haiti. Cardiovascular disease represents the most prevalent cause of admissions to the medical service of the University Hospital of the State of Haiti. No previous study has examined the demographics of congestive heart failure in urban Haiti.. Two hundred forty-seven patients presented to the inpatient service between May 2011 and May 2013. Evaluation included history and physical, CBC, renal/metabolic profile, serum glucose, anti-HIV antibody, ECG, chest radiograph and echocardiogram. Treatment included angiotensin converting enzyme inhibitors, furosemide and spironolactone, carvedilol, digoxin and anticoagulation.. Women (62.4%) outnumbered men; patients were relatively young (mean age 50.1) and from the lowest socio-economic levels of the population. Nearly all (98.8%) presented with NYHA III-IV status, with correspondingly high mortality (23.3%). Echocardiography showed 73% dilated cardiomyopathy; 83% showed moderate to severe LV systolic dysfunction (mean EF 36.5 +/- 15%) and 17% preserved LV systolic function. The three principal etiologies were dilated cardiomyopathy (29%) hypertensive cardiomyopathy (27%) and peripartum cardiomyopathy (20%). Ischemic cardiomyopathy was rare (3.4%). At 27 months follow-up, 76.7% of the patients were alive and well. Among those who died, mean survival time was 113 days. Readmission carried a poor prognosis.. This congestive heart failure study from Haiti shows an unusually high proportion of young women, primarily due to peripartum cardiomyopathy. Ischemic cardiomyopathy is rare, as in Africa. Further study is warranted to address the particular problem of the high frequency of peripartum cardiomyopathy in this population.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Age Distribution; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Carbazoles; Cardiomyopathy, Dilated; Cardiotonic Agents; Carvedilol; Cohort Studies; Digoxin; Diuretics; Echocardiography; Electrocardiography; Female; Furosemide; Haiti; Heart Failure; Hospitalization; Hospitals, University; Hospitals, Urban; Humans; Hypertension; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Propanolamines; Prospective Studies; Puerperal Disorders; Sex Distribution; Spironolactone; Stroke Volume; Young Adult

The effects of digitalis on mortality in patients with structural heart disease are controversially discussed. We aimed to assess the effects of digitalis administration in implantable cardioverter defibrillator (ICD) recipients.. This retrospective analysis comprises 1020 consecutive patients who received an ICD at our institution and who were followed for up to 10 years (median 37 months). A total of 438 patients were receiving digitalis at the time of ICD implantation and 582 did not. Patients on digitalis were more often in atrial fibrillation and had more often a prolonged QRS duration of ≥120 ms, a severely impaired left ventricular ejection fraction, and higher New York Heart Association (NYHA) classification heart failure. Crude Kaplan-Meier analysis demonstrated significantly higher mortality in patients on digitalis (HR = 2.47; 95% CI 1.87-3.25; P = 0.001). After adjustment for patient characteristics found statistically significant in adjusted Cox regression analysis (age, gender, NYHA classification, and QRS duration of ≥120 ms), a HR of 1.65 remained (95% CI 1.14-2.39; P = 0.01). Patients on digitalis died more often from cardiac arrhythmic and cardiac non-arrhythmic causes than patients not on digitalis (P = 0.04). There was no difference in mortality between patients receiving digitoxin and those receiving digoxin (HR = 1.55; 95% CI 0.74-3.25; P = 0.25).. In this large ICD patient population, digitalis use at baseline was independently associated with increased mortality even after careful adjustment for possible confounders. Digitalis should be used with great caution in this population.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Cohort Studies; Defibrillators, Implantable; Digitalis Glycosides; Digitoxin; Digoxin; Female; Follow-Up Studies; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Treatment Outcome

The zebrafish-based assay is a widely used animal model system for cardiovascular research. In this study, we investigated the cardiac defects caused by terfenadine and tested the pharmacological response of digoxin to zebrafish with cardiac defects. The study suggested that zebrafish could be a suitable model for phenotype-based screening and evaluation of positive inotropic agents. This phenotype-based heart failure zebrafish model system was then utilized in in-house library screen. Some positive inotropic compound was discovered, which could attenuate the cardiac defects by increasing the flow velocity of caudal artery blood.

Topics: Animals; Blood Pressure; Cardiotonic Agents; Digoxin; Disease Models, Animal; Embryo, Nonmammalian; Heart; Heart Failure; Heart Rate; Male; Myocardium; Phenotype; Rats; Rats, Sprague-Dawley; Terfenadine; Zebrafish

Some evidences suggest that the use of digoxin may be harmful inatrial fibrillation (AF) patients. The aim of the study was to investigate in a "real world" of AF patients receiving vitamin K antagonists (VKAs), the relationship between digoxin use and mortality.. Prospective single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs. Total mortality was the primary outcome of the study. We also performed a sub-analysis considering only cardiovascular (CV) deaths. Time in therapeutic range (TTR) was used for anticoagulation quality.. Median follow-up was 33.2months (2460 person-years); 171 (21.0%) patients were taking digoxin. Compared to those without, patients on digoxin were older (p=0.007), with a clinical history of HF (p<0.001) and at higher risk of thromboembolic events (p<0.001). No difference in TTR between the two groups was registered (p=0.598). During the follow-up, 85 deaths occurred: 47 CV and 38 non-CV deaths; 35 deaths occurred in digoxin users (20.6%). A significant increased rate of total mortality was observed in digoxin-treated patients (p<0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p<0.001) and CV death (HR: 4.686, p<0.001). A propensity score-matched analysis confirmed that digoxin was associated with total mortality (HR: 2.073, p=0.0263) and CV death (HR: 4.043, p=0.004).. In AF patients on good anticoagulation control with VKAs, digoxin use was associated with a higher rate of total and CV mortality.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cause of Death; Digoxin; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Male; Propensity Score; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Survival Rate

Topics: Adult; Cardiotonic Agents; Digoxin; Drug Interactions; Heart Failure; Humans; Male; Middle Aged; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Young Adult

Rural residence is a negative prognostic factor for heart failure (HF). The objective was to explore rural and urban differences in the utilization, adherence, and persistence with medications, and mortality among incident HF patients.. Using administrative databases from Alberta (Canada), subjects > 65 years old with a first hospitalization for HF between 1999 and 2008 who survived ≥ 90 days after discharge were identified. Pharmacy claims for renin-angiotensin system (RAS) agents, β-blockers (BBs), digoxin, or spironolactone were identified. The association between rural and urban residence and medication utilization, adherence (optimal adherence defined as ≥ 80% adherence over 1 year), persistence, and 1-year mortality was assessed.. The cohort included 10,430 patients, with a mean age of 80.2 (SD, 7.7) years, 47% were male, and 25% were rural residents. Rural residents were less likely to receive RAS agents (74% vs 79%, adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69-0.89) or BBs (44% vs 54%; aOR, 0.83; 95% CI, 0.73-0.93) than urban residents, but had similar use of other medications. Although < 69% of patients who received RAS agents and 53% who received BBs had optimal adherence, few differences in adherence or persistence were detected among patients in rural vs urban areas. The 1-year mortality rate was significantly lower for patients who demonstrated optimal adherence to RAS agents or BBs (aOR, 0.78; 95% CI, 0.65-0.94) with no significant differences in the first 6 months between patients residing in rural vs urban areas.. Rural residents with HF were less likely to receive RAS agents or BBs, but few differences in adherence were noted compared with their urban counterparts. Suboptimal adherence with evidence-based HF therapy was associated with increased risk of mortality.

Topics: Adrenergic Antagonists; Aged; Aged, 80 and over; Canada; Cardiotonic Agents; Cardiovascular Agents; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Humans; Male; Medication Adherence; Renin-Angiotensin System; Retrospective Studies; Rural Population; Spironolactone; Treatment Outcome; Urban Population

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Patient Readmission

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Patient Readmission

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Risk Assessment; Stroke

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Risk Assessment; Stroke

Topics: Adrenergic beta-Antagonists; Adult; Aged; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Availability; Carbazoles; Cardiotonic Agents; Carvedilol; Clinical Trials as Topic; Cross-Over Studies; Digoxin; Drug Interactions; Heart Failure; Humans; Male; Middle Aged; Propanolamines

Therapeutic and toxic effects of digoxin are related to its serum concentrations, recent evidence suggests that a lower therapeutic range 0.5-0.9 ng/ml is associated with reduced mortality.. To show the advantages of therapeutic drug monitoring for dosing of digoxin.. Trough serum levels of digoxin were estimated by immunoassay MEIA (AxSym Abbott). The long term serum concentration - time profile of digoxin has been predicted by the Bayesian analysis computer program MW-Pharm 3.30 MediWare.. Sex case reports of the patients between 71 to 92 years are presented to show the different doses to receive digoxin levels in the therapeutic range. The doses varies between 0.03-0.25 mg per day.. Therapeutic drug monitoring is very usefull for prediction of serum level of digoxin. There is no need to wait for a steady-state condition before performing therapeutic drug monitoring.

Topics: Aged; Aged, 80 and over; Bayes Theorem; Cardiotonic Agents; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Male

Although digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial.. This study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF, to characterize the predictors of digoxin use and initiation, and to correlate digoxin use with outcomes.. Longitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011.. Among 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) received digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. After adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers (p < 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity adjusted HR: 1.05), but was associated with subsequent death in those without HF (propensity adjusted HR: 1.99).. After adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Because of the multiple conflicting observational reports about digoxin's safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Prospective Studies; Quality of Life; Registries; Time Factors; Treatment Outcome

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Stroke Volume; Withholding Treatment

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans

Placental P-glycoprotein (P-gp) plays a significant role in controlling digoxin transplacental rate. Investigations on P-gp regulation in placenta of women with different pregnant pathology are of great significance to the individualized transplacental digoxin treatment for fetal heart failure (FHF). This study aimed to explore the effect of maternal obesity on the expression and functionality of placental P-gp both in human and in mice.. Placenta tissues from obese and lean women were collected. Female C57BL mice were fed with either a normal chow diet or a high-fat diet for 12 weeks before mating and throughout pregnancy. Maternal plasma glucose, HDL-C, LDL-C, TC, TGs, insulin, IL-1β, IL-6 and TNF-α concentrations was detected. Placental ABCB1/Abcb1a/Abcb1b/IL-1β/IL-6/TNF-α mRNA and P-gp/IL-1β/IL-6/TNF-α protein expression were determined by real-time quantitative PCR and western-blot, respectively. Maternal plasma and fetal-unit digoxin concentrations were detected by a commercial kit assay.. Both ABCB1 gene mRNA and protein expression of obesity group was significantly lower than that of control group in human. The high-fat dietary intervention resulted in an overweight phenotype, a significant increased Lee's index, higher levels of plasma glucose, HDL-C, LDL-C, insulin and TGs, increased peri-renal and peri-reproductive gland adipose tissue weight, and larger size of adipose cell. Compared with control group at the same gestational day (E12.5, E15.5, E17.5), placental Abcb1a mRNA and P-gp expression of obese group were significantly decreased in mice, while digoxin transplacental rates were significantly increased. Higher maternal plasma IL-1β/TNF-α concentrations and placental IL-1β/TNF-α expression were observed in obesity groups in comparison with control group at the same gestational age.. Maternal obesity could inhibit placental P-gp expression and its functionality both in human and in mice, which might be resulted from a heightened inflammatory response.

Topics: Adult; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiotonic Agents; Case-Control Studies; Digoxin; Disease Models, Animal; Female; Fetal Diseases; Heart Failure; Humans; Mice, Inbred C57BL; Obesity; Placenta; Precision Medicine; Pregnancy; Pregnancy Complications; Random Allocation

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Rate and rhythm control strategies for atrial fibrillation (AF) are not always effective or well tolerated in patients with congestive heart failure (CHF). We assessed reasons for treatment failure, associated characteristics, and effects on survival.. A total of 1,376 patients enrolled in the AF-CHF trial were followed for 37  ±  19 months, 206 (15.0%) of whom failed initial therapy leading to crossover. Rhythm control was abandoned more frequently than rate control (21.0% vs. 9.1%, P < 0.0001). Crossovers from rhythm to rate control were driven by inefficacy, whereas worsening heart failure was the most common reason to crossover from rate to rhythm control. In multivariate analyses, failure of rhythm control was associated with female sex, higher serum creatinine, functional class III or IV symptoms, lack of digoxin, and oral anticoagulation. Factors independently associated with failure of rate control were paroxysmal (vs. persistent) AF, statin therapy, and presence of an implantable cardioverter-defibrillator. Crossovers were not associated with cardiovascular mortality (hazard ratio [HR] 1.11 from rhythm to rate control; 95% confidence interval [95% CI, 0.73-1.73]; P = 0.6069; HR 1.29 from rate to rhythm control; 95% CI, 0.73-2.25; P = 0.3793) or all-cause mortality (HR 1.16 from rhythm to rate control, 95% CI [0.79-1.72], P = 0.4444; HR 1.15 from rate to rhythm control, 95% [0.69, 1.91], P = 0.5873).. Rhythm control is abandoned more frequently than rate control in patients with AF and CHF. The most common reasons for treatment failure are inefficacy for rhythm control and worsening heart failure for rate control. Changing strategies does not impact survival.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Creatinine; Defibrillators, Implantable; Digoxin; Disease Progression; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Sex Factors; Treatment Failure

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans; Risk Factors

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Topics: Cardiotonic Agents; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Practice Patterns, Physicians'

Recent data on digoxin prescribing and adverse events are lacking but could help inform the management of digoxin in contemporary heart failure treatment.. We determined nationally representative numbers and rates of emergency department (ED) visits for digoxin toxicity in the United States using 2005 to 2010 reports from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project and the National Ambulatory (and Hospital Ambulatory) Medical Care Surveys. Based on 441 cases, an estimated 5156 (95% confidence interval [CI], 2663-7648) ED visits for digoxin toxicity occurred annually in the United States; more than three fourths (78.8% [95% CI, 73.5%-84.1%]) resulted in hospitalization. Serum digoxin level was ≥2.0 ng/mL for 95.8% (95% CI, 93.2%-98.4%) of estimated ED visits with levels reported (n=251 cases). The rate of ED visits per 10 000 outpatient prescription visits among patients≥85 years was twice that of patients 40 to 84 years (rate ratio, 2.4 [95% CI, 1.2-5.0]); among women, the rate was twice that of men (rate ratio, 2.3 [95% CI, 1.1-4.7]). Digoxin toxicity accounted for an estimated 1.0% (95% CI, 0.6%-1.4%) of ED visits for all adverse drug events among patients≥40 years, but an estimated 3.3% (95% CI, 2.3%-4.4%) of ED visits and 5.9% (95% CI, 4.0%-7.9%) of hospitalizations for all adverse drug events among patients≥85 years. Estimated annual ED visits and hospitalizations remained relatively constant from 2005 to 2010.. Digoxin toxicity is not declining; more careful prescribing to high-risk groups and improved monitoring of serum levels might be needed to reduce morbidity from outpatient digoxin use.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Anti-Arrhythmia Agents; Digoxin; Disease Management; Emergency Service, Hospital; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Sex Factors; United States

Topics: Beverages; Chemistry, Clinical; Digoxin; Drug Monitoring; False Positive Reactions; Female; Flavonoids; Heart Failure; Herb-Drug Interactions; Hibiscus; Humans; Rosa

Topics: Adult; Aged; Cardiotonic Agents; Chromatography, High Pressure Liquid; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Immunoassay; Male; Mass Spectrometry; Middle Aged; Outpatients

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiotonic Agents; Digoxin; Female; Fetal Diseases; Heart Failure; Maternal-Fetal Exchange; Pregnancy; Rats; Rats, Sprague-Dawley

To obtain more information regarding the influence of various covariates on the disposition of digoxin in Chinese neonates and infants, routine clinical pharmacokinetic data were retrospectively collected from 131 hospitalized patients. A nonlinear mixed effects modeling (NONMEM) method was applied to the data. A one-compartment/first-order absorption model was employed to estimate the influence of total body weight (allometric power model), postnatal age, serum creatinine, gender, presence of heart congestive failure, and concomitant medications on apparent total clearance and apparent drug distribution of digoxin. Pharmacokinetic parameter estimates for CL/F and V/F were 0.147 L∙h(-1)∙kg(-1) and 15.7 L/kg, respectively. Total body weight and postnatal age were identified as the important factors affecting total clearance of digoxin; total body weight was the covariate identified to influence the apparent distribution volume. Both internal (bootstrap method, visual predictive checks, and normalized prediction distributed error) and external validation supported the stable and predictive performance of the final model. We concluded that the model can be used to choose an appropriate dose regimen in Chinese neonates and infants.

Topics: Age Factors; Asian People; Body Weight; Cardiotonic Agents; Creatinine; Digoxin; Female; Heart Failure; Humans; Infant; Infant, Newborn; Male; Models, Biological; Predictive Value of Tests; Retrospective Studies

Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4-1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8-2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC.. The study subjects comprised 72 patients with cardiac failure or/and atrial tachyarrhythmia seen at our hospital from January 2012 to December 2013. The patients were divided into five groups according to Kidney Diseases Outcome Quality Initiative guidelines. SDCs were measured using the Abbott Architect i1000 immunology analyzer. The correlations between measured SDCs and calculated SDCs and between clearance of digoxin and creatinine clearance rate were assessed retrospectively.. The correlation between measured and predicted SDC calculated by the Konishi equation was significant (r=0.655, P<0.001) for the 72 patients overall; however, correlations within the different stages of renal function were nonsignificant, with a correlation found only in patients with stage 3 (30 mL per minute < creatinine clearance <60 mL per minute). With regard to the correlation between clearance of digoxin and creatinine clearance, our results show that although there was a significant correlation between clearance of digoxin and creatinine clearance in the group overall, correlations were not evident within the different stages of renal function.. The results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease. Further research in larger numbers of patients across all stages of renal function will be required in the future to verify the original Konishi model.

Topics: Administration, Oral; Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Drug Monitoring; Female; Heart Failure; Humans; Male; Middle Aged; Models, Theoretical; Retrospective Studies; Tachycardia, Ectopic Atrial

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Digoxin; Dose-Response Relationship, Drug; Down-Regulation; Drug Synergism; Drugs, Chinese Herbal; Female; Fetal Heart; Heart Failure; Lactates; Mice; Mice, Inbred C57BL; Phenanthrenes; Placenta; Pregnancy; Random Allocation; Treatment Outcome

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Hospitalization; Humans; Treatment Outcome

The aims of this study were to investigate the clinical outcomes of patients with low-gradient aortic stenosis despite preserved left ventricular ejection fraction and to assess reliable prognostic clinical-instrumental features in patients experiencing or not experiencing aortic valve replacement (AVR). Clinical-laboratory and echocardiographic data from 167 patients (median age 78 years, interquartile range 69 to 83) with aortic valve areas <1.0 cm(2), mean gradients ≤30 mm Hg, and preserved left ventricular ejection fraction (≥55%), enrolled from 2005 to 2010, were analyzed. During a mean follow-up period of 44 ± 23 months, 33% of patients died. On multivariate analysis, independent predictors of death were baseline New York Heart Association functional class III or IV (hazard ratio 2.16, p = 0.038) and atrial fibrillation (hazard ratio 2.00, p = 0.025). Conversely, AVR was protective (hazard ratio 0.25, p = 0.01). The magnitude of the protective effect of AVR seemed to be relatively more important in patients with atrial fibrillation than in those in sinus rhythm, independently of the severity of symptoms. Age >70 years showed a trend toward being a prognostic predictor (p = 0.082). In conclusion, in patients with low-gradient aortic stenosis despite a preserved left ventricular ejection fraction, AVR was strongly correlated with a better prognosis. Patients with atrial fibrillation associated with advanced New York Heart Association class had the worst prognosis if treated medically but at the same time a relative better benefit from surgical intervention.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Atrial Fibrillation; Calcium Channel Blockers; Cardiovascular Agents; Digoxin; Diuretics; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Multivariate Analysis; Nitroglycerin; Platelet Aggregation Inhibitors; Prognosis; Proportional Hazards Models; Severity of Illness Index; Stroke Volume; Treatment Outcome

Topics: Acute Disease; Aged; Cardiotonic Agents; Digoxin; Electrocardiography; Female; Heart Conduction System; Heart Failure; Humans; Systole; Tachycardia; Ventricular Dysfunction

This study aimed to evaluate the effectiveness of digoxin in children with heart failure secondary to left-to-right shunt lesions and normal left ventricular systolic function. The study registered 37 such patients (ages 10 days to 24 months, groups 1 and 2) and used 20 healthy children as a control group (group 3). Left ventricular systolic function, as assessed by conventional echocardiography, was normal in all the subjects. Congestive heart failure was diagnosed by clinical evaluation and modified Ross scoring. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations and complete blood counts were assessed in all the children. Group 1 was treated with digoxin, enalapril, and furosemide and group 2 with enalapril and furosemide. Approximately 1 month after starting treatment, the patients were reevaluated by physical and echocardiographic examinations, modified Ross scoring, plasma NT-proBNP concentrations, and complete blood counts. The pre- and posttreatment Ross scores of group 1 (p = 0.377) and group 2 (p = 0.616) did not differ significantly. The NT-proBNP values in both groups decreased after treatment (p = 0.0001). The pre- and posttreatment NT-proBNP values did not differ significantly in group 1 (p = 0.094)) and group 2 (p = 0.372). The pretreatment NT-proBNP values in groups 1 and 2 (p = 0.0001) were significantly higher than in the control group (p = 0.003). A smaller difference was observed between posttreatment NT-proBNP values in group 1 and the control group (p = 0.045). We found no significant difference between the posttreatment NT-proBNP values of group 2 and those of the control group (p = 0.271). The study showed that both treatments currently used to treat heart failure secondary to congenital heart disease with left-to-right shunts and preserved left ventricular systolic function are effective and do not differ significantly. Thus, digoxin does not provide any extra benefit in the treatment of such patients.

Topics: Biomarkers; Child, Preschool; Digoxin; Echocardiography; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Failure; Heart Ventricles; Humans; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Retrospective Studies; Systole; Treatment Outcome; Ventricular Function, Left

Chronic heart failure may increase risk of pneumonia due to alveoli flooding and reduced microbial clearance. We examined whether chronic heart failure is a risk factor for pneumonia-related hospitalization.. In this large population-based case-control study we identified adult patients with a first-time primary or secondary discharge diagnosis of viral or bacterial pneumonia between 1994 and 2008, using health care databases in Northern Denmark. For each case, ten sex- and age-matched population controls were selected from Denmark's Civil Registration System. We used conditional logistic regression to compute relative risk (RR) for pneumonia-related hospitalization among persons with and without pre-existing heart failure, overall and stratified by medical treatment. We controlled for a wide range of comorbidities, socioeconomic markers and immunosuppressive treatment.. The study included 67,162 patients with a pneumonia-related hospitalization and 671,620 population controls. The adjusted OR for pneumonia-related hospitalization among persons with previous heart failure was 1.81 (95% confidence interval (CI): 1.76-1.86) compared with other individuals. The adjusted pneumonia RR was lower for heart failure patients treated with thiazides only (adjusted OR=1.56, 95% CI: 1.46-1.67), as compared with patients whose treatment included loop-diuretics and digoxin as a marker of increased severity (adjusted OR=1.95, 95% CI: 1.85-2.06) or both loop-diuretics and spironolactone (adjusted OR=2.02, 95% CI: 1.90-2.15). The population-attributable risk of pneumonia hospitalizations caused by heart failure in our population was 6.2%.. Patients with chronic heart failure, in particular those using loop diuretics, have markedly increased risk of hospitalization with pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Case-Control Studies; Chronic Disease; Denmark; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Pneumonia; Risk Factors

The impact of digoxin on outcomes of patients with advanced heart failure (HF) remains uncertain and its effect may be different for patients in atrial fibrillation (AF) or sinus rhythm (SR).. To determine the impact of digoxin on outcomes of advanced HF patients and to assess whether prognosis differs in patients in AF and SR.. A total of 268 consecutive patients admitted to an intensive care unit with decompensated HF were evaluated. Patients were divided into two groups: A - patients with AF (n=89), and B - patients in SR (n=179). For each group we compared patients medicated and not medicated with digoxin. A mean follow-up of 3.3 years was performed.. Addition of digoxin to contemporary standard HF therapy showed no impact on mortality of patients in group B (all-cause mortality in follow-up: 19.1% vs. 22.5%, p=0.788). Regarding group A, we observed significantly lower medium-term mortality for patients on digoxin therapy (18.6% vs. 46.6%, p=0.048). Digoxin therapy did not influence readmissions for decompensated HF. Among AF patients, no differences were found regarding demographic, clinical, echocardiographic and laboratory variables between patients medicated and not medicated with digoxin.. Digoxin therapy may improve the prognosis of advanced HF patients with AF under optimal medical therapy. However, no benefit of digoxin was demonstrated for patients in SR. These results may help to improve patient selection for digoxin therapy.

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Severity of Illness Index

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Failure; Humans; Randomized Controlled Trials as Topic

Topics: Cardio-Renal Syndrome; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Laboratories, Hospital; Randomized Controlled Trials as Topic; Reference Values; Surveys and Questionnaires; United States

Chronic heart failure (CHF) is a condition that is daily confronted by clinicians in a variety of medical specialties, where physicians routinely seek optimum pharmacotherapy for their outpatients with CHF. We conducted a population- based study on pharmacotherapy for outpatients with CHF in Taiwan from 2000 to 2010, which focused on drug prescription patterns of different physician specialties.. We retrieved records from the National Health Insurance Research Database of patient ambulatory visits with diagnosed chronic heart failure, when cardiovascular drugs were prescribed. For purposes of this study, anti-chronic heart failure drugs were separated into categories: mortality reducing agents (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, spironolactone, hydralazine plus nitrates) and symptom-relieving agents (digoxin, diuretics). Thereafter, the trends of prescription patterns related to different physician specialties were analyzed.. From 2000 to 2010, the prescription rate of any mortality-reducing agent for CHF outpatients rose from 61.5% to 76.3% while the concomitant rate for digoxin decreased from 47.3% to 45.4%. Compared to internists and family physicians, cardiologists not only prescribed far more mortality-reducing agents from 2000 to 2010 (53.9 - 72.7%, 54.1 - 64.3%, 74.7 - 84.4%, respectively), but also prescribed two or three mortality-reducing drugs.. There was a significant improvement of optimal pharmacotherapy for chronic heart failure in Taiwan. We observed that cardiologists were more aggressive than non-cardiologists when deciding whether to prescribe mortality-reducing drugs for heart failure management. However, those factors which influence the prescription patterns of internists and family physicians for their patients with CHF still require additional research.

Topics: Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Female; Heart Failure; Humans; Male; Practice Patterns, Physicians'; Specialization; Taiwan; Time Factors

A 27 year old female with a complex history of congenital heart disease, cardiac surgery, heart failure, and arrhythmias was admitted for a Pseudomonas aeruginosa sternal wound infection and treated with intravenous antibiotics. After discharge and completion of an outpatient course of intravenous antibiotics, suppressive antibiotic therapy with ciprofloxacin was initiated. She presented to clinic with nausea and anorexia within a few days of addition of ciprofloxacin to her current regimen of medications, which included digoxin. The digoxin was discontinued, with all other medications remaining the same, and the symptoms resolved in 48 h. The dose of digoxin was restarted at 50 % of the previous dose with no further complications. The proposed cause of the nausea and anorexia was digoxin toxicity secondary to a drug-drug interaction with ciprofloxacin.. Patients receiving ciprofloxacin and digoxin should be monitored closely for the risk of digoxin toxicity.

Topics: Adult; Anorexia; Anti-Bacterial Agents; Cardiotonic Agents; Ciprofloxacin; Digoxin; Drug Interactions; Drug Monitoring; Female; Heart Failure; Humans; Nausea; Pacemaker, Artificial; Pseudomonas aeruginosa; Pseudomonas Infections; Reoperation; Surgical Wound Infection; Treatment Outcome

Topics: Adult; Anti-Arrhythmia Agents; Biomarkers; Blood Transfusion, Intrauterine; Case-Control Studies; Cytokines; Digoxin; Female; Fetal Diseases; Heart Failure; Humans; Infant, Newborn; Male; Pregnancy; Tachycardia; Treatment Outcome; Young Adult

The management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration (CVVH) is reported.. A 46-year-old African-American woman with New York Heart Association class IV, American College of Cardiology- American Heart Association stage D heart failure arrived from an outside facility with complaints of dyspnea after minimal exertion, orthopnea, and lower-extremity edema. A transthoracic echocardiogram revealed an estimated left ventricular ejection fraction of 15%. The patient subsequently required left ventricular assist device placement on hospital day 5 as a potential bridge to transplantation. A total digoxin loading dose of 500 μg i.v. (8.2 μg/kg) was given in two divided doses six hours apart. The next morning, the serum digoxin concentration was 1.9 ng/mL, and the patient was started on a maintenance digoxin dosage of 125 μg i.v. daily. On postoperative day (POD) 20, the patient developed acute kidney injury, and CVVH was initiated. The sieving coefficient (Sc), transmembrane clearance (CLtm), digoxin concentration in ultrafiltration fluid (Cuf), and need for supplemental digoxin were determined to account for CVVH- associated digoxin loss. After 14 days of CVVH, the patient's clinical condition improved, and CVVH was transitioned to intermittent hemodialysis. On POD 66, the patient was discharged to an extended-care facility without adverse reactions related to digoxin therapy.. Analysis of serum digoxin concentration and digoxin Cuf values suggested that digoxin was cleared by CVVH, allowed calculation of Sc and CLtm values, and facilitated determination of digoxin requirements in a critically ill patient requiring CVVH.

Topics: Acute Kidney Injury; Cardiotonic Agents; Critical Illness; Digoxin; Dose-Response Relationship, Drug; Echocardiography; Female; Heart Failure; Heart-Assist Devices; Hemofiltration; Humans; Middle Aged

Topics: Aged; Blood Pressure; Carcinoma, Hepatocellular; Cardiotonic Agents; Digoxin; Fatal Outcome; Heart Failure; Humans; Liver Neoplasms; Male; Pulmonary Embolism; Renal Insufficiency, Chronic; Systole

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male

Readmission for heart failure remains a major focus of policymakers, clinicians, and patients. Despite meeting key national performance measures and frequent use of evidence-based therapies, rates of 30-day post-discharge rehospitalization may be as high as 25%. Digoxin and mineralocorticoid antagonists are known to reduce admissions for heart failure, but are significantly underused in current clinical practice despite their proven benefits.

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Patient Readmission; Risk; Time Factors

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male

Recent years have witnessed new innovation in Bayesian techniques to adjust for unmeasured confounding. A challenge with existing methods is that the user is often required to elicit prior distributions for high-dimensional parameters that model competing bias scenarios. This can render the methods unwieldy. In this paper, we propose a novel methodology to adjust for unmeasured confounding that derives default priors for bias parameters for observational studies with binary covariates. The confounding effects of measured and unmeasured variables are treated as exchangeable within a Bayesian framework. We model the joint distribution of covariates by using a log-linear model with pairwise interaction terms. Hierarchical priors constrain the magnitude and direction of bias parameters. An appealing property of the method is that the conditional distribution of the unmeasured confounder follows a logistic model, giving a simple equivalence with previously proposed methods. We apply the method in a data example from pharmacoepidemiology and explore the impact of different priors for bias parameters on the analysis results.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bayes Theorem; Bias; Cardiotonic Agents; Confounding Factors, Epidemiologic; Data Interpretation, Statistical; Digoxin; Diuretics; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pharmacoepidemiology; Regression Analysis

Topics: Acute Coronary Syndrome; Algorithms; Cardiology; Cardiotonic Agents; Cardiovascular Diseases; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Medicare

The importance of heart rate in the pathophysiology of heart failure with reduced LVEF has recently attracted attention. In particular, the findings of the Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial (SHIFT) have put special emphasis on heart rate reduction with ivabradine for improvement in clinical outcomes. Of course, there is a much older drug that reduces heart rate, i.e. digoxin.. In this short commentary, we retrospectively analyse the Digitalis Investigation Group (DIG) Trial looking at the primary composite endpoint used in SHIFT (i.e. cardiovascular death or hospital admission for worsening heart failure) and compare the effect of digoxin on this endpoint with that of ivabradine. A remarkably similar risk reduction in the composite outcome and in its components appears evident among patients receiving the active treatment in both studies (although ivabradine was added to a beta-blocker, whereas digoxin was not).. This raises the question of whether the Cardiological community dismissed digoxin too readily and if we should reappraise its potential role in the treatment of heart failure.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzazepines; Digoxin; Female; Heart Failure; Humans; Ivabradine; Kaplan-Meier Estimate; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Practice Guidelines as Topic; Reference Values

Topics: Adrenergic beta-Antagonists; Adult; Cardiotonic Agents; Digoxin; Drug Synergism; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Severity of Illness Index

Heart failure is a heterogeneous syndrome. Approximately 30-50% of patients with heart failure have normal or near normal left ventricle function. Several epidemiological studies confirm that the prevalence of heart failure with normal ejection fraction is increasing. Given the current trends, heart failure with normal ejection fraction will become the most common form of heart failure, for which we do not currently have an evidence-based successful treatment. This article summarizes the etiology, current recommended guidelines and management options for this clinical manifestation.

Topics: Calcium Channel Blockers; Cardiotonic Agents; Digoxin; Diuretics; Global Health; Heart Failure; Humans; Pandemics; Prevalence; Renin-Angiotensin System; Stroke Volume; Ventricular Function, Left

To establish the role of patient characteristics in estimating doses of digoxin for infants and young children using routine therapeutic drug monitoring data, the steady-state blood-level data (n = 245) after repetitive oral administration in 117 hospitalized infants and young children were analyzed using nonlinear mixed effects modeling (NONMEM), a computer program designed for analyzing drug pharmacokinetics in study populations through pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished using a 1-compartment pharmacokinetic model. Estimates generated by NONMEM indicated that the clearance of digoxin (CL/F; L/h) was influenced by the following demographic variables: total body weight (TBW), presence of congestive heart failure (CHF), and infant-young children clearance factor (trough serum concentration of digoxin; Conc). These influences could be modeled by the equation CL/F (L/h) = 0.302 · TBW (kg)¹·¹⁷ · 0.905(CHF) · Conc (trough serum digoxin concentration >1.7 ng/mL)⁻⁰·⁵⁴⁰; F = 0.754, where CHF is 1 for presence of congestive heart failure, 0 otherwise; F is bioavailability, 1 for elixirs, 0.754 for powders; and Conc⁻⁰·⁵⁴⁰ is 1 for digoxin concentration <1.7 ng/mL. Clinical application of the model to patient care may permit selection of an appropriate initial maintenance dose, thus enabling the clinician to achieve the desired therapeutic effect. However, the digoxin dosage regimen for the individual patient should be based on a careful appraisal of his or her clinical need for the drug.

Topics: Asian People; Cardiotonic Agents; Child, Preschool; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Infant; Male; Models, Statistical; Nonlinear Dynamics; Pharmaceutical Solutions; Powders; Reproducibility of Results; Retrospective Studies

Management of systolic heart failure can be particularly challenging in patients with chronic kidney disease, especially those who are not yet receiving dialysis. Few clinical trials have been performed in this particular population, so management is directed by evidence from studies of patients with limited or no renal impairment. Their heightened risk for many treatment complications mandates additional considerations regarding drug selection, dosing, and monitoring. Subspecialty consultation is driven by patient instability or disease progression, intolerance of standard treatment, or need for device placement.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Digoxin; Heart Failure; Humans; Hyperkalemia; Kidney Diseases; Mineralocorticoid Receptor Antagonists

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

We assessed, in patients with a first hospitalization for heart failure (HF), the temporal relationship of the incidence of cardiovascular events, all-cause mortality, and cardiovascular drug treatment.. Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. Patients were selected based on a first hospital discharge diagnosis of documented HF. Two time-periods were compared: 1998-2002 and 2003-07. In each time-period, we analysed all prescribed cardiovascular medications, all-cause mortality, and cardiovascular events (rehospitalization for HF and ischaemic events) within the first year after hospitalization, and the occurrence of ischaemic events separately (myocardial infarction and ischaemic stroke). Cox-regression analysis was performed to calculate hazard ratios (HR) with 95% confidence intervals (CI). We identified 8276 patients in 1998-2002 and 9548 patients from 2003-07. There was an increase in almost all cardiovascular medication prescriptions in the second period: in particular, beta-blocker prescriptions rose from 36% in 1998-2002 to 55% in 2003-07. In the first year after hospitalization, there was no difference in all-cause mortality or any cardiovascular event (HR 1.00, 95%CI: 0.95-1.05), as a composite endpoint or when analysed separately. The incidence of ischaemic events decreased from 2.7 to 1.9% in the first and second time-period, respectively (HR 0.74, 95%CI: 0.61-0.90).. Prescription of cardiovascular medications in patients with a first hospitalization for HF has increased in recent years, particularly for beta-blockers, and the incidence of ischaemic events may have decreased. There was no decrease in all-cause mortality or cardiovascular events.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Practice Patterns, Physicians'; Prognosis; Spironolactone; Stroke

The force-frequency relationship (FFR) reflects alterations in intracellular calcium cycling during changing heart rate (HR). Tachycardia-induced heart failure is associated with depletion of intracellular calcium. We hypothesized (1) that the relative resistance to tachycardia-induced heart failure seen in neonatal pigs is related to differences in calcium cycling, resulting in different FFR responses and (2) that pretreatment with digoxin to increase intracellular calcium would modifies these changes. LV +dP/dt was measured during incremental right atrial pacing in 16 neonatal and 14 adult pigs. FFR was measured as the change in +dP/dt as HR was increased. Animals were randomized to control or intravenous bolus digoxin (n = 8 neonate pigs in the 0.05 mg/kg group and n = 7 adult pigs in the 0.025 mg/kg group) and paced for 90 min at 25 bpm greater than the rate of peak +dP/dt. Repeat FFR was then obtained. The postpacing FFR in neonatal control pigs shifted rightward, with peak force occurring 30 bpm greater than baseline (P < 0.03). There was no vertical shift; thus, force at 150 bpm decreased (P < 0.03) and force at 300 beats/min increased (P < 0.08). In adult control pigs, FFR shifted downward (P < 0.01), with decreased force generation at all HRs. In both neonates and adult pigs, digoxin increased +dP/dt at all HRs; however, in neonate pigs digoxin decreased the contractile reserve by abrogation of the rightward shift of FFR. An adaptive response to tachycardia in the neonate pig leads to improved force generation at greater HRs. Conversely, the response of the mature pig heart is maladaptive with decreased force generation. Pretreatment with digoxin modifies these responses.

Topics: Age Factors; Animals; Animals, Newborn; Calcium Channels; Cardiac Pacing, Artificial; Cardiotonic Agents; Cytoplasm; Cytosol; Digoxin; Electrocardiography; Heart Failure; Heart Rate; Models, Theoretical; Myocardial Contraction; Sarcoplasmic Reticulum; Swine; Tachycardia; Ventricular Function, Left

Paediatric cardiomyopathy and heart failure are distinct but frequently associated conditions, which have a high mortality. Traditional medical therapy has evolved to incorporate newer classes of heart failure drugs, although the evidence to support efficacy in children is limited. This perspective article discusses the rationale, benefits and limitations of the various classes of drug therapy used in paediatric heart failure due to cardiomyopathy or congenital heart disease. Controversies in management and challenges for future development are highlighted.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Cardiotonic Agents; Child; Digoxin; Diuretics; Heart Defects, Congenital; Heart Failure; Humans; Hydrazones; Natriuretic Peptide, Brain; Pyridazines; Simendan

We investigated the prevalence and indications of digoxin use in elderly patients presenting to a cardiology outpatient clinic of a tertiary hospital in Turkey.. On a prospective basis, the study included 800 consecutive patients aged 70 or over (mean age 77 ± 6 years) who presented to our cardiology outpatient clinic. There were 124 patients (15.5%) receiving digoxin. All the patients underwent transthoracic echocardiography. Digoxin use was considered inappropriate if the patient had normal left ventricle systolic function or if there was no atrial fibrillation (AF).. The reasons for use of long-term digoxin were persistent AF (n=55, 44.4%), heart failure (HF) (n=51, 41.1%), and paroxysmal AF (n=8, 6.5%). The exact reason could not be determined in 10 patients (8.1%). Digoxin use was based on appropriate indications in 76 patients (61.3%), whereas 48 patients (38.7%) were taking digoxin with inappropriate indications. Of 51 patients for whom HF was the only reason for digoxin therapy, diagnosis of HF was incorrect in 30 patients (24.2%). Other inappropriate indications were paroxysmal AF and undetermined indication for digoxin prescription. Concerning digoxin dose, 24 patients (19.4%) received one tablet (0.25 mg) and 30 patients (24.2%) received a half tablet (0.125 mg) on a daily basis, while 10 patients (8.1%) used six tablets per week with one day off (0.214 mg/day) and 60 patients (48.4%) took five tablets per week with two days off (0.179 mg/day). The median daily dose was 0.182 mg/day. Digoxin dose was higher than the recommended doses for elderly patients in 75.8% of the patients.. Our findings show that nearly 40% of elderly patients receive digoxin with inappropriate indications and 75% of these patients take digoxin at higher doses than the recommended doses for this age group.

Topics: Aged; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Echocardiography, Transesophageal; Female; Health Services for the Aged; Health Services Misuse; Heart Failure; Humans; Male; Outpatient Clinics, Hospital; Prevalence; Prospective Studies; Turkey

Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity.. This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94).. The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.

Topics: Aged; Aged, 80 and over; Anthraquinones; Case-Control Studies; Constipation; Digoxin; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Male; Middle Aged; Senna Extract; Sennosides

Topics: Atrial Fibrillation; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Recent quality initiatives require that the routine annual therapeutic drug-monitoring (TDM) parameters for the high-risk medication digoxin include a measure of renal function and a serum potassium level but not a serum digoxin concentration (SDC) measurement. Several studies have shown that the majority of the SDCs obtained in hospital settings provide little clinically actionable information.. To evaluate the appropriateness and utility of SDCs ordered in a medical group practice setting by categorizing the reason the SDC was ordered and identifying action taken in response to the result.. The descriptive study was conducted as a retrospective, electronic medical record (EMR) review of 90 primary care patients with continuous prescriptions for digoxin current on their medication profile with no gaps in therapy for at least 2 years prior to an SDC result entered into the EMR between January 1, 2009, and September 30, 2009. The reason the SDC was ordered was abstracted independently by 2 reviewers, who then assigned it to 1 of 8 predefined indication categories based on previously published criteria and practice guidelines. A third reviewer resolved inter-reviewer discrepancy (n = 1).. A total of 90 patients with at least 1 SDC met inclusion criteria. Routine monitoring was the most frequent SDC order indication category with 35 patients (38.9%), 17 (48.6%) of whom did not have the recommended monitoring measures of potassium or renal function drawn concurrently. Patients were included in other categories as follows: confirmation of signs/symptoms of toxicity 30 (33.3%); assessment of factors altering pharmacokinetics 5 (5.6%); assessment of dosage change 5 (5.6%); assessment of drug interaction 3 (3.3%); assessment of clinical response 3 (3.3%); assessment of adherence 1 (1.1%); and other 2 (2.2%). Across all categories, a total of 19 (21.1%) of SDC results were outside the therapeutic range of 0.5 nanograms (ng) per mL and 2.0 ng per mL, 18 of which were below 0.5 ng per mL, with none of the subtherapeutic levels leading to a change in digoxin therapy. Only 1 patient (1.1%) had therapy changed in response to an elevated abnormal SDC result of 2.1 ng per mL and was in the routine monitoring category.. The majority of SDC results obtained in our medical group setting did not lead to clinical action, such as dose adjustment or drug discontinuation. SDCs were commonly measured as part of routine monitoring, which is considered an inappropriate indication, and often without being accompanied by better markers for digoxin toxicity such as serum potassium levels and measures of renal function as recommended by drug-monitoring quality initiatives. Provider education is needed regarding the most indicative digoxin TDM parameters to obtain in order to satisfy quality initiatives.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Data Interpretation, Statistical; Digoxin; Drug Interactions; Drug Monitoring; Electronic Health Records; Female; Heart Failure; Humans; Kidney Function Tests; Male; Middle Aged; Patient Compliance; Potassium; Retrospective Studies

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male

The role of digoxin in the prognosis of patients with heart failure (HF) remains unclear.. To evaluate the relationship of commencing treatment with digoxin (CTDig) with the mortality and the morbidity of patients with HF.. Prospective study over 8 years on 4467 patients with HF. Main outcomes were all-cause and cardiovascular mortality, hospitalisations and visits. We analyse the independent relationship of CTDig, with the mortality and the morbidity, stratifying patients for cardiovascular comorbidity, after propensity score-matching for potential confounders (1421 patients who CTDig vs. another 1421 patients non-exposed to digoxin).. During a median follow up of 46.1 months, 1872 patients (65.9%) died, and 2203 (77.5%) were hospitalised. CTDig was associated with a lower all-cause mortality (HR = 0.90 [95% CI, 0.84-0.97]), and cardiovascular mortality (HR = 0.87 [0.81-0.96]), hospitalisation (HR = 0.91 [0.86-0.97]), 30-day readmission for HF (HR = 0.88 [0.79-0.95]), and visits (HR = 0.94 [0.90-0.98]) (p < 0.001 in all cases), after adjustment for the propensity to take digoxin, other medications, and other potential confounders. These effects of digoxin were independent of gender, or type of HF (systolic or non-systolic).. The data suggest that therapy with digoxin is associated with an improved mortality and morbidity of HF, including women and patients with non-systolic HF.

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Propensity Score; Prospective Studies; Treatment Outcome

We report the synthesis and biological properties of novel analogues of Istaroxime acting as positive inotropic compounds through the inhibition of the Na(+),K(+)-ATPase. We explored the chemical space around the position 6 of the steroidal scaffold by changing the functional groups at that position and maintaining a basic oximic chain in position 3. Some compounds showed inhibitory potencies of the Na(+),K(+)-ATPase higher than Istaroxime and many of the compounds tested in vivo were safer than digoxin, the classic digitalis compound currently used for the treatment of congestive heart failure as inotropic agent. The 3D-QSAR analyses using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to a set of 63 androstane derivatives as Na(+),K(+)-ATPase inhibitors. The contour plots provide many useful insights into relationships between structural features and inhibitory potency.

Topics: Androstanes; Animals; Enzyme Inhibitors; Etiocholanolone; Guinea Pigs; Heart Failure; Sodium-Potassium-Exchanging ATPase; Stereoisomerism; Structure-Activity Relationship

Here we develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of digoxin in serum.. The serum samples were extracted with methyl tert-butyl ether using an isotope-labeled digoxin-d3 as internal standard. The analyte was separated on a reverse phase Capcell C18 column and detected in positive electrospray ionization multiple reaction monitoring mass spectrometry.. The chromatographic analysis was carried out within 3 min, but the complete analysis took longer because of the liquid-liquid extraction. The lower limit of quantification was 0.1 ng/mL for digoxin. The intra- and inter-batch precisions were less than 12%, and the bias ranged from -9.1% to 10.7%. The external quality assessment (EQA) results obtained with the LC-MS/MS method were comparable to target values. Subsequently, this method has been applied to the therapeutic monitoring of digoxin in a clinical setting.. In this study, we have developed a rapid and reliable LC-MS/MS method for the therapeutic monitoring of digoxin in human serum.

Topics: Chromatography, Liquid; Digoxin; Heart Failure; Humans; Molecular Structure; Quality Control; Reproducibility of Results; Tandem Mass Spectrometry

Acute heart failure syndromes, commonly recognized as de novo heart failure or acute decompensated chronic heart failure (ADHF), are characterized by a rapid onset or change in signs and symptoms of heart failure requiring urgent treatment. Coexisting renal dysfunction is associated with poor prognosis in these patients. We sought to determine whether renal impairment in particular and other admission factors in general predict long-term mortality after hospitalization for ADHF.. We studied 128 patients (age 63 + or - 12 years, 76% male) in NYHA class 2.6 + or - 0.7 with a left ventricular ejection fraction (LVEF) < or = 39%, hospitalized due to ADHF. Mortality rates (per 100 person-years) were 21.9 at 12 months and 12.0 at 60 months. We found that admission serum creatinine level was the best predictor of mortality after 1 (P < 0.001, log-transformed due to skewed distribution) and 5 years (P = 0.001), followed by creatinine clearance, the use of loop diuretics, and digoxin. Moreover, higher NYHA class, decreased body mass index (BMI) and increased levels of urea predicted 1 and 5 years mortality on univariate analysis. In the multivariate analysis, creatinine, NYHA class, and LVEF emerged as independent predictors of mortality after 1 year, whereas BMI and the use of diuretics did not reach significance (joint chi(2) = 29.40, P < 0.001). After 5 years, creatinine and NYHA class independently predicted all-cause mortality (joint chi(2) = 22.71, P < 0.001), but BMI and age did not remain significant.. Admission creatinine level strongly predicts medium- and long-term mortality after hospitalization in patients with ADHF, and serves as a cheap and fast clinical marker to identify patients at risk of death.

Topics: Aged; Body Mass Index; Cardiotonic Agents; Confidence Intervals; Creatinine; Digoxin; Female; Germany; Heart Failure; Humans; Kaplan-Meier Estimate; Kidney Diseases; Linear Models; Male; Middle Aged; Multivariate Analysis; Prognosis; Retrospective Studies; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Statistics as Topic; Stroke Volume; Treatment Outcome; Ventricular Function, Left

The purpose of this study was to report the efficacy of intravenous amiodarone alone or in combination with digoxin in neonates and small infants with life-threatening supraventricular tachyarrhythmia (SVT).. We retrospectively analyzed 9 neonates and small infants with life-threatening or resistant SVT who were treated with intravenous amiodarone alone or in combination with digoxin.. This report consists of 8 patients with reentrant SVT and 1 with atrial flutter. On admission, 7 patients had a congestive heart failure and 3 of whom had cardiovascular collapse. Intravenous rapid bolus of adenosine caused a sustained sinus rhythm in 4 patients. These patients were given digoxin initially, but recurrence of persistent tachyarrhythmia necessitated the use of intravenous amiodarone in all these patients. Amiodarone was given initially to the other 4 patients in whom adenosine caused only temporary conversion to the sinus rhythm. It was effective in 2 patients. In the other 2, digoxin was added to therapy for tachycardia control. Amiodarone alone or in combination with digoxin effectively controlled reentrant SVT in all patients. This combined treatment caused ventricular rate control in patient with atrial flutter, and conversion to the stable sinus rhythm was achieved at approximately 8 months.. Intravenous amiodarone alone or in combination with digoxin was found to be safe and effective in controlling refractory and life-threatening SVT in neonates and small infants.

Topics: Adenosine; Amiodarone; Anti-Arrhythmia Agents; Atrial Flutter; Digoxin; Drug Evaluation; Drug Therapy, Combination; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Failure; Heart Neoplasms; Heart Rate; Humans; Hypotension; Infant; Infant, Newborn; Infusions, Intravenous; Injections, Intravenous; Male; Retrospective Studies; Rhabdomyoma; Shock, Cardiogenic; Tachycardia, Supraventricular; Thyrotropin; Treatment Outcome

The necessity of implantable cardioverter-defibrillator (ICD) implantation in patients with systolic heart failure (HF) who undergo cardiac resynchronization therapy (CRT) may be questioned. The aim of this study was to identify patients at low risk for sustained ventricular arrhythmia. One hundred sixty-nine consecutive patients with HF (mean age 60 +/- 12 years, 125 men, 73% in New York Heart Association class III) referred for CRT and prophylactic, primary prevention ICD implantation underwent baseline clinical and echocardiographic assessment and regular device follow-up. The primary study end point was appropriate ICD therapy. During a mean follow-up period of 654 +/- 394 days, 35 patients (21%) had sustained ventricular arrhythmias requiring appropriate ICD therapy. Of the 3 patients who experienced sudden cardiac death, 2 had been treated with appropriate ICD therapy before sudden cardiac death. In a multivariate model, only history of nonsustained ventricular tachycardia (p = 0.001), a severely (<20%) decreased left ventricular ejection fraction (p = 0.001), and digitalis therapy (p = 0.08) independently predicted appropriate ICD therapy. Patients with 0 (n = 46), 1 (n = 36), 2 (n = 73), and 3 (n = 14) risk factors for appropriate ICD therapy had a 7%, 14%, 27%, and 64% and 0%, 6%, 10%, and 43% incidence of appropriate ICD therapy for ventricular arrhythmias and for rapid ventricular tachycardia or ventricular fibrillation, respectively. In conclusion, apart from commonsense considerations (age and significant co-morbidities), ICD addition seems ineffective in CRT patients without nonsustained ventricular tachycardia, digoxin therapy, and severely reduced left ventricular systolic function.

Topics: Cardiotonic Agents; Death, Sudden, Cardiac; Decision Making; Defibrillators, Implantable; Digoxin; Echocardiography, Doppler; Electric Countershock; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Prognosis; Risk Factors; Stroke Volume; Time Factors

A 42-year-old man with ankylosing spondylitis that was refractory to nonsteroidal anti-inflammatory drugs as well as various disease-modifying antirheumatic drugs was subjected to anti-TNF compounds. Administration of infliximab and adalimumab gave excellent clinical response but was discontinued due to adverse events. Introduction of etanercept was also clinically effective but followed by development of severe heart failure. Discontinuation of etanercept led to control of heart function. The unusually though potentially life-threatening possibility of heart failure secondary to anti-TNF use in ankylosing spondylitis merits attention.

Topics: Adult; Anti-Arrhythmia Agents; Digoxin; Diuretics; Etanercept; Heart Failure; Humans; Immunoglobulin G; Immunologic Factors; Male; Receptors, Tumor Necrosis Factor; Spondylitis, Ankylosing

Recent investigations have demonstrated that the occurrence of implantable cardioverter-defibrillator (ICD) shocks is associated with adverse long-term outcomes. These studies have emphasized that the risk is most reasonably due to arrhythmias rather than to the shock itself. We sought to compare the impact of shock delivery for induced ventricular arrhythmias during implantation defibrillation threshold testing and noninvasive electrophysiology study (NIPS) to clinical shocks on long-term outcomes among patients with ICDs.. This was a cohort evaluation of 1,372 patients undergoing ICD implantation at a tertiary hospital from December 1997 to January 2007. The probability of all-cause mortality and hospitalization for acute decompensated heart failure (ADHF) was evaluated based upon the type of ICD shock received using multivariable Cox proportional analyses. The four shock types analyzed were implantation shocks only (n = 694), additional NIPS shocks only (n = 319), additional appropriate shocks only (n = 128), or additional inappropriate shocks only (n = 104).. The risk of death (adjusted hazard ratio [AHR] 0.91 [95% confidence interval (CI) 0.69-1.20]; P = .491) or ADHF (AHR 0.71 [95% CI 0.46-1.16]; P = .277) were similar between recipients of NIPS shocks and recipients of implantation shocks. Receiving an appropriate ICD shock increased the risk of death (AHR 2.09 [95% CI 1.38-2.69]; P <.001) and ADHF (AHR 2.40 [95% CI 1.51-3.81]; P <.002) as compared with implantation shocks and also increased the risk of death (AHR 2.61 [95% CI 1.86-3.67]; P <.001) and ADHF (AHR 2.29 [95% CI 1.33-3.97]; P = .003) as compared with NIPS shocks.. ICD shocks delivered during induced ventricular arrhythmias at the time of NIPS testing does not increase the risk of death or ADHF as compared with recipients of appropriate ICD shocks. The occurrence of spontaneous arrhythmias in vulnerable substrates may explain the increased risk.

Topics: Aged; Anti-Arrhythmia Agents; Cohort Studies; Confidence Intervals; Connecticut; Defibrillators, Implantable; Digoxin; Electrophysiology; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Phenethylamines; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Sulfonamides; Tachycardia, Ventricular; Treatment Outcome; Ventricular Fibrillation

Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents.. We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI.. The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality.. Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Case-Control Studies; Diabetes Mellitus, Type 2; Digoxin; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Metformin; United Kingdom

The purpose of this study is to describe an in utero management strategy for fetuses with immune-mediated 2° or 3° atrioventricular (AV) block.. The management strategy as applied to 29 fetuses consisted of three parts. First, using fetal echocardiography and obstetrical ultrasound, we assessed fetal heart rate (FHR), heart failure, growth and a modified biophysical profile score (BPS) assessing fetal movement, breathing and tone. Second, we treated all fetuses with transplacental dexamethasone, adding terbutaline if the FHR was<56 bpm. Digoxin and/or intravenous immune globulin (IVIG) was added for progressive fetal heart failure. Third, we delivered fetuses by cesarean section for specific indications that included abnormal BPS, maternal/fetal conditions, progression of heart failure, or term pregnancy. We assessed perinatal survival, predictors of delivery and maternal/fetal complications in 29 fetuses with 3° (n=23) or 2° (n=6) AV block. There were no fetal deaths. In utero therapy included dexamethasone (n=29), terbutaline (n=13), digoxin (n=3) and/or IVIG (n=1). Delivery indications included term gestation (66%), fetal/maternal condition (14%), low BPS (10%) and progression of fetal heart failure (10%). An abnormal BPS correlated with urgent delivery.. These results suggest that applying this specific management strategy that begins in utero can improve perinatal outcome of immune-mediated AV block.

Topics: Atrioventricular Block; Cardiotonic Agents; Cesarean Section; Dexamethasone; Digoxin; Female; Fetal Diseases; Glucocorticoids; Heart Failure; Heart Rate, Fetal; Humans; Immunoglobulins, Intravenous; Maternal-Fetal Exchange; Pregnancy; Terbutaline; Ultrasonography, Prenatal

To establish a population pharmacokinetic (PPK) model of digoxin in older Chinese patients to provide a reference for individual medication in clinical practice.. Serum concentrations of digoxin and clinically related data including gender, age, weight (WT), serum creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), albumin (ALB), and co-administration were retrospectively collected from 119 older patients taking digoxin orally for more than 7 d. NONMEM software was used to get PPK parameter values, to set up a final model, and to assess the models in clinical practice.. Spironolactone (SPI), WT, and Cr markedly affected the clearance rate of digoxin. The final model formula is Cl/F=5.9x[1-0.412 x SPI] x [1-0.0101x(WT-62.9)] x [1-0.0012x(Cr-126.8)] (L/h); Ka=1.63 (h(-1)); V(d)/F=550 (L). The population estimates for Cl/F and V(d)/F were 5.9 L/h and 550 L, respectively. The interindividual variabilities (CV) were 49.0% for Cl/F and 94.3% for V(d)/F. The residual variability (SD) between observed and predicted concentrations was 0.365 microg/L. The difference between the objective function value and the primitive function value was less than 3.84 (P>0.05) by intra-validation. Clinical applications indicated that the percent of difference between the predicted concentrations estimated by the PPK final model and the observed concentrations were -4.3%-+25%. Correlation analysis displayed that there was a linear correlation between observed and predicted values (y=1.35x+0.39, r=0.9639, P<0.0001).. The PPK final model of digoxin in older Chinese patients can be established using the NONMEM software, which can be applied in clinical practice.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Asian People; Computer Simulation; Digoxin; Female; Heart Failure; Humans; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Regression Analysis; Retrospective Studies; Software

Digoxin therapy is used to treat heart failure patients for more than 200 years. However, absence of effect on overall mortality found in the DIG study associated with frequent adverse effects due to overdosing in elderly patients with impaired renal function finally persuaded medical opinion to the weak interest of digoxin in chronic heart failure. Its image of old-fashioned drug in the mind of young cardiology generations appears widely distorted, and suffers from the absence of promotion by pharmaceutical industry, given a very low cost and a rapid arrival onto the generic market. Yet, regarding strict data from the literature, it remains a lot of positive factors in favor of the interest for digoxin: reduction of morbidity, reduction of mortality at low serum concentration <1.0 ng/ml, very low cost with favorable cost-effectiveness ratio. This article challenges some arguments for defending digoxin as another first-line therapy as well as ACE inhibitors and beta-blockers in the treatment of chronic heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cost-Benefit Analysis; Digoxin; Drug Costs; Drug Therapy, Combination; Evidence-Based Medicine; Heart Failure; Humans; Risk Assessment; Treatment Outcome

Acute heart failure represents an increasingly common cause of hospitalization, and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. However, currently available therapies may have deleterious effects and increase mortality. An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects. Such a drug is not available yet. New agents with different biological targets are under clinical development. In particular, istaroxime seems to dissociate the inotropic effect exerted by digitalis (inhibition of the membrane sodium/potassium adenosine triphosphatase) from the arrhythmic effect and to ameliorate diastolic dysfunction (via sarcoendoplasmic reticulum calcium adenosine triphosphatase activation). Additionally, the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in animal studies only. Further investigations are needed to confirm and expand the effectiveness and safety of these agents in patients with acute heart failure and low cardiac output.

Topics: Acute Disease; Animals; Cardiac Output; Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Dobutamine; Etiocholanolone; Genetic Therapy; Heart Failure; Humans; Hydrazones; Pyridazines; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Simendan; Sodium-Potassium-Exchanging ATPase; Urea

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Increased frequency of electrolyte abnormalities and cardiac arrhythmias among patients exposed to digoxin-diuretic interactions has been well-documented in numerous descriptive studies. * Nonetheless, a clear causal relationship has not been established in these studies. WHAT THIS STUDY ADDS * The risks of digoxin intoxication associated with use of digoxin in combination with any diuretic use, types of diuretics, combinations of diuretics, and individual diuretics were quantified using a population-based nested case-control study design. * The combined therapy of digoxin with any diuretic is associated with a 3.08-fold increase in the risk of digoxin intoxication. * Regarding diuretic class, the risk carried by loop diuretics is greater than that of thiazides or potassium-sparing diuretics, and the risk varies with different combinations of diuretic classes and individual diuretics. AIMS To quantify the digoxin intoxication risk associated with exposure to digoxin-diuretic interactions, and evaluate whether the risk varies by diuretic type, individually or in combination. METHODS This was a population-based nested case-control study in which data from the National Health Insurance Research Database (NHIRD) in Taiwan were analysed. RESULTS The study cohort comprised 154 058 heart failure (HF) patients taking digoxin between 2001 and 2004, in whom digoxin intoxication requiring a hospitalization (ICD-9 code 972.1) occurred in 595 cases. A total of 28 243 matched controls were also selected for analysis. Cases were 3.08 times (adjusted OR 3.08, 95% CI 2.50, 3.79) more likely to have been prescribed diuretic medication in the previous month than controls. Regarding the class of diuretics, loop diuretics carried the greatest risk (adjusted OR 2.97, 95% CI 2.35, 3.75), followed by thiazides (OR 2.36, 95% CI 1.70, 3.29) and potassium-sparing diuretics (OR 1.72, 95% CI 0.83, 3.56). The risk was also observed to vary with different combinations of diuretics, and the loops/thiazides/potassium-sparing diuretics combination carried the greatest risk (adjusted OR 6.85, 95% CI 4.93, 9.53). Among the individual diuretics examined, hydrochlorothiazide carried the greatest risk (adjusted OR 4.63, 95% CI 2.50, 8.57). CONCLUSIONS This study provided empirical evidence that digoxin-diuretic interactions increased the risk of hospitalization for digoxin intoxication in HF patients. The risk was particularly high for concomitant use

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Case-Control Studies; Cohort Studies; Digoxin; Diuretics; Drug Interactions; Drug Therapy, Combination; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies

Topics: Benzazepines; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiovascular Agents; Digoxin; Diuretics; Echocardiography; Electrocardiography; Furosemide; Heart Atria; Heart Failure; Heart Rate; Heart Ventricles; Humans; Ivabradine; Male; Middle Aged; Myocardial Infarction; Spironolactone; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Digoxin; Diuretics; Drug Prescriptions; Evidence-Based Medicine; Health Knowledge, Attitudes, Practice; Heart Failure; Humans; Outpatients; Practice Patterns, Physicians'; Surveys and Questionnaires; United States

Topics: Digitalis; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic; Renal Dialysis

Topics: Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Heart Failure; Humans

To explore the effects of Shenmai Injection (SMI), a compound traditional Chinese herbal medicine, on pharmacokinetics and serum concentration of digoxin when applied together with digoxin.. Twenty dogs with heart failure were randomly divided into 4 groups: control group and low-, medium- and high-dose SMI groups, with 5 dogs in each group. After intravenous injection of digoxin injection at a dose of 7.41 μg/kg, dogs in the control group were administered intravenously with normal saline 20 mL daily for 5 d, and the other groups were intravenously administered with SMI at the doses of 0.517, 1.034 and 1.551 mL/kg respectively. After the administration, the blood was collected at designed time points. Serum concentration of digoxin was determined by high-performance liquid chromatography with electrospray tandem mass spectrometry (HPLC/MS/MS).. The low-, medium- and high-dose SMI showed different effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI revealed a tendency to decrease the elimination half-life (T(1/2β)) of digoxin. The low-dose SMI showed a tendency to decrease the digoxin concentration. Serum clearance (CL) in the low-dose SMI group was higher than that in the control, and also significantly higher than those in the medium- and high-dose SMI groups (P<0.05). The area under concentration-time curve (AUC(0→∞)) in the low-dose SMI group was lower than that in the control group (P=0.05); the AUC(0→72 h) and AUC(0→∞) in the low-dose SMI group were significantly lower than those in the medium- and high-dose SMI groups. Low-dose SMI accelerated the clearance of digoxin in blood.. Low-, medium- and high-dose SMI shows different effects on pharmacokinetics of digoxin and reveals a tendency to shorten T(1/2β) of digoxin. Low-dose SMI can accelerate the clearance of digoxin in blood.

Topics: Animals; Digoxin; Disease Models, Animal; Dogs; Drug Combinations; Drug Interactions; Drugs, Chinese Herbal; Heart Failure; Injections

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

Topics: Animals; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Randomized Controlled Trials as Topic; Rats

Topics: Aged; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans

In patients with atrial fibrillation (AF) and heart failure (HF), beta blockers and digoxin reduce the ventricular rate, but controversy exists concerning how these drugs affect prognosis in this setting. This study compared the effects of beta blocker and digoxin on mortality in patients with both AF and HF. In a single-center institution, patients with AF and HF seen between January 2000 and January 2004 were identified and followed until September 2007. Of 1,269 consecutive patients with both AF and HF, 260 were treated with a beta blocker alone, 189 with beta blocker plus digoxin, 402 with digoxin alone, and 418 without beta blocker or digoxin (control group). During a follow-up of 881+/-859 days, 247 patients died. Compared with the control group, treatment with beta blocker was associated with a decreased mortality (relative risk=0.58, 95% confidence interval 0.40 to 0.85, p=0.005 for beta blocker alone and 0.59, 95% confidence interval 0.40 to 0.87, p=0.008 for beta blocker plus digoxin). By contrast, treatment with digoxin alone was not associated with a better survival (relative risk=0.97, 95% confidence interval 0.73 to 1.30, p=NS). Results remained significant after adjustment for potential confounders and similar when we considered, separately, HF with permanent or nonpermanent AF, presence or absence of coronary disease, and patients with decreased or preserved systolic function. In conclusion, in unselected patients with AF and HF, treatments with beta blocker alone or with beta blocker plus digoxin are associated with a similar decrease in the risk of death. Digoxin alone is associated with a worse survival chance, similar to that of patients without any rate control treatment.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Humans; Logistic Models; Male; Proportional Hazards Models; Treatment Outcome

Cognitive dysfunction is a prevalent condition among patients with heart failure (HF), and is independently associated with disability and mortality. A large study of patients with atrial fibrillation incidentally demonstrated superior cognitive performance among participants who received digoxin. Interestingly, endogenous cerebral digoxin influences neuronal Na(+)-dependent transport of calcium and amino acids, as well as the release and reuptake of several neurotransmitters involved in cognitive functioning.. To assess whether treatment with digoxin might improve cognition in patients with HF.. This pharmacoepidemiological cohort study included hospitalized elderly people (age > or = 65 years) from the GIFA (Gruppo Italiano di Farmacoepidemiologia nell'Anziano [Italian Group of Pharmacoepidemiology in the Elderly]) study. The GIFA study included 13,598 patients (1590 with a verified diagnosis of HF) without cerebrovascular or Alzheimer's disease. The main outcome measure was cognitive performance, which was assessed on admission and immediately before discharge using the Hodkinson Abbreviated Mental Test. The diagnosis of HF was verified by the study investigators.. Among participants with HF, cognitive performance improved in 25% of 1172 participants who received digoxin compared with 16% of remaining patients (p < 0.0001). Among participants without HF, cognition improved in 23% of 2431 patients receiving digoxin compared with 17% of untreated patients (p < 0.0001). According to logistic regression analysis, the probability (odds ratio) of improving cognitive performance associated with administration of digoxin was 1.69 (95% CI 1.20, 2.38) among patients with HF, and 1.13 (95% CI 0.98, 1.31) among patients without HF, after adjusting for potential confounders. Analysis of the interaction term 'use of digoxin by diagnosis of HF' in fully adjusted logistic regression confirmed (p = 0.018) that the association between use of digoxin and improving cognitive performance varied according to diagnosis of HF.. Treatment with digoxin might selectively improve cognitive performance among older patients with HF.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Cognition; Digoxin; Female; Heart Failure; Humans; Italy; Male; Middle Aged; Pharmacoepidemiology

Heart failure (HF) with preserved ejection fraction (EF) has a high prevalence in the geriatric population, and this cohort may be at risk of complications caused by polypharmacy. Effects of commonly used cardiac medications on long-term survival of patients >80 years with HF and preserved left ventricular EF were assessed. One hundred forty-two patients were evaluated. During a 5-year follow-up, 98 patients died (69%). There were no significant differences in baseline parameters in patients who died compared with those who survived at 5 years. None of the drug therapies appeared to make a significant difference in long-term survival, including beta blockers (p = 0.89), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (p = 0.91), calcium channel blockers (p = 0.69), diuretics (p = 0.30), digoxin (p = 0.22), and statins (p = 0.32). In conclusion, based on the present data, it appears that use of certain common cardiac medications may not be associated with a significant effect on long-term survival in octogenarians with HF and preserved EF.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Digoxin; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Hospitalization; Humans; Male; Stroke Volume; Survival Rate; Treatment Outcome

Over 80% of all heart failure patients are 65 years and older. The diagnosis and management of heart failure in older adults can be challenging. However, with the correct clinical skill and experience, most geriatric heart failure can be properly diagnosed and managed. Management of geriatric heart failure can be simplified by following this useful mnemonic: DEFEAT Heart Failure. This covers the essential aspects of geriatric heart failure management: Diagnosis, Etiology, Fluid, Ejection fraAction, and Treatment. The process begins with a clinical Diagnosis, which must be established, before ordering an echocardiogram, as nearly half of all geriatric heart failure patients have normal left ventricular ejection fraction. Because heart failure is a syndrome and not a disease, an underlying Etiology must be sought and determined. Determination of the Fluid volume status by careful examination of the external jugular veins in the neck is vital to achieve euvolemia. An echocardiography should be ordered to obtain left ventricular Ejection frAction to assess prognosis and guide Therapy. However, if left ventricular ejection fraction cannot be determined, as in many developing nations, all geriatric heart failure patients should be treated as if they have low ejection fraction, and should be prescribed an angiotensin-converting enzyme inhibitor and a beta-blocker. Diuretic and digoxin should be prescribed for all symptomatic patients with heart failure. An aldosterone antagonist may be used in select patients with advanced systolic heart failure, carefully avoiding hyperkalemia.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Body Fluids; Cardiac Output, Low; Digoxin; Diuretics; Echocardiography; Family Practice; Female; Heart Failure; Humans; Male; Stroke Volume; Vasodilator Agents

Digoxin overdose is closely related to Chronic Kidney Disease and creatinine dosage adjustment is usually needed. Our goal was to assess the advantages of serum creatinine and the MDRD equation to detect hidden renal insufficiency to reduce the overdose Digital risk.. We describe all digoxin samples processed and registered in our hospital laboratory database for a year. Patients under 18 years and samples below therapeutic ranges were excluded. Chi square (p<0.05), ROC curves and logistic regression analysis were conducted. SPSS software was used.. Between 1228 digoxin samples taken to 679 patients (273 men, 77 +/- 10 years old , and 406 women 82 +/- 8 years old), 14% were over therapeutic range (28 men and 67 women). Significant differences were observed in over dosage between high creatinine group regarding to normal creatinine group (31% vs. 10% in men, 44% vs. 15% in women). ROC curves showed that the most accurate levels to predict digoxin over dosage were MDRD<56 ml/min/1.73 m(2) in men and MDRD<52 ml/min/1.73 m(2) in women. 68% of over dosage men had declines of MDRD levels, compared to 61% with high creatinine levels, 81% of over dosage women had declines of MDRD compared to 51% with elevated creatinine levels.. Even in patients with normal creatinine levels, chronic kidney disease enhances digoxin over dose risk. Using the decline of glomerular filtration rate estimated by the MDRD equation is better than elevated creatinine levels to detect digoxin overdose, thus constituting a very useful tool to reduce the risk of overdose, especially among women.

Topics: Aged; Aged, 80 and over; Algorithms; Creatinine; Cross-Sectional Studies; Digoxin; Drug Overdose; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; ROC Curve

Topics: Digoxin; Drug Combinations; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans; Imidazoles; Male; Propantheline

Topics: Aged; Cardiotonic Agents; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Immunoassay; Kidney Failure, Chronic; Male

Of 209 patients with heart failure treated with combined cardiac resynchronization therapy and implantable cardioverter-defibrillator therapy, appropriate cardioverter-defibrillator shocks occurred at 34-month follow-up in 22 of 121 patients (18%) on statins and in 30 of 88 patients (34%) not on statins (P = .009). Deaths occurred in 3 of 121 patients (2%) on statins and in 9 of 88 patients (10%) not on statins (P = .017). Stepwise Cox regression analysis showed that significant independent prognostic factors for appropriate shocks were use of statins (risk ratio = 0.46), smoking (risk ratio = 3.5), and diabetes (risk ratio = 0.34). Significant independent prognostic factors for the time to mortality were use of statins (risk ratio = 0.05), use of digoxin (risk ratio = 4.2), systemic hypertension (risk ratio = 14.2), diabetes (risk ratio = 4.3), and left ventricular ejection fraction (risk ratio = 1.1).

Topics: Aged; Aged, 80 and over; Cardiac Pacing, Artificial; Cardiotonic Agents; Combined Modality Therapy; Defibrillators, Implantable; Diabetes Complications; Digoxin; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Risk Assessment; Risk Factors; Smoking; Stroke Volume; Tachycardia, Ventricular; Time Factors; Treatment Outcome; Ventricular Fibrillation; Ventricular Function, Left

To quantify the effect of exposures to digoxin–clarithromycin interactions on the risk of digoxin toxicity requiring hospitalizations in a population-based manner in a Taiwanese population.. This is a retrospective population-based nested case–control study. Data were retrieved from the National Health Insurance Research Database. Heart failure (HF) patients newly treated with digoxin between 1 January 2001 and 31 December 2004 were retrieved from the database as the study cohort. Case patients, admitted to the hospitals with the diagnosis of digoxin intoxication (ICD-9 code 972.1) were identified from the study cohort and compared with the matched controls for the receipt of clarithromycin.. A total of 154,058 patients were identified as the study cohort; from these, 595 cases and 27,020 matched controls were selected for study. The prescription of clarithromycin at 7, 14, and 30 days prior to the index date was associated with a 4.36- (95% CI 1.28–14.79), 5.07- (95% CI 2.36–10.89), and 2.98-fold (95% CI 1.59–5.63) increase in hospitalization for digoxin intoxication, respectively. The results of the dose–response relationship also indicated that clarithromycin prescribed with a prescribed daily dose (PDD)/defined daily dose (DDD) ratio >2 led to a 55.41-fold (95% CI 9.31–329.9) increase of the risk, which is significantly greater than that prescribed with a 1–2 PDD/DDD ratio (adjusted OR  4.81; 95% CI 1.88–12.30) or with a <1 PDD/DDD ratio (adjusted OR  0.78; 95% CI 0.19–3.20).. This study provides empirical evidence that digoxin–clarithromycin interactions do increase the risk of hospitalization for digoxin intoxication in HF patients and that this risk could reach as high as 55.4-fold. We strongly recommend that the combined use of digoxin with clarithromycin should be avoided and that digoxin concentrations should be monitored closely in situations where the combination can not be avoided.

Topics: Aged; Anti-Bacterial Agents; Cardiotonic Agents; Case-Control Studies; Clarithromycin; Cohort Studies; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Failure; Hospitalization; Humans; Male; Retrospective Studies

The aim of this study was to compare the estimated glomerular filtration rate (GFR) using the Cockcroft-Gault and the 4-, 5-, and 6-variable Modification of Diet in Renal Disease (MDRD) formulas for digoxin dose adjustment.. Steady-state serum digoxin concentrations were determined in 100 patients with heart failure and normal to severely impaired renal function. Total clearance (CL) and predicted average concentrations of digoxin were calculated using general pharmacokinetic principles.. The mean+/-SEM (median) estimated GFR values were 48.9+/-2.8 (46.5) mL/min/1.73 m(2) using the Cockcroft-Gault formula, 61.4+/-3.6 (56.4) mL/min/1.73 m(2) using the MDRD4 formula, 56.8+/-3.3 (52.1) mL/min/1.73 m(2) using the MDRD5 formula, and 53.3+/-3.0 (48.7) mL/min/1.73 m(2) using the MDRD6 formula, with high correlation coefficients between the estimates (r > or = 0.928, P < 0.001). Significant correlations were found between the digoxin total CL and estimated GFR by the Cockcroft-Gault (r = 0.649, P < 0.001), MDRD4 (r = 0.634, P <0.001), MDRD5 (r = 0.635, P < 0.001), and MDRD6 (r = 0.652, P < 0.001) formulas. A significant negative correlation of the digoxin total CL/GFR ratio with estimated GFR was obtained (r = -0.356, P < 0.001), with a high variability for this ratio for GFR lower than 60 mL/min. Analogous correlation coefficients were found between the obtained and predicted digoxin concentrations calculated using the estimated GFR by the Cockcroft-Gault (r = 0.628, P < 0.001), MDRD4 (r = 0.642, P < 0.001), MDRD5 (r = 0.650, P < 0.001), and MDRD6 (r = 0.665, P < 0.001) formulas, with a wide dispersion between the values in all cases.. For GFR lower than 60 mL/min, the high interindividual variation of the digoxin total CL found among patients with similar renal function is an important limiting factor in the prediction of digoxin dosage regimens.

Topics: Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Diseases; Male; Middle Aged

Topics: Cardiology; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Prognosis; Severity of Illness Index; Ventricular Function

The impact of digoxin on outcomes of patients with advanced heart failure (HF) receiving optimal contemporary therapy is not known.. We retrospectively reviewed data of 455 advanced HF patients referred for transplant evaluation (age, 52+/-12 years; ejection fraction, 18.3+/-8%); 227 (49.9%) were on digoxin at baseline. Primary outcome was death (n=101), urgent transplantation (n=14), or ventricular assist device implantation (n=4); secondary outcomes included HF and all-cause hospitalizations. Digoxin use was evaluated (1) in the original cohort; (2) in a propensity score-matched subset (n=322); (3) as a time-dependent covariate; and (4) after adjustment for Seattle Heart Failure Score. Patients were on optimal therapy: angiotensin-II modulation, 92.5%; beta-blockers, 91.2%; aldosterone antagonists, 45.6%; and devices, 71.0%. After a median of 27 months, 83 of 277 (36.6%) patients treated with digoxin versus 36 of 228 (15.8%) patients without digoxin met primary outcome (hazard ratio [HR], 2.28; 95% CI, 1.51 to 3.43; P<0.001). This risk persisted in the matched subset (HR, 1.73; 95% CI, 1.09 to 2.75; P=0.021) and with time-varying digoxin use (HR, 2.05; 95% CI, 1.23 to 3.41; P=0.011). Digoxin was associated with higher risk among patients in sinus rhythm compared with atrial fibrillation. Digoxin was not associated with improvement in either all-cause or HF hospitalization rates. These results were similar across sex and race and when adjusted for Seattle Heart Failure Score and renal function.. This study suggests that digoxin therapy may be of no benefit in patients with advanced HF referred for cardiac transplantation who received optimal medical therapy. Treatment with digoxin should be used cautiously in such patients because of risk for adverse outcomes.

Topics: Adolescent; Adult; Aged; Cardiotonic Agents; Cohort Studies; Cross-Over Studies; Digoxin; Echocardiography; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Referral and Consultation; Retrospective Studies; Severity of Illness Index; Stroke Volume; Treatment Outcome; Young Adult

The prevalence of stroke is increased in individuals with heart failure (HF). The stroke mechanism in HF may be cardiogenic embolism or cerebral hypoperfusion. Stroke risk increases with decreasing ejection fraction and low cardiac output is associated with hypotension and poor survival. We examine the relationship among blood pressure level, history of stroke/transient ischemic attack (TIA), and HF.. We compared the prevalence of self-reported history of stroke or TIA in the REasons for Geographic And Racial Differences in Stroke (REGARDS) participants with HF (as defined by current digoxin use) and without HF. We excluded participants with atrial fibrillation or missing data. We examined the relationship between HF and history of stroke/TIA within tertiles of systolic blood pressure (SBP) adjusting for patient demographic and health characteristics.. Prevalent stroke/TIA were reported by 66 (26.3%) of 251 participants with and 1805 (8.5%) of 21 202 participants without HF (P<0.0001). Within each tertile of SBP, the unadjusted OR (95% CI) for prior stroke/TIA among those with HF compared with those without HF (the reference group) was, 4.0 (2.8 to 5.8) for SBP <119.5 mm Hg, 2.7 (1.8 to 3.9) for SBP >or=119.5 but <131.5 mm Hg, and 2.3 (1.6 to 3.2) for SBP >or=131.5 mm Hg. After adjustment, the relationship between prior stroke/TIA and HF remained significant only within the lowest tertile of SBP (<119.5 mm Hg; 3.0; 1.5 to 6.1).. The odds of prevalent self-reported stroke/TIA are increased in participants with HF and most markedly increased in participants with low SBP. Longitudinal data are needed to determine whether this reflects stroke/TIA secondary to thromboembolism from poor cardiac function or secondary to cerebral hypoperfusion.

Topics: Aged; Aged, 80 and over; Biomarkers; Black People; Blood Pressure; Cohort Studies; Comorbidity; Digoxin; Female; Geography; Heart Failure; Humans; Hypotension; Ischemic Attack, Transient; Male; Medical History Taking; Middle Aged; Odds Ratio; Prevalence; Racial Groups; Risk Factors; Stroke; Surveys and Questionnaires; White People

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Drug Therapy, Combination; Electrocardiography; Enalapril; Furosemide; Heart Failure; Humans; Infant; Male; Spironolactone

Topics: Acute Disease; Cardiology; Cardiotonic Agents; Digoxin; Drug Utilization; Heart Failure; Humans

To evaluate the effects of digoxin on the progression of congestive heart failure (CHF), and to determine the best predictors of perinatal death in fetuses with sinus rhythm and CHF.. This was a retrospective case series of fetuses with CHF treated with transplacental digoxin, evaluated at baseline (before treatment), weekly during treatment, and prior to death or delivery, using a 10-point cardiovascular profile score (CVPS) consisting of echocardiographic markers of cardiac dysfunction: cardiomegaly, valve insufficiency, hydrops, and abnormal venous and arterial Doppler flow profiles. Composite CVPS and component markers were compared before and after digoxin treatment by nonparametric testing and best predictors of perinatal survival assessed by regression analysis and receiver operating characteristics.. The overall mortality of the 28 subjects was 32%. First, last, and CVPS after 1 week of treatment predicted survival (odds ratio 2.34, 95% confidence interval 1.10-4.96) with a CVPS of > or=6 being the best predictor of survival (sensitivity 0.83, specificity 0.75). All fetuses that died had notching of the umbilical venous flow. CVPS increased from baseline during treatment (p = 0.003) in all subjects.. The CVPS score is useful in assessing therapeutic effects of digoxin in the fetus with multiple etiologies for CHF. Further studies are needed to test the efficacy of digoxin in specific defects causing CHF.

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Pregnancy; Retrospective Studies; Severity of Illness Index; Survival Analysis

Heart failure (HF) with preserved systolic function (ejection fraction [EF] >50%) is common, yet no proven therapies exist. Large registries could shed light on what medications may or may not be useful to reduce hospitalization and mortality. The EFFECT Registry, which prospectively enrolled 9,943 patients admitted to the hospital for HF from 1999 to 2001 in 103 hospitals in Ontario, Canada, was used. Patients discharged alive were divided into those with EF >50% and EF <50%. Discharge medications (angiotensin-converting enzyme [ACE] inhibitors, beta blockers [BBs], spironolactone, and digoxin) were examined for their association with HF rehospitalization or death during 1 year. In the HF group with EF >50% (n = 1,026), 199 patients died within 1 year and 349 patients died or were hospitalized for HF within 1 year. In the HF group with EF <50% (n = 1,898), 427 patients died and 720 patients died or were hospitalized for HF. In the HF group with EF >50%, 67% were administered an ACE inhibitor; 32%, a BB; 37%, digoxin; and 12%, spironolactone. No differences were seen in adjusted survival for any medications (ACE inhibitors, BBs, digoxin, or spironolactone) examined in the HF group with EF >50% despite an adjusted survival benefit with ACE inhibitors (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.77 to 0.94), BBs (HR 0.80, 95% CI 0.72 to 0.89), and spironolactone (HR 0.80, 95% CI 0.66 to 0.98) in patients with low EF. In conclusion, none of the medications proved to improve outcomes in patients with HF with low EF showed an association with outcomes in patients with HF and EF >50%, highlighting the need for randomized trial evidence to define therapies that will be beneficial in patients with HF and preserved systolic function.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Patient Readmission; Spironolactone; Stroke Volume; Time Factors; Treatment Outcome; Ultrasonography

Alternative splicing has emerged as a promising therapeutic target in a number of human disorders. However, the discovery of compounds that target the splicing reaction has been hindered by the lack of suitable high-throughput screening assays. Conversely, the effects of known drugs on the splicing reaction are mostly unclear and not routinely assessed. We have developed a two-color fluorescent reporter for cellular assays of exon inclusion that can accommodate nearly any cassette exon and minimizes interfering effects from changes in transcription and translation. We used microtubule-associated protein tau (MAPT) exon 10, whose missplicing causes frontotemporal dementia, to test the reporter in screening libraries of known bioactive compounds. These screens yielded several compounds that alter the splicing of the exon, both in the reporter and in the endogenous MAPT mRNA. One compound, digoxin, has long been used in the treatment of heart failure, but was not known to modulate splicing. The positive compounds target different signal transduction pathways, and microarray analysis shows that each compound affects the splicing of a different set of exons in addition to MAPT exon 10. Our results identify currently prescribed cardiotonic steroids as modulators of alternative splicing and demonstrate the feasibility of screening for drugs that alter exon inclusion.

Topics: Alternative Splicing; Cardiotonic Agents; Cell Line; Dementia; Digoxin; Drug Evaluation, Preclinical; Exons; Gene Expression Profiling; Genes, Reporter; Heart Failure; Humans; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Signal Transduction; tau Proteins

Heralded as the oldest known cardiovascular drug, digoxin remains widely used today in the face of increasing rates in heart failure and atrial fibrillation despite the emergence of newer medications. Its hemodynamic, neurohormonal and electrophysiologic actions make it a suitable adjunctive, evidence-based therapy for the above conditions. Its narrow therapeutic index and its toxicity, however, have become more relevant as aging, comorbid diseases, and polypharmacy make more patients vulnerable. Because signs and symptoms of digoxin toxicity are mostly nonspecific, a high index of suspicion is crucial for early recognition and appropriate management.

Topics: Aging; Atrial Fibrillation; Cardiotonic Agents; Contraindications; Digoxin; Drug Interactions; Heart Failure; Humans; Kidney Diseases

Topics: Adrenergic beta-Antagonists; Benzazepines; Cardiotonic Agents; Confounding Factors, Epidemiologic; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Ivabradine

In heart failure (HF), digoxin at low serum digoxin concentrations (SDC) reduces all-cause mortality and HF hospitalizations. However, the effects of digoxin on other cause-specific outcomes have not been studied in a propensity-matched cohort.. The Digitalis Investigation Group trial, conducted during 1991-1993, enrolled 7788 ambulatory chronic HF patients. This analysis focuses on 4843 patients: 982 receiving digoxin with low (0.5-0.9 ng/ml) SDC at one month, and 3861 receiving placebo and alive at one month. Propensity scores for low SDC, calculated using a non-parsimonious multivariable logistic regression model, were used to match 982 low-SDC patients with 982 placebo patients. Matched Cox regression analyses were used to determine the effect of digoxin at low SDC on outcomes.. All-cause mortality occurred in 315 placebo (rate, 1071/10,000 person-years) and 288 low-SDC digoxin (rate, 871/10,000 person-years) patients, respectively, during 2940 and 3305 years of follow up (hazard ratio {HR}, 0.81, 95% confidence interval {CI}, 0.68-0.98; p=0.028). Cardiovascular hospitalizations occurred in 493 placebo (2359/10,000 person-year) and 471 low-SDC digoxin (1963/10,000 person-year) patients, respectively during 2090 and 2399 years of follow up (HR, 0.82, 95% CI, 0.70-0.95; P=0.010). Low-SDC digoxin to placebo HR (95%CI) for HF mortality and HF hospitalizations were respectively, 0.65 (0.45-0.92; P=0.015) and 0.63 (0.52-0.77; P<0.0001). Low-dose digoxin (< or = 0.125 mg/day) was the strongest independent predictor of low SDC (adjusted odd ratio, 2.07, 95% CI 1.54-2.80).. Digoxin at low SDC significantly reduced mortality and hospitalizations in ambulatory chronic systolic and diastolic HF patients.

Topics: Aged; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies

The prognosis of acute heart failure is such that many children are considered for transplantation. Recovery of severe heart failure in a proportion of patients diagnosed with either dilated cardiomyopathy or myocarditis is well recognized, and this complicates the assessment for transplantation. There is little data on the time scale of recovery of heart function in children.. To describe the time course over which echocardiographic improvement of systolic function occurred in a cohort of children who presented in acute heart failure, without structural or metabolic abnormality.. Children with a first presentation of acute severe heart failure between 1990 and 2005. Time from presentation to the echocardiogram before left ventricular fractional shortening (FS) improved to 20% and 30% (complete recovery) was recorded.. Twenty-seven children (11 male) were identified, and all had an initial FS <15%. Twenty-one patients required intravenous inotropes and three patients required extracorporeal membrane oxygenation. Seven patients had been on the active transplant list for a mean duration of 155 days. Four patients had probable viral myocarditis. Mean age at presentation was 15.7 (range, 0.1-72) months. Mean time to an FS of 20% was 3.6 (0.2-18) months and to 30% was 8.9 (0.7-24) months. Complete recovery occurred within 6, 9, 12, 18, and 24 months of presentation in 44%, 55%, 66%, and 96%, respectively. There was no correlation between age of presentation and length of time to recovery.. Complete recovery of left ventricular systolic function is often delayed to more than 1 year from presentation. This may have major implications for timing of transplantation in an era where prolonged mechanical cardiac support is feasible even in infants.

Topics: Acute Disease; Captopril; Carbazoles; Cardiotonic Agents; Carvedilol; Child; Child, Preschool; Databases, Factual; Digoxin; Enalapril; Enoximone; Female; Heart Failure; Heart Function Tests; Humans; Infant; Infant, Newborn; Male; Propanolamines; Treatment Outcome

International differences in prescribing patterns for chronic heart failure (CHF) have been demonstrated repeatedly. It is not clear whether these differences arise entirely from patient characteristics or factors related to the country itself, such as health care systems or culture. We aim to assess the role of countries in this international variation, aside from the role of patient characteristics.. In this European primary care practice survey (from 1999/2000) 11062 CHF patients from 14 countries were included. The influence of country (corrected for patient characteristics) on prescribed drug regimes was assessed by multinomial logistical regression.. Prescribing of guideline-recommended drug regimes ranged from 28.1% in Turkey to 61.8% in Hungary. Including additional regimes justifiable by patients' co-morbidities, increased overall 'rational' prescribing by 11%, but differences among countries remained similar. Multivariate analysis for one-drug and two-drug regimes explained between 35% and 42% of the total variance, country contributed 7%-8% (p < 0.005). Countries determined the number of drugs used and the likelihood of individual drug regimes. For example, in Czech Republic digoxin alone was more likely to be given than the recommended ACE-inhibitors (OR: 3.45; 95%CI: 2.56-4.64), while the combination of digoxin with ACE-inhibitors was as likely as the recommended combination of ACE-inhibitors and beta-blockers (OR: 1.17; 95%CI: 0.88-1.55).. Country of residence clearly influenced prescribed drug volume and choice of drug regimes. Therefore, optimal CHF management cannot be achieved without considering country specific factors. It remains to be established which factors within health-care systems are responsible for these effects.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Data Collection; Digoxin; Drug Prescriptions; Drug Therapy, Combination; Europe; Female; Guideline Adherence; Heart Failure; Humans; Male; Multivariate Analysis; Patients; Physicians, Family; Practice Guidelines as Topic; Practice Patterns, Physicians'; Sex Factors

Topics: Digoxin; Heart Failure; Humans; Treatment Outcome

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Drug Utilization; Female; Heart Failure; Humans; Male

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male

Topics: Adolescent; Cardiomyopathy, Dilated; Cardiotonic Agents; Child; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Immunologic Factors; Male

Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling, causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure.. Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with end points of cardiac death or rehospitalization. Serum concentration of pentosidine was significantly higher in New York Heart Association (NYHA) Class III/IV patients than in NYHA class I/II patients (P < .0001). Serum pentosidine was also higher in patients with cardiac events than in event-free patients (P < .001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume, and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = .002). The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold).. Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure. Patients were divided into 4 groups based on the serum pentosidine levels.

Topics: Aged; Arginine; Biomarkers; Cardiotonic Agents; Case-Control Studies; Comorbidity; Diabetes Complications; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Japan; Lysine; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Insufficiency; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis

Topics: Cardiotonic Agents; Digitoxin; Digoxin; Heart Failure; Humans; Practice Guidelines as Topic; Risk Factors

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study showed that rhythm-control treatment of patients with atrial fibrillation (AF) offered no survival advantage over a rate-control strategy. In a subgroup analysis of that study, it was found that digoxin increased the death rate [relative risk (RR) = 1.42), but it was suggested that this may have been attributable to prescription of digoxin for patients at greater risk of death, such as those with congestive heart failure (CHF). No study has investigated a priori the effect of digoxin on mortality in patients with AF. This study aimed to address this question.. Using data from the Registry of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), we studied the 1-year mortality among patients admitted to coronary care units with AF, CHF, or AF+CHF with or without digoxin (n = 60,764) during 1995-2003. Adjustment for differences in background characteristics and other medications and treatments was made by propensity scoring.. Twenty percent of patients with AF without CHF in this cohort were discharged with digoxin. This group had a higher mortality rate than the corresponding group not given digoxin [adjusted RR 1.42 (95% CI 1.29-1.56)], whereas no such difference was seen among patients with CHF with or without AF, although these patients had a nearly three-times higher mortality.. The results suggest that long-term therapy with digoxin is an independent risk factor for death in patients with AF without CHF.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Creatinine; Digoxin; Female; Heart Failure; Humans; Male; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Registries; Research Design; Risk Assessment; Risk Factors; Stroke Volume; Sweden; Time Factors; Treatment Outcome; Ventricular Function, Left

Supraventricular tachycardia (SVT) is the second most frequent form of arrhythmia in pediatrics after extrasystole.. 1. To determine the clinical characteristics and treatment of SVT in infants and children. 2. To determine treatment response and the drugs used.. A retrospective review of 61 cases of SVT requiring PICU admission (1999-2004) was performed. PICU admission was due to persistent SVT after vagal maneuvers.. There were 61 patients and 39 were boys (63.9%). The mean age was 2.1 years (SD +/- 3.1). Twelve patients had congenital heart disease (19.7%); three (4.9%) were admitted after heart surgery, and the remaining patients had no antecedents (60.7%). The mean cardiac frequency was 238 beats/min (SD +/- 42.86). Heart failure (HF) was observed in 14 patients (23%). Statistically significant differences were found between the presence of HF and time since onset (p < 0.01) and younger age (p < 0.01). The most frequent diagnosis was SVT due to re-entry in 28 patients (45.9%). Medical treatment was required in 46 patients (75.4%) and response was achieved in 35 (57.4%). At crisis the first drug used was adenosine triphosphate (ATP) in 35 patients (61.4%) with good response in 21 (36.8%). As maintenance therapy digoxin was used in 29 patients (50.9%) without relapses in 22 (78.6%). Radiofrequency ablation was required in 17 patients (27.9%), and there were three relapses (17.6%). The ages of patients who underwent ablation ranged from 3.5 days to 13 years.. 1. HF was observed mainly in infants. 2. Most of the patients had good response to ATP therapy. 3. Radiofrequency ablation was mainly required in patients aged more than 1 year.

Topics: Adenosine Triphosphate; Adolescent; Age Factors; Anti-Arrhythmia Agents; Cardiotonic Agents; Catheter Ablation; Child; Child, Preschool; Data Interpretation, Statistical; Digoxin; Female; Heart Defects, Congenital; Heart Failure; Heart Rate; Humans; Infant; Infant, Newborn; Male; Retrospective Studies; Sex Factors; Tachycardia, Supraventricular; Treatment Outcome

A case of a 62-year-old woman presenting with a 20-year history of vulvodynia previously unresponsive to medical treatment is described. The epidemiology, phenomenology and medical management of vulvodynia is reviewed. The case presentation illustrates the role of pregabalin in successful medical management of this chronic pain disorder, as well as the management of common psychiatric morbidities associated with this condition.

Topics: Amitriptyline; Analgesics; Anti-Ulcer Agents; Anticoagulants; Antidepressive Agents; Anxiety; Cardiotonic Agents; Cataract; Cataract Extraction; Cholecystectomy; Chronic Disease; Citalopram; Digoxin; Female; gamma-Aminobutyric Acid; Heart Failure; Humans; Hypertension; Hysterectomy; Lorazepam; Middle Aged; Mitral Valve Insufficiency; Omeprazole; Ovarian Neoplasms; Pain; Pregabalin; Sterilization, Tubal; Stomach Diseases; Vulvar Diseases

We report a patient who presented with congestive heart failure (ejection fraction 24.4%) and who had previous history of convulsions. Our investigations found him to be a case of primary hypoparathyroidism. He showed a dramatic response with the addition of calcium infusion therapy with almost full recovery of left ventricular function (67% ejection fraction after 16 days of the initial echo). We conclude that in a young patient a thorough investigation for heart failure is never complete without looking for endocrine and metabolic causes. The prognosis in these cases is much better, identification and treatment of the same will yield dramatic results.

Topics: Adolescent; Calcium; Digoxin; Heart Failure; Heart Ventricles; Humans; Hypocalcemia; Hypoparathyroidism; Male; Risk Factors; Stroke Volume

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans

The association between higher New York Heart Association (NYHA) class and outcomes in patients with heart failure and preserved systolic function is not well known.. We performed a retrospective follow-up study of 988 patients with heart failure with ejection fraction > 45% who participated in the DIG trial. Using Cox proportional hazard models, we estimated risks and all-cause mortality, heart failure mortality, all-cause hospitalization, and hospitalization due to worsening heart failure during a median follow-up of 38.5 months.. Patients had a median age of 68 years; 41.2% were women and 13.9%, nonwhites. Overall, 23.4% of patients died, and 19.9% were hospitalized because of worsening heart failure. Proportion of patients with NYHA classes I, II, III, and IV were 19.9%, 58.0%, 20.9%, and 1.2%, respectively, and 14.7%, 21.1%, 35.9%, and 58.3%, respectively, died of all causes (P < .001 for trend). Respective rates for heart failure-related hospitalizations were 14.2%, 17.1%, 32.5%, and 33.3% (P < .001 for trend). Compared with NYHA class I patients, adjusted hazard ratios (HRs) for all-cause mortality for class II, III, and IV patients were 1.54 (95% CI 1.02-2.32, P = .042), 2.56 (95% CI 1.64-24.01, P < .001), and 8.46 (95% CI 3.57-20.03, P < .001), respectively. Respective adjusted HRs (95% CI) for hospitalization due to heart failure for class II, III, and IV patients were 1.16 (0.76-1.77) (P = .502), 2.27 (1.45-3.56) (P < .001), and 3.71 (1.25-11.02) (P = 018). New York Heart Association classes II through IV were also associated with higher risk of all-cause hospitalization.. Higher NYHA classes were associated with poorer outcomes in patients with heart failure and preserved systolic function.

Topics: Aged; Cardiotonic Agents; Cause of Death; Diabetes Complications; Digoxin; Female; Heart Failure; Hospitalization; Humans; Kidney Diseases; Male; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index; Statistics, Nonparametric; Stroke Volume

To determine whether a sex-based difference in digoxin pharmacokinetics exists in patients receiving long-term digoxin therapy for chronic heart failure or atrial fibrillation.. Single-center, retrospective review of medical records.. University-based teaching hospital and outpatient clinic.. Sixty-seven adults (32 men, 35 women) with chronic heart failure or atrial fibrillation who were receiving digoxin therapy.. Serum digoxin concentrations and daily digoxin doses were obtained from patients' medical records. Daily doses were adjusted for patients' actual and ideal body weight and body mass index (BMI). The ratio between the serum digoxin concentration and each of the adjusted daily doses of digoxin was compared between men and women. The mean +/- SD serum digoxin concentration was 0.85 +/- 0.51 ng/ml for men compared with 1.02 +/- 0.51 ng/ml for women. Mean +/- SD unadjusted doses of digoxin were 0.180 +/- 0.063 and 0.164 +/- 0.059 mg/day for men and women, respectively; the difference was not statistically significant. Ratios of serum digoxin concentration to daily digoxin doses did not differ by sex when doses were estimated with actual or ideal weight. Only the ratio of the digoxin concentration to the BMI-adjusted dose was significantly different between men and women (0.14 +/- 0.09 and 0.19 +/- 0.11, respectively, p<0.05).. Sex-based differences in digoxin pharmacokinetics were absent when actual or ideal body weight was used. However, the ratio of serum digoxin concentration to daily digoxin dose adjusted for BMI differed by sex. Because digoxin is distributed to lean body mass, use of the BMI could have overadjusted body weight, leading to inaccurate pharmacokinetic assumptions and calculations. The pharmacokinetics of digoxin do not appear to differ by sex.

Topics: Aged; Atrial Fibrillation; Body Mass Index; Body Weight; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Retrospective Studies; Sex Characteristics

The objective of this study was to describe the characteristics of long-term care residents with heart failure (HF), to evaluate the management of HF, and to compare their management with nationally published American College of Cardiology/American Heart Association guidelines.. Residents in long-term care facilities were identified by diagnosis of HF within their electronic medical record.. Data were collected on 302 residents in 19 long-term care facilities. The average age of the study population was 83.2 +/- 11.1 years and comprised 68.5% females.. Diabetes, obesity, hypertension, coronary artery disease, dementia, and hypothyroidism were identified in greater than 30% of residents. A diuretic was prescribed in 76.8% of residents. Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers were prescribed to 40.7% and 38.4% of residents, respectively; 16.2% of residents received both agents. Residents with diabetes or hypertension were not prescribed ACE inhibitors more often than residents without these comorbidities. Digoxin was prescribed more frequently in residents with atrial fibrillation (P = 0.028). Hospital admissions related to HF were documented in 30 (9.9%) residents within the past 12 months.. According to guidelines, most patients with HF should be routinely managed with a combination of four types of drugs: a diuretic, an ACE inhibitor, a betablocker, and, often, digoxin. Improvement in HF outcomes resulting in reduced morbidity and mortality may be achieved through greater adherence to nationally recognized guidelines. Opportunities exist for health care professionals to improve the management of residents with HF through appropriate drug therapy management.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Digoxin; Diuretics; Drug Therapy, Combination; Drug Utilization; Female; Heart Failure; Homes for the Aged; Humans; Long-Term Care; Male; Middle Aged; Nursing Homes

Non-potassium-sparing diuretics are commonly used in heart failure (HF). They activate the neurohormonal system, and are potentially harmful. Yet, the long-term effects of chronic diuretic use in HF are largely unknown. We retrospectively analysed the Digitalis Investigation Group (DIG) data to determine the effects of diuretics on HF outcomes.. Propensity scores for diuretic use were calculated for each of the 7788 DIG participants using a non-parsimonious multivariable logistic regression model, and were used to match 1391 (81%) no-diuretic patients with 1391 diuretic patients. Effects of diuretics on mortality and hospitalization at 40 months of median follow-up were assessed using matched Cox regression models. All-cause mortality was 21% for no-diuretic patients and 29% for diuretic patients [hazard ratio (HR) 1.31; 95% confidence interval (CI) 1.11-1.55; P = 0.002]. HF hospitalizations occurred in 18% of no-diuretic patients and 23% of diuretic patients (HR 1.37; 95% CI 1.13-1.65; P = 0.001).. Chronic diuretic use was associated with increased long-term mortality and hospitalizations in a wide spectrum of ambulatory chronic systolic and diastolic HF patients. The findings of the current study challenge the wisdom of routine chronic use of diuretics in HF patients who are asymptomatic or minimally symptomatic without fluid retention, and are on complete neurohormonal blockade. These findings, based on a non-randomized design, need to be further studied in randomized trials.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Cardiotonic Agents; Chronic Disease; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Prognosis; Regression Analysis; Retrospective Studies

Chronic left heart failure is the result of the activation of pathophysiological mechanisms which over time lead to progressive deterioration of the cardiac function. As pharmacotherapy aims at these mechanisms and as treatment possibilities are increasing, we find it relevant to provide a survey. Treatment evidence is based mainly on systolic dysfunction. It consists of angiotensin-converting enzyme inhibitor, aldosterone antagonist, beta-blocker, digoxin and diuretics. Incorporation of evidence-based medicine and treatment of diastolic dysfunction should be focussed on in the future.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Ventricular Dysfunction, Left

Topics: Cardiotonic Agents; Cause of Death; Clinical Trials as Topic; Digoxin; Heart Failure; Humans

The Digitalis Investigation Group (DIG) clinical train randomized 6800 congestive heart failure patients (ejection fraction > or =45%) to a daily regimen of either digoxin or placebo. At 37 months average follow-up, patients in both groups had similar mortality. We determined the incremental costs associated with the use of digoxin in this high-risk population.. Hospitalizations and medical costs were compared by using a societal perspective. Hospitalizations were assigned Medicare DRG codes by using descriptive information from the clinical trial. Digoxin use was assigned a cost by using the 1998 average wholesale price as reported by Red Book. On average, there were fewer hospitalizations in digoxin-treated patients. These patients had lower heart failure yet higher non-heart failure hospitalization costs than placebo patients. Digoxin therapy was cost saving versus placebo in only 27% of 1000 bootstrap samples using Medicare costs (mean costs 12,648 dollars vs. 12,362 dollars) and in 44% of samples using commercial carrier costs (mean costs 17,400 dollars vs. 17,306 dollars). How ever, digoxin was cost saving in >50% of samples for several higher-risk patient subgroups.. The use of digoxin therapy versus placebo was associated with reduced hospitalizations. Moreover, the resulting cost-savings could cover the costs of this inexpensive therapy in selected subgroups of higher-risk patients. In the remainder, there is a modest cost associated with this therapy.

Topics: Aged; Cardiotonic Agents; Cost Control; Digoxin; Drug Costs; Female; Health Care Costs; Heart Failure; Hospitalization; Humans; Male; Medicare; Randomized Controlled Trials as Topic

The advent of medical therapies for congestive heart failure that have proven survival benefits, specifically angiotensin-converting enzyme (ACE) inhibitors, beta-adrenergic antagonists, and the aldosterone antagonists, have called into question the use of digoxin for patients with normal sinus rhythm, left ventricular dysfunction, and symptomatic heart failure. This issue appears to have been heightened after the publication of the results of the Digitalis Investigation Group (DIG) Trial in 1997 that did not demonstrate a statistically significant impact of digoxin on mortality.. We used data from a large heart failure registry to examine digoxin use at the time of hospital admission for heart failure, a surveillance system for recording toxic drug exposures to describe patterns in digoxin toxicity and industry estimates for the use of digoxin antibody. Digoxin use has decreased significantly from 31.4% in late 2001 to 23.5% in late 2004 (P < .00001) independent of patient age, gender, or baseline creatinine. Conversely, the number of toxic or potentially toxic exposures to digoxin requiring hospitalization has not decreased.. Digoxin use is decreasing but there has not been a similar decline in cases of toxicity. Further analyses are required to delineate the reasons underlying these trends and the appropriateness of prescribing practices for both digoxin and its antidote.

Topics: Aged; Cardiotonic Agents; Commerce; Digoxin; Drug Utilization; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Male; Registries

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Heart Rate; Humans; Systole; Ventricular Dysfunction, Left

The authors present a case of an elderly female patient with heart failure and renal dysfunction treated with digoxin, where 2 commercial immunoassay methods (DRI, Microgenics, and DGNA, Dade Behring) showed a clinically very significant discrepancy on the same plasma sample, viz. 0.5 and 2.3 nmol/L, respectively. The sample was also referred to a third external laboratory that returned a result of 0.9 nmol/L using mFPIA (AxSYM, Abbott). Subsequent ultrafiltration (30,000 Dalton) on the sample essentially eliminated the difference, suggesting an interference from a large molecular weight compound(s), potentially the well-described digoxin-like immunoreactive substance(s) (DLIS). Although further study is required to verify that the DLIS implicated was indeed the interfering species, it does again highlight the importance of careful method selection in the clinical therapeutic drug monitoring laboratory to ensure that such well-established potential problems do not result in inappropriate dosage reduction with consequent lack of adequate drug exposure and serious clinical sequelae.

Topics: Aged; Cardenolides; Cardiotonic Agents; Digoxin; Drug Monitoring; Female; Heart Failure; Humans; Immunoassay; Saponins

Surgical intervention is playing an increasingly important therapeutic role in congestive heart failure (CHF) patients with ischemia and dilated cardiomyopathy. Their mitral regurgitation (MR) is a result of left ventricular (LV) geometrical distortion. The optimal type of ring for CHF patients with geometric ventricular-based MR is unknown. This study reviewed the results of flexible versus nonflexible complete mitral valve rings in CHF patients with geometric mitral regurgitation.. Using a prospectively maintained database, patients undergoing mitral valve reconstruction (MVR) with either a flexible or nonflexible complete ring were identified on the basis of preoperative ejection fraction (EF) < or = 30% and no primary mitral pathology. These 2 groups of CHF patients with severe geometric MR were then compared in terms of recurrent MR requiring reoperation. Between 1992 and 2004, 289 patients with EF < or = 30%, received an undersized complete mitral annuloplasty ring as their MVR procedure. Of these, 170 patients had a flexible complete ring. In follow-up, 16 "flexible" patients (9.4%) required a repeat procedure for significant recurrent geometric MR and CHF (10 replacements, 3 re-repairs, 3 transplants). The average time to reoperation was 2.4 years. In contrast, 119 patients with an EF < or = 30% received a MVR using an undersized nonflexible complete ring. Only 3 "non-flexible" patients required a repeat operation, MVR (1), and 2 patients required a transplant. The time to reoperation was 4.0 years. A significant difference in reoperation rates, for recurrent MR, between the 2 groups (P=0.012). There were no differences between groups, in terms of age, ring size used, preoperative EF, LV size, MR grade, or New York Heart Association class.. Patients with CHF having a flexible ring have a higher likelihood of developing recurrent MR requiring reoperation. The use of a nonflexible ring appears to significantly reduce the need for repeat surgical procedures. Further refinement and development of nonflexible ring systems, aimed at LV restoration, deserve ongoing investigation.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiomyopathy, Dilated; Combined Modality Therapy; Databases, Factual; Digoxin; Diuretics; Drug Therapy, Combination; Equipment Design; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Heart-Assist Devices; Humans; Male; Middle Aged; Milrinone; Mitral Valve; Mitral Valve Insufficiency; Norepinephrine; Pliability; Postoperative Complications; Prospective Studies; Recurrence; Reoperation; Spironolactone; Stroke Volume; Time Factors; Tricuspid Valve Insufficiency; Ultrasonography

Digoxin therapy has long been used to treat heart failure; however, its effectiveness was not completely known until recently. Results of the Digitalis Investigation Group trial showed that adding digoxin to standard heart failure therapy had no effect on mortality. However, adding digoxin decreased hospitalizations related to heart failure and improved symptoms in patients treated for heart failure. Reanalyses of the trial's findings have raised new questions about the role of digoxin in heart failure treatment. These new analyses showed that low serum digoxin concentrations used in patients with more severe disease offered the most benefit. Digoxin use in women was associated with increased mortality risk. This finding should be interpreted with caution, however, because it was based on retrospective data, and the cause of this phenomenon has not been fully elucidated. Prospective clinical trials are needed to determine the serum digoxin concentration that is associated with the most clinical benefit and to determine the role of digoxin therapy for women. Digoxin generally does not have a role in the treatment of diastolic heart failure and is not a first-line therapy for managing atrial fibrillation in patients with heart failure.

Topics: Algorithms; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Sex Factors; Treatment Outcome

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Failure; Humans

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Female; Heart Failure; Humans; Male

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Prospective Studies

A neonate presented on the first day of life with tachypnea and poor feeding. The infant's initial echocardiogram demonstrated outpouching of the lateral wall of the right ventricle (RV) associated with a large ventricular septal defect (VSD). At 9 days of age he was diagnosed with osteogenesis imperfecta (OI). Despite treatment with digoxin, diuretics, and captopril he required hospitalization twice during his first 2 months of life for congestive heart failure (CHF). The VSD was closed at three and one-half months of age without resection of the diverticulum and CHF symptoms resolved. At 26 months of age he is doing well despite the residual RV diverticulum. Congenital cardiac diverticula are rare forms of cardiac malformations and their echo-Doppler features are herein discussed.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Captopril; Cardiac Surgical Procedures; Digoxin; Diuretics; Diverticulum; Echocardiography; Furosemide; Heart Failure; Heart Septal Defects, Ventricular; Heart Ventricles; Humans; Infant, Newborn; Male; Myocardial Contraction; Osteogenesis Imperfecta; Stroke Volume

Topics: Cardiotonic Agents; Diastole; Digoxin; Heart Failure; Hospitalization; Humans; Stroke Volume

Topics: Aged; Cardiotonic Agents; Diagnosis, Differential; Digoxin; Heart Failure; Humans; Ischemia; Male; Mesentery; Time Factors; Ultrasonography, Doppler

The indications of digoxin therapy has been significantly narrowed and also the effective target therapeutic blood level has been decreased (0.9 micromol/L) compared to the previously desired one.. In this retrospective trial the data of 60 consecutive patients over 65 years (25 male, 35 female, mean age 77.3 +/- 5.0 y), hospitalized between 01. 01. 2002 and 31. 12. 2003 with a diagnosis of chronic heart failure and elevated (> 1.2 microg/I) serum level of digoxin, were analyzed.. Beside the analysis of the age, sex, serum level of digoxin and potassium, creatinine clearance value, symptoms and ECG-signs of digitalis intoxication, presence of atrial fibrillation, concomitant diseases and left ventricular ejection fraction value, the reasonability of digitalis treatment and therapy applied at the time of discharge (considering actual treatment guidelines) were also reviewed.. At the admission mean serum level of digoxin was 2.1 +/- 0.9 microg/l. 20 patient's value (33.3%) was found above 2.2 microg/l. Symptoms characteristic for digitalis intoxication were observed in 28 patients. On the ECG performed at admission signs of digitalis effect/overdose were observed in 54 cases ("bigemin" ventricular extrasystoles, bradycardia, characteristic down-sloping ST-depressions). The mean left ventricular ejection fraction of the patients (51.5 +/- 12.7%) did not suggest to a significant left ventricular systolic dysfunction. For the elevated serum level of digoxin the impaired renal function (mean creatinine clearance 42.9 +/- 21.3 mL/min) was responsible in most cases. In patients with the highest serum level of digoxin (n = 20, 3.2 +/- 0.7 microg/L) the creatinine clearance was even lower, 30.4 +/- 13.7 mL/min. During hospital treatment the administration of digitalis was found to be unnecessary and thus terminated in 44 patients. At the discharge only 16 patients were receiving digitalis, 14 of them digoxin and 2 patients digitoxin.. The authors emphasize, that in case of elderly patients the indication and control of digitalis therapy requires greater precaution and tight doctor-patient cooperation.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Bradycardia; Cardiotonic Agents; Creatinine; Digoxin; Drug Prescriptions; Electrocardiography; Female; Heart Failure; Humans; Hungary; Male; Patient Admission; Patient Discharge; Potassium; Retrospective Studies; Stroke Volume; Ventricular Premature Complexes

Digoxin has been used to treat congestive heart failure (CHF) for more than two centuries. It's clinical efficacy, however, has been under question in recent years because recent clinical trials showed that digoxin therapy in CHF patients was associated with no beneficial effects in mortality, but only a modest reduction in clinical symptoms and the frequency of heart failure related hospitalisation. Digoxin's effect on mortality seems closely related to its serum concentrations; high serum concentrations (e.g. >or=1.2 ng/ml) have been found to increase the risk of all-cause mortality in heart failure patients. Digoxin-associated risk in mortality may be due to an increases in myocardial oxygen consumption and arrhythmogenesis at higher serum concentrations. We hypothesized that the serum concentration of digoxin is a major determinant factor of its efficacy on mortality rates in patients with congestive heart failure. The maintenance of digoxin's serum concentration at the lower end of the reference range, i.e., between 0.5 and 0.8 ng/ml, may reduce mortality rates as well as improve clinical symptoms.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Incidence; Risk Assessment; Risk Factors; Treatment Outcome

The medical management of heart failure (HF) in clinical practice varies considerably by country and by medical specialty.. To assess the treatment of HF patients admitted to Internal Medicine departments, and to evaluate out-patient management prior to admission, by specialty.. Prospective cross-sectional multi-centre survey.. Of 55 randomly selected Spanish hospitals, 51 agreed to participate. All patients (n = 2145) consecutively admitted for decompensated HF to the Departments of Internal Medicine of these hospitals, over 5 months, were included. Twenty variables were analysed, including aspects relating to out-patient management prior to admission.. Mean +/- SD age was 77.2 +/- 10.5 years, 57.3% were female, 47% had systolic dysfunction. Prescriptions at discharge: loop diuretics 85.6%, spironolactone 29.8%, ACEIs 65.8%, beta-blockers 8.7%, cardiac glycosides 39%. At admission, 86% already had a diagnosis of HF. Of these, 53% (older patients and more women) were being treated on an out-patient basis by primary care physicians. Primary care physicians requested fewer echocardiograms than internists (38% vs. 69%, p<0.001) and prescribed fewer drugs (ACEIs 40% vs. 54%, p<0.001; spironolactone 15% vs. 23%, p<0.05; beta-blockers 6% vs. 13%, p<0.01). The internists treated more incapacitated patients than the cardiologists (p<0.001), prescribed more high-dose ACEIs (20% vs. 13%, p<0.01) and spironolactone (26% vs. 20%, p<0.05), and fewer anticoagulants (32% vs. 39%, p<0.05).. Patients admitted to medical departments with HF are different to those found in clinical trials. Their management is currently suboptimal. Differences in treatment between internists and cardiologists appear to be accounted for by differences in the patients they treat.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiac Glycosides; Cardiotonic Agents; Cross-Sectional Studies; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Nitrates; Prospective Studies; Spironolactone

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Female; Heart Failure; Humans; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sex Factors; Survival Analysis; Ventricular Dysfunction, Left

Digoxin is often used in long-term care (LTC) residents with heart failure despite a high risk of toxicity associated with increased age, comorbidities and polypharmacy. This toxicity may occur at serum digoxin concentrations that are as low as 1.54 nmol/L.. To determine the prevalence of digoxin use, estimate the proportion at risk of toxicity and identify correlates of digoxin use in LTC residents with heart failure.. Cross-sectional survey in eight LTC facilities that lodge a total of 1223 residents.. The prevalence of heart failure was 20%. Digoxin was prescribed for 32% of residents with heart failure and was associated with arrhythmia (primarily atrial fibrillation), anticoagulant and diuretic use, and higher serum thyroid-stimulating hormone. Digoxin doses higher than those that achieve the recommended therapeutic peak body stores of 6 microg/kg and 10 microg/kg were prescribed to 80% and 33% of residents with heart failure, respectively. Serum digoxin concentrations were greater than 1.5 nmol/L in 30% of patients. Comorbidities and concurrently prescribed medications that increase the risk of digoxin toxicity were prescribed to 26% of the patients.. Approximately one-third of LTC residents with heart failure received digoxin. Atrial fibrillation was the most important determinant of use. At least 26% of these residents were exposed to an increased risk of digoxin toxicity. Studies are required to determine safe and effective digoxin dosing regimens for frail elderly heart failure patients. Clinicians should exercise caution when using digoxin in LTC residents.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Cross-Sectional Studies; Digoxin; Drug Monitoring; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization; Female; Frail Elderly; Guideline Adherence; Health Care Surveys; Heart Failure; Humans; Male; Multivariate Analysis; Nursing Homes; Ontario; Patient Selection; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prevalence; Risk Factors

We defined the prevalence and impact on survival of clinical bedside variables in 385 patients with symptomatic congestive heart failure (CHF), of whom there were 176 with and 209 without diabetes mellitus. Patients were consecutively hospitalized and admitted for various acute conditions. Following discharge all-cause mortality was recorded. Prevalence and association of various variables with mortality were statistically analyzed. Prevailing in the diabetics versus nondiabetics were younger age (p < 0.05), pulmonary edema on admission (p = 0.002), using furosemide > 80 mg/day (p < 0.01) for > 1 year (p < 0.01) and hyponatremia (p = 0.01). Less prevalent were chronic lung disease (p < 0.01) and cardiac arrhythmias (p = 0.001). On follow-up extending up to 60 months, diabetic patients, especially those with fasting blood glucose levels on admission > or = 180 mg/dl, survived for a shorter period of time than nondiabetics (p = 0.02). Associated with increased mortality in the diabetic group were female gender (p = 0.04), furosemide > or = 80 mg/day (p < 0.001) and renal dysfunction (RD; p = 0.04). The respective variables in the nondiabetics were advanced age (p < 0.001) and RD (p = 0.002). Although they were younger, diabetic patients presented more severe CHF. It is recommended that special attention should be given to diabetic females, those using higher furosemide dosages and those suffering from RD.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Diabetic Angiopathies; Digoxin; Diuretics; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Prevalence; Prognosis; Risk Factors; Survival Analysis

Congestive heart failure (CHF) is responsible for significant morbidity, mortality and health resource consumption. There have been major advances in the treatment of this condition over the past two decades, yet little information is currently available regarding the current status of CHF management in Canada.. To describe the pharmacological management of patients hospitalized with CHF in five provinces: Alberta, British Columbia, Nova Scotia, Ontario and Quebec.. Administrative data sources were used to identify all consecutive patients hospitalized with a principal diagnosis of CHF and discharged alive in the provinces of Alberta, British Columbia, Quebec and Ontario. Rates of use of prespecified medications at 30 days after hospital discharge were obtained for patients 65 years of age and older by linkage of their hospital records with drug benefit plans in these provinces. For Nova Scotia, the disease-specific registry of the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) study was used to obtain discharge medications of individuals consecutively hospitalized with a diagnosis of CHF. Where available, data were acquired from 1997 to 2002.. Data were obtained for a total of 115,037 patients in the five provinces over the five-year period. Overall, 54.9% of patients received an angiotensin-converting enzyme inhibitor at or 30 days after hospital discharge, with minimal change in prescription rates over the five-year period. Beta-blocker prescription rates increased steadily during the study, more than doubling from 15.0% in 1997/1998 to 32.0% in 2001/2002. Spironolactone use increased dramatically, with only 2.2% of patients receiving this medication in 1997/1998 compared with 18.7% in 2001/2002. The rates of digoxin prescription decreased each year, while the use of angiotensin receptor blockers increased slightly throughout the observation period.. While the use of evidence-based treatment for CHF in Canada is increasing and is currently at levels similar to those reported in other developed countries, there is still the potential in every province for further improvement.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Canada; Cardiotonic Agents; Digoxin; Diuretics; Drug Utilization; Heart Failure; Humans; Spironolactone

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Defibrillators, Implantable; Digoxin; Drug Interactions; Drug Therapy, Combination; Heart Failure; Humans

In a series of papers the authors analyze literature data on the use of cardiac glycosides for long term treatment of chronic heart failure. Part II is devoted to analysis of results of small controlled studies of pharmacological effects of low dose digoxin in patients with sinus rhythm. Low dose digoxin improves exercise tolerance and lowers risk of decompensation of heart failure but produces no substantial effect on contractility of left ventricular myocardium. Therefore its favorable action on clinical course and outcomes of chronic heart failure is most probably related to modulation of neuro-humoral systems. Retrospective analysis of some trials shows that digoxin is able to increase mortality of survivors of acute myocardial infarction. Hence great care is required when digoxin is used for long term treatment of chronic heart failure due to systolic left ventricular dysfunction after myocardial infarction.

Topics: Algorithms; Cardiac Glycosides; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Treatment Outcome

Topics: Acute Kidney Injury; Aged; Cardiotonic Agents; Chronic Disease; Digoxin; Emergency Medicine; Fatal Outcome; Female; Heart Failure; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Natriuretic Peptide, Brain

The purpose of this study was to investigate the relationship of serum digoxin concentration (SDC) and outcomes in women with heart failure (HF).. Controversy continues concerning the clinical utility of digoxin in women with HF.. Our analysis was retrospective with data from the Digitalis Investigation Group (DIG) trial. The principal study analysis reviewed 4,944 patients with HF due to systolic dysfunction who survived for at least 4 weeks (all 3,366 patients randomized to placebo and the 1,578 of 3,372 patients randomized to digoxin who had serum concentration measured 6 to 30 h [inclusive] after the last dose of study drug at 4 weeks).. Continuous multivariable analysis demonstrated a significant linear relationship between SDC and mortality in women (p = 0.008) and men (p = 0.002, p = 0.766 for gender interaction). Averaging hazard ratios (HRs) across serum concentrations from 0.5 to 0.9 ng/ml in women produced a HR for death of 0.8 (95% confidence interval [CI] 0.62 to 1.13, p = 0.245) and for death or hospital stay for worsening HF of 0.73 (95% CI 0.58 to 0.93, p = 0.011). In contrast, SDCs from 1.2 to 2.0 ng/ml were associated with a HR for death for women of 1.33 (95% CI 1.001 to 1.76, p = 0.049).. Retrospective analysis of data from the DIG trial indicates a beneficial effect of digoxin on morbidity and no excess mortality in women at serum concentrations from 0.5 to 0.9 ng/ml, whereas serum concentrations > or =1.2 ng/ml seem harmful.

Topics: Age Factors; Aged; Biological Availability; Cardiotonic Agents; Confidence Intervals; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Failure; Humans; Maximum Tolerated Dose; Middle Aged; Multivariate Analysis; Probability; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Severity of Illness Index; Survival Analysis; Treatment Outcome

Topics: Aged; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Treatment Outcome; Ventricular Function, Left

Resting left ventricular ejection fraction (LVEF) and functional capacity do not correlate in chronic heart failure patients treated with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. We sought to determine whether substantial improvement in LVEF, as may occur during long-term beta-blockade or after coronary artery bypass graft (CABG) surgery, leads consistently to improvement in functional class. Doppler echocardiogram and assessment of functional class were obtained at baseline and 12 months after initiation of beta-blockade (87 patients) or CABG surgery (51 patients). At 12 months the effects of beta-blockade were variable: LVEF increased greatly by >or=11% (median value) in 45 patients (52%) and by <11% in 19 (22%), but it decreased or remained unchanged in 23 patients (26%). In contrast, functional class was unchanged or worsened in 59 patients (68%) and improved in only 28 (32%). Similarly, surgery had variable effects on LVEF. LVEF increased by >or=12% (median) in 28 patients (55%) and by <12% in 14 (27%), whereas it decreased or remained unchanged in 9 patients (18%). Functional class was unchanged or worsened in 41 patients (80%) and improved in only 10 (20%). Changes in functional class and LVEF were unrelated for both interventions. Both beta-blockade and CABG surgery improve LVEF in the majority of patients. However, significant improvement in LVEF does not enhance functional capacity consistently in chronic heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Chronic Disease; Coronary Artery Bypass; Digoxin; Diuretics; Echocardiography, Doppler; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Ventricular Function, Left

Inappropriate medication use in patients with heart failure (HF) presents challenges in providing optimal, evidence-based care.. To evaluate the incremental differences of concurrent and persistent use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, loop diuretics, and digoxin on the one-year, all-cause risk of hospitalization and total healthcare costs associated with treatment of HF in patients enrolled in a managed care organization within the US.. A retrospective database analysis was conducted spanning from January 1, 1997, to December 31, 1999. Multivariate regression methods were used to examine the association between treatment regimens and hospitalizations or costs after controlling for patient demographics and risk factors.. Of the 1903 patients meeting inclusion criteria, 32.3% (n = 615) received none of the 4 HF agents studied and were associated with a 2.5 times greater risk (p < or = 0.001) of hospitalization and 43.6% higher (p < or = 0.001) total costs compared with all other patients with HF. Comparatively, 13.9% (n = 264) utilized the HF medications investigated for at least 6 months. Of those with persistent use of > or =3 agents, approximate decreases in hospitalizations were noted of 80% (p < or = 0.001) and total costs of 70% (p < or = 0.001) relative to patients receiving no HF therapy.. A substantial portion of patients with HF may be receiving suboptimal pharmacotherapeutic care in real-world practice settings, potentially incurring large increases in hospitalizations and total costs. Quality improvement initiatives should seek to identify and manage those not being treated according to guideline recommendations.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Costs and Cost Analysis; Digoxin; Drug Prescriptions; Drug Utilization Review; Female; Heart Failure; Hospitalization; Humans; Male; Managed Care Programs; Multivariate Analysis; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Time Factors

Topics: Aged; Cardiotonic Agents; Digoxin; Electrocardiography; Heart Failure; Humans; Male

Congestive heart failure (CHF) is the most common cause of cardiovascular hospital admission. A significant proportion of the costs of CHF is due to hospitalizations. The present study evaluated the economic impact of a modest increase in the use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, spironolactone and digoxin on CHF hospitalizations. Patients with CHF were identified through the Canadian Institute for Health Information (CIHI) database. The efficacy of ACE inhibitors, beta-blockers, spironolactone and digoxin in the first year of treatment were retrieved from the Survival and Ventricular Enlargement (SAVE) trial, a meta-analysis, the Randomized Aldactone Evaluation Study (RALES) and the Digitalis Investigation Group (DIG) trial, respectively. Cost of CHF hospitalization was based on the National List of Provincial Costs. Costs of drug treatment were based on the 2002 Alberta Health and Wellness Drug Benefit list. Physician visits for drug titration were also included in the model. A total of 85,679 patients with CHF were identified with a total of 106,130 hospital discharges. A 10% increase in use of ACE inhibitors, beta-blockers, spironolactone and digoxin would incur in a total cost due to avoidable hospital admissions of 0.4 million dollars, 1.3 million dollars, 3.7 million dollars and 1.2 million dollars, respectively. Similarly, the costs of drug treatment would be 2.2 million dollars, 1.3 million dollars, 0.3 million dollars and 0.5 million dollars, respectively. An increase in the use of the above medications would save 6.6 million dollars due to avoidable hospital admissions. The total cost of drug treatment was 4.3 million dollars, giving a net savings of 2.3 million dollars in the first year. The implementation of evidence-based therapy for CHF treatment is not only clinically efficacious, but also economically attractive.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Canada; Databases as Topic; Digoxin; Drug Costs; Drug Utilization Review; Guideline Adherence; Heart Failure; Hospital Costs; Hospitalization; Humans; Practice Guidelines as Topic; Spironolactone

Heart failure is a leading cause of morbidity and mortality, but there are no reliable models based on readily available clinical variables to predict outcomes in patients taking angiotensin-converting enzyme (ACE) inhibitors.. A multivariate statistical model to predict mortality was developed in a random sample (n = 4277 patients [67%]) of the 6422 patients enrolled in the Digitalis Investigation Group trial who had a depressed ejection fraction (

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Models, Statistical; Multivariate Analysis; Proportional Hazards Models; Stroke Volume; Survival Rate; Systole; Ventricular Dysfunction, Left

Two patients are reported, each with heart failure, who were treated with digoxin (case 1) and furosemide (case 2). Indications for medical treatment of patients with heart failure, the role of various drugs, and exercise therapy, are reviewed. At a time when the population of people over 65 years of age is increasing, it is important for physicians to recognize the symptoms of heart failure and to know the most up-to-date treatment for this disorder. These cases demonstrate the significance of the anesthesiologist as a perioperative physician.

Topics: Aged; Aged, 80 and over; Anesthetics; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Female; Furosemide; Heart Failure; Humans; Male

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Synergism; Drug Therapy, Combination; Electrocardiography; Emergency Treatment; Heart Failure; Humans; Male; Tachycardia, Ventricular

In patients with congestive heart failure (CHF), use of submaximal doses of angiotensin-converting enzyme (ACE) inhibitors (ie, low-dose ACE inhibitors) represents usual care in routine clinical practice, whereas high-dose ACE inhibitors, beta-blockers, and digoxin have each been shown to improve outcomes.. We examined whether treatment with high dose-ACE inhibitors, beta-blockers, and digoxin would each provide incremental benefits over that achieved with usual care and whether concurrent use of high-dose ACE inhibitors, beta-blockers, and digoxin would provide maximal benefits.. We conducted a secondary analysis of a randomized, controlled, active-comparator trial. Specifically, we studied 1-year outcomes data from the Assessment of Treatment with Lisinopril and Survival trial (ATLAS), which assessed high-dose ACE inhibitors (mean dosage, 33.2 mg daily lisinopril) versus low-dose ACE inhibitors (mean dosage, 4.5 mg daily lisinopril) in patients of any age with advanced CHF in 287 centers in 19 countries in the 1990s. In our analysis, patients were classified by their use of low-dose or high-dose ACE inhibitors, beta-blockers, and/or digoxin at the time of randomization. The primary outcome of interest was the ATLAS composite end point of all-cause mortality or hospitalization for any reason at 1 year. Multiple logistic regression analyses were used to adjust for baseline differences in patient characteristics.. The 3164 patients in the ATLAS study had a mean (SD) age of 64 (10) years; 2516 patients (80%) were men and 648 (20%) were women; mean (SD) left-ventricular ejection fraction was 23% (6%); and 2671 patients (84%) had New York Heart Association class III or IV symptoms. At 1 year, the mortality rate was 13% (408 patients); 43% (1369 patients) had > or =1 hospitalization; and the composite end point of mortality or hospitalization was 47% (1489 patients). Most patients (2873; 91%) remained on their initial treatment regimen. Compared with low-dose ACE inhibitors (n = 471), the composite end point decreased incrementally with the use of high-dose ACE inhibitors (n = 475) (adjusted odds ratio [aOR], 0.93; P = NS), high-dose ACE inhibitors plus beta-blockers (n = 72) (aOR, 0.89; P = NS), and high-dose ACE inhibitors plus beta-blockers plus digoxin (n = 77) (aOR, 0.47; P = 0.006). In absolute proportions, patients receiving high-dose ACE inhibitors plus beta-blockers plus digoxin for 1 year had 12% fewer deaths and hospitalizations than patients receiving low-dose ACE inhibitors alone.. Compared with usual care for patients with CHF, in this analysis, an evidence-based strategy that incorporated high-dose ACE inhibitors plus beta-blockers plus digoxin was associated with incrementally greater reductions in morbidity and mortality. These findings support treatment guidelines that recommend the concurrent use of all available proven efficacious treatment in patients with advanced CHF.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Randomized Controlled Trials as Topic; Survival Analysis; Ventricular Function, Left

The anesthetic management of labor and delivery in patients with peripartum cardiomyopathy is not well defined. Using continuous spinal anesthesia in such a rare clinical situation has not been previously reported. A patient with recurrent peripartum cardiomyopathy presented in congestive heart failure for emergent cesarean section. Continuous spinal anesthesia was successfully employed as the anesthetic technique for the procedure. In addition, it also markedly reduced the patient's symptoms. Continuous spinal anesthesia is a reliable, rapidly titratable technique, which provides excellent analgesia with minimal undesirable hemodynamic changes for patients with peripartum cardiomyopathy undergoing cesarean delivery.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Cardiomyopathy, Dilated; Cardiotonic Agents; Cesarean Section; Digoxin; Diuretics; Echocardiography; Female; Furosemide; Heart Failure; Hemodynamics; Humans; Pregnancy; Recurrence

In 1,009 patients with atrial fibrillation and congestive heart failure, the 2-year mortality rate was 31% in patients treated with rate control (n = 505) versus 29% in patients treated with rhythm control (n = 504). After adjusting for differences in baseline characteristics and medications, no significant difference in mortality was found between the 2 groups.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Chi-Square Distribution; Digoxin; Female; Heart Failure; Humans; Male; Proportional Hazards Models; Statistics, Nonparametric; Treatment Outcome; Warfarin

To compare patients treated for heart failure in relation to the management in general practices versus hospital admission.. Twelve randomly selected general practices (GP) were screened for patients receiving ACE-inhibitor, digoxin, or loop diuretic treatment. The first 500 volunteers of 959 potential subjects were invited to a cardiac examination after exclusion of 235 frail, physically or mentally disabled patients. A diagnosis of heart failure during hospital admission (Hospital-HF, n = 102) was more related (p < 0.05) to male sex (45% vs. 21%), advanced age (73 vs. 70 years), breathlessness (75% vs. 62%), LV systolic dysfunction (47% vs. 20%), objective cardiac abnormality (92% vs. 65%) and higher 4-year mortality (33% vs. 15%) than patients taking loop diuretics due to signs and symptoms of heart failure in GP (GP-HF). Patients without clinical heart failure (n = 301) had the same survival but less symptoms and cardiac abnormalities than GP-HF patients.. A surplus morbidity and mortality was related to a hospital-based rather than a GP based diagnosis of HF. Patients managed in GP were different from patients entering previous clinical trials of heart failure. We estimate that the pool of patients hospitalised with systolic heart failure would be increased from 1.3 to 1.4 more if all patients from primary care were included.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cross-Sectional Studies; Digoxin; Diuretics; Family Practice; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Prevalence; Scotland

The need for new treatment strategies for cardiac arrhythmias has motivated our continuing development of gene therapeutic options. Previously, we reported a decreased heart rate in an acute model of atrial fibrillation after atrioventricular nodal gene transfer. Here, we expand those observations to persistent atrial fibrillation and severe heart failure.. After 3 weeks of atrial fibrillation, domestic swine received atrioventricular nodal gene transfer with adenoviruses encoding beta-galactosidase (beta-gal), wild-type Galpha(i2) (wtGi), or constitutively active mutant (cGi). Heart rates in awake, alert animals were not altered by beta-gal or wtGi. cGi caused a sustained 15% to 25% decrease in heart rate. The wtGi effect became evident with sedation. A tachycardia-induced cardiomyopathy was present before gene transfer. In the beta-gal group, cardiomyopathy worsened over time. In the wtGi group, the condition improved slightly, and in the cGi group, ejection fraction was near normal at the end of the study. TUNEL staining results corroborated this finding.. cGi overexpression in the porcine atrioventricular node causes physiologically relevant heart rate control in persistent atrial fibrillation. These data advance the development of gene therapy as a potential treatment for common cardiac arrhythmias.

Topics: Acute Disease; Adenoviridae; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrioventricular Node; Cardiac Pacing, Artificial; Digoxin; Diltiazem; Gene Expression Regulation; Genetic Therapy; Genetic Vectors; GTP-Binding Protein alpha Subunit, Gi2; GTP-Binding Protein alpha Subunits, Gi-Go; Heart Failure; Heart Rate; Propanolamines; Proto-Oncogene Proteins; Recombinant Fusion Proteins; Stroke Volume; Sus scrofa; Ultrasonography

In patients with dilated cardiomyopathy (DCM) and severe congestive heart failure, immunoadsorption (IA) and subsequent IgG substitution leads to an acute and prolonged hemodynamic improvement. Goal of this study was to investigate the long-term effect of immunoadsorption on morbidity.. In a retrospective analysis of 34 patients (17 patients who have received immunoadsorption therapy and 17 control patients) were included. Inclusion criteria were DCM, left ventricular ejection fraction less than 35%, NYHA classes II-III. The average time after immunoadsorption was 3.0 years (median 2.3 years). Both groups did not differ concerning sex, age, duration of disease, medication, baseline ejection fraction and NYHA class.. In patients who have received immunoadsorption (IA) the days of hospitalisation for congestive heart failure per year could be significantly reduced in contrast to the control patients (17.2 days prior to IA, 4.3 days after IA). Even if the procedural days for immunoadsorption were included there was still a significant reduction of hospitalisation if IA therapy was longer than 2.5 years ago. The days of hospitalisation increased gradually with time during the follow up period. IA induced an acute increase in EF (19.8-25.7%, p<0.01 vs. baseline).. IA not only leads to an acute hemodynamic improvement in patients with DCM but may also reduce morbidity in these patients during the next 3 years.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Digoxin; Diuretics; Heart Failure; Hospitalization; Humans; Immunosorbent Techniques; Immunotherapy; Male; Middle Aged; Morbidity; Retrospective Studies; Time

Digoxin is used to treat congestive heart failure and atrial fibrillation. Blood levels need to be monitored to optimize therapeutic performance, detect noncompliance and reduce toxicity. The aim of this study was to evaluate the use of digoxin by measuring blood levels of this drug. The influence of sex and age were also considered.. A retrospective study reviewed determinations of blood digoxin concentration in hospitalized and ambulatory patients with congestive heart failure, atrial fibrillation, or both, seen at the University of Granada Teaching Hospital (Spain) from 1992 to 2002. A chi square test was applied to results.. A total of 5,623 laboratory tests for digoxin were done for 2,849 adult patients. Patients whose medical record was incomplete were excluded, and the final sample consisted of 2,629 patients. The 55.4% had inappropriate blood levels of digoxin. Inappropriate concentrations to digoxin were significantly higher in women (p < 0.001). The percentage of patients with high levels of the drug was significantly greater among men (p < 0.001). Very low concentrations (< 0.5 ng/ml) were found in 16% of the patients, with no significant difference between sexes.. We detect a large percentage of older patients with inappropriate levels of digoxin in blood. Women were more likely than men to have high levels to digoxin in blood. There is evidence that therapeutic monitoring of blood levels of digoxin is not done as often as is advisable; this has implications for the care of patients being treated with this drug.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Drug Monitoring; Female; Heart Failure; Hospitals, University; Humans; Male; Middle Aged; Retrospective Studies; Sex Factors

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Cardiotonic Agents; Catheterization, Swan-Ganz; Cesarean Section; Diagnosis, Differential; Digoxin; Diuretics; Dobutamine; Electrocardiography; Female; Furosemide; Heart Failure; Humans; Hydralazine; Intubation, Intratracheal; Nitroprusside; Pulmonary Edema; Twins; Vasodilator Agents

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Sex Factors

Topics: Cardiotonic Agents; Confounding Factors, Epidemiologic; Digoxin; Female; Heart Failure; Humans; Male; Sex Factors

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Sex Factors

Internationally, research indicates that pharmacotherapy for chronic heart failure (CHF) is sub-optimal. Traditionally, assessment of drug use in heart failure has focused on the use of individual agents irrespective of CHF severity. This study investigates drug use for CHF patients in general practice with respect to the available evidence, incorporating both disease severity and the use of combination drug regimes.. A cross-sectional survey of 769 Dutch CHF patients was performed as part of IMPROVEMENT of HF study. For each New York Heart Association severity classification the minimum treatment appropriate for the heart failure severity according to the scientific evidence available at the time of the study (1999) was defined. The proportion of patients treated with each drug increased with increasing severity, with the exception of the beta-blockers. Patients with less severe heart failure were approximately four to eight times more likely to receive evidence-based treatment than those with more severe heart failure.. To assess pharmacological treatment of heart failure, in relation to the available evidence, it is important to take severity into account. While the number of drugs prescribed increased with increasing severity, the use of evidence-based regimes was lower in patients with more severe heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Atrial Fibrillation; Comorbidity; Cross-Sectional Studies; Digoxin; Diuretics; Drug Therapy; Drug Therapy, Combination; Evidence-Based Medicine; Family Practice; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Severity of Illness Index; Treatment Outcome

Topics: Anti-Arrhythmia Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Ventricular Dysfunction, Left

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Ventricular Dysfunction, Left

The different therapeutic schedules used for the prescription of digoxin have little theoretical support.. To measure digoxin plasma levels in patients using four different prescription schedules.. Four groups of patients were studied. Group I corresponded to 56 patients taking digoxin 0.25 mg/day, from Monday to Friday. Group II corresponded to 30 patients taking digoxin 0.25 mg/day, from Monday to Saturday. Group III corresponded to 53 patients taking digoxin 0.25 mg/day continuously. Group IV corresponded to 36 patients taking digoxin 0.125 mg/day continuously. Plasma digoxin levels were measured in two consecutive Mondays before taking the daily dose of the drug. Serum creatinine was also measured and creatinine clearance was calculated. The therapeutic plasma concentration range was set between 0.5 and 2 ng/ml.. Mean plasma digoxin levels were 1.15 +/- 0.8 ng/ml in group I, 1.4 +/- 0.55 ng/ml in group II, 1.68 +/- 0.7 ng/ml in group III and 1.14 +/- 0.43 ng/ml in group IV. 93% of patients in group I, 80% of patients in group II, 75% of patients in group III and 94% of patients in group IV had therapeutic digoxin levels. A low creatinine clearance, an age over 65 and interactions with other drugs were risk factors associated with supratherapeutic levels, mostly seen in group II and group III with 20% and 24% respectively.. Most patients using digoxin with different therapeutic schedules had plasma drug levels within the therapeutic range.

Topics: Aged; Cardiotonic Agents; Creatinine; Digoxin; Drug Administration Schedule; Drug Interactions; Female; Heart Failure; Humans; Male; Middle Aged

There are now a number of guidelines outlining the diagnosis and management of patients with chronic heart failure (CHF). The extent to which these guidelines are used and the effects on patient outcomes are not well known. The aim of this study was to examine the implementation of a heart failure guideline among cardiologist and non-cardiologist physicians in a university hospital setting. Case record data were examined from 400 patients with a primary diagnosis of CHF. Management of these patients was assessed using a systolic heart failure guideline (Scottish Intercollegiate Guideline Network, number 35) as a benchmark. Hospital admission data were examined contemporaneously over a 17-month period to assess associations between adherence to drug therapies and number of admissions. Overall, there was poor adherence to the guideline, with relatively high use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) (80%), low use of beta-blockers (32%) and digoxin (36%), and very low use of spironolactone (13%). Cardiologists used more beta-blockers (37 vs. 21%, P=0.003) and digoxin in sinus rhythm (18 vs. 5%, P<0.001) than non-cardiologists. Hospital admission rate was individually associated with increasing age, NYHA status, beta-blocker, diuretic and spironolactone prescription (all P<0.001). At multivariable analysis, only age, NYHA status and increased diuretic prescription were associated with more frequent admission (P<0.001, R(2)=0.15). Despite carefully designed guidelines, the implementation of evidence-based therapies for CHF remains inadequate, even in a university hospital environment. This may reflect a lack of organisational developments to facilitate the increasingly complex management of patients with CHF.

Topics: Aged; Cardiology; Chronic Disease; Digoxin; Diuretics; Female; Guideline Adherence; Heart Failure; Hospitalization; Humans; Male; Practice Guidelines as Topic; Practice Patterns, Physicians'; Spironolactone; Ventricular Dysfunction, Left

The cardiac safety of digoxin therapy for congestive heart failure (CHF) is a source of concern, especially among those with renal impairment.. Using a case-control design, we examined the risk of primary cardiac arrest (PCA) associated with digoxin therapy within three levels of renal function.. After adjustment for other clinical characteristics, digoxin therapy for CHF was not associated with an increased risk of PCA [odds ratio (OR)=0.97, 95% confidence interval (CI) 0.59-1.62] among patients with normal renal function (serum creatinine

Topics: Aged; Cardiotonic Agents; Case-Control Studies; Creatinine; Digoxin; Female; Heart Arrest; Heart Failure; Humans; Kidney; Male; Middle Aged; Odds Ratio; Risk Factors

trans-1,2-Cyclohexanediol, the major metabolite of the cilexetil moiety of candesartan cilexetil (CC), has been reported to have potent pro-arrhythmic effects in dogs with congestive heart failure (CHF), especially when co-administered with digoxin. To verify this and to clarify the clinical relevance and the underlying mechanisms, a series of in vivo and in vitro experiments was conducted. When CC up to 300 mg/kg was administered orally to intact dogs, no changes in the electrocardiograms (ECG) or the required cumulative doses of ouabain to induce ventricular arrhythmias were observed. In dogs with CHF, intravenous bolus administration of trans-1,2-cyclohexanediol at 4 mg/kg followed by continuous infusion at 0.1 mg x kg(-)(1) x min(-)(1) had no effects on the ECG parameters, the type, incidence, and onset time of digoxin-induced arrhythmias or the metabolism of digoxin. In an in vitro experiment using isolated guinea pig papillary muscle, trans-1,2-cyclohexanediol (1 - 100 micromol/L) showed no effects on any parameter of the action potentials. Because no effects were observed in these experiments where the exposure levels of trans-1,2-cyclohexanediol were extremely high compared to those in humans given the maximum therapeutic dose of CC, it is unlikely that CC would induce arrhythmias in clinical use even in patients treated with cardiac glycosides.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Benzimidazoles; Biphenyl Compounds; Cyclohexanols; Digoxin; Dogs; Drug Interactions; Guinea Pigs; Heart Failure; In Vitro Techniques; Male; Papillary Muscles; Tetrazoles

To evaluate the prognostic roles of prolonged signal-averaged P wave duration (SAPWD), raised levels of natriuretic peptides, and clinical characteristics in patients with stable congestive heart failure (CHF).. The SAPWD was assessed from a signal-averaged electrocardiogram (SAECG), and the plasma levels of N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP) were measured in 43 consecutive patients with stable CHF without prior supraventricular arrhythmia. Echocardiographic and clinical data were also recorded. Time to death, hospitalization due to deteriorated CHF, or ECG-documented atrial fibrillation (AF) was recorded over a 438-day median follow-up.. During follow-up, 17 patients met an endpoint defined as death, AF, or hospitalization due to deteriorated CHF. Proportional hazard regression including the variables high age, prolonged SAPWD, raised levels of Nt-proANP and Nt-proBNP, and low ejection fraction (EF) showed that only prolonged SAPWD > or =149 ms was associated with an increased risk of meeting an early endpoint; the hazard ratio 3.94 with 95% confidence interval 1.50-10.42; p = 0.006.. Prolonged SAPWD appears to predict early death, AF development, or hospitalization due to deterioration of CHF in patients with stable CHF.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Natriuretic Factor; Biomarkers; Calcium Channel Blockers; Digoxin; Electrocardiography, Ambulatory; Endpoint Determination; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Morbidity; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Risk Factors; Statistics, Nonparametric; Stroke Volume; Treatment Outcome

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans

Topics: Anti-Arrhythmia Agents; Digoxin; Heart Failure; Humans; Quality of Life

Topics: Animals; Cardiomyopathy, Dilated; Cat Diseases; Cats; Diagnosis, Differential; Digoxin; Enalapril; Furosemide; Heart Failure; Male; Nitroglycerin; Oxygen Inhalation Therapy; Radiography; Ultrasonography

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Black or African American; Digoxin; Diuretics; Drug Therapy, Combination; Ethnicity; Female; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Patient Selection; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Spironolactone; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Cross-Sectional Studies; Digoxin; Diuretics; Drug Interactions; Echocardiography; Europe; Heart Failure; Humans; Incidence; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Ventricular Dysfunction, Left

The Digitalis Investigation Group (DIG) trial was a large simple trial (LST) begun in 1990 as a collaboration between the National Heart, Lung, and Blood Institute and the Department of Veterans Affairs (VA) Cooperative Studies Program (CSP). Its primary objective was to determine whether digitalis had beneficial, harmful, or no effect on total mortality in patients with congestive heart failure and an ejection fraction < or =0.45. The Perry Point VA CSP Coordinating Center served as the trial's data coordinating center (DCC). The DCC was involved in all phases of the study from planning and design, organization and start-up, and patient recruitment and follow-up through closeout, final analyses, and manuscript preparation. While DCC responsibilities for an LST are basically the same as for other multicenter randomized clinical trials, their size and the inclusion of many inexperienced research sites can add a complexity that the DCC must be prepared to handle from the beginning. This paper describes the role of the DCC in the DIG trial.

Topics: Canada; Cardiotonic Agents; Data Collection; Digoxin; Heart Failure; Humans; Multicenter Studies as Topic; Organization and Administration; Randomized Controlled Trials as Topic; United States

Congestive heart failure is a major public health problem in the United States, Canada, and other Western countries. The Digitalis Investigation Group (DIG) trial was a randomized, double-blind placebo-controlled trial that evaluated the effects of digoxin on all-cause mortality and on hospitalization for heart failure in patients with heart failure and left ventricular ejection fraction < or =0.45 with normal sinus rhythm. It was designed as a large simple trial. There were 6800 patients entered into the main study over a 31.5-month recruitment period at 302 participating centers in the United States and Canada. All patients were followed for a minimum of 28 months. In order for this study to succeed, many groups had to work together successfully. In this supplement, we present practical aspects of organizing and conducting a large simple trial such as DIG.

Topics: Canada; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Multicenter Studies as Topic; Organization and Administration; Randomized Controlled Trials as Topic; Research Design; United States

Large simple trials (LSTs) emerged in response to the need for large sample sizes to answer important clinical questions in which treatments have a moderate effect on clinical endpoints. Between 1991 and 1996 the National Heart, Lung, and Blood Institute and the Department of Veterans Affairs (VA) Cooperative Studies Program conducted an LST entitled "Digitalis Investigation Group (DIG): Trial to Evaluate the Effect of Digitalis on Mortality in Heart Failure." The VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center served as the DIG pharmacy coordinating center (PCC). As a direct result of involvement in the DIG trial, the PCC identified the need for an increased emphasis on computerization and automated support of clinical trials, especially LSTs.

Topics: Canada; Cardiotonic Agents; Digoxin; Drug Packaging; Heart Failure; Humans; Multicenter Studies as Topic; Pharmaceutical Services; Randomized Controlled Trials as Topic; United States

The Digitalis Investigation Group (DIG) trial was a large simple clinical trial that involved 302 participating centers in the United States and Canada. In order to encourage participation by Canadian investigators, to provide additional help to what were expected to be largely research-inexperienced investigators in Canada, and to provide the study's data coordinating center with resources in Canada to deal with potentially different rules, regulations, and cultural differences, regional coordinating centers were established in four regions of Canada: the maritime provinces, Quebec, Ontario, and western Canada. Canadian centers recruited significantly better than their U.S. counterparts and had slightly better retention and follow-up. While it is not possible to declare that the regional coordinating centers were responsible for this improvement, it is believed that these regional centers did play a role. This role included being able to identify investigators who could be expected to do well, providing one-on-one training and instruction to investigators, and being able to solve problems and implement change in the relatively fewer centers in their regions. The regional coordinating center also reduced the intensity of the workload on the data coordinating center by serving as the primary point of contact for Canadian investigators. The use of regional coordinating centers in studies with a large number of participating centers is highly recommended.

Topics: Canada; Cardiotonic Agents; Digoxin; Heart Failure; Interinstitutional Relations; Multicenter Studies as Topic; Organization and Administration; Program Evaluation; Randomized Controlled Trials as Topic; United States

Before any clinical trial can begin to recruit patients, participating clinical centers must obtain approval from their institutional review board (IRB). When studies are federally funded, such as by the U.S. Department of Health and Human Services (DHHS), centers must also have or obtain a federal compliance agreement from the Office of Human Research Protections (formerly the Office for Protection from Research Risks [OPRR]). The Digitalis Investigation Group trial was a large, international, double-blind, DHHS-funded randomized trial on the effect of digoxin on mortality in heart failure. Due to the anticipated number of centers (>200), the study's data coordinating center (DCC) was requested to assume additional responsibilities that included: (1) acting as a liaison between the OPRR and all study centers; (2) reviewing and correcting all assurance statements before submission to the OPRR; (3) reviewing and approving all centers' informed consent forms; and (4) helping the many research-inexperienced centers to establish IRBs or to locate an IRB in their region that would accept IRB responsibility for them. Although a heavy burden was placed on the DCC, the IRB and OPRR approval process was probably shortened by many weeks at those centers not already possessing a federal compliance agreement. This enabled the study to be completed on schedule and within budget.

Topics: Canada; Cardiotonic Agents; Digoxin; Ethics Committees, Research; Forms and Records Control; Heart Failure; Informed Consent; Multicenter Studies as Topic; Organization and Administration; Patient Advocacy; Peer Review, Research; Randomized Controlled Trials as Topic; Risk Management; United States

The Digitalis Investigation Group (DIG) trial was the first large simple trial conducted by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs. A large simple trial is a major undertaking. Simplification at the sites requires careful planning and discipline. Lessons learned from the DIG trial were: (1) keep a large simple trial very simple and keep all study procedures very simple; (2) ancillary studies are important and can complement a large simple trial but require careful advanced planning; (3) anticipate special needs when shipping study drugs internationally; (4) regional coordinating centers can be very useful; (5) recruit as many capable sites as possible; (6) provide research-inexperienced sites/investigators with extra help to obtain federalwide assurance statements from the Office for Human Research Protections and institutional review board approvals; (7) adequately reimburse sites for the work completed; (8) maintain investigator enthusiasm; (9) monitor the slow performers and sites with numerous personnel changes; (10) choose an endpoint that is easy to ascertain; (11) keep the trial simple for participants; and (12) plan early for closeout and for activities between the end of the trial and publication of results.

Topics: Canada; Cardiotonic Agents; Digoxin; Heart Failure; Multicenter Studies as Topic; Organization and Administration; Program Evaluation; Randomized Controlled Trials as Topic; United States

Topics: Cardiotonic Agents; Clinical Trials as Topic; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Hospitalization; Humans; Potassium; Survival Rate; Treatment Failure

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Female; Heart Failure; Humans; Male; Sex Factors; Survival Rate

The measurement and assessment of digoxin concentrations are often performed poorly. We have conducted an audit to assess the appropriateness of digoxin therapeutic drug monitoring in Christchurch Hospital.. One hundred consecutive requests for digoxin concentrations in Christchurch Hospital inpatients were assessed. The case notes and hospital medication records were reviewed to determine the indication for testing, the appropriateness of the sampling time and of the subsequent alteration to dosing.. In 53% of requests no clear indication for digoxin therapeutic drug monitoring (TDM) could be determined. In the remainder, 'suspected toxicity' accounted for 31% and 'therapeutic failure' for 16%. Samples were inappropriately taken within eight hours post-dose in 32% of requests. In 19% of cases, the samples did not reflect steady-state conditions. In 5% of occasions, the subsequent decision regarding dose adjustment was felt to be clearly inappropriate, and there was uncertainty regarding appropriateness in some other cases. Overall, in only 29% of requests was TDM performed appropriately with regard to indication, sampling and subsequent dose alteration.. At Christchurch Hospital, the practice of TDM for digoxin is often inappropriate. It would seem that medical staff education is required to improve this practice.

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Digoxin; Drug Monitoring; Heart Failure; Humans; Medical Audit; New Zealand; Practice Patterns, Physicians'

Nonlinear mixed effects modeling was used to estimate the effects of digoxin-calcium channel blockers (verapamil, diltiazem, nifedipine) in 336 serum levels gathered from 172 patients (104 male and 68 female) receiving oral digoxin as hospital in-patients. The final model describing digoxin clearance (CL) was CL (l/day)=(87.9+2.71C(cr))0.872(CCB)0.880(CHF)0.937(SPI)0.854(DFAC), where C(cr) is the estimated creatinine clearance (ml/min); CCB=1 for concomitant administration of calcium channel blockers and CCB=zero otherwise; CHF=1 for the patients with congestive heart failure and CHF=zero otherwise; SPI=1 for concomitant administration of spironolactone and SPI=zero otherwise; DFAC=1 for administration of a half-tablet of digoxin and DFAC=zero otherwise. Concomitant administration of calcium channel blockers resulted in a 13% decrease in digoxin relative clearance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Calcium Channel Blockers; Creatinine; Digoxin; Diltiazem; Drug Interactions; Female; Heart Failure; Humans; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Models, Statistical; Nifedipine; Pharmacoepidemiology; Regression Analysis; Reproducibility of Results; Spironolactone; Verapamil

To formulate a simple equation for determining the daily dose requirements of digoxin by inclusion of creatinine clearance (Ccr) values as an explanatory variable.. We included 235 routine monitoring and clinical laboratory test data (steady-state serum digoxin concentration and Ccr values), obtained from hospitalized patients receiving digoxin for treatment of congestive heart failure. The 107 data sets were fitted to a hyperbolic model to account for the relation between the ratio of serum digoxin level to the daily dose (L/D) and the Ccr values determined by six methods. Their correlation coefficients (r) were computed by non-linear regression analysis. To evaluate the validity of the best-fitting model, the predictive performance of the L/D ratios was compared with those given by seven reference models previously published, using another 128 data sets.. The hyperbolic model involving the Ccr values estimated by Cockcroft and Gault's equation showed the closest correlation (r = 0.81) between the actual and estimated Ccr values. Mean prediction error (ME), a measure of bias, of the L/D ratio (0.018 ng/mL) was almost negligible when other data were fitted to the proposed model, and this ME value proved to be much smaller than those calculated from the previously published prediction models. Mean absolute prediction error, a measure of precision, by the proposed model was also satisfactory for prediction.. The newly developed model provided good predictive performance of serum digoxin level. Taking simplicity in practical use into account, the clinical application of the proposed model will allow for accurate and rapid determination of the initial maintenance dosing regimen of digoxin based on the individual Ccr value, without actual measurement of its serum concentration.

Topics: Adult; Aged; Aged, 80 and over; Cardiotonic Agents; Creatinine; Digoxin; Drug Administration Schedule; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Models, Theoretical; Predictive Value of Tests; Regression Analysis

Topics: Cardiotonic Agents; Digoxin; Electrocardiography; Heart Failure; Humans; Tachycardia, Ectopic Junctional

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Humans

Potential risks of cyclohexanol (CH) and cyclohexanediol (CHD) isomers, which are the metabolites derived from cilexetil ester side-chain of several prodrugs such as antibiotics (e.g. cefotiam hexetil) and an antihypertensive agent (candesartan cilexetil), were examined in beagles that were made congestive heart failure (CHF) by rapid ventricular pacing. The following three experiments tested the cardiac effects of i.v. doses of: (1) the metabolites alone, (2) the metabolites under the digoxin-induced bradycardia, and (3) the metabolites given concomitantly with digoxin (0.02 mg kg(-1)). Experiment 1: t-1,2- or 1,4-CHD alone (0.1-12 mg kg(-1)) exerted transient yet reproducible supraventricular or ventricular arrhythmia dose-dependently, whereas CH and 1,3-CHD at 12 mg kg(-1) showed no cardiac effect at all. Experiment 2: t-1,2-CHD (0.1-4 mg kg(-1)), but not CH or 1,3-CHD, induced the additive arrhythmia dose-dependently; t-1,2-CHD (12 mg kg(-1)) caused frequent premature supraventricular contractions and/or irreversible paroxysmal supraventricular tachycardia. Experiment 3: t-1,2-CHD, not CH or 1,3-CHD, caused fatal arrhythmia: one dog showed torsade de pointes followed by ventricular fibrillation, while another showed 3rd degree atrioventricular block and eventually cardiac arrest. In both Experiments 2 and 3, saline vehicle added onto digoxin never caused the irreversible, fatal arrhythmia. In a separate study using healthy dogs without CHF, none of these metabolites did produce cardiac effect. Given the potential risk of generating cardiotoxic metabolites from cilexetil-bearing prodrugs, the use of such prodrugs should be avoided from the patients with CHF, particularly from those who are receiving cardiac glycosides.

Topics: Animals; Antihypertensive Agents; Arrhythmias, Cardiac; Benzimidazoles; Biphenyl Compounds; Cardiac Pacing, Artificial; Cardiotonic Agents; Digoxin; Dogs; Dose-Response Relationship, Drug; Heart Failure; Heart Ventricles; Prodrugs; Tetrazoles

Topics: Cardiotonic Agents; Digoxin; Female; Heart Failure; History, 18th Century; History, 20th Century; Humans; Male; Sex Factors

ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult are summarized in detail. According to statements of these Guidelines most patients with chronic heart failure as a rule should receive combination of representatives of 4 different drug classes - diuretic, angiotensin converting enzyme inhibitor, beta-adrenoblocker and usually digoxin. Special indications have been formulated for inclusion in complex therapy of aldosterone receptor blockers (first of all spironolactone), angiotensin1 receptor blockers and direct vasodilators (hydralazine, isosorbide dinitrate).

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiology; Chronic Disease; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Practice Guidelines as Topic; United States

Older adults are more likely to suffer from the adverse effects of digoxin. Studies have described the inappropriate use of digoxin in various populations. The objective of this study was to determine the correlates of inappropriate digoxin use in older heart failure patients.. We studied older hospitalized heart failure patients with documented left ventricular (LV) function evaluation and electrocardiography. Digoxin use was considered inappropriate if patients had preserved LV systolic function (ejection fraction greater > or =40%) or if they had no atrial fibrillation (AF). We compared baseline patient characteristics by indication for digoxin and tested statistical significance using Pearson's chi-square analysis and Student's t tests. Using logistic regression, we determined the correlates of inappropriate use and initiation of digoxin.. Subjects (N = 603) had a mean age of 79 (+/-7) years; 59% were women, and 18% were African American. A total of 376 patients (62%) were discharged on digoxin, and 223 (37%) had no indication for its use. Half of the patients without an indication for digoxin received the drug. Of 132 patients without an indication and not already on digoxin, 38 (29%) were initiated on it. After adjustment for various patient and care characteristics, prior digoxin use (adjusted odds ratio [OR] 11.47, 95% confidence interval [CI] 5.72-23.02) and pulse > or =100/min (adjusted OR 2.33, 95% CI 1.10-4.94) were associated with inappropriate digoxin use. Pulse > or =100/min was also associated with inappropriate initiation of the drug (adjusted OR 2.95, 95% CI 1.28-6.78).. Inappropriate use of digoxin was common and was associated with prior use. Tachycardia was associated with inappropriate use and initiation. Electrocardiography and echocardiography should be performed in all older heart failure patients. Digoxin therapy should not be initiated or continued in patients without any evidence of LV systolic dysfunction or chronic AF.

Topics: Aged; Cardiotonic Agents; Digoxin; Drug Utilization; Female; Heart Failure; Hospitalization; Humans; Male

Topics: Cardiotonic Agents; Diastole; Digoxin; Heart Failure; Hospitalization; Humans; Patient Selection; Practice Guidelines as Topic; Research Design; Stroke Volume; Survival Analysis; Treatment Outcome

Topics: Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Stroke Volume; Treatment Outcome

A reduced cardiac output in chronic heart failure (CHF) evokes renal NaCl and water retention, and, therefore, activates mechanisms promoting natriuresis. Atrial natriuretic peptide (ANP) is one such factor. We hypothesized that another NaCl sensitive endogenous natriuretic factor, i.e., marinobufagenin (MBG), a specific ligand of the alpha-1 subunit of Na/K ATPase (the main kidney isoform) and also a vasoconstrictor and cardiotonic substance, would be elevated in CHF patients in a graded manner with the severity of CHF.. We measured the plasma levels of MBG, alpha-hANP, ouabain-like compound (OLC) and left ventricular (LV) volumes and ejection fraction in 23 consecutive hypertensive male patients with CHF. Plasma MBG levels exhibited progressive increases (0.59 +/- 0.15, 1.08 +/- 0.20, 1.35 +/- 0.17 and 1.88 +/- 0.05 nmol/l NYHA 1-4, respectively) and paralleled the changes of alpha-hANP. Conversely, plasma OLC did not exhibit such increases. Plasma MBG correlated with alpha-hANP (r = 0.82; P < 0.0001). Both MBG and alpha-hANP correlated with LV systolic (r = 0.55 and r = 0.47; P < 0.01) diameter and inversely with ejection fraction (r = -0.73 and r = -0.60; P < 0.01). OLC did not exhibit correlations with alpha-hANP or LV volumes, but positively correlated with systolic brachial blood pressure and with pulse pressure.. In CHF, MBG exhibits progressive increases similar to ANP, varies with CHF severity and correlates with LV systolic function. We hypothesize, that, in CHF, the concurrent production of these two natriuretic hormones, a vasorelaxant, ANP, and a vasoconstrictor, MBG, potentiate each other's natriuretic effects, but may offset their vasoactive actions.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Volume; Brachial Artery; Bufanolides; Cardenolides; Digoxin; Enzyme Inhibitors; Heart Failure; Humans; Isoenzymes; Ligands; Male; Middle Aged; Saponins; Severity of Illness Index; Sodium-Potassium-Exchanging ATPase; Stroke Volume; Systole; Vasoconstrictor Agents; Ventricular Function, Left

The efficacy and safety of amiodarone in the management of atrial fibrillation (AF) or flutter in 108 Japanese patients with heart failure was retrospectively examined. Thirty-four (41%) of the 82 patients who were in sinus rhythm after 1 month of amiodarone administration had their first recurrence, 70% of cases occurring within 1 year of initiation. The cumulative rates of maintenance of sinus rhythm were 0.68, 0.55, and 0.47 at 1, 3, and 5 years, respectively. Amiodarone was more effective in maintaining sinus rhythm in patients with paroxysmal AF or flutter than in those with the persistent form (p<0.05). The cumulative rates for cases that remained in permanent AF were 0.04, 0.11, and 0.14 at 1, 3, and 5 years, respectively. Apart from suppressing AF, the mean heart rate during Holter monitoring was significantly decreased with amiodarone therapy in cases of permanent AF. Adverse effects requiring the discontinuation of amiodarone therapy occurred in 16% of patients. Low-dose amiodarone therapy may prevent AF or flutter in Japanese patients with heart failure.

Topics: Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Cause of Death; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Survival Analysis; Tachycardia, Ventricular; Time Factors; Treatment Outcome

Chronic heart failure (CHF) in children occurs mostly as a result of systolic dysfunction of the systemic ventricle or of congenital defects leading to large left-to-right shunts and pulmonary overcirculation. The ensuing symptoms and signs are similar in both cases, and include respiratory distress, poor feeding and growth, and hepatic congestion. Grading the severity of the symptoms accurately and reproducibly is important for studying CHF and the response to therapy. The Ross classification for young children and the New York Heart Association classification for older children are frequently utilized for such grading. The standard therapy for CHF in children consists of diuretics, to reduce cardiac preload and improve symptoms, and the maximization of nutritional support. The role of digoxin in treating CHF in children is controversial, especially regarding those children with pulmonary overcirculation where the function of the systemic ventricle is usually well preserved. As the importance of neurohormonal changes in the pathogenesis of worsening CHF is elucidated, newer medications aimed at counteracting such changes are becoming more important in the medical therapy of CHF in children. ACE inhibitors improve function and survival in adults with CHF, and they probably do the same in children with systemic ventricular dysfunction. It is less clear how effective they are in pulmonary overcirculation, but patients with high flow and low pulmonary resistance are most likely to benefit. In infants receiving treatment with ACE inhibitors, it is necessary to monitor for renal insufficiency or renal failure. beta-Adrenoceptor blockade has also been established as an effective therapy for adults with CHF with beneficial effects on survival and left ventricular function. While data for the pediatric population are limited, early studies suggest that beta-adrenoceptor antagonists (beta-blockers) may work well in infants and children with CHF. Caution must be used by starting treatment with very low dosages of beta-blockers and gradually increasing to the desired goals with close monitoring of blood pressure and heart rate. It is clear that larger multicenter trials are crucial to our ability to provide the most appropriate treatment for children with CHF. The demand for effective medical treatment will increase as more patients with palliated single ventricles survive surgery and then develop CHF from dysfunction of a hypertrophic and dilated single ventricle.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Child; Clinical Trials as Topic; Digoxin; Diuretics; Heart Failure; Humans; Infant; Neurotransmitter Agents; Nutrition Therapy

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Cisapride; Digoxin; Drug Interactions; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Heart Failure; Humans

Congestive heart failure was diagnosed in a 27-year-old Indian ringneck parakeet with exercise-induced dyspnea. A grade IV/VI holosystolic murmur that radiated to the right sternal area was auscultated over the left side of the sternum. Radiography revealed progressive cardiomegaly, hepatomegaly, pulmonary edema, and accumulation of fluid within the coelomic cavity. Echocardiography revealed biatrial enlargement and enlargement of the right ventricle. Doppler recording revealed high velocity left and right atrioventricular valve regurgitation. Treatment with digoxin and furosemide alleviated clinical signs for approximately 10 months. Gross postmortem examination revealed cardiac enlargement and eccentric hypertrophy of both ventricles on cross-section. Pulmonary congestion and edema, hepatomegaly, hepatic congestion, and ascites were also evident. Histologic examination of the heart revealed myxomatous degeneration of the left atrioventricular valve, muscular hypertrophy of the right atrioventricular valve, and biventricular chronic myofiber degeneration and necrosis.

Topics: Animals; Bird Diseases; Digoxin; Diuretics; Echocardiography, Doppler, Color; Electrocardiography; Fatal Outcome; Furosemide; Heart Auscultation; Heart Failure; Heart Valve Diseases; Parakeets; Radiography, Thoracic; Ventricular Dysfunction

Much evidence has been accumulated that human plasma contains digitalis-like factor(s) with Na/K ATPase inhibitor properties. Increased concentrations of ouabain-like factor (OLF) have been reported in patients with moderate to severe hypertension and in patients with overt congestive heart failure due to dilated cardiomyopathy.. The presence of circulating OLF has not been investigated in borderline to mild hypertension or in the early stage of dilated cardiomyopathy.. The study population consisted of 18 normal volunteers, 24 patients with borderline to mild hypertension, 47 patients with asymptomatic left ventricular dysfunction (ALVD) due to dilated cardiomyopathy and 26 patients with cardiac arrhythmias but normal left ventricular function. OLF values (pM ouabain equivalent) were assayed in extracted plasma, using a radioimmunoassay for ouabain. OLF was, respectively, 29.4+/-20.6 pM in normal controls, 39.1+/-23.8 pM in hypertensives, 35+/-18 pM in patients with cardiac arrhythmias, 52.3+/-25.8 pM in ALVD patients not treated with digoxin and 64.6+/-29.6 pM in ALVD patients treated with digoxin. Patients with ALVD, both treated and not treated with digoxin, had OLF significantly higher (P<0.05) than all the other groups. In patients with ALVD no correlation between OLF and left ventricular ejection fraction was observed. In the hypertensive group no correlation between OLF and both diastolic and systolic pressure was found.. Increased concentrations of OLF were observed in patients with left ventricular dysfunction due to dilated cardiomyopathy, before the occurrence of overt heart failure, suggesting that OLF may be an early marker of the disease.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardenolides; Cardiomyopathy, Dilated; Digoxin; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Prognosis; Reference Values; Saponins; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cytokines; Digoxin; Disease Models, Animal; Diuretics; Endothelins; Etanercept; Heart Failure; Humans; Immunoglobulin G; Immunosuppressive Agents; Mice; Mice, Transgenic; Neprilysin; Randomized Controlled Trials as Topic; Receptors, Tumor Necrosis Factor; Spironolactone; Tumor Necrosis Factor-alpha

As outpatients with long-term chronic illness often show a high incidence of medication noncompliance, we investigated the influence of digoxin noncompliance on hospitalization, left ventricular ejection fraction, and mortality in outpatients in long-term therapy having congestive heart failure with tachycardia at a rate over 100 beats/min before starting digoxin therapy, but abnormal sinus rhythm.. Before starting this study, the digoxin compliance/noncompliance of patients was determined by measuring the serum digoxin concentration (SDC). SDC was determined once a month, followed for six consecutive months, and patients were defined as noncompliant if their SDC was zero (0.0 ng/ml) on at least three consecutive occasions. According to SDC data, 218 patients were assigned to the compliant group and 213 patients were assigned to the noncompliant group. All 431 patients received diuretics, angiotensin converting-enzyme inhibitors, or nitrates as well as conventional therapy with digoxin throughout the trial. The duration of follow-up was 72 months.. After 72 months of follow-up, the digoxin noncompliant patients showed significant increases in the number and duration of hospitalizations compared with the compliant patients. The digoxin noncompliant patients had a marked decrease in the left ventricular ejection fraction from 49.1% to 41.8%. The cumulative rate of mortality from any cause in noncompliant patients was twofold higher (15.0%) than in compliant patients (7.8%; risk ratio when noncompliant was compared with compliant: 1.95; 95% confidence interval 1.11, 3.45; P = 0.029) at the 72-month follow-up. The higher mortality in digoxin noncompliant patients was exclusively attributed to worsening heart failure rather than other cardiac and noncardiac causes (risk ratio 2.13; 95% confidence interval 1.12, 4.07; P = 0.033). In addition, multiple regression analyses demonstrated that patient noncompliance as well as lower left ventricular ejection fraction at baseline were significantly involved in increased mortality.. These results indicate that digoxin noncompliance, at least in part, increases the rate of both hospitalization and mortality due to worsening heart failure in outpatients who have congestive heart failure with tachycardia in long-term therapy.

Topics: Aged; Analysis of Variance; Cardiotonic Agents; Confidence Intervals; Digoxin; Female; Heart Failure; Hospitalization; Humans; Linear Models; Male; Middle Aged; Odds Ratio; Prospective Studies; Regression Analysis; Tachycardia, Supraventricular; Treatment Refusal; Ventricular Dysfunction, Left

Body wasting is a clinical feature of a variety of chronic illnesses including congestive heart failure. The wasting associated with chronic congestive heart failure (cardiac cachexia) has recently been shown to portend a worse prognosis, and it is an independent predictor of mortality. The mechanisms underlying cardiac cachexia are multi-factorial, including metabolic, nutritional, neuroendocrine and immunological aberrations. There is, however, no direct evidence that current medical treatment reverses cachexia in chronic heart failure.. The effect of enalapril, digoxin and frusemide combination on clinical, biochemical and anthropometric indices were determined in eight cachectic Nigerians with chronic congestive heart failure [body mass index (BMI) 20.80+/-2.7 kg/m(2), left ventricular ejection fraction 29+/-4% and LV mass index 161+37 g/m(2)] at baseline, and again after 3 and 6 months of therapy. Ten age- and sex-matched healthy volunteers whose anthropometric data were concurrently measured served as controls.. The anthropometric and clinical measurements were significantly (P<0.001) reduced in heart failure compared to the healthy controls. Congestive hepatomegaly significantly regressed from 161+/-20 mm to 123+/-13 mm after 6 months therapy (P<0.001 ANOVA). There was a significant increase in the sum of four skin fold thickness from 27.6+/-3.3 mm to 30.1+/-3.9 mm at 6 months (P<0.001 ANOVA) 95% confidence intervals for the difference being 1.42 to 3.4 mm. There was a significant increase in the mid-upper arm circumference (P<0.001 ANOVA) with a 95% confidence interval of 0.87-2.1 cm, and a similar trend for increased mid-thigh circumference (95% confidence limits 0.93-5.30 cm) was apparent. Plasma albumin and sodium increased significantly (P<0.05) from 30.1+/-3.8 g/l and 136+/-5.9 mmol/l to 32.9+/-2.5 g/l and 139+/-3.9 mmol/l, respectively. There was a positive and significant correlation between the treatment induced increases in plasma albumin and the increase in mid-upper arm circumference (y=0.25x+0.8, r=0.76, P=0.03 ANOVA) but not with the change in skin fold thickness.. The preliminary results demonstrate increased subcutaneous fat (increased skin fold thickness), greater muscle bulk (increased mid-upper arm and thigh circumferences) together with a significant elevation in plasma albumin and the hematocrit, which reflect the anabolic state in patients treated with ACE inhibitor-digoxin-diuretic with congestive heart failure.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anthropometry; Body Mass Index; Cachexia; Cardiotonic Agents; Chronic Disease; Confidence Intervals; Digoxin; Diuretics; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Humans; Linear Models; Male; Middle Aged; Nutrition Assessment; Serum Albumin; Skinfold Thickness; Sodium; Treatment Outcome

The choice of administering digitalis to older patients with congestive heart failure (CHF) cannot be made on the account of univocally defined criteria because of uncertainty about efficacy and concern about safety of digitalis in this population. The purpose of this study was to verify whether the clinical characteristics on admission to the acute care hospital determine the use of digitalis therapy in elderly patients.. A total of 1239 patients (mean age 77.8 +/- 7.1 years, range 65-100 years, males 49.8%) consecutively admitted to 69 General Medicine and Geriatrics wards over a 4-month period were grouped by combining two dichotomous factors (Carlson's score > 4: definite or possible diagnosis of CHF; Carlson's score < 5: unlikely diagnosis of CHF; in-hospital adoption of digitalis therapy: yes or no) as follows: Group A: Carlson's score > 4, digitalis (n = 413); Group B: Carlson's score > 4, no digitalis (n = 260); Group C: Carlson's score < 5, digitalis (n = 104); Group D: Carlson's score < 5, no digitalis (n = 462). Variables significantly distinguishing groups were entered into a discriminant analysis aimed at assessing the group specificity of individual clinical profiles.. Use of digoxin at home, atrial fibrillation, older age, and comorbidity (mainly COPD and chronic renal failure) characterized most of the patients given digoxin with or without a definite diagnosis of CHF. Clinical profiles of groups A, B, and C largely overlapped.. Age, historical use of digitalis, and comorbidity might lead to seemingly incongruous digitalis prescription. The choice of adopting digitalis therapy cannot be reliably predicted on the basis of clinical variables only. Presently unexplored physician-related factors, such as cultural background, likely outweigh clinical variables in prompting digitalis prescription.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Discriminant Analysis; Female; Heart Failure; Hospitals; Humans; Lung Diseases, Obstructive; Male; Medical Records

Topics: Cardiotonic Agents; Diastole; Digoxin; Heart Failure; Humans; Systole

The effects of captopril on serum digoxin concentrations were studied in 8 patients with severe (NYHA Class IV) congestive heart failure. Serum digoxin concentrations were determined before and after the administration of captopril for 1 week in patients on chronic digoxin therapy. Each patient who was taking 0.25 mg of digoxin PO q.d., was administered 12.5 mg of captopril PO t.i.d. for 7 days. The peak serum concentration of digoxin (Cmax) before and after (on Days 0 and 7) captopril administration was 1.7+/-0.2 ng/ml and 2.7+/-0.2 ng/ml, the time to peak (tmax) was 2.4+/-0.5 h and 1.3+/-0.2 h, and the area under the 24-hour digoxin concentration-time curve (AUC0-24h) was 30.0+/-1.5 ng x h/ml and 41.7+/-3.4 ng x h/ml, respectively. While captopril caused a significant increase in peak serum concentration and the area under the digoxin concentration-time curve, it decreased the time to digoxin peak (p = 0.01, p = 0.04, p = 0.01, respectively). No patient developed evidence of digoxin toxicity. Concomitant administration of captopril with digoxin increases serum digoxin concentration in patients with severe congestive heart failure.

Topics: Administration, Oral; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiotonic Agents; Digoxin; Drug Administration Schedule; Drug Interactions; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Cardiac Glycosides; Cardiotonic Agents; Controlled Clinical Trials as Topic; Digitalis Glycosides; Digitoxin; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Practice Guidelines as Topic

Several large clinical trials conducted over the past decade have shown that pharmacologic interventions can dramatically reduce the morbidity and mortality associated with heart failure. These trials have modified and enhanced the therapeutic paradigm for heart failure and extended treatment goals beyond limiting congestive symptoms of volume overload. Part II of this two-part article presents treatment recommendations for patients with left ventricular systolic dysfunction. The authors recommend that, if tolerated and not contraindicated, the following agents be used in patients with left ventricular systolic dysfunction: an angiotensin-converting enzyme inhibitor in all patients; a beta blocker in all patients except those who have symptoms at rest; and spironolactone in patients who have symptoms at rest or who have had such symptoms within the past six months. Diuretics and digoxin should be reserved, as needed, for symptomatic management of heart failure. Other treatments or treatment programs may be necessary in individual patients.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiotonic Agents; Diet; Digoxin; Diuretics; Exercise; Heart Failure; Humans; Patient Education as Topic; Referral and Consultation; Systole; Ventricular Dysfunction, Left

We surveyed Accident and Emergency (A&E) consultants in England by questionnaire, on their management of patients presenting with AF. Completed questionnaires were received from 124 (45%). Most (42%) would use digoxin as first-line treatment for rate control of AF; 28% would not treat AF acutely but would refer the patient to the medical team; 59% would cardiovert a patient with AF in A&E, if there was evidence of cardiovascular compromise. Some 51% would not routinely initiate any anticoagulation therapy. Faced with a patient in fast AF who was haemodynamically unstable, 67% would immediately opt for electrical cardioversion, 13% would refer the patient directly to the medics and 15% would initially treat with intravenous digoxin. Given a patient in fast AF and cardiac failure, 55% would treat with digoxin. Asked about AF related to Wolff-Parkinson-White syndrome, 37% would initially give adenosine, 23% would opt for immediate DC cardioversion and 25% would refer directly to the medics; however, a minority would still give a rate-limiting calcium antagonist or digoxin. The majority (79%) would not treat AF in a known alcoholic with acute intoxication who was haemodynamically stable. Consultants were more likely to initiate treatment if the patient had signs of shock or heart failure. Where there were underlying medical problems they were more likely to refer the patient directly to the medical team. There was a general reluctance to initiate anticoagulation, and some difference in opinion over how long AF should have persisted for anticoagulation to be necessary in the context of electrical cardioversion. Given the current evolution of A&E as an acute speciality, A&E clinicians should at least initiate management of patients with AF and be prepared to care for them for some time in A&E.

Topics: Alcoholism; Anticoagulants; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Electric Countershock; Emergency Service, Hospital; England; Health Care Surveys; Heart Failure; Humans; Practice Patterns, Physicians'; Referral and Consultation; Surveys and Questionnaires; Thyroid Diseases; Wolff-Parkinson-White Syndrome

To clarify the observed variability of digoxin disposition by performing a population pharmacokinetic analysis in a Japanese population.. Retrospective analysis of clinical pharmacokinetic data.. Data were obtained from 106 patients with heart failure and atrial fibrillation (43 males and 63 females).. Digoxin concentrations in serum were measured by fluorescence polarisation immunoassay. Population pharmacokinetic analysis was performed using a 2-compartment open pharmacokinetic model with the computer program NONMEM.. 246 serum concentrations were obtained. Final pharmacokinetic parameters were: CL (L/h) = (0.036 x TBW + 0.112 x CL(CR)) x 0.77SPI x 0.784CCB, V1 = 1.83 L/kg, V2 = 22.6 L/kg and Q = 0.629 L/h/kg, where CL is total body clearance, V1 and V2 are the apparent volumes of distribution in the central and peripheral compartments, Q is intercompartmental clearance, TBW is total bodyweight (in kg), CL(CR) is creatinine clearance (in ml/min), SPI = 1 for concomitant administration of spironolactone (and zero otherwise) and CCB = 1 for concomitant administration of calcium antagonists (and zero otherwise). Concomitant administration of digoxin and spironolactone resulted in a 23% decrease in digoxin clearance. Concomitant administration of digoxin and calcium antagonists (diltiazem, nicardipine, nifedipine or verapamil) resulted in a 21.6% decrease in digoxin clearance.. The estimated population parameter values may assist clinicians in the individualisation of digoxin dosage regimens.

Topics: Cardiotonic Agents; Computers; Digoxin; Female; Heart Failure; Humans; Japan; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Retrospective Studies; Tissue Distribution

Cardiac autonomic dysfunction is common in heart disease with or without congestive heart failure, and can cause sudden cardiac death. However, cardiac autonomic abnormalities in non-ischemic (hypertensive) heart failure, which is prevalent in Black Africans is poorly documented. We conducted a cross-sectional study of 32 patients with congestive heart failure, mostly secondary to hypertension (aged 52 +/- 15 years, with ejection fraction of 0.38 +/- 11) and 30 age- and sex-matched healthy volunteers (aged 51 +/- 11 years, 14 males/16 females). Cardiac autonomic function was assessed by the Valsalva's maneuver, respiratory sinus arrhythmia (for cardiac vagal tone) and the pressor and chronotropic changes following forearm isometric handgrip exercise and the assumption of upright posture (tests of sympathetic function). The exercise tolerance of the cardiac patients was assessed by the distance covered during 6 min of walking. The Valsalva ratio was significantly lower in chronic heart failure, 1.10 +/- 0.08 compared to the healthy controls 1.47 +/- 0.20 (p<0.001). Specifically, the phase IV bradycardia in heart failure, was significantly attenuated to 650 +/- 121 msec compared to the value of 935 +/- 101 msec in healthy controls (p<0.001). The phase 11 Valsalva tachycardia did not differ between the patients and controls. The respiratory sinus arrhythmia was also significantly reduced in chronic heart failure (p<0.05) compared to controls. Treatment of the heart failure patients with enalapril-digoxin and diuretics by 4 weeks, resulted in a reversal of the autonomic abnormalities. The phase IV bradycardia increased significantly to 798 +/- 164 msec (p<0.01) and the Valsalva ratio to 1.35 +/- 0.25 (p<0.01) and the respiratory sinus arrhythmia increased toward normal. There was close positive correlation between the Valsalva's ratio and the 6 min self paced distance covered (r = 0.44, p = 0.03 ANOVA), and a weak inverse correlation to cardiac size and cardiothoracic ratio (r = -0.31, p = 0.09). This study demonstrates cardiac autonomic dysfunction (especially reduced vagal tone) in Black Nigerians with mainly non-ischemic congestive heart failure. The parasympathetic dysfunction significantly correlates with severity of heart failure. Current treatment reverses autonomic dysfunction to values seen in healthy age matched controls, mainly through augmentation of cardiac parasympathetic activity.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Nervous System; Black People; Blood Pressure; Central Nervous System; Cross-Sectional Studies; Digoxin; Diuretics; Electrocardiography; Enalapril; Exercise Test; Female; Furosemide; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Nigeria; Prospective Studies; Sympathetic Nervous System; Vagus Nerve

OBJECTIVE - To describe clinical observations of marked improvement in ventricular dysfunction in a medical office environment under circumstances differing from those in study protocols and multicenter studies performed in hospital or with outpatient cohorts. METHODS - Eleven cardiac failure patients with marked ventricular dysfunction receiving treatment at a doctors office between 1994 and 1999 were studied. Their ages ranged from 20 and 66 years (mean 39.42+/-14.05 years); 7 patients were men, 4 were women. Cardiopathic etiologies were arterial hypertension in 5 patients, peripartum cardiomyopathy in 2, nondefined myocarditis in 2, and alcoholic cardiomyopathy in 4. Initial echocardiograms revealed left ventricular dilatation (average diastolic diameter, 69.45+/-8.15mm), reduced left ventricular ejection fraction (0.38+/-0.08) and left atrial dilatation (43.36+/-5.16mm). The therapeutic approach followed consisted of patient orientation, elimination of etiological or causal factors of cardiac failure, and prescription of digitalis, diuretics, and angiotensinconverting enzyme inhibitors. RESULTS - Following treatment, left ventricular ejection fraction changed to 0.63+/-0.09; left ventricular diameters changed to 57.18+/-8.13mm, and left atrium diameters changed to 37.27+/-8.05mm. Maximum improvement was noted after 16.9+/-8.63 (6 to 36) months. CONCLUSION - Patients with serious cardiac failure and ventricular dysfunction caused by hypertension, alcoholism, or myocarditis can experience marked improvement in ventricular dysfunction after undergoing appropriate therapy within the venue of the doctor's office.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Captopril; Digoxin; Diuretics; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Treatment Outcome; Ventricular Dysfunction, Left

Neurohumoral factors play important role in the pathogenesis of congestive heart failure (CHF) and digoxin (dig) is one of the most frequently used drugs in this condition. The aim of this study was to assess the effects of dig on atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their "second messenger" cyclic 3',5'-guanosine monophosphate (cGMP).. The study group consisted of 25 patients (pts) aged 25-81 with CHF (NYHA II/III), 13 women and 12 men. Control group consisted of 10 healthy volunteers, 2 women and 8 men. The blood samples for evaluation of ANP, BNP and cGMP plasma level was taken at baseline conditions and 3 hours (h) after intravenous injection of 0.25 mg of dig. From the next day 0.25 mg dig was administrated orally for 6 days and plasma levels of ANP, BNP and cGMP were assessed on the 3rd and 6th day of treatment. Medium serum dig concentration on the 6th day was 0.98 ng/mL.. The baseline ANP, BNP and cGMP plasma level was significantly higher in pts with CHD than in control group (ANP 144.4 vs 98.8 pg/ml p < 0.001; BNP 130.0 vs 97.2 pg/ml p < 0.001; cGMP 1.44 vs 0.86 pg/ml p < 0.001). In pts with CHF there was a significant increase ANP, BNP and cGMP plasma level 3 h after dig intravenous injection (ANP 205.2 vs 144.4 pg/ml p < 0.01; BNP 227.1 vs 130.0 pg/ml p < 0.01; cGMP 1.84 vs 1.44 pg/ml p < 0.01). The ANP and BNP plasma level after 3 days of oral dig was still significantly increased (ANP 171.1 vs 144.4 pg/ml p < 0.05; BNP 223.7 vs 130.0 pg/ml p < 0.01). ANP, BNP and cGMP plasma level was higher in pts with CHF also after 6 days of oral dig, but the difference was statistically significant. After 6 days of digoxin treatment there was a significant increase of ejection fraction (p < 0.005), with reduction of end-diastolic diameter of left ventricle (p < 0.05) and diameter of left atrium (p < 0.01). ANP at baseline correlated positively with baseline cGMP (r = 0.702 p < 0.05). On the 6th day BNP correlated positively with cGMP (r = 0.628 p < 0.05). 3 h after dig intravenous injection ANP correlated positively with BNP (r = 0.881 p < 0.05), but on the 3rd day of oral dig ANP correlated negatively with BNP (r = -0.536 p < 0.05). On the 6th day of oral dig end-diastolic diameter of left ventricle correlated negatively with BNP (r = -0.483 p < 0.05) and cGMP (r = -0.824 p < 0.05).. 1. In pts with CHF a single intravenous digoxin injection increases ANP, BNP and cGMP plasma level. 2. Oral digoxin administration supports this beneficial neurohumoral effect and improves hemodynamic parameters of left ventricle as well as reduces left atrium diameter.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Cardiotonic Agents; Case-Control Studies; Cyclic GMP; Digoxin; Female; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Time Factors; Treatment Outcome

Peripartum cardiomyopathy is rare in developped countries, but still frequent in Africa. It is defined as a heart failure occurring during peripartum, without any underlying etiology. Authors present 3 cases showing that heart failure before or after delivery may be due to causes which are frequent in the Sahelian area but generally misdiagnosed. Anemia, hypertension and rheumatic fever were the causes of heart failure in these 3 patients, but they were not apparent when the initial diagnosis was made. These observations emphasize that, despite the complex hypothesis trying to explain heart failure during the peripartum period, one should think about some frequent causes which can be misdiagnosed because of the pregnant state or the heart failure itself.

Topics: Adult; Africa, Northern; Anemia; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiotonic Agents; Causality; Developing Countries; Digoxin; Diuretics; Echocardiography; Female; Furosemide; Heart Failure; Humans; Hypertension; Incidence; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Rheumatic Fever; Sudan

Topics: Cardiotonic Agents; Chronic Disease; Digoxin; Heart Failure; Humans

Increasing prevalence, use of health services, and number of deaths have made congestive heart failure (CHF) a new epidemic in the United States. Yet there are no adequate data to guide treatment of the more typical and complex cases of patients who are very old and frail.. Using the SAGE database, we studied the cases of 86,094 patients with CHF admitted to any of the 1492 long-term care facilities of 5 states from 1992 through 1996. We described their clinical and functional characteristics and their pharmacologic treatment to verify agreement with widely approved guidelines. We evaluated age- and sex-related differences, and we determined predictors of receiving an angiotensin-converting enzyme (ACE) inhibitor by developing a multiple logistic regression model.. The mean age of the population was 84.9 +/- 8 years. Eighty percent of the patients 85 years of age or older were women. More than two thirds of patients underwent frequent hospitalizations related to CHF in the year preceding admission to a long-term care facility. Coronary heart disease and hypertension were the most common causes. Half of the patients received digoxin and 45% a diuretic, regardless of background cardiovascular comorbidities. Only 25% of patients had a prescription for ACE inhibitors. The presence of cardiovascular comorbidity, already being a recipient of a large number of medications, a previous hospitalization for CHF, and admission to the facility in recent years were associated with an increased likelihood of receiving an ACE inhibitor. The presence of severe physical limitation was inversely related to use of ACE inhibitors, as were a series of organizational factors related to the facilities.. Patients in long-term care who have CHF little resemble to those enrolled in randomized trials. This circumstance may explain, at least in part, the divergence from pharmacologic management consensus guidelines. Yet the prescription of ACE inhibitors varies significantly across facilities and depends on organizational characteristics.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Cross-Sectional Studies; Digoxin; Diuretics; Drug Therapy, Combination; Female; Health Services for the Aged; Health Status; Heart Failure; Humans; Long-Term Care; Male; Practice Guidelines as Topic; Retrospective Studies

Heart failure is increasing in both incidence and prevalence and is associated with a high mortality. In patients with heart failure, coronary artery disease is the cause for about two thirds. Pathophysiologic changes have been linked to altered muscle function and hemodynamics, elevated neurohormones, and, more recently, cellular mechanisms, including apoptosis. Standard triple therapy for symptomatic heart failure consists of an angiotensin-converting enzyme (ACE) inhibitor, digoxin, and a diuretic. In patients with severe heart failure, spironolactone should be added. In large clinical trials, ACE inhibitors, spironolactone, and beta-blockers have reduced mortality. Other drugs may be helpful in the treatment of heart failure. Amiodarone is the antiarrhythmic drug of choice in patients with symptomatic arrhythmias and also has a role in the treatment of dilated cardiomyopathy. Angiotensin II receptor blockers are being compared with ACE inhibitors and appear promising. Newer agents being tested include antagonists to endothelin and tumor necrosis factor. Overall, it is clear that polypharmacy is the standard of care for patients with heart failure. A future challenge will be to prevent heart failure from occurring.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Hemodynamics; Humans; Neurotransmitter Agents