digoxin and Atrial-Fibrillation

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

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

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Humans

Once a routine part of atrial fibrillation (AF) management, digoxin use has declined. Likely hastening this decline are findings from several studies and systematic reviews identifying a potential association between digoxin use and all-cause mortality in AF populations. However, inconsistency exists within some of these studies potentially leading to confusion among clinicians. To critically evaluate the current literature to contextualize the associations between digoxin and mortality risk in patients with AF by performing an overview of systematic reviews. We searched MEDLINE, Cochrane Central Database of Systematic Reviews, and SCOPUS from their earliest date through October 12, 2020, to identify systematic reviews (SRs) that included studies enrolling patients with AF or atrial flutter and evaluated the association between digoxin use and all-cause mortality. We used the AMSTAR 2 tool to assess the risk of bias for each included SR. Results from reviews are qualitatively synthesized. Our search identified 10 SRs that met our inclusion criteria. Of the 41 unique AF studies included in these SRs, 41% were cohort studies, 29% were post hoc analyses of randomized controlled trials (RCTs), 15% were RCTs, and 15% were registry studies. Based on our AMSTAR 2 assessment, the overall confidence in the results of the 10 reviews was rated as "moderate" in three SRs, "low" in three SRs, and "critically low" in the rest. Except for one review, each included SR shows that digoxin use in AF is associated with a 15 to 38% higher risk of all-cause mortality. This association may be greater when AF-only populations are considered compared with a mix of AF and heart failure populations. Serum digoxin concentration (SDC) data were infrequently considered, but available data suggested a greater association between increasing SDC and all-cause mortality. This overview of reviews found general consistency regarding the association between digoxin use and higher all-cause mortality in AF populations. However, heterogeneity exists among and between SRs and an unmet need exists for additional study in a RCT setting with close monitoring and reporting of SDC to better inform clinical practice.

Topics: Atrial Fibrillation; Digoxin; Humans; Randomized Controlled Trials as Topic; Systematic Reviews as Topic

Atrial fibrillation (AF) is one of the main cardiac arrhythmias associated with higher risk of cardiovascular morbidity and mortality. AF can cause adverse symptoms and reduced quality of life. One of the strategies for the management of AF is rate control, which can modulate ventricle rate, alleviate adverse associated symptoms and improve the quality of life. As primary management of AF through rate control or rhythm is a topic under debate, the purpose of this review is to explore the rationale for the rate control approach in managing AF by considering the guidelines, recommendations and determinants for the choice of rate control drugs, including beta blockers, digoxin and non- dihydropyridine calcium channel blockers for patients with AF and other comorbidities and atrioventricular nodal ablation and pacing. Despite the limitations of rate control treatment, which may not be effective in preventing disease progression or in reducing symptoms in highly symptomatic patients, it is widely used for almost all patients with atrial fibrillation. Although rate control is one of the first line management of all patient with atrial fibrillation, several issues remain debateable.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Quality of Life

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

Digoxin has been used for more than 50 years in patients with Atrial Fibrillation (AF), with the goal of Controlling Heart Rate (HR) and restoring sinus rhythm. In the last two decades, several studies have correlated therapeutic use of digoxin with increased mortality. However, such studies have potential biases that cannot be disregarded, mainly because they are cross-sectional experiments or post-hoc analyses of Randomized Controlled Trials (RCTs). Despite uncertainties regarding the safety of digoxin in this setting, it remains one of the most prescribed drugs for AF worldwide. On the other hand, the absence of any RCTs designed to evaluate mortality makes a definitive conclusion more difficult to reach; therefore, this medication must be used with care. In this review, we explored the therapeutic use of digoxin in the context of AF, discussed mortality data by means of critical analysis in the light of the best available evidence, and position ourselves in relation to more rigorous control of serum levels of this drug in daily practice.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cross-Sectional Studies; Digoxin; Humans

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

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

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

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

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

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

Digoxin has long been used for rate control in atrial fibrillation (AF); its safety remains controversial.We performed a literature search using MEDLINE (source PubMed, January 1, 1966, to July 31, 2015) and EMBASE (January 1, 1980, to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis.Twenty-two studies involving 586,594 patients were identified. Patients taking digoxin, as compared with those who took no digoxin, experienced an increased risk of death from any cause (RR: 1.29[95% CI 1.16-1.43]), even after reported adjustment for propensity scores (RR: 1.28[95% CI 1.18-1.39]). The risk of death was increased with patients with or without heart failure (RR: 1.12[95% CI 1.02-1.23] and RR: 1.26[95% CI 1.15-1.29], respectively), and patients taking or not taking beta blockers (RR: 1.17 [95% CI 1.06-1.30] and RR: 1.28 [95% CI 1.08-1.51], respectively). Digoxin use was also associated with increased risk of cardiovascular death (RR: 1.32 [95% CI 1.07-1.64]), arrhythmic death (RR: 1.38 [95% CI 1.07-1.79]), and stroke (RR: 1.20 [95% CI 1.004-1.44]). Digoxin treatment is associated with an absolute risk increase of 19 (95% CI 13-26) additional deaths from any cause per 1000 person-years.Digoxin use is associated with a significant increased risk for death from any cause in patients with AF. This finding suggests a need for reconsideration of present treatment recommendations on use of digoxin in AF.

Topics: Atrial Fibrillation; Cause of Death; Digoxin; Humans; Risk; Survival Rate

There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). The aim of this analysis was to systematically review digoxin use and risk of mortality in patients with AF.. MEDLINE, EMBASE, GoogleScholar, CINAHL, meeting abstracts, presentations, and Cochrane central databases were searched from inception through December 2014, without language restrictions. For a study to be selected, it had to report the risk of mortality associated with digoxin use in AF patients as an outcome measure. Data were extracted by 2 independent authors. Evidence tables were created.. A total of 16 studies (6 post hoc analyses of randomized controlled trials) with 111,978 digoxin users and 389,643 non-digoxin users were included. In a random effects model, patients treated with digoxin had a 27% increased risk of all-cause mortality (pooled HR 1.27; 95% CI 1.19-1.36) and 21% increased risk of cardiovascular mortality (pooled HR 1.21; 95% CI 1.12-1.30) compared with those who did not use digoxin. In a random effects model, the association of digoxin with all-cause mortality was stronger for AF patients without heart failure (pooled HR 1.47; 95% CI 1.25-1.73) than AF patients with heart failure (pooled HR 1.21; 95% CI 1.07-1.36, interaction p = 0.06).. Digoxin use in AF is associated with increased risk of all-cause and cardiovascular mortalities. The effect size was larger for AF patients without heart failure than AF patients with heart failure. The study suggests further directed analyses to study the effect that is suggested by this meta-analysis, especially in AF without heart failure.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Global Health; Humans; Survival Rate

Topics: Adrenergic beta-Antagonists; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Digoxin; Humans; Incidence; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Factors; Stroke; Thromboembolism

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

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

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update.

Topics: Acute Coronary Syndrome; Algorithms; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Pacing, Artificial; Cardiotonic Agents; Catheter Ablation; Coronary Artery Disease; Digoxin; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Magnesium; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; ST Elevation Myocardial Infarction; Stroke

There is an ongoing debate on the safety of digoxin use in patients with atrial fibrillation (AF). To address this issue, the investigators assembled a synthesis of the available evidence on the relation between digoxin and all-cause mortality in patients with AF. PubMed and the Embase database were systematically searched to identify all eligible studies examining the association between digoxin use and the mortality risk in AF. Overall hazard ratios and 95% confidence intervals were calculated using the random-effects model. Eleven observational studies were identified that met the inclusion criteria, 5 of which additionally used propensity score matching for statistical adjustment. In total, 318,191 patients were followed up for a mean of 2.8 years. Overall, digoxin use was associated with a 21% increased risk for mortality (hazard ratio 1.21, 95% confidence interval 1.12 to 1.30). Sensitivity analyses found the results to be robust. In the propensity score-matched AF patients, digoxin use was associated with a 17% greater risk for mortality (hazard ratio 1.17, 95% confidence interval 1.13 to 1.22). When the AF cohort was grouped into patients with and without heart failure, the use of digoxin was associated with an increase in mortality in patients with and those without heart failure, and no significant heterogeneity was seen between the groups (p >0.10). In conclusion, the results suggest that digoxin use was associated with a greater risk for mortality in patients with AF, regardless of concomitant heart failure. A well-powered randomized trial is necessary to reveal the true effect of digoxin.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Digoxin; Humans; Risk Factors; Survival Rate

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

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

Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found four studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (rate-limiting, with or without digoxin), calcium-channel blockers (with or without digoxin), and digoxin.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Humans; 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

Digoxin is still commonly used in atrial fibrillation (AF) patients with and without heart failure (HF) for heart rate control. Studies concerning the detrimental effects of digoxin therapy in AF patients are inconsistent. This updated meta-analysis examined the association of digoxin therapy with all-cause mortality in AF patients, stratified by heart function status. We included observational studies with multivariate-adjusted data on digoxin and all-cause mortality in the analysis. The relative risks (RRs) of all-cause mortality were calculated and reported with 95% confidence intervals (95% CIs). Seventeen studies comprising 408,660 patients were included. Overall, in AF patients, digoxin treatment was associated with a significant increase in all-cause mortality after multivariate-adjustment (RR = 1.22; 95% CI 1.15-1.30). When stratified by heart function status, digoxin treatment was associated with a 14% increase in all-cause mortality in AF patients with HF (RR = 1.14, 95% CI 1.04-1.24), and a 36% increase in those without HF (RR = 1.36, 95% CI 1.18-1.56). The increased risk of all-cause mortality was significantly higher in AF patients without HF compared with those with HF (P for interaction = 0.04). This meta-analysis demonstrates that digoxin therapy was associated with a significant increase in all-cause mortality in AF patients, especially in those without HF. Given other available options, digoxin should be avoided as a first-line agent for heart rate control in AF patients.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Mortality

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

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

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

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

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

Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? What is the effect of different treatment strategies (rate versus rhythm) for people with persistent non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (with or without digoxin), calcium channel blockers (with or without digoxin), calcium channel blockers (rate-limiting), digoxin, and rate versus rhythm control strategies.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Cardiovascular Diseases; Digoxin; Humans

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery that increases patient morbidity, length of stay, and hospital costs. A substantial body of evidence exists evaluating various pharmacologic and nonpharmacologic methods to decrease the occurrence of POAF in an effort to decrease its burden on the health care system. Evidence-based guidelines support the use of beta-blockers as standard prophylaxis of POAF in patients undergoing cardiac surgery. Traditional prophylactic therapy for POAF targets the sympathetic nervous system, refractory period, and atrial conduction. However, associations between the development of POAF and the inflammatory process, oxidative stress, and atrial remodeling have prompted the investigation of novel therapies targeting these processes. To evaluate the role of pharmacologic strategies beyond beta-blockers in the prevention of POAF, we conducted a search of the PubMed database to identify studies published from 1950-February 2009. Emphasis was placed on how these therapies could be used in patients intolerant to beta-blockers or as additive therapy in high-risk patients. We found that sufficient evidence exists to recommend the use of amiodarone, sotalol, and possibly magnesium as monotherapy in patients unable to take beta-blockers or as add-on therapy for the prevention of POAF. Currently, available evidence does not support the use of propafenone, procainamide, digoxin, thiazolidinediones, triiodothyronine, or calcium channel blockers in the prevention of POAF. Preliminary evidence suggests that dofetilide, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), nonsteroidal antiinflammatory drugs, corticosteroids, omega-3 fatty acids, ascorbic acid, N-acetylcysteine, and sodium nitroprusside may be effective in preventing POAF. Additional large-scale, adequately powered clinical studies are needed to determine the benefit of these agents before they can be considered for routine use.

Topics: Acetylcysteine; Adrenergic beta-Antagonists; Amiodarone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiac Surgical Procedures; Digoxin; Fatty Acids, Omega-3; Hospital Costs; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Postoperative Period; Sotalol

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

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Emergency Service, Hospital; Emergency Treatment; Humans

Recent guidelines by the National Institute for Health and Clinical Excellence (NICE) and the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) on rate control management for chronic atrial fibrillation have relegated digoxin to second line treatment, recommending instead the use of beta-blockers or rate limiting calcium antagonists as first line treatment. The objective of this review is to assess the efficacy of these drugs in controlling heart rate, and in improving symptoms and exercise tolerance.. We electronically searched the Medline, Embase and Cochrane databases, hand searched journals and relevant bibliographies for articles.. We included all study designs evaluating or comparing oral digoxin, beta-blockers and calcium antagonists, alone or in combination, for rate control in chronic atrial fibrillation. 46 studies satisfied our inclusion and quality criteria.. Published studies are small and too heterogeneous to be quantitatively combined. Descriptive synthesis of the data shows little evidence that monotherapy with beta-blockers or calcium antagonists improves symptoms or exercise capacity in patients with chronic atrial fibrillation. Instead it is associated with dose related side effects.. Based on the limited data available, we conclude that the combination of digoxin with either a beta-blocker or calcium antagonist should be first line management in patients with chronic atrial fibrillation.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Humans

Digoxin remains one of the most frequently prescribed drugs in the management of atrial fibrillation. The main indications for digoxin in atrial fibrillation are restoration of sinus rhythm, prevention of recurrence and slowing of the ventricular rate. However, none of these effects of digoxin have been confirmed in placebo controlled studies. In addition, recent reports suggest increased mortality in patients with atrial fibrillation without heart failure taking digoxin. The aim of this article is to review the role of digoxin in atrial fibrillation without heart failure.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Evidence-Based Medicine; Heart Conduction System; Heart Rate; Humans; Risk Assessment; Secondary Prevention; Treatment Outcome; Ventricular Function, Left

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Emergency Service, Hospital; Evidence-Based Medicine; Female; Humans; Middle Aged

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

Atrial fibrillation is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. It is a common arrhythmia that presents various treatment options. Pharmacologic therapy is used to maintain sinus rhythm, to control the ventricular response, or to convert atrial fibrillation to sinus rhythm and prevention of thromboembolism. Cardioversion shocks are applied through surface or intrathoracic electrodes to convert atrial fibrillation to sinus rhythm. The tendency for recurrence of atrial fibrillation is high. Treatment with antiarrhythmic drugs has decreased its recurrence. Drugs that slow conduction through the AV node (such as digoxin, beta blockers and calcium channel blockers) have been used as adjuvants to therapy for the prevention of atrial fibrillation. Drugs used for the prevention of atrial fibrillation are antiarrhythmic drugs of class IA and C, and type III. Drug combination acting through different electrophysiological channels and mechanisms may prove beneficial in the prevention of atrial fibrillation.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Humans; Secondary Prevention; Thromboembolism

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Monitoring; Female; Humans; Male; Middle Aged; Practice Guidelines as Topic; Safety Management

Digoxin has traditionally been the drug of choice for ventricular rate control in patients with chronic atrial fibrillation (AF), with or without heart failure (HF) with systolic dysfunction. In patients with permanent AF, digoxin monotherapy is ineffective to control ventricular rate during exercise, but the combination of digoxin with a beta-blocker or a non-dihydropyridine calcium channel antagonist can control heart rate both at rest and during exercise. Only a few randomised, controlled studies have evaluated the adverse effects of digoxin in patients with AF in a systematic way and side effects requiring drug withdrawal have rarely been reported. When reported, the most frequent adverse effects were cardiac arrhythmias (ventricular arrhythmias, AV block of varying degrees and sinus pauses). This evidence suggested that, in contrast to other antiarrhythmic drugs, digoxin is a safe drug in patients with AF. However, this safety profile can be erroneous due to the short follow-up of the studies and patient selection. Because patients with HF have been excluded in most studies, the safety profile of digoxin in this population has not been directly addressed. Early recognition that an arrhythmia is related to digoxin intoxication as well as recognition of concomitant medications or medical conditions that may directly alter the pharmacokinetic profile of digoxin, or indirectly alter its cardiac effects by pharmacodynamic interactions remain essential for safe and effective use of digoxin in patients with AF.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Interactions; Drug Monitoring; Electrocardiography; Humans

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

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

Postoperative atrial fibrillation (AF) occurs in 20%-40% of patients undergoing open-heart surgery. Numerous pharmacological and electrical therapies have been used as a prophylaxis to prevent this dysrhythmia. The purpose of this study was to examine the selective use of amiodarone and early cardioversion (CVN) postoperatively to restore normal sinus rhythm (NSR).. A retrospective nonrandomized review of patients who received amiodarone and early electrical CVN (study group) for postoperative AF after coronary artery bypass grafting (CABG) were compared with patients who received nonamiodarone therapies (control group). The study group received 150 mg of amiodarone bolus intravenously and thereafter received an infusion of 1 g over a 24-hour period. If NSR was established within 24 hours, then the intravenous (IV) infusion was continued for another 24 hours with concomitant oral amiodarone overlap. If NSR was not established within 24 hours, then external electrical CVN was performed. After 48 hours, the IV infusion was discontinued and the oral regimen maintained through discharge. Control group patients received either combination digoxin and procainamide or diltiazem. Postoperative beta-blocker administration was instituted in all patients.. Six-hundred forty consecutive CABG patients were examined between July 1995 and June 2003. Postoperative AF developed in 160 of these patients (25%). One-hundred patients constituted the study group and 60 patients represented the control group. Restoration of NSR within 24 and 48 hours occurred in 79 (79%) and 90 patients (90%) for the study group, respectively, compared with 38 (64%) and 44 patients (73%) for the control group, respectively. The presence of NSR at discharge was achieved in 98 study patients (98%) and 50 control patients (83%). The length of stay (LOS) for the study and control patients was 7.4 and 9.1 days, respectively. There was no mortality in either group.. Amiodarone and early CVN was more effective than nonamiodarone therapies with regard to restoring NSR for patients in whom AF developed after elective CABG. A trend toward a decrease in LOS was observed in the study group, but was not statistically significant. The overall LOS using amiodarone therapy with early CVN was similar to postoperative AF for patients in whom the condition did not develop.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Combined Modality Therapy; Coronary Artery Bypass; Digoxin; Diltiazem; Drug Therapy, Combination; Electric Countershock; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Length of Stay; Male; Middle Aged; Postoperative Complications; Procainamide; Retrospective Studies; Treatment Outcome

Postoperative atrial fibrillation is a common complication after open heart surgery; it increases morbidity, hospital stay, and costs. In an analysis of 8 large cardiac surgery trials totaling 20,193 patients, the incidence of postoperative atrial fibrillation was estimated to be 26% and ranged from 17% to 35%. We reviewed the results of 52 studies published between 1966 and 2003 that evaluated pharmacologic strategies to prevent postoperative atrial fibrillation in nearly 10,000 patients undergoing open heart operations. Supraventricular tachyarrhythmias, including atrial fibrillation, after open heart operations occurred in 29% of patients who did not receive prophylactic drugs, compared with 12% in patients who received intravenous followed by oral amiodarone, 15% in those given sotalol, 16% in those given oral amiodarone, and 19% in those given beta-blockers. Pharmacologic strategies and regimens aimed at preventing postoperative atrial fibrillation are necessary to optimize the postoperative care of patients undergoing open heart operations. Although no strategy has consistently been shown to be superior to another, the most effective approach to preventing postoperative atrial fibrillation likely involves multiple interventions. In the absence of contraindications, all patients should receive beta-blocker therapy before and after the operation. For patients with 1 or more risk factors for postoperative atrial fibrillation, regimens consisting of either sotalol (beta-blocker with class III antiarrhythmic properties) alone or beta-blockers in combination with amiodarone seem to be the safest, most effective pharmacologic strategies for preventing postoperative atrial fibrillation.

Topics: Adrenergic beta-Antagonists; Amiodarone; Angiotensin II; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiac Surgical Procedures; Digoxin; Humans; Postoperative Care; Risk Factors; Sotalol; Tachycardia, Supraventricular

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

Atrial fibrillation (AF) in heart failure develops commonly in older individuals and its prevalence increases as heart failure severity progresses. Because of deteriorating hemodynamics, patients with heart failure are at increased risk for developing AF and, conversely, AF in heart failure patients is associated with adverse hemodynamic changes. AF is believed to increase the mortality risk in heart failure, which may be minimized by treatment that includes the control of ventricular rate, prevention of thrombotic events, and conversion to normal sinus rhythm. Clinical guidelines recommend amiodarone or dofetilide in heart failure patients, but these drugs have certain drawbacks, such as an increased risk for bradyarrhythmias with amiodarone and proarrhythmic reaction with dofetilide. Some but not all clinical trials have suggested that rate control should be the primary therapeutic goal in high-risk heart failure patients with AF and, if unsuccessful, followed by rhythm control. The former is effectively achieved with rate-lowering beta-blockers alone or in combination with digoxin. Recent studies evaluating the effects of combination carvedilol/digoxin therapy demonstrate synergistic effects between the two drugs. This combination therapy decreased heart failure symptoms, effectively reduced ventricular rate, and improved ventricular function to a greater extent compared with that produced by either drug alone. Although digoxin alone is an effective heart failure treatment, its use as a single rate-control therapy is often ineffective in heart failure patients with AF associated with rapid ventricular response. Carvedilol is effective, alone or in combination, with digoxin in such heart failure patients with AF, and has been shown to reduce mortality risk in patients with chronic heart failure during prolonged therapy.

Topics: Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Carbazoles; Cardiac Output, Low; Carvedilol; Digoxin; Disease Progression; Humans; Propanolamines; Randomized Controlled Trials as Topic

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

The optimal management of atrial fibrillation is of considerable clinical importance, and with the recent publication of four studies suggesting the equivalence of rate and rhythm control strategies, new attention has been focused on rate control. Reasons for rate control include reduction of symptoms and the prevention of tachycardia-mediated cardiomyopathy; yet, evidence-based definitions of optimal rate control are lacking. This article examines an approach to rate control that includes serial assessment of heart rate and symptoms, both at rest and with exertion, and the use of therapy tailored to the individual and modified over time (as no single therapy demonstrates clear superiority). Often, multidrug regimens including digoxin and a calcium channel blocker or beta-blocker are required, and in a minority of patients atrioventricular nodal ablation and pacing are necessary. Several novel therapies currently under development are also discussed.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Heart Conduction System; Heart Rate; Humans; Wolff-Parkinson-White Syndrome

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Flecainide; Humans; Propafenone; Verapamil

To control ventricular rate in patients with AF, physicians should seek to control heart rate at rest and with exertion. The goal has to be achieved while minimizing costs and adverse effects. For emergency use, i.v. diltiazem or esmolol are drugs useful because of their rapid onset of action. They have to be used with caution in patients with concomitant left ventricular failure symptoms, however. For most patients with AF, chronic control of the ventricular rate can be achieved with one drug. For the chronic control of ventricular rate in patients with AF and normal ventricular function, diltiazem, atenolol, are metoprolol are probably the drugs of choice. For patients with AF and structurally abnormal hearts, atenolol, metoprolol, or carvedilol are appropriate choices. Adequate ventricular rate control by pharmacological agents should be evaluated by either 24-hour Holter monitoring or a submaximal stress test to determine the resting and exercise ventricular rate. If the mean ventricular rate is not close to 80 beats per minute, or the heart rate on moderate exertion is not between 90 to 115 beats per minute, a second agent to control the rate should be added. Excessive reductions in ventricular rates that could limit exercise tolerance should be avoided.

Topics: Amiodarone; Atenolol; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Diltiazem; Heart Rate; Humans; Metoprolol; Randomized Controlled Trials as Topic; Verapamil

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: 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: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Flecainide; Humans; Propafenone; Verapamil

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

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Humans; Timolol; Verapamil

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Flecainide; Humans; Propafenone; Timolol; Verapamil

Topics: Acute Disease; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Electrocardiography; Fibrinolytic Agents; Humans; Prognosis; Randomized Controlled Trials as Topic; Thromboembolism; Timolol; Treatment Outcome; Verapamil

Digoxin toxicity is a major public health issue in the United States. Often this is due to drug interactions, and renal transplant recipients are at particularly high risk for drug-drug interactions. We present cases of 2 renal transplant recipients who received itraconazole and digoxin concomitantly and experienced digoxin toxicity. We have also reviewed the relevant literature to elicit the mechanisms, signs, and symptoms of digoxin toxicity in the presence of itraconazole. When clinicians know the potential drug-drug interactions that may lead to digoxin toxicity, the mechanisms of interaction, the signs and symptoms of digoxin toxicity, and appropriate monitoring, digoxin toxicity is largely preventable.

Topics: Anti-Arrhythmia Agents; Antifungal Agents; Atrial Fibrillation; Digoxin; Drug Interactions; Humans; Immunosuppressive Agents; Itraconazole; Kidney Transplantation; Male; Middle Aged; Tacrolimus

Atrial fibrillation (AF), the most common form of sustained arrhythmia, is associated with a frightening risk of embolic complications, tachycardia-related ventricular dysfunction, and often disabling symptoms. Pharmacologic therapy is the treatment used most commonly to restore and maintain sinus rhythm, to prevent recurrences, or to control ventricular response rate.. This article reviews published data on pharmacologic treatment and discusses alternative systems to classify AF and to choose appropriate pharmacologic therapy.. AF is either paroxysmal or chronic. Attacks of paroxysmal AF can differ in duration, frequency, and functional tolerance. In the new classification system described, 3 clinical aspects of paroxysmal AF are distinguished on the basis of their implications for therapy. Chronic AF usually occurs in association with clinical conditions that cause atrial distention. The risk of chronic AF is significantly increased by the presence of congestive heart failure or rheumatic heart disease. Mortality rate is greater among patients with chronic AF regardless of the presence of coexisting cardiac disease. The various options available for the treatment of chronic AF include restoration of sinus rhythm or control of ventricular rate. Cardioversion may be accomplished with pharmacologic or electrical treatment. For patients in whom cardioversion is not indicated or who have not responded to this therapy, antiarrhythmic agents used to control ventricular response rate include nondihydropyridine calcium antagonists, digoxin, or beta-blockers. For patients who are successfully cardioverted, sodium channel blockers or potassium channel blockers such as sotalol, amiodarone, or a pure class III agent such as dofetilide, a selective potassium channel blocker, may be used to prevent recurrent AF to maintain normal sinus rhythm.. The ultimate choice of the antiarrhythmic drug will depend on the presence or absence of structural heart disease. An additional concern with chronic AF is the risk of arterial embolization resulting from atrial stasis and the formation of thrombi. In patients with chronic AF the risk of embolic stroke is increased 6-fold. Therefore anticoagulant therapy should be considered in patients at high risk for embolization. Selection of the appropriate treatment should be based on the concepts recently developed by the Sicilian Gambit Group (based on the specific channels blocked by the antiarrhythmic agent) and on clinical experience gained over the years with antiarrhythmic agents. For example, termination of AF is best accomplished with either a sodium channel blocker (class I agent) or a potassium channel blocker (class III agent). In contrast, ventricular response rate is readily controlled by a beta-blocker (propranolol) or a calcium channel blocker (verapamil). Alternatively, antiarrhythmic drug therapy may be chosen based on the Vaughan-Williams classification, which identifies the cellular electrophysiologic effects of the drug.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Dihydropyridines; Drug Administration Routes; Electrocardiography; Embolism; Heart Rate; Humans; Practice Guidelines as Topic; Prognosis; Propranolol; Secondary Prevention; Tachycardia, Paroxysmal; Verapamil

Atrial fibrillation (AF) is the commonest arrhythmia. It presents in distinct patterns of paroxysmal, persistent and chronic AF, and patient management aims differ according to the pattern. In paroxysmal AF, drug treatment with beta-blockers, class Ic and class III agents reduce the frequency and duration of episodes. In persistent AF (recent onset, non-paroxysmal), early cardioversion with either pharmacological agents or by direct current (DC) cardioversion should be actively considered, in those patients who are suitable. Patients most likely to cardiovert and remain in sinus rhythm include those with duration of AF of <1 year, an acute reversible cause, left atrial diameter <50 mm and good left ventricular function on echocardiography. Recent data show that maintenance of sinus rhythm after successful cardioversion is enhanced by the use of class III drugs including amiodarone and dofetilide. In chronic or permanent AF, management is aimed at controlling the ventricular rate response with combinations of digoxin, beta-blockers and calcium antagonists with atrio-ventricular nodal activity (diltiazem and verapamil). There is some debate about the prognostic significance of AF. Certainly AF is associated with an excess mortality but this is largely accounted for by its association with serious intrinsic heart disease and the thrombo-embolic complications of the arrhythmia. Atrial fibrillation is a common default arrhythmia for the sick heart.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiovascular Surgical Procedures; Digoxin; Echocardiography; Electric Countershock; Humans; Postoperative Complications; Prognosis; Risk Factors; Thromboembolism

Our goal was to determine what drugs are most efficacious for controlling the ventricular rate in patients with atrial fibrillation.. We conducted a systematic review of the literature published before May 1998, beginning with searches of The Cochrane Collaboration's CENTRAL database and MEDLINE.. We included English-language articles describing randomized controlled trials of drugs used for heart rate control in adults with atrial fibrillation.. Abstracts of trials were reviewed independently by 2 members of the study team. We reviewed English-language abstracts of non-English-language publications to assess qualitative consistency with our results.. Forty-five articles evaluating 17 drugs met our criteria for review. In the 5 trials of verapamil and 5 of diltiazem, heart rate was reduced significantly (P <.05), both at rest and with exercise, compared with placebo, with equivalent or improved exercise tolerance in 6 of 7 comparisons. In 7 of 12 comparisons of a beta-blocker with placebo, the beta-blocker was efficacious for control of resting heart rate, with evidence that the effect is drug specific, as nadolol and atenolol proved to be most efficacious. All 9 comparisons demonstrated good heart rate control with beta-blockers during exercise, although exercise tolerance was compromised in 3 of 9 comparisons. In 7 of 8 trials, digoxin administered alone slowed the resting heart rate more than placebo, but it did not significantly slow the rate during exercise in 4 studies. The trials evaluating other drugs yielded insufficient evidence to support their use, but those drugs may yet be promising.. The calcium-channel blockers verapamil or diltiazem, or select beta-blockers are efficacious for heart rate control at rest and during exercise for patients with atrial fibrillation without a clinically important decrease in exercise tolerance. Digoxin is useful when rate control during exercise is less a concern.

Topics: Adrenergic beta-Antagonists; Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Bias; Calcium Channel Blockers; Digoxin; Diltiazem; Evidence-Based Medicine; Exercise; Heart Rate; Humans; Research Design; Rest; Treatment Outcome; Ventricular Function; Verapamil

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

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Drug Interactions; Electrophysiology; Heart; Humans; Potassium Channels; Quinidine; Sodium Channels

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and its prevalence increases with age. Etiologies include coronary artery disease, hypertension, valvular heart disease, thyrotoxicosis, and other cardiac and noncardiac conditions. AF can lead to reversible impairment of left ventricular (LV) function, LV dilatation, clinical heart failure, angina pectoris, stroke, and increased mortality. Digoxin, beta blockers, or calcium channel blockers are used to control ventricular rate in new-onset AF with hemodynamically stable rhythm and in chronic AF where rhythm cannot be restored. These drugs can be used alone or in combination, depending on the clinical situation. The most complete relief of symptoms occurs when sinus rhythm is restored. Class IA, IC, and III antiarrhythmic agents can be used to restore and maintain sinus rhythm in selected patients.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Drug Therapy, Combination; Electrocardiography; Heart Rate; Humans; Ventricular Function, Left

Atrial fibrillation is the most common cardiac rhythm disorder associated with hospitalization. Two therapeutic options have been available: antiarrhythmic drug therapy, and external or internal electrical cardioversion. Electrical cardioversion of atrial fibrillation remains one of the most widely used and effective treatments for the restoration of normal sinus rhythm. However, many patients continue to receive an antiarrhythmic drug before and after cardioversion in an attempt either to cardiovert the arrhythmia chemically or to maintain sinus rhythm after successful cardioversion. Because some pharmacological agents can affect the cardioversion procedure for atrial fibrillation or flutter, and because many patients with such arrhythmias may require electrical cardioversion when they are taking antiarrhythmic drugs, the question of a possible effect of drug therapy on the efficacy and safety of electrical cardioversion of atrial fibrillation arises. Early reports of direct current cardioversion provoking potentially lethal ventricular arrhythmias raised suspicions of an arrhythmogenic role for digoxin antiarrhythmic therapy, and it is customary to withhold these drugs for 24 to 48 h before cardioversion is attempted. However, this complication is likely to arise only in patients who are close to, or actually manifesting, signs of drug toxicity. On the other hand, treatment with therapeutic concentrations of antiarrhythmic drugs before cardioversion may in some cases be associated with a significant reduction in the number of shocks and decreased energy required to restore sinus rhythm, a lower incidence of postshock arrhythmias and a reduced risk of early recurrence of atrial fibrillation.

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Combined Modality Therapy; Digoxin; Electric Countershock; Flecainide; Humans; Procainamide; Quinidine; Verapamil

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

A recently conducted observational study of the prehospital treatment of uncontrolled atrial fibrillation brought to light therapeutic inconsistencies by emergency providers in dealing with this dysrhythmia. A review of the literature suggests that digoxin lacks efficacy in controlling ventricular rate in atrial fibrillation and that the slow onset of digoxin makes its use in the emergency setting questionable. Because of their demonstrated ability to rapidly slow ventricular rate, the calcium channel blocker, diltiazem, or the beta-adrenergic blocker, esmolol, should be the preferred agents for treating rapid atrial fibrillation in the emergency department or the paramedic ambulance.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Diltiazem; Emergency Medical Services; Humans; Propanolamines

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Coronary Artery Bypass; Costs and Cost Analysis; Digoxin; Heart Rate; Humans; Postoperative Complications; Risk Factors; Sulfonamides

Because of its prevalence in the population and its associated underlying diseases and morbidity, atrial fibrillation (AF) is an important and costly health problem. Advancing age, diabetes, heart failure, valvular disease, hypertension, and myocardial infarction predict the occurrence of AF within a population. The management of AF is complex and involves prevention of thromboembolic complications and treatment of arrhythmia-related symptoms. Stroke occurs in 4.5% of untreated patients with AF per year. Independent risk factors for stroke in nonrheumatic patients with AF are advanced age; a history of prior embolism, hypertension, or diabetes; and echocardiographic findings of left atrial enlargement and left ventricular dysfunction. Warfarin decreases stroke by two-thirds and death by one-third; aspirin is only about half as effective overall and is insufficient therapy for those with risk factors for stroke. Options for thromboembolic prophylaxis are use of warfarin for all in whom it is safe or, alternatively, warfarin for those with risk factors and aspirin for those without risk factors. One-half of the patients with AF are 75 years of age or older. The uniform applicability and relative safety of warfarin therapy in this age-group are controversial. Specific therapy for the arrhythmia should be dictated by the need to control symptoms. Symptomatic treatments include rate-control medications and strategies designed to terminate and prevent arrhythmia recurrence. Digoxin, beta-adrenergic blockers, verapamil, and diltiazem slow excessive ventricular rates in patients with AF and may favorably manage comorbid conditions. The efficacy of anti-arrhythmic medications is only 40 to 70% per year in preventing recurrences of AF, and these agents, except amiodarone, may increase the risk of sudden death in patients with certain types of organic heart disease and AF. The use of nonpharmacologic symptomatic therapies such as atrioventricular node modification or ablation with a rate-response pacemaker or surgical intervention is increasing.

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Anti-Arrhythmia Agents; Aspirin; Atrial Fibrillation; Catheter Ablation; Cerebrovascular Disorders; Diabetes Complications; Digoxin; Diltiazem; Embolism; Humans; Hypertension; Thromboembolism; Verapamil; Warfarin

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

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Catheter Ablation; Digoxin; Heart Rate; Humans; Tachycardia

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Humans; Myocardial Infarction; Quinidine

Atrial fibrillation is associated with a resting heart rate in excess of age-matched subjects in sinus rhythm, and there is an additional steep rise in rate during exertion. This article reviews the factors responsible for this tachycardia, the pharmacologic agents commonly used for heart rate control, and the effects of atrial antiarrhythmic agents on the heart rate during paroxysmal atrial fibrillation.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Heart Rate; Heart Ventricles; Humans; Magnesium; Physical Exertion; Rest

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

Antiarrhythmic drugs are widely used in atrial fibrillation. The demonstration of severe pro-arrhythmic effects in recent years has led to the reappraisal of their indications in this pathology. Antiarrhythmic agents have three roles: reduction of the fibrillation, maintenance of sinus rhythm and, in case of failure, control of the ventricular response. In the first indication, although intravenous injection of Class Ic antiarrhythmics is effective in 70% of cases, there is an alternative: electrical cardioversion, which is effective in 90% of cases with the transthoracic method when a certain number of technical conditions are respected. The success rate is even better with endocavitary defibrillation. Sinus rhythm is sustained in only 25% of patients at one year with placebo and in 50% of patients with antiarrhythmic therapy. The alternatives in this indication are few at present and consist in right atrial pacing in cases of vagal fibrillation and biatrial pacing for resynchronizing the activation of the two atriae when there is a major interatrial conduction defect. The control of the ventricular response, in cases of permanent atrial fibrillation, is usually reserved to digitalis, betablockers, amiodarone and some calcium antagonists. They are often inadequate and an alternative is radiofrequency catheter ablation of the atrioventricular node, which requires permanent ventricular pacing. In conclusion, there are a few alternatives to antiarrhythmic drug therapy in atrial fibrillation, but they are relatively ineffective in maintaining sinus rhythm.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Catheter Ablation; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electric Countershock; Female; Follow-Up Studies; Heart Rate; Humans; Male; Quinidine

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

Atrial fibrillation (AF) with rapid ventricular response is a common tachyarrhythmia requiring hospitalization. The increased morbidity and mortality due to the hemodynamic consequences of acute AF is well recognized. Management strategies may be formed based on the evaluation of the entire clinical context including cardiovascular status and the associated noncardiac clinical disorders. Intravenous (i.v.) beta blockers and calcium channel blockers are equally effective in rapidly controlling the ventricular rate in acute AF in selected individuals. The addition of digoxin to the regimen causes a favorable outcome. However, digoxin as a single agent is generally inefficacious in slowing the ventricular rate in acute AF. These standard pharmacotherapies however, are contraindicated in ventricular preexcitation syndrome associated with rapid ventricular rate due to AF. In this situation the drug of choice is i.v. procainamide. When clinical condition is unstable or hemodynamically compromised, cardioversion is the treatment of choice in all cases of AF with rapid ventricular rate. Radiofrequency ablation of the AV node or anomalous tract may be considered in refractory or high risk subjects as a last resort.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Heart Rate; Humans; Propranolol; Verapamil; Wolff-Parkinson-White Syndrome

The epidemiology, pathophysiology, diagnosis, evaluation, and treatment of atrial fibrillation (AF) and atrial flutter (AFl) are reviewed, and recent developments and controversies in the approach to these arrhythmias are addressed. AF and AFl are the arrhythmias most frequently encountered in clinical practice. Although occasionally unaware of their arrhythmia, patients usually complain of palpitations, weakness, dyspnea, and decreased exercise tolerance. The initial goal of therapy is control of the ventricular rate. Rate control is accomplished with atrioventricular node-blocking agents such as digoxin, calcium-channel blockers, or beta-adrenergic blockers. Along with a rapid, irregular ventricular response, other detrimental outcomes of AF and AFl include compromised hemodynamics and increased vulnerability to thromboembolism. After the cause of the patient's arrhythmia has been evaluated, pharmacologic treatment is directed at converting the rhythm to normal sinus rhythm and maintaining it. Antiarrhythmic drugs have proved effective in about 50% of cases but may be associated with increased mortality. More effective and safer forms of drug therapy for AF and AFl are needed. Nonpharmacologic alternatives to antiarrhythmic medications for refractory AF and AFl include radio-frequency catheter ablation of the bundle of His with pacemaker placement and surgery. Patients who remain in AF despite therapy should receive long-term warfarin treatment. Drugs may be used to control the ventricular response in patients with AF and AFl, terminate and prevent the arrhythmias, and prevent thromboembolism. Nonpharmacologic treatments are reserved for patients whose arrhythmias are poorly controlled by drugs.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Electric Countershock; Humans

Pacing is indicated in patients with AF when clinical symptoms are readily attributable to slow ventricular rate and prolonged ventricular pauses. When choosing a pacemaker for implantation, one should consider the importance of a reasonable chronotropic response to exercise and provide a rate-responsive system (VVIR) for those patients who show chronotropic incompetence. In the case of paroxysmal AF, an AV synchronized system may provide protection against deterioration to chronic AF and heart failure and is preferred over VVI pacing, providing that paroxysms are infrequent. Drug-pacemaker interaction is rare, but it is recommended that class IC antiarrhythmic agents should not be used in pacemaker-dependent patients. Cardioversion should be performed with care in patients with a permanent pacemaker, and certain protective measures must be employed to avoid pacemaker destruction or malfunction. Pacemakers, when used according to strict criteria, constitute an integral part of treatment and may improve the quality of life and facilitate the use of necessary drugs in selected patients with AF.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Digoxin; Electric Countershock; Humans; Pacemaker, Artificial

The main goal of therapy in atrial fibrillation is to restore sinus rhythm, if this is possible, to avoid adverse hemodynamic, electrical, and embolic consequences. The restoration of sinus rhythm is urgent if the patient is unstable. In a stable patient, if the duration is shorter than 48 hours and an atrial thrombus is unlikely, then sinus rhythm can be restored after initial rate control. If the duration of atrial fibrillation is more than 48 hours, the embolic risk may be significant, and anticoagulation will be required for 2 to 4 weeks before an attempt at cardioversion. In patients in whom sinus rhythm cannot be restored or maintained, the goal of therapy is rate control and reduction of embolic risk unless the risk of anticoagulation outweighs its benefit. In difficult cases, rate control may be accomplished with AV nodal ablation and pacemaker implantation or with one of the surgical procedures described above with varying degrees of normalization of the physiology. Although not included in this flow chart, we do not advocate episodic intermittent therapy for patients with infrequent episodes of atrial fibrillation because this could be potentially dangerous and may place the patient at a higher risk for developing proarrhythmia.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Catheter Ablation; Cerebrovascular Disorders; Digoxin; Electric Countershock; Humans; Pacemaker, Artificial

Atrial fibrillation is associated with potentially life-threatening strokes. Anticoagulation with warfarin or aspirin reduces the risk of embolic events in patients with chronic atrial fibrillation and mitral valve stenosis or other underlying heart disease. In patients with acute onset of atrial fibrillation, anticoagulation is not necessary before cardioversion. However, in patients with chronic atrial fibrillation, anticoagulation should be started three weeks before cardioversion and continued for four weeks after the return of normal sinus rhythm. Quinidine remains the agent most commonly used for medical cardioversion in patients who are hemodynamically stable. If a patient is hemodynamically unstable or the atrial fibrillation is not corrected with drug therapy, direct-current electrical cardioversion has a high success rate. Antiarrhythmic (quinidine) therapy is often continued indefinitely to help maintain sinus rhythm.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Cerebrovascular Disorders; Diagnosis, Differential; Digoxin; Drug Monitoring; Electric Countershock; Electrocardiography; Family Practice; Humans

Atrial fibrillation (AF) encompasses a variety of discrete clinical syndromes, including paroxysmal, chronic, acute, and postoperative. Digoxin, long considered the mainstay of therapy for rate control in all types of AF, appears to have only modest electrophysiologic effects, which are mediated primarily by the autonomic nervous system. Digoxin has less potency than the calcium antagonists or beta-blocking drugs with respect to atrioventricular nodal blockade. Although less potent than calcium antagonists or beta-blocking drugs on the atrioventricular node, digoxin provides positive inotropic support, whereas the other 2 agents can suppress left ventricular function. Thus, digoxin is the agent of choice in patients with AF in the setting of significant left ventricular dysfunction. However, in the absence of left ventricular dysfunction, digoxin should be considered second-line therapy for the treatment of all AF syndromes.

Topics: Acute Disease; Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Contraindications; Digoxin; Drug Therapy, Combination; Electrophysiology; Humans; Infant, Newborn; Premedication

The possible interference of drugs with the function of implanted electrical cardiac devices in two patients is described, and the literature on the interaction between these drugs and devices is reviewed. A 59-year-old woman had a permanent pacemaker implanted after diagnosis of tachycardia-bradycardia syndrome, and her drug regimen of digoxin, verapamil, and warfarin was supplemented with flecainide to prevent paroxysmal atrial fibrillation. A Holter monitor recording performed after five days of flecainide therapy showed the pacemaker was sensing and pacing normally. Approximately three weeks after pacemaker implantation and initiation of flecainide therapy, a Holter monitor recording showed high-grade atrioventricular block and failure of the pacemaker to capture. A chest roentgenogram showed that the pacemaker lead was properly placed. The pacemaker's pulse amplitude and pulse width were increased, and the device again functioned reliably. Six months later the pacing threshold was noted to have returned to normal. A 64-year-old man had a history of aborted sudden cardiac death from ventricular tachyarrhythmias. The patient received an automatic implanted cardioverter-defibrillator (AICD); at that time, a 15-J discharge was required to terminate induced ventricular fibrillation (VF). Three years later, the AICD was replaced; the energy required for VF termination with the new unit was 16 J. Seven months after implantation of the new unit, the patient had several episodes of ventricular tachycardia (VT). Moricizine therapy was initiated. An electrophysiologic study (EPS) three days later showed that a larger shock (28 J) was required to terminate VF and that the pacing threshold had increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Death, Sudden, Cardiac; Digoxin; Drug Interactions; Electric Countershock; Female; Flecainide; Humans; Male; Middle Aged; Pacemaker, Artificial; Prostheses and Implants; Verapamil; Warfarin

For over 200 years digitalis compounds have been used to treat atrial fibrillation. The rapid ventricular response to atrial fibrillation is frequently treated with digoxin to produce a controlled heart rate. Digoxin has also been proposed as a treatment for terminating recent-onset atrial fibrillation, for maintaining sinus rhythm after an episode of atrial fibrillation, and as prophylactic therapy in patients with paroxysmal atrial fibrillation to prevent excessive tachycardia during a paroxysm. Perhaps because it has been used for so long, few of these indications have been studied scientifically until recently. Studies now suggest that in patients with atrial fibrillation, digoxin is a poor drug for controlling heart rate during exertion, has little or no effect in terminating the arrhythmia, and may occasionally aggravate paroxysmal atrial fibrillation. Despite adequate digitalization, the heart rate at the onset of a paroxysm of fibrillation in patients receiving the drug does not differ from the heart rate in patients not receiving it. This article discusses the current role of digoxin in the management of patients with chronic, recent-onset, or paroxysmal atrial fibrillation.

Topics: Atrial Fibrillation; Digoxin; Heart Rate; Humans; Recurrence

Therapeutic uses of calcium antagonists have expanded to include not only ischemic heart disease but arrhythmias, systemic hypertension, congestive heart failure and various pulmonary and gastrointestinal diseases. Many patients receiving calcium antagonists concomitantly receive digoxin. Although the potential interactions between these agents have frequently been investigated, literature reports are confusing and inconsistent. The pharmacokinetics and mechanisms of interaction are summarized in order to help clinicians to evaluate the potential calcium antagonist digoxin interaction. From the investigations to date, changing the digoxin dosage prior to initiating calcium antagonist therapy is, however, not justifiable. The best approach would be to monitor pharmacodynamic values, SDC, and the patient's clinical status.

Topics: Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Diltiazem; Drug Interactions; Humans; Nifedipine; Verapamil

For decades, atrial fibrillation was treated exclusively with digoxin. The introduction of Ca-antagonists and beta-blockers has, however, produced valuable alternatives as ventricular function can now be controlled both at rest and during exercise whereas, with digoxin, ventricular function could only be controlled at rest. This review deals with the etiology and electrophysiology of atrial fibrillation together with the effects of Ca-antagonists and beta-blockers on conduction and control of the heart rate during exercise. Documentation of the effects of the different drugs, separately and combined, in the treatment of atrial fibrillation during rest and exercise is presented. It is concluded that alteration in the therapeutic strategy appears reasonable in favour of a combination of digoxin and also Ca-antagonists/beta-blocker.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Drug Therapy, Combination; Humans

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

Topics: Atrial Fibrillation; Atrial Flutter; Atrioventricular Node; Digitalis Glycosides; Digoxin; Drug Interactions; Electrocardiography; Electrophysiology; Humans; Kinetics; Myocardial Contraction; Physical Exertion; Time Factors

Serum digoxin assay is a useful clinical tool in monitoring the administration of digoxin. Its value, however, is generally overrated; judicious use of it applies only to specific clinical problems. Its primary use involves assay values at the two ends of the scale: low ranges may help detect noncompliant patients or those with serious absorption difficulties. Higher ranges are helpful in the clinical recognition of digitalis toxicity.

Topics: Atrial Fibrillation; Digoxin; Drug Administration Schedule; Electrocardiography; Heart Rate; Humans; Kinetics; Radioimmunoassay; Sinoatrial Node; Tissue Distribution

Topics: Anti-Arrhythmia Agents; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Pacing, Artificial; Child; Child, Preschool; Digoxin; Electrocardiography; Electrophysiology; Heart Block; Humans; Infant; Mitral Valve Prolapse; Pacemaker, Artificial; Tachycardia

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

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: Aged; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Atropine; Bradycardia; Digitalis Glycosides; Digoxin; Heart Block; Heart Ventricles; Humans; Infant; Isoproterenol; Lidocaine; Phenytoin; Potassium; Procainamide; Propranolol; Quinidine; Tachycardia; Tachycardia, Paroxysmal

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; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Catheterization; Cardiac Surgical Procedures; Coronary Disease; Depression, Chemical; Digitalis; Digoxin; Heart; Heart Diseases; Humans; Injections, Intravenous; Ouabain; Phenytoin; Plants, Medicinal; Plants, Toxic; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Atrioventricular Node; Diagnosis, Differential; Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Heart Rate; Heart Ventricles; Humans; Myocardium; Poisoning; Radioimmunoassay

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrioventricular Node; Digitalis Glycosides; Digoxin; Diuretics; Electrocardiography; Fatigue; Female; Gastrointestinal Diseases; Glucose; Heart Block; Humans; Lidocaine; Male; Middle Aged; Phenytoin; Poisoning; Potassium; Procainamide; Saliva; Tachycardia; Time Factors; Vision Disorders

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

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

Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting.. The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation.. The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite β-blocker or calcium channel blocker treatment.. Ivabradine 1 μM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 μM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10).. Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Ivabradine

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

Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF).. A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques.. New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF.. The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF.. http://www.clinicaltrials.gov. Identifier: NCT03718273.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiovascular Agents; Digoxin; Equivalence Trials as Topic; Heart Rate; Humans; Ivabradine; Treatment Outcome

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

Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously.. In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (<36 hours), symptomatic atrial fibrillation in the emergency department to be treated with a wait-and-see approach (delayed-cardioversion group) or early cardioversion. The wait-and-see approach involved initial treatment with rate-control medication only and delayed cardioversion if the atrial fibrillation did not resolve within 48 hours. The primary end point was the presence of sinus rhythm at 4 weeks. Noninferiority would be shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was more than -10.. The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively.. In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Electric Countershock; Emergency Service, Hospital; Female; Heart Rate; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Quality of Life; Recurrence; Time-to-Treatment; Treatment Outcome

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

Type 2 diabetes mellitus (T2DM) is a well-recognised risk factor for cardiovascular disease and the prevalence of atrial fibrillation (AF) is higher among patients with T2DM. Direct current cardioversion (DCCV) is an important management option in persistent AF. We sought to determine independent risk factors for immediate and short-term outcomes of DCCV for treatment of AF in patients with T2DM.. Retrospective outcome analysis of DCCV for persistent AF in 102 T2DM patients compared with 102 controls.. DCCV was successful in 68 (66.6%) people with T2DM compared to 86 (84.3%) in the control group (. T2DM, higher HbA1c, digoxin treatment, and structural and functional cardiac abnormalities are independent risk factors for immediate DCCV failure and AF relapse.

Topics: Aged; Atrial Fibrillation; Diabetes Complications; Diabetes Mellitus, Type 2; Digoxin; Electric Countershock; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke Volume

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

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

Results from the multicenter trial (J-Land study) of landiolol versus digoxin in atrial fibrillation (AF) and atrial flutter (AFL) patients with left ventricular (LV) dysfunction revealed that landiolol was more effective for controlling rapid HR than digoxin. The subgroup analysis for patient characteristics was conducted to evaluate the impact on the efficacy and safety of landiolol compared with digoxin.. Two hundred patients with AF/AFL, heart rate (HR) ≥ 120 beats/min, and LV ejection fraction (LVEF) 25-50% were randomized to receive either landiolol (n = 93) or digoxin (n = 107). Successful HR control was defined as ≥20% reduction in HR together with HR < 110 beats/min at 2 h after starting intravenous administration of landiolol or digoxin. The subgroup analysis for patient characteristics was to evaluate the impact on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunction.. The efficacy in patients with NYHA class III/NYHA class IV was 52.3%/35.3% in landiolol, and 13.8%/9.1% in digoxin (p < 0.001 and p = 0.172), lower LVEF (25-35%)/higher LVEF (35-50%) was 45.7%/51.1% in landiolol, and 14.0%/12.7% in digoxin (p < 0.001 and p < 0.001), CKD stage 1 (90 < eGFR)/CKD stage 2 (60 ≤ eGFR < 90)/CKD stage 3 (30 ≤ eGFR < 60)/CKD stage 4 (15 ≤ eGFR < 30) was 66.7%/59.1%/39.6%/66.7% in landiolol, and 0%/13.8%/17.0%/0% in digoxin (p = 0.003, p < 0.001, p = 0.015 and p = 0.040).. This subgroup analysis indicated that landiolol was more useful, regardless of patient characteristics, as compared with digoxin in AF/AFL patients complicated with LV dysfunction. Particularly, in patients with impaired renal function, landiolol should be preferred for the purpose of acute rate control of AF/AFL tachycardia.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Monitoring; Female; Heart Rate; Humans; Male; Middle Aged; Morpholines; Severity of Illness Index; Stroke Volume; Treatment Outcome; Urea; Ventricular Dysfunction, Left

The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation.. To assess the association of digoxin with cardiovascular (CV) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF: A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets.. The primary outcome was a composite of CV morbidity and mortality. Secondary outcomes included CV hospitalization and all-cause mortality or heart failure (HF) hospitalization. Of the 614 patients, 608 (99%) completed the dose-adjustment phase. Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up. The median follow-up period was 2.9 years (interquartile range 2.7-3.0 years).. In total, 284 patients (46.7%) used digoxin after the dose-adjustment phase (median dosage 0.250 mg; interquartile range 0.0625-0.750 mg). These patients were more often women, previously admitted for HF, had an increased left ventricular end-systolic diameter, and more often randomized to strict rate control. By using Cox proportional hazards regression analysis, the use of digoxin was not associated with an increased risk for the primary and secondary outcomes. For the primary outcome, the 3-year estimated cumulative incidence was 12.9% vs 13.4% in the digoxin group vs the no-digoxin group (unadjusted hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.62-1.52). Incidence was 19.4% vs. 19.5% for CV hospitalization (unadjusted HR 1.00; 95% CI 0.69-1.45) and 6.6% vs. 9.9% for all-cause mortality or HF hospitalization (unadjusted HR 0.62; 95% CI 0.34-1.13) in the digoxin group vs the no-digoxin group.. The use of digoxin was not associated with increased morbidity and mortality.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Rate; Humans; Male; Netherlands; Retrospective Studies; Survival Rate; Time Factors; Treatment Outcome

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

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

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cohort Studies; Digoxin; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Population Surveillance; Risk Factors; Stroke

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

We examined cognitive function in older hospitalised patients with chronic atrial fibrillation (AF).. A prospective substudy of a multicentre randomised trial of an AF-specific disease management intervention (the Standard versus Atrial Fibrillation spEcific managemenT studY; SAFETY).. Three tertiary referral hospitals within Australia.. A total of 260 patients with chronic AF: mean age 72±11 years, 53% men, mean CHA2DS2-VASc score 4±2.. Cognitive function was assessed at baseline (during inpatient stay) using the Montreal Cognitive Assessment (MoCA).. The extent of mild cognitive impairment (MCI-defined as a MoCA score <26) in AF patients and identification of independent predictors of MCI.. Overall, 169 patients (65%, 95% CI 59% to 71%) were found to have MCI at baseline (mean MoCA score 21±3). Multiple deficits in cognitive domains were identified, most notably in executive functioning, visuospatial abilities and short-term memory. Predictors of MCI (age and sex-adjusted) were lower education level (technical/trade school level OR 6.00, 95% CI 2.07 to 17.42; <8 years school education OR 5.29, 95% CI 1.95 to 14.36 vs 8-13 years), higher CHA2DS2-VASc score (OR 1.46, 95% CI 1.23 to 1.74) and prescribed digoxin (OR 2.19, 95% CI 1.17 to 4.10).. MCI is highly prevalent amongst typically older high-risk patients hospitalised with AF. Routine assessment of cognitive function with adjustment of clinical management is indicated for this patient group.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Attention; Australia; Cardiotonic Agents; Chronic Disease; Cognition; Cognitive Dysfunction; Digoxin; Educational Status; Executive Function; Female; Humans; Linear Models; Male; Memory, Short-Term; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Odds Ratio; Orientation; Prevalence; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Tertiary Care Centers

The aim of this study was to investigate the influence of rate control on quality of life (QOL).. The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation II) trial showed that lenient rate control is not inferior to strict rate control in terms of cardiovascular morbidity and mortality. The influence of stringency of rate control on QOL is unknown.. In RACE II, a total of 614 patients with permanent atrial fibrillation (AF) were randomized to lenient (resting heart rate [HR] <110 beats/min) or strict (resting HR <80 beats/min, HR during moderate exercise <110 beats/min) rate control. QOL was assessed in 437 patients using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) questionnaire, AF severity scale, and Multidimensional Fatigue Inventory-20 (MFI-20) at baseline, 1 year, and end of study. QOL changes were related to patient characteristics.. Median follow-up was 3 years. Mean age was 68 ± 8 years, and 66% were males. At the end of follow-up, all SF-36 subscales were comparable between both groups. The AF severity scale was similar at baseline and end of study. At baseline and at end of study there were no differences in the MFI-20 subscales between the 2 groups. Symptoms at baseline, younger age, and less severe underlying disease, rather than assigned therapy or heart rate, were associated with QOL improvements. Female sex and cardiovascular endpoints during the study were associated with worsening of QOL.. Stringency of heart rate control does not influence QOL. Instead, symptoms, sex, age, and severity of the underlying disease influence QOL. (Rate Control Efficacy in Permanent Atrial Fibrillation; NCT00392613).

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Calcium Channel Blockers; Cardiovascular Agents; Digoxin; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Quality of Life

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

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

To compare the clinical efficacy of intravenous diltiazem, digoxin, and amiodarone for acute ventricular rate (VR) control in patients with acute symptomatic atrial fibrillation (AF) necessitating hospitalization.. Randomized control trial.. Acute emergency medical admission unit in a regional teaching hospital in Hong Kong.. One hundred fifty adult patients with acute AF and rapid VR (>120 bpm).. Patients were randomly assigned in 1:1:1 ratio to receive intravenous diltiazem, digoxin, or amiodarone for VR control.. The primary end point was sustained VR control (<90 bpm) within 24 hours; the secondary end points included AF symptom improvement and length of hospitalization. At 24 hours, VR control was achieved in 119 of 150 patients (79%). The time to VR control was significantly shorter among patients in the diltiazem group (log-rank test, p < 0.0001) with the percentage of patients who achieved VR control being higher in the diltiazem group (90%) than the digoxin group (74%) and the amiodarone group (74%). The median time to VR control was significantly shorter in the diltiazem group (3 hours, 1-21 hours) compared with the digoxin (6 hours, 3-15 hours, p < 0.001) and amiodarone groups (7 hours, 1-18 hours, p = 0.003). Furthermore, patients in the diltiazem group persistently had the lowest mean VR after the first hour of drug administration compared with the other two groups (p < 0.05). The diltiazem group had the largest reduction in AF symptom frequency score and severity score (p < 0.0001). In addition, length of hospital stay was significantly shorter in the diltiazem group (3.9 +/- 1.6 days) compared with digoxin (4.7 +/- 2.1 days, p = 0.023) and amiodarone groups (4.7 +/- 2.2 days, p = 0.038).. As compared with digoxin and amiodarone, intravenous diltiazem was safe and effective in achieving VR control to improve symptoms and to reduce hospital stay in patients with acute AF.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cohort Studies; Digoxin; Diltiazem; Female; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Tachycardia, Ventricular; Treatment Outcome

A prospective, randomized study was conducted to evaluate the efficacy and tolerability of oral propafenone and quinidine for the conversion of paroxysmal atrial fibrillation (AF).. Eighty one consecutive patients (female/male 46/35; mean age 64.0 +/- 11.6), admitted to hospital with AF lasting no longer than 48 hours, were randomized in terms of their pharmacological therapy. Forty three patients (55%) were randomly assigned to Group I and received propafenone 600 mg orally as the initial therapy, with an additional dose of 300 mg after eight hours, if the sinus rhythm had not been restored by then. Thirty eight patients (45%) (Group II) received 1 mg digoxin IV followed by an oral loading of quinidine (400 mg followed by 200 mg every two hours).. The conversion rate assessed after 24 hours was the same in both groups (Gr. I vs. Gr. II: 90.7 vs. 91.4%), with the same number of mild side effects (Gr. I vs. Gr. II: 37.2% vs. 45.7%). No life-threatening adverse events were reported. Propafenone achieved a higher efficacy rate during the first eight hours (83.3 vs. 54.3%; p = 0.01), with a significantly shorter time required to sinus rhythm recovery throughout the study period, with a median time of 165 min (95% confidence interval 120-278) vs. 360 min (95% confidence interval 298-650; p < 0.05). There was some indication of greater effectiveness of propafenone than quinidine in early sinus rhythm restoration in patients with: no structural heart disease, in those with an AF duration shorter than 12 hours, and in patients with an ejection fraction > 55%.. Although both drugs revealed the same effectiveness, the conversion to sinus rhythm in the group treated with propafenone was observed more quickly despite the longer paroxysmal AF episode duration.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Digoxin; Drug Therapy, Combination; Electrocardiography, Ambulatory; Female; Heart Conduction System; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Propafenone; Prospective Studies; Quinidine; Recurrence; Time Factors; Treatment Outcome

Atrial fibrillation (AF) is a very common cardiac arrhythmia, and is associated with an increased mortality in patients with hypertension. Whether the best therapeutic approach for these patients is to restore sinus rhythm (SR) or to adequately control the ventricular rate is still controversial. The aim of this study is to compare both strategies in patients with hypertension.. Two hundred and twenty-one patients with hypertension and AF of duration >48 h were randomly assigned to either the rhythm (n=155) or rate (n=66) control group. Exercise capacity was improved in the rhythm control group in the 1st year of the study (p<0.0001). There were no statistically significant differences in the embolic event rate and the total mortality between the 2 groups at the end of the study (p=NS).. Although restoring and maintaining SR had a beneficial effect on exercise capacity in patients with hypertension and AF, no significant difference was found in terms of the total mortality and the embolic event rates. Thus, rate control is an acceptable primary strategy in patients with AF and hypertension.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Calcium Channel Blockers; Cardiotonic Agents; Digoxin; Electric Countershock; Female; Follow-Up Studies; Humans; Hypertension; Losartan; Male; Metoprolol; Middle Aged; Survival Analysis; Treatment Outcome; Verapamil

Atrial fibrillation (AF) remains a significant contributor to cardiovascular morbidity. Amiodarone is a potent antiarrhythmic drug. The safety and efficacy of oral versus intravenous (i.v.) Amiodarone in the treatment of AF of recent onset (duration <48 h) was investigated.. The study population consisted of 223 patients with symptomatic AF, of whom 110 received 600 mg oral Amiodarone (Group A) in three divided doses and 113 received i.v. Amiodarone (5 mg/kg over 30 min followed by 1000 mg over the next 24 h) (Group B). Digoxin was administered to all patients, who had not previously received it. All patients were monitored for 24 h.. Conversion to sinus rhythm occurred in 85.45% of group A and 82.30% in group B (p=NS). Mean time of cardioversion in group A was 20+/-4.5 h and in group B was 12+/-8 h (p<0,001). However, blood pressure (BP) in group A remained stable for the observation period, whereas it fell significantly in group B. Treatment was not discontinued in any of the patients in either group, however 13 patients in group B developed superficial phlebitis.. Both forms of the drug are extremely efficient in restoring sinus rhythm in AF of recent onset, although the i.v. form acts quicker. The oral form of the drug does not alter significantly the patients' BP.

Topics: Administration, Oral; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Digoxin; Electrocardiography; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Statistics, Nonparametric; Treatment Outcome

The aim of the present study was to compare the safety and efficacy of amiodarone and procainamide in the acute cardiology setting.. The study population consisted of 223 patients with symptomatic atrial fibrillation (AF). After administration of digoxin for ventricular rate control, all patients who failed to restore sinus rhythm (SR) were randomized into 2 groups: group A (113 patients) were administered 300 mg amiodarone intravenously over 30 min and, in case of failure to restore SR, amiodarone of 20 mg/kg/24 h was administered intravenously. Group B (110 patients) were intravenously administered a bolus dose of 1 gm procainamide, at an infusion rate 50/mg/min, and, in case of failure to restore SR, 2 mg/min for the next 24 h.. The rate of cardioversion to SR was similar between amiodarone (81.4%) and procainamide (82.7%) (P=NS). Procainamide loading recorded faster cardioversion times than amiodarone loading (P=0.02), but there was no significant difference after that. Amiodarone caused a significant decrease on systolic blood pressure compared to procainamide for the first 18 h (P<0.001), and a significant decrease in the diastolic blood pressure for the first 6 h (P<0.001). Side-effects for either medication were sparse. The only real prognostic factor for successful cardioversion remains the size of left atrium.. Both drugs were equally effective in restoring SR, though procainamide acts quicker in the loading phase. Both medications are safe and side effects develop only in the maintenance phase.

Topics: Acute Disease; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Digoxin; Drug Therapy, Combination; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Procainamide; Time Factors; Treatment Outcome

Amiodarone, given as intravenous bolus has not yet been studied in patients with atrial fibrillation and a high ventricular rate.. One hundred consecutive patients with atrial fibrillation and a ventricular rate above 135 bpm were randomized to receive either 450 mg amiodarone or 0.6 mg digoxin given as a single bolus through a peripheral venous access. If the ventricular rate exceeded 100 bpm after 30 min, another 300 mg amiodarone or 0.4 mg digoxin were added. Primary endpoints of the study were the ventricular rate and the occurrence of sinus rhythm after 30 and 60 min. Secondary endpoints were blood pressure during the first hour after drug administration, and safety regarding drug induced hypotension, and phlebitis at the infusion site.. Baseline heart rate was 144+/-19 in the amiodarone group and 145+/-15 in the digoxin group (p=0.72). Following amiodarone, heart rate was 104+/-25 after 30 min compared to 116+/-23 in the digoxin group (p=0.02) and 94+/-22 versus 105+/-22 after 60 min (p=0.03). After 30 min, sinus rhythm was documented in 14 (28%) patients following amiodarone compared to 3 (6%) patients in the digoxin group (p=0.003), and after 60 min in 21 (42%) versus 9 (18%) patients (p=0.012). Asymptomatic hypotension was observed in 4 amiodarone treated patients, and superficial phlebitis in 1 patient.. Amiodarone, given as an intravenous bolus is relatively safe and more effective than digoxin for heart rate control and conversion to sinus rhythm in patients with atrial fibrillation and a rapid ventricular rate.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Female; Heart Rate; Heart Ventricles; Humans; Infusions, Intravenous; Male

The VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by verapamil, decrease intractability of AF.. Rhythm control is desirable in patients suffering from symptomatic AF.. A total of 144 patients with persistent AF were included. Seventy-four (51%) patients were randomized to the acute (within 24 h) and 70 (49%) patients to the routine serial ECVs, and 74 (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control before ECV and continued during follow-up (2 x 2 factorial design). Class III antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months.. At baseline, there were no significant differences between the groups, except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%, respectively, p = 0.01). At follow-up, no difference in the occurrence of permanent AF between the acute and the routine cardioversion groups was observed (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44], respectively, p = NS), and also no difference between the verapamil- and the digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48] respectively, p = NS). Multivariate Cox regression analysis revealed that lone digoxin use was the only significant predictor of failure of rhythm control treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02).. An acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy. Furthermore, verapamil has no beneficial effect in a serial cardioversion strategy.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium; Digoxin; Electric Countershock; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Recurrence; Thromboembolism; Treatment Outcome; Verapamil

Aim of the study was to investigate mechanisms of amiodarone action on atrial and ventricular rhythm during persistent atrial fibrillation (PAF), and to assess efficacy of amiodarone as monotherapy or in combination with digoxin. Holter ECG monitoring and registration of high resolution ECG with construction of periodograms of ff waves and histograms of RR intervals (MATLAB 5.3 environment) were carried out in 34 patients (mean age 63.1+/-11.0 years) with PAF. Amiodarone (550.0+/-143.4 mg/day), digoxin (0.30+/-0.09 mg/day) with amiodarone (571.4+/-106.9 mg/day) were given for 21 days with recordings of high resolution ECG at baseline and on day 21. Long term therapy (1.7 years) with combination of digoxin 0.19+/- 0.07 mg/day) and amiodarone (254+/-82.0 mg/day) was controlled by Holter ECG monitoring. Monotherapy with amiodarone was not associated with significant lowering of heart rate (HR) (small er, Cyrillic=0.054) because of complex effect of amiodarone of HR: significant increase of period of ff waves (by 0.031+/-0.011 s), with facilitation of their conduction to ventricles combined with significant 0.10+/-0.08 s increment of minimal RR. Amiodarone combined with digoxin caused significantly lesser (by 0.009+/-0.017 s) enlargement of ff waves and significant lowering of HR (by 21.24+/-15.77 bpm) at the account of slowing of AV conduction (minimal RR increased by 0.12+/-0.08 s) and suppression of early RR peaks (0.28-0.46 s). The combination effectively suppressed tachysystolia resistant to other therapy (maximal HR 170-215 bpm) with significant lowering of mean (by 16.5+/-13.1 bpm) and maximal (by 43.3+/-35.6 s) HR, with suppression of ventricular extrasystoles in 83% of patients, and without significant lowering of minimal HR and appearance of pauses from 3 s. Level of thyrotrophic hormone rose from 2.4 to 5/9 IU/ml (p >0.05).

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Middle Aged; Severity of Illness Index; Ventricular Function

Amiodarone and sotalol are commonly used for the maintenance of sinus rhythm, but the efficacy of these agents administered as high-dose infusions for rapid conversion of atrial fibrillation is unknown. Use in this context would facilitate drug initiation in patients in whom ongoing prophylactic therapy is indicated.. We assessed the efficacy and safety of rapid high-dose intravenous infusions of amiodarone and sotalol for heart rate control and rapid reversion to sinus rhythm in patients who came to the emergency department with recent-onset symptomatic atrial fibrillation. Patients (n = 140) were randomized to receive 1.5mg/kg of sotalol infused in 10 minutes, 10mg/kg of amiodarone in 30 minutes, or 500 microg of digoxin in 20 minutes. Electrical cardioversion was attempted for patients not converting to sinus rhythm within 12 hours.. The rapid infusion of sotalol or amiodarone resulted in more rapid rate control than digoxin. Each of the 3 trial strategies resulted in similar rates of pharmacological conversion to sinus rhythm (amiodarone, 51%; sotalol, 44%; digoxin, 50%; P = not significant). The overall rates of cardioversion after trial drug infusion and defibrillation were high for all groups (amiodarone, 94%; sotalol, 95%,; digoxin, 98%; P = not significant), but there was a trend toward a higher incidence of serious adverse reactions in the amiodarone group.. The rapid infusion of sotalol or amiodarone in patients with symptomatic recent-onset atrial fibrillation results in rapid control of ventricular rate. Even with high-dose rapid infusions, all 3 agents are associated with a poor overall reversion rate within 12 hours. Almost all patients were returned to sinus rhythm with a combination of pharmacological therapy and electrical cardioversion.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Humans; Infusions, Intravenous; Linear Models; Male; Middle Aged; Sotalol; Statistics, Nonparametric

The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time.. Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model.. Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Combined Modality Therapy; Comorbidity; Digoxin; Electric Countershock; Follow-Up Studies; Heart Rate; Humans; Models, Cardiovascular; Myocardial Contraction; Phenethylamines; Proportional Hazards Models; Retrospective Studies; Risk; Stroke; Sulfonamides; Survival Analysis; Treatment Failure; Treatment Outcome; Warfarin

We sought to evaluate approaches used to control rate, the effectiveness of rate control, and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.. The AFFIRM study showed that atrial fibrillation (AF) can be treated effectively with rate control and anticoagulation, but drug efficacy to control rate remains uncertain.. Patients (n = 2,027) randomized to rate control in the AFFIRM study were given rate-controlling drugs by their treating physicians. Standardized rate-control efficacy criteria developed a priori included resting heart rate and 6-min walk tests and/or ambulatory electrocardiographic results.. Average follow-up was 3.5 +/- 1.3 years. Initial treatment included a beta-adrenergic blocker (beta-blocker) alone in 24%, a calcium channel blocker alone in 17%, digoxin alone in 16%, a beta-blocker and digoxin in 14%, or a calcium channel blocker and digoxin in 14% of patients. Overall rate control was achieved in 70% of patients given beta-blockers as the first drug (with or without digoxin), 54% with calcium channel blockers (with or without digoxin), and 58% with digoxin alone. Adequate overall rate control was achieved in 58% of patients with the first drug or combination. Multivariate analysis revealed an association between first drug class and several clinical variables. There were more changes to beta-blockers than to the other two-drug classes (p < 0.0001).. Rate control in AF is possible in the majority of patients with AF. Beta-blockers were the most effective drugs. To achieve the goal of adequate rate control in all patients, frequent medication changes and drug combinations were needed.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Catheter Ablation; Digoxin; Drug Therapy, Combination; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Multivariate Analysis; Pacemaker, Artificial; Stroke Volume; Treatment Outcome

To evaluate prospectively the effects of pretreatment with verapamil on the maintenance of sinus rhythm after direct current (DC) cardioversion.. Randomised, active control, open label, parallel group comparison of verapamil versus digoxin.. Multicentre study in three teaching and three non-teaching hospitals in Sweden.. 100 consecutive patients with atrial fibrillation (AF) of at least four weeks' duration and indications for cardioversion were assigned randomly to two groups, one treated with verapamil (verapamil group) and the other with digoxin (digoxin group) before cardioversion. Fifty patients were assigned randomly to each treatment arm. After dropout of four patients from the digoxin group and seven patients from the verapamil group, data obtained from 89 patients were analysed.. After randomly assigned pretreatment with either verapamil or digoxin for four weeks, DC cardioversion was performed. If sinus rhythm was restored then verapamil treatment was discontinued.. The rate of AF recurrence was assessed one, four, eight, and 12 weeks after cardioversion.. 6 patients in the verapamil treated group and none in the digoxin treated group reverted to sinus rhythm spontaneously (p < 0.05). DC cardioversion restored sinus rhythm in 24 of 37 (65%) patients in the verapamil group and 41 of 46 patients (89%) in the digoxin group (p < 0.05). After 12 weeks' follow up 28% (13 of 46) of digoxin pretreated patients versus 9% (four of 43) of verapamil pretreated patients remained in sinus rhythm (p < 0.05).. Pretreatment with verapamil alone does not improve maintenance of sinus rhythm after DC cardioversion in patients with AF. The rate of spontaneous cardioversion may be improved by verapamil.

Topics: Administration, Oral; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Humans; Male; Treatment Outcome; Verapamil

Atrial fibrillation is commonly treated with intravenously administered digoxin. The main objective of this study was to investigate the relationship between plasma concentration of digoxin and heart rate.. Plasma concentrations of digoxin were analysed in 105 patients allocated to digoxin therapy in the Digitalis in Acute Atrial Fibrillation (DAAF) trial. A pharmacokinetic/pharmacodynamic (PK/PD) model for the relationship among digoxin dose, plasma concentration and heart rate in patients remaining in atrial fibrillation was constructed using non-linear, mixed-effect modelling. One hundred and twenty-two placebo-treated patients were included as a control group. In 56 patients, one late sample at 16 h after the first dose of digoxin was obtained while in 49 patients an early sample at 0.25-0.5 h and a late sample 16 h after the first dose were obtained. Heart rate was measured at 0, 2, 6, 12 and 16 h after inclusion, with data from 98, 89, 67, 56 and 53 patients available at each time point, respectively.. A two-compartment model best described the time course of digoxin concentrations in plasma. Digoxin and creatinine clearance correlated strongly and mean plasma concentration of digoxin at 16 h was within recommended levels (1.6+/-1.0 nM). The decrease in heart rate in placebo-treated patients was, on average, 0.5 beats/min (bpm) per hour. In patients on digoxin, a linear relationship between the estimated digoxin concentration at the effect site and the drop-in heart rate was found. The half-life for the digoxin distribution to the effect compartment was approximately 3.8 h. The degree of reduction was related to the initial heart rate and patients with higher heart rate had a more pronounced decrease. The model predicted that a digoxin concentration of 1 nM at the effect site reduces heart rate by 9.4%.. A PK/PD model for the relationship between the plasma concentration of digoxin, the estimated concentration at the effect site and the reduction in heart rate during atrial fibrillation could be defined using a population pharmacokinetic approach. Our data indicate that a more aggressive dosing regimen of digoxin may be more effective in terms of heart rate reduction.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Half-Life; Heart Rate; Humans; Injections, Intravenous; Linear Models; Middle Aged; Time Factors

The relation between heart rate and left ventricular function during rate control in atrial fibrillation is incompletely understood.. Twenty-four patients (age 67 +/- 11 years) with symptomatic recent onset rapid atrial fibrillation and rapid ventricular rate (> 110 bpm) were randomly assigned to receive either intravenous digoxin (13 mcg/kg) or intravenous diltiazem (0.25 mg/kg bolus plus a maintenance infusion). A portable radionuclide detector was used to collect validated measures of relative left ventricular volumes, along with heart rate data, every 15 seconds for 6 hours.. Heart rate decreased significantly at 15 minutes and 180 minutes in the diltiazem group (from 133 +/- 18 bpm to 111 +/- 26 bpm [P <.01] to 94 +/- 24 bpm [P <.001]) but not in the digoxin group (from 129 +/- 18 bpm to 126 +/- 17 bpm [P = NS] to 118 +/- 15 bpm [P = NS]). Left ventricular ejection fraction improved in both groups to a similar extent (from 39 +/- 10% to 50 +/- 8%, [P <.05] after diltiazem, and from 38 +/- 8% to 52 +/- 11% [P <.05] after digoxin at baseline vs 180 minutes, respectively). The ejection fraction vs heart rate slope was steeper in the digoxin group than in the diltiazem group (-0.34 +/- 0.18 vs -0.16 +/- 0.17, P =.048) indicating a more pronounced improvement in ejection fraction per unit decrease in heart rate.. In patients with acute atrial fibrillation, digoxin led to similar improvements in ejection fraction compared to diltiazem despite a slower and less potent heart rate slowing.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Cardiac Output; Digoxin; Diltiazem; Female; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Single-Blind Method; Stroke Volume; Time Factors

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

The most frequent arrhythmia after coronary artery bypass surgery is atrial fibrillation (AF). The prevention and treatment of this type of arrhythmia is subobtimal. Digitalis, beta-blockers, diltiazem and amiodarone are the preferred drugs for the treatment. This study was designed to compare the effects of preoperatively started digitalis and atenolol in combination and separately, on the incidence of AF that occurs within 7 days following the operation.. One-hundred and sixty patients who had similar demographic properties were randomly grouped as group I, that preoperatively received combined drug therapy (n=40), group II preoperatively used digitalis (n=40), group III atenolol (n=40), and group IV was the control group (n=40).. Postoperative AF incidence was 25, 15,4, and 17,9% in groups IV, III, and II, respectively, whereas it was 5% in group I which was lower than all other groups, but the difference was only significant between groups I and IV (P=0.012).. The combined use of atenolol and digitalis preoperatively was considered as an efficient treatment for lowering the incidence of AF following coronary artery bypass surgery.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Anti-Arrhythmia Agents; Atenolol; Atrial Fibrillation; Coronary Artery Bypass; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Postoperative Complications; Premedication

The aim of this prospective, randomized study was to determine the efficacy of a serial external electrical cardioversion strategy in maintaining sinus rhythm after 12 months in patients with recurrent persistent atrial fibrillation.. Ninety patients with persistent atrial fibrillation lasting more than 72 h but less than 1 year were randomized in a one to one fashion to repetition of up to two electrical cardioversions in the event of relapse of atrial fibrillation detected within 1 month of the previous electrical cardioversion (Group AGG), or to non-treatment of atrial fibrillation relapse (Group CTL). ECGs were scheduled at 6 h, 7 days, and 1 month. Clinical examination and ECGs were repeated during the 6-month and 12-month follow-up examinations. Echocardiography was repeated during the 6-month follow-up examination. Clinical and echocardiographic characteristics were similar in the two groups. All patients were treated with antiarrhythmic drugs before electrical cardioversion and throughout follow-up. After 12 months, sinus rhythm was maintained in 53% of Group AGG patients and in 29% of Group CTL patients (P<0.03). After 6 months, left ventricular ejection fraction had recovered significantly only in Group AGG (56.8 +/- 9.0% at enrollment vs 60.4 +/- 9.4% at 6 months,P <0.001).. These results demonstrate that an aggressive policy towards persistent atrial fibrillation by means of repetition of electrical cardioversion after early atrial fibrillation recurrence is useful in maintaining sinus rhythm after 12 months.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cross-Over Studies; Digoxin; Echocardiography; Electric Countershock; Electrocardiography; Female; Follow-Up Studies; Humans; Incidence; Italy; Male; Middle Aged; Prospective Studies; Recurrence; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

This prospective randomized study aims at evaluation and comparison of the prophylactic effects of amiodarone versus digoxin and metoprolol combination in postcoronary bypass atrial fibrillation.. A total of 241 consecutive patients undergoing elective coronary artery bypass grafting were randomly allocated into three groups. Patients in Group1 (n=77) received metoprolol 100 mg/24 h per oral (P.O.), preoperatively, 2x0.5 mg digoxin intravenously on the operating day and digoxin 0.25 mg P.O.+metoprolol 100 mg P.O. on the first postoperative day until discharge. Patients in Group 2 (n=72) received totally 1200 mg intravenous/24 h amiodarone which the 300 mg - bolus dose/1 h was given as soon as the operation had been finished. On the next day patients were administered 450 mg/24 h amiodarone i.v. and 600 mg/day in three doses P.O. were given until discharge. Group 3 (n=92) was the control group with no antiarrhythmic prophylaxis.. Preoperative patient characteristics and operative parameters were similar in three groups. Atrial fibrillation occurred in 13 patients (16.8%) in Group 1, six patients (8.3%) in Group 2 and 31 patients (33.6%) in Group 3.. Both study groups were effective in the prevention of postcoronary bypass atrial fibrillation with respect to control (P<0.01 in Group 1 and P<0.001 in Group 2).

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Bypass; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Metoprolol; Middle Aged; Postoperative Complications; Prospective Studies

A multicenter, placebo-controlled, randomized, double-blind trial compared the preventive effect of aprindine and digoxin on the recurrence of atrial fibrillation (AF) with placebo, and also compare the effectiveness of these 2 drugs in the prevention of AF. Patients with symptomatic paroxysmal or persistent AF who had converted to sinus rhythm (SR) were randomly assigned aprindine (40 mg/day), digoxin (0.25 mg/day) or placebo and followed up on an outpatient basis every 2 weeks for 6 months. Of the 141 patients from 36 participating centers, 47 were given aprindine, 47 digoxin, and 47 were on placebo. After the 6-month follow-up, the Kaplan-Meier estimates of the percentage of patients remaining free of recurrent symptomatic AF on aprindine, digoxin and placebo were 33.3%, 29.2% and 21.5%, respectively. In patients remaining in SR for 15 days after from the start of follow-up, freedom from recurrence was significantly more prevalent in the aprindine group than in the placebo group (p=0.0414), but there was no significant difference between the digoxin and placebo groups. The rate of adverse events was similar in the 3 groups. In conclusion, neither aprindine nor digoxin had a significant effect on preventing relapse of symptomatic AF; however, recurrence of AF occurred later with aprindine than with placebo or digoxin.

Topics: Aged; Anti-Arrhythmia Agents; Aprindine; Atrial Fibrillation; Coronary Disease; Diabetic Angiopathies; Digoxin; Double-Blind Method; Electric Countershock; Female; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Placebos; Safety; Time Factors

To analyze the efficacy of an IV combination of diltiazem and digoxin vs IV diltiazem alone for acute ventricular rate control in patients with atrial fibrillation.. Prospective, randomized, open-label study.. Fifty-two patients with atrial fibrillation and uncontrolled ventricular rates were randomized to receive either an IV combination of diltiazem and digoxin or IV diltiazem alone and were observed for 12 h. The successful rate control was defined as a ventricular rate < 100 beats per minute (bpm) persisting for 1 h or conversion to sinus rhythm. The loss of rate control was defined as an increase in the ventricular rate to > 100 bpm persistently for > 30 min or rebound to atrial fibrillation.. In both treatment arms (n = 26 each), all patients achieved successful and comparable ventricular rate control at 12 h. The mean (+/- SD) time taken to achieve successful rate control was shorter in the combination arm (15 +/- 16 vs. 22 +/- 22 min). Six patients in the combination arm and 11 in the diltiazem-alone arm experienced episodes of loss of rate control. This loss in the combination arm was less than that in the diltiazem-alone arm (14 vs 39 episodes; p = 0.05). The loss of rate control per patient in the combination arm was also less than that in the diltiazem-alone arm (2.0 +/- 1.0 vs. 3.5 +/- 1.9 episodes per patient; p = 0.04).. This study demonstrates that in patients with atrial fibrillation who have a rapid ventricular response, the IV combination of diltiazem and digoxin results in a more efficacious ventricular rate control with fewer fluctuations than that achieved by therapy with IV diltiazem alone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Agents; Digoxin; Diltiazem; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Prospective Studies

To compare the effects of sotalol and metoprolol on heart rate, during isotonic (ITE) and isometric (IME) exercise and daily activities, in digitalized patients with chronic atrial fibrillation.. The study had a randomized, single-blinded, crossover design. Twenty-three patients with chronic atrial fibrillation received placebo for 4 weeks, followed by a 4-week period of treatment with sotalol and metoprolol in random order. At the end of each period, the patients were assessed with 24-h ECG monitoring, a cardiopulmonary exercise test and a handgrip manoeuvre. Both agents produced a lower heart rate than placebo at rest and at all levels of isotonic exercise (P < 0.001) without affecting oxygen uptake. Sotalol produced a lower heart rate than metoprolol only at submaximal exercise (116 +/- 9 bpm for sotalol vs 125 +/- 11 bpm for metoprolol, P < 0.001). During isometric exercise, sotalol produced a lower maximum heart rate than did metoprolol (113 +/- 22 vs 129 +/- 18 bpm, respectively). Both agents produced a lower mean heart rate than placebo over 24 h (P < 0.001 for all), while sotalol produced a lower mean heart rate than metoprolol during the daytime (P < 0.01).. Sotalol is a safe and effective agent for control of heart rate in digitalized patients with atrial fibrillation. Sotalol is superior to metoprolol at submaximal exercise, resulting in better rate control during daily activities.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Cross-Over Studies; Digoxin; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Heart Ventricles; Humans; Male; Metoprolol; Middle Aged; Single-Blind Method; Sotalol

Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV). The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing) for maintenance of sinus rhythm after ECV.. Ninety-seven patients with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for 1 month before and 1 month after ECV. The first month after ECV, patients recorded heart rhythm using daily transtelephonic monitoring. No additional antiarrhythmic drugs were given. Of the 97 patients, 43 patients (20 verapamil) underwent ECV per protocol. Median previous AF duration was 18 and 26 days for verapamil and digoxin, respectively. There were no differences in atrial dimensions and underlying heart disease between the two groups. The success rate of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had recurrence of AF. Median time to recurrence was 5 days (range 0 to 26) versus 8 days (range 2 to 28) (P = NS), respectively.. Stand-alone intracellular calcium lowering by verapamil around ECV does not enhance cardioversion outcome.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium; Calcium Channel Blockers; Digoxin; Electric Countershock; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Verapamil

The role of digoxin and verapamil in the control of ventricular response in rapid atrial fibrillation is well established. This study investigates how clonidine compares with these standard therapies in rate control for new-onset rapid atrial fibrillation. We set out to test the hypothesis that clonidine effectively reduces heart rate in patients with new-onset rapid atrial fibrillation.. Forty patients were seen in the emergency department with new-onset (< or =24 hours' duration), stable, rapid atrial fibrillation. Eligible patients were randomized to receive either clonidine, digoxin, or verapamil. Changes in heart rate and blood pressure over 6 hours, as well as frequency of conversion to sinus rhythm were recorded and analyzed.. The mean reduction in heart rate over 6 hours was 44.4 beats/min (95% confidence interval [CI] 28.4-60.4 beats/min) in the clonidine group, 52.1 beats/min (95% CI 40.8-63.4 beats/min) in the digoxin group, and 41.8 beats/min (95% CI 22.5-61.0 beats/min) in the verapamil group. Analysis of variance of the heart rate changes in the 3 groups after 6 hours was not significant (P =.55). At 6 hours, 7 of 12 clonidine patients, 8 of 15 digoxin patients, and 7 of 13 verapamil patients remained in atrial fibrillation (P =.962 on chi(2)).. Clonidine controls ventricular rate in new-onset atrial fibrillation with an efficacy comparable to that of standard agents.

Topics: Acute Disease; Administration, Oral; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Clonidine; Digoxin; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Prospective Studies; Treatment Outcome; Verapamil

A prospective, randomized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone (active treatment) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours.. We prospectively randomly assigned 120 patients with atrial fibrillation of less than 24 hours' duration to treatment with sotalol, amiodarone, or digoxin using a single intravenous dose followed by 48 hours of oral treatment. Patients had ECG monitoring for 48 hours, and time of reversion, adequacy of rate control, and numbers of adverse events were compared. After 48 hours, those still in atrial fibrillation underwent cardioversion according to a standardized protocol. After 48 hours of therapy and attempted cardioversion, the number of patients whose rhythms had successfully reverted were compared.. There was a significant reduction in the time to reversion with both sotalol (13. 0+/-2.5 hours, P <.01) and amiodarone (18.1+/-2.9 hours, P <.05) treatment compared with digoxin only (26.9+/-3.4 hours). By 48 hours, the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group (95% versus 78%, P <.05; risk ratio 5.4, 95% confidence interval [CI] 1.5 to 19.2 ). In those patients whose rhythms did not revert to sinus rhythm, there was superior ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin. There were also fewer adverse events in the active treatment group compared with the rate control group.. Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs (sotalol or amiodarone) improves complication-free 48-hour reversion rates compared with rate control with digoxin.

Topics: Aged; Algorithms; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digoxin; Electric Countershock; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Prospective Studies; Sotalol

Atrial fibrillation (AF) shortens the atrial effective refractory period (ERP) and predisposes to further episodes of AF. The acute changes in atrial refractoriness may be related to tachycardia-induced intracellular calcium overload. The purpose of this study was to determine whether digoxin, which increases intracellular calcium, potentiates the acute effects of AF on atrial refractoriness in humans.. In 38 healthy adults, atrial ERP was measured at basic drive cycle lengths (BDCLs) of 350 and 500 ms after autonomic blockade. Nineteen patients had been treated with digoxin for 2 weeks. After a several-minute episode of AF, atrial ERP was measured serially at alternating BDCLs. Compared with pre-AF ERPs, the first post-AF ERPs were significantly shorter in both the digoxin and the control groups (P:<0.001). The post-AF ERP at a BDCL of 350 ms shortened to a greater degree in the digoxin group (37+/-16 ms) than in the control group (20+/-13 ms, P:<0.001); similar changes occurred at a BDCL of 500 ms. During post-AF determinations of the atrial ERP, secondary AF episodes occurred significantly more often in the digoxin group (32% versus 16%; P:<0. 04).. After a brief episode of AF, digoxin augments the shortening that occurs in atrial refractoriness and predisposes to the reinduction of AF. These effects occur in the setting of autonomic blockade and therefore are more likely to be due to the effects of digoxin on intracellular calcium than to its vagotonic effects.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Adult; Atrial Fibrillation; Calcium; Cardiac Pacing, Artificial; Cardiotonic Agents; Digoxin; Electrocardiography; Female; Heart Atria; Heart Rate; Humans; Infusions, Intravenous; Intracellular Fluid; Male; Parasympatholytics; Reaction Time; Tachycardia, Supraventricular; Tachycardia, Ventricular

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Sotalol; Treatment Outcome

Atrial fibrillation remains a frequent complication after heart surgery. The optimal strategy to treat the condition has not been established. Several retrospective studies have suggested that a primary rate-control strategy may be equivalent to a strategy that restores sinus rhythm.. Fifty patients with atrial fibrillation after heart surgery were randomly assigned to a strategy of antiarrhythmic therapy with or without electrical cardioversion or ventricular rate control. Both arms received anticoagulation with heparin overlapped with warfarin. The primary end point was time to conversion to sinus rhythm analyzed by the Kaplan-Meier method. Atrial fibrillation relapse after the initial conversion was monitored in the hospital over a 2-month period.. There was no significant difference between an antiarrhythmic conversion strategy (n = 27) and a rate-control strategy (n = 23) in time to conversion to sinus rhythm (11.2 +/- 3. 2 vs 11.8 +/- 3.9 hours; P =.8). With the use of Cox multivariate analysis to control for the effects of age, sex, beta-blocker usage, and type of surgery, the antiarrhythmic strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P =.08). The length of hospital stay was reduced in the antiarrhythmic arm compared with the rate-control strategy (9.0 +/- 0.7 vs 13.2 +/- 2.0 days; P =.05). In-hospital relapse rates in the antiarrhythmic arm were 30% compared with 57% in the rate-control strategy (P =.24). There were no significant difference in relapse rates at 1 week (24% vs 28%), 4 weeks (6% vs 12%), and 6 to 8 weeks (4% vs 9%). At the end of the study, 91% of the patients in the rate-control arm were in sinus rhythm compared with 96% in the antiarrhythmic arm (P =.6).. This pilot study shows little difference between a rate-control strategy and a strategy to restore sinus rhythm. Regardless of strategy, most patients will be in sinus rhythm after 2 months. A larger randomized, controlled study is needed to assess the impact of restoration of sinus rhythm on length of stay.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Surgical Procedures; Digoxin; Drug Administration Routes; Electric Countershock; Electrocardiography; Female; Heart Rate; Humans; Length of Stay; Male; Pilot Projects; Procainamide; Prognosis; Propafenone; Prospective Studies; Recurrence; Sotalol

We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate (VR) in patients with chronic atrial fibrillation (CAF).. Systematic comparison of standardized drug regimens on 24 h VR control in CAF have not been reported.. In 12 patients (11 male, 69+/-6 yr) with CAF, the effects on VR by 5 standardized daily regimens: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 4) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol; were studied after 2 week treatment assigned in random order. The VR data were analyzed by ANOVA with repeated measures. The circadian phase differences were evaluated by cosinor analysis.. The 24-h mean (+/-SD) values of VR (bpm) were - digoxin: 78.9 +/- 16.3, diltiazem: 80.0+/-15.5, atenolol: 75.9+/-11.7, digoxin + diltiazem: 67.3+/-14.1 and digoxin + atenolol: 65.0+/-9.4. Circadian patterns were significant in each treatment group (p < 0.001). The VR on digoxin + atenolol was significantly lower than that on digoxin (p < 0.0001), diltiazem (p < 0.0002) and atenolol (p < 0.001). The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol (p < 0.03). During exercise, digoxin and digoxin + atenolol treatments resulted in the highest and lowest mean VR respectively. The exercise Time-VR plots of all groups were nearly parallel (p = ns). The exercise duration was similar in all treatment groups (p = ns).. This study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF.

Topics: Aged; Anti-Arrhythmia Agents; Atenolol; Atrial Fibrillation; Calcium Channel Blockers; Circadian Rhythm; Cross-Over Studies; Digoxin; Diltiazem; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise; Female; Follow-Up Studies; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged

Studies of healthy volunteers or patients in sinus rhythm have indicated that treatment with digoxin produces characteristic changes in the electrocardiogram (ECG). No randomized, placebo-controlled studies are available and no study has investigated the effect on ECG in patients with atrial fibrillation.. In a substudy to a trial comparing the therapeutic effect of intravenously administered digoxin with placebo in patients with acute atrial fibrillation, we investigated these effects as well as the relation between ECG changes and serum concentration of digoxin.. In all, 167 patients were included. Standard ECGs recorded at baseline, and at 2, 6, 12, and 16 h after randomization were digitized, and changes in RR-intervals, QRS width, ST-segment amplitude at 60 ms after the J point, T-wave amplitude, and QTc interval were calculated. Furthermore, the correlation between the serum concentration of digoxin at 16 h after inclusion and changes on the ECG was analyzed.. Compared with placebo, digoxin resulted in an increase in RR-interval (p < 0.0001), a decrease in ST-segment and T-wave amplitude (p = 0.009 and p = 0.002, respectively), and in the QTc interval (p = 0.01). These changes were present 2 h after the first dose, but were more pronounced after 16 h. There was no significant correlation between serum concentration of digoxin and ECG changes at 16 h.. Compared with placebo, digoxin produces significant changes on ECG in patients with acute atrial fibrillation. The changes are in accordance with previous findings in individuals in sinus rhythm. There was no correlation between serum concentration of digoxin and ECG changes.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Prospective Studies; Signal Processing, Computer-Assisted; Treatment Outcome

Digoxin is commonly prescribed in symptomatic paroxysmal atrial fibrillation (AF) but has never been evaluated in this condition.. From a multicenter registry, 43 representative patients with frequent symptomatic AF episodes were recruited into a randomized, double-blind crossover comparison of digoxin (serum concentration, 1.29+/-0.35 nmol/L) and placebo. The study end point was the occurrence of 2 AF episodes (documented by patient-activated monitors), censored at 61 days. The median time to 2 episodes was 13.5 days on placebo and 18.7 days on digoxin (P<0. 05). The relative risk (95% CI) of 2 episodes (placebo:digoxin) was 2.19 (1.07 to 4.50). A similar effect was seen on the median time to 1 episode: increased from 3.5 to 5.4 days (P<0.05), relative risk 1. 69 (0.88 to 3.24). The mean+/-SD ventricular rates during AF recordings during placebo and digoxin treatment were 138+/-32 and 125+/-35 bpm, respectively (P<0.01). Twenty-four-hour ambulatory ECG recordings did not show significant differences in the frequency or duration of AF or in ventricular rate.. Digoxin reduces the frequency of symptomatic AF episodes. However, the estimated effect is small and may be due to a reduction in the ventricular rate or irregularity rather than an antiarrhythmic action.

Topics: Ambulatory Care; Anti-Arrhythmia Agents; Atrial Fibrillation; Cross-Over Studies; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Humans; Male; Middle Aged; Placebos; Tachycardia, Paroxysmal; Treatment Failure

Functional refraction of atrio-ventricular node and the phenomenon of concealed conduction are basic factors which determine the frequency of ventricular beats as well as the duration of R-R intervals in atrial fibrillation. R-R intervals may be ordered according to their size and presented graphically in the form of histograms. The morphology of histograms depends on the ability of A-V node. Digoxin influences the morphology of histograms of R-R intervals, which may have a diagnostic value and become a therapeutic indicator. The purpose of the study was to evaluate the correlation between the morphology of histograms and digoxin serum concentration, as well as the clinical treatment with digoxin. In the study a classification was used which divided R-R intervals into 4 types and several sub-types. The study covers 91 patients treated with digoxin upon whom 161 histograms were made. Two groups of patients were studied: A-patients in whom digoxin concentration was determined, B-patients in whom treatment with digoxin was evaluated on the basis of their clinical condition. The study confirmed a hypothesis that treatment with digoxin causes specific changes in the statistical distribution of R-R intervals even though no strict correlation was found between the direction of these changes and the digoxin serum concentration. The dependence, however, was observed between histograms of R-R intervals in atrial fibrillation and the clinical course of treatment with digoxin.

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Humans; Middle Aged; Retrospective Studies; Statistical Distributions; Treatment Outcome

Atrial fibrillation (AF) after coronary bypass graft surgery may result in hypotension, heart failure symptoms, embolic complications, and prolongation in length of hospital stay (LOHS). The purpose of this study was to determine whether intravenous diltiazem is more effective than digoxin for ventricular rate control in AF after coronary artery bypass graft surgery. A secondary end point was to determine whether ventricular rate control with diltiazem reduces postoperative LOHS compared with digoxin.. Patients with AF and ventricular rate > 100 beats/min within 7 days after coronary artery bypass graft surgery were randomly assigned to receive intravenous therapy with diltiazem (n = 20) or digoxin (n = 20). Efficacy was measured with ambulatory electrocardiography (Holter monitoring). Safety was assessed by clinical monitoring and electrocardiographic recording. LOHS was measured from the day of surgery. Data were analyzed with the intention-to-treat principle in all randomly assigned patients. In addition, a separate intention-to-treat analysis was performed excluding patients who spontaneously converted to sinus rhythm. In the analysis of all randomly assigned patients, those who received diltiazem achieved ventricular rate control (> or = 20% decrease in pretreatment ventricular rate) in a mean of 10 +/- 20 (median 2) minutes compared with 352 +/- 312 (median 228) minutes for patients who received digoxin (p < 0.0001). At 2 hours, the proportion of patients who achieved rate control was significantly higher in patients treated with diltiazem (75% vs 35%, p = 0.03). Similarly, at 6 hours, the response rate associated with diltiazem was higher than that in the digoxin group (85% vs 45%, p = 0.02). However, response rates associated with diltiazem and digoxin at 12 and 24 hours were not significantly different. At 24 hours, conversion to sinus rhythm had occurred in 11 of 20 (55%) patients receiving diltiazem and 13 of 20 (65%) patients receiving digoxin (p = 0.75). Results of the analysis of only those patients who remained in AF were similar to those presented above. There was no difference between the diltiazem-treated and digoxin-treated groups in postoperative LOHS (8.6 +/- 2.2 vs 7.7 +/- 2.0 days, respectively, p = 0.43).. Ventricular rate control occurs more rapidly with intravenous diltiazem than digoxin in AF after coronary artery bypass graft surgery. However, 12- and 24-hour response rates and duration of postoperative hospital stay associated with the two drugs are similar.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Bypass; Digoxin; Diltiazem; Double-Blind Method; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Postoperative Complications; Treatment Outcome; Vasodilator Agents

Atrial filling pressures are increased in acute atrial fibrillation, which stimulates the release of atrial natriuretic factor pro-hormone, proANF.. In a randomized trial comparing digoxin with placebo in 216 patients, we investigated whether the baseline plasma level of N-terminal proANF is a predictor for conversion to sinus rhythm and the relation among N-terminal proANF, conversion to sinus rhythm, and changes in heart rate.. N-terminal proANF was increased at baseline and decreased significantly in patients converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N-terminal proANF was not a predictor of conversion to sinus rhythm. A relation was found between relative changes in heart rate and N-terminal proANF in nonconverters.. The level of N-terminal proANF does not predict conversion to sinus rhythm, which indicates that hemodynamics per se is not important. There is a correlation between relative changes in heart rate and N-terminal proANF in nonconverters.

Topics: Acute Disease; Atrial Fibrillation; Atrial Function; Atrial Natriuretic Factor; Biomarkers; Digoxin; Heart Rate; Humans; Natriuresis; Protein Precursors

To investigate the defibrillator waiting time (time between the recognition of atrial fibrillation and the actual shock) by studying paroxysmal atrial fibrillation episodes with RR intervals shorter than a certain limit (that is, episodes during which defibrillation should not be attempted).. Long term 24 hour Holter recordings from a digoxin v placebo crossover study in patients with paroxysmal atrial fibrillation were analysed. In all, 23 recordings with atrial fibrillation episodes of at least 1000 ventricular cycles and with < 20% Holter artefacts or noise were used (11 recorded on placebo and 12 on digoxin). For each recording, the mean ("mean waiting time") and maximum ("maximum waiting time") duration of continuous sections of atrial fibrillation episodes with all RR intervals shorter than a certain threshold were evaluated, ranging the threshold from 400 to 1000 ms in 10 ms steps. For each threshold, the mean and maximum waiting times were compared between recordings on placebo and on digoxin.. Both the mean and maximum waiting times increased exponentially with increasing threshold. Practically acceptable mean waiting times less than one minute were observed with thresholds below 600 ms. There were no significant differences in mean waiting times and maximum waiting times between recordings on placebo and digoxin, and only a trend towards shorter waiting times on digoxin.. Introduction of a minimum RR interval threshold required to deliver atrial defibrillation leads to practically acceptable delays between atrial fibrillation recognition and the actual shock. These delays are not prolonged by digoxin treatment.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Cross-Over Studies; Digoxin; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Male; Middle Aged; Time Factors

In recent-onset atrial fibrillation, intravenous propafenone has been shown to effectively restore sinus rhythm, whereas the efficacy of intravenous digoxin has been questioned. We directly compared these 2 drugs and placebo in acute atrial fibrillation. One hundred twenty-three patients with atrial fibrillation lasting <72 hours were randomized to a 10-minute intravenous infusion of either propafenone (2 mg/kg, 41 patients) or digoxin (0.007 mg/kg, 40 patients) or placebo (42 patients). After 1 hour, nonconverted propafenone or digoxin patients were switched to the alternative drug, while nonconverted placebo patients were randomized to either propafenone or digoxin. The observation time ended 1 hour later. By 1 hour, conversion rates were 49% in the propafenone group, 32% in the digoxin group (p = 0.12), and 14% in placebo group (p <0.001 vs propafenone, p = 0.08 vs digoxin). After crossover, digoxin converted 5% of propafenone patients, while propafenone converted 48% of digoxin patients (p <0.05). In the 36 nonconverted placebo patients, sinus rhythm was obtained in 53% of cases with propafenone, and in 5% with digoxin (p < 0.05). Globally, among the 116 patients who received a drug as first treatment, 30 of 60 patients (50%) were converted by propafenone versus 14 of 56 (25%) by digoxin (p <0.01) (odds ratio 2.0, 95% confidence interval 1.19 to 3.36). In nonconverters, the ventricular rate reduction was faster (15 vs 45 minutes) and more prominent (-24% vs -14%) with propafenone than with digoxin. In conclusion, intravenous propafenone terminates atrial fibrillation more effectively than either placebo or intravenous digoxin. In addition, in nonconverted patients, it obtains a more rapid and marked control of the ventricular rate.

Topics: Acute Disease; Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Propafenone; Single-Blind Method; Treatment Outcome

The effects of digoxin on ventricular response during atrial fibrillation (AF) and consequent effects on arrhythmic symptoms have still not been fully explained. This study investigated whether the treatment by digoxin contributes to mid- and long-term stabilization of ventricular cycles in patients with paroxysmal AF. A population of 45 patients with paroxysmal AF underwent 24-hour ECG recordings during each arm of a randomized crossover trial comparing digoxin and placebo. This yielded 30 Holter recordings from 22 patients that contained AF episodes lasting in excess of 2 minutes and with acceptably low Holter noise. Each AF episode was divided into nonoverlapping segments of 30 seconds and the distribution of RR intervals in each segment was compared with the distribution of all other AF segments in the same recording using the Kolmogorov-Smirnov test. The percentage of tests that revealed significant differences at levels of P < or = 0.01, and P < or = 0.001 were sorted according to the time between the segments compared. The comparisons of these results were performed between: (a) all recordings on placebo (n = 16) and all recordings on digoxin (n = 14), and (b) between recordings on placebo and on digoxin in 8 patients in whom paired analysis was possible. Adjacent AF segments (distance 0) differed significantly only in < 30% of both recordings on placebo and on digoxin. However, with increasing the distance between segments, the proportion of the significant differences between RR interval distributions increased more with placebo than with digoxin (P < 10(-300), Chi-square test). Paired data revealed larger differences between placebo and digoxin with increasing distance between segments. Thus in patients with paroxysmal AF, digoxin leads to more reproducible patterns of ventricular cycles that may be better tolerated clinically.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cross-Over Studies; Digoxin; Electrocardiography, Ambulatory; Female; Heart Ventricles; Humans; Male; Middle Aged

The management of permanent atrial fibrillation (PAF) consists primarily of long-term anticoagulation with either aspirin or warfarin to prevent systemic embolization, and modulation of ventricular rate (VR) to improve cardiac function by prolonging the ventricular diastolic filling time.. The effects of slow-release formulations of gallopamil (100 mg b.i.d.), diltiazem (120 mg b.i.d.), or verapamil (120 mg b.i.d.) on VR were evaluated in 18 patients with PAF without organic heart disease.. In all patients, each treatment was administered randomly, was compared with oral digoxin, and was assessed by 24-h Holter monitoring during daily life and by a 6-min walking test.. There were no significant differences in mean and minimum VR recorded during 24-h Holter monitoring among the four treatments. Peak heart rates recorded during the 6-min walking test with digoxin treatment was 167 +/- 12 beats/min. This was significantly reduced by gallopamil (149 +/- 23 beats/min, p = 0.01), diltiazem (142 +/- 24 beats/min, p < 0.001), and verapamil (137 +/- 30 beats/min, p < 0.001). There were no significant differences in peak VR during the walking test among the three calcium antagonists. Pauses of > 3 s were observed in 3 of 18 (17%) patients who received digoxin (max 3.4 s) and in 5 of 18 (28%) patients who received diltiazem (max 3.4 s); p = NS. Periods of bradycardia < 30 beats/min were observed in 5 of 18 (28%) patients during digoxin treatment, and in 3 of 18 (17%) patients during treatment with gallopamil, diltiazem, and verapamil; p = NS.. Gallopamil, diltiazem, or verapamil are superior to digoxin in controlling VR during mild exercise in patients with PAF without organic heart disease. The reduction of peak VR is obtainable without further slowing of resting VR. However, gallopamil appears to be the least effective calcium blocker at controlling resting and exercise VR; thus, there are no advantages over the other calcium blockers in its use in the clinical setting.

Topics: Administration, Oral; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiotonic Agents; Cross-Over Studies; Delayed-Action Preparations; Digoxin; Diltiazem; Electrocardiography, Ambulatory; Female; Gallopamil; Heart Rate; Humans; Male; Middle Aged; Verapamil

The influence of age and gender on the character of paroxysmal atrial fibrillation (PAD) has not been described.. The heart rate (HR) during PAF in patients receiving placebo or antiarrhythmic therapy was analyzed. Data from 177 24-hour Holter recordings were analyzed to mark the onset and termination of PAF and converted into RR interval files. PAF episodes lasting at least 2 minutes and containing < or = 20% noise were included. HR during the first 30-second segment versus during the remainder of the episode, and the duration of PAF episodes were compared among groups of different ages and sex (Wilcoxon test).. 236 episodes from 55 recordings in 32 patients (all patients: 61.4 +/- 12.8 years; men (19): 58.5 +/- 12.6 years; women (13) 65.5 +/- 12.4 years, P = ns for difference in age) fulfilled the inclusion criteria. Women had a higher mean heart rate at AF onset (123 +/- 35 beats/min vs 115 +/- 20 beats/min, P = 0.02) and during the remainder of the episode (120 +/- 25 beats/min vs 112 +/- 22 beats/min at the start, P = 0.01, and 116 +/- 26 beats/min vs 108 +/- 18 beats/min subsequently, P = 0.01). Episodes tended to be longer in women (mean 89.8 min vs 50.5 min, P = NS) and in the aged (mean 83.8 min vs 46.9 min, P = NS).. PAF episodes are associated with faster heart rates and last longer in women, which may reflect differing autonomic responses to AF. A slower ventricular rate during PAF in older patients probably reflects an increasing prevalence of impaired atrioventricular conduction.

Topics: Age Factors; Aged; Anti-Arrhythmia Agents; Atenolol; Atrial Fibrillation; Cross-Over Studies; Digoxin; Disopyramide; Double-Blind Method; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Male; Middle Aged; Sex Factors; Signal Processing, Computer-Assisted; Time Factors

Changes in the RR interval within episodes of paroxysmal atrial fibrillation (PAF) have not been fully characterized. A database of 177 24-hour Holter recordings were created from patients with PAF in the CRAFT studies. PAF episodes of > or = 1 minute duration containing < or = 20% noise and preceded by > or = 1 minute of sinus rhythm with < or = 20% noise were selected. Sections of each AF episode containing 10 and 25 RR intervals were identified at the onset, middle, and termination of each episode. Descriptive characteristics (mean, SD, and RMSSD of RR intervals) were calculated within each section, and compared using a nonparametric, paired Wilcoxon test. In 25 patients (17 men, 60.6 +/- 12.2 years old), 231 episodes from 44 recordings met the selection criteria. The mean RR interval increased slightly between the onset and mid-portion of AF episodes (565.9 +/- 128.3 vs 580.3 +/- 144.7 ms, P < 0.001). The RR interval at the termination of AF was significantly greater than that at the start (627.1 +/- 156.1 vs 565.9 ms, P < 10-11) or mid-portion (627.1 +/- 156.1 vs 580.3 +/- 144.7 ms, P < 10-13). SD of the RR interval increased significantly between onset and mid-portion (111.1 +/- 60.2 vs 118.2 +/- 66.7 ms, P < 0.001) and more substantially between mid-portion and termination (118.2 +/- 66.7 vs 201.8 +/- 93.7 ms, P < 10-21). During paroxysms of AF, the mean RR interval and the variability of RR intervals increases. Termination of a paroxysm is preceded by a marked increase in RR interval variability.

Topics: Anti-Arrhythmia Agents; Atenolol; Atrial Fibrillation; Cross-Over Studies; Digoxin; Disopyramide; Double-Blind Method; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Male; Middle Aged; Time Factors

The efficacy and safety of intravenous propafenone, amiodarone, or placebo were compared in the treatment of atrial fibrillation (AF) of recent onset (duration < or = 48 hours).. 143 patients (77 men, mean age 63 +/- 12 years) were studied, of whom 46 received propafenone (2 mg/kg over 15 minutes followed by 10 mg/kg over the next 24 hours), 48 received amiodarone (300 mg intravenously over 1 hour, followed by 20 mg/kg over the next 24 hours, plus 1,800 mg/day orally, in 3 divided doses), and 49 received placebo (the equivalent amount of saline i.v. over 24 hours). Digoxin was administered to all patients who had not previously received it.. Conversion to normal sinus rhythm occurred in 36 of 46 patients (78.2%) receiving propafenone, in 40 of 48 patients (83.3%) receiving amiodarone, and in 27 of the 49 (55.10%) controls (P < 0.02, drug vs placebo, between drugs NS). The mean time to conversion was 2 +/- 3 hours for propafenone, 7 +/- 5 hours for amiodarone, and 13 +/- 9 for placebo (P < 0.05). Patients who converted had smaller atria than those who did not (diameter: 42.7 +/- 5 vs 47.2 +/- 7 mm, P < 0.001 for all). Treatment was discontinued in one patient in the amiodarone group because of an allergic reaction and in two patients in the propafenone group because of excessive QRS widening. No side effects were observed in the placebo group.. Both drugs tested intravenously were equally effective and safe for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm. However, propafenone offered the advantage of more rapid conversion than amiodarone.

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Humans; Infusions, Intravenous; Logistic Models; Male; Middle Aged; Propafenone; Time Factors

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

Lorenz plot is an acknowledged method of the evaluation of sequences of ventricular beats in cardiac arrhythmias, particularly in atrial fibrillation. Lorenz plots are scatterplots that show the R-R intervals as a function of the preceding R-R intervals. The authors of this paper conducted studies of 83 cases of atrial fibrillation; histograms of 500 consecutive R-R intervals were made, determining the mean R-R interval, the functional refraction period (FRP) of AV node and Lorenz plots. In 22 cases (26.5%) the presence of the silent zone on a Lorenz plot was observed, similarly to the study of Nakatsu and al. The silent zone appeared only in cases when the statistical distribution of R-R intervals was reflected by a bimodal histogram (less frequently by a trimodal histogram). The silent zone was never observed in cases of monomodal distribution of R-R intervals. The authors discuss Nakatsu's findings and argue that the silent zone in a Lorenz plot is a morphological expression of bimodal distribution of R-R intervals in atrial fibrillation. The silent zone may be caused by pharmacotherapy (e.g. digoxin), increased parasympathetic tension or other factors prolonging FRP. The presence of the silent zone is not a predictor of a spontaneous termination of atrial fibrillation.

Topics: Atrial Fibrillation; Cardiovascular Physiological Phenomena; Digoxin; Electrocardiography; Heart Conduction System; Humans; Normal Distribution; Sensitivity and Specificity

To compare the effects of i.v. diltiazem and i.v. digoxin on ventricular rate control in the emergency treatment of acute atrial fibrillation and flutter (AFF).. This prospective, randomized, open-label trial involved 30 consecutive patients who presented with acute AFF to the emergency department of an urban, 420-bed community teaching hospital from April 1993 through March 1994. Exclusion criteria included systolic blood pressure lower than 100 mm Hg, treatment with calcium-channel blockers other than diltiazem, lack of informed consent, and objection of the private physician. Patients were randomly assigned to receive either i.v. diltiazem alone, i.v. digoxin alone, or both. Heart rate control was defined as a ventricular rate of less than 100 beats/minute. I.v. digoxin, 25 mg, was given as a bolus at time 0 and at time 30 minutes. An initial dose of .25 mg/kg diltiazem was given intravenously over the first 2 minutes, followed by a dose of .35 mg/kg at time 15 minutes and then a titratable i.v. infusion at a rate of 10 to 20 mg/hour to maintain heart rate control. The dosing regimens were the same whether the drugs were given alone or in combination. Heart rhythm, heart rate, and blood pressure were measured at time 0, 5, 10, 15, 30, 60, 120, and 180 minutes. Statistical significance was assessed with the use of Student's t test and ANOVA methodology.. At time 0, the heart rate (mean +/- SD) was 150 +/- 19 beats/minute in the diltiazem group and 144 +/- 12 in the digoxin group (difference not significant, P = .432). The decrease in heart rate from time 0 reached statistical significance at time 5 minutes in the diltiazem group (P = .0006); the mean rates at time 5 minutes were 111 +/- 26 beats/minute for diltiazem and 144 +/- 13 for digoxin. The decrease in heart rate achieved with digoxin did not reach statistical significance until time 180 minutes (P = .0099), at which time the rates were 90 +/- 13 for diltiazem and 117 +/- 22 for digoxin.. Treatment of acute AFF with i.v. diltiazem decreases ventricular heart rate significantly within 5 minutes, compared with 3 hours for treatment with i.v. digoxin. No advantage was noted within 3 hours for i.v. treatment with a combination of diltiazem and digoxin. I.v. diltiazem is superior to i.v. digoxin in the emergency control of ventricular rate in acute AFF and should be considered as a drug of choice for this condition. This study was not large enough to adequately assess adverse effects, and further studies may be warranted for clinical validation.

Topics: Acute Disease; Aged; Aged, 80 and over; Analysis of Variance; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digoxin; Diltiazem; Emergency Medical Services; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Prospective Studies; Treatment Outcome

To determine the relative effectiveness of a verapamil-quinidine sequential combination versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation (PAF).. This prospective, double-blind, randomized, controlled trial involved patients, aged 18 to 75 years, with new-onset (< 48 hours) atrial fibrillation who presented to a community-based urban hospital with an annual ED census of 65,000. Exclusion criteria included ventricular response rate lower than 100 or higher than 200 beats/minute, allergy to study drugs, hypotension with evidence of end-organ hypoperfusion, and conduction abnormalities. Consenting patients were randomly assigned to receive rapid digitalization (1.0 mg over 2 hours) or i.v. verapamil (sequential 5-mg boluses up to 20 mg). After ventricular rate was controlled (< 100 beats/minute), oral quinidine (200 mg) was initiated and repeated every 2 hours until conversion to normal sinus rhythm (NSR) occurred, until 1 g of quinidine was administered, or until adverse effects supervened. Heart rate, blood pressure, cardiac rhythm, time to conversion, and adverse effects were documented.. Forty-four patients received the study drugs. Three were withdrawn, leaving 19 in the verapamil-quinidine (VER-Q) group and 22 in the digoxin-quinidine (DIG-Q) group. Sixteen patients (84%) in the VER-Q group and 10 (45%) in the DIG-Q group converted to NSR within 6 hours (P < .02). Mean time to conversion (+/-SD) was 185 +/- 146 minutes for VER-Q and 368 +/- 386 minutes for DIG-Q patients (P = NS). Twelve VER-Q patients (63%) and 6 DIG-Q patients (27%) were discharged from the ED (P < .05). Minor adverse effects were more common in the VER-Q group. No mortality or significant morbidity occurred.. The sequential combination of verapamil and quinidine, in the doses studied, is an effective treatment for PAF and is superior to digoxin-quinidine. Digoxin should no longer be considered the treatment of choice for uncomplicated PAF.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Double-Blind Method; Drug Therapy, Combination; Emergency Medical Services; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Prospective Studies; Quinidine; Tachycardia, Paroxysmal; Treatment Outcome; Verapamil

In this study, a beta-adrenergic blocker in combination with digoxin provided marginal protection against atrial fibrillation/flutter after coronary artery surgery. The economic comparison of patients who did and did not develop atrial fibrillation/flutter indicates that prevention of these arrhythmias can have a significant impact on length of hospital stay and cost of this common surgical procedure.

Topics: Acebutolol; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Coronary Artery Bypass; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Single-Blind Method; Time Factors; Treatment Outcome

A randomized, double-blind study with a high dose of digoxin administered intravenously for conversion of atrial fibrillation (not due to haemodynamic alternations) to sinus rhythm, and for rate control in converters and non-converters was set up. Outcome measures were conversion within 12 h; time to conversion; early rate control; and stable slowing within 12 h.. We studied 40 patients with recent onset (< 1 week) atrial fibrillation; controls received saline intravenously, the other patients digoxin 1.25 mg.. One patient converted before digoxin administration. Conversion occurred in 9/19 patients on digoxin and in 8/20 on placebo (ns). The mean time to conversion tended to be shorter only for digoxin. Two late conversions on placebo were observed within 24 h. Heart rate during atrial fibrillation decreased after 30 min for converters and non-converters (P < 0.05). For all patients on digoxin, heart rate after 30 min was lower compared to baseline (P < 0.002) and to placebo (P < 0.02). Persistent, stable slowing occurred only in 3/10 non-converters on digoxin (P < 0.05), and two patients developed bradyarrhythmias. QTc was shortened immediately after conversion in all patients. Converters had baseline characteristics similar to those of non-converters.. Intravenous digoxin offers no substantial advantages over placebo in recent onset atrial fibrillation with respect to conversion, and provides weak rate control.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged

The DAAF Trial was designed to investigate whether digoxin, within 16 h of its use, increases the rate of conversion to sinus rhythm in patients with acute atrial fibrillation.. In a randomized, double-blind multicentre trial the effects of intravenous digoxin and placebo, (mean dose 0.88 +/- 0.35 mg and 0.96 +/- 0.37 mg) were compared in 239 patients with a mean age of 66.2 +/- 13.0 years and atrial fibrillation of, at most, 7 days' duration. The mean arrhythmia duration was 21.7 +/- 30.4 h and baseline heart rate 122.0 +/- 23.0 beats.min-1. At 16 h, 46% of the placebo group and 51% of the digoxin group had converted to sinus rhythm, (ns). Time to sinus rhythm was shorter in the digoxin group, but the difference was not significant. Digoxin had a pronounced and rapid effect on heart rate, which was already significant at 2 h; 104.6 +/- 20.9 beats.min-1 vs 116.8 +/- 22.5 beats.min-1 (P = 0.0001).. Acute intravenous treatment with digoxin does not increase the rate of conversion to sinus rhythm, but has a fast acting and clinically significant effect on heart rate and should remain an alternative in haemodynamically stable patients.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Sweden

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Double-Blind Method; Heart Rate; Hospitalization; Humans; Propafenone; Retrospective Studies

A construction of a purpose designed graphical display is demonstrated in a study investigating the circadian distribution of patterns of RR interval sequences preceding episodes of paroxysmal atrial fibrillation (PAF). Based on a comparison with a (80%, 120%) range around the median of preceding 10 RR intervals, each RR interval is classified as normal, short, or long. Classifications of RR intervals in n-tuplets (n = 1, ...,5) preceding PAF episodes are used to compute probabilities of individual types of sequences occurring within 4-hour periods of the day (between 1 am, 5 am, 9 am, 1 pm, 5 pm, and 9 pm). Graphical representation of the data is proposed using a hierarchy of bar graphs. The graphical system has been filled with data of 327 atrial fibrillation episodes recorded in 46 24-hour ECGs in PAF patients. The graphical analysis supports a link between PAF initiation and cardiac autonomic status.

Topics: Anti-Arrhythmia Agents; Atenolol; Atrial Fibrillation; Circadian Rhythm; Computer Graphics; Cross-Over Studies; Digoxin; Disopyramide; Double-Blind Method; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Probability

Chronic atrial fibrillation (CAF) is a serious condition with significant morbidity and mortality. The mainstay of drug therapy for the conversion of atrial fibrillation to sinus rhythm continues to be quinidine. The value and safety of intravenously (i.v.) administered amiodarone therapy vs quinidine sulfate therapy was compared in a cohort of patients with CAF of more than 3 weeks' duration.. To evaluate the efficacy of i.v. administered amiodarone and oral quinidine sulfate containing 300 mg of quinidine in the conversion of CAF and to assess the effect of oral amiodarone in the conversion of CAF in the patients in whom CAF did not convert with IV amiodarone.. Thirty-two patients with CAF of more than 3 weeks' duration were randomized to either i.v. amiodarone treatment or oral digoxin/quinidine treatment in a randomized unblinded single crossover study. The converters continued either oral amiodarone therapy or quinidine extended-action tablet (Quinidex) therapy.. Seventeen patients were randomized to the quinidine group and 15 patients to the amiodarone group. Nonconverters from the quinidine group crossed over to the amiodarone group. Amiodarone and quinidine were equally effective at 24 hours in converting CAF (eight [47%] of 17 patients in the quinidine group vs 12 [44%] of 27 patients in the amiodarone group; P, not significant). At 2 and 9 months of oral therapy, amiodarone was superior to quinidine in maintaining sinus rhythm. Only two of eight patients in the quinidine group tolerated the medication. All patients in the amiodarone group tolerated the medication. One additional patient converted to sinus rhythm at 2 months (13 [48%] of 27), and five more patients converted at 9 months (18 [67%] of 27). Amiodarone therapy and digoxin/quinidine therapy were equally effective at 48 hours in controlling ventricular response at rest.. During the first 48 hours of treatment, i.v. amiodarone and oral quinidine were equally effective in converting CAF to sinus rhythm. At 2 and 9 months of therapy, treatment with oral amiodarone was superior to that of quinidine in restoring sinus rhythm. Long-term treatment with oral amiodarone is better tolerated than with quinidine.

Topics: Administration, Oral; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Quinidine; Treatment Outcome

A population of 283 patients with recent onset (< 72 hours) AF, without heart failure, who received a single 450- or 600-mg oral dose of propafenone, or digoxin 1 mg, or placebo for conversion to sinus rhythm (SR), was studied to determine whether a routine admission to the hospital for drug administration is justified. Previous bradyarrhythmias or sick sinus syndrome (SSS), and concomitant use of antiarrhythmic drugs were exclusion criteria. None of the 283 patients studied experienced VT or VF and none of them needed implantation of a temporary pacemaker. Periods of atrial tachyarrhythmias with regularization of atrial waves and 1:1 AV conduction were observed in only two cases, both receiving placebo. No predictor of proarrhythmia was found among the clinical variables considered (age, etiology, arrhythmia duration, atrial dimension, and blood potassium). No serious hemodynamic adverse effects were noted in either group. The rates of conversion to SR after 4 hours were: 80 (57%) of 141 patients who received propafenone and 35 (25%) of 142 patients who received digoxin or placebo (P < 0.001). Acute oral treatment with propafenone is simple and effective for the conversion of recent onset AF to SR in patients without clinical signs of heart failure. The routine admission of these patients to the hospital is not necessary. Home-based administration of oral propafenone to a selected group of patients could significantly increase the cost effectiveness of this treatment.

Topics: Administration, Oral; Age Factors; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Function; Atrioventricular Node; Bradycardia; Cost-Benefit Analysis; Digoxin; Female; Forecasting; Heart Rate; Hemodynamics; Home Care Services; Humans; Male; Middle Aged; Pacemaker, Artificial; Patient Admission; Placebos; Potassium; Propafenone; Retrospective Studies; Sick Sinus Syndrome; Tachycardia; Tachycardia, Ventricular; Ventricular Fibrillation

This study investigated whether the irregularity of ventricular cycle length during atrial fibrillation (AF) is affected by digoxin. Patients (n = 41) with paroxysmal AF enrolled in a randomized crossover comparison of digoxin and placebo underwent 24-hour ambulatory monitoring during each treatment. Tapes containing AF episodes lasting at least 2 minutes were selected (24 recordings on placebo and 17 on digoxin). The mean (mRR) and standard deviation (SDRR) of RR intervals was calculated for each 30-second segment of AF. The resulting SDRR values were clustered according to bins of mRR values ranging from 350-650 ms in 25-ms steps. In each bin, the SDRR values of all placebo and all digoxin recordings were statistically compared for the top 5, 10, and 15 percentiles of each bin which represented the extremes of ventricular cycle length irregularity during AF. There were no significant differences between the total data of SDRR values in individual bins of mRR. However, the top 5, 10, and 15 percentiles of SDRR values corresponding to mRR values from 350-550 ms were significantly reduced by digoxin (P < 0.0001). The study concludes that although digoxin does not influence the mean variability of RR cycles during AF paroxysms, it suppresses episodes in which a fast ventricular response is associated with extreme variability of RR periods.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cross-Over Studies; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Information Systems; Male; Middle Aged; Placebos; Signal Processing, Computer-Assisted; Time Factors; Ventricular Function

Twenty digitalized elderly patients with chronic atrial fibrillation were randomized into a double-blind cross-over study. None was in overt heart failure and all were taking < 80 mg frusemide daily. They received xamoterol 200 mg b.d. for 2 months with their usual dose of digoxin for 1 month and placebo digoxin for the other month. Twenty-four-hour heart rate analysis was done at baseline and at the end of each treatment period. Compared with baseline digoxin, xamoterol alone significantly increased nocturnal minimum heart rate [85 +/- 17 vs. 62 +/- 9 (mean +/- SD), p < 0.0001] without affecting daytime maximum heart rate (132 +/- 18 vs. 122 +/- 20, p = NS). Compared with baseline digoxin, xamoterol plus digoxin significantly increased nocturnal minimum heart rate (68 +/- 8, p < 0.05) and reduced daytime heart rate (114 +/- 17, p < 0.05). The mean number of pauses > 1.5 s was significantly reduced by xamoterol alone. Walking distance in 6 minutes was 406.1 +/- 27.1 m (mean +/- SE) at baseline and improved significantly on both treatments (450.3 +/- 19.8 on xamoterol; p < 0.02 and 453.7 +/- 19.2 on xamoterol plus digoxin; p < 0.01). No significant change was found in subjective measurements of palpitations, breathlessness and well-being using visual analogue scales. Xamoterol combined with digoxin improves effort tolerance and heart-rate control by reducing diurnal tachycardia and nocturnal bradycardia and pauses.

Topics: Adrenergic beta-Agonists; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Cross-Over Studies; Digoxin; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Exercise Test; Furosemide; Geriatric Assessment; Heart Rate; Humans; Xamoterol

We randomized 61 patients with paroxysmal atrial fibrillation (AF) ( < 48 hours from onset) to either sotalol or quinidine treatment. Conversion of rhythm was recorded by Holter monitoring. The starting 80 mg dose of sotalol was repeated at 2, 6, and 10 hours if AF persisted (heart rate > 80 beats/min), and if systolic blood was > or = 120 mm Hg. In the quinidine group, if heart rate > 100 beats/min, it was decreased with intravenous digoxin, whereafter 200 mg of oral quinidine sulfate was given maximally 3 times, each dose 2 hours apart. Conversion of AF to sinus rhythm occurred in 17 or 33 patients (52%) taking sotalol, and in 24 of 28 patients (86%) taking quinidine (p < 0.0001). Electric cardioversion was necessary in 39% of the former and in 14% of the latter group. The mean delay from first trial drug to sinus rhythm with the trial medication was 10.2 +/- 7.6 hours in the sotalol group and 4.0 +/- 2.9 hours in the quinidine group (p < 0.01). Treatment was discontinued in 16 patients taking sotalol (48%) because of asymptomatic bradycardia or hypotension, and in 20 taking quinidine (71%) because of rhythm conversion. Asymptomatic wide complex tachycardia (QRS > 0.12 second) was found in 13% and 27% of patients taking sotalol and quinidine, respectively. The longest RR intervals were 6.4 and 3.8 seconds in the sotalol and quinidine groups, respectively. Oral sotalol did not appear as effective as quinidine sulfate treatment in conversion of paroxysmal AF.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Aged; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Quinidine; Sotalol; Tachycardia; Time Factors

Current systems for analyzing ambulatory electrocardiograms (ECGs) are unable to distinguish precisely between sinus rhythm and atrial fibrillation (AF) episodes, and are unable to produce RR interval listings that distinguish AF from sinus rhythm on a beat-to-beat basis. We describe a method for obtaining such a computerized listing ("Composite Rhythm" file) from ambulatory recordings containing episodes of AF. The file lists the rhythm of each beat, its real time, and the QRS complex morphology. A visual inspection is made of a full printout of the recording to identify the precise time of onset and termination of each episode of AF. These times are entered into a computer and identified with the corresponding beats on a conventional RR interval file generated by Holter analysis. The method was validated using 1-hour segments from 20 ambulatory ECGs containing 145 episodes of AF. These were visually identified by four independent observers with a mean sensitivity of 99.1%. The first beat of AF was identified concordantly in 96% of episodes, with a discrepancy of < or = 3 beats in the other episodes. The times of 200 selected QRS complexes were then entered into the computer by each observer; 91.1% of these complexes were identified exactly and 100% were identified to within one beat. The Composite Rhythm files have several potential applications for testing AF detection algorithms and studying the mode of onset of AF.

Topics: Algorithms; Atrial Fibrillation; Digoxin; Electrocardiography, Ambulatory; Humans; Sensitivity and Specificity; Signal Processing, Computer-Assisted

A 24 h intravenous dosing regimen of amiodarone was designed to reach a peak plasma concentration at 1 h and to maintain the concentration above a certain level during the infusion period. A randomized, open-label, digoxin-controlled study was undertaken to observe the efficacy and safety of the dosing regimen of amiodarone in treating recent-onset, persistent, atrial fibrillation and flutter with ventricular rates above 130 beats.min-1. Fifty patients with a mean age of 70 +/- 7 (SD) years were enrolled and randomly assigned to receive either amiodarone intravenously (n = 26) or digoxin (n = 24). Amiodarone HCl was infused over 24 h according to the following regimen: 5 mg.min-1, 3 mg.min-1, 1 mg.min-1 and 0.5 mg.min-1 for 1, 3, 6 and 14 h, respectively, for a 70-kg subject. Digoxin (0.013 mg.kg-1) was infused in three divided doses, each dose 2 h apart and infused over 30 min. The mean heart rates in the amiodarone group decreased significantly from 157 +/- 20 beats.min-1 to 122 +/- 25 beats.min-1 after 1 h (P < 0.05 vs baseline), and then decreased further to stabilize at 96 +/- 25 beats.min-1 after 6 h (P < 0.05). The digoxin group had fewer dramatic alterations in heart rates, compared to the amiodarone group, in the first 8 h (P < 0.05, respectively). Maximum reduction was reached only after 8 h. The amiodarone infusion was prematurely aborted in two patients due to severe bradycardia and death after conversion in one patient and aggravation of heart failure in the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Amiodarone; Analysis of Variance; Atrial Fibrillation; Atrial Flutter; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Betaxolol; Chronic Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Ventricular Function

The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects. But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period.. The purpose of this study was three-fold: (1) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study; (2) to evaluate whether the beneficial effects of medication will be maintained after 7 months; (3) to evaluate the safety of the combination therapy in patients with impaired left ventricular function.. We did a prospective randomized crossover study in 35 patients with chronic atrial fibrillation (AF) including 15 patients with left ventricular dysfunction. After enrollment, each patient was evaluated for heart rate, blood pressure, rate-pressure products, maximal exercise tolerance at rest and during symptom-limited treadmill test before medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients at the end of each phase of treatment. We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication.. (1) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.) beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4, 213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105 +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05). (4) At 7 months evaluation, there was no significant difference between at 4 weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same findings as on treadmill test. (6) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy, they were minimal and no patient had to withdraw medication. Worsening of left ventricular dysfunction was not observed.. Our study suggested that (1) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products; (2) the effects controlling ventricular rate, reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Betaxolol; Blood Pressure; Calcium Channel Blockers; Chronic Disease; Cross-Over Studies; Digoxin; Diltiazem; Drug Therapy, Combination; Exercise Tolerance; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Ventricular Dysfunction, Left

The incidence of fast atrial tachycardias with regular ventricular rhythm was assessed in a population of 243 patients with recent onset (< 72 hours) atrial fibrillation (AF), without heart failure, randomly treated with single loading oral dose of propafenone (600 mg), flecainide (300 mg), digoxin (1 mg), or placebo for acute conversion to sinus rhythm (SR). Fast atrial arrhythmias developed in 14 (6%) patients: 6/92 treated with propafenone, 3/34 treated with flecainide, 1/25 treated with digoxin, and 4/92 who received placebo (P = NS). Heart rate > 175 beats/min with 1:1 AV conduction ensued in 4 cases: 2 treated with flecainide and 2 treated with placebo; in the other cases 2:1 AV conduction was observed. Widening of QRS during regular tachycardia was observed in 4 patients; 3 who received propafenone and 1 who received flecainide. Conversion to SR within 4 hours was achieved in 55/92 (60%) patients treated with propafenone, 20/34 (59%) patients treated with flecainide, 7/25 (28%) patients treated with digoxin, and 19/92 (20%) treated with placebo (P < 0.001 propafenone vs placebo and flecainide vs placebo; P < 0.05 propafenone vs digoxin and flecainide vs digoxin). Periods of regular tachycardia are expected in recent onset AF and may not necessarily represent a proarrhythmic effect of Class 1C drugs, rather than mark the transition from AF to SR. Class 1C agents are probably responsible for widening of the QRS complex seen during these tachycardias. Propafenone and flecainide appear equally effective in converting recent onset AF.

Topics: Atrial Fibrillation; Digoxin; Electrocardiography; Electrocardiography, Ambulatory; Female; Flecainide; Heart Rate; Humans; Male; Middle Aged; Propafenone; Ventricular Function

The role of cardiac glycosides for conversion of atrial fibrillation to simus rhythm is controversially discussed. In a prospective study, 45 patients with paroxysmal atrial fibrillation were randomly assigned to one of three treatment groups (of 15 patients each). Group I received oral digoxin, three times 0.125 mg up to twice 0.25 mg daily; group II oral digoxin twice 0.125 mg and quinidine hydrogen sulphate 750-1000 mg daily; group III oral digoxin three times 0.125 mg and flecaimide 200-300 mg daily. During a mean observation period of 11 months, digoxin alone was significantly less effective (p < 0.05) in reducing or suppressing paroxyms of atrial fibrillation than digoxin plus quinidine or flecainide. The use of digoxin remains a mainstay of treatment for rate control in atrial fibrillation. To convert atrial fibrillation to sinus rhythm, however, the addition of a type I or III antiarrhythmic agent is necessary.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Flecainide; Heart Rate; Humans; Male; Middle Aged; Prospective Studies; Quinidine; Tachycardia, Paroxysmal

Physical exercise has been found to increase digoxin binding in working skeletal muscle along with a concomitant decrease in serum digoxin concentration. In a recent study on healthy volunteers, moderate physical activity during maintenance digoxin treatment was shown to decrease the renal excretion of digoxin secondary to this redistribution of the drug, thereby affecting the body content of digoxin. In the present study the influence of changes in everyday physical activities, carried out during a 10-h period after ingestion of the daily maintenance digoxin dose, on the steady-state serum digoxin concentration (24 h after the last dose) was studied in 10 digoxin-treated outpatients (61-81 years of age). Compared to normal daily activity, complete bed rest for 10 h after ingestion of the maintenance dose did not affect the steady-state serum digoxin concentration. The lack of such an influence may be explained either by a low degree of everyday physical activity in the investigated patients or to a compensatory increase in the renal excretion of digoxin during the night preceding the serum digoxin measurement. Thus, standardization of physical activity 1-2 h before blood sampling is adequate when analysing the serum digoxin concentration in elderly outpatients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Circadian Rhythm; Cross-Over Studies; Digoxin; Dose-Response Relationship, Drug; Exercise; Female; Heart Rate; Humans; Male; Middle Aged; Motor Activity; Time Factors

1. The ideal drug treatment for atrial fibrillation will control resting heart rate, blunt exercise induced tachycardia whilst not exacerbating nocturnal bradycardia. Monotherapy with digoxin may not be ideal. We have compared the effect of combining digoxin (0.25 mg daily) with atenolol 50 mg and 100 mg or pindolol 5 mg twice daily and 15 mg twice daily in a cross-over randomised single-blind trial in eight symptomatic patients (six male; mean age 62 years) with poorly controlled atrial fibrillation. 2. Heart rate control was measured by 24 h ECG at baseline on digoxin therapy and after 2 weeks with each treatment. Symptom scores for breathlessness and palpitation were measured using visual analogue scales. 3. The addition of both beta-adrenoceptor blockers significantly reduced mean diurnal maximum heart rate from baseline (all P < 0.001 ANOVA). Atenolol at both doses caused a greater reduction than either dose of pindolol (P < 0.001 ANOVA). Nocturnal maximum heart rate was not significantly reduced from baseline by either beta-adrenoceptor blocker, but both doses of pindolol caused increases in nocturnal maximum heart rate compared with atenolol (P < 0.001 ANOVA). 4. Atenolol caused a reduction in diurnal minimum heart rate compared with baseline and caused a reduction in nocturnal minimum heart rate whereas pindolol caused an increase (P < 0.001 ANOVA). 5. Atenolol 100 mg caused longer nocturnal pauses compared with baseline but pindolol 15 mg twice daily reduced the number of nocturnal pauses > 1.5 s (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Aged; Analysis of Variance; Atenolol; Atrial Fibrillation; Bradycardia; Digoxin; Drug Synergism; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Pindolol; Single-Blind Method

The objectives of this study were to assess the efficacy of parenteral magnesium sulfate (MgSO4), digoxin, and combined MgSO4-digoxin therapies in acutely lowering ventricular rates in patients with newly recognized atrial fibrillation.. A randomized, double-blinded, placebo-controlled clinical study.. US Army tertiary care facility.. Fifteen adults (mean age, 62 +/- 19 years) presenting with newly recognized atrial fibrillation and rapid ventricular rate (more than 99).. Patients were given an initial parenteral MgSO4 bolus with continuous infusion or placebo. After 30 minutes, all patients were given 0.5 mg IV digoxin and followed for 3.5 hours.. Ventricular rates were obtained at baseline, every 5 minutes for the first 30 minutes, and then every 30 minutes for 3.5 hours. At 5 minutes, ventricular rates decreased 16 +/- 7% (P < .02) with MgSO4; this was comparable with rate control with digoxin (18 +/- 9%) at 4 hours. Rate control tended (26 +/- 7%) to improve with combined therapy.. Parenteral MgSO4 may be useful in the acute management of rapid ventricular rates in patients with atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Digoxin; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Heart Ventricles; Humans; Magnesium Sulfate; Male; Middle Aged; Prospective Studies; Treatment Outcome

Despite the widespread use of amiodarone in non-surgical patients, its role in the management of supraventricular tachyarrhythmias after cardiac surgery is not clear. We set out to compare the relative efficacy of amiodarone and digoxin in the management of atrial fibrillation and flutter in the early postoperative period. This prospective randomised trial comprised 30 patients, previously in sinus rhythm, who developed sustained atrial fibrillation or flutter following myocardial revascularisation, valve surgery or combined procedures. Amiodarone was administered as an intravenous loading dose followed by a continuous infusion. Digoxin was given as an intravenous loading dose followed by oral maintenance therapy. Electrocardiographic and haemodynamic monitoring was continued for 24 h after the commencement of treatment. There was a marked reduction in heart rate in both groups, mainly in the first 6 h, from 146 to 89 beats per minute in the amiodarone group and from 144 to 95 in the digoxin group. At the end of the 24 h, one of the 15 patients in the amiodarone group and 3 of the 15 patients in the digoxin group remained in atrial fibrillation. No patient in either group developed adverse reactions. We conclude that intravenous amiodarone therapy is safe and at least as effective as digoxin in the initial management of arrhythmias after cardiac surgery.

Topics: Aged; Amiodarone; Atrial Fibrillation; Atrial Flutter; Cardiac Surgical Procedures; Digoxin; Female; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Time Factors

To establish the value of adjuvant dl-sotalol to digoxin for control of the ventricular response in chronic atrial fibrillation, 60 patients were evaluated in a multicenter, randomized, double-blind, parallel, placebo-controlled study. Patients were evaluated with serial ambulatory ECG monitoring and exercise testing during stable digoxin dosing and then with the addition of either a placebo or dl-sotalol, 80 mg/day, or dl-sotalol, 160 mg/day. The combination of digoxin and dl-sotalol, at either 80 or 160 mg/day, resulted in a statistically significant reduction in heart rate at rest and with exercise during both exercise testing and ambulatory monitoring. No significant difference was observed between the two doses of dl-sotalol. There was no significant difference with regard to symptoms or side effects among the three groups. In summary, dl-sotalol was noted to be a safe and effective adjuvant to digoxin for control of the ventricular response in chronic atrial fibrillation.

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Sotalol; Tachycardia, Ventricular

Eighty-seven patients with recent onset atrial fibrillation (< or = 8 days) without clinical signs of heart failure were randomly allocated to one of the following treatments: (i) oral propafenone (600 mg as a loading dose followed after 8 h by 300 mg t.i.d.); (ii) intravenous digoxin as acute scheme (up to 1.125 mg/24 h) followed after 6 h by hydroquinidine chlorhydrate (total dose, 1350 mg); or (iii) placebo. The patients were submitted to Holter monitoring for 48 h.. propafenone achieved higher successful conversion rates at 6, 12 and 24 h compared either with placebo (62% vs. 17%, 83% vs. 34%; 86% vs. 55%; P < 0.01, respectively) or with digoxin at 6 h (62% vs. 38%; P < 0.05) and digoxin plus quinidine at 12 h (83% vs. 48%; P < 0.05). At 48 h, a placebo conversion rate of 76% was observed with consequent lack of any significant difference with the active treatments. Mean conversion times within 48 h were 267 +/- 238 min for propafenone, 648 +/- 631 min for digoxin plus quinidine (P < 0.01 vs. propafenone) and 893 +/- 622 min for placebo (P < 0.001 vs. propafenone). Propafenone and digoxin plasma levels were within the therapeutic range. Asymptomatic phases of atrial flutter with > or = 2:1 atrio-ventricular conduction ratio were observed during Holter monitoring, before conversion to sinus rhythm, in four patients treated with propafenone, in one patient taking digoxin plus quinidine and in four patients with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Digoxin; Drug Combinations; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Placebos; Propafenone; Quinidine; Remission Induction; Single-Blind Method; Ventricular Function

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Double-Blind Method; Drug Combinations; Female; Heart Rate; Humans; Magnesium; Male; Middle Aged; Placebos; Prospective Studies; Tachycardia, Ventricular; Time Factors; Ventricular Function

Safety and efficacy of simultaneous use of intravenous digoxin and esmolol in the control of rapid heart rate in 21 patients with atrial fibrillation or flutter was assessed. The mean age was 67 (range 40 to 90) years. Seven patients had class III congestive heart failure, with left ventricular ejection fraction between 18% and 61%. Baseline mean heart rate was 143 +/- 4. After 0.25 mg or 0.5 mg intravenous digoxin, esmolol was titrated with initial boluses from 2 mg/min to 16 mg/min in 25 minutes. A tolerated dose of esmolol infusion was adjusted for up to 48 hours. Rapid control of heart rate (29% decrease with heart rate 101 +/- 4) occurred at a mean interval of 21 minutes. Minimum heart rate was 87 +/- 4 at 90 minutes of treatment. Conversion to sinus rhythm occurred in five patients (25%), and one patient experienced mild transient congestive heart failure. No symptomatic hypotension or bronchospasm occurred. In conclusion, simultaneous use of digoxin and esmolol is effective in safely and rapidly controlling heart rate in atrial fibrillation or flutter.

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Therapy, Combination; Heart Rate; Humans; Propanolamines; Time Factors

Clinical outcomes and costs associated with the use of digoxin in atrial fibrillation and flutter were evaluated in a prospective, observational study at 18 academic medical centers in the United States. Data were collected on 115 patients (aged > 18 years) with atrial fibrillation or flutter who were treated with digoxin for rapid ventricular rate (> or = 120 beats/min). The median time to ventricular rate control (i.e., resting ventricular rate < 100 beats/min, decrease in ventricular rate of > 20%, or sinus rhythm) was 11.6 hours from the first dose of digoxin for all evaluable patients (n = 105) and 9.5 hours for those only receiving digoxin (n = 64). Before ventricular rate control, the mean +/- SD dose of digoxin administered was 0.80 +/- 0.74 mg, and a mean of 1.4 +/- 1.8 serum digoxin concentrations were ordered per patient. Concomitant beta-blocker or calcium antagonist therapy was instituted in 47 patients (41%); in 19 of these, combination therapy was initiated within 2 hours. Adenosine was administered to 13 patients (11%). Patients spent a median of 4 days (range 1 to 25) in the hospital; 28% spent time in a coronary/intensive care unit and 79% in a telemetry bed. Loss of control (i.e., resting ventricular rate returned to > 120 beats/min) occurred at least once in 50% of patients and was associated with a longer hospital stay (p < 0.05). Based on 1991 data, the estimated mean hospital bed cost for patients with atrial fibrillation or flutter was $3,169 +/- $3,174.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Costs; Drug Therapy, Combination; Female; Hospitals, University; Humans; Length of Stay; Male; Middle Aged; Prospective Studies; Regression Analysis; Treatment Outcome; United States

In 30 patients who developed atrial fibrillation after open-heart surgery the efficacy of intravenous procainamide was evaluated and compared with standard acute digoxin digitalisation. The patients were randomized to two groups of 15. One group received procainamide intravenously at a rate of 25 mg/min and with maximum dose 15 mg/kg. In the other group digoxin 0.75-1.0 mg was given intravenously according to renal function and body weight. Conversion to sinus rhythm occurred during or immediately after the infusion in 87% of the procainamide group, but only in 60% of the digoxin group (p < 0.05). The mean time from start of treatment to conversion was 40 min in the procainamide vs. 540 min in the digoxin group (p < 0.002). There were no serious complications of the procainamide treatment. Intravenous procainamide conversion of postoperative atrial fibrillation is concluded to be effective and safe and can be recommended as the treatment of first choice in awake and nonintubated postoperative cardiac patients.

Topics: Adolescent; Adult; Aged; Atrial Fibrillation; Blood Pressure; Cardiac Surgical Procedures; Digoxin; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Procainamide; Recurrence; Time Factors

The efficacy and safety of intravenous flecainide to convert recent-onset atrial fibrillation (AF) (present for greater than or equal to 30 minutes and less than or equal to 72 hours and a ventricular response greater than or equal to 120 beats/min) was investigated. A total of 102 patients without severe heart or circulatory failure were randomized to receive either intravenous flecainide (2 mg/kg, maximum dose 150 mg; 51 patients) or placebo (51 patients) in a double-blind trial. Digoxin (500 micrograms intravenously) was administered to all patients who had not previously been receiving digoxin. The electrocardiogram was monitored continuously during the study. In 29 (57%) patients stable sinus rhythm was restored within 1 hour after flecainide and in only 7 (14%) given placebo (chi square 18.9; p = 0.000013; odds ratio 8.3; 95% confidence interval 2.9-24.8). Reversion to sinus rhythm within 1 hour after starting the trial medication was considered a pretrial end point and likely to be due to a drug effect. At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide group were in sinus rhythm whereas only 18 (35%) in the placebo group had reverted (chi square 8.83, p = 0.003; odds ratio 3.67; 95% confidence interval 1.5-9.1). Significant hypotension, although short lived, was more common in the flecainide group. One patient given flecainide developed torsades de pointes and was successfully electrically cardioverted. Flecainide is useful for the management of recent-onset AF both for control of the ventricular response and conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Double-Blind Method; Drug Evaluation; Female; Flecainide; Humans; Hypotension; Male; Middle Aged; Monitoring, Physiologic; Time Factors

The effect of the combined treatment with propranolol 20 mg tid and diltiazem 60 mg tid in patients with chronic atrial fibrillation treated with digoxin was evaluated. Thirteen patients entered a double-blind, three-phase crossover study. Heart rate was significantly reduced during rest and at maximal exercise (p less than 0.05) during combined treatment compared with treatment with any single drug. No significant changes in maximal work load, exercise time, systolic blood pressure at maximal work load, or subjective sensation of well-being could be demonstrated during combined drug treatment. The RR distribution pattern was unaffected by the addition of propranolol, diltiazem, or their combination to the chronic digoxin treatment. It is concluded that the combination of diltiazem and propranolol has no advantages over any of these drugs singly, in the moderation of heart rate in patients with atrial fibrillation even combined with basic digitalis treatment, and that the intrinsic AV nodal function is unaffected by these drugs or their combination.

Topics: Atrial Fibrillation; Digoxin; Diltiazem; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Propranolol

The bioavailability of digoxin in solution (Lanoxicaps, 90-100 percent) is superior to that of Lanoxin tablets (60-80 percent) in young healthy volunteers. The alleged bioequivalence of digoxin in tablets (Lanoxin 0.25, 0.125 mg) and capsules (Lanoxicaps 0.2, 0.1 mg) was studied in 20 elderly inpatients (14 women, 6 men, aged 84 +/- 5 years), treated with digoxin for atrial fibrillation. In a crossover design, steady-state digoxin concentrations were measured in 16 patients after once-daily administration of Lanoxin 0.125 mg or Lanoxicaps 0.1 mg, each for at least ten days. Four other patients took Lanoxin 0.25 mg and Lanoxicaps 0.2 mg successively. The steady-state digoxin concentrations were statistically significantly different, being 1.3 +/- 0.5 nmol/L for Lanoxin and 0.9 +/- 0.4 nmol/L for Lanoxicaps (p = 0.003). Whereas in young healthy volunteers the bioavailability of digoxin from Lanoxicaps (90-100 percent) exceeds that from Lanoxin (80 percent), in elderly patients the absorption appears to be similar. This suggests a lower than expected bioavailability of Lanoxicaps, which may result in subtherapeutic serum concentrations.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biological Availability; Capsules; Digoxin; Female; Humans; Male; Tablets; Therapeutic Equivalency

Spontaneous reversion to sinus rhythm is a frequent occurrence in recent-onset atrial fibrillation (AF). In a randomized, double-blind, controlled study, intravenous flecainide (2 mg/kg, maximum dose 150 mg) was compared with placebo in the treatment of recent-onset AF (present for greater than or equal to 30 minutes and less than or equal to 72 hours' duration and a ventricular response greater than or equal to 120 beats/min). Intravenous digoxin (500 micrograms) was administered concurrently to all patients in both groups who had not previously taken digoxin. The trial medication was administered over 30 minutes. Exclusion criteria included hemodynamic instability, severe heart failure, recent antiarrhythmic therapy, hypokalemia and pacemaker dependence. One hundred two consecutive patients with recent-onset AF were enrolled in the study. All patients underwent continuous electrocardiographic monitoring in the intensive care or coronary care unit. Twenty-nine (57%) patients given flecainide and digoxin, but only 7 (14%) given placebo and digoxin, reverted to sinus rhythm in less than or equal to 1 hour after starting the trial medication infusion and remained in stable sinus rhythm (chi-square 18.9, p = 0.000013; odds ratio 8.3, 95% confidence interval 2.9 to 24.8). At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide-digoxin group were in stable sinus rhythm, whereas only 18 patients (35%) in the placebo-digoxin group had reverted (chi-square 8.83, p = 0.003; odds ratio 3.67, 95% confidence interval 1.5 to 9.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Fibrillation; Coronary Care Units; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Flecainide; Humans; Hypotension; Infusions, Intravenous; Male; Middle Aged

Ambulatory Holter monitoring was performed in 58 patients during the early convalescence after myocardial revascularization in order to determine the incidence of recurrent atrial arrhythmias following treatment for postoperative atrial fibrillation. Fifteen patients who had undergone coronary bypass and had not developed spontaneous atrial fibrillation following operation served as the controls (group 1). The remaining patients developed spontaneous symptomatic atrial fibrillation after coronary bypass that required digitalization for rate control. Sixteen patients (group 2) continued taking digoxin for 8 weeks following operation, 13 patients (group 3) discontinued digoxin treatment 5 weeks following operation, and 14 patients (group 4) discontinued digoxin treatment 3 weeks following operation. Twenty-four-hour Holter monitoring indicated that asymptomatic atrial fibrillation was common in the treatment groups after digitalization just before discharge from hospital. Atrial fibrillation, however, rarely recurred following discharge from hospital and was never symptomatic. Our data indicate that patients who develop spontaneous postoperative atrial fibrillation should be treated with digoxin for 3 weeks following operation and then drug therapy may be discontinued indefinitely.

Topics: Atrial Fibrillation; Coronary Artery Bypass; Digoxin; Electrocardiography, Ambulatory; Humans; Incidence; Middle Aged; Recurrence; Time Factors

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Sotalol

We have examined the effects of magnesium replacement therapy upon post-exercise heart rate and incidence of ventricular premature beats (VPB) in digitalised patients with AF. In 11 such patients, all of whom had serum magnesium concentrations of less than 0.85 mmol/l, treatment with magnesium glycerophosphate was associated with a significant reduction in number of VPBs (982 v. 416 VPB/24 h). Five patients had a high prevalence of ventricular ectopy (greater than 300 VPB/24 h) and these subjects showed particularly marked decreases in VPBs during magnesium treatment (1998 v. 690 VPB/24 h). Three patients had slightly increased QTc intervals but these did not change during magnesium replacement. No significant changes were seen in the mean post-exercise heart rate although 2 subjects did show falls of 25% or more during magnesium replacement. We conclude that treatment with magnesium glycerophosphate may be associated with a decreased prevalence of ventricular ectopy in some digitalised patients with chronic AF and mild-moderate hypomagnesaemia.

Topics: Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Digoxin; Electrocardiography; Exercise; Exercise Test; Female; Heart Rate; Humans; Magnesium; Magnesium Deficiency; Male; Middle Aged

Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were randomised to treatment periods of two weeks on xamoterol (200 mg twice daily), low dose digoxin, or placebo, in a blind crossover study. The results (mean SEM) of symptom scores, a treadmill exercise test, and 24 hour ambulatory electrocardiographic monitoring were obtained. Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin. Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration. Xamoterol, by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate, significantly reduced the difference between the two compared with placebo. In contrast, digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night. Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin. Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity. These changes were translated into symptomatic benefit for the patients studied.

Topics: Adrenergic beta-Agonists; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Propanolamines; Time Factors; Xamoterol

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

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

Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation (AF) but often reduce exercise capacity. To investigate the advantage of labetalol--a unique beta blocker with alpha-blocking property--in chronic AF, 10 patients without underlying structural heart disease were studied with treadmill test, 12-minute walk and 24-hour ambulatory electrocardiographic monitoring. Patients were randomized and crossed over to receive 4 phases of treatment (placebo, digoxin, digoxin with half-dose labetalol, and full-dose labetalol). Exercise durations were 14.1 +/- 1.5, 14.2 +/- 1.5, 16.1 +/- 1.1 and 15.6 +/- 1.1 minutes, respectively, indicating that labetalol did not reduce exercise tolerance. Although digoxin had no advantage over placebo in controlling maximal heart rate (177 +/- 2 vs 175 +/- 3 beats/min), labetalol, both as monotherapy or as an adjunct to digoxin, was advantageous (156 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, and 154 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, respectively). The rate-pressure product was consistently lowered by labetalol at rest and during exercise. At peak exercise, the addition of labetalol to digoxin reduced the maximal rate-pressure product achieved from 30,900 +/- 1300 to 24,100 +/- 2,000 mm Hg/min (p less than 0.01) and the maximal rate-pressure product was lowest with full-dose labetalol (22,300 +/- 1,600 mm Hg/min). During submaximal exercise on treadmill or during the 12-minute walk, the combination of labetalol and digoxin produced the best heart rate control, whereas labetalol monotherapy was comparable to digoxin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Labetalol; Male; Middle Aged

Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections, using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added. The validity of the simulations was tested in 11 patients with rapid atrial fibrillation. Serum digoxin concentrations, ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart. In agreement with the predictions of the model, the maximal fall in ventricular rate was reached after 8-9 h in the infusion group and after 19-20 h in the bolus injection group, without any detectable difference in side effects. There were certain discrepancies between the results of the clinical study and the predictions of the model, e.g. in serum digoxin concentrations, perhaps due to impaired clearance in the patients. However, it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation.

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Double-Blind Method; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Models, Biological

The effects of esmolol, an ultrashort-acting beta blocker, and verapamil were compared in controlling ventricular response in 45 patients with atrial fibrillation or atrial flutter, in a randomized, parallel, open-label study. Patients with either new onset (less than 48 hours, n = 31) or old onset (greater than 48 hours, n = 14) of atrial fibrillation or flutter with rapid ventricular rate were stratified to receive esmolol (n = 21) or verapamil (n = 24). Drug efficacy was measured by ventricular rate reduction and conversion to sinus rhythm. The heart rate declined with esmolol from 139 to 100 beats/min (p less than 0.001) and with verapamil from 142 to 97 beats/min (p less than 0.001). Fifty percent of esmolol-treated patients with new onset of arrhythmias converted to sinus rhythm, whereas only 12% of those who received verapamil converted (p less than 0.03). Mild hypotension was observed in both treatment groups. Esmolol compares favorably with verapamil with respect to both efficacy and safety in acutely decreasing ventricular response during atrial fibrillation or flutter. Moreover, conversion to sinus rhythm is significantly more likely with esmolol.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Atrial Fibrillation; Atrial Flutter; Blood Pressure; Clinical Trials as Topic; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Multicenter Studies as Topic; Propanolamines; Random Allocation; Verapamil

The effect and choice of a drug to control heart rate for symptomatic improvement in patients with isolated mitral stenosis with normal sinus rhythm (n = 10) or atrial fibrillation (n = 10) were studied. Digoxin (0.25-0.5 mg daily), metoprolol (50-100 mg twice a day) and verapamil (40-80 mg three times a day) were evaluated for this purpose. An open randomised cross-over design was followed. The efficacy of a drug was evaluated by: (1) subjective improvement on a visual analog scale, and (2) objective improvement on repeated multi-stage symptom-limited treadmill exercise. In patients with sinus rhythm greater than or equal to 50% subjective improvement was seen in 90%, 40% and nil with metoprolol, verapamil and digoxin, respectively. The total work done by these patients was 1008 +/- 541 kpm (control), 2869 +/- 1418 kpm on metoprolol, 2369 +/- 884 kpm on verapamil and 1654 +/- 918 kpm on digoxin. In patients with atrial fibrillation greater than or equal to 50% subjective improvement was seen in 80%, 40% and 30% with verapamil, metoprolol and digoxin, respectively. The total work done by these patients was 555 +/- 232 kpm (control), 1379 +/- 553 kpm on verapamil, 1251 +/- 575 kpm on metoprolol and 716 +/- 340 kpm on digoxin. The degree of improvement on a drug appeared to be a function of its ability to control resting and exercise heart rates in two different rhythms in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arrhythmia, Sinus; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Metoprolol; Mitral Valve Stenosis; Random Allocation; Verapamil

This study has compared the effect on heart rate control of the addition of pindolol 15 mg bd or verapamil 40 mg tds to maintenance digoxin therapy in 12 patients with chronic atrial fibrillation. The study was performed in a randomized cross-over fashion. Treatment effects were assessed by 24-h ambulatory electrocardiography and symptomatic improvement by symptom scores. The results show that the combination of pindolol and digoxin provides better control of atrial fibrillation. With an attenuation of daytime tachycardia, prevention of nocturnal bradycardia and reduction in the length of nocturnal pauses in rhythm. Overall heart rate variability was significantly less with digoxin and pindolol (523 beats min-1 h-1) than with digoxin and verapamil (745 beats min-1 h-1). We conclude that, in the dosages employed, combined digoxin and pindolol therapy is superior to either digoxin and verapamil in combination or digoxin alone for the treatment of atrial fibrillation.

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Dyspnea; Female; Heart Rate; Humans; Middle Aged; Pindolol; Verapamil

Although digoxin is often the drug of choice to control the ventricular response in chronic atrial fibrillation, it fails to control exercise-induced increase in heart rate. The efficacy of diltiazem to control ventricular response and to improve cardiovascular performance during maximal exercise was investigated in 13 digitalized patients with chronic atrial fibrillation. A placebo controlled prospective randomized double-blind study, was preceded by open titration phase. During the diltiazem treatment phase, mean ventricular response diminished at rest (85 +/- 12 versus 107 +/- 19 during digoxin therapy and versus 101 +/- 18 during digoxin and placebo therapy; p less than 0.001), as well as during maximal exercise (142 +/- 13 versus 159 +/- 17 during digoxin treatment and versus 160 +/- 14 during digoxin plus placebo treatment; p less than 0.001). During exercise (50 W), in a subgroup of 7 patients, mean ventricular rate dropped: 109 +/- 19 versus 142 +/- 21 during digoxin treatment and versus 143 +/- 17 during digoxin plus placebo treatment; p less than 0.001). In all patients, the mean rate at rest decreased about 19.3 +/- 6.9% and at maximal exercise about 10.3 +/- 4.9%. In the subgroup of the 7 patients ventricular mean rate at a load of 50 W decreased about 23.6 +/- 7.9%. In all the patients, maximal exercise capacity improved: the MET mean value increased from 3.59 +/- 1.3 to 4.52 +/- 1.18 (p less than 0.001); the mean value of the maximum exercise (MEC), according to the Redfords formula, increased from 65 +/- 48 to 132 +/- 70 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Fibrillation; Chronic Disease; Depression, Chemical; Digitalis; Digoxin; Diltiazem; Double-Blind Method; Drug Evaluation; Female; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Random Allocation

In eight patients with chronic atrial fibrillation, treatment with digoxin (plasma drug concentration 1.3 to 2.0 nmol l-1) was associated with a significantly higher incidence of ventricular premature beats (VPBs) (mean 22.8 h-1) than diltiazem 120 mg three times daily (mean 6.8 h-1) (P less than 0.05). Seven out of the eight patients showed an increase in numbers of VPBs recorded over 24 h during treatment with digoxin when compared with diltiazem. The clinical importance of these results is unclear, but atrial fibrillation and ischaemic heart disease frequently co-exist, and increases in ventricular ectopy may predispose to serious ventricular arrhythmias following myocardial infarction.

Topics: Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Chronic Disease; Digoxin; Diltiazem; Female; Humans; Male; Middle Aged

It has been suggested that patients in whom atrial fibrillation (AF) is associated with poor exercise tolerance respond better to treatment with xamoterol plus digoxin than to digoxin alone; this may be attributable to better control of exercise induced tachycardia. We have examined data obtained during studies comparing digoxin and two calcium antagonists in the treatment of AF to see whether subgroups of patients with particularly poor exercise tolerance, rheumatic heart disease or rapid post-exercise heart rates might derive particular benefit from one modality of treatment as opposed to another. The results do not indicate that calcium antagonists improve exercise tolerance compared with digoxin in any of these subgroups despite achieving consistently better control of exercise induced tachycardia.

Topics: Atrial Fibrillation; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Diltiazem; Double-Blind Method; Heart Rate; Humans; Physical Exertion; Random Allocation; Rheumatic Heart Disease; Verapamil

In a prospective study 45 patients with paroxysmal atrial fibrillation were randomly assigned to one of three groups (of 15 patients each): group I received oral digoxin, three times 0.125 mg up to twice 0.25 mg daily; group II oral digoxin twice 0.125 mg and quinidine hydrogen sulphate 750-1000 mg daily; group III oral digoxin three times 0.125 mg and flecainide 200-300 mg daily. During a mean observation period of 11 months digoxin alone was significantly less effective (P less than 0.05) in reducing or suppressing paroxysms of atrial fibrillation than digoxin plus quinidine or flecainide. Flecainide with digoxin was more effective than the drug regimen in groups I and II (P less than 0.05). Two patients each in groups I and III had side effects, eight in group II. The results suggest that, at the chosen dosage, flecainide produces fewer side effects than quinidine.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Female; Flecainide; Humans; Male; Middle Aged; Prospective Studies; Quinidine; Random Allocation; Time Factors

Six patients with chronic atrial fibrillation (AF) took single doses of digoxin, verapamil and diltiazem, alone and in combination. Three hours after dosing, resting and post-exercise heart rate, exercise tolerance and resting and post-exercise cardiac output were measured. Post-exercise heart rates ranged from 167 bpm (after placebo) to 122 bpm (after digoxin plus diltiazem) (P less than 0.05). However, the lower ventricular rates seen after treatment with the calcium antagonists were not associated with improved exercise tolerance, which did not differ significantly between the various treatments. Reduction of the ventricular rate was associated with a small increase in stroke volume but the benefits of this were offset by a rate related reduction in cardiac output. Further reduction of the rapid ventricular rates seen in digitalized patients with AF does not appear to be of benefit in terms of improving either exercise tolerance or cardiac output.

Topics: Aged; Atrial Fibrillation; Cardiac Output; Chronic Disease; Digoxin; Diltiazem; Heart Rate; Humans; Middle Aged; Physical Exertion; Verapamil

1. The efficacy of verapamil alone, or in combination with digoxin, was compared with digoxin alone in eight patients with chronic atrial fibrillation in this double-blind placebo-controlled study. 2. After 2 weeks on each treatment regimen, heart rate at rest and during progressive load treadmill exercise, left ventricular function at rest and nocturnal heart rate were measured. 3. Oral verapamil alone at a dose of 80 mg three times daily, or 40 mg of verapamil three times daily in combination with 0.25 mg of digoxin daily, was superior to digoxin alone in doses associated with high serum digoxin concentrations (mean +/- SEM 1.6 +/- 0.3 micrograms/l). This superiority manifested as greater control of heart rate during work rates equivalent to regular daily activities, and was not associated with deterioration in left ventricular function or worsening nocturnal bradycardia. 4. We conclude that the treatment of choice in patients with chronic atrial fibrillation is either 80 mg of verapamil three times daily or 40 mg of verapamil three times daily in combination with digoxin.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Random Allocation; Verapamil

Fourteen patients (four females) with chronic atrial fibrillation were entered into a randomized, double-blind crossover study to compare the effects of treatment with diltiazem alone, digoxin alone, and a combination of diltiazem plus digoxin. The dose of digoxin was adjusted so as to achieve serum concentrations within the range 1.3-2.6 nmol l-1 between six and eight hours after dosing. Four patients were withdrawn from the study; three patients experienced side effects while taking diltiazem and one reverted to sinus rhythm while taking digoxin. Among the remaining 10 patients, mean heart rates were significantly lower during treatment with the combination of digoxin and diltiazem than with digoxin alone both at rest, after exercise and during ambulatory ECG monitoring. Post-exercise heart rates were reduced by 15% with combination therapy when compared with digoxin alone (151.9 vs. 128.1 bpm), but there was no evidence that this reduction in ventricular rate was associated with improved exercise tolerance. The results suggest that further reduction of the rapid ventricular rates seen in digitalized patients with AF by the use of diltiazem does not appear to be of benefit in the majority of patients.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Diltiazem; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Random Allocation

The safety and efficacy of diltiazem were compared with digoxin maintenance therapy for control of ventricular response in 19 patients with chronic atrial fibrillation. The relationship between drug plasma levels and cardiovascular effects was also investigated. After 7 days of combined therapy with diltiazem (60 mg three times a day in 10 patients and four times a day in nine patients) and digoxin (0.125 mg/day in two patients and 0.250 mg/day in 17 patients), the 24-hour mean heart rate derived from ambulatory ECG recording was reduced by 16.3% in comparison with digoxin therapy alone; the serum digoxin level was not significantly changed (1.06 +/- 0.43 vs 1.05 +/- 0.61 ng/ml). After a standardized bicycle exercise test (50 watts for 3 minutes), maximal heart rate was reduced by 19.9%, diastolic blood pressure was decreased by 8.9%, and systolic pressure-rate product was decreased by 12.5%. Diltiazem plasma levels (mean 120.9 +/- 63.3 ng/ml) were linearly correlated with percentage variations in maximal heart rate, diastolic blood pressure, systolic blood pressure, and pressure-rate product during exercise. Eighteen patients in succession discontinued digoxin therapy; after 14 days of diltiazem alone, the 24-hour mean heart rate returned to control values of digoxin therapy, whereas maximal heart rate and pressure-rate product during exercise were significantly reduced (-17.2% and -14.1%, respectively), with no changes in blood pressure. Diltiazem plasma levels (135.0 +/- 83.2 ng/ml) showed a linear correlation with the percentage of reduction in maximal heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Fibrillation; Blood Pressure; Chronic Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion

Nine male patients (mean age 65 yr) with chronic atrial fibrillation underwent maximal exercise testing during placebo, beta-adrenergic (celiprolol, 600 mg), or calcium (diltiazem, 30 or 60 mg four times daily) channel blockade. The results were analyzed to determine which factors most closely related to ratings of perceived exertion (RPE) during exercise. Heart rate (HR), blood pressure (BP), oxygen uptake (VO2), minute ventilation (VE), and carbon dioxide production (VCO2) were evaluated at rest, 3.0 mph/0% grade, the gas exchange anaerobic threshold (ATge), 80% of placebo maximal O2 uptake, and maximal exercise. Both beta-adrenergic and calcium channel blockade significantly reduced heart rate and systolic blood pressure relative to placebo; these effects were more profound during beta-adrenergic blockade and as exercise progressed. Correlation coefficients and estimates of slope were derived for changes in RPE during exercise vs. changes in HR, VO2, VE, and VCO2 during the three treatments (r = 0.76 to 0.92, P less than 0.001). Although RPE was significantly correlated with HR during placebo and diltiazem therapy (r = 0.45, P less than 0.01), this was not the case during beta-adrenergic blockade (r = 0.31, NS). Slope of the regression lines between RPE and VO2, VE, and VCO2 did not differ between the three treatments. Slope of the regression lines between RPE and HR differed only during calcium channel blockade. Because the presence of atrial fibrillation and beta-adrenergic blockade altered the associations between RPE, VO2, and HR, these results suggest that VE is more closely related to RPE than the other parameters.

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Blood Pressure; Carbon Dioxide; Celiprolol; Chronic Disease; Clinical Trials as Topic; Digoxin; Diltiazem; Double-Blind Method; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Oxygen; Oxygen Consumption; Physical Exertion; Propanolamines; Random Allocation

Multiple trials have suggested the use of digoxin, digoxin and propranolol, or timolol to prevent atrial fibrillation after coronary artery bypass grafting. No trial has evaluated the efficacy of digoxin verus propranolol. Furthermore, the predictors of postoperative atrial fibrillation and the long-term consequence of atrial fibrillation that reverts to sinus rhythm have not been established. One hundred fifty patients were randomized to receive no drug, propranolol (20 mg every 6 hours), or digoxin (0.5 mg followed by 0.25 mg daily). Twenty-seven patients were excluded from data analysis. In the remaining 123 patients, no preoperative parameter (age, sex, diabetes, hypertension, smoking, electrocardiographic p wave morphology, or preoperative digoxin or propranolol therapy), intraoperative parameter (bypass time, aortic cross-clamp time, or number of vessels bypassed), or postoperative parameter (peak creatinine kinase, congestive heart failure, or pericarditis) by univariate or multivariate analysis predicted patients at risk for atrial fibrillation. Sustained atrial fibrillation developed in 37.5% of control and 32.6% of digoxin-treated patients. Only 16.2% of propranolol-treated patients had sustained atrial fibrillation (p less than 0.03). There were no in-hospital complications in those patients with atrial fibrillation. After 26 +/- 7 months follow-up, those patients with postoperative atrial fibrillation had no increased incidence of angina, cerebral vascular accident, myocardial infarction, or sudden death. Therefore, in this select population, propranolol prophylaxis is effective but discretionary.

Topics: Atrial Fibrillation; Clinical Trials as Topic; Coronary Artery Bypass; Digoxin; Female; Humans; Male; Middle Aged; Prognosis; Propranolol; Random Allocation; Risk; Time Factors

In some patients with chronic atrial fibrillation, treatment with digitalis alone may fail to produce a satisfactory decrease in heart rate at rest or during exercise or emotional stress. Findings of a few clinical studies suggest that beta blockade in combination with digitalis therapy may be of benefit in these patients. In a randomized, double-blind, placebo-controlled, parallel-group, 8-week study of 32 patients with chronic atrial fibrillation, the effects of digoxin therapy alone were compared with a combination of digoxin and nadolol. Criteria for entry into the study included ventricular rate at rest greater than or equal to 80/min or greater than or equal to 120/min with exercise, and serum digoxin levels within the therapeutic range. After digoxin dose titration to produce therapeutic levels, digoxin dosage remained constant throughout the balance of the study. After a 2-week, single-blind placebo lead-in period, patients were randomized to receive either digoxin plus placebo or a combination of digoxin and nadolol. The dose of nadolol/placebo was titrated from 20 to 120 mg daily as tolerated. Twenty-four hour ambulatory electrocardiographic (Holter) recordings, symptom-limited exercise treadmill tests and serum digoxin and nadolol levels were obtained at the end of the single and double-blind treatment periods. Comparing endpoint with baseline, results from Holter recordings showed that patients treated with a combination of digoxin and nadolol had significant (p less than 0.001) decreases in 24 hour average (78 +/- 4 to 63 +/- 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Nadolol; Random Allocation

to determine whether digoxin is effective in converting atrial fibrillation of recent onset to normal sinus rhythm.. randomized, double-blinded, placebo-controlled trial with a maximum 18-hour treatment period.. emergency room and medical floors of a non-referral city hospital.. consecutive sample of 36 patients with atrial fibrillation of 7 days' duration or less, not on digitalis glycoside or anti-arrhythmic agents, with ventricular rate between 85 to 175 beats/min, without evidence of heart failure, acute myocardial infarction, unstable angina, preexcitation syndrome, thyrotoxicosis, hypokalemia, renal impairment, or severe metabolic disturbances.. digoxin solution in capsules or identical placebo, given in doses of 0.6, 0.4, 0.2, and 0.2 mg, at 0, 4, 8, and 14 hours, respectively, or until conversion to sinus rhythm, whichever occurred first. Continuous electrocardiographic recording by Holter monitor.. nine of eighteen patients receiving digoxin and 8 of 18 receiving placebo had a return to sinus rhythm within 18 hours of study entry (95% confidence interval for the difference in proportions, -11% to 22%). Mean time to conversion was 5.1 hours in the digoxin group and 3.3 in the placebo group (95% Cl, -3.6 to 7.0 hours).. spontaneous reversion to sinus rhythm is common in patients with atrial fibrillation of recent onset. Digitalization was not shown to affect the likelihood of reversion to sinus rhythm, and thus cannot be recommended for this purpose in patients with atrial fibrillation.

Topics: Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Double-Blind Method; Heart Rate; Humans; Middle Aged; Myocardial Contraction; Random Allocation; Stroke Volume

Patients with atrial fibrillation frequently show a wide variation in heart rate with digoxin therapy. We have compared the effect on heart rate variability, of doubling the digoxin dosage or adding verapamil 120 mg daily in a randomized cross-over study in 14 patients. Twenty-four hour ambulatory electrocardiographic recordings, six minute walking tests and palpitation and breathlessness scores were obtained on each regime. All patients exhibited a diurnal pattern in heart rate variability. Both treatments significantly lowered heart rate but high dose digoxin lowered minimum heart rate significantly more than digoxin and verapamil, causing more night time bradycardia. Overall, digoxin with verapamil produced significantly less heart rate variability than digoxin alone. Day time but not night time pauses were prolonged by digoxin and verapamil but were prolonged more by high dose digoxin. Five (36%) patients had serum digoxin levels in the toxic range when taking high dose digoxin. Palpitations were significantly reduced by both treatments but most improvement occurred with digoxin and verapamil. No significant effect was found on six minute walking distances or breathlessness scores. In conclusion, the addition of verapamil to digoxin was superior to increasing the dose of digoxin alone, producing significantly better control of heart rate variability with less night time bradycardia.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Random Allocation; Verapamil

Twelve patients (including 2 females) with chronic atrial fibrillation were entered into a randomized, double blind crossover study to compare the effects of digoxin and verapamil upon heart rate, exercise tolerance and symptom control. The dose of digoxin was adjusted so as to give serum concentrations within the range 1.3 to 2.6 nmol l-1 between four and six hours after dosing, and was continued for six weeks. The dose of verapamil was increased from 40 mg tds to 80 mg tds to 120 mg tds at fortnightly intervals. Three patients did not complete the study; two because of adverse effects attributable to verapamil. In the remaining nine patients, mean post exercise heart rates were significantly lower during treatment with verapamil 80 mgs tds (126.7 bpm) than with verapamil 40 mg tds (148.6 bpm) or digoxin (146.7 bpm). However, exercise tolerance was similar with both verapamil and digoxin and the superior control of exercise induced tachycardia achieved with higher doses of verapamil was not associated with improved exercise endurance. Visual analogue scale scores for constipation were significantly higher during treatment with verapamil; scores for other possible side effects and for overall wellbeing were similar. The results do not confirm the findings of others who have reported that verapamil is superior to digoxin in the treatment of atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Double-Blind Method; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Verapamil

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 study the effect of hypomagnesemia on control of atrial fibrillation (AF), serum magnesium levels were determined in 45 consecutive patients with symptomatic AF; 20% were hypomagnesemic (serum magnesium less than 1.5 mEq/liter). In a blinded treatment protocol, hypomagnesemic patients required twice the amount of intravenous digoxin to effect control of AF (p less than 0.05). Underlying diagnoses, blood chemistries and the use of other medications that could affect digoxin therapy were similar for the 2 groups. Diuretic therapy before inclusion into the study was not significantly associated with hypomagnesemia. Thus, hypomagnesemia is common among patients with symptomatic AF. Moreover, it appears to interfere with the effect of intravenous digoxin on AF. These results suggest that monitoring of serum magnesium and, where necessary, replacement of magnesium deficiency may be beneficial in patients with symptomatic AF for whom digoxin therapy is being contemplated.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Diuretics; Electric Countershock; Humans; Infusions, Parenteral; Magnesium; Prospective Studies; Time Factors

Topics: Amiodarone; Atrial Fibrillation; Benzofurans; Digoxin; Humans; Myocardial Infarction

The efficacy of sotalol in treating acute atrial fibrillation and flutter after open heart surgery was compared with that of a digoxin/disopyramide combination. Forty adult patients with postoperative atrial arrhythmias were randomised into either group 1 (sotalol 1 mg/kg bolus intravenously plus 0.2 mg/kg intravenously over 12 hours) or group 2 (digoxin 0.75 mg intravenously, then two hours later disopyramide 2 mg/kg intravenous bolus and 0.4 mg/kg/h intravenously for 10 hours). In each group, 17 out of 20 patients reverted to sinus or junctional rhythm within 12 hours. The time to reversion in group 1 was significantly shorter than in group 2. Systolic blood pressure fell by greater than or equal to 20 mm Hg or to less than or equal to 90 mm Hg during drug administration in 17 out of 20 patients in group 1 (sotalol withdrawn in two) and in none out of 20 in group 2. Two patients in group 1 developed transient bradycardia (sotalol withdrawn in one). None of 17 patients in group 1 and two of 17 in group 2 relapsed temporarily into atrial fibrillation during the 12 hours of intravenous treatment. On continued oral treatment, one late relapse occurred in group 1 and five in group 2, and five patients in group 2 had disopyramide withdrawn because of anticholinergic side effects (acute urinary retention in four). Sotalol was as effective as the digoxin/disopyramide combination and acted significantly faster. Sensitivity to beta blockade in these patients may be related to high plasma catecholamine concentrations known to occur after cardiopulmonary bypass.

Topics: Atrial Fibrillation; Atrial Flutter; Cardiopulmonary Bypass; Clinical Trials as Topic; Digoxin; Disopyramide; Female; Humans; Infusions, Parenteral; Injections, Intravenous; Male; Middle Aged; Postoperative Complications; Sotalol

The possible kinetic and hemodynamic interactions between digoxin and nifedipine were evaluated in nine patients with atrial fibrillation who were receiving chronic digoxin. After 2 control weeks, nifedipine (20 mg b.i.d.), in a new formulation with sustained release characteristics, was added to the therapeutic regimen for 2 weeks. Trough serum digoxin concentrations and peak nifedipine concentrations were determined repeatedly. On the same days, resting blood pressure and heart rate were measured. During nifedipine administration, serum digoxin levels increased by 15% from 0.87 +/- 0.38 to 1.04 +/- 0.37 ng/ml (mean +/- SD, p less than 0.05). This was accompanied by a reduction in systolic and diastolic blood pressure of 16 +/- 6 (p less than 0.01) and 12 +/- 5 mm Hg (p less than 0.001), respectively. In two patients, noncardiac side effects were reported. In two other patients, nifedipine was discontinued because of skin rash and severe headache, respectively. In conclusion, plasma digoxin levels were elevated slightly in the presence of nifedipine, but this probably has little clinical relevance.

Topics: Adult; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nifedipine

Heart rate at rest and during increasing workloads was measured in a double blind study of 12 patients with chronic atrial fibrillation when serum concentrations of digoxin were nil and at low and high therapeutic values. Twelve normal subjects were studied for comparison. The heart rate at all levels of exercise in most patients with atrial fibrillation was not adequately controlled by any serum digoxin concentration tested despite a reduction in heart rate with increasing serum digoxin concentrations. Control of the resting heart rate, even in patients with high serum digoxin concentrations, did not ensure adequate control of the heart rate during work rates equivalent to regular daily activities.

Topics: Adult; Atrial Fibrillation; Digoxin; Double-Blind Method; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion

The effect of Corwin, a new oral beta, partial agonist, on the ventricular response to atrial fibrillation was studied in digitalised patients during 24 hour ambulatory electrocardiography and during exercise on a treadmill in a double blind placebo controlled crossover trial. Corwin reduced the maximum heart rate during exercise from 162(16) beats/min to 120(9) beats/min and reduced the peak heart rate during ambulatory electrocardiography from 113(11) to 90(6) beats/min consistent with a beta adrenoreceptor antagonist action at higher levels of sympathetic nervous system activity. Minimum heart rate during ambulatory electrocardiography was increased from 62(5) to 70(5) beats/min indicating that at lower levels of sympathetic activity the drug acts as a beta agonist. The drug increased exercise tolerance significantly. Serum digoxin concentrations were not affected by the drug. Thus Corwin appears to be effective in stabilising heart rate during atrial fibrillation both at rest and during exercise in digitalised patients.

Topics: Adrenergic beta-Agonists; Adult; Aged; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Propanolamines; Xamoterol

Nadolol, a long-acting beta-adrenergic-blocking agent, was evaluated in 20 patients with chronic atrial fibrillation by means of a randomized, double-blind, crossover study. Patients were required either to demonstrate resting heart rates in excess of 80 bpm or to show a rate of 120 bpm or an increment of greater than 50 bpm during mild treadmill exercise provocation (3 minutes, 1.75 mph, 10% grade). With placebo the group averaged a heart rate of 92 +/- 19 bpm, determined by 24 hours of ambulatory ECG recordings; this rate was significantly reduced to 73 +/- 16 bpm (p less than 0.001) with nadolol (mean dosage, 87 +/- 43 mg/day). During standardized exercise testing, heart rates increased to 153 +/- 26 bpm with placebo and to 111 +/- 24 bpm with nadolol (p less than 0.001), representing 65% and 52% increments, respectively. Digoxin blood levels averaged 0.8 +/- 0.5 ng/ml with placebo and were similar with nadolol (0.9 +/- 0.4; p = NS). Total exercise time on a modified Bruce treadmill protocol was 466 +/- 143 seconds with placebo and was significantly decreased by nadolol (380 +/- 143; p less than 0.01). During initial dose titration with nadolol, one patient was dropped from study for intolerable fatigue and one for worsened claudication. No patients were dropped from the double-blind treatment periods, although two patients receiving nadolol and one patient receiving placebo complained of moderate fatigue. We conclude that nadolol is a safe and effective agent for the control of spontaneous and exercise-provoked heart rates in patients with chronic atrial fibrillation who were already receiving digoxin treatment.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Nadolol; Physical Exertion; Propanolamines; Random Allocation; Time Factors

The indication for digitalis treatment was investigated in a controlled and prospective study lasting 12 months in 110 patients on long-term haemodialysis. In ten patients, digitalis was needed because of tachyarrhythmia due to atrial fibrillation and in five because of recurrent pulmonary edema. In 57 patients receiving digitoxin, therapy was discontinued for 4 to 6 weeks, whereas 13 patients not yet treated with digitalis, received digitoxin for 4 weeks. Without digitoxin, trial fibrillation occurred in 4 patients, while no patient experienced atrial fibrillation with digitoxin (P = 0.002). In 13 patients, radiological findings (heart enlargement, pulmonary congestion) were better with digitoxin than without. Thus digitoxin appeared to be clearly indicated in 29% of the haemodialysed patients. Additionally, digitalis was indicated in 31 patients because of heart enlargement, pulmonary congestion and (or) previous pulmonary edema. Initially, 76% of the patients were receiving digitoxin, whereas, after the investigation, the rate was only 57% (P less than 0.001). The prospective frequency of clinically apparent digitoxin intoxication was low (3%) and so were the overall toxic plasma digitoxin levels (5%). Digitalis should be given deliberately but not restrictively to haemodialysis patients, since atrial fibrillation (13%) and heart failure (50%) are frequent and often concealed.

Topics: Adult; Aged; Atrial Fibrillation; Cardiomegaly; Clinical Trials as Topic; Digitalis; Digitoxin; Digoxin; Female; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Pulmonary Edema; Renal Dialysis; Tachycardia; Time Factors

The efficacy and safety of oral verapamil, 240 mg, with or without digoxin were studied in 52 patients with chronic atrial fibrillation at rest, and during mild and maximal exercise. Twenty-four patients were studied during the following therapeutic modalities: no therapy; digoxin, 0.25 mg and 0.5 mg daily; digoxin, 0.25 mg and verapamil; and verapamil alone. Heart rate at rest and during all levels of exercise was decreased significantly (p less than 0.005), either by combining digoxin with verapamil or by verapamil therapy alone. In contrast, the excessive heart rate response to exercise was not prevented by digoxin even with good serum concentrations. The improved control of heart rate with verapamil was associated with a significantly improved exercise capacity. Verapamil is an important and safe modality of treatment, with or without digoxin, in the long-term control of heart rate in chronic atrial fibrillation. It is superior to digoxin in controlling the ventricular rate and in improving exercise capacity.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Drug Therapy, Combination; Exercise Test; Female; Half-Life; Heart Rate; Humans; Male; Middle Aged; Time Factors; Verapamil

The safety and efficacy of oral verapamil to control exercise tachycardia in 27 patients with atrial fibrillation and 3 with atrial flutter receiving digitalis was evaluated in a double-blind, randomized, crossover study. The heart rate in patients who received verapamil compared with placebo group was lower at rest (mean 69 +/- 13 versus 87 +/- 20 beats/min, p less than 0.01), as was the degree of tachycardia at the end of 3 minutes of a standardized exercise test (104 +/- 14 versus 136 +/- 23 beats/min, p less than 0.01). Doses of verapamil required to achieve suppression of tachycardia were 240 mg/day in 18 patients, 320 mg/day in 6 patients, and 480 mg/day in 3 patients. Only 3 patients complained of adverse effects from verapamil during the double-blind phase of the study. Two patients were discontinued from the study because of adverse reactions. No clinically significant changes during verapamil therapy were observed on the electrocardiogram, chest roentgenogram, echocardiogram or in the laboratory evaluation. Digoxin blood levels were higher in patients who received concomitant verapamil compared with placebo (1.23 +/- 0.59 versus 0.85 +/- 0.46 ng/ml, p less than 0.01), but no patient had signs or symptoms of digitalis toxicity. Thus, oral verapamil given in addition to digitalis is a safe and effective agent in the treatment of patients with chronic atrial fibrillation or flutter to decrease exercise-induced tachycardia.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Atrial Flutter; Chronic Disease; Clinical Trials as Topic; Digitalis; Digoxin; Double-Blind Method; Female; Humans; Male; Middle Aged; Physical Exertion; Placebos; Plants, Medicinal; Plants, Toxic; Random Allocation; Tachycardia; Verapamil

Oral verapamil has previously been shown to reduce heart rate at rest and during mild exercise in chronic atrial fibrillation. Its efficacy in improving cardiovascular performance at higher levels of exercise and its safety were investigated in a prospective, randomized, placebo controlled double-blind study preceded by an open label titration phase in 20 digitalized patients with chronic atrial fibrillation. Maximal exercise capacity was improved (from 522 +/- 257 to 806 +/- 348 work units, p less than 0.0005) when tested by a standardized multistage ergometry exercise test. Heart rate was also reduced at rest, at the end of 3 minutes of 300 KPM exercise, and at the point of maximal exercise. Blood pressure and double product were also reduced. Its efficacy and safety may make verapamil the treatment of choice in chronic atrial fibrillation.

Topics: Adult; Aged; Atrial Fibrillation; Blood Pressure; Digoxin; Double-Blind Method; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Prospective Studies; Random Allocation; Verapamil

Topics: Adult; Aged; Atrial Fibrillation; Atrial Flutter; Blood Pressure; Cardiac Surgical Procedures; Clinical Trials as Topic; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Verapamil

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Female; Humans; Male; Medigoxin; Middle Aged

This study concerns 8 elderly patients with age-related chronic atrial fibrillation that required control of the ventricular response. The effects of oral administration of placebo, pindolol, verapamil, digoxin and digoxin + pindolol were assessed (each for a week) during three daily activity and sleep sessions, over a six-week period. Cardiac rhythm was monitored by taped electrocardiograms. Either digoxin or pindolol was effective, but digoxin was the best tolerated of all the drugs. A combination of pindolol and digoxin reduced the maximum ventricular rate without further depression of the minimum ventricular rate. Digoxin seems to be well tolerated in the control of atrial fibrillation in the elderly, and beta blockade may be a useful therapeutic adjunct.

Topics: Aged; Atrial Fibrillation; Digoxin; Drug Tolerance; Electrocardiography; Evaluation Studies as Topic; Female; Heart Rate; Humans; Male; Middle Aged; Pindolol; Placebos; Verapamil

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

1 Medigoxin (Lanitop) 300 microgram/day and digoxin (Lanoxin) 500 microgram/day were compared in cross-over studies on healthy volunteers and on patients with uncontrolled atrial fibrillation. Serum glycoside concentrations were measured by radioimmunoassay and ventricular rates by ECG. The two regimens appeared to be therapeutically equivalent. 2 The mean serum glycoside concentration in the steady state and the rate at which this state was attained were similar with both drug regimens in the healthy volunteer group. The between-subject variation in serum glycoside concentration was not significantly less during medigoxin administration. 3 The renal clearance of serum glycoside was much lower during medigoxin administration both in healthy volunteers and in patients. This was not due to a difference in serum protein binding. The relatively small dosage requirement for medigoxin was attributed partly to a lower clearance rate and partly to more nearly complete absorption. 4 During the first 2 weeks of the patient study there was a substantial rise in mean serum glycoside concentration and a corresponding fall in ventricular rate. This was attributed to more consistent self-administration of digoxin. The subsequent change to medigoxin had no further effect on mean glycoside concentration, ventricular rate or frequency of ventricular ectopic beats. 5. An attempt to compare the onset of the ventricular rate response to a single oral dose of medigoxin with that to digoxin gave inconclusive results.

Topics: Adult; Analysis of Variance; Atrial Fibrillation; Digoxin; Female; Humans; Male; Medigoxin; Metabolic Clearance Rate

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

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

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: Activities of Daily Living; Adult; Aged; Atrial Fibrillation; Blood Pressure; Cardiac Volume; Digoxin; Disability Evaluation; Electrocardiography; Female; Humans; Male; Middle Aged; Spirometry

Topics: Atrial Fibrillation; Digoxin; Exercise Test; Female; Heart Function Tests; Heart Rate; Heart Ventricles; Humans; Male

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Berlin; Digoxin; Heart Block; Heart Failure; Humans; Myocardial Infarction; Myocardium; Oxygen Consumption; Tachycardia; Ventricular Fibrillation

Atrial fibrillation is one of the most common arrhythmias, but the optimal drug choice for a rate control strategy remains uncertain.. A retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta-blockers, digoxin, or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovascular (CV) hospitalization. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model.. A total of 12,723 patients were discharged on beta-blockers alone, 406 on digoxin alone, and 1499 discharged on combined beta-blocker and digoxin therapy with a median follow-up time of 356 days. After baseline covariate adjustment, the digoxin alone (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.85-1.81) and the combined group (HR, 1.09; 95% CI, 0.90-1.31) were not associated with increased risk for the composite endpoint compared with the beta- blocker-alone group. These results were robust to sensitivity analyses.. Patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta-blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared with those discharged on isolated beta-blocker therapy. However, additional studies are required to refine the precision of these estimates.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Prospective Studies; Retrospective Studies; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Rate; Humans

De novo atrial fibrillation (AF) is rare in pregnancy. The exact pathophysiology of AF is unclear; it might be caused by several cardiovascular and hemodynamic changes that occur in pregnancy, leading to an increased stretch in myocardial cells of the atrial wall.. A 26-year-old primigravida with a thus far uncomplicated pregnancy presents with symptoms of heart palpitations, shortness of breath and chest pain. The CTG was normal but an ECG showed de novo atrial fibrillation. The patient was given two doses of digoxin 0.25mg after which sinus rhythm was achieved. No anatomical substrate was found; hence it was seen as most likely caused by increased hemodynamic demands in pregnancy. The delivery and postpartum period were uncomplicated.. AF is rarely seen in pregnancy. Treatment favours rate and/or rhythm control with metoprolol and digoxin, respectively. Anticoagulation is not indicated in lone AF during pregnancy. Vaginal birth is preferred.

Topics: Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Heart Atria; Humans; Metoprolol; Pregnancy; Pregnant Women

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

The safety of digoxin therapy in atrial fibrillation (AF) remains ill-defined. We aimed to evaluate the effects of digoxin over beta-blocker therapy in AF.. Patients with AF who were treated with either digoxin or a beta blocker from the ESC-EHRA EORP AF (European Society of Cardiology-European Heart Rhythm Association EURObservational Research Programme Atrial Fibrillation) General Long-Term Registry were included. Outcomes of interest were all-cause mortality, cardiovascular (CV) mortality, non-CV mortality, quality of life, and number of patients with unplanned hospitalizations. Of 6377 patients, 549 (8.6%) were treated with digoxin. Over 24 months, there were 550 (8.6%) all-cause mortality events and 1304 (23.6%) patients with unplanned emergency hospitalizations. Compared to beta blocker, digoxin therapy was associated with increased all-cause mortality [hazard ratio (HR) 1.90 (95% confidence interval, CI, 1.48-2.44)], CV mortality [HR 2.18 (95% CI 1.47-3.21)], and non-CV mortality [HR 1.68 (95% CI 1.02-2.75)] with reduced quality of life [health utility score 0.555 (±0.406) vs. 0.705 (±0.346), P < 0.001] but no differences in emergency hospitalizations [HR 1.00 (95% CI 0.56-1.80)] or AF-related hospitalizations [HR 0.95 (95% CI 0.60-1.52)]. On multivariable analysis, there were no differences in any of the outcomes between both groups, after accounting for potential confounders. Similar results were obtained in the subgroups of patients with permanent AF and coexisting heart failure. There were no differences in outcomes between AF patients receiving digoxin with and without chronic kidney disease.. Poor outcomes related to the use of digoxin over beta-blocker therapy in terms of excess mortality and reduced quality of life are associated with the presence of other risk factors rather than digoxin per se. The choice of digoxin or beta-blocker therapy had no influence on the incidence of unplanned hospitalizations.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Digoxin; Humans; Quality of Life; Registries

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

New-onset of atrial fibrillation (NOAF) in critically ill patients is the most common acute cardiac dysrhythmia, but evidence-based data regarding treatment strategies are scarce. In this retrospective monocentric study, we compared effectiveness of amiodarone versus digitalis for heart rate control in critically ill patients with new-onset of atrial fibrillation. We identified a total of 209 patients for the main analysis. Amiodarone as compared to digitalis was associated with a clinically relevant faster time to heart rate control < 110 bpm (2 h (IQR: 1 h to 6 h) versus 4 h (2 h to 12 h); p = 0.003) and longer durations of sinus rhythm during the first 24 h of treatment (6 h (IQR: 6 h to 22 h) versus 0 h (IQR: 0 h to 16 h); p < 0.001). However, more bradycardic episodes occurred in association with amiodarone than with digitalis (7.7% versus 3.4%; p = 0.019). Use of amiodarone was associated with an increase of noradrenalin infusion rate compared to digitalis (23.9% versus 12.0%; p = 0.019). Within the tertile of patients with the highest CRP measurements, amiodarone treated patients presented with a higher decrease in heart rate than digoxin treated patients. Clinical trials comparing different NOAF treatment strategies are much needed and should report on concomitant sympathetic activity and inflammatory status.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Critical Illness; Digitalis; Digoxin; Female; Heart Rate; Humans; Inflammation; Male; Middle Aged; Propensity Score; Retrospective Studies; Sepsis; Treatment Outcome

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

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Emergency Service, Hospital; Heart Rate; Humans

Digoxin treatment has come under scrutiny in recent years after reports from several studies that it is associated with increased mortality in patients with atrial fibrillation (AF). The clinical effects of digoxin on mortality were closely related to serum digoxin concentrations (SDC) in these studies. In the present work, we evaluated the role of the SAMe-TT. Medical records from our institution were screened for patients who were under digoxin treatment between 2008 and 2018. A total of 2418 patients for whom SDC were recorded were included in the study. An SDC of <0.5 or >1.2 ng/ml was defined as being out of the therapeutic range (oTR).. In multivariable regression analyses, abnormal body mass index (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.29-1.95, p < 0.01), white blood cell count (OR: 1.12, 95% CI: 1.01-1.27, p < 0.01), and the modified SAMe-TT. Digoxin is still widely used in the treatment of heart failure and AF despite concerns about the increased risk of mortality when levels are oTR. In the present study, the modified SAMe-TT. HINTERGRUND: In den letzten Jahren wurde die Digoxintherapie kritisch betrachtet, nachdem verschiedene Studien über einen Zusammenhang mit erhöhter Mortalität bei Patient(inn)en mit Vorhofflimmern (VF) berichtet hatten. Die klinischen Wirkungen von Digoxin auf die Mortalität waren eng mit den Serumdigoxinkonzentrationen (SDC) in diesen Studien verknüpft. In der vorliegenden Arbeit untersuchten die Autor(inn)en die Rolle des SAMe-TT. Die Krankenakten der Klinik der Autor(inn)en wurden auf Patient(inn)en hin durchsucht, die zwischen 2008 und 2018 mit Digoxin behandelt wurden. In die Studie wurden 2418 Patient(inn)en einbezogen, für welche die SDC dokumentiert waren. Eine SDC von <0,5 oder >1,2 ng/ml wurde als außerhalb der therapeutischen Breite liegend definiert.. In multivariablen Regressionsanalysen wurden ein anomaler Body Mass Index (Odds Ratio, OR: 1,59; 95 %-Konfidenzintervall, 95 %-KI: 1,29–1,95; p < 0,01), die Leukozytenzahl (OR: 1,12; 95 %-KI: 1,01–1,27; p < 0,01) und der modifizierte SAMe-TT. Weiterhin ist Digoxin zur Therapie der Herzinsuffizienz und des VF weit verbreitet – trotz Bedenken hinsichtlich des erhöhten Mortalitätsrisikos, wenn die Spiegel außerhalb der therapeutischen Breite liegen. In der vorliegenden Studie erwies sich der modifizierte SAMe-TT

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Humans; Treatment Outcome; Vitamin K

Topics: Atrial Fibrillation; Atrial Flutter; COVID-19; Digoxin; Humans; SARS-CoV-2

Topics: Atrial Fibrillation; Atrial Flutter; COVID-19; Digoxin; Humans; SARS-CoV-2

Atrial fibrillation (AF) with rapid ventricular response frequently complicates the management of critically ill patients with sepsis and may necessitate the initiation of medication to avoid hemodynamic compromise. However, the optimal medication to achieve rate control for AF with rapid ventricular response in sepsis is unclear.. What is the comparative effectiveness of frequently used AF medications (β-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate (HR) reduction among critically ill patients with sepsis and AF with rapid ventricular response?. We conducted a multicenter retrospective cohort study among patients with sepsis and AF with rapid ventricular response (HR > 110 beats/min). We compared the rate control effectiveness of β-blockers to calcium channel blockers, amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing risk models (for death and addition of another AF medication), adjusting for fixed and time-varying confounders.. Among 666 included patients, 50.6% initially received amiodarone, 10.1% received a β-blocker, 33.8% received a calcium channel blocker, and 5.6% received digoxin. The adjusted hazard ratio for HR of < 110 beats/min by 1 h was 0.50 (95% CI, 0.34-0.74) for amiodarone vs β-blocker, 0.37 (95% CI, 0.18-0.77) for digoxin vs β-blocker, and 0.75 (95% CI, 0.51-1.11) for calcium channel blocker vs β-blocker. By 6 h, the adjusted hazard ratio for HR < 110 beats/min was 0.67 (95% CI, 0.47-0.97) for amiodarone vs β-blocker, 0.60 (95% CI, 0.36-1.004) for digoxin vs β-blocker, and 1.03 (95% CI, 0.71-1.49) for calcium channel blocker vs β-blocker.. In a large cohort of patients with sepsis and AF with rapid ventricular response, a β-blocker treatment strategy was associated with improved HR control at 1 h, but generally similar HR control at 6 h compared with amiodarone, calcium channel blocker, or digoxin.

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Comparative Effectiveness Research; Critical Illness; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Retrospective Studies; Sepsis; United States

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

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Humans; Potassium; Tachycardia, Ventricular

Dronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein. Using real-world data, we evaluated the risk of digitalis intoxication in concomitant users of dronedarone and digoxin compared digoxin-alone users.. We used the Clinformatics DataMart, a US claims database, to identify adult patients with atrial fibrillation (AF) or atrial flutter (AFL) who concomitantly used dronedarone and digoxin and those who used digoxin alone between July 2009 and March 2016. Digitalis intoxication during follow-up until March 2016 was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Adjusted hazard ratios (HR) for digitalis intoxication in concomitant users versus users of digoxin alone were estimated, controlling for age, sex, cohort entry year, number of medical encounters for AF or AFL, history of congestive heart failure, diabetes, hypertension, stroke, myocardial infarction, renal failure, use of drugs interacting with digoxin, and digoxin dose.. Overall, 524 concomitant users and 32,459 users of digoxin alone were identified, among which 3 and 301 events of digitalis intoxication occurred during follow-up, respectively. Incidence rates were 17.25 and 9.17 cases per 1000 person-years, respectively. The adjusted HR for digitalis intoxication in concomitant users versus users of digoxin alone was 1.56 (95% CI, 0.50-4.88; P = 0.45). When digitalis intoxication was defined by ICD-9-CM and ICD-10-CM codes accompanied by laboratory testing for digoxin/digitoxin or hospitalization within 30 days, no events occurred in the concomitant users and 40 events occurred in the users of digoxin alone (incidence rate of 1.22 cases per 1000 person-years).. Concomitant use of dronedarone and digoxin was uncommon in this study, and no significant increase in the risk of digitalis intoxication with concomitant use was found.

Topics: Adult; Atrial Fibrillation; Atrial Flutter; Digitalis; Digoxin; Dronedarone; Humans

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

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Digoxin; Heart Rate; Humans; Patient Reported Outcome Measures; Quality of Life

Kotecha D, Bunting KV, Gill SK, et al.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Digoxin; Heart Rate; Humans; Quality of Life

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

We describe the case of a patient on continuous venovenous hemodiafiltration with atrial fibrillation with rapid ventricular response and hypotension requiring vasopressor use, which warranted digoxin therapy. In the absence of guidelines specifying appropriate digoxin dosing in patients undergoing continuous venovenous hemodiafiltration, anecdotal evidence-guided digoxin dosing was performed for this patient using plasma digoxin concentration-based therapeutic drug monitoring. We use this case to demonstrate the potential role of physiologically based pharmacokinetic modeling in assisting therapeutic decision making.

Topics: Aged; Atrial Fibrillation; Body Weight; Cardiotonic Agents; Continuous Renal Replacement Therapy; Digoxin; Drug Dosage Calculations; Drug Monitoring; Hemodiafiltration; Humans; Hypotension; Kidney Function Tests; Male; Models, Biological; Point-of-Care Systems; Renal Insufficiency

Combination use of digoxin and other medications might lead to worse outcomes in patients with atrial fibrillation (AF). We sought to investigate whether digoxin-amiodarone combination would lead to worse outcome than digoxin alone in patients with AF. Adult patients with AF and received digoxin treatment from random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included. Baseline characteristics including risk factors and medications were matched by propensity score (PS) in those with and without addition of amiodarone treatment. A total of 5,040 AF patients taking digoxin therapy was included. PS matching identified 1,473 patients receiving digoxin-amiodarone combination and 2,660 patients receiving digoxin with a median follow-up of 1,331 days. Digoxin-amiodarone combination was associated with increased all-cause mortality (adjusted hazard ratio (HR): 1.640, 95% confidence interval (CI): 1.470-1.829, P < 0.001). The risk of mortality increased regardless of duration of combination. Risk of sudden cardiac death was not increased in the combination group (HR: 1.304, 95% CI: 1.049-1.622, P = 0.017). Death due to non-arrhythmic cardiac disease, cerebrovascular disease, and other vascular disease were higher in the combination group than the digoxin group. In conclusion, in patients with AF, digoxin-amiodarone combination therapy is associated with excess mortality than digoxin alone.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Risk Assessment

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

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

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Stroke

Topics: Atrial Fibrillation; Bisoprolol; Digitalis Glycosides; Digoxin; Heart Rate; Humans; Patient Reported Outcome Measures; Quality of Life

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

Drug-drug interactions between digoxin and the triazole antifungal agents, mediated via various cytochrome P450 isozymes, have been described in the literature. Posaconazole is not extensively metabolized by these isozymes but is both a p-glycoprotein (P-gp) substrate and inhibitor. To our knowledge, there have been no published cases of clinically significant posaconazole-digoxin drug-drug interactions. We report an interaction between posaconazole (300 mg by mouth daily) and digoxin (0.25 mg by mouth daily, Monday through Friday) resulting in atrial fibrillation with slow ventricular response and degenerating into polymorphic ventricular tachycardia.

Topics: Aged; Antifungal Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Digoxin; Drug Interactions; Female; Humans; Triazoles

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Registries; Rheumatic Heart Disease

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

Topics: Acute Kidney Injury; Aged, 80 and over; Amoxicillin; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Atrial Fibrillation; Bradycardia; Bundle-Branch Block; Clarithromycin; Digoxin; Drug Interactions; Electrocardiography; Female; Helicobacter Infections; Helicobacter pylori; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Omeprazole; Tachycardia, Ventricular

Topics: Aged; Atrial Fibrillation; Benzamides; Digoxin; Drug Interactions; Drug Overdose; Drug Substitution; Hematemesis; Humans; International Normalized Ratio; Male; Nitriles; Phenindione; Phenylthiohydantoin; Polypharmacy; Prostatic Neoplasms; Tinzaparin

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

To evaluate the effects of multi-drug resistance gene (MDR1) gene factor which is significant in medicinereceptor relationship, on readmission to the emergency department (ED) and medical therapy modifications in patients with atrial fibrillation (AF) readmitting to the emergency department.. Descriptive, analytical study.. Department of Emergency Medicine, Adnan Menderes University, Aydin, Turkey, from January 2016 to January 2017.. Fifty patients who did not have AF with rapid ventricular response, and 32 controls have been included in the study. Electronic recording system of the hospital was checked regularly to detect any readmission of these patients due to palpitation; and they were asked whether they had any ED readmission and any changes in medical therapy by calling them during the one-year period. Then, MDR1 1236TC, 2677TG and 3435TC gene analyses and medical treatment regimens of the patients after 1 year were compared.. No significant differences were found neither between the study and the control group nor between the genders in the study group regarding the results of MDR1 gene analyses. Besides, there were no differences in medical treatment regimens compared to MDR1 gene analyses in the group with AF. There were no statistically significant differences in the results of MDR1 gene analysis in patients whose medical treatment regimen had been changed during the one-year period.. MDR1 gene analyses did not have any significant effect on the development of AF, readmission to the ED and modification of the treatment regimenin the Turkish population.

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; ATP Binding Cassette Transporter, Subfamily B; Atrial Fibrillation; Case-Control Studies; Digoxin; Emergency Service, Hospital; Female; Hospitalization; Humans; Male; Middle Aged; Mutation; Turkey

Topics: Aged; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Humans

Management of atrial fibrillation (AF) with rate and/or rhythm control could lead to fall-related injuries and syncope, especially in the older AF population. We aimed to determine the association of rate and/or rhythm control with fall-related injuries and syncope in a real-world older AF cohort.. A retrospective cohort study.. Danish nationwide administrative registries from 2000 to 2015.. A total of 100 935 patients with AF aged 65 years or older claiming prescription of rate-lowering drugs (RLDs) and/or anti-arrhythmic drugs (AADs) were included. We compared the use of rate-lowering monotherapy with rate-lowering dual therapy, AAD monotherapy, and AAD combined with rate-lowering therapy.. Outcomes were fall-related injuries and syncope as a composite end point (primary) or separate end point (secondary).. In this population, the median age was 78 years (interquartile range [IQR] = 72-84 y), and 53 481 (53.0%) were women. During a median follow-up of 2.1 years (IQR = 1.0-5.1), 17 132 (17.0%) experienced a fall-related injury, 5745 (5.7%) had a syncope, and 21 093 (20.9%) experienced either. Compared with rate-lowering monotherapy, AADs were associated with a higher risk of fall-related injuries and syncope. The incidence rate ratio (IRR) for the composite end point was 1.29 (95% confidence interval [CI]: 1.17-1.43) for AAD monotherapy and 1.46 [95% CI = 1.34-1.58] for AAD combined with rate-lowering therapy. When stratifying by individual drugs, amiodarone significantly increased the risk of fall-related injuries and syncope (IRR = 1.40 [1.26-1.55]). Compared with more than 180 days of rate-lowering monotherapy, a higher risk of all outcomes was seen in the first 90 days of any treatment; however, the greatest risk was in the first 14 days for those treated with AADs.. In AF patients aged 65 years and older, AAD use was associated with a higher risk of fall-related injuries and syncope, and the risk was highest within the first 14 days for those treated with AADs. Only amiodarone use was associated with a higher risk. J Am Geriatr Soc 67:2023-2030, 2019.

Topics: Accidental Falls; Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cohort Studies; Comorbidity; Denmark; Digoxin; Drug Therapy, Combination; Female; Follow-Up Studies; Fractures, Spontaneous; Head Injuries, Closed; Humans; Male; Retrospective Studies; Syncope

Topics: Adult; Apocynaceae; Atrial Fibrillation; Colectomy; Digoxin; Electrocardiography; Extracorporeal Membrane Oxygenation; Fruit; Humans; Immunoglobulin Fab Fragments; Intestines; Ischemia; Life Support Care; Male; Ventricular Fibrillation

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

Hypomagnesemia is a known predisposing condition for the appearance of digitalis toxicity. The detection of a genetic form of Mg urinary wasting with hypomagnesemia being caused by a mutation in the γ subunit (FXYD2) of the Na,K-ATPase, the pharmacological target of Digoxin, prompted us to investigate whether Digoxin administration increases urinary Mg excretion.. Two groups of subjects, with rapid atrial fibrillation, received intravenous Digoxin (n = 9) or verapamil (n = 8), for heart rate control. During the following 4 h, blood and urinary creatinine, sodium, potassium, calcium, and magnesium levels were determined, and fractional excretion (Fex) values for Na, K, Ca, and Mg were calculated.. In the Digoxin group, at 60 min Fex Mg rose from 3.07 ± 1.21 to 7.58 ± 2.51% (an increase of 269 ± 107% of baseline, p < 0.001), and at 240 min to 6.05 ± 2.30% (204 ± 56% of baseline, p < 0.01). No significant change was observed for Fex Na, Fex K, and Fex Ca. A striking correlation was found between individual values of Fex Mg and serum Digoxin concentration (r = 0.678, p < 0.0001). No significant correlation was found between Fex Na or Fex K and serum Digoxin. A correlation of borderline significance was found between Fex Ca and serum Digoxin (r = 0.349, p = 0.073).. The hypermagnesuric effect of acute Digoxin treatment is reminiscent of the effect of the missense mutation in FXYD2, which assumes that FXYD2 is a positive regulator of Na,K-ATPase in the distal convoluted tubule (DCT). The borderline calciuric effect of Digoxin may point to an additional site of action, more proximal to the DCT, that is, the thick ascending limb.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Heart Rate; Humans; Kidney Function Tests; Magnesium; Male; Sodium-Potassium-Exchanging ATPase; Verapamil

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

The aim of the present study was to compare clinical features of patients with elevated serum digoxin concentrations who were treated with digoxin-Fab with those where the immunotherapy was not given by a tertiary hospital toxicology service.. This was a retrospective series of patients with supratherapeutic serum digoxin concentrations referred to the toxicology service from August 2013 to October 2015. Data collected included demographics, presenting complaint, digoxin dose, other medications taken, serum digoxin, potassium and creatinine concentration on presentation and initial and post-digoxin-Fab heart rate.. There were 47 referrals. Digoxin-Fab was administered in 21 cases. It was given more commonly when the heart rate was <51/min or serum potassium was >5.0 mmol/L. Patients receiving digoxin-Fab were more likely to be on maintenance therapy with beta-blockers or calcium channel blockers (95% vs 61%; OR 13.1; 95% CI 1.5-113) and/or potassium-sparing medications (95% vs 54%; OR 17.1; 95% CI 2.0-147). They had elevated serum creatinine (76% vs 42%; OR 8.2; 95% CI 1.9-34), higher serum potassium (median: 5.1 mmol/L vs 4.2 mmol/L, P = 0.02), higher serum digoxin concentration (median: 3.5 nmol/L vs 2.3 nmol/L, P = 0.02) and pretreatment heart rate <51/min (66% vs 31%; OR 4.5; 95% CI 1.3-15). There were no patients with ventricular arrhythmias or hypotension. Median heart rate increased by 10/min 1 and 4 h after digoxin-Fab. However, individual heart rate response to digoxin-Fab was variable.. Digoxin-Fab was more commonly administered when heart rate was <51/min. It had a small effect on increasing heart rate; however, individual response to digoxin-Fab was variable as patients were using other negative chronotropic medications. In symptomatic bradycardic patients on multiple heart failure medications, positive chronotropic and potassium-lowering therapies should be considered in concert with digoxin-Fab.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Cohort Studies; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Heart Rate; Humans; Male; Retrospective Studies; Victoria

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 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

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

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: Acute Kidney Injury; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Humans

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

Digitalis remains a treatment that is difficult to manage, especially in the elderly.. A retrospective, unicentric study carried out within the unit of Internal medicine and geriatrics, Reims University Hospital Center, between January and June 2014. Collection of all patients hospitalized, after 75 years, receiving treatment with digitalis, either as soon as they enter (present on the usual prescription of the patient), during their hospitalization and on their exit.. 20 patients were included. The median age was 89 years (range: 78-94). Digitalis was only used in slowing down the ventricular rate during atrial fibrillation; 7 patients (35%) had a high serum digoxin concentration, of which 4 had renal failure. Three patients presented a digital cup on the electrocardiogram. In our series, in digoxin overdosage, 3 patients with electrical signs of digoxin overdosage have all 3 digoxin-beta-blockers. We are in the limit of the significance, for the connection between digoxinemia and the appearance of electrical signs of overdose in digitalis (p=0.06).. Digoxin therefore remains a drug that is difficult to manage, mainly in the elderly, as there are many clinical, biological drug and therapeutic constraints. Failure to comply with the rules for the use and monitoring of digoxin may prove fatal in the elderly.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Monitoring; Drug Utilization; Electroencephalography; Female; Geriatrics; Hospital Departments; Humans; Inpatients; Male; Medication Therapy Management; Retrospective Studies

Topics: Atrial Fibrillation; Digoxin; Humans

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

Topics: Atrial Fibrillation; Digoxin; Humans; Kidney

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

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

Rate-control medications are considered first-line treatment for patients with atrial fibrillation (AF). However, obstructive lung disease (OLD), a condition prevalent in those with AF, often makes it difficult to use those medications because of the lack of studies on new-onset AF in patients with OLD.. The purpose of this study was to investigate clinical outcomes after administration of each class of rate-control medication in patients with concomitant AF and OLD (AF-OLD).. This study used the entire database provided by the National Health Insurance Service from 2002 to 2015. Risk of all-cause mortality was compared between use of calcium channel blocker (CCB) and use of other drug classes in AF-OLD patients using Cox regression analyses after propensity score matching.. Among the 13,111 patients, the number of AF-OLD patients treated with a CCB, cardioselective β-blocker (BB), nonselective BB, and digoxin was 2482, 2379, 2255, and 5995, respectively. The risk of mortality was lower with use of selective BB (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75-0.94; P = .002) and nonselective BB (HR 0.85; 95% CI 0.77-0.95; P = .003) compared to use of CCBs. Digoxin use was related with worse survival, with marginal statistical significance (HR 1.09; 95% CI 1.00-1.18; P = .053).. Among patients with AF-OLD, rate-control treatment using selective and nonselective BB was associated with a significant reduction in mortality compared with CCB use. Further prospective randomized trials are required to confirm these findings.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Digoxin; Female; Heart Rate; Humans; Lung Diseases, Obstructive; Male; Propensity Score; Republic of Korea; Retrospective Studies; Survival Rate

Transcatheter aortic valve implantation (TAVI) is frequently associated with cardiac conduction defects (CCD) requiring permanent pacemaker implantation (PPI). Although new-onset left bundle branch block (LBBB) is often seen, the rate of progression to severe CCD is unclear. We aimed to find clinical and electrocardiographic (ECG) parameters associated with severe CCD requiring PPI in patients with a new-onset LBBB after TAVI and assess its effect on clinical outcome.. All consecutive patients undergoing TAVI who developed a new-onset LBBB were retrospectively analysed. We excluded patients with pre-existing bundle branch block or pacemaker. Patients were divided into two groups: with or without PPI after TAVI. We included 155 patients (50% female, 80 ± 7 years), of which 37 (24%) developed CCD requiring PPI, mainly due to a total atrioventricular block (n = 17; 46%). Cardiac conduction defects requiring PPI were associated with the following pre-existing parameters: atrial fibrillation (AF), the use of digoxin, CoreValve implantation, and left heart axis. Furthermore, it was associated with the following post-procedural parameters: left heart axis, lower mean heart rate, and prolonged PQ and QRS times. During follow-up, patients with PPI showed a lower mortality rate (11 vs. 29%, P = 0.03). In patients without PPI, mortality was lower in those with narrower QRS complex and transient LBBB.. The severity and persistence of a new-onset LBBB after TAVI is associated with mortality. Cardiac conduction defects requiring PPI are associated with prior AF, the use of digoxin, CoreValve implantation, and a left heart axis. In these patients, PPI portends a better prognosis than no PPI.

Topics: Action Potentials; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Bundle-Branch Block; Cardiac Pacing, Artificial; Digoxin; Disease Progression; Electrocardiography; Female; Heart Conduction System; Heart Rate; Heart Valve Prosthesis; Humans; Kaplan-Meier Estimate; Male; Pacemaker, Artificial; Prosthesis Design; Retrospective Studies; Risk Factors; Severity of Illness Index; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome

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

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

Differences in the management of atrial fibrillation (AF) between men and women were investigated by using Gulf SAFE data in the Middle East. The study included 2,043 patients presenting with AF to emergency room (ER) were prospectively enrolled and followed for one-year. Women were older, have higher body mass index (BMI), comorbidities, and health complications than men. With regard to management of AF, cardioversion was recommended more often for men (16.7% vs. 9.3%), and underwent electrical cardioversion (2.2% vs. 1.1%). Women were prescribed digoxin more frequently than men (25.6% vs. 17.4%) and a significant number women received warfarin alone (31.1% vs. 8.7%). No difference between the sexes was noticed in One-year rates of stroke/transient ischemic attacks (TIA) and all-cause of mortality after one-year follow-up (3.1% men vs. 3.3% women, and 7.5% vs. 7.4%). Older age (≥ 65 years), smoking, alcohol use, CHADS2 scores ≥5 were some of the significant risk factors in men with AF. Suboptimal use of anticoagulants, higher mortality and stroke/TIA events at one year are high but similar between the sexes. ER management revealed high use of rate control strategy and high rate of hospital admission was noticed in women.

Topics: Adult; Age Factors; Aged; Alcohol Drinking; Atrial Fibrillation; Body Mass Index; Digoxin; Female; Humans; Male; Middle Aged; Middle East; Sex Factors; Smoking; Warfarin

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

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiovascular Diseases; Digoxin; Heart Rate; Humans

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

This study aimed to reveal the incidence of clinical endpoints in elderly patients with atrial fibrillation (AF) during a 2-year follow-up and evaluate the related prognostic factors of these endpoints.In total, 200 elderly patients with AF and 400 age- and sex-matched patients without AF were enrolled in this prospective observational cohort study. The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, during the 2-year follow-up was analyzed. Other follow-up data, including disease history, laboratory examinations, medication status, and other clinical endpoints, were collected. The prognostic factors of these clinical endpoints were then evaluated by Cox-survival analysis. In addition, the predicative role of C-reactive protein (CRP) and platelet-activating factor (PAF) on these clinical endpoints was analyzed.The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, was significantly higher in patients with AF than in those without AF (27.8% vs 9.8%, 29.4% vs 12.7%, and 28.7% vs 11.6%, respectively; all P < .001). Antithrombotic therapy significantly reduced the incidences of all-cause deaths (P < .05). Body mass index (BMI) and digoxin were prognostic risk factors of thromboembolism; age, massive hemorrhage history, and digoxin were prognostic risk factors of hemorrhage and age, renal insufficiency history, massive hemorrhage history, and digoxin were prognostic risk factors of all-cause death (P < .05). Further, both CRP and PAF were prognostic risk factors of thromboembolism and massive hemorrhage (P < .05).Age, BMI, massive hemorrhage history, and digoxin appear to be prognostic risk factors of clinical endpoints in elderly patients with AF. Appropriate drug use during follow-up may be beneficial in preventing the occurrence of clinical endpoints in elderly patients with AF.. ChiCTR-OCH-13003479.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Body Mass Index; C-Reactive Protein; Case-Control Studies; China; Digoxin; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Male; Platelet Activating Factor; Prognosis; Proportional Hazards Models; Prospective Studies; Thromboembolism

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

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

Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients.. ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0.5 mg) without (group I, n = 58) or with the co-administration of P-gp inhibitors (group II, n = 44). SDCs were determined at 6 h following the oral dose.. SDCs levels were significantly higher in patients who were co-administered P-gp inhibitors. No influence was noted in ABCB1 and SLCO1B3 polymorphisms on SDC in group I patients. However, SDCs values were significantly different among ABCB1 single nucleotide polymorphisms (SNPs) genotypes of 2677G>T/A (TT, GG>GT, p < 0.05) and 3435C>T (TT, CC>CT, p < 0.05) only in group II with no effect of 1236C>T and SLCO1B3 SNPs.. Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics.

Topics: Adult; Aged; Aged, 80 and over; ATP Binding Cassette Transporter, Subfamily B; Atrial Fibrillation; Digoxin; Female; Genotype; Humans; Male; Middle Aged; Organic Anion Transporters, Sodium-Independent; Polymorphism, Single Nucleotide; Solute Carrier Organic Anion Transporter Family Member 1B3; Tunisia

Digoxin is a cardiac glycoside that is frequently prescribed in atrial fibrillation and heart failure. Symptoms such as nausea, hyperkalaemia, cardiac arrhythmias and cardiac arrest are seen in digoxin toxicity. The treatment focuses on reduction of digoxin absorption, prevention of hypokalaemia and hyperkalaemia, treatment of symptoms and, in severe toxicity, administration of digoxin antibodies.. A 73-year-old man with a history of extensive cardiac disease was seen 45 minutes after ingesting 20 mg of digoxin. The patient developed ventricular fibrillation within 3 hours of ingestion, before arrival of the digoxin antibodies. The patient passed away despite resuscitation and administration of an insufficient amount of digoxin antibodies.. The national supply of digoxin antibodies in the Netherlands proved to be too limited for the treatment of a patient with severe digoxin toxicity. An increase in the supply, and central storage, of digoxin antibodies could promote faster administration of an adequate amount of the antibodies. Timely transportation to an extra corporeal membrane oxygenation centre should also be considered.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Fatal Outcome; Heart Arrest; Humans; Male; Netherlands; Ventricular Fibrillation

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

Atrial fibrillation (AF) during sepsis is associated with increased morbidity and mortality, but practice patterns and outcomes associated with rate- and rhythm-targeted treatments for AF during sepsis are unclear.. This was a retrospective cohort study using enhanced billing data from approximately 20% of United States hospitals. We identified factors associated with IV AF treatments (?-blockers [BBs], calcium channel blockers [CCBs], digoxin, or amiodarone) during sepsis. We used propensity score matching and instrumental variable approaches to compare mortality between AF treatments.. Among 39,693 patients with AF during sepsis, mean age was 77 ± 11 years, 49% were women, and 76% were white. CCBs were the most commonly selected initial AF treatment during sepsis (14,202 patients [36%]), followed by BBs (11,290 [28%]), digoxin (7,937 [20%]), and amiodarone (6,264 [16%]). Initial AF treatment selection differed according to geographic location, hospital teaching status, and physician specialty. In propensity-matched analyses, BBs were associated with lower hospital mortality when compared with CCBs (n = 18,720; relative risk [RR], 0.92; 95% CI, 0.86-0.97), digoxin (n = 13,994; RR, 0.79; 95% CI, 0.75-0.85), and amiodarone (n = 5,378; RR, 0.64; 95% CI, 0.61-0.69). Instrumental variable analysis showed similar results (adjusted RR fifth quintile vs first quintile of hospital BB use rate, 0.67; 95% CI, 0.58-0.79). Results were similar among subgroups with new-onset or preexisting AF, heart failure, vasopressor-dependent shock, or hypertension.. Although CCBs were the most frequently used IV medications for AF during sepsis, BBs were associated with superior clinical outcomes in all subgroups analyzed. Our findings provide rationale for clinical trials comparing the effectiveness of AF rate- and rhythm-targeted treatments during sepsis.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Female; Hospitalization; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Propensity Score; Retrospective Studies; Sepsis; Treatment Outcome; United States

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

Topics: Adenosine; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Catheter Ablation; Defibrillators, Implantable; Digoxin; Evidence-Based Medicine; Heart Conduction System; Humans; Pacemaker, Artificial; Pulmonary Veins; Randomized Controlled Trials as Topic

Topics: Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male

Topics: Aged; Atrial Fibrillation; Cardiovascular Agents; Contraindications; Digoxin; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Heart Failure, Diastolic; Humans; Hypertension; Renal Insufficiency, Chronic; Treatment Outcome; Withholding Treatment

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

Even though digoxin causes many side effects, few cases of skin involvement are recorded in the French Pharmacovigilance Database. We report a case of leukocytoclastic vasculitis (LV) very probably due to digoxin. A 91-year-old woman, hospitalized following a fall, presented cardiac decompensation in a context of rapid atrial fibrillation requiring treatment with digoxin. Eight days later, a rash appeared on her back and trunk. It was neither itchy, nor painful and persisted despite local treatment. There were no other clinical anomalies. After a few days, the rash spread with appearance of bullous lesions, ulcerations and a necrosis on lymphedema of the two legs. Among the complementary examinations, skin biopsy revealed LV with necrosis and subepidermal detachment suggested toxic dermal necrolysis, while direct immunofluorescence was negative. The rash resolved progressively once the digoxin was stopped. The pharmacovigilance department recorded that digoxin was the probable cause. The evidence allowed us to conclude that digoxin was the cause.

Topics: Aged, 80 and over; Atrial Fibrillation; Biopsy; Digoxin; Female; Humans; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digitoxin; Digoxin; Female; Humans; Male; Models, Biological

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digitoxin; Digoxin; Female; Humans; Male; Models, Biological

The safety of digoxin has been a subject of debate for decades, most recently among patients with atrial fibrillation (AF). Digoxin has been used during the acute phase of ST elevation myocardial infarction (STEMI) complicated with AF or heart failure. Data about digoxin in this setting are scarce.. We hypothesize that digoxin maybe associated with increased mortality when used during the acute phase of ST segment myocardial infarction.. We investigated the association between digoxin and mortality in patients enrolled in the MAGnesium In Coronaries (MAGIC) study, which evaluated the efficacy of early magnesium administration in STEMI. Multiple Cox proportional hazards models were examined to assess the aforementioned association after correction for clinical characteristics and comorbidities.. After excluding 639 (10.3%) patients for missing data, we analyzed the remaining 5574 patients. There were 852 (15.3%) deaths during the one month follow-up and 170 (3.0%) patients on digoxin concomitantly, among which 42 patients (24.7%) died. There was a statistically significant association between digoxin and increased mortality in the unadjusted statistical analysis; however, this association disappeared after correction for clinical characteristics and comorbidities in the primary multivariable analysis (estimated hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.62-1.19, p=0.372) and in three additional multivariable analyses.. Digoxin use as a new or preexisting medication during the acute phase of STEMI in the MAGIC trial was not associated with a significant increase in mortality after correcting for clinical characteristics and comorbidities.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Digoxin; Double-Blind Method; Female; Humans; Magnesium Sulfate; Male; Middle Aged; Proportional Hazards Models; ST Elevation Myocardial Infarction

This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin.. All patients with non-valvular atrial fibrillation and/or atrial flutter as hospitalization diagnosis from January 1, 1997 to December 31, 2012 were identified in Danish nationwide administrative registries. Cox proportional hazard model was used to compare the adjusted risk of all-causes and cardiovascular mortality among patients with and without chronic kidney disease and among patients with different chronic kidney disease stages within 180 days and 2 years from the first digoxin prescription.. We identified 37,981 patients receiving digoxin; 1884 patients had the diagnosis of chronic kidney disease. Cox regression analysis showed no statistically significant differences in all-causes (Hazard Ratio, HR 0.89; 95% confident interval, CI 0.78-1.03) and cardiovascular mortality (HR 0.88; 95%CI 0.74-1.05) among patients with and without chronic kidney disease within 180 days of follow-up period. No statistically significant differences was found using a 2 years follow-up period neither for all causes mortality (HR 0.90; 95%CI 0.79-1.03), nor for cardiovascular mortality (HR 0.87; 95%CI 0.74-1.02). No statistically significant differences was found comparing patients with and without estimated Glomerular Filtration Rate <30ml/min/1.73m2 and patients with different stages of chronic kidney disease, for all-causes and cardiovascular mortality within 180 days and 2 years from the first digoxin prescription.. This study suggest no direct effect of chronic kidney disease and chronic kidney disease stages on all-causes and cardiovascular mortality within both 180 days and 2 years from the first digoxin prescription in patients treatment-naïve with digoxin for non-valvular atrial fibrillation.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Denmark; Digoxin; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Proportional Hazards Models; Registries; Retrospective Studies; Survival Analysis

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

To evaluate the adequacy of atrial fibrillation (AF) management 6 years after the establishment of a coordinated AF Unit.. Patients with AF attended during 14 consecutive days in the Emergency Room, Internal Medicine, Neurology and Arrhythmia departments of a tertiary hospital, and 3 primary health care centers of the same urban health care area were included. Treatment for AF and its adequacy to current clinical guidelines, tests performed and knowledge about the arrhythmia were evaluated. Results were compared with a population of 239 patients treated 6 years earlier.. One hundred and sixty-eight patients were included. Knowledge of the arrhythmia improved. The adequacy of treatment (rate control, rhythm control and antithrombotic prophylaxis) remained at the same level as in the previous period in all areas. The adequacy of thromboprophylaxis was negatively associated with advanced age (P < .001) and positively associated with knowledge of arrhythmia (P = .026).. Treatment of AF in a coordinated health area remains appropriate 6 years after the establishment of a coordinated AF unit. Elderly patients are still poorly anticoagulated. Health education may improve this deficit.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catchment Area, Health; Comorbidity; Diagnostic Techniques, Cardiovascular; Digoxin; Drug Therapy; Drug Utilization; Emergency Service, Hospital; Female; Guideline Adherence; Heart Rate; Hospital Departments; Hospital Units; Humans; Male; Middle Aged; Patient Education as Topic; Patients; Practice Guidelines as Topic; Primary Health Care; Spain; Tertiary Care Centers; Thrombophilia; Urban Population

Digoxin remains commonly used for rate control in atrial fibrillation, but limited data exist supporting this practice and some studies have shown an association with adverse outcomes. We examined the independent association between digoxin and risks of death and hospitalization in adults with incident atrial fibrillation and no heart failure.. We performed a retrospective cohort study of 14,787 age, sex, and high-dimensional propensity score-matched adults with incident atrial fibrillation and no previous heart failure or digoxin use in the AnTicoagulation and Risk factors In Atrial fibrillation-Cardiovascular Research Network (ATRIA-CVRN) study within Kaiser Permanente Northern and Southern California. We examined the independent association between newly initiated digoxin and the risks of death and hospitalization using extended Cox regression. During a median 1.17 (interquartile range, 0.49-1.97) years of follow-up among matched patients with atrial fibrillation, incident digoxin use was associated with higher rates of death (8.3 versus 4.9 per 100 person-years; P<0.001) and hospitalization (60.1 versus 37.2 per 100 person-years; P<0.001). Incident digoxin use was independently associated with a 71% higher risk of death (hazard ratio, 1.71; 95% confidence interval, 1.52-1.93) and a 63% higher risk of hospitalization (hazard ratio, 1.63; 95% confidence interval, 1.56-1.71). Results were consistent in subgroups of age and sex and when using intent-to-treat or on-treatment analytic approaches.. In adults with atrial fibrillation, digoxin use was independently associated with higher risks of death and hospitalization. Given other available rate control options, digoxin should be used with caution in the management of atrial fibrillation.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; California; Chi-Square Distribution; Digoxin; Female; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Selection; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome

Topics: Acute Kidney Injury; Aged; Agglutinins; Anti-Arrhythmia Agents; Atrial Fibrillation; Bradycardia; Digoxin; Dosage Forms; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Fatigue; Humans; Male; Treatment Outcome; Vision Disorders; Vomiting

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: Atrial Fibrillation; Digoxin; Female; Humans; Male; Outpatients; Risk Assessment

Topics: Atrial Fibrillation; Digoxin; Female; Humans; Male; Outpatients; Risk Assessment

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Heart Conduction System; Humans; Hypokalemia; Male

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: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Humans; Male

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Risk Assessment; Stroke

Topics: Aged; Atrial Fibrillation; Cardenolides; Digoxin; Electrocardiography; Female; Foodborne Diseases; Humans

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Risk Assessment; Stroke

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Risk Factors

Atrial fibrillation (AF), the most common sustained arrhythmia requiring treatment worldwide, is one of the major causes of ischemic stroke. Although amiodarone is commonly used for rhythm control in AF, its relationship with stroke has rarely been addressed.We evaluated 16,091 patients who were diagnosed with AF (Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 427.31 and 427.32) between 1998 and 2011; the date of AF diagnosis was set as the index date. Patients with a history of stroke (ICD-9-CM 430-438) who received amiodarone before the index date or during the following 30 days, or who experienced stroke within 30 days of receiving amiodarone were excluded. Finally, 7548 patients with AF were included in this study and divided into 2 groups according to whether they received amiodarone (Anatomical Therapeutic Chemical code C01BD01) during the study period.The risk of ischemic stroke in AF patients receiving amiodarone was 1.81-fold (95% confidence interval [CI] 1.52-2.16), 1.79-fold (95% CI 1.50-2.14), and 1.78-fold (95% CI 1.49-2.13) higher than in those who did not receive amiodarone, according to crude, Model 1, and Model 2 Cox proportional hazard regression models, respectively. In a demographically stratified analysis, the risk of ischemic stroke was significantly higher in patients aged <65 years, with no comorbidities, who were also taking digoxin or had a low CHA2DS2VASc score.Amiodarone treatment is associated with an increased risk of stroke in patients with AF, especially in those who have an initial low risk of stroke. Antiplatelet drugs and warfarin could reduce the stroke risk in AF patients receiving amiodarone. However, as the combination of digoxin and amiodarone increases the risk of stroke in these patients, the combination of these 2 drugs should be avoided.

Topics: Age Factors; Aged; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Comorbidity; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Stroke; Taiwan; Warfarin

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Humans; Hypertension; 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: Atrial Fibrillation; Digoxin; Female; Humans; Male

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

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

Current American and European guidelines emphasize the importance of rate-control treatments in treating atrial fibrillation with a Class I recommendation, although data on the survival benefits of rate control are lacking. The goal of the present study was to investigate whether patients receiving rate-control drugs had a better prognosis compared with those without rate-control treatment.. This study used the National Health Insurance Research Database in Taiwan. There were 43 879, 18 466, and 38 898 patients with atrial fibrillation enrolled in the groups receiving β-blockers, calcium channel blockers, and digoxin, respectively. The reference group consisted of 168 678 subjects who did not receive any rate-control drug. The clinical end point was all-cause mortality. During a follow-up of 4.9±3.7 years, mortality occurred in 88 263 patients (32.7%). After adjustment for baseline differences, the risk of mortality was lower in patients receiving β-blockers (adjusted hazard ratio=0.76; 95% confidence interval=0.74-0.78) and calcium channel blockers (adjusted hazard ratio=0.93; 95% confidence interval=0.90-0.96) compared with those who did not receive rate-control medications. On the contrary, the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 (95% confidence interval=1.10-1.14). The results were observed consistently in subgroup analyses and among the cohorts after propensity matching.. In this nationwide atrial fibrillation cohort, the risk of mortality was lower for patients receiving rate-control treatment with β-blockers or calcium channel blockers, and the use of β-blockers was associated with the largest risk reduction. Digoxin use was associated with greater mortality. Prospective, randomized trials are necessary to confirm these findings.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Cause of Death; Cohort Studies; Comorbidity; Confounding Factors, Epidemiologic; Digoxin; Drug Utilization; Female; Heart Rate; Humans; Income; Male; Middle Aged; Practice Guidelines as Topic; Proportional Hazards Models; Residence Characteristics; Risk Reduction Behavior; Taiwan

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Female; Heart Rate; Humans; Male

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

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

In patients with chronic digoxin toxicity, especially in the presence of renal impairment, a prolonged duration of continuous monitoring is required with consideration given to further doses of immune fab if necessary for re-emergence of toxicity.

Topics: Aged; Atrial Fibrillation; Cardiovascular Agents; Digoxin; Female; Heart Rate; Humans; Immunoglobulin Fab Fragments; Recurrence; Renal Insufficiency, Chronic

Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample.. Data from RealiseAF, an international, observational, cross-sectional survey of 10,491 patients with atrial fibrillation, were used to characterize permanent atrial fibrillation (N = 4869) and nonpermanent atrial fibrillation (N = 5622) patients. Permanent atrial fibrillation patients were older, had a longer time since atrial fibrillation diagnosis, a higher symptom burden, and were more likely to be physically inactive. They also had a higher mean (SD) CHADS2 score (2.2 [1.3] vs. 1.7 [1.3], p<0.001), and a higher frequency of CHADS2 score ≥2 (67.3% vs. 53.0%, p<0.001) and comorbidities, most notably heart failure. Physicians indicated using a rate-control strategy in 84.2% of permanent atrial fibrillation patients (vs. 27.5% in nonpermanent atrial fibrillation). Only 50.2% (N = 2262/4508) of permanent atrial fibrillation patients were controlled. These patients had a longer time since atrial fibrillation diagnosis, a lower symptom burden, less obesity and physical inactivity, less severe heart failure, and fewer hospitalizations for acute heart failure than uncontrolled permanent atrial fibrillation patients, but with more arrhythmic events. The most frequent causes of hospitalization in the last 12 months were acute heart failure and stroke.. Permanent atrial fibrillation is a high-risk subset of atrial fibrillation, representing half of all atrial fibrillation patients, yet rate control is only achieved in around half. Since control is associated with lower symptom burden and heart failure, adequate rate control is an important target for improving the management of permanent atrial fibrillation patients.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiovascular Diseases; Cross-Sectional Studies; Digoxin; Echocardiography; Electrocardiography; Female; Health Surveys; Heart; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Risk Factors; Sotalol

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

This report examined the role of digitalis pharmacokinetics in helping to guide therapy with digitalis glycosides with regard to converting atrial fibrillation (AF) or flutter to regular sinus rhythm (RSR). Pharmacokinetic models of digitoxin and digoxin, containing a peripheral non-serum effect compartment, were used to analyze outcomes in a non-systematic literature review of five clinical studies, using the computed concentrations of digitoxin and digoxin in the effect compartment of these models in an analysis of their outcomes. Four cases treated by the author were similarly examined. Three literature studies showed results no different from placebo. Dosage regimens achieved ≤11 ng/g in the model's peripheral compartment. However, two other studies achieved significant conversion to RSR. Their peripheral concentrations were 9-14 ng/g. In the four patients treated by the author, three converted using classical clinical titration with incremental doses, plus therapeutic drug monitoring and pharmacokinetic guidance from the models for maintenance dosage. They converted at peripheral concentrations of 9-18 ng/g, similar to the two studies above. No toxicity was seen. Successful maintenance was achieved, using the models and their pharmacokinetic guidance, by giving somewhat larger than average recommended dosage regimens in order to maintain peripheral concentrations present at conversion. The fourth patient did not convert, but only reached peripheral concentrations of 6-7 ng/g, similar to the studies in which conversion was no better than placebo. Pharmacokinetic analysis and guidance play a highly significant role in converting AF to RSR. To the author's knowledge, this has not been specifically described before. In my experience, conversion of AF or flutter to RSR does not occur until peripheral concentrations of 9-18 ng/g are reached. Results in the four cases correlated well with the literature findings. More work is needed to further evaluate these provocative findings.

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Digitalis; Digitoxin; Digoxin; Female; Humans; Male; Middle Aged; Models, Biological

Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF).. The goal of this study was to evaluate the association of digoxin with mortality in AF.. Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis.. Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin.. Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cause of Death; Confidence Intervals; Digoxin; Female; Follow-Up Studies; Humans; Male; Outpatients; Prognosis; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate; United States

Topics: Atrial Fibrillation; Digoxin; Female; Humans; Male; Outpatients; Risk Assessment

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Brain Ischemia; Digoxin; Humans; Stroke

Digoxin and related cardiac glycosides have been used for almost 100 years in atrial fibrillation (AF). However, 2 recent analyses of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial showed inconsistent results regarding the risk of mortality associated with digoxin use. The goal of the present study was to investigate the relationship between digoxin and the risk of ischemic stroke and mortality in Asians.. This study used the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 4781 patients with AF who did not receive any antithrombotic therapy were selected as the study population. Among the study population, 829 participants (17.3%) received the digoxin treatment. The risk of ischemic stroke and mortality in patients who received digoxin and those who did not was compared.. The use of digoxin was associated with an increased risk of clinical events, with an adjusted hazard ratio of 1.41 (95% confidence interval [CI], 1.17-1.70) for ischemic stroke and 1.21 (95% CI, 1.01-1.44) for all-cause mortality. In the subgroup analysis based on coexistence with heart failure or not, digoxin was a risk factor for adverse events in patients without heart failure but not in those with heart failure (interaction P < 0.001 for either end point). Among patients with AF without heart failure, the use of β-blockers was associated with better survival, with an adjusted hazard ratio of 0.48 (95% CI, 0.34-0.68).. Digoxin should be avoided for patients with AF without heart failure because it was associated with an increased risk of clinical events. β-Blockers may be a better choice for controlling ventricular rate in these patients.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Digoxin; Humans; Risk Factors; Stroke

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

We aimed to assess and compare the effect of digoxin on clinical outcomes in patients with atrial fibrillation vs those under beta-blockers or none of these drugs.. AFBAR is a prospective registry study carried out by a team of primary care physicians (n=777 patients). Primary endpoints were survival, survival free of admission due to any cause, and survival free of admission due to cardiovascular causes. The mean follow up was 2.9 years. Four groups were analyzed: patients receiving digoxin, beta-blockers, or digoxin plus beta-blockers, and patients receiving none of these drugs.. Overall, 212 patients (27.28%) received digoxin as the only heart control strategy, 184 received beta-blockers (23.68%), 58 (7.46%) were administered both, and 323 (41.57%) received none of these drugs. Digoxin was not associated with all-cause mortality (estimated hazard ratio=1.42; 95% confidence interval, 0.77-2.60; P=.2), admission due to any cause (estimated hazard ratio=1.03; 95% confidence interval, 0.710-1.498; P=.8), or admission due to cardiovascular causes (estimated hazard ratio=1.193; 95% confidence interval, 0.725-1.965; P=.4). No association was found between digoxin use and all-cause mortality, admission due to any cause, or admission due to cardiovascular causes in patients without heart failure. There was no interaction between digoxin use and sex in all-cause mortality or in survival free of admission due to any cause. However, an association was found between sex and admission due to cardiovascular causes.. Digoxin was not associated with increased all-cause mortality, survival free of admission due to any cause, or admission due to cardiovascular causes, regardless of underlying heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Humans; Kaplan-Meier Estimate; Male; Prospective Studies; Treatment Outcome

Topics: Adrenergic beta-1 Receptor Antagonists; Age Factors; Algorithms; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Comorbidity; Digoxin; Drug Interactions; Heart Rate; Humans; Patient Preference; Quality of Life

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: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans

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

Digoxin is widely used to manage heart failure and atrial fibrillation, and requires careful patient monitoring to avoid toxicity. Vision disturbances are a specific indicator of toxicity and may be the initial sign. Treatment depends on the patient's clinical presentation.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Gout; Humans; Immunoglobulin Fab Fragments; Male; Renal Insufficiency, Chronic; Vision Disorders

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

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Ventricular Dysfunction, Left

Parathyroid hormone (PTH) secretion is regulated mainly by the calcium sensor receptor. Recently, other components of calcium homoeostasis have been revealed, namely the effect of Klotho on stimulation of PTH secretion by the recruitment of Na-K-ATPase and by its being a cofactor in the inhibitory effect of FGF 23 on PTH secretion. It seems that ouabain, a Na-K-ATPase inhibitor, prevents the increase in PTH secretion in a hypocalcemic environment, as observed in mouse and bovine tissues. We hypothesized that digoxin, which is similar to ouabain in its effect on the sodium pump, might decrease PTH levels in humans.. Twenty patients with atrial fibrillation were studied. Ten patients were treated with digoxin and the other ten patients with verapamil. Baseline chemistry parameters were determined and 0·25 mg digoxin injected. Plasma PTH concentrations, ionized calcium concentrations and digoxin levels were recorded at 30 min, 1 h, 2 h and 4 h postinjection.. Baseline blood parameters were similar in both groups. In the control group plasma PTH concentrations increased, whereas in the digoxin group, they decreased. Ionized calcium concentrations did not change over time in either groups. There seemed to be blunting of the circadian rhythm of PTH levels in the morning hours.. Although the patients were normocalcemic, plasma PTH concentrations decreased with digoxin treatment. The effect of the sodium pump on PTH secretion might be important in human PTH homoeostasis and might be a potential target for the treatment of disturbances in calcium homoeostasis.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium; Digoxin; Female; Fibroblast Growth Factor-23; Humans; Male; Middle Aged; Parathyroid Hormone; Verapamil

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

Topics: Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Bradycardia; Cardiac Pacing, Artificial; Digoxin; Female; Humans; Ventricular Fibrillation

The authors report about a patient who was admitted after developing nausea, vomiting, change in vision and lethargy. She was on digoxin 250 mcg once daily among all her other medications in the wake of a recent stroke that was accompanied by atrial fibrillation (AF). Her digitalis levels shortly before and on admission were 3.4 and 2.9 ng/ml, respectively. Her admission rhythm was slowly conducted AF at an average of 35 bpm. After a careful assessment by the cardiology consultant in charge, she received Digibind infusion for a chronic digitalis toxicity with the digoxin immune Fab dose based on the formula recommended in the product literature.(3) A few days observation on the ward ensured that her resting heart rate rose to 65 bpm and that she did not need a pacemaker for a slow AF. Her functional status remained reasonably good as she enjoyed a satisfactory recovery postthrombolysis for her recent stroke.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digitalis Glycosides; Digoxin; Female; Heart Rate; Humans; Immunoglobulin Fab Fragments; Stroke

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Heart Rate; Humans; Metoprolol

Pharmacologic cardioversion of atrial fibrillation (AF) is a reasonable mode of treatment if the arrhythmia is of recent onset. Results concerning the response rates of different drugs, respectively, in daily clinical practice and data with regard to the parameters associated with successful cardioversion are not very prevalent.. Three-hundred seventy-six patients who were admitted to the emergency department with acute AF and a duration of shorter than 48 hours were enrolled into the AF registry.. The most effective drugs were flecainide and ibutilide (95% and 76%). Low response rates were observed with amiodarone (36%) and the individual use of digoxin or diltiazem (19% and 18%). Factors associated with a successful cardioversion were a lower blood pressure on admission (P = .002), a shorter time interval between the onset of AF and admission to the ED (P = .003), and adherence to treatment guidelines (P < .0001).. The use of flecainide and ibutilide is associated with a much higher rate of cardioversion than other drugs we studied.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Emergency Service, Hospital; Female; Flecainide; Humans; Male; Middle Aged; Sulfonamides; Time Factors; Treatment Outcome

Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity.. We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥ 1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥ 3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P < 0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P < 0.0001).. In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Bypass; Defibrillators, Implantable; Digoxin; Electric Countershock; Follow-Up Studies; Hospitalization; Humans; Myocardial Infarction; Survival Rate

Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Dog Diseases; Dogs; Electrocardiography; Female

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Practice Guidelines as Topic

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

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Autoimmune Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diagnosis, Differential; Digoxin; Female; Humans; Nausea; Weight Loss

Topics: Atrial Fibrillation; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Heart Failure; Humans

Digitalis glycosides are among the oldest drugs used in cardiology. Nowadays, due to the limited indications for their use (advanced heart failure, usually concomitant with atrial fibrillation), cases of poisoning induced by this class of drugs are rarely observed. Digoxin produces a positive inotropic and bathmotropic effect on the heart, but has a negative chronotropic and dromotropic effect. Cardiac glycosides have a narrow therapeutic window, so digitalis treatment can easily lead to symptoms of overdose. In patients taking digoxin, the drug therapeutic level should be maintained at 1-2 ng/ml; the toxic effects occur at concentrations > 2.8 ng/ml and are mainly related to disturbances of cardiac function and of the circulatory system, as well as gastrointestinal symptoms and CNS disturbances. We present, a 45-years-old patient who was hospitalized following the ingestion with suicidal intent of 100 0.25 mg tablets of digoxin. In spite of rapidly applied gastric irrigation and administration of activated charcoal, the drug level in the patient's blood was estimated at 12.0 ng/ml. During her stay on the ward, typical symptoms of severe poisoning were observed: from gastric symptoms (severe nausea, vomiting) to numerous severe arrhythmias and conduction disturbances. Type I, II and III AV blocks were detected, as well as numerous ventricular and supraventricular extrasystoles. These conduction disorders required the use of temporary endocardial pacing. Due to the unavailability of specific antidotes (antidigitalis antibodies) and lack of efficient methods of extracorporeal elimination of the drug, symptomatic treatment comprising the correction of electrolyte disturbances and heart rate control remains the most effective.

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Fluid Therapy; Humans; Middle Aged; Nausea; Suicide, Attempted; Vomiting; Water-Electrolyte Imbalance

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

Recent studies of patients with heart failure and of patients receiving intensive care indicate that digoxin may increase mortality if the patient has atrial fibrillation (AF). Objective To study which patients receive digoxin treatment for AF and what the prognosis is for patients given this treatment.. 2824 patients with AF were studied prospectively for a mean of 4.6 years. Information about medication was obtained from the local hospital registry. Information about diagnoses, hospitalisations and deaths was obtained from national registries. Propensity score matching and Cox regression was used to account for confounding.. Factors associated with digoxin use were permanent AF (hazard ratio (HR) = 3.2, confidence interval (CI) 2.7 to 3.9), absence of pacemaker (HR = 2.3, CI 1.6 to 3.2), history of heart failure (HR = 2.0, CI 1.7 to 2.5), treatment in an internal medicine ward rather than a cardiology ward (HR = 1.6, CI 1.3 to 2.0), female sex (HR = 1.6, CI 1.3 to 1.9) and age >or=80 years (HR = 1.4, CI 1.1 to 1.7). More patients with than without digoxin died (51% vs 31%, p<0.001). After adjustment for covariates, however, no disadvantages related to digoxin use could be found for all-cause mortality, myocardial infarction, ischaemic stroke, time to readmission to hospital or days at hospital/year at risk. The only end point significantly associated with digoxin use was pacemaker implantations, which were more common in digoxin-treated patients (HR = 2.0, CI 1.2 to 3.4).. Digoxin is mainly given to an elderly and frailer subset of patients with AF and is thus associated with an increased mortality. When differences in patient characteristics are accounted for digoxin use seems to have a neutral effect on mortality and major cardiovascular events in patients with AF.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Humans; Male; Prospective Studies; Regression Analysis; Retrospective Studies; Risk Factors

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Atrial Fibrillation; Bisoprolol; Bradycardia; Calcium Channel Blockers; Cardiovascular Agents; Combined Modality Therapy; Digoxin; Diltiazem; Female; Humans; Hypothyroidism; Kidney Failure, Chronic; Myocardial Infarction; Pacemaker, Artificial; Renal Dialysis

Topics: Atrial Fibrillation; Bradycardia; Burns; Digoxin; Electrocardiography; Follow-Up Studies; Heart Rate; Humans; Injections, Intravenous; Male; Metoclopramide; Middle Aged; Tachycardia, Paroxysmal

From April 2000 to March 2001 in BEACH (Bettering the Evaluation and Care of Health), atrial fibrillation (AF) was managed at a rate of 0.6 per 100 encounters, suggesting it was managed by general practitioners about 578 000 times per year nationally. From April 2008 to March 2009, AF was managed at more than double the earlier rate, 1.3 per 100 encounters, suggesting it was now managed by GPs about 1.5 million times per year nationally.

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Australia; Digoxin; Humans; International Normalized Ratio; Practice Patterns, Physicians'; Primary Health Care; Warfarin

Although no clinical trial data exist on the optimal management of atrial fibrillation (AF) in patients with diastolic heart failure, it has been hypothesized that rhythm-control is more advantageous than rate-control due to the dependence of these patients' left ventricular filling on atrial contraction. We aimed to determine whether patients with AF and heart failure with preserved ejection fraction (EF) survive longer with rhythm versus rate-control strategy.. The Duke Cardiovascular Disease Database was queried to identify patients with EF > 50%, heart failure symptoms and AF between January 1,1995 and June 30, 2005. We compared baseline characteristics and survival of patients managed with rate- versus rhythm-control strategies. Using a 60-day landmark view, Kaplan-Meier curves were generated and results were adjusted for baseline differences using Cox proportional hazards modeling.. Three hundred eighty-two patients met the inclusion criteria (285 treated with rate-control and 97 treated with rhythm-control). The 1-, 3-, and 5-year survival rates were 93.2%, 69.3%, and 56.8%, respectively in rate-controlled patients and 94.8%, 78.0%, and 59.9%, respectively in rhythm-controlled patients (P > 0.10). After adjustments for baseline differences, no significant difference in mortality was detected (hazard ratio for rhythm-control vs rate-control = 0.696, 95% CI 0.453-1.07, P = 0.098).. Based on our observational data, rhythm-control seems to offer no survival advantage over rate-control in patients with heart failure and preserved EF. Randomized clinical trials are needed to verify these findings and examine the effect of each strategy on stroke risk, heart failure decompensation, and quality of life.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Diuretics; Female; Heart Failure, Diastolic; Heart Rate; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Warfarin

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Research Design

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

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Echocardiography, Transesophageal; Electric Countershock; Electrocardiography; Humans; Lung; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Radiography; Warfarin

Topics: Administration, Oral; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Heart Conduction System; Humans; Injections, Intravenous; Propafenone; Quinidine; Recurrence; Time Factors; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Humans; Metoprolol; Treatment Failure; Warfarin

Clinical practice guidelines for patients with atrial fibrillation (AF) recommended a heart rate (HR) of 60 to 80 beats/min at rest and 90 to 115 at moderate exercise. The degree to which HR control at rest and with exercise in patients with AF complies with these recommendations is unknown. HR at rest and at peak exercise was retrospectively examined in 1,097 consecutive patients with AF referred for exercise myocardial perfusion imaging. In a subgroup of 195 patients, HR was also measured at an intermediate "moderate" level. Median HR at rest was 80 beats/min, at the upper end of the recommended range of 60 to 80. Only patients administered a beta blocker (BB; 31%) had lower (p <0.001) median HRs at rest. Median HR at moderate exercise was 128 beats/min, higher than the range of 90 to 115 recommended by the guidelines. Only patients administered a BB had significantly reduced HRs (p <0.003) at moderate exercise. Median peak exercise HR was 147 beats/min. Forty-five percent of patients exceeded their age-predicted maximal HR. Patients administered BBs were significantly less likely (p <0.01) to exceed their age-predicted maximal HR. In conclusion, in patients with AF, HR control at rest and during exercise often did not comply with guideline recommendations. Regimens including a BB were more effective in achieving HR control.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Exercise Test; Female; Heart Rate; Humans; Male; Physical Exertion; Rest; Retrospective Studies

This report describes the diagnosis and treatment of pulmonary arterial hypertension (PAH) in an adult male captive chimpanzee. Although cardiovascular disease in general is common in human and great apes, diagnosis and treatment of PAH in nonhuman primates are uncommon. In the case we present, the adult chimpanzee was diagnosed with an arrhythmia during an annual physical examination and later with PAH during a scheduled cardiovascular evaluation. PAH can either be primary or secondary and can lead to right ventricular overload and heart failure. This description is the first case study of pulmonary arterial hypertension in a great ape species.

Topics: Animals; Antihypertensive Agents; Aspirin; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Diuretics; Enalapril; Furosemide; Hypertension, Pulmonary; Liver; Lung; Male; Myocardium; Pan troglodytes; Platelet Aggregation Inhibitors; Primate Diseases

Topics: Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Digitalis; Digoxin; Drug Combinations; Hemorrhage; Humans; Phytotherapy

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

Clinical autopsy rate have been declining since the 1950s, but it remains a useful investigation tool.. Through six examples of our experience, we underline its interest for clinical, didactic and public health purposes.. We try to understand the reasons for its decline and, as demonstrated, it can be attributed to a number of factors. These need to be addressed in order to reassert the status of the autopsy as an investigation and audit tool which is crucial to the future effectiveness of modern medicine.

Topics: Adult; Aged; Atherosclerosis; Atrial Fibrillation; Autopsy; Cardiotonic Agents; Casuistry; Cause of Death; Coronary Artery Disease; Coronary Thrombosis; Diagnosis, Differential; Digoxin; Education, Medical; Female; France; Hallucinations; Hospitals, University; Humans; Male; Marfan Syndrome; Meningitis, Listeria; Meningitis, Pneumococcal; Middle Aged; Myocardial Infarction

To study evolvement in pharmacotherapy of atrial fibrillation from 1995 to 2004.. All Danish patients were discharged following first-time atrial fibrillation and their pharmacotherapy was identified by individual-level-linkage of nationwide registers of hospitalization and drug dispensing from pharmacies. A total of 108 791 patients survived 30 days after discharge and were included. In 1995-1996, 7.4% of the patients received beta-blockers, increasing to 44.3% in 2003-2004. The corresponding figures for amiodarone were 2.9 and 5.4%. In contrast, use of nondihydropyridine calcium-channel blockers, digoxin, sotalol, and class 1C antiarrhythmics decreased from 20.6, 63.9, 21.3, and 4.0% in 1995-1996 to 12.6, 43.8, 4.2, and 1.3% in 2003-2004, respectively. Notably, patients receiving anticoagulants increased from 29.8 to 43.5%. Multivariate logistic regression analysis revealed females to be associated with more use of digoxin, but less use of amiodarone and oral anticoagulants than males. Patients above 80 years received less pharmacotherapy, apart from digoxin treatment that was more commonly used in elderly.. Pharmacotherapy of atrial fibrillation has changed towards increased beta-blocker use with a coincident decrease in the use of other rate-limiting drugs and sotalol. Treatment with amiodarone or class 1C antiarrhythmics remained very low. Oral anticoagulant therapy increased considerably, but women and elderly were apparently undertreated.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Denmark; Digoxin; Drug Therapy; Female; Humans; Logistic Models; Longitudinal Studies; Male; Middle Aged; Patient Discharge; Registries; Retrospective Studies; Sotalol

Little is presently known regarding whether a rhythm-control or a rate-control strategy is more frequently used in patients hospitalized for atrial fibrillation (AF). This study was conducted to assess patient and physician characteristics associated with each treatment strategy and with the use of anticoagulants. Hospitalizations for primary diagnoses of AF were examined using hospital claims from January 2000 to December 2004. Patients who received antiarrhythmic drugs, ablation, or cardioversion for AF were categorized as receiving rhythm control. Patients managed only with beta blockers, calcium channel blockers, or digoxin were categorized as receiving rate control. Characteristics associated with rhythm compared with rate control and anticoagulant use with CHADS(2) score were determined. The study cohort included 155,731 hospitalizations from 464 hospitals. Of these, 75,397 (48%) were categorized as involving rhythm control and 80,334 (52%) as involving rate control. Care by a noncardiologist (adjusted odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31 to 0.36) and increasing age >65 years (adjusted OR 0.87, 95% CI 0.86 to 0.88) were associated with lower odds of rhythm versus rate control; hypertrophic cardiomyopathy was associated with greater odds (adjusted OR 2.3, 95% CI 1.81 to 2.84) of rhythm control. Warfarin use was greater in the rhythm-control group compared with the rate-control group (adjusted OR 1.56, 95% CI 1.52 to 1.60), and warfarin use was greater with a CHADS(2) score > or =2 (unadjusted OR 1.21, 95% CI 1.19 to 1.24). In conclusion, rhythm- and rate-control strategies were used equally in patients hospitalized for AF. Some observations, such as greater use of the rate-control strategy with increasing age, were consistent with recommendations, but others, such as lower use of warfarin in the rate-control group, were not.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Catheter Ablation; Digoxin; Drug Utilization; Electric Countershock; Female; Hospitalization; Humans; Male; Medicine; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Severity of Illness Index; Specialization; United States; Warfarin; Wolff-Parkinson-White Syndrome

Cardiac arrhythmias and osteoporotic fractures are common in the elderly.. We studied whether tachyarrhythmia and/or the drugs used to treat arrhythmias affect risk of fracture.. In a population-based nation-wide pharmaco-epidemiological case-control design, we compared 124,655 patients that sustained a fracture during 2000 with 373,962 age- and gender-matched controls. We used computerized registers to assess individual drug use and related these data to individual fracture data and information on confounders.. Risk of any fracture was increased in patients with atrial fibrillation [Odds ratio (OR): 1.14; 95% confidence interval (95%CI): 1.08-1.21] and in patients currently treated with amiodarone (OR: 1.47; 95%CI: 1.21-1.78). Conversely, current use of digoxin decreased fracture risk (OR: 0.75; 95%CI: 0.71-0.79). Subanalysis showed similar effects in men and in women, but drug treatment only affected fracture risk in subjects older than 65 years of age. In current users of digoxin, risk of any fracture and risk of hip and forearm fracture decreased dose-dependently with increased dose. The use of other antiarrhythmics did not affect fracture risk.. Special attention should be paid to patients on treatment with amiodarone and/or a diagnosis of atrial fibrillation as they may have an increased risk of fracture. Conversely, treatment with digoxin may reduce fracture risk.

Topics: Adult; Age Factors; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Case-Control Studies; Digoxin; Dose-Response Relationship, Drug; Female; Forearm Injuries; Fractures, Bone; Hip Fractures; Humans; Male; Osteoporosis; Risk Factors; Sex Factors; Tachycardia

A 31-year-old man with dilated cardiomyopathy was hospitalized for new-onset atrial fibrillation. Oral amiodarone 600 mg/day was started to control his arrhythmia, and the patient continued to receive digoxin 0.125 mg/day, which was prescribed 4 days earlier at a heart failure clinic. The patient's digoxin plasma concentration peaked early on hospital day 3 at 2.93 ng/ml; digoxin was withheld. Over the next 3 days, the patient's digoxin plasma concentrations rose and fell daily. These fluctuations correlated with the timing of blood sampling in relation to oral amiodarone administration. The patient's renal function remained stable, and he developed no signs or symptoms of digoxin toxicity. To our knowledge, no case reports have associated significant fluctuations of digoxin plasma concentrations that correspond to the timing of oral amiodarone administration. Tissue-to-plasma redistribution appears to be a possible mechanism for this interaction, with the most significant effect occurring 8-10 hours after amiodarone administration. Clinicians should be aware that digoxin plasma concentrations may not correlate with digoxin tissue concentrations in this setting. When a loading dose of oral amiodarone is required in a patient receiving digoxin, the digoxin dosage should first be reduced, and digoxin therapy should be adjusted based on signs and symptoms of digoxin toxicity.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiomyopathy, Dilated; Digoxin; Drug Interactions; Drug Monitoring; Humans; Male; Time Factors

Topics: Atrial Fibrillation; Cognition Disorders; Dementia; Digoxin; France; Humans

Topics: Aged; Atrial Fibrillation; Chronic Disease; Contraindications; Coronary Artery Bypass; Digoxin; Drug Interactions; Electrocardiography; Humans; Hypertension; Male; Postoperative Complications; Quinine; Syncope; Tachycardia, Ventricular; Torsades de Pointes; United Kingdom

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Drug Interactions; Drug Therapy, Combination; Enzyme Inhibitors; Female; Gastroesophageal Reflux; Humans; Omeprazole; Proton Pump Inhibitors; Risk Factors; Warfarin

Omeprazole is a commonly prescribed inhibitor of the gastric proton pump and has numerous indications in the treatment of gastrointestinal diseases. It is primarily metabolized through the CYP2C19 enzyme, a member of the P450 mixed-function oxidase group, although a minor pathway of metabolism is through CYP3A4, another P450 enzyme. Digoxin is primarily metabolized outside the P450 system, but a minor pathway of metabolism is by CYP3A4. To our knowledge, this is the first known case of digoxin toxicity associated with omeprazole. The possible pathways for such an interaction are reviewed, including increased stomach absorption, p-glycoprotein activity and interactions in the P450 system.

Topics: Aged; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Drug Interactions; Enzyme Inhibitors; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Immunoglobulin Fab Fragments; Omeprazole; Poisoning; Tachycardia, Paroxysmal

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Dizziness; Electrocardiography; Humans; Immunoglobulin Fab Fragments; Kidney Failure, Chronic; Male; Muscle Weakness; Vision Disorders

Topics: Aged; Amlodipine; Atrial Fibrillation; Digoxin; Female; Graves Disease; Humans; Hypertension, Pulmonary; Methimazole; Recurrence; Syncope; Treatment Outcome; Vertigo

To examine if appropriate antithrombotic therapy in atrial fibrillation is implemented nationally.. Using prescriptions for digoxin as a surrogate for atrial fibrillation, we identified its coprescription with antithrombotic therapy, aspirin or warfarin in a national prescribing database in 27 571 patients over 45 years old.. Proportionately significantly more men were on warfarin, and use in those >75 years old was three times less than in those <65 years. Reluctance to use antithrombotics was confirmed in a postal survey.. Data suggest a missed opportunity to prevent stroke with women and those >75 years old least likely to receive warfarin.

Topics: Age Factors; Aged; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Cyclooxygenase Inhibitors; Digoxin; Female; Humans; Male; Middle Aged; Sex Factors; Thrombosis; Treatment Outcome; Warfarin

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

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Randomized Controlled Trials as Topic

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Humans

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Humans; Metoprolol; Quality of Life; Treatment Failure; Warfarin

Topics: Acute Kidney Injury; Aged; Atrial Fibrillation; Bundle-Branch Block; Digitalis; Digoxin; Electrocardiography; Humans; Male; Metoprolol; Tachycardia, Ventricular

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Bradycardia; Digoxin; Drug Interactions; Electrocardiography; Female; Humans; Hypotension; Middle Aged; Sotalol; Time Factors; Verapamil

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

Topics: Aged; Antidepressive Agents, Second-Generation; Atrial Fibrillation; Depressive Disorder, Major; Digoxin; Drug Interactions; Fatal Outcome; Female; Humans; Paroxetine

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

The loss of atrial contractile function after cardioversion of atrial fibrillation (AF) contributes to the thromboembolic risk associated with AF. The newly developed blocker of the transient outward current (I(to)) and ultrarapid delayed rectifier current (I(Kur)) AVE0118 prolongs atrial action potential duration and might therefore enhance atrial contractility. We compared the ability of AVE0118 to restore atrial contraction after cardioversion of AF with the efficacy of conventional positive inotropic compounds in the goat model of AF.. Eighteen goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. Atrial contractility and refractoriness and QT duration were measured before and after 1 week (3 to 8 days) of AF induced by repetitive burst pacing. The measurements were repeated after administration of digoxin (0.02 mg/kg), dobutamine (5 microg x kg(-1) x min(-1)), the Ca2+ sensitizer EMD57033 (1 mg x kg(-1) x min(-1)), the L-type Ca2+ channel agonist BayY5959 (0.1 mg x kg(-1) x min(-1)), and AVE0118 (0.01 to 0.2 mg x kg(-1) x min(-1)). The effect of AVE0118 on the configuration of atrial monophasic action potentials was determined for comparison. After 1 week of AF, atrial contractility during sinus rhythm or slow atrial pacing was reduced to <10%. Digoxin and dobutamine failed to increase atrial contractility. EMD57033 restored 41% and BayY5959 restored 48% of atrial contractility at baseline. BayY5959 significantly prolonged QT duration by 24.7%. AVE0118 enhanced atrial contraction to 156% of the baseline value. The positive inotropic effect was accompanied by a pronounced prolongation of atrial action potential duration and refractoriness, whereas QT duration remained unchanged.. Conventional positive inotropic drugs showed limited effect on atrial contractility after cardioversion of AF or produced QT prolongation. In contrast, the I(to)/I(Kur) blocker AVE0118 fully restored atrial contraction without proarrhythmic effects on the ventricle.

Topics: Action Potentials; Animals; Atrial Fibrillation; Atrial Function, Right; Biphenyl Compounds; Cardiotonic Agents; Delayed Rectifier Potassium Channels; Digoxin; Dihydropyridines; Disease Models, Animal; Dobutamine; Electric Countershock; Electrocardiography; Goats; Myocardial Contraction; Potassium Channel Blockers; Potassium Channels, Voltage-Gated; Quinolines; Thiadiazines

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

Fetal tachyarrhythmia may cause fetal hydrops and lead to fetal morbidity and mortality. Supraventricular tachycardia and atrial flutter have been the most diagnosed. We present a case of fetal atrial flutter diagnosed during the second trimester treated with digoxin and sotalol and delivered at term.. A 30-year-old primigravid woman was diagnosed with fetal atrial flutter at the gestational age of 25 weeks with atrial rates of 480-520 bpm and ventricular rates of 200-250 bpm. Initially, she was treated with digoxin then with a combination of digoxin and sotalol. The fetal heart beat slowed after sotalol treatment but did not return to sinus rhythm. The fetus was delivered vaginally. Neonatal echocardiography showed a small apical ventricular septal defect and small patent ductus arteriosus. Electrocardiography also revealed atrial flutter with occasional atrial fibrillation.. The efficacy of antiarrhythmic drug therapy for fetal atrial flutter has not been well established. In our case, we used sotalol combined with digoxin and the fetal heart beat slowed after therapy. Sotalol may be considered the drug of choice for fetal atrial flutter. If the fetal atrial flutter is resistant to these therapies, a combination of other congenital cardiac diseases or organic abnormalities should be considered.

Topics: Administration, Oral; Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Delivery, Obstetric; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ductus Arteriosus, Patent; Echocardiography; Female; Fetal Diseases; Heart Rate, Fetal; Heart Septal Defects, Ventricular; Humans; Infant, Newborn; Pregnancy; Sotalol

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

Topics: Administration, Oral; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Drug Interactions; Humans; Propafenone; Warfarin

The purpose of this study was to determine whether digoxin use is associated with increased flow cytometric markers of endothelial cell and platelet activation in patients with nonvalvular atrial fibrillation (AF).. Increased intracellular calcium is a key event in platelet activation, and several studies have demonstrated that digitalis activates platelets in vitro. Intracellular calcium also is a key regulator of endothelial cell function, and endogenous digitalis-like substances have been shown to affect biologic processes in endothelial cells.. We studied 30 patients with nonvalvular AF. We measured the levels of (1) platelet expression of P-selectin (CD62P), (2) platelet microparticles (PMP); and (3) endothelial microparticles (EMP) identified by anti-CD31 (EMP31) and by anti-E-selectin antibodies (EMP62E).. Patients who were taking digoxin (n = 16; mean digoxin level = 0.93 ng/dL) did not demonstrate any significant differences in clinical or echocardiographic characteristics compared with patients not taking digoxin (n = 14). Patients taking digoxin had significantly increased levels of CD62P expression in platelets and platelet-leukocyte conjugates and markedly increased markers of endothelial activation: EMP62E and EMP31. After adjusting for potential confounders (including age, congestive heart failure, coronary artery disease, ejection fraction, antiplatelet, beta-blocker, and calcium channel blocker use), the differences persisted.. Digoxin use in patients with AF is associated with increased levels of endothelial and platelet activation. If digitalis activates endothelial cells and platelets at pharmacologic doses, use of digitalis in conditions such as AF could predispose to thrombosis and vascular events.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Platelets; Cross-Sectional Studies; Digoxin; Endothelial Cells; Humans; Middle Aged; Multivariate Analysis; P-Selectin

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Platelets; Digoxin; Endothelial Cells; Humans; Stroke; Thrombosis

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Diltiazem; Heart Rate; Humans; Infusions, Intravenous; Remission, Spontaneous

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Stroke Volume

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Chronic Disease; Digoxin; Electrocardiography; Female; Humans; Tachycardia, Ventricular

Topics: Administration, Oral; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Humans; Tachycardia, Ventricular; Time Factors

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Sotalol; Time Factors

To analyze action of digoxin and some non-digitalis drugs (beta-blockers, verapamil, amiodarone, d,l-sotalol) and their combinations on electrical activity of atria, frequency and structure of ventricular rhythm in patients with permanent atrial fibrillation.. One hundred patients with permanent atrial fibrillation and heart rate at rest above 80 bpm were divided into 9 treatment groups. High-resolution orthogonal Frank lead ECG was recorded before and after allocated treatment. Analysis included construction of ff-waves periodograms, histograms of RR interval, cardiointervalograms and application of autocorrelation function.. It was demonstrated that frequency and form (structure) of ventricular rhythm was determined not only by the state of AV conduction but also by value of basic period of ff-waves. The mechanisms of ventricular rate deceleration by investigated drugs were not identical. beta-blockers and verapamil directly slowed AV conduction without changing parameters of ff-waves and differed from each other only in action on parameters of concealed conduction in AV node. Action of digoxin in patients with ff-waves period equal to or exceeding 0,15 s was biphasic. During phase I shortening of ff-wave period (by 0.025+/-0.012 s) occurred. This was associated with increase of their concealed conduction through AV node. The latter phenomenon represented independent mechanism of ventricular rhythm deceleration. During phase II of digoxin action direct inhibition of AV conduction took place. Amiodarone and d,l-sotalol increased basic ff-waves period. This facilitated their conduction through AV node. Greater heart rate slowing effect of d,l-sotalol was attributed to its ability to augment concealed conduction. Due to their antiarrhythmic qualities amiodarone and d,l-sotalol slowed heart rate in patients with peak RR duration in the region of 0.28-0.46 s. These patients often had bi- and tri-modal structure of interval RR histogram. Changes of ventricular rhythm structure during use of various drugs were different. Action of digoxin was most whilst that of beta-blockers least favorable.. Choice of a drug for treatment of permanent atrial fibrillation should be conducted with consideration of ff-waves periodicity, parameters of RR interval histogram, and characteristics of ventricular rhythm structure.

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Periodicity; Sotalol; Ventricular Premature Complexes; Verapamil

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Catheter Ablation; Digoxin; Heart Rate; Humans; Pacemaker, Artificial; Stroke Volume

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Synergism; Drug Therapy, Combination; Electrocardiography; Emergency Treatment; Heart Failure; Humans; Male; Tachycardia, Ventricular

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Calcium Channel Blockers; Digoxin; Humans

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiology; Digoxin; Drug Monitoring; Family Practice; Humans; International Normalized Ratio; Warfarin

Electrical injury can cause a variety of cardiac arrhythmias. Atrial fibrillation as a result of such injury is fairly rare, however, and is rarer still in cases of low-tension electrical injury. We present the case of a patient who developed acute atrial fibrillation in association with low-voltage electrical injury, which resolved after the intravenous administration of digoxin.

Topics: Accidents, Occupational; Adult; Atrial Fibrillation; Digoxin; Electric Injuries; Electrocardiography; Humans; Infusions, Intravenous; Male

A number of reports have raised the possibility that myocardial strain could be associated to increased plasma levels of troponin I. A 69-year-old, male, Caucasian, patient was admitted with prolonged chest pain and dyspnoea. The electrocardiogram showed atrial fibrillation with a ventricular rate of about 120 to 150/minute. After treatment with digoxin and amiodarone, the patient returned to sinus rhythm. An elevation in the plasma levels of troponin I was noted, with a maximum value of 0.66 ng/ml. Coronary angiography showed absence of coronary artery atherosclerotic lesions. Atrial fibrillation of recent onset and with a relatively high heart rate may be yet another situation in which acute myocardial strain could be the cause of the abnormal release of cardiac troponin I.

Topics: Aged; Amiodarone; Atrial Fibrillation; Digoxin; Humans; Male; Troponin I

Topics: Adult; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Contraindications; Digoxin; Electric Countershock; Humans; Practice Guidelines as Topic; Warfarin

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

Topics: Anti-Bacterial Agents; Anticoagulants; Atrial Fibrillation; Clarithromycin; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Middle Aged; Pneumonia, Bacterial; Warfarin

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

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

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; Atrial Fibrillation; Atrioventricular Node; Combined Modality Therapy; Digoxin; Electric Stimulation; Humans; Vagus Nerve

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Disease Management; Electric Countershock; Heart Rate; Humans; Practice Guidelines as Topic; Sotalol; Treatment Outcome; United States

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Ventricular Dysfunction, Left

Topics: Anti-HIV Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Cardiotonic Agents; Contraindications; Digoxin; Drug Interactions; Female; HIV Infections; Humans; Kidney; Middle Aged; Ritonavir

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Humans

To assess the contribution of the Na, K pump current (I(p)) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether I(p) contributes to the changes in APD and ERP associated with chronic atrial fibrillation (AF).. Action potentials and ion currents were recorded by whole-cell patch clamp in atrial myocytes isolated from consenting patients undergoing cardiac surgery, who were in sinus rhythm (SR) or AF (>3 months).. In cells from patients in SR, the I(p) blocker, ouabain (10 microM) significantly depolarised the membrane potential, V(m), from -80+/-2 (mean+/-S.E.) to -73+/-2 mV, and lengthened both the APD (174+/-17 vs. 197+/-23 ms at 90% repolarisation) and ERP (198+/-22 vs. 266+/-14 ms; P<0.05 for each, Student's t-test, n=7 cells, 5 patients). With an elevated pipette [Na(+)] of 30 mM, I(p) was measured by increasing extracellular [K(+)] ([K(+)](o)) from 0 to 5.4 mM. This produced an outward shift in holding current at -40 mV, abolished by 10 microM ouabain. K(+)- and ouabain-sensitive current densities were similar, at 0.99+/-0.13 and 1.12+/-0.11 pA/pF, respectively (P>0.05; n=9 cells), confirming the K(+)-induced current as I(p). I(p) increased linearly with increasing V(m) between -120 and +60 mV (n=25 cells). Stepwise increments in [K(+)](o) (between 0 and 10 mM) increased I(p) in a concentration-dependent manner (maximum response, E(max)=1.19+/-0.09 pA/pF; EC(50)=1.71+/-0.15 mM; n=27 cells, 9 patients). In cells from patients in AF, the sensitivity of I(p) to both V(m) and [K(+)](o) (E(max)=1.02+/-0.05 pA/pF, EC(50)=1.54+/-0.11 mM; n=44 cells, 9 patients) was not significantly different from that in cells from patients in SR. Within the group of patients in AF, long-term digoxin therapy (n=5 patients) was associated with a small, but significant, reduction in E(max) (0.92+/-0.07 pA/pF) and EC(50) (1.35+/-0.15 mM) compared with non-treatment (E(max)=1.13+/-0.08 pA/pF, EC(50)=1.76+/-0.14 mM; P<0.05 for each, n=4 patients). In cells from non-digoxin-treated patients in AF, the voltage- and [K(+)](o)-sensitivity (E(max) and EC(50)) were similar to those in cells from patients in SR.. The Na, K pump current contributes to the human atrial cell V(m), action potential shape and ERP. However, the similarity in I(p) sensitivity to both [K(+)](o) and V(m) between atrial cells from patients with and without chronic AF indicates that I(p) is not involved in AF-induced electrophysiological remodelling in patients.

Topics: Action Potentials; Aged; Atrial Fibrillation; Atrial Function; Cardiotonic Agents; Cells, Cultured; Chronic Disease; Coronary Artery Bypass; Digoxin; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Myocardium; Ouabain; Patch-Clamp Techniques; Sodium-Potassium-Exchanging ATPase

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI) with a reported incidence of 7-18%. Recently, P-wave signal-averaged electrocardiogram (P-SAECG) has been used to assess the risk of paroxysmal AF attacks in some diseases. The aim of this study was to determine prospectively whether patients with AMI at risk for paroxysmal AF would be identified by P-SAECG and other clinical variables.. A total of 100 patients (mean age: 59+/-12, 77 male, 23 female) with ST segment elevation AMI were enrolled in this study. Patients with chronic AF were excluded. At entry, all patients underwent standard 12-lead ECG and in the first 24 hours, P-SAECG was taken, and echocardiography and coronary angiography were performed on the patients. Patients are followed for a month in terms of paroxysmal AF attacks and mortality.. AF was determined in 19 patients (19%). In patients with AF, abnormal P-SAECG more frequently occurred than in patients without AF (37% vs 15%, P<0.05). Patients with AF were older (70+/-14 vs 56+/-10, P<0.001) and had lower left ventricular ejection fraction (42%+/-8 vs 49%+/-11, P<0.05). AF was less common in thrombolysis-treated patients (47% vs 74%, P<0.05). Thirty-day mortality was higher in patients with AF (16% vs 2%, P=0.05).. An abnormal P-SAECG may be a predictor of paroxysmal AF in patients with AMI. Advanced age and systolic heart failure were detected as two important clinical risk factors for the development of AF.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Coronary Angiography; Digoxin; Echocardiography; Electric Countershock; Electrocardiography; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Prospective Studies; Risk Factors; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

5-Fluorouracil, a widely used drug in cancer treatment, is known to have cardiotoxic effects: chest pain with ECG changes, arrhythmias, arterial hypertension or hypotension, myocardial infarction, cardiogenic shock and sudden death have been described in the literature. Coronary artery vasospasm is the pathogenetic mechanism hypothesized in most cases, but mechanisms other than myocardial ischemia had been advocated in some patients. The approach to the patient with persistent chest pain, despite therapy and persistent ST-segment elevation mimicking an acute myocardial infarction, has not been well addressed, and the appropriate diagnostic and therapeutic pathways have not yet been defined. We present our experience regarding 2 patients treated with 5-fluorouracil and referred to our coronary care unit because of prolonged chest pain (in one case with clinical evidence of hemodynamic impairment) and persistent ST-segment elevation, in whom an acute myocardial infarction was suspected. One patient was treated with systemic fibrinolysis, and coronary angiography was performed 6 days later; the other was submitted to urgent coronary angiography shortly after admission. In both cases the ECG and echocardiographic abnormalities were transient and normalized within a few days, the serum markers of myocardial necrosis were persistently in the normal range and the coronary artery trees were normal. The diagnostic and therapeutic approach to patients with this unusual clinical presentation is also discussed.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antimetabolites, Antineoplastic; Atrial Fibrillation; Captopril; Chest Pain; Colorectal Neoplasms; Coronary Angiography; Digoxin; Disease Management; Echocardiography; Electrocardiography; Fluorouracil; Humans; Laryngeal Neoplasms; Middle Aged; Myocardial Infarction; Nitrates; Verapamil

Left ventricular contractility in atrial fibrillation is known to change in a beat to beat fashion, but there is no gold standard for contractility indices in atrial fibrillation, especially those measured non-invasively.. To determine whether the non-invasive index of contractility "preload-adjusted PWR(max)" (maximal ventricular power divided by the square of end diastolic volume) can accurately measure left ventricular contractility in a beat to beat fashion in atrial fibrillation.. Atrial fibrillation was induced experimentally using 60 Hz stimulation of the atrium and maintained in 12 sheep; four received diltiazem, four digoxin, and four no drugs (control). Aortic flow, left ventricular volume, and left ventricular pressure were monitored simultaneously. Preload-adjusted PWR(max), the slope of the end systolic pressure-volume relation (E(max)), and the maximum rate of change of left ventricular pressure (dP/dt(max)) were calculated in a beat to beat fashion.. Preload-adjusted PWR(max) correlated linearly with load independent E(max) (p < 0.0001) and curvilinearly with load dependent dP/dt(max) (p < 0.0001), which suggested the load independence of preload-adjusted PWR(max). After five minutes of diltiazem administration, preload-adjusted PWR(max), dP/dt(max), and E(max) fell significantly (p < 0.0001) to 62%, 64%, and 61% of baseline, respectively. Changes were not significant after five minutes of digoxin (103%, 98%, and 102%) or in controls (97%, 96%, and 95%).. Preload-adjusted PWR(max) correlates linearly with E(max) and is a useful measure of contractility even in atrial fibrillation. Non-invasive application of this method, in combination with echocardiography and tonometry, may yield important information for optimising the treatment of patients with atrial fibrillation.

Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiovascular Agents; Digoxin; Diltiazem; Myocardial Contraction; Sheep; Ventricular Function, Left

A 65-year-old woman with a history of alcoholic liver disease and presenting with fever and vomiting was admitted to an internal medicine unit. In view of recent atrial fibrillation with inadequate heart rate control, digoxin and propafenone were included in the therapeutic regimen. After a few days sinus rhythm was restored but suddenly ventricular arrhythmias with the characteristics of a non-responsive electrical storm arose shortly following the appearance of clinical symptoms of drug intoxication.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Humans; Liver Diseases, Alcoholic; Propafenone

Topics: Atrial Fibrillation; Digoxin; Humans; United Kingdom; Verapamil

Topics: Animals; Anti-Arrhythmia Agents; Atenolol; Atrial Fibrillation; Diagnosis, Differential; Digoxin; Dog Diseases; Dogs; Electrocardiography; Fatal Outcome; Female; Heart Rate; Histiocytic Sarcoma; Tachycardia

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Electrocardiography; Fatal Outcome; Female; Humans; Immunoglobulin Fab Fragments

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digitalis; Digoxin; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Heart Conduction System; Humans; Male

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Combined Modality Therapy; Digoxin; Electric Countershock; Heart Rate; Humans; Randomized Controlled Trials as Topic

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

An ethylic hypertensive patient with a BMI of 51.4 developed persistent atrial fibrillation with high ventricular rates. External electrical cardioversion was attempted, but failed in spite of high energy shocks (350 joules). Sinus rhythm was restored by internal cardioversion (12 joules). The value and indications of the techniques are briefly discussed.

Topics: Alcoholism; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Body Mass Index; Chronic Disease; Combined Modality Therapy; Digoxin; Electric Countershock; Humans; Hypertension; Male; Middle Aged; Obesity, Morbid; Patient Selection

This was a retrospective analysis of patients who had CABG surgery at our hospital over a 12-month period to determine the intermediate-term prognosis of those who had developed PAF after their operation before hospital discharge. Of 317 patients who were operated by a single surgical group, 116 (37%) had AF postoperatively of whom 112 had the paroxysmal form. Of these, 36 were treated with class I or III antiarrhythmic drugs and rate control drugs (group 1) and 76 were treated with rate control alone (group 2). Group 3 consisted of 151 randomly selected patients who did not have AF. All patients were reevaluated at 6 weeks to determine their rhythm and clinical status. Only one patient each in groups 1 and 2 was in AF 6 weeks after discharge. There was a trend toward a higher mortality and morbidity in group 2 patients. PAF after coronary surgery appears to be a self-limited disease process. In this cohort of patients, the rate of recurrence of AF after discharge was similar in patients receiving class I or class III antiarrhythmic drugs together with rate control agents compared to those receiving rate control drugs alone.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Case-Control Studies; Coronary Artery Bypass; Digoxin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morbidity; Postoperative Complications; Prognosis; Random Allocation; Recurrence; Retrospective Studies; Time Factors

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: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Sotalol; Time Factors; Treatment Outcome

Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Goats

Although risk factors for the development of atrial fibrillation (AF) after cardiac operations have been studied extensively, predictors of conversion to sinus rhythm within 24 hours of onset have not been examined.. Eleven hundred consecutive adults undergoing cardiovascular operations from July 1997 to June 1998 were screened for new onset AF after operation. Patients with chronic persistent preoperative AF or those who died within 48 hours of the operation were excluded.. Three hundred fifty-three patients develop

Topics: Adrenergic beta-Antagonists; Aged; Analysis of Variance; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiac Surgical Procedures; Digoxin; Female; Heart Rate; Humans; Logistic Models; Male; Prospective Studies; Time Factors

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiac Output, Low; Digoxin; Evidence-Based Medicine; Frail Elderly; Health Services for the Aged; Humans; Medical History Taking; Monitoring, Physiologic; Outcome and Process Assessment, Health Care; Patient Education as Topic; Physical Examination; Stroke Volume

Atrial fibrillation (AF) is a fairly common complication of acute myocardial infarction (AMI). The aim of this study was to examine the safety and efficacy of intravenous amiodarone in converting AF associated with AMI.. Seventy patients with AMI complicated with AF were prospectively divided into 3 groups: a) In group D (n = 26), 0.75 mg digoxin was administered intravenously and thereafter as needed, b) In group AM (n = 16), 300 mg of amiodarone was infused over 2 hours followed by 44 mg/hour for up to 60 hours or until sinus rhythm was restored, c) In group D + AM (n = 28), 0.75 mg of digoxin was administered (as in group D) for the initial 2 hours followed by amiodarone infusion as in group AM.. Sinus rhythm was restored: a) by the end of the 2nd hour in 9/26 patients from group D, 4/16 from group AM, and 10/28 from group D + AM (p = NS), b) by the end of the 96th hour, in 18/26 patients from group D, and in all patients from group AM and groupd D + AM. The corresponding duration of AF was 51 +/- 34 hours, 17 +/- 15 hours and 9 +/- 13 hours, respectively (F = 15.4, p < 0.001). AF recurred in 9/26, 5/16 and 1/28 patients of groups D, AM and D + AM, respectively (p = 0.026). The required dosage of amiodarone was lower in the D + AM group than in the AM group (603 +/- 563 mg versus 1058 +/- 680 mg, p = 0.037).. Intravenous amiodarone was well tolerated in patients with AMI complicated by AF and was effective in decreasing the duration of AF. However, the combination of amiodarone and digoxin was superior to amiodarone alone in restoring sinus rhythm faster, maintaining sinus rhythm longer, and allowing the use of a lower cumulative amount of amiodarone.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Treatment Outcome

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

This study investigated the association of COPD and postoperative cardiac arrhythmias, specifically supraventricular tachycardia (SVT), as well as mortality in patients undergoing pulmonary resection for non-small cell lung cancer (NSCLC).. A retrospective chart review of 244 patients who had undergone lung resection for NSCLC at Indiana University Hospital between 1992 and 1997 was undertaken. COPD, which was defined as an FEV(1) of < or = 70% predicted and an FEV(1)/FVC ratio of < or = 70% based on the results of a preoperative pulmonary function test (PFT), was diagnosed in 78 of the 244 patients (COPD group). In the remaining 166 patients, the results of preoperative PFTs did not meet these criteria (non-COPD group). Both groups were otherwise well-matched with respect to multiple variables, including age, comorbid conditions, extent of pulmonary resection, and final pathologic stage. The incidence of cardiac arrhythmias and operative mortality were compared between the two groups using univariate and multivariate analysis.. Seventy-six patients (31.9%) experienced new onsets of postoperative SVT, with 58 of these patients (76.3%) demonstrating atrial fibrillation. The COPD group had a 58.7% incidence of SVT (n = 44) compared to a 27.0% incidence (n = 44) in the non-COPD group (p < 0.0 0 1). Moreover, following initial digoxin therapy, the COPD group required more second-line antiarrhythmic therapy than did the non-COPD group (66.7% vs 37.8%, respectively; p = 0.0 03). Overall, there were 16 operative deaths (6.6%), and the mortality rate was significantly higher in the COPD group (14.1%) than in the non-COPD group (3.0%; p = 0.0 04). Patients who developed SVT had a significantly longer hospital course than did patients who did not (p < 0.0001). Thirteen of the 16 patients who died experienced SVT; however, SVT was not an independent risk factor for death. Finally, of the 19 variables evaluated, major resection (ie, pneumonectomy and bilobectomy) and COPD were identified as independent risk factors for the development of cardiac arrhythmias (p = 0.0 033 and p = 0.0 009, respectively).. Patients with COPD, as defined by the results of preoperative PFTs, are at significantly higher risk for SVT, and in particular SVT refractory to digoxin, following pulmonary resection for NSCLC. Although SVT was not an independent risk factor for death, a significantly longer hospitalization was observed.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Carcinoma, Non-Small-Cell Lung; Cause of Death; Digoxin; Female; Forced Expiratory Volume; Hospital Mortality; Humans; Lung Neoplasms; Male; Middle Aged; Pneumonectomy; Postoperative Complications; Pulmonary Disease, Chronic Obstructive; Risk Factors; Survival Rate; Tachycardia, Supraventricular; Vital Capacity

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Female; Humans; Warfarin

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Interactions; Drug Therapy, Combination; Heart Failure; Humans; Phenethylamines; Sulfonamides

We experienced sudden cardiac arrest after induction of general anesthesia using isoflurane. The patient had had paroxysmal atrial fibrillation for one year and had been treated with digoxin and cibenzoline succinate. Sinus rhythm appeared soon after the start of closed chest compression. However cardiac arrest recurred, and we inserted a temporary pacemaker catheter to stabilize the circulatory status. She awoke from anesthesia without any complications. The diagnosis of sick sinus syndrome (SSS) was made postoperatively and she had a permanent pacemaker implanted. We thought that the hidden SSS had been the cause of this sudden cardiac arrest.

Topics: Aged; Anesthesia, General; Anesthetics, Inhalation; Anti-Arrhythmia Agents; Atrial Fibrillation; Breast Neoplasms; Digoxin; Female; Heart Arrest; Humans; Imidazoles; Isoflurane; Mastectomy; Pacemaker, Artificial; Sick Sinus Syndrome

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Atrial Fibrillation; Data Collection; Digoxin; Exercise Therapy; Fee-for-Service Plans; Heart Failure; Humans; Information Services; Length of Stay; Outcome and Process Assessment, Health Care; Patient Education as Topic; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality of Health Care; Referral and Consultation; Stroke Volume; United States; Ventricular Dysfunction, Left

Topics: Acebutolol; Aged; Anti-Arrhythmia Agents; Antibodies, Antiphospholipid; Anticoagulants; Atrial Fibrillation; Digoxin; Fever of Unknown Origin; Humans; Immunoglobulins; Lupus Coagulation Inhibitor; Male; Phenindione; Q Fever

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Humans; Male; Methylprednisolone; Middle Aged; Multiple Sclerosis, Chronic Progressive; Propafenone; Pulse Therapy, Drug; Treatment Outcome

Little information exists about the early outcomes of initiating amiodarone for atrial fibrillation in patients with advanced heart failure. This study assessed the initial rate of success and complications of amiodarone therapy initiated for patients with atrial fibrillation during hospitalization for heart failure.. We reviewed medical records for 37 consecutive patients with left ventricular ejection fractions

Topics: Administration, Oral; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Cardiotonic Agents; Digoxin; Drug Interactions; Electric Countershock; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Retrospective Studies; Stroke Volume; Treatment Outcome

Topics: Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Drug Approval; Drug Interactions; Humans; Secondary Prevention; Warfarin

67 year old patient with chronic heart failure and persistent atrial fibrillation had overdosed glycosides for several months. The symptoms of gastrointestinal system and nervous system appeared after long term therapy with toxic doses of glycosides. Originally depression was diagnosed based on the central nervous system disturbances. Even though overdose of glycosides was diagnosed the blood serum glycoside level was within the therapeutic limits. Based on the precise analysis of the data, it was concluded that the reason for normal blood serum glycoside level in this case was coexisting hyperthyreosis.

Topics: Aged; Atrial Fibrillation; Color Vision Defects; Depression; Digoxin; Drug Overdose; Heart Failure; Humans; Hyperthyroidism; Male

In patients taking digoxin, the exercise electrocardiogram has a lower specificity for detecting coronary artery disease. However, the effect of digoxin on adenosine-induced ST-segment depression is unknown. The purpose of this study was to evaluate the specificity of the electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin.. Between May 1991 and September 1997, patients (n = 99) taking digoxin who underwent adenosine stress imaging with thallium-201 or technetium-99m sestamibi and coronary angiography within 3 months were retrospectively identified. Exclusion criteria included prior myocardial infarction, coronary artery angioplasty or bypass surgery, left bundle branch block, paced ventricular rhythm, or significant valvular disease. Twelve-lead electrocardiograms were visually interpreted at baseline, during adenosine infusion, and during the recovery period. The stress electrocardiogram was considered positive if there was > or =1 mm additional horizontal or downsloping ST-segment depression or elevation 0.08 seconds after the J-point compared with the baseline tracing.. ST-segment depression and/or elevation occurred in 24 of 99 patients. There were only 2 false-positive stress electrocardiograms, yielding a specificity of 87% and positive predictive value of 92%. All 8 patients with > or =2 mm ST segment depression had multivessel disease by coronary angiography.. ST-segment depression or elevation during adenosine myocardial perfusion imaging in patients taking digoxin is highly specific for coronary artery disease. Marked (> or =2 mm) ST-segment depression and/or ST-segment elevation is associated with a high likelihood of multivessel disease.

Topics: Adenosine; Aged; Atrial Fibrillation; Cardiotonic Agents; Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Radionuclide Ventriculography; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Vasodilator Agents

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Humans

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Defibrillators, Implantable; Digoxin; Humans

Verapamil and digoxin have been shown to modulate tachycardia-induced atrial electrical remodeling. The goal of the present study was to determine the direct effects of verapamil and digoxin on atrial fibrillation (AF), before and after electrical remodeling.. In six goats we measured the AF cycle length (AFCL) and duration of AF (DurAF) of 50 consecutive induced paroxysms, before (t = 0) and after 24 hours (t = 24) of electrical remodeling. During AF, conduction velocity (CV(AF)), refractory period (RP(AF)), and type of AF (I, II, III) were determined. Verapamil was administered at a loading dose of 0.1 mg/kg, followed by a continuous (2-hour) infusion of 5 microg/kg/min. Digoxin was given intravenously as a single 0.02 mg/kg bolus. At t = 0 and t = 24, digoxin and verapamil caused a significant slowing of the ventricular rate of >40%. Digoxin had no effect on DurAF, AFCL, CV(AF), or RP(AF). Infusion of verapamil had a direct proarrhythmic effect. Both at t = 0 and t = 24, AFCL and RP(AF) were shortened by about 15%. During acute AF, verapamil prolonged the average duration of AF paroxysms from 7 to 16 seconds. After 24 hours of AF, the proarrhythmic effect was much stronger. Shortly after starting infusion (6 +/- 2 min), verapamil converted paroxysmal AF into sustained AF. As long as verapamil infusion was maintained, AF no longer terminated in any of the goats. This effect was associated with an increase in AF fragmentation from type I to type II-III.. Verapamil shortens AFCL and RP(AF) in the presence and absence of electrical remodeling. After 24 hours, it exerted a marked proarrhythmic effect and converted paroxysmal (type I) into sustained (type III) AF. In contrast, digoxin had no effect on the rate or stability of AF.

Topics: Acute Disease; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Chronic Disease; Digoxin; Disease Models, Animal; Electrocardiography; Electrodes, Implanted; Electrophysiologic Techniques, Cardiac; Goats; Heart Atria; Heart Conduction System; Heart Rate; Injections, Intravenous; Verapamil

An analysis of 183 patients in sinus rhythm who underwent coronary artery bypass grafting was conducted to determine the association of multiple preoperative factors, including an elevated left ventricular end-diastolic pressure, with early postoperative atrial fibrillation. An association with advanced age, a history of atrial fibrillation, and preoperative digoxin use was found, but not with an elevated left ventricular end-diastolic pressure, irrespective of left ventricular systolic function.

Topics: Age Factors; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Causality; Coronary Artery Bypass; Digoxin; Female; Humans; Male; Middle Aged; Postoperative Complications; Stroke Volume; Ventricular Function, Left

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Family Practice; Humans; Mass Screening; Warfarin

Atrial fibrillation (AF) is a common comorbid condition in patients admitted to hospital. In managing patients with AF, recent research has highlighted the importance of heart rate control, cardioversion, maintenance of sinus rhythm and anticoagulation for the prevention of thromboembolism.. To determine the prevalence of AF in patients admitted acutely to the general medical service at Auckland Hospital and to assess the adequacy of heart rate control, the number cardioverted and the use of warfarin to prevent thromboembolism.. Prospective review of all acute admissions to the general medical service over a 12 week period. Information was collected from hospital notes on the patients' present and past medical conditions, admission and discharge cardiac medication and the use of investigations, particularly thyroid function tests and echocardiography. The heart rate on discharge, number cardioverted either during the admission or after discharge and the number given warfarin and aspirin were recorded.. One hundred and forty-seven patients (aged 38-96, mean age 76 years and 52% male) were admitted in AF 165 times out of the 1637 admissions over the study period (a prevalence of 10.4%, 95% CI 8.6-11.5%). The main causes of admission were heart failure (23%), pneumonia or sepsis (17%), cerebrovascular accident (CVA) or transient ischaemic attack (TIA) (14%) and ischaemic heart disease (11%). Past medical history included hypertension (46%), ischaemic heart disease (39%), congestive heart failure (58%), valvular heart disease (12%), chronic obstructive airways disease (24%), CVA, TIA or thromboembolic event (24%) and diabetes (17%). Thyroid function tests were performed in 50% of patients and echocardiograms in 38%. Heart rate control at discharge could not be assessed, as this was not recorded prior to any patient's discharge. Seventy-eight per cent of patients were discharged on digoxin but only 29% on drugs that control the heart rate with exercise. Five patients out of 11 considered for cardioversion had a successful cardioversion in hospital and two were later cardioverted as outpatients. Twenty-eight per cent were discharged on warfarin, 33% on aspirin and one patient on both. Fifty-two per cent were considered to have contraindications to warfarin therapy. Prescribing rates for warfarin did not vary according to the patients' clinical risk for thromboembolism.. AF is a common comorbid condition in the acute general medical ward. Standard investigations were under-utilised. Attention needs to be paid to the recording and control of heart rate at rest and on exercise. Cardioversion is considered infrequently. This patient group had a high risk for thromboembolism and after excluding the large group in whom warfarin was contraindicated, warfarin was still under-utilised.

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Humans; Male; Middle Aged; New Zealand; Patient Admission; Platelet Aggregation Inhibitors; Prospective Studies; Thromboembolism; Warfarin

To define the contemporary practice patterns of digoxin utilization for the management of patients with atrial fibrillation (AF).. A retrospective medical records audit of 2490 patients with documented AF, from 12 Canadian hospitals and six outpatient clinics, during fiscal year 1993-1994, was conducted.. There were 1158 women and 1332 men, with a mean age of 72 years; 956 patients were < 70 years of age and 1534 were > or = 70 years old. The majority of patients had nonvalvular AF (75% of those with a documented etiology). Paroxysmal AF (PAF) was documented in 800 patients, 936 had chronic AF, and 754 had new-onset AF. While the prescribing patterns were heterogeneous, the predominant strategy pursued in all subgroups appeared to be that of achieving rate control. Digoxin was the most commonly prescribed medication (79%) and was prescribed for the majority of patients in all subgroups, including patients with PAF (74%) and patients with a history of chronic AF who were currently in sinus rhythm (83%). Only 10% of the patients with PAF who were prescribed digoxin had congestive heart failure. Similarly, less than 25% of the patients with chronic AF who were prescribed digoxin after conversion to sinus rhythm had evidence of heart failure.. In the absence of clinical trial evidence supporting either a strategy of antiarrhythmic therapy or rate control with anticoagulation, the appropriateness of the observed prescribing practices cannot be judged. However, digoxin is not the best rate-controlling agent for all patients and may be overused in certain subgroups of patients, such as those with PAF and those successfully converted to sinus rhythm.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Canada; Digoxin; Drug Utilization; Female; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies

Topics: Acute Disease; Anti-Arrhythmia Agents; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Follow-Up Studies; Heart Rate; Humans; Treatment Outcome

Topics: Acarbose; Aged; Anticoagulants; Antihypertensive Agents; Atrial Fibrillation; Captopril; Diabetes Mellitus, Type 1; Digoxin; Drug Interactions; Female; Furosemide; Glycated Hemoglobin; Heart Failure; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Trisaccharides

An 88-year-old woman was admitted to our hospital because of palpitations, dyspnea, orthopnea and appetite loss. On admission, small crackles were heard on her lower back, and her liver was swollen. Chest rentogenogram showed cardiomegaly (cardio-thoracic ratio 65.5%) and bilateral pleural effusion. Electrocardiograms showed atrial fibrillation with an average heart rate of 95 per minute. Echocardiography revealed mitral stenosis. Because the patient was considered to be suffered from heart failure due to mitral stenosis with atrial fibrillation, furosemide (20 mg per day) and digoxin (0.25 mg per day) was started. After digoxin had been raised to a dose of 0.50 mg per day because of sustained rapid ventricular response on the fourth hospital day, she complained of nausea and vomiting. Serum digoxin concentration was 2.55 ng/ml on the next day, and 1.08 ng/ml 96 hours after discontinuing digoxin. There was no complaint after digoxin was restarted with a dose of 0.05 mg per day. She complained of nausea again on the third day when the digoxin was raised to a dose of 0.083 mg in a blinded study. This observation indicates that digoxin intoxication could occur even in the smaller dose of digoxin than usual in the elderly.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Female; Furosemide; Humans; Mitral Valve Stenosis; Nausea; Vomiting

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Randomized Controlled Trials as Topic; Tachycardia, Paroxysmal; Treatment Outcome

Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium. On the basis of these characteristics, we hypothesized that digoxin would aggravate tachycardia-induced electrical remodeling.. We analyzed the atrial effective refractory period (AERP) at cycle lengths of 430, 300, and 200 ms during 24 hours of rapid atrio/ventricular (300/150 bpm) pacing in 7 chronically instrumented conscious goats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteristics. In addition to a moderate increase in the rate of electrical remodeling during rapid pacing, digoxin significantly delayed the recovery from electrical remodeling after cessation of pacing (at 430, 300, and 200 ms: P=0. 001, P=0.0015, and P=0.007, respectively). This was paralleled by an increased inducibility and duration of AF during digoxin. Multivariate analysis revealed that both a short AERP and treatment with digoxin were independent predictors of inducibility (P=0.001 and P=0.03, respectively) and duration (P=0.001 for both) of AF.. Dioxin aggravates tachycardia-induced atrial electrical remodeling and delays recovery from electrical remodeling in the goat, which increases the inducibility and duration of AF.

Topics: Animals; Anti-Arrhythmia Agents; Aortic Bodies; Atrial Fibrillation; Atrial Function; Digoxin; Electrophysiology; Goats; Heart Rate; Refractory Period, Electrophysiological; Tachycardia, Ectopic Atrial

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Data Collection; Digoxin; Heart Failure; Humans; Spain; Time Factors

It is conventionally thought that electrical cardioversion in patients with atrial fibrillation (AF) of longstanding duration or with a large left atrial diameter, only seldom results in long term success. Recurrence is common, although antiarrhythmic drugs often effectively decrease the number and duration of recurrent AF episodes. We analysed clinical, functional and pharmacological variables which could possibly influence the long term outcome after a first electrical cardioversion for AF in a retrospective study on 85 patients. Univariate and multivariate analysis was used to identify factors predicting maintenance of sinus rhythm at 100 days, and absence of recurrence during the entire follow-up. In univariate analysis, the only significant predictor for maintenance of sinus rhythm at 100 days was the duration of the preceding AF episode. Multivariate analysis with persistence of sinus rhythm at 100 days as endpoint confirmed this as a prognostic factor (p < 0.03), but sotalol treatment also contributed to maintenance of sinus rhythm (p < 0.05). When considering the entire observation period, class III antiarrhythmic drugs, i.e. sotalol and amiodarone, were useful in preventing recurrence (p < 0.01 and < 0.02). High age (above 75 years) was a predictor of recurrence. In conclusion, class III antiarrhythmic drugs, the duration of atrial fibrillation and high age were the most important determinants of long term outcome, while echocardiographic parameters and the presence of heart disease played no role.

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Prognosis; Recurrence; Retrospective Studies; Risk Factors; Sotalol; Time Factors

A woman presented during two pregnancies (at 25 and 23 weeks' gestation, respectively) because the fetuses had rapid, irregular tachycardia and hydrops. After maternal drug treatment and achievement of slower fetal heart rates, the hydrops gradually resolved. Both babies were born full term with continuing atrial fibrillation. In the first, an ectopic atrial rhythm was temporarily achieved during high dose flecainide treatment but, in the younger sibling, all medications and repeated cardioversions failed even temporarily to convert the atrial fibrillation with an almost isoelectric baseline in ECG to sinus rhythm. Good rate control has been achieved with digoxin in both patients. No infective, immunological, or structural cause was found in either case, and thus an inherited aetiology is probable.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Child, Preschool; Digoxin; Echocardiography, Doppler; Electrocardiography; Female; Fetal Diseases; Humans; Infant, Newborn; Pregnancy; Prenatal Diagnosis

Although there is renewed enthusiasm for the use of digoxin in patients with heart failure, current dosing guidelines are based on a nomogram published in 1974. We studied the incidence of and risk factors for elevated digoxin levels in patients admitted to a community hospital, and compared their dosage regimens to published guidelines.. We reviewed the charts of all patients who had serum digoxin levels greater than 2.4 ng/mL during a 6-month period. We collected demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, and clinical and electrocardiographic features of digoxin toxicity.. Of the 1,433 patients with digoxin assays, 115 (8%) patients had elevated levels. Of the 82 patients with complete records and correctly timed digoxin levels, 59 (72%) had electrocardiographic or clinical features of digoxin toxicity. Patients with serum digoxin levels >2.4 ng/mL were slightly older (78 +/- 8 versus 73 +/- 9 years of age; P = 0.12) and had greater serum creatinine levels (3.1 +/- 7.3 versus 1.4 +/- 0.3 mg/dL; P = 0.01) than those with levels < or =2.4 ng/mL. Forty-seven patients had elevated digoxin levels on admission, including 21 patients admitted for digoxin toxicity. Impaired or worsening renal function contributed to high levels in 37 patients, and a drug interaction was a contributory factor in 10 cases. Twenty (43%) of these patients were taking the recommended maintenance dose based on the scheme employed in the Digitalis Investigation Group study. Thirty-five patients developed high digoxin levels while in hospital. In 26 patients, this followed a loading dose of digoxin for the control of rapid atrial fibrillation. Impaired renal function was implicated in all of these patients. Despite the elevated digoxin level, rate control was achieved in only 11 patients of these patients.. Elevated digoxin levels and clinical toxicity remains a common adverse drug reaction. Elderly patients, particularly those with impaired renal function and low body weights, are at the greatest risk. As published digoxin nomograms often result in toxicity, clinical variables need to be monitored. In patients with congestive heart failure and normal sinus rhythm the potential benefit of digoxin is small; thus, patients should receive a dose that minimizes the risk of toxicity. For patients with new onset atrial fibrillation, other agents may be preferable for rate control.

Topics: Age Factors; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Chi-Square Distribution; Creatinine; Digoxin; Drug Interactions; Drug Monitoring; Electrocardiography; Female; Heart Failure; Hospitalization; Humans; Kidney Diseases; Male; Risk Factors

Cerebrovascular disease is increasingly recognized as a cause of dementia and cognitive decline. We have previously reported an association between hypertension and diabetes and low cognitive function in the elderly. Atrial fibrillation is another main risk factor for cerebrovascular disease. The aim of this study was to investigate whether atrial fibrillation is associated with low cognitive function in elderly men with and without previous manifest stroke.. This was a cross-sectional study based on a cohort of 952 community-living men, aged 69 to 75 years, in Uppsala, Sweden. Cognitive functions were assessed by the Mini-Mental State Examination and the Trail Making Tests, and a composite z score was calculated. The relation between atrial fibrillation and cognitive z score was analyzed, with stroke and other vascular risk factors taken into account.. All analyses were adjusted for age, education, and occupational level. Men with atrial fibrillation (n=44) had lower mean adjusted cognitive z scores (-0.26+/-0.11) than men without atrial fibrillation (+0.14+/-0.03; P=0.0003). The exclusion of stroke patients did not alter this relationship; the mean cognitive z score was -0.24+/-0.12 in the 36 men with atrial fibrillation and +0.17+/-0.03 in those without atrial fibrillation (P=0.0004), corresponding to a difference of 0.4 SDs between groups. Adjustments for 24-hour diastolic blood pressure and heart rate, diabetes, and ejection fraction did not change this relationship. Men with atrial fibrillation who were treated with digoxin (n=27) performed markedly better (-0.05+/-0.21) than those without treatment (n=9; -1.14+/-0.34; adjusted P=0.0005). Previous myocardial infarction was not associated with impaired cognitive results.. In these community-living elderly men, we found an association between atrial fibrillation and low cognitive function independent of stroke, high blood pressure, and diabetes. Interventional studies are needed to answer the question of whether optimal treatment of atrial fibrillation may prevent or postpone cognitive decline and dementia.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cerebrovascular Disorders; Cognition; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Digoxin; Female; Humans; Male; Neuropsychological Tests; Risk Factors

Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Drug Administration Schedule; Drug Overdose; Humans

Little is known about national patterns of pharmacological treatment of atrial fibrillation, in particular, use of medications for ventricular rate control and for restoration and maintenance of sinus rhythm.. We analyzed 1555 visits by patients with atrial fibrillation to randomly selected office-based US physicians included in National Ambulatory Medical Care surveys conducted in 1980, 1981, 1985, and 1989 through 1996. To determine national trends, we evaluated the proportion of atrial fibrillation visits with reported use of rate control medications (digoxin and antiarrhythmics in classes II and IV) and sinus rhythm medications (classes IA, IC, and III).. The use of rate control agents decreased from 79% of atrial fibrillation visits in 1980-1981 to 62% in 1994-1996. Declining use was noted for both digoxin (76% in 1980-1981 to 53% in 1994-1996) and beta-blockers (19%-13%). After their introduction, the use of verapamil hydrochloride and diltiazem hydrochloride increased to 15% of atrial fibrillation visits in 1994-1996. Sinus rhythm agent use decreased from 18% of visits in 1980-1981 to 4% in 1992-1993 and then rose to 13% in 1994-1996. The use of class IA agents declined from 18% in 1980-1981 to 3.5% in 1992-1993 and then increased to 8% in 1994-1996. Quinidine remained the most widely used sinus rhythm medication, despite its declining share of this category. Newly available sotalol hydrochloride and amiodarone hydrochloride were used in 3.6% of visits in 1994-1996.. Despite changes in the treatment of atrial fibrillation, digoxin remains the dominant rate control medication. Medications for sinus rhythm maintenance are not widely used. Quinidine use declined prominently in the 1980s, possibly because of concerns about proarrhythmic effects. The use of sinus rhythm agents, however, is now rising.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Drug Therapy, Combination; Drug Utilization; Heart Rate; Humans; Linear Models; Office Visits; Retrospective Studies; United States

Atrial fibrillation (AF) is a common complication of coronary artery bypass surgery (CABS). Because conventional antiarrhythmic therapy may cause proarrhythmia, a rate control approach to AF was evaluated in 59 patients post-CABS. The use of digoxin with or without verapamil for AF was associated with spontaneous conversion to normal sinus rhythm in 55 of 59 patients. Two to four weeks later, all patients were on digoxin and 12% were on verapamil, with two of four AF patients having converted to normal sinus rhythm and two others previously in normal sinus rhythm now in AF. A rate control approach to treating AF post-CABS resulted in over 90% of patients being in normal sinus rhythm for two to four weeks after the onset of the arrhythmia.

Topics: Administration, Oral; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Bypass; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Patient Selection; Postoperative Complications; Time Factors; Verapamil

Topics: Age Factors; Aged; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Atrial Fibrillation; Clarithromycin; Digoxin; Drug Interactions; Drug Therapy, Combination; Echocardiography; Ethambutol; Humans; Male; Mycobacterium avium-intracellulare Infection; Rifabutin

Topics: Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Humans; Tachycardia, Ventricular

To document a case in which the administration of itraconazole was associated with an apparent decrease in digoxin clearance, resulting in an increase in the serum digoxin concentration.. A man receiving digoxin for atrial fibrillation was concurrently treated with itraconazole 200 mg/d for esophageal candidiasis. The estimated urinary digoxin clearance was decreased during this combination therapy.. Digoxin is primarily cleared by the kidneys, and the mechanism of renal clearance involves both glomerular filtration and tubular secretion. We postulate that itraconazole or a metabolite of this compound may have resulted in decreased tubular secretion of digoxin, accounting for decreased urinary digoxin clearance.. Monitoring of serum digoxin concentrations should be performed if patients taking digoxin are treated with itraconazole. Further investigation is necessary to elucidate the nature of the interaction between digoxin and itraconazole.

Topics: Aged; Anti-Arrhythmia Agents; Antifungal Agents; Atrial Fibrillation; Candidiasis; Digoxin; Drug Interactions; Esophageal Diseases; Humans; Itraconazole; Male

Topics: Acute Disease; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Humans; Infusions, Intravenous

To assess the clinical characteristics and management of patients with atrial fibrillation (AF), we performed a prospective survey of all acute medical admissions over six months to our hospital. Of 7,451 such admissions, 245 had AF (110 male, 135 female; mean age 74.4 years). Of these, 213 were Caucasian, 10 black/Afro-Caribbean and 22 Asian. Complete data were available for 185 patients. Of these, 82 had newly diagnosed AF, 83 had previous chronic AF and 20 had paroxysmal AF. The main presenting features was dyspnoea, stroke and syncope. A history of ischaemic heart disease was present in 64, heart failure in 46, hypertension in 51 and rheumatic heart disease in 13, while 31 had a previous stroke. Chest X-ray showed cardiomegaly and pulmonary oedema in 121 patients, but was normal in 28. Echocardiography showed poor cardiac function in eight patients and enlarged left atria in five. Only 28% of those with previously diagnosed AF were on anticoagulation. Of the newly diagnosed patients, only 18% were started on anticoagulants. Cardioversion was attempted or planned in only 6%. The primary diagnosis on discharge was heart failure in 45, stroke in 24 and myocardial infarction in 12. AF remains a common arrhythmia among acute medical admissions and is commonly associated with heart failure and a high mortality. There is still a reluctance to start anticoagulant therapy or to perform cardioversion in such patients.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Prospective Studies

We present two families with atrial fibrillation in 20 of 50 members, during three generations, with known cardiac rhythms, in order to communicate their infrequent existence and the most relevant clinical facts.. Clinical situation, evolution, ECG and ECHO findings, treatments and complications related with the disease are investigated.. The presence of atrial fibrillation in 20 members is demonstrated, although one of them was on sinus rhythm at the time of the study; 3 patients had left ventricular enlargement on the ECHO study; the clinical situation was good in all patients except two who died because of complications related to the arrythmia and a third patient that had a brain stroke. The patients received different treatments because they where controlled by different physicians; the possible lethal proarrythmic effect in such cases must be taken into account.. Familiar atrial fibrillation is a very infrequent arrythmia, usually well tolerated, that follows a dominant autosomic hereditary pattern. The use of antiagregants is advised because of the risk of embolism, or the use of anticoagulants in the presence of associated risk factors. Electric cardioversion has been show not be useful. The possible proarrythmic effect of some antiarrythmic agents, used in the control of cardiac frequency, must be taken into account.

Topics: Adolescent; Adult; Aged; Anti-Arrhythmia Agents; Anticoagulants; Atenolol; Atrial Fibrillation; Digoxin; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Pedigree; Propafenone

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Pulse

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Plants, Medicinal

To investigate variations in the management of patients with atrial fibrillation among consultant physicians.. Questionnaire survey.. Consultant physicians in England, Wales, and Scotland.. 214 consultant physicians (88 cardiologists and 126 non-cardiologists) were surveyed between May and July 1994. Most physicians (47.7%) reported that they saw one to five patients with atrial fibrillation weekly. Some 52% of cardiologists and 40% of non-cardiologists considered that the main factor influencing their decision of whether or not to anticoagulate was the clinical history--that is, heart failure, valve disease, or stroke. When encountering a patient admitted acutely with new onset atrial fibrillation, significantly more cardiologists (66% v 52%, chi 2 = 6.89, P = 0.03) would immediately start anticoagulant treatment, most favouring intravenous heparin. Most physicians would also introduce antiarrhythmic treatment or digoxin, but more cardiologists would attempt immediate pharmacological (39% v 18% of non-cardiologists, P < 0.001) or later electrical (86% v 69%, chi 2 = 11.7, P = 0.003) cardioversion to sinus rhythm, while non-cardiologists tended to prefer "rate control" with digoxin. Although many physicians would not continue antiarrhythmic treatment post-cardioversion, more cardiologists than non-cardiologists would do so (the commonest choice being class III agents) (31% v 17%, P = 0.04). Fewer non-cardiologists would continue anticoagulant treatment post-cardioversion (27% v 69% of cardiologists, chi 2 = 39.8, P < 0.0001). When treating patients with atrial fibrillation, decisions about anticoagulation were usually related to the perceived relative risk of thromboembolism versus haemorrhage derived for each of six case management scenarios in the questionnaire. There was, however, general agreement between cardiologists and non-cardiologists in the use of antithrombotic treatment in the management of lone atrial fibrillation, paroxysmal atrial fibrillation, and patients with atrial fibrillation and mitral valve disease or thyrotoxicosis.. There is considerable variation in the management of atrial fibrillation, with more cardiologists than non-cardiologists considering cardioversion to sinus rhythm (and the use of antiarrhythmic and anticoagulant treatment post-cardioversion) and thrombo-prophylaxis with anticoagulation. Guidelines on the management of this common arrhythmia are clearly required.

Topics: Acute Disease; Adult; Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiology; Digoxin; Electric Countershock; Female; Heparin; Humans; Male; Medical Audit; Middle Aged; Practice Patterns, Physicians'

Changes in left atrial (LA) appendage pulsed-wave Doppler velocities and changes in grades of spontaneous contrast occur immediately after electrical cardioversion of atrial fibrillation (AF) using transesophageal echocardiography (TEE). The effect of sequential ineffective electrical cardioversion attempts or chemical cardioversion on these parameters is unknown. TEE was performed in 23 patients with chronic AF. Doppler velocities and grades of spontaneous contrast were assessed before and after each cardioversion attempt until sinus rhythm was achieved. Doppler emptying and filling velocities were significantly decreased after electrical (0.39 +/- 0.14 vs 0.27 +/- 0.16 [p = 0.01] and 0.43 +/- 0. 18 vs 0.30 +/- 0.14 m/s [p = 0.01]) or chemical cardioversion to sinus rhythm (0.65 +/- 0.18 vs 0.31 +/- 0.06 [p = 0.03] and 0.64 +/- 0.22 vs 0.44 +/- 0.17 m/s [p = 0.04]). Spontaneous contrast developed in 1 of 3 patients after chemical conversion to sinus rhythm and was present in 11 of 20 patients before electrical cardioversion, developing in 4 patients and intensifying in 2 patients immediately after successful cardioversion. These phenomena were not seen after ineffective electrical or chemical cardioversion attempts. This suggests that restoration of sinus rhythm is in itself responsible for these phenomena, not the method by which sinus rhythm is achieved.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Function, Left; Blood Flow Velocity; Cardiac Output; Chronic Disease; Contrast Media; Digoxin; Echocardiography, Doppler, Pulsed; Echocardiography, Transesophageal; Electric Countershock; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Diltiazem; Drug Therapy, Combination; Emergency Medicine; Heart Failure; Humans; Propanolamines; Verapamil

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Research Design; Time Factors

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electric Countershock; Humans; Warfarin

We describe a patient with cirrhotic liver disease and atrial fibrillation who was treated with spironolactone and digoxin. He was hospitalized because of an incidental finding of a high serum digoxin level (4.2 micrograms/L), but he remained asymptomatic without emerging arrhythmias. Despite discontinuation of both drugs, his serum digoxin level persisted at or above 3.0 micrograms/L for approximately 5 weeks, drawing into question the accuracy of the digoxin assay.. Additional digoxin methods gave lower, discrepant results, providing evidence of an assay interference, and several possible sources of digoxin false positivity were evaluated. This included assessment of the contribution of digoxin-like immunoreactive factor (DLIF), digoxin metabolites, and spironolactone. Because the routine digoxin assay used a monoclonal antibody, we also tested for another hypothetical interference: human heterophilic ("anti-mouse") antibodies.. We found no contribution from DLIF, digoxin antibodies, or spironolactone to the apparent digoxin results. However, the use of protein A to complex and selectively remove immunoglobulin G molecules markedly lowered the apparent digoxin value, as did the less specific process of ultrafiltration.. These results suggest a previously unreported cause of digoxin false positivity: heterophilic antibodies, which have been reported to bind murine monoclonal antibodies in other assays. Because newer digoxin assays now use murine monoclonal antibodies, the possible presence of heterophilic, anti-mouse antibodies should now be considered in the interpretation of a high digoxin level.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Cardenolides; Digoxin; Diuretics; Drug Interactions; Drug Therapy, Combination; False Positive Reactions; Humans; Immunoenzyme Techniques; Male; Middle Aged; Saponins; Spironolactone

Topics: Atrial Fibrillation; Cardiac Complexes, Premature; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Middle Aged; Poisoning; Rheumatic Heart Disease

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Digoxin; Diuretics; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Humans; Male

Topics: Atrial Fibrillation; Atrial Flutter; Diagnosis, Differential; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Humans; Middle Aged; Quinidine

Topics: Atrial Fibrillation; Digoxin; Heart Rate; Humans

Two hundred and ninety one patients admitted with atrial fibrillation through the emergency room of a regional hospital in the year 1993 were reviewed to evaluate the presenting features and in-hospital treatment of patients with symptomatic atrial fibrillation. The incidence of atrial fibrillation increased with age (mean age was 73 +/- 12 years) and the ratio of female to male was 1.8:1. The commonest presenting features were palpitation (42.3%), dyspnoea (38.1%) and heart failure (16.4%). The most frequently associated cardiac conditions were hypertension (28.9%), atherosclerotic cardiovascular disease (24.7%) and rheumatic heart disease (17.5%). Pulmonary diseases (18.6%), diabetes mellitus (12.7%) and thyrotoxicosis (6.2%) were the principal associated non-cardiac conditions. Thromboembolic complications were found in 15 patients at presentation (5.2%). Cardiac enzyme assessment was investigated in two thirds of the patients (68.1%), while thyroid function test (59.5%) and echocardiography (29.6%) were less commonly investigated. Digoxin was still the most popular drug used for ventricular rate control, and cardioversion was performed in only 6.9% of patients. Antithrombotic therapy was used in 5.8% of patients only although it was clinically indicated in more than half of the patients (52%). Contraindications of anticoagulation were found in 23 patients (7.9%), including a history of gastrointestinal or cerebrovascular bleeding, active bleeding, chronic renal failure and poor drug compliance. The mean hospital stay was 5 +/- 4 days, compared to a mean stay of 2.7 days for other medical patients. Fourteen patients (4.8%) died during hospitalisation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Amiodarone; Atrial Fibrillation; Comorbidity; Digoxin; Electric Countershock; Emergencies; Female; Hong Kong; Hospitalization; Humans; Incidence; Length of Stay; Male; Thrombolytic Therapy; Treatment Outcome

The benefits of digoxin in patients with atrial fibrillation may be reduced due to its limited effect on atrioventricular conduction. The aim of this work was to compare digoxin and atenolol on functional class, resting and exercise heart rate and exercise capacity in patients with atrial fibrillation. Thirteen subjects with this condition, normal echocardiographic left ventricular function and size, a resting heart rate less than 80 beats/min and with no contraindication for beta blocker or digoxin use were studied. Patients were randomly assigned to receive initially digoxin 0.25 mg o.d. or atenolol 100 mg o.d. in a double blind fashion. The doses were adjusted to obtain a heart rate between 60 and 80 beats/min at the end of the first week of treatment. After two weeks of treatment, outcomes were assessed, patients were left without treatment for one week and crossed over to the other drug after that. Resting heart rates achieved with digoxin and atenolol were similar (67 +/- 11 and 65 +/- 23 beats/min respectively). However, maximal exercise heart rates and maximal exercise time were higher during digoxin treatment (166 +/- 23 vs 135 +/- 27 beats/min and 9.95 +/- 1.68 vs 8.5 +/- 2 min respectively). NYHA functional class deteriorated in three patients receiving atenolol. We conclude that atenolol achieves a better control of heart rate during exercise but also reduces maximal exercise capacity.

Topics: Adult; Aged; Analysis of Variance; Atenolol; Atrial Fibrillation; Blood Pressure; Chronic Disease; Cross-Over Studies; Digoxin; Ergometry; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Random Allocation; Rest; Ventricular Function, Right

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Diltiazem; Drug Therapy, Combination; Humans; Prospective Studies

In patients with Wolff-Parkinson-White syndrome and atrial fibrillation, digoxin may increase the ventricular rate by facilitating conduction over the accessory pathway either directly by enhancing accessory pathway conduction and/or indirectly as a consequence of its effect on atrioventricular nodal conduction. Two cases are presented in which the intravenous administration of magnesium sulfate reversed digoxin facilitation of the ventricular rate to atrial fibrillation in the Wolff-Parkinson-White syndrome.

Topics: Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Rate; Heart Ventricles; Humans; Magnesium Sulfate; Male; Middle Aged; Wolff-Parkinson-White Syndrome

Atrial fibrillation is a very common arrhythmia and frequently seen by general practitioners. Its rational management entails careful consideration of the goals of therapy. These differ from patient to patient and may include control of ventricular rate, conversion to and maintenance of sinus rhythm and prophylaxis against thromboembolism. This article will focus on the various therapeutic agents available for achieving these aims and will attempt to provide some guidance through what has become a confusing maze of potential therapeutic strategies.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Conduction System; Humans; Thromboembolism

To assess current strategies used to investigate and manage acute atrial fibrillation in hospital.. Prospective survey of all acute admissions over 6 months.. District general hospital serving a population of 230,000 in north east Glasgow.. 2686 patients admitted as emergency cases over 6 months.. Of the 2686 patients, 170 (age range 38-95, mean (SD) 73.5 (10.6) years; 70 men (41%) and 100 women (59%)) were admitted with atrial fibrillation. The principal underlying medical conditions were ischaemic heart disease in 79 (46.5%), rheumatic heart disease in 26 (15.3%), and thyroid disease in six (3.5%). Cardiac failure was present on admission in 61 (36%), cerebrovascular events in 23 (14%), and myocardial infarction in 17 (10%). Of those with a history of atrial fibrillation (102 (60%) including 10 with paroxysmal atrial fibrillation) treatment on admission included digoxin in 71 (70%), warfarin in 20 (20%), and aspirin in 17 (17%); the aspirin was predominantly given for concomitant vascular disease. The mean (SD) inpatient stay was 16 days (19.7) (range 1-154) largely due to the patients with stroke. Thyroid function tests were performed in only 63% and echocardiography in 33%. Overall, the rate of introduction of anticoagulation (seven patients) and attempted cardioversion (21 patient: 19 pharmacological and two electrical) was surprisingly low. Only 49 patients (34% of those not on warfarin) had contraindications to anticoagulation: these included peptic ulcer or gastrointestinal bleeding in 18 (12%), dementia in eight (6%), chronic renal failure or dialysis in eight (6%), and alcohol excess in four (3%).. Standard investigations were inadequately used in patients with atrial fibrillation and there was a reluctance to perform cardioversion or to start anticoagulant treatment.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Digoxin; Echocardiography; Electric Countershock; Emergencies; Female; Hospitalization; Humans; Length of Stay; Male; Medical Audit; Middle Aged; Scotland; Thyroid Function Tests; Warfarin

Topics: Adenosine; Aged; Atrial Fibrillation; Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography; Humans; Male; Postoperative Complications; Tachycardia; Verapamil

Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Flecainide; Heart; Humans; Propafenone; Quinidine

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Block; Humans; Ventricular Function

With the aim of studying the characteristics of the use of digoxin in a population which attended a hospital emergency department for heart failure or auricular fibrillation a 3 month observational study was carried out in the emergency department of the Ciudad Sanitaria de la Vall d'Hebron.. One hundred twelve patients treated with digoxin who went to the emergency department for heart failure and/or decompensated auricular fibrillation were studied. Clinical and pharmacological histories, determination of digoxinemia and the usual complementary explorations were performed.. It was found that 50% of the patients were not adequately controlled and treatment was not followed in 21% of the patients. No significant relation was found between the doses of digoxin and the age of the patients. In multivariant analysis (multiple lineal regression) digoxinemia was related with the doses (beta = 0.22, p = 0.01), cardiac frequency (beta = 0.19, p < 0.05), and compliance (beta = 0.18, p = 0.05). Among the patients in whom the cause of decompensation of cardiac failure could not be identified, one third (31%) were found to have infratherapeutic digoxinemia.. Most patients with cardiac decompensation attending an emergency department are those who are not adequately controlled in primary health care and the rate of incomplete following of the prescription is high. Furthermore, one third of the patients who decompensate with no clinically apparent reason has an infratherapeutic plasma concentration of digoxin.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Atrial Fibrillation; Chi-Square Distribution; Digoxin; Drug Utilization; Emergencies; Female; Heart Failure; Humans; Male; Middle Aged; Regression Analysis; Spain

Atrial fibrillation is the commonest arrhythmia observed in hypertrophic cardiomyopathy, and is associated with an acute deterioration in symptoms. Digoxin is the drug of choice in established atrial fibrillation and amiodarone the drug of choice in paroxysmal atrial fibrillation and ventricular arrhythmia. Non-sustained ventricular tachycardia occurs in 20% of patients and is the single best predictor of sudden death in adults. Sustained monomorphic ventricular tachycardia occurs only rarely. The mechanism of sudden death is likely to involve initiating factors such as arrhythmia and peripheral autonomic dysfunction causing haemodynamic instability and myocardial ischaemia. Myocardial disarray may provide the arrhythmogenic substrate such that haemodynamic instability and ischaemia results in ventricular fibrillation and sudden death.

Topics: Amiodarone; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Digoxin; Electrocardiography; Humans; Tachycardia, Ventricular

Digoxin frequently fails to control the heart rate in patients of chronic atrial fibrillation particularly during exertion. We have studied in 20 such patients the effect of adding diltiazem (180 mg/day) on resting and peak exercise heart rates. An attempt was also made to determine its effects on exercise tolerance by using treadmill and 6 minute walk test. Addition of diltiazem resulted in significant attenuation of heart rate both at rest and at peak exercise. The resting and exercise mean heart rates on digoxin alone were 98.9 +/- 21.5 b.p.m. and 160.2 +/- 35.68 b.p.m. respectively. After diltiazem this reduced to 78.7 +/- 12.30 b.p.m. at rest and 132.4 +/- 40.4 b.p.m. at peak exercise (p < 0.01). There was no significant effect on exercise tolerance. In conclusion, the addition of diltiazem substantially reduced the excessive heart rate response to exercise in digitalised patients of chronic atrial fibrillation.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Exercise; Female; Heart Rate; Humans; Male; Middle Aged

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Heart Rate; Humans

We describe, to the best of our knowledge for the first time, the occurrence of idiopathic atrial flutter (AF) in two male children of a family. The two brothers are the third and sixth of seven children, and the only males. The parents do not suffer from any heart disease. The first sister died in Turkey at the age of twenty days. The parents do not know the cause of death. The fourth sister died at de age of five years, also in Turkey, probably because of meningitis. Electrocardiograms of the parents and the other three sisters are normal. Besides the unique familial occurrence, the AF themselves offer some unusual features. In the first patient, the AF could not be converted to sinus rhythm. In the second patient, the AF occurred paroxysmally, and in addition to the AF, the electrocardiogram tracings revealed paroxysmal atrial tachycardia.

Topics: Adolescent; Atrial Fibrillation; Atrial Flutter; Cardiac Complexes, Premature; Child; Digoxin; Drug Therapy, Combination; Electrocardiography; Humans; Male; Pedigree; Propafenone

The study was undertaken to examine 105 patients with various circulatory diseases complicated by atrial fibrillation. Patients with refractory atrial fibrillation who had taken combined antiarrhythmic therapy were found to be more responsive to the combinations of cordarone + kinilentin (quinidine disulphate) and cordarone + ethacizin. The combinations of cordarone+digoxin and cordarone + finoptin were demonstrated to be less beneficial.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Humans; Middle Aged; Moricizine; Quinidine; Verapamil

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Verapamil

Topics: Adult; Atrial Fibrillation; Atrial Flutter; Digoxin; Echocardiography; Female; Fetal Diseases; Fetal Heart; Humans; Pregnancy; Ultrasonography, Prenatal

Topics: Atrial Fibrillation; Digoxin; Drug Evaluation; Drug Therapy, Combination; Electrocardiography, Ambulatory; Heart Rate; Humans; Pindolol

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Digitalis Glycosides; Digoxin; Humans; Platelet Aggregation Inhibitors; Procainamide; Randomized Controlled Trials as Topic; Sotalol

Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.

Topics: Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Chronic Disease; Digoxin; Electrocardiography; Female; Humans; Magnesium Deficiency; Male; Middle Aged

In 9 patients with atrial fibrillation the effect of zero, low and high levels of serum digoxin on exercise-induced hyperkalemia was assessed by bicycle exercise tests. Exercise at each level of serum digoxin was associated with a significant (up to 20%) rise in plasma potassium. At a work load of 75 W the highest level of serum digoxin was associated with a significantly higher maximum plasma potassium concentration as compared to the maximum valueatazero serum digoxin. The enhancement of exercise-induced hyperkalemia may add to the arrhythmogenic effect of digitalis.

Topics: Adult; Aged; Atrial Fibrillation; Coronary Disease; Digoxin; Exercise Test; Humans; Hyperkalemia; Male; Middle Aged; Potassium

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Drug Incompatibility; Drug Monitoring; Female; Humans; Male; Middle Aged; Quinidine; Rheumatic Heart Disease

Topics: Atrial Fibrillation; Digoxin; Humans

The accuracy of population-based methods and of Bayesian analysis to predict individual digoxin pharmacokinetic variables have been evaluated by their ability to predict a measured peak and trough serum digoxin concentration. We studied 13 digitalized patients (three women) whose mean (range) age and weight was 65.8 (60-78) years and 76.6 (68-101.6) kg and who had stable renal function. The population-based methods (using a clearance of 48.87 + 0.87 x creatinine clearance in ml/h/kg and volume of distribution, in litres, of either 7.3 x weight (kg) or 269 + 3.12 x creatinine clearance) were more than adequate for clinical purposes. The mean prediction errors of a measured steady-state peak concentration from these two population methods were -0.074 and 0.013 microgram/l respectively, whilst those of a measured trough concentration were -0.058 and 0.005 microgram/l. Bayesian analysis, using a sample drawn 11 h after the dose on day five of therapy, gave overall the least biased and most precise of the revised estimates. The mean prediction errors of peak and trough values using this sample were 0.069 and -0.005 microgram/l respectively. As expected, the closer the sample was drawn to the time of the trough concentration the more precise were the Bayesian-derived predictions. The value of the Bayesian technique to individualize digoxin doses could not be validated because it was not possible to distinguish between this and the population methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Atrial Fibrillation; Bayes Theorem; Creatinine; Digoxin; Drug Administration Schedule; Female; Humans; Metabolic Clearance Rate; Middle Aged

Topics: Atrial Fibrillation; Chromatography, High Pressure Liquid; Digoxin; Female; Fluorescein; Fluoresceins; Fluorescence Polarization Immunoassay; Humans; Middle Aged; Reproducibility of Results

The aim was to evaluate the effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation.. Patients with chronic isolated atrial fibrillation underwent maximal exercise testing before and after the administration of digoxin, propranolol, or verapamil. Heart rate, oxygen uptake and oxygen pulse were observed at rest, at gas exchange anaerobic threshold, and at peak exercise.. The subjects were 10 patients (aged 48-78 years, mean age 60, SD 9, years) with chronic isolated atrial fibrillation.. During exercise without medication, the heart rate was 85 (SD 8) beats.min-1 at rest, 127(19) at the level of anaerobic threshold, and 175(17) at peak exercise. With digoxin, heart rate was reduced to 75(9) beats.min-1 at rest (control v digoxin, p less than 0.01). However, reduction of heart rate was not seen at anaerobic threshold or at peak exercise. With propranolol, heart rate was 63(7) beats.min-1 at rest, 99(16) at anaerobic threshold, and 138(28) at peak exercise (control v propranolol, all p less than 0.01). Heart rate with verapamil was 70(13) beats.min-1 at rest, 107(30) at anaerobic threshold, and 138(28) at peak exercise (control v verapamil, p less than 0.05 at rest and at anaerobic threshold, p less than 0.01 at peak exercise. Neither digoxin, nor propranolol, nor verapamil changed the oxygen uptake during exercise. Without medication, oxygen pulse was 6.5(2.0) ml.beat-1 at anaerobic threshold and 7.7(2.1) ml.beat-1 at peak exercise. With digoxin, the change of oxygen pulse, versus without medication, was not significant at rest or at anaerobic threshold but was increased at peak exercise, at 8.3(2.1) v 7.7(2.1) ml.beat-1, p less than 0.05. With propranolol, oxygen pulse was increased to 8.2(1.9) ml.beat-1 at anaerobic threshold and 9.2(2.3) ml.beat-1 at peak exercise (control v propranolol, both p less than 0.01). With verapamil, oxygen pulse was increased to 8.7(1.8) ml.beat-1 at anaerobic threshold and 10.0(2.1) ml.beat-1 at peak exercise (control v verapamil, both p less than 0.01).. Digoxin was effective in reducing heart rate at rest, but failed to reduce it during exercise. Propranolol and verapamil reduced heart rate at all levels of exercise as well as at rest. Oxygen uptake during exercise (total exercise capacity) was not reduced with propranolol or verapamil; this was thought to have been accomplished by an increased oxygen pulse.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Exercise; Heart Rate; Humans; Male; Middle Aged; Oxygen Consumption; Propranolol; Verapamil

Topics: Aged; Atrial Fibrillation; Digoxin; Humans

Digitalis is frequently prescribed to patients with paroxysmal atrial fibrillation to reduce the ventricular rate during subsequent paroxysms. To verify the validity of this assumption, we determined the ventricular rate during paroxysmal atrial fibrillation in 13 patients receiving long-term digoxin therapy (mean plasma digoxin level + 1.28 +/- 0.4 ng/ml) and compared it with that of a group of 14 patients who had not taken digoxin or beta-adrenergic and calcium-blocking agents before the attack. The treated and the untreated groups were similar statistically. The mean ventricular rate of the digitalized patients was 121 +/- 15 beats per minute, while that of the patients in the control group was 118 +/- 16 beats per minute. It is concluded that long-term digoxin therapy is not effective in reducing the ventricular response in patients with paroxysmal atrial fibrillation despite adequate therapeutic levels.

Topics: Aged; Atrial Fibrillation; Digoxin; Female; Heart Rate; Humans; Male; Time Factors

Topics: Atrial Fibrillation; Digoxin; Humans

Heart rate and serum digoxin concentration in eight patients with atrial fibrillation were studied at rest and during exercise when initial serum digoxin concentrations were zero and at low and high therapeutic values. Eight patients with ischemic heart disease and in sinus rhythm were studied for comparison. Though the serum digoxin concentration decreased significantly during exercise, the absolute reduction in heart rate was the same at rest and during exercise in patients with atrial fibrillation. Compared with the control patients in sinus rhythm, the heart rate in patients with atrial fibrillation was not adequately controlled during exercise by any serum digoxin concentration tested despite a reduction in heart rate with increasing digoxin concentration. The effects of digoxin on heart rate regulation in atrial fibrillation are complex and include direct effects on the myocardium as well as indirect effects mediated by modulation of the autonomic nervous system; the present results indicate that the drug is not displaced from the target organs by decreasing serum concentrations during exercise. In atrial fibrillation, because the demands on the filter function of the atrioventricular node are highly unphysiological, the effect of digoxin on heart rate during exercise is not adequate.

Topics: Adult; Atrial Fibrillation; Coronary Disease; Digoxin; Heart Rate; Humans; Male; Middle Aged; Physical Exertion

Factors thought to affect the success of and energy requirements for cardioversion of atrial fibrillation were studied in 80 (49 male, 31 female) patients aged 21-88 (mean 61.5 years). Transthoracic impedance was measured in advance of the countershock using a 30 kHz low amplitude AC current passed through self-adhesive ECG/defibrillator pads (diameters 8-12 cm) applied to the chest in the antero-posterior (AP) position in 57 patients and the anteroapical (AA) position in 23 patients. Mean transthoracic impedance for all patients was 69.3 +/- 16 (SD) ohms (range 39-131 ohms), but transthoracic impedance was significantly greater in the AA than the AP position (75.4 +/- 13 vs. 66.7 +/- 16 ohms, p = 0.02). Initial energy was 50 J (delivered) and was gradually increased to a maximum of 360 J if required. Cardioversion was successful in 73 of 80 (91.2 per cent), and low energy shocks (less than or equal to 200 J) were successful in 45 of 80 (56.2 per cent) patients. Using single factor analysis, sex, left atrial enlargement, electrode pad positions, aetiology of atrial fibrillation, presence of left ventricular failure, and prior treatment with verapamil or beta-adrenergic blockers were not significant determinants of cardioversion success or success of low energy shocks but prior treatment with digoxin was, both for cardioversion success and success at low energies. In patients with transthoracic impedance less than or equal to 70 ohms, low energy shocks were more often successful (33 or 50, 66 per cent) than in patients with transthoracic impedance greater than 70 ohms (12 of 30, 40 per cent), p = 0.04. Using univariate analysis, cardioversion success with low energy shocks was not only significantly associated with prior treatment with digoxin but also with the duration of atrial fibrillation (24 hours to one month and one month to three years) and for shocks of less than or equal to 100 J, with prior treatment with amiodarone. Multifactorial linear regression analysis selected, in rank order, only duration of atrial fibrillation of 24 hours to less than one month and one month to three years as significant predictors of both cardioversion success irrespective of shock strength, and success of low energy shocks.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Digoxin; Electric Countershock; Electrophysiology; Female; Humans; Male; Middle Aged; Prospective Studies; Regression Analysis; Time Factors

Topics: Atrial Fibrillation; Digoxin; Heart Conduction System; Humans

All 32 patients treated with digoxin for over three months in one practice population had treatment withdrawn under supervision to assess its continued requirement. In 18 instances (56%) digoxin proved necessary and was restarted to correct clinical deterioration, while in 14 instances (44%) it was successfully discontinued. Successful withdrawal was more frequently achieved in those with sinus rhythm (91% of 14 patients) than in atrial fibrillation (19% of 21 patients). Where digoxin was required dosage increases were necessary to achieve optimum clinical control. Adherence to a strict protocol allows unnecessary therapy to be withdrawn and facilitates improved care when therapy is required, with accompanying savings in costs and time.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Clinical Protocols; Digoxin; Drug Administration Schedule; Female; Heart Failure; Humans; Male

Topics: Atrial Fibrillation; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Heart Rate; Humans

Paraxysmal and recent cardiac fibrillations have been treated in 42 patients with cordaron combined with digoxin. The arrest of fibrillation was achieved for 5 days in 29 patients (69%) suggesting high efficacy of the combination.

Topics: Administration, Oral; Adult; Aged; Amiodarone; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Middle Aged

One hundred and thirty nine episodes of atrial fibrillation were identified from Holter recordings in 72 patients with paroxysmal atrial fibrillation. Paroxysms occurred more often by day than by night, suggesting that attacks are more closely associated with sympathetic than with vagal activity. In 41 patients who were not taking digoxin there were 79 episodes, and in 31 patients who were taking digoxin there were 60 episodes. Significantly more of the episodes that lasted for 30 minutes or more occurred in patients taking digoxin (13/17); the relative risk of a prolonged paroxysm associated with taking digoxin was 4.3 (95% confidence intervals 1.6-11.9). The mean (SD) ventricular rate at the onset of the paroxysms was not significantly different in those taking digoxin (140 (25) beats/min) and in those who were not (134 (22) beats/min). In paroxysmal atrial fibrillation, pretreatment with digoxin does not seem to reduce the frequency of paroxysms, or the ventricular rate when paroxysms occur, but it is associated with longer attacks.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Digoxin; Female; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Risk Factors; Time Factors

The efficacy of magnesium therapy in patients with ventricular tachycardia has previously been reported. Recently completed and ongoing studies validate earlier observations that potassium and magnesium supplementation may control other cardiac arrhythmias, particularly in hypomagnesemic patients. Magnesium treatment is a viable therapeutic option when other antiarrhythmic agents fail to suppress ventricular tachycardia, ventricular fibrillation, multifocal atrial tachycardia, atrial fibrillation and supraventricular tachycardia.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Humans; Magnesium; Magnesium Deficiency; Male; Middle Aged; Tachycardia

Atrial fibrillation is described in a champion pacer which earlier had been named Australian Harness Horse of the Year as a 3-year-old in 1986-87. Prior to conversion atrial fibrillation had been present for at least 6 weeks, during which the horse had not raced. Successful treatment was achieved with two 10g doses of quinidine sulphate per oesophageal tube, after slow digitalisation with intravenous digoxin over 4d. Four hours after commencement of quinidine therapy the arrhythmia had regressed to atrial flutter and converted to sinus rhythm 10 min later. Considering his age, standard of racing and high reputation the horse's overall performance as a 5-year-old after conversion from atrial fibrillation appeared comparable to his previous performance as a 4-year-old before the disorder occurred. In one of the wins since his return to sinus rhythm, the horse recorded his fastest winning speed and created a new track record at the major Melbourne racetrack. The absence of abnormalities of atrial and atrio-ventricular conduction after the cessation of the arrhythmia, together with the horse's return to successful racing, indicate that this was case of atrial fibrillation occurring as a functional disorder without persistent atrial pathology.

Topics: Animals; Atrial Fibrillation; Digoxin; Electrocardiography; Horse Diseases; Horses; Male; Quinidine

Topics: Adult; Atrial Fibrillation; Depression, Chemical; Digoxin; Diltiazem; Drug Therapy, Combination; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Male; Middle Aged

Pulmonary affections in patients with legionellosis are the main ones. The affections of the heart, gastrointestinal tract and other organs and systems are less frequent. Some characteristic features of the legionellosis clinical process in the case described are indicated. The torpid process of chronic bronchitis, the two-phase pattern of the disease, dyspnea at 3-4 month intervals, intermissions, edema and failure of complex therapy with antibiotics and cardiac glycosides provided a tentative diagnosis of Legionella pneumonia with affection of the myocardium. The importance of early serological diagnosis (enzyme immunoassay) was shown. A new approach to the treatment of legionellosis with cefuroxime was of interest.

Topics: Atrial Fibrillation; Cefuroxime; Cephalosporins; Digoxin; Drug Therapy, Combination; Female; Humans; Legionnaires' Disease; Middle Aged; Myocarditis; Pneumonia, Pneumococcal

To assess the cause of the digoxin-amiodarone interaction, the systemic availability and renal excretion of digoxin were examined in 10 patients. Patients were studied before and after 1 week and 6 weeks of concurrent amiodarone therapy, and four were also studied after 4-8 months. Mean (+/- SD) peak plasma digoxin concentration rose from 1.55 +/- 0.6 microgram /1 prior to amiodarone therapy to 2.85 +/- 1.3 micrograms/1 after 1 week of combined therapy (p less than 0.01). Mean AUC also rose from 7.2 +/- 2.1 micrograms/1.h to 12.1 +/- 6.4 micrograms/1.h (p less than 0.01) during this period. Mean peak plasma digoxin concentration and AUC remained elevated after 6 weeks and, in the patients studied, at 4-8 months. Mean urinary digoxin clearance remained unchanged. Plasma amiodarone and desethylamiodarone concentrations were consistent with the prescribed doses. This study confirmed previous findings of raised plasma digoxin concentrations following the addition of amiodarone. It has also shown that this interaction is sustained for at least several months. The cause has not been fully elucidated but does not appear to be due to a change in the renal clearance of digoxin.

Topics: Aged; Amiodarone; Atrial Fibrillation; Biological Availability; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged

Topics: Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Interactions; Drug Therapy, Combination; Humans; Pilot Projects; Quinidine

Flecainide acetate has a recognized proarrhythmic effect in patients treated for ventricular tachycardia. Three patients developed severe ventricular arrhythmias while taking flecainide for atrial fibrillation. Patient 1 had normal ventricular function and idiopathic atrial fibrillation. Treadmill exercise tests during digoxin therapy showed no ventricular arrhythmia; however, during flecainide therapy the patient developed ventricular flutter at his peak exercise level that required cardioversion. Patient 2 had normal ventricular function and a prosthetic mitral valve. During therapy with flecainide, 150 mg twice daily, he had an episode of sustained ventricular tachycardia, also at his peak exercise level. Patient 3 had paroxysmal atrial fibrillation and hypertrophic cardiomyopathy but no previous ventricular arrhythmia. She died suddenly within 10 days of starting flecainide therapy. Judged from previous findings none of these patients was considered at high risk for proarrhythmia. These cases suggest a possible relation between vigorous exercise, atrial fibrillation, and the proarrhythmic properties of flecainide and indicate the limitations of classifying patients as "high-risk" or "low-risk" for proarrhythmic complications of anti-arrhythmic therapy.

Topics: Adult; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Flecainide; Heart Ventricles; Humans; Male; Tachycardia; Ventricular Fibrillation

The elimination of total digoxin after digoxin-specific Fab fragment therapy in a patient in end-stage renal disease is described. Two-component, nonlinear exponential regression of the patient's total digoxin concentration data revealed biphasic elimination: a fast phase with a half-life of 43 h and a slow phase with a half-life of 330 h. Serum total digoxin concentration decreased 20% 12 h after the initiation of Fab fragment therapy. The mean serum concentrations of total digoxin and apparent total digoxin as measured by fluorescence polarization immunoassay during a 520-h period after the initiation of therapy were 18.42 and 14.77 ng/ml, respectively (n = 15). The correlation between the two measurements was good (r = 0.987). The time course of free digoxin concentration obtained after ultrafiltration at 2, 20, or 37 degrees C is also described. The free digoxin concentrations (n = 10) at these temperatures averaged over a 282-h period were 0.35, 0.53, and 0.82 ng/ml, respectively (p less than 0.001, 2 degrees C vs. 37 degrees C).

Topics: Aged; Atrial Fibrillation; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Kidney Failure, Chronic; Regression Analysis; Renal Dialysis; Ultrafiltration

Restoration of the sinus rhythm in atrial fibrillation and flutter can be achieved by cardioversion, using an electric discharge, or by medicamentous treatment. Medicamentous treatment is based above all on a combination of antiarrhythmic drugs. By the concurrent administration of quinidine, verapamil and digoxin restoration of the sinus rhythm is achieved in 80% patients, on average after 37 hours at plasma quinidine levels of 2.57 +/- 1.4 (SD) micrograms/ml and digoxin levels of 1.90 +/- 1.3 (SD) nmol/l. Restoration of the sinus rhythm in atrial flutter calls for higher quinidine and digoxin levels than in atrial fibrillation (p less than 0.01). Prolonged persistence of the sinus rhythm during treatment with maintenance doses of quinidine, verapamil and digoxin is not satisfactory so far and after 12 months the sinus rhythm persists only in 30% of the patients where the rhythm was originally restored.

Topics: Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Quinidine; Verapamil

Everyday physical activity previously has been shown to affect serum digoxin concentrations. Standardized rest in the supine position increases outpatient serum digoxin levels 0% to 75%. The present study comprising 56 outpatients treated with digoxin was undertaken to elucidate the clinical importance of a standardized period of rest before collection of the blood sample. Blood samples were taken about 24 hours after the latest dose, before and after 2 hours of rest in the supine position. A careful clinical examination, including electrocardiogram (ECG) findings, systolic time intervals, and chest x-ray studies, was performed to identify adverse effects/intoxication or failure of digitalis treatment. Signs of failure of digitalis treatment occurred in 12% of the patients, with a serum digoxin concentration of 0.68 +/- 0.15 (mean +/- SD) nmol/L before rest and 0.85 +/- 0.22 nmol/L after rest. Eleven percent showed signs of adverse effects/intoxication, with serum digoxin concentrations of 1.70 +/- 0.70 nmol/L before rest and 2.08 +/- 0.80 nmol/L after rest. The serum digoxin concentrations of the adequately treated patients (77%) were 1.02 +/- 0.35 nmol/L before rest and 1.28 +/- 0.41 nmol/L after rest. The importance of standardized rest before blood sampling is illustrated by the fact that only one third of the patients without signs of adverse effects/intoxication or failure of digitalis treatment had serum digoxin concentrations within the therapeutic range most commonly used (1.2 to 2.6 nmol/L) without supine rest. If allowed to rest in the supine position before blood sampling, approximately 60% of the adequately treated patients had serum digoxin concentrations within this range.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Blood Specimen Collection; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Outpatient Clinics, Hospital; Potassium; Radiography, Thoracic; Rest; Supination; Systole; Time Factors

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Diagnosis, Differential; Digoxin; Female; Humans

The potential interaction between certain antibiotics and digoxin has been discussed in the literature; however, few cases of actual erythromycin-induced digoxin toxicity have been reported. We present a case in which an 86-year-old woman who was taking digoxin 0.25 mg/d developed probably digoxin toxicity after the administration of erythromycin for the treatment of otitis media and streptococcal pharyngitis. Her digoxin concentration increased from a trough of 1.9 to 5.1 nmol/L six days after the erythromycin was started. Digoxin was discontinued and restarted approximately six weeks later when the patient's atrial fibrillation and congestive heart failure recurred. Her digoxin dose at this time was 0.125 mg/d and resulted in steady-state concentrations of 1.2, 1.4, and 1.2 nmol/L over the next year. Erythromycin inhibition of Eubacterium lentum, which converts digoxin into digoxin-reduction products in the gut, is the proposed mechanism of this interaction.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Digoxin; Erythromycin; Female; Humans; Myocardial Infarction

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Heart Rate; Heart Ventricles; Humans; Shock, Septic

Digoxin was studied for its effects on the function of sinus nodal automatism and atrioventricular conduction in an acute experiment and during a course therapy. Digoxin was shown to exert substantial effects on the sinus node with its retained function and dysfunction. When digoxin was given in a daily dose of 0.375 mg, there was an increase in sinoatrial conduction time. When the drug was administered in a single dose of 0.4 mg, there was no substantial change in the atrioventricular conduction. During its course therapy, digoxin failed to produce antirecurrent antiarrhythmic effects.

Topics: Adolescent; Adult; Aged; Atrial Fibrillation; Atrioventricular Node; Digoxin; Female; Heart Conduction System; Humans; Male; Middle Aged; Recurrence; Sinoatrial Node

Atrial fibrillation due to hyperthyroidism is characterized by a rapid ventricular response which is typically resistant to digoxin therapy. We report a patient with atrial flutter-fibrillation who developed cyclic sinus node dysfunction with profound ventricular pauses in response to small doses of digoxin, verapamil, and propranolol, which resolved with discontinuation of the medications. Caution is necessary to avoid paradoxical ventricular slowing when treating hyperthyroid-induced atrial fibrillation.

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Humans; Hyperthyroidism; Middle Aged; Propranolol; Verapamil

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Drug Therapy, Combination; Humans; Pindolol; Verapamil

This study was conducted to ascertain if critical peak body stores of digoxin were needed to protect patients from the debilities that result from supraventricular tachycardias occurring after open heart operations. We gave digoxin peak body stores of 15 micrograms/kg of lean body weight to 100 consecutive patients after open heart operations. If supraventricular tachycardias persisted four hours, we increased peak body stores to 17 or 19 micrograms/kg. The operations included coronary artery bypass grafts, heart valve replacements, and congenital defect correction. After operation, 18 patients had atrial fibrillation or flutter. During supraventricular tachycardias, ventricular rates were 150 beats per minute or slower. In the 100 patients, the median hospital stay after operation was four days. No patient required rehospitalization. The patients who had supraventricular tachycardias stayed in the hospital no longer than the patients who were at all times in regular sinus rhythm. All patients who entered the hospital with regular sinus rhythm went home with regular sinus rhythm. The critical safe peak body stores of digoxin needed to prevent debilities resulting from supraventricular tachycardias after open heart operations were 15 to 19 micrograms/kg of lean body weight.

Topics: Aged; Atrial Fibrillation; Atrial Flutter; Cardiac Surgical Procedures; Digoxin; Female; Humans; Male; Middle Aged; Postoperative Complications; Tachycardia, Supraventricular

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Tachycardia, Supraventricular

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Hemodynamics; Humans; Middle Aged

Topics: Aged; Atrial Fibrillation; Delayed-Action Preparations; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Verapamil

Topics: Adolescent; Adult; Aged; Atrial Fibrillation; Digoxin; Female; Heart Failure; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged

Thirty-two patients with atrial fibrillation and normal ventricular rates who complained of dizziness or loss of consciousness underwent 24-hour ambulatory electrocardiographic monitoring. A control group of 25 patients in atrial fibrillation but without symptoms of dizziness or loss of consciousness was likewise investigated. All patients remained in atrial fibrillation; periods of ventricular standstill (mean, 2.9; range, 1.8-8.0) were present in 31 symptomatic patients but in only three of the control patients (mean, 1.9 s; range, 1.7-2.4). Twenty-three symptomatic patients with pauses greater than or equal to 2.0 s received a demand pacemaker. Following pacing, nineteen became completely asymptomatic; four patients continued to have dizziness but three of these, who also experienced syncope, no longer did so (mean follow-up, 13 months; range, 6-30). It is suggested that ventricular standstill may commonly occur in patients with controlled atrial fibrillation who complain of dizziness or syncope and that the majority will benefit from permanent cardiac pacing.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Chronic Disease; Combined Modality Therapy; Digoxin; Dizziness; Electrocardiography; Female; Heart Block; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Pacemaker, Artificial; Syncope

Topics: Aged; Atrial Fibrillation; Diazepam; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Heart Failure; Humans; Hydrochlorothiazide; Kinetics; Male; Warfarin

Quinidine syncope and factors associated with it are well known among adult patients treated for cardiac arrhythmias. To define factors that may influence the occurrence of syncope in children taking quinidine, the clinical, anatomic, electrocardiographic, roentgenographic and pharmacologic data were compared in six patients with syncope (Group A) and 22 patients without syncope (Group B). There was a significant (chi-square = 10.2, p = 0.001) relation between heart disease and quinidine syncope: all six Group A (syncopal) patients had heart disease whereas 15 of the 22 Group B (non-syncopal) patients had no structural heart disease. In contrast, no significant difference was noted between Group A and Group B patients in mean age (11.4 versus 11.4 years), mean quinidine serum concentration (2.9 versus 2.3 micrograms/ml), mean corrected QT interval before quinidine (0.43 versus 0.40 second) or mean corrected QT interval during quinidine therapy (0.46 versus 0.46 second) or between those taking digitalis and those not. Two of the six Group A (syncopal) patients died during therapy, one 6 days after initiating therapy and one suddenly at home 6 months after beginning quinidine. Another two of the six Group A patients exhibited hypokalemia (both 2.9 mEq/liter) at the time of syncope, 2 weeks and 6 months, respectively, after initiation of quinidine therapy; both survived. Syncope occurred within 8 days of initiation of quinidine therapy in three of the six patients. Sustained ventricular tachycardia was observed during quinidine associated arrhythmia in three of six patients with syncope; nonsustained ventricular tachycardia or complex ventricular ectopic activity while on this therapy was observed before syncope in the other three patients in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Child, Preschool; Digitoxin; Digoxin; Drug Administration Schedule; Electrocardiography; Heart Diseases; Hemodynamics; Humans; Quinidine; Syncope

Topics: Atrial Fibrillation; Digoxin; Humans; Statistics as Topic

Topics: Adult; Aged; Atrial Fibrillation; Blood Pressure; Chronic Disease; Digoxin; Diltiazem; Female; Heart Rate; Humans; Male; Middle Aged

Although digoxin is often the first choice for control of ventricular response in chronic atrial fibrillation, it fails to slow exercise rates. Diltiazem, a calcium channel antagonist that slows atrioventricular conduction, was administered to 16 patients who failed to achieve adequate rate control on low level exercise testing despite digoxin therapy. Therapeutic response to diltiazem was assessed with submaximal and maximal exercise tests and 24 hour ambulatory electrocardiographic monitoring. During the diltiazem treatment phase, ventricular response at rest diminished (96 +/- 17 versus 69 +/- 10 beats/min, p less than 0.001) as did rate during submaximal exercise (155 +/- 28 versus 116 +/- 26, p less than 0.001), maximal exercise (163 +/- 14 versus 133 +/- 26, p less than 0.001) and average ventricular response during 24 hour monitoring (87 +/- 13 versus 69 +/- 10, p less than 0.001). Rate at rest decreased 26 +/- 15% and submaximal exercise rate diminished 24 +/- 12%. Thirteen (81%) of the 16 patients exhibited at least 15% slowing of rate at rest and during submaximal exercise. Eleven patients (69%) reported alleviation of symptoms. There was no change in serum digoxin levels during diltiazem treatment (1.3 +/- 0.5 versus 1.3 +/- 0.6 ng/ml, p = NS). On withdrawal of diltiazem, ventricular response returned to baseline values. Diltiazem is an effective agent for control of ventricular response, both at rest and during exercise, in digoxin-treated patients with chronic atrial fibrillation.

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Diltiazem; Drug Evaluation; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Physical Exertion; Rest; Tachycardia, Supraventricular

Topics: Adult; Atrial Fibrillation; Blood Proteins; Cardenolides; Digoxin; Humans; Saponins; Sodium-Potassium-Exchanging ATPase; Tachycardia; Time Factors

Topics: Aged; Amiodarone; Atrial Fibrillation; Benzofurans; Digoxin; Female; Humans; Male

Intravenous verapamil hydrochloride was used alone in 63 episodes of atrial fibrillation and flutter and six episodes of supraventricular tachycardia (SVT) (group A). Calcium chloride was given intravenously prior to verapamil in 41 episodes of fibrillation and flutter and 18 episodes of SVT (group B). All patients with SVT converted to normal sinus rhythm, with eight in group B converting after administration of calcium alone. Therapy lowered the heart rate in all patients with fibrillation and flutter; however, those given verapamil alone had a mean decrease in systolic pressure of 18.8 mm Hg; there was no change in those pretreated with calcium. The mean dose of verapamil required by group B was significantly lower than in group A. Many with atrial fibrillation or flutter who received digoxin subsequently converted to sinus rhythm. Thus, pretreatment with calcium decreased the hypotensive effect of verapamil without compromising its antiarrhythmic effect.

Topics: Adolescent; Adult; Aged; Atrial Fibrillation; Atrial Flutter; Calcium Chloride; Digoxin; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypotension; Infusions, Parenteral; Male; Middle Aged; Premedication; Verapamil

The belief that there is total irregularity of the pulse in atrial fibrillation has been re-examined. In a computerised analysis of R-R intervals and pulse volumes, 100-500 (mean 237) consecutive cycles were examined in 74 patients with atrial fibrillation, of whom 36 were on digoxin and 38 were not taking any antiarrhythmic treatment. A Doppler ultrasound technique was used to assess pulse volumes, against which R-R intervals were correlated. Although the sequence of consecutive R-R intervals was random in 52 (70%), patients there was a significant correlation between consecutive intervals in 22 (30%), the correlation coefficient being negative in 11 and positive in 11. In 43 (58%) cases the sequence of consecutive pulse volumes was significantly non-random; 34 (46%) showed pulsus alternans, indicated by a negative correlation between consecutive volumes. The proportion of patients with a non-random sequence of R-R intervals or pulse volumes was the same whether or not they were taking digoxin. Thus patients with atrial fibrillation often have patterns of regularity of the pulse, with the ventricular rhythm being non-random in almost one third and the sequence of pulse volumes being non-random in over a half. Contrary to classic teaching, in many patients with atrial fibrillation the pulse is not irregularly irregular.

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Pulse; Time Factors

Topics: Adolescent; Adult; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Verapamil

Topics: Aged; Atrial Fibrillation; Digoxin; Female; Humans; Male; Middle Aged; Patient Care Planning; Risk

Propafenon's influence on the pharmacokinetic and actions of digitalis and viceversa have been evaluated in 27 patients (25 with ventricular hyperkinetic arrhythmias and 2 with paroxismal atrial fibrillation). Patients were divided in two groups according to whether the drug firstly administered were digoxin or propafenon. Plasmatic digoxin and/or propafenon's concentrations, these last performed only in 12 patients, were determined before and during the association and after propafenon's interruption at 7.55-9-11 and at 3-8 p.m. During drug's association area under the plasmatic digoxin concentration curve (AUC 12h) increased on the average by 13.8% (from 19.27 +/- 6.002 ng hours/ml to 21.94 +/- 6.198 ng hours/ml: P less than 0.05) and by 19% at the first hour. Neverthless individual behaviour was not homogeneous since the plasmatic digoxin concentration (PDC) increased in 22 cases (81.4%) and decreased in 5 (18.6%). In 6 patients mean increase was 38.8% (from 16.72 +/- 3.0 ng hours/ml to 23.21 +/- 5.44 ng hours/ml) without signs of digoxin intoxication. Another patient with congestive heart failure and basal PDC 1.87 ng/ml experienced digoxin poisoning with fatal ventricular fibrillation after propafenon. Digoxin administration in the second group's patients produced a not significant increase of plasmatic propafenon concentration (PPC). There was a good correlation among propafenon's absolute amount and plasmatic concentration and antiarrhythmic effect and no correlation among PPC and body-weight related dose. Propafenon's to digitalis association induced, in propafenon's steady state, significant P-R longation from 170 to 190 ms (P less than 0.01) but HR, QRS and QTc didn't show any important change (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Propafenone

We evaluated the efficacy and the safety of medium-(240 mn/day) and high-dose (360 mg/day) diltiazem alone and in combination with digoxin when used for control of heart rate in 12 patients with chronic atrial fibrillation. Medium-dose diltiazem was comparable to therapeutic dose of digoxin at rest (88 +/- 19 vs 86 +/- 12 beats/min) but superior during peak exercise (154 +/- 23 vs 170 +/- 20 beats/min; p less than .05). High-dose diltiazem resulted in better control of heart rate than digoxin both at rest (79 +/- 17 beats/min; p less than .05) and exercise (136 +/- 25 beats/min; p less than .05) but was associated with side effects in 75% of the patients. Combined therapy of digoxin and diltiazem enhanced the effect of digoxin alone and resulted in significantly better control of heart rate at rest (67 +/- beats/min with medium-dose and 65 +/- beats/min with high-dose diltiazem) and during peak exercise (132 +/- 32 and 121 +/- 24 beats/min, respectively). However, the difference in heart rate between these two doses was not significant. Reduction of heart rate combined with concomitant effect on blood pressure resulted in a significant fall in pressure-rate product at rest from 10,077 +/- 1708 mm Hg/min on digoxin alone to 7877 +/- 1818 mm Hg/min after the addition of medium-dose diltiazem (p less than .05) and during exercise form 25,670 +/- 3606 to 18,439 +/- 4115 mm Hg/min (p less than .05). Continued therapy with digoxin combined with diltiazem 240 mg/day for 21 +/- 8 days in nine patients showed persistent effect on heart rate and blood pressure without any toxic manifestations or change in serum digoxin (1.5 +/- 0.4 vs 1.3 +/- 0.4 ng/ml) or plasma diltiazem concentrations (204 +/- 72 vs 232 +/- 129 ng/ml). In conclusion, medium-dose diltiazem when combined with digoxin is an effective and safe regimen for the treatment of patients with chronic atrial fibrillation and enhances digoxin-mediated control of heart rate both at rest and during exercise.

Topics: Adult; Atrial Fibrillation; Benzazepines; Blood Pressure; Digoxin; Diltiazem; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Rest

The electrocardiographic diagnosis of uncomplicated hypokalemia rests on ST segment depression, a decrease in T-wave amplitude, prominent U waves and a U-wave to T-wave ratio of greater than 1. The diagnosis is more difficult in a patient receiving digitalis, but the upsloping ST segment of digitalis can be distinguished from that of hypokalemia. The changes of hypokalemia are most apparent in leads V2 and V3.

Topics: Atrial Fibrillation; Diagnosis, Differential; Digoxin; Electrocardiography; Humans; Hypokalemia

An encapsulated solution of digoxin has been repeatedly shown to have greater bioavailability than tablet forms of the drug. It is predicted that such a preparation would show reduced within- and between-patient variability in absorption, as most studies in normal subjects have shown reduced intersubject variation with the capsule. We tested inter- and intrapatient variability during 4-week periods of dosing with digoxin capsules and tablets in 28 subjects with cardiac disease. In the overall group there were no significant differences between the formulations at steady state in between-patient variability in trough serum digoxin concentrations or 24-hour urinary digoxin excretion. Within-patient variability in urinary digoxin excretion was somewhat lower for the capsules. In a subgroup of six patients who excreted significant amounts of cardioinactive bacterial metabolites (digoxin reduction products [DRP]), the mean (+/- SD) percent urinary DRP excretion was less (p less than 0.05) during capsule (20.5% +/- 15.1%) than tablet (34.4% +/- 10.9%) dosing. Within-patient variability in urinary DRP excretion was much greater after tablets than capsules. Certain subgroups of patients should benefit from the enhanced bioavailability of digoxin capsule preparations.

Topics: Absorption; Adult; Aged; Atrial Fibrillation; Biological Availability; Blood; Capsules; Digoxin; Evaluation Studies as Topic; Female; Heart Failure; Humans; Male; Middle Aged; Radioimmunoassay; Tablets

Topics: Adult; Aged; Amiodarone; Atrial Fibrillation; Benzofurans; Digoxin; Drug Resistance; Female; Heart Rate; Humans; Male; Middle Aged

Prompt control of heart rate is important for successful treatment of supraventricular tachyarrhythmias early after open heart surgery when sympathetic tone is high and ventricular response rates may be rapid. Esmolol, a new ultrashort-acting (9 minute half-life) beta-receptor blocking agent, was given by continuous intravenous infusion for up to 24 hours in 24 patients (21 with isolated coronary bypass surgery and 3 with valve replacement) 1 to 7 days after surgery. Atrial fibrillation was present in 9 patients, atrial flutter in 2 and sinus tachycardia in 13. Eleven patients had received intravenous digoxin (average dose 0.6 mg, average serum level 1.19 mg/100 ml) before esmolol infusion without adequate control of the supraventricular tachyarrhythmia. After a 1 minute loading infusion of esmolol (500 micrograms/kg per min), maintenance dose, titrated to heart rate and blood pressure response, varied from 25 to 300 micrograms/kg per min. After esmolol administration, at an average dose of 139 +/- 83 micrograms/kg per min, mean heart rate decreased from 130 +/- 15 to 99 +/- 15 beats/min. Within 5 to 18 minutes after initiation of therapy, all patients had achieved a 15% reduction in heart rate at a maintenance dose of 150 micrograms/kg per min or less. A 20% reduction in heart rate was attained in 19 of the 24 patients, and conversion to sinus rhythm occurred during esmolol infusion in 5 of the 11 patients with atrial flutter or fibrillation. Transient asymptomatic hypotension (less than 90/50 mm Hg) was seen in 13 patients, requiring cessation of esmolol therapy in 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Blood Pressure; Cardiac Surgical Procedures; Digoxin; Dose-Response Relationship, Drug; Heart Rate; Humans; Hypotension; Infusions, Parenteral; Middle Aged; Postoperative Complications; Premedication; Propanolamines; Tachycardia

The importance of cardiovascular system involvement in hyperthyroidism has been recognized for many years. In the middle-aged and elderly patient, often with mild but prolonged elevation of plasma thyroid hormones, symptoms and signs of heart failure and complicating atrial fibrillation may dominate the clinical picture and mask the more classical endocrine manifestations of the disease. Pitfalls in diagnosis and the importance of early recognition and treatment are discussed. Despite experimental evidence for a short-term inotropic action of thyroid hormone excess, clinical data support the existence of a reversible cardiomyopathy in hyperthyroidism with impaired contractile reserve. Enhanced myocardial performance at rest primarily reflects the peripheral actions of thyroid hormone excess. Most, if not all, of the cardiac abnormalities return to normal once a euthyroid state has been achieved, although atrial fibrillation may persist in a minority. Optimum treatment requires rapid and definitive antithyroid therapy, usually using a large dose of radio-iodine, and rapid control of heart failure. Systemic anticoagulation is indicated in the presence of atrial fibrillation and should be continued until sinus rhythm has been present for at least three months, either spontaneously or after cardioversion.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiomyopathies; Digoxin; Drug Therapy, Combination; Heart Diseases; Heart Rate; Hemodynamics; Humans; Hyperthyroidism; Myocardial Contraction; Myocardial Infarction; Sympathetic Nervous System; Thyroid Function Tests; Thyroid Hormones

Of 1,247 consecutive patients who underwent cardiac surgery, 297 (24%) developed a post-operative atrial tachyarrhythmia. Of these patients, 201 were suitable for treatment according to the study protocol. All patients were initially given digoxin 0.75 mg intravenously (i.v.). After two hours, those 156 patients whose atrial arrhythmias persisted were given a 2 mg/kg loading dose of disopyramide (i.v.), followed by a constant i.v. infusion (0.4 mg kg-1 h-1) or oral therapy (600 mg daily). Within a further 12 hours, 75 patients (48%) reverted to sinus rhythm, 24 within one hour. Thus 120/201 patients (60%) reverted to sinus rhythm within 14 hours of commencing therapy. Reversion rates of those patients with both atrial fibrillation and flutter (AF/AFL) were significantly lower than those with AF (p less than 0.001) or AFL (p less than 0.02) alone. A further 70 patients reverted to sinus rhythm in one to 13 (mean four) days on continued drug therapy. Elective cardioversion restored sinus rhythm in six subjects. Atrial arrhythmias persisted in five patients (2.5%) at hospital discharge. Side-effects of disopyramide were noted in 19% of patients. Urinary retention was common (11.5%). Four patients with atrial flutter developed 1:1 atrioventricular conduction with the disopyramide loading dose. One patient with atrial fibrillation developed ventricular tachycardia during injection of the loading dose of disopyramide, but was successfully cardioverted to sinus rhythm. Two further patients developed significant hypotension (less than 90 mmHg systolic). Disopyramide is effective in the treatment of post-operative atrial tachyarrhythmias, but its routine use in this situation may be associated with an unacceptably high incidence of side-effects.

Topics: Atrial Fibrillation; Atrial Flutter; Cardiac Surgical Procedures; Digoxin; Disopyramide; Drug Therapy, Combination; Heart Conduction System; Humans; Hypotension; Postoperative Complications; Urination Disorders

Topics: Atrial Fibrillation; Atrial Flutter; Digoxin; Edrophonium; Electric Countershock; Emergencies; Humans; Pressure; Propranolol; Tachycardia, Paroxysmal; Verapamil; Wolff-Parkinson-White Syndrome

To determine the incidence of cardioversion-induced ventricular arrhythmias in patients with therapeutic serum levels of digoxin, 19 patients (average age [+/- standard deviation] 61 +/- 12 years) undergoing elective direct current cardioversion for atrial fibrillation were studied. Only patients with therapeutic serum digoxin levels (range 0.5 to 1.9 ng/ml; mean 1.1 +/- 0.5) at the time of cardioversion were included. Patients with acute myocardial ischemia or unstable angina, serious electrolyte disturbance or those requiring class I antiarrhythmic agents for control of ventricular or supraventricular arrhythmias were excluded. Ambulatory electrocardiograms were recorded for 24 hours before and 6 hours after cardioversion. No patient developed malignant ventricular arrhythmias (ventricular triplets or tachycardia) in the immediate 3 hour period after cardioversion. Furthermore, there were no significant (p less than 0.05) differences in the frequency of ventricular premature beats or couplets before and after cardioversion. To determine whether the level of serum digoxin or the strength of the applied shock had a significant effect on the development of postcardioversion arrhythmias, the change in frequency of single premature ventricular beats after cardioversion was compared with the serum digoxin level (ng/ml) and the applied energy level (joules) by means of linear regression analysis. There was no significant (p less than 0.05) relation between these variables. These findings suggest that patients with therapeutic serum levels of digoxin may safely undergo cardioversion without the concomitant use of class I antiarrhythmic agents.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electric Countershock; Heart Ventricles; Humans; Middle Aged; Time Factors

To determine whether treatment with digitalis is associated with decreased survival after acute myocardial infarction (AMI), data from 504 patients who were enrolled in a postinfarction natural history study were analyzed. At the time of discharge, 229 patients (45%) were taking digitalis. After 3 years of follow-up, the cumulative survival rate for patients discharged on a regimen of digitalis was 66%, compared with 87% for those not treated (p less than 0.001). Univariate analysis showed that statistically significant differences existed between the 2 groups with respect to age, previous AMI, left ventricular failure in the coronary care unit, atrial fibrillation in the coronary care unit, peak creatine kinase levels, enlarged heart and pulmonary vascular congestion on the discharge chest x-ray, ventricular arrhythmias and treatment with diuretic, antiarrhythmic and beta-blocking drugs. Survival analysis using Cox's regression model showed that the association between digitalis and decreased survival was of borderline significance after adjustment for atrial fibrillation and left ventricular failure. Serum digoxin concentration was measured in 83% of the patients who took digitalis. Survival was inversely and significantly related to serum digoxin, i.e., the higher the serum digoxin concentration, the lower the long-term survival rate. After adjusting for atrial fibrillation and left ventricular failure, serum digoxin was not significantly related to survival. Taken together with the results of 3 other large, nonrandomized studies of digitalis treatment after AMI, this study suggests that digitalis treatment may have adverse effects on survival during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Fibrillation; Digitalis; Digoxin; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Risk

Topics: Adult; Aged; Amiodarone; Atrial Fibrillation; Benzofurans; Digoxin; Drug Resistance; Female; Heart Rate; Humans; Male; Middle Aged

In a review of the records of 81 patients with the discharge diagnosis of digitalis toxicity, I found a preponderance of very old patients, many of whom had anorexia, nausea, and prerenal azotemia. Arrhythmias were common (93%) and reflected enhanced automaticity, enhanced AV block, or both. Atrial fibrillation with complete heart block and a regular junctional rhythm should particularly elicit suspicion of digitalis toxicity. Atrial tachycardia with block is less specific and less frequent.

Topics: Adult; Age Factors; Aged; Anorexia; Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Digoxin; Heart Atria; Heart Block; Humans; Middle Aged; Nausea; Plants, Medicinal; Plants, Toxic; Radioimmunoassay; Tachycardia; Uremia

The efficacy and the risk of toxicity of long-term digoxin therapy were assessed in 81 elderly patients. The findings show that the serum digoxin level did not correlate with the clinical state. Only 47% of the patients were on a dosage considered to be effective by serum digoxin analysis, whereas 38% of the patients had levels below the therapeutic range; 51% of the patients had been treated with pediatric or semipediatric doses only. Electrocardiographic evidence of digoxin toxicity was found in 17%. Routine periodic measurement of serum digoxin did not correlate with better management. The optimum dosage of digoxin in the elderly patient who is not in overt renal failure and who is not particularly underweight would seem to be 0.19 mg/day, i.e., one and one-half tablets of 0.25 mg on alternate days.

Topics: Aged; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Risk

Renal digoxin clearance was compared in patients suffering from atrial fibrillation with well preserved cardiac function (n = 9; salt intake +/- 170 mmol daily) and patients with chronic congestive heart failure (n = 10; salt intake 50 mmol daily and maintenance treatment with diuretics). There was no difference between the groups concerning digoxin dosage, creatinine clearance, diuresis or sodium excretion in the urine. Digoxin clearance in chronic heart failure proved to be significantly lower than in atrial fibrillation (48 +/- 21 vs 71 +/- 36 ml X min-1, p less than 0.05), and Cdig/Ccreat was similarly reduced at 0.73 +/- 0.15 compared to 1.09 +/- 0.27 (p less than 0.005). Steady state serum digoxin concentration was significantly higher in patients with congestive heart failure (1.44 +/- 0.47 vs 0.87 +/- 0.33 micrograms X 1(-1), p less than 0.01). Chronic congestive heart failure is a state with reduced digoxin clearance by the kidney, which could lead to digoxin intoxication not explicable by overdose, reduced renal function or the effect of interacting drugs.

Topics: Aged; Atrial Fibrillation; Creatinine; Digoxin; Heart Failure; Humans; Kidney; Metabolic Clearance Rate; Middle Aged

We report two patients who developed symptomatic life-threatening ventricular tachyarrhythmias with changing QRS axes (resembling torsades de pointes), during treatment of their supraventricular tachycardias with oral amiodarone. Like other effects of amiodarone on the body, the arrhythmias became evident several days after initiating therapy, at which time electrocardiographic QT prolongation was present. The arrhythmias subsided after amiodarone treatment was withdrawn. No other drugs or electrolyte disturbances could be incriminated as a cause.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Digoxin; Electrocardiography; Female; Humans; Tachycardia

To assess the effects of digoxin as single therapy and in combination with quinidine in the treatment of atrial fibrillation, the atrial fibrillation threshold was determined from the right atrial appendage and Bachmann's bundle in 11 open chest dogs. In group 1 (six dogs), the atrial fibrillation threshold was determined at baseline, post-quinidine (10 mg/kg intravenously) and then post-digoxin (50 micrograms/kg intravenously). In group 2 (five dogs), the order of drug administration was reversed. The results of this study were: 1) Digoxin had no significant effect on the atrial fibrillation threshold when given alone. 2) Quinidine significantly increased the atrial fibrillation threshold (p less than 0.002) and the addition of digoxin resulted in a further increase in threshold (p less than 0.002). 3) Quinidine produced greater suppression of atrial fibrillation induction at the right atrial site than at the Bachmann's bundle site, suggesting differential effects of quinidine on atrial fibers.

Topics: Animals; Atrial Fibrillation; Differential Threshold; Digoxin; Dogs; Drug Combinations; Drug Interactions; Electric Stimulation; Quinidine

The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. In a single-dose cross-over study in healthy volunteer subjects cimetidine increased the area under the plasma digoxin concentration curve and the peak plasma digoxin concentration. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.25 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.15 ng/ml. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.5 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.19 ng/ml. In a repeated-dose study in patients receiving long-term digoxin therapy for atrial fibrillation co-administration of cimetidine had no significant effect on plasma digoxin concentrations. We have shown that co-administration of cimetidine and digoxin in volunteer subjects causes a statistically significant but small increase in plasma digoxin concentration but no such increase was found in patients. We conclude that it is doubtful that this interaction is of any clinical significance.

Topics: Adult; Aged; Atrial Fibrillation; Cimetidine; Digoxin; Drug Interactions; Female; Humans; Kinetics; Male

In 25 outpatients taking digoxin for chronic atrial fibrillation (established for at least six months) a prospective study identified only one case in which rapid availability of the results of a plasma digoxin assay altered the dose which had already been selected on the basis of simple clinical assessment. No patient received more than 375 micrograms digoxin per day and none showed clinical evidence of toxicity even though seven had renal impairment. Six other patients had poorly controlled ventricular rates requiring larger doses of digoxin, but even in these patients the dose could be selected on clinical grounds alone. Despite the availability of a very rapid fluorescence polarisation immunoassay for digoxin, simple but careful clinical monitoring is an adequate basis for the selection of a suitable dose in most patients taking digoxin for atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Diagnostic Tests, Routine; Digoxin; Fluorescence Polarization; Heart Rate; Humans; Middle Aged; Outpatient Clinics, Hospital; Prospective Studies; Time Factors

Topics: Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Humans; Radioimmunoassay; Verapamil

Nursing home patients were studied to determine the usefulness of a maintenance dose of digoxin in elderly patients with normal sinus rhythm. Of 64 patients, 26 were identified to be on digoxin. Thorough history and physical examination were done on all the patients. Baseline electrocardiogram showed normal sinus rhythm in 19 patients, who were observed very closely for the period of four months after withdrawal of digoxin. Eighteen of 19 patients did well without digoxin, which suggests that most of the elderly nursing home patients with normal sinus rhythm do not need a maintenance dose of digoxin.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Nursing Homes; Substance Withdrawal Syndrome

Topics: Atrial Fibrillation; Digoxin; Drug Synergism; Drug Therapy, Combination; Female; Humans; Middle Aged; Ventricular Fibrillation; Verapamil

Topics: Aged; Atrial Fibrillation; Bufanolides; Digoxin; Electrocardiography; Humans; Lown-Ganong-Levine Syndrome; Male; Proscillaridin; Wolff-Parkinson-White Syndrome

Cardiac glycosides exert an acute positive inotropic effect on the normal and failing heart. Recent evidence establishes that the positive inotropic effect is maintained over several months in many patients. The effectiveness of long-term treatment with cardiac glycosides in relieving symptoms is less certain; only a small subset of patients benefits. An effect on mortality is not established. The use of digoxin in the treatment of mild heart failure is questionable since the drug has serious side-effects and the efficacy in patients already taking diuretics has not been established. The use of glycosides in the treatment of severe chronic heart failure is being challenged because of the availability of powerful diuretics, new vasodilators and alternative positive inotropes.

Topics: Atrial Fibrillation; Digitalis Glycosides; Digoxin; Diuretics; Erythrocytes; Exercise Test; Forecasting; Heart Failure; Humans; Myocardial Contraction; Vasodilator Agents

An adaptation of a previously published program for nonlinear regression analysis of serum drug concentrations which can utilize data obtained during multiple-dose administration is described. Specific programs have been developed for aminoglycosides, digoxin, and theophylline. The programs provide initial parameter estimates (for a one-compartment linear model) for each drug based on mean population parameters and refined estimates based on observed concentration data. Clinical examples which demonstrate the flexibility of these programs are provided. The programs may also be employed for fitting data for any drug that can be adequately described by a one-compartment linear model.

Topics: Adult; Aged; Amikacin; Aminophylline; Asthma; Atrial Fibrillation; Computers; Digoxin; Female; Humans; Leukemia; Male; Microcomputers; Pharmaceutical Preparations; Regression Analysis; Software

It has earlier been shown that verapamil given intravenously or orally in sufficiently high single doses, may result in regular ventricular rhythm in patients with atrial fibrillation. We have analyzed whether this effect of verapamil can be utilized in long-term oral treatment. Eleven patients with lone atrial fibrillation were studied. Verapamil was given in gradually increasing doses from 40 mg three times a day to 320 mg three times a day, either alone or in combination with digoxin. Resting ECG was recorded and supine and standing blood pressures were measured on each dose level. When the patients were treated with verapamil alone, only a slight decrease in heart rate was noted, while during combined treatment with verapamil and digoxin a more marked heart rate decrease occurred with increasing doses of verapamil. The variation coefficient of the RR interval, a sign of ventricular regularity, decreased during verapamil treatment regardless of whether or not digoxin was also taken. A dose-dependent blood pressure decrease was noted during verapamil treatment. Side effects were common and led to discontinuation of the attempted protocol in all patients. Three patients were unexpectedly converted to stable sinus rhythm. Five patients improved subjectively, with a marked decrease in the sensation of palpitations during intake of increasing doses of verapamil. The study indicates that chronic oral treatment with verapamil may sometimes relieve the subjective sensation of palpitations in patients with atrial fibrillation. Side effects do, however limit the value of this mode of treatment in the majority of patients.

Topics: Administration, Oral; Adult; Atrial Fibrillation; Digoxin; Drug Interactions; Heart Rate; Humans; Male; Middle Aged; Verapamil

Topics: Atrial Fibrillation; Benzazepines; Digoxin; Diltiazem; Drug Interactions; Humans

Topics: Aged; Arrhythmia, Sinus; Atrial Fibrillation; Digoxin; Female; Humans; Male; Middle Aged

Topics: Aged; Amiodarone; Atrial Fibrillation; Benzofurans; Digoxin; Female; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction

Topics: Atrial Fibrillation; Circadian Rhythm; Digoxin; Drug Evaluation; Electrocardiography; Heart Rate; Humans; Isomerism; Male; Middle Aged

Topics: Atrial Fibrillation; Circadian Rhythm; Digoxin; Heart Rate; Humans; Male; Middle Aged

Forty-seven episodes of acute atrial fibrillation (AF) in 45 patients were examined prospectively to determine the course of the disorder treated with rapid digitalization. Patients received 1.5 mg of digoxin intravenously over 12 hours. In 40 of the 47 attacks, reversion to sinus rhythm occurred with no additional therapy at 1 to 96 hours (median 4 hours) after beginning digoxin. In thirty-two patients, conversion occurred within 8 hours; only one patient showed important ventricular slowing before conversion. Thus, if digoxin facilitates conversion, it does not do so by slowing the ventricular response. Of the 11 patients still in AF at 16 hours, conversion subsequently occurred in only four who were receiving digoxin alone. We conclude that the prognosis for quick reversion to sinus rhythm in patients with acute AF treated with rapid digitalization alone is excellent. If reversion does not occur by 16 to 24 hours, additional measures to restore sinus rhythm are indicated.

Topics: Acute Disease; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Middle Aged

Topics: Atrial Fibrillation; Digoxin; Electrocardiography; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia

We present two cases in which thrombocytopenia developed during low-dose heparin therapy. They seem to represent the spectrum of heparin-associated thrombocytopenia described by Carreras. Because of the increasing use of low-dose heparin for thromboembolism prophylaxis, and because patient reexposure to heparin is not uncommon, the identification of even a modest fall in platelet count in association with heparin therapy is important.

Topics: Aged; Atrial Fibrillation; Collateral Circulation; Digoxin; Electric Countershock; Female; Heparin; Humans; Platelet Count; Thrombocytopenia; Thrombosis; Time Factors

Topics: Atrial Fibrillation; Digoxin; Drug Interactions; Heart Ventricles; Humans; Kinetics; Verapamil; Wolff-Parkinson-White Syndrome

Although most cases of sustained atrial fibrillation are associated with mitral valve disease, hypertension, cardiac failure and atherosclerotic heart disease, some cases occur in the absence of any identifiable organic pathology. The consequences of atrial fibrillation include reduction in cardiac output, systemic emboli and an exaggerated ventricular response to exercise. In most clinical situations, digoxin is the drug of choice for controlling the ventricular response. Cardioversion should be undertaken in appropriately selected patients.

Topics: Age Factors; Aged; Atrial Fibrillation; Cardiomegaly; Digoxin; Electric Countershock; Electrocardiography; Heart Failure; Humans; Hypertension; Male; Middle Aged; Mitral Valve Stenosis; Myocardial Infarction; Verapamil

To investigate further the handling of digoxin by the kidneys during quinidine therapy, clearances of digoxin, 51Cr-EDTA, PAH and endogenous creatinine were measured together with beta 2-microglobulin in the urine before and during quinidine therapy in 10 patients on maintenance digoxin therapy. Renal clearance of digoxin (corrected for 30% plasma binding) decreased on the average by 55% (137 +/- 73 to 73 +/- 25 ml/min, mean +/- SD). The steady state plasma concentration of digoxin increased more than twofold (1 . 0 +/- 0 . 34 to 2 . 5 +/- 0 . 79 nmol/L, mean +/- SD). The clearances of 51Cr-EDTA and PAH were not altered during quinidine therapy, indicating that neither glomerular filtration nor total renal blood flow changed when quinidine was added. The ratio of the renal clearance of unbound digoxin to that of the glomerular filtration rate was above one for all 10 patients before quinidine, indicating the involvement of tubular secretion in the renal elimination of digoxin. After the administration of quinidine this ratio decreased in all patients (from 1 . 51 +/- 0 . 30 to 0 . 83 +/- 0 . 38, mean +/- SD). Some patients had ratios well below one suggesting re-absorption of digoxin. Beta 2-microglobulin excretion was unchanged during treatment with quinidine. It is concluded that a significant portion of the renal elimination of digoxin in man results from tubular secretion and that this excretory mechanism is inhibited by quinidine.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Quinidine

The effect of verapamil on the pharmacokinetics of digoxin was studied in 49 patients with chronic atrial fibrillation. A dose of 240 mg/day of verapamil was given to the patients who were receiving a stable dose of digoxin. Serum digoxin levels rose from 0.76 +/- 0.54 ng/ml (mean +/- SD) to 1.31 +/- 0.54 ng/ml during verapamil treatment (p less than 0.0005). This effect was dose-dependent, as shown in seven subjects who received 160 mg and then, 240 mg of verapamil: There was a stepwise rise in serum digoxin concentration from a control value of 0.60 +/- 0.11 ng/ml to 0.84 +/- 0.18 ng/ml and 1.24 +/- 0.40 ng/ml, respectively (p less than 0.01 for both steps). The effect of verapamil developed gradually within the first few days in seven subjects in whom serum digoxin concentration reached, within 7 days, 90% of the increase observed 14 days after onset of verapamil. Renal digoxin clearance decreased significantly (26.1 +/- 0.7 vs 55.1 +/- 12.3 ml/min, p less than 0.005) in six patients in whom serum digoxin concentration increased. It did not change in one patient in whom serum digoxin concentration was not influenced by verapamil. Creatine clearance did not change in any of these seven. The same effects on digoxin clearance were observed in three normal subjects. Among the 49 patients, verapamil resulted in the development of signs and symptoms that suggested digitalis toxicity in seven. Verapamil significantly increased serum digoxin concentration. The process is dose-dependent and gradual, and it is at least partially explained by reduced renal excretion without reduction in glomerular filtration. The dose of digoxin may need readjustment in patients who are concomitantly receiving verapamil.

Topics: Adult; Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Kidney; Kinetics; Male; Middle Aged; Verapamil

Topics: Administration, Oral; Atrial Fibrillation; Blood Pressure; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Infusions, Parenteral; Male; Middle Aged; Physical Exertion; Verapamil

Topics: Adult; Aged; Atrial Fibrillation; Chronic Disease; Circadian Rhythm; Digitoxin; Digoxin; Drug Therapy, Combination; Heart Rate; Humans; Medigoxin; Middle Aged; Pindolol; Propranolol

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Electric Countershock; Female; Heart Diseases; Humans; Male; Middle Aged; Tachycardia

Topics: Aged; Ambulatory Care; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Benzofurans; Digoxin; Humans; Middle Aged

We have measured the effects of digoxin on the cation transport mechanisms of patients' erythrocytes during treatment with digoxin for atrial fibrillation and cardiac failure in sinus rhythm. The results show that during short-term treatment with digoxin there is occupation of erythrocytic cardiac glycoside receptors by digoxin with resultant inhibition of active cation transport. These effects correlate well with the patients' clinical responses to treatment. During long-term treatment, however, these effects are not seen, suggesting that there is pharmacological tolerance to the effects of digoxin. The clinical implications of these results are discussed.

Topics: Atrial Fibrillation; Digoxin; Electrolytes; Erythrocytes; Heart Failure; Heart Rate; Hemodynamics; Humans; Ion Channels; Sodium-Potassium-Exchanging ATPase

While the principles of drug management of supraventricular tachyarrhythmias have remained essentially unchanged, such treatment remains empirical in many patients. Recent advances in the understanding of electrophysiological mechanisms have not only rationalised treatment but dictated newer approaches to these and other arrhythmias.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electric Countershock; Electrocardiography; Exercise Test; Heart Ventricles; Humans; Pacemaker, Artificial; Procainamide; Propranolol; Quinidine; Tachycardia

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Humans; Male; Middle Aged

Topics: Adult; Atrial Fibrillation; Digoxin; Drug Interactions; Humans; Middle Aged; Muscle, Smooth; Quinidine; Tissue Distribution

The influence of digoxin concentration in blood on its therapeutic effect was studied in 59 patients with chronic circulatory insufficiency and cardiac fibrillation and in 89 patients with chronic circulatory insufficiency and sinus cardiac rhythm. The changes in blood digoxin concentration in patients with cardiac insufficiency complicated by cardiac fibrillation with maintained sinus cardiac rhythm both during the "saturation" period and during maintenance treatment were of the same type. The content of digoxin in the blood does not determine the potency of its therapeutic effect. The optimum therapeutic effect of digoxin in all patients with cardiac fibrillation and signs of cardiac insufficiency persists for quite a long period of time. Continuously used cardiac glycosides lose their inotropic effect in patients with sinus cardiac rhythm.

Topics: Adult; Aged; Arrhythmia, Sinus; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Aged; Atrial Fibrillation; Digoxin; Echocardiography; Electrocardiography; Female; Fluoroscopy; Heart Ventricles; Humans; Mitral Valve Prolapse; Mitral Valve Stenosis; Radionuclide Imaging; Warfarin

Topics: Aged; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Humans; Hypokalemia; Male

Topics: Adult; Aged; Atrial Fibrillation; Diazepam; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Myocardium; Saliva; Spironolactone

Results of studies of 15 adults placed on quinidine therapy after their serum digoxin concentrations were stabilized showed significantly increased digoxin concentrations. The average digoxin concentration before quinidine therapy was 0.75 +/- 0.28 ng/mL and after 4 days of quinidine therapy was 1.41 +/- 0.43 ng/mL. During this period, the renal clearance of digoxin decreased from 53.4 +/- 21 mL/min . 1.73 m to 35.3 +/- 12.6 mL/ min . 1.73 m. No significant correlation was found between the individual rise in serum digoxin concentrations and the rise in serum quinidine concentrations. These results suggest that serum digoxin concentration should be monitored closely for at least the first 4 days of quinidine therapy.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Heart Failure; Heart Ventricles; Humans; Middle Aged; Prospective Studies; Quinidine; Tachycardia, Paroxysmal

Topics: Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Interactions; Humans; Male; Middle Aged; Propranolol; Sweating

Topics: Adult; Aged; Ambulatory Care; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis Glycosides; Digoxin; Humans

Serum, right atrial myocardium and skeletal muscle collected from 32 adult patients undergoing open heart surgery were analyzed for digoxin by radioimmunoassay. Preoperatively 20 patients were in sinus rhythm, but not in patients with atrial fibrillation, there was a highly significant correlation between digoxin concentration in serum and right atrial myocardium, in skeletal muscle and right atrial myocardium, and in serum and skeletal muscle. The means and variances of the ratios right atrial myocardium/serum and right atrial myocardium skeletal muscle were significantly higher in patients with atrial fibrillation than in those with sinus rhythm. This, plus the lack of difference in ratios skeletal muscle serum between these groups of patients, indicate increased right atrial digoxin binding in atrial fibrillation in man. This conclusion is further supported by the finding of similar or higher digoxin concentration in right atrial myocardium than in left ventricular myocardium in atrial fibrillation (6 patients), and a lower digoxin concentration in right atrial myocardium than in left ventricular myocardium in sinus rhythm (3 patients).

Topics: Adult; Aged; Arrhythmia, Sinus; Atrial Fibrillation; Cardiac Surgical Procedures; Creatinine; Digoxin; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Muscles; Myocardium; Potassium

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Aged; Atrial Fibrillation; Digoxin; Female; Humans; Male; Middle Aged; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: Adrenergic beta-Antagonists; Ajmaline; Amiodarone; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Pacing, Artificial; Digoxin; Disopyramide; Electric Countershock; Humans; Phenytoin; Procainamide; Quinidine; Tachycardia; Tachycardia, Paroxysmal; Verapamil

In isolated perfused guinea-pig hearts, digoxin produced a concentration dependent release of creatine kinase (ATP-creatine-transphosphorylase; CK). A corresponding decrease of the CK activity in the myocardium was obtained. The enzyme release seems to be a sign of glycoside intoxication, as its extent paralleled the severity of digoxin induced arrhythmias. Especially high CK activities were liberated when ventricular fibrillation occurred. Likewise, electrically induced fibrillation, in control hearts, led to enzyme release. However, the digoxin effect was not matched. Reserpine pretreatment antagonized the CK release by electrical fibrillation, whereas it increased excessively the enzyme liberating effect of higher digoxin concentrations. Also, propranolol decreased the enzyme release due to electrical fibrillation. The glycoside induced CK liberation, however, was not diminished, although the ventricular fibrillation was prevented. Increase of the potassium concentration of the perfusion fluid prevented the glycoside induced fibrillation, and reduced the enzyme release. The significance of the enzyme loss from the myocardium, and the mechanisms of enzyme release are discussed.

Topics: Adrenergic beta-Antagonists; Animals; Atrial Fibrillation; Creatine Kinase; Digoxin; Female; Guinea Pigs; Heart; In Vitro Techniques; Male; Myocardium; Potassium; Reserpine

Topics: Aged; Atrial Fibrillation; Digoxin; Heart Rate; Humans

On the patients with moderate and severe heart insufficiency haemodynamic, clinical and electrocardiographic examinations were carried out. After the application of digitoxin at the beginning in the majority of cases no favourable effects on clinical and haemodynamic findings could be proved. In 2 patients with cor pulmonale even a drastic deterioration with increase of the pulmonary pressure and formation of a pulmonary oedema developed. The temporary analysis of the systole and the estimation of the glycoside level did not give any reliable references. The recompensation began only after 2-3 days. In 5 out of 10 patients in whom the cardiac rhythm was continuously controlled by means of a tape storage device, after the application of digoxin ventricular extrasystoles appeared. Also in these cases increased as well as subtherapeutic digoxin-plasma levels were present. In 2 patients with hypertrophic obstructive cardiomyopathy the infundibular gradients were considerably increased by strophantin. The causes of the different reaction patters are to be sought in disease-specific peculiarities, in the degree of severity of the heart insufficiency, in the speed of the flooding of glycoside and several extracardiac factors.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Pressure; Cardiac Complexes, Premature; Cardiomyopathy, Hypertrophic; Digitalis Glycosides; Digoxin; Female; Heart; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Edema; Pulmonary Heart Disease

Accelerated quinidine metabolism was observed in a 94-year-old woman also receiving daily doses of digoxin and pentobarbital sodium. Discontinuation of pentobarbital produced a sharp increase in serum digoxin concentrations coupled with symptoms highly suggestive of digoxin toxicity. Associated with these findings was 3.8-fold increase in quinidine half-life. These data seemed consistent with an interaction between quinidine and digoxin that was precipitated by pentobarbital withdrawal.

Topics: Aged; Atrial Fibrillation; Digoxin; Drug Interactions; Female; Half-Life; Humans; Liver; Pentobarbital; Quinidine; Sleep Wake Disorders

Topics: Adult; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Heart Rate; Humans; Male; Medigoxin; Middle Aged; Physical Exertion; Rest

We examined digoxin-prescribing in 47,000 prescriptions written predominantly by physicians in a large family medicine practice. Two hundred fifty-four patients received 511 digoxin prescriptions. Dose adjustments for age (16% decrease in patients older than 64 years), for renal disease (33% decrease), and for atrial fibrillation (39% increase) followed good prescribing practices. Appropriately lower loading doses were used for digitalization. However, despite continuing concern over the bioavailability of generic digoxin tablets, less than 40% of digoxin prescriptions in this study were written for the innovator's brand-name product (Lanoxin).

Topics: Adult; Age Factors; Aged; Atrial Fibrillation; Digoxin; Female; Humans; Kidney Diseases; Male; Middle Aged; Therapeutic Equivalency

Digitalis preparations frequently fail to control heart rate in many patients who have chronic atrial fibrillation, particularly during physical exertion. The effects of orally administered verapamil, 160 to 240 mg/day, on the heart rate at rest and during mild exercise were studied in 23 digitalized patients with chronic atrial fibrillation of various causes. Verapamil substantially reduced the excessive heart rate response to exercise in well-digitalized patients who had chronic atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Verapamil

The association between steady-state serum digoxin concentrations and control of ventricular response rate (VRR) was studied in 53 consecutive patients with atrial fibrillation. Decreases in VRR were significantly correlated with serum digoxin (rs = -0.22, P less than 0.05). Clinical responses were appropriate to serum digoxin concentrations in 37 patients (69.8%) and were inappropriate in 16 (30.2%) (P less than 0.05). Complicating clinical factors were present in all eight patients with inappropriate responses to therapeutic serum digoxin (0.5 to 2.0 ng/ml) (P = 0.046), but were also found in many patients with appropriate responses and thus could not serve to differentiate between the two categories. Digitalis intoxication occurred in one of the three patients with a concentration of serum digoxin greater than 2 ng/ml (P = 0.056). In 30% of our patients with atrial fibrillation, monitoring of serum digoxin was of value in identifying inappropriate therapeutic responses indistinguishable by clinical means and in defining the subgroup of refractory cases, which allows the prevention of digitalis intoxication.

Topics: Atrial Fibrillation; Digoxin; Female; Humans; Male; Middle Aged

Topics: Aged; Atrial Fibrillation; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Quinidine

1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocytic 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of patients receiving digoxin in the short-term for atrial fibrillation or cardiac failure in regular rhythm. 2 During the first few days of treatment [3H]-digoxin binding and 86rubidium uptake fall and intraerythrocytic sodium concentrations rise. 3 Subsequently parallel fluctuations occur in [3H]-digoxin binding and 86rubidium uptake but not in intraerythrocytic sodium concentrations and the significance of the fluctuations is discussed. 4 The values of all three measurements correlate significantly with the response of the heart in sinus rhythm as measured by QS2I. 5 Plasma digoxin concentrations do not correlate with QS2I.

Topics: Adult; Aged; Atrial Fibrillation; Cardiac Glycosides; Digoxin; Erythrocytes; Female; Heart Failure; Humans; Male; Middle Aged; Radioisotopes; Receptors, Drug; Rubidium; Sodium; Time Factors

A patient with chronic paroxysmal atrial fibrillation, receiving maintenance doses of digoxin, was admitted for addition of quinidine therapy. With stable serum digoxin levels, the institution of oral quinidine sulfate resulted in a rise in the serum digoxin level in less than 24 hours. The serum digoxin concentration increased more than threefold before digoxin was discontinued. The rise and fall of the digoxin serum concentration appeared to correlate directly with an increase and decrease in the PR interval. With the reinstitution of digoxin at lower doses, apparently stable therapeutic levels of both digoxin and quinidine were achieved. However, discontinuation of quinidine alone was followed by a prompt fall in the serum digoxin level. This study demonstrates that quinidine produces a significant increase in the serum digoxin level. The increased digoxin concentration appears to correlate with enhanced electrophysiologic effects of digoxin and emphasizes the caution required when these two drugs are used simultaneously.

Topics: Atrial Fibrillation; Digoxin; Drug Synergism; Drug Therapy, Combination; Humans; Male; Middle Aged; Quinidine

A newborn baby shows atrial tachycardia and gets into cardiac failure by atrial fibrillation at 12 weeks of age. With digoxin and chinidin spontaneous conversion to multifocal atrial tachycardia occurs. Treatment with additional propranolol leads to atrial fibrillation and paroxysmal atrial tachycardia with block. When chinidin was discontinued atrial flutter occurred. With a maintenance therapy with digoxin and chinidin the baby remained asymptomatic, and sinusrhythm occurred at 6 months of age. At 9 months chinidin was discontinued. At 14 months of age, the child is well and in sinusrhythm with a maintenance digoxin therapy. This seems to be the third described case of multifocal atrial tachycardia in infancy.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Heart Rate; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Propranolol; Quinidine; Tachycardia; Tachycardia, Paroxysmal

Topics: Adult; Arrhythmia, Sinus; Atrial Fibrillation; Binding Sites; Digoxin; Heart Atria; Humans; Muscles; Myocardium

Fifty-eight patients with atrial fibrillation treated with digoxin were studied to determine the correlation between serum digoxin levels and the ventricular rate. The study was a computer-based exercise, processing a signal consisting of R-R intervals, derived by point-digitising electrocardiograms. The means, variances and centers of gravity of power-spectra from the signal were correlated with serum digoxin levels, the peripheral pulse and with each other. A poor negative correlation of -0.31 was calculated between the means of interbeat-intervals and serum digoxin levels. Other Ecg-derived rate parameters did not correlate any better with serum digoxin. The mean interbeat-interval in a group of patients with higher serum digoxin levels (2 ng/ml) was significantly (p is less than or equal to 0.05) shorter than in a group with a low level (1 ng/ml). The negative correlation and this significant difference are best explained by the gradual increase in the dose administered to non-responders by the attending physicians who did not fear over-dosage because of frequent serum level determinations. It is concluded that the serum digoxin level is a poor predictor of the ventricular rate in patients with atrial fibrillation because of marked individual differences. These are due to the poor representation by serum levels of drug concentration at the point of interest (A-V node) and the non-linearity of the chronotropic effect of digitalis.

Topics: Adult; Aged; Atrial Fibrillation; Atrioventricular Node; Computers; Digoxin; Electrocardiography; Female; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged

To assess atrial and ventricular rate changes after lidocaine injection, 18 atrial flutter patients and 35 atrial fibrillation patients were given intravenous lidocaine, mean dose 100 mg. Continuous electrocardiographic recording for 5 minutes before and at least 10 minutes after lidocaine injection was used to determine rate changes. The atrial flutter rate decreased after lidocaine in 17 of 18 patients (94 per cent), mean maximal decrease 27 beats/minute. The ventricular rate response in atrial flutter was variable but in three patients increased 21, 27, and 47 beats/minute respectively (P less than 0.001). In atrial fibrillation, the mean ventricular rate after rapid lidocaine injection increased six beats/minute (P less than 0.01). In three of 35 atrial fibrillation patients (9 per cent), the ventricular rate increase was greater than 20 beats/minute (P less than 0.001), and in two patients (6 per cent), the ventricular rate increase was associated with potentially serious clinical events. Lidocaine-induced ventricular rate increases are common in atrial flutter and fibrillation, particularly in patients who are also receiving quinidine.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Interactions; Electrocardiography; Heart Rate; Heart Ventricles; Humans; Lidocaine; Middle Aged; Potassium; Quinidine

An assessment was made of the clinical value of routine periodic measurement of serum digoxin levels in 51 elderly nursing home patients with cardiac disease. The findings showed that the serum digoxin level was not correlated with the dosage of digoxin nor the patient's clinical state of digitalization. All patients were effectively digitalized, as judged clinically, and no digitalis toxicity occurred despite a wide range of serum digoxin levels. When adequate medical supervision, electrocardiograms, roentgenograms, serum electrolyte determinations and renal function tests are available, the routine periodic measurement of serum digoxin concentration does not offer any additional benefit in the management of nursing home patients with cardiac disease.

Topics: Aged; Atrial Fibrillation; Digoxin; Heart Failure; Humans; Middle Aged; Nursing Homes

The purpose of this study was to determine if there is a linear relationship between oral doses of digoxin and various measurements of steady-state digoxin plasma concentration and urinary excretion in patients with wide range of renal function. Ten patients (mean age 58 years) with creatinine clearances greater than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 80 ml/min/1.73 m2 BSA) and nine patients mean age 61 years) with creatinine clearances less than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 20 ml/min/1.73 m2 BSA) were given digoxin tablets orally at two or three different dose levels (dose range 0.0313--0.5 mg/day). After a dosing period equal to at least five half-lives, three to four consecutive daily digoxin plasma concentrations were determined. Plasma concentrations and urinary digoxin excretion were measured during one 24-hour dosing interval at each dose level. Digoxin plasma and urine concentrations were determined in triplicate using radioimmunoassay. Individual patient plots provided evidence of linearity for: digoxin 24-hour steady-state plasma concentration vs dose; digoxin 24-hour cumulative urinary excretion versus dose; and area under the digoxin plasma concentration-time curve during a 24-hour dosing interval vs dose. Absolute values for these various parameters indicated substantial interpatient variation probably due to patient differences in both digoxin absorption and digoxin total body clearance. These results indicate that there is a linear relationship between digoxin plasma concentration and dose in patients with normal and decreased renal function. This linearity is support for dose-independent pharmacokinetics of digoxin in man. We conclude from these data that a change in digoxin dose should result in a proportional change in digoxin plasma concentration over the dose range examined.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Tablets; Time Factors

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Humans; Male; Middle Aged

Topics: Adult; Atrial Fibrillation; Digoxin; Disopyramide; Humans; Male; Organophosphorus Compounds; Refractory Period, Electrophysiological; Wolff-Parkinson-White Syndrome

Forty patients with atrial fibrillation and 20 patients with congestive heart failure and sinus rhythm were studied. Patients were divided into two groups. Group A consisted of 20 patients with atrial fibrillation in whom systolic time intervals were measured. Twenty to 50 beats were analyzed. Five of the patients had high-fidelity measurements of left ventricular pressure simultaneous with determination of systolic time intervals. Analysis of the systolic time intervals for the entire group showed that the preejection period lengthened at faster heart rates and that the left ventricular ejection time was relatively constant at slower heart rates. This resulted in a progressive increase in the ratio of preejection period over left ventricular ejection time (PEP/LVET) as the heart rate increased. The rate of increase in PEP/LVET was minimal below a heart rate of 75 beats per minute. The increase in preejection period at faster heart rates is due to greater isovolumic developed pressure without a corresponding increase in left ventricular dp/dt. Group B consisted of 40 additional patients (20 with atrial fibrillation and 20 with sinus rhythm). In group B, the total electromechanical systole corrected for heart rate (QS2I) and the levels of digoxin in the blood were compared. The QS2I was significantly shorter in atrial fibrillation (497 +/- 5 msec vs 528 +/- 4 msec; P less than 0.01), while the levels of digoxin in the blood were identical (0.9 +/- 0.1 vs 1.0 +/- 0.1 ng/ml). The results of this study must be considered when systolic time intervals are to be employed in patients with atrial fibrillation.

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Female; Heart Failure; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Contraction; Systole

A novel benzanilide derivative, MJ 9067, has been shown to abolish experimental atrial and ventricular arrhythmiase effectively and promote the return of normal sinus rhythm in a variety of animal models. At intravenous dose levels ranging from 0.5 to 3.2 mg/kg, MJ 9067 successfully converted atrial fibrillation induced by either local application of aconitine or electrical stimulation, and ventricular tachycardia elicited by intravenous injection of ouabain or digoxin. The compound was equally effective in vagotomized or nonvagotomized dogs, and in intact cats and monkeys. The ventricular ectopic rate in conscious dogs 18 to 20 hours after two-stage ligation of a coronary artery was also markedly reduced by the drug at 2 mg/kg i.v. At antiarrhythmic dose levels, there were no undesirable effects noted on peripheral blood pressure, heart rate or the configuration of the electrocardiogram.

Topics: Aconitine; Anilides; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Pressure; Cats; Digoxin; Dogs; Electric Stimulation; Electrocardiography; Female; Haplorhini; Heart Rate; Male; Ouabain; Piperidines; Saimiri; Tachycardia

Eighteen patients with atrial fibrillation were given digoxin 0.13 mg twice daily for 3 weeks and beta-methyldigoxin 0.10 mg twice daily for another 3 weeks. At the end of each 3 week period an exercise test was performed and the effects on the heart rate of the two drugs were compared. No difference in heart rate was obtained at rest, whereas the heart rate after 6 min of exercise was higher during treatment with digoxin (131 beats/min) than when the patients were taking beta-methyldigoxin (124 beats/min). There were no significant differences between digoxin and beta-methyldigoxin in their effects on the ECG (R-R intervals, T-wave, Q-T duration). The plasma concentrations of the two glycosides were determined by radioimmunoassay and by 86Rb-uptake inhibition assay. Comparable plasma concentration values (1.0 ng/ml for digoxin, 1.1 ng/ml for beta-methyldigoxin, mean values) were obtained by radioimmunoassay, but the 86Rb-technique gave significantly higher values (mean 1.5 ng/ml) for beta-methyldigoxin. It is concluded that beta-methyldigoxin is equal to digoxin for producing slowing of the heart rate in patients with atrial fibrillation.

Topics: Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Exercise Test; Female; Heart Rate; Humans; Kinetics; Male; Middle Aged

This report describes the case of a patient with a supraventricular tachycardia with a ventricular rate of 109/min and no visible P waves in the electrocardiogram. The recording of the monophasic action potential of the right atrium disclosed an atrial tachycardia with a rate of 218/min. There was an alternans of the phase 2 of repolarisation in the action potential. This report emphasises the fact that the phenomenon of alternans occurs in man, as in the experimental animal, at a cellular level.

Topics: Action Potentials; Aged; Atrial Fibrillation; Digoxin; Heart Atria; Heart Block; Humans; Male; Tachycardia

Topics: Aged; Atrial Fibrillation; Digoxin; Humans; Tachycardia

Twenty-three elderly patients with normal renal function were studied during digitalisation for cardiac failure or atrial fibrillation. Mean serum digoxin concentrations were in the therapeutic range from the fourth day in seven patients given digoxin 0.25 mg daily, from the second day in seven patients given 0.5 mg followed by 0.25 mg daily, and from the first day in nine patients given 0.75 mg followed by 0.25 mg daily. Toxic effects were not encountered in any patient. Serial measurement of serum digoxin concentrations in six patients recovering from digitalis intoxication, all of whom had severe renal impairment, allowed calculation of serum half-times (62 to 189 hours), and elimination constants (9 to 27% per day). The apparent volumes of distribution of digoxin were around 300 litres, and the apparent body contents of the drugs around 20-25 mug/kg body weight. Differences between these figures and those determined by others for younger patients seem mainly to reflect the consequences of renal impairment. If reasonable assumptions are made for fractional absorption, volume of distribution, and elimination constant, serum digoxin levels during digitalisation can be predicted, and are found to agree well with those observed.

Topics: Aged; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Half-Life; Heart Failure; Humans; Metabolic Clearance Rate; Middle Aged

Topics: Aged; Atrial Fibrillation; Digoxin; Humans

Topics: Aged; Atrial Fibrillation; Calcium; Digoxin; Drug Resistance; Humans; Hypocalcemia; Male

Topics: Amphotericin B; Atrial Fibrillation; Candidiasis; Digoxin; Embolism; Endocarditis; Female; Flucytosine; Heart Valve Prosthesis; Humans; Middle Aged; Mitral Valve; Warfarin

In many patients with chronic atrial fibrillation, it is difficult to prevent an excessive ventricular rate under stress, even with high levels of digoxin in the blood. The effect of adding beta-adrenergic blockade with practolol to digoxin on the heart rate at rest and during low-grade controlled exercise was investigated in 28 patients with chronic atrial fibrillation and in ten normal control subjects who were receiving maintenance dosages (0.25 to 0.75 mg) of digoxin. In atrial fibrillation, therapy with practolol decreased the mean heart rate at rest from 99.8 beats per minute to 77.5 beats per minute (23 percent reduction; P less than 0.01) and during mild exercise from 148.9 beats per minute to 105.4 beats per minute (29 percent) reduction (P less than 0.001). Fifteen patients had clinically significant heart failure; therapy with practolol did not worsen it. Reversible side effects were detected in two patients. When therapy with digoxin is not sufficient to control atrial fibrillation, the addition of a beta-adrenergic blocking agent is recommended as adjunctive treatment in selected patients.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Chronic Disease; Digoxin; Drug Evaluation; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Physical Exertion; Practolol

Atrial fibrillation (AF) characteristically results in random variation of the intervals between successive ventricular depolarizations. However, when a patient with AF is treated with excessive amounts of digitalis, regular junctional rhythms may occur. The detection of "regularization" of the ventricular rhythm in patients with AF may signal early digitalis toxicity. In this paper, we describe a new method for quantifying the extent of ventricular regularization by the statistical analysis of the intervals between successive ventricular depolarizations (R-R intervals). This method yields a single index (Z score) which reflects the degree to which a sequence of R-R intervals deviates from a random distribution. Simulation studies demonstrate that our method is sensitive to "regularization" of as little as two to four percent of R-R intervals, even when equal intervals occur in small groups that might easily escape detection by visual electrocardiographic interpretation. Analysis of records from six nondigitalized subjects in AF shows that the sequence of R-R intervals is usually random, or very nearly so. Records obtained from the same patients when digitalized often demonstrate more regularized activity, reflected by an index (Z score) which is higher than expected from chance deviation if a random process is assumed. Preliminary data also suggeest that exercise is associated with substantial regularization of ventricular depolarization.

Topics: Atrial Fibrillation; Atropine; Digoxin; Electrocardiography; Humans; Models, Biological; Physical Exertion

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Humans; Middle Aged

The effect of digitalis in 21 patients with Wolff-Parkinson-White syndrome was anlayzed with respect to the ventricular response during atrial fibrillation and antegrade and retrograde refractory periods of accessory pathways. Digitalis shortened the cycle length of the most rapid ventricular response (shortest R-R) (i.e., increased the ventricle response) in 6/21 patients, increased the cycle length in 7/21 patients, had no effect on the cycle length in 5/21, and could not be determined in 3/21. Digitalis could be directly related to the onset of ventricle fibrillation resulting from atrial fibrillation in 9/21 patients. Each of these patients had shortest R-R intervals (220 msec or less) during atrial fibrillation in the control data. The results of this study indicate that no a priori prediction about the effect of digitalis on the antegrade conduction of accessory pathways can be made. By elective induction of atrial fibrillation it is possible to separate WPW patients into groups at high and low risk for developing ventricular fibrillation with the administration of digitalis.

Topics: Adolescent; Adult; Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Wolff-Parkinson-White Syndrome

The structure of cardiac rhythm was studied with the help of specialized computers during digitalization in 60 patients with atrial fibrillation of different etiology. The reduction of the heart contractions rate under digitalization is accompanied by certain changes in the structure of cardiac rhythm: the arrhythmic pattern of the ventricular contractions increases with a predominant growth of the number of long R--R intervals, the transitions from short intervals to longer ones become sharper, and portions of a relatively stable ventricular rhythm appear. Three main types of dynamics of the rhythm structure were distinguished on the basis of the changes in the interval R--R histogram. The described changes in the structure of cardiac rhythm are not specific, but when Digitalis drugs are used alone they can be used as additional criteria for digitalization.

Topics: Adult; Aged; Atrial Fibrillation; Atrioventricular Node; Coronary Disease; Digoxin; Electrocardiography; Heart Conduction System; Humans; Hyperthyroidism; Middle Aged; Rheumatic Heart Disease

The influence of practolol or verapamil on the activity of digoxin in atrial fibrillation has been studied in 16 hospitalized patients by determining plasma levels of the cardiac glycoside and its effects on the ventricular rate, before and during the association with each of the above drugs. Digoxin alone (0.25 mg/day p.o.) demonstrated a rather feeble activity, giving a satisfactory control of ventricular rate in only 3 patients. The association with low doses of practolol (50 or 100 mg twice a day p.o.) or with verapamil (80 mg three times a day p.o.) clearly improves the effects of digoxin. The action both of practolol and of verapamil is related to the pre-existing ventricular rate, the tachycardic patients being the most sensitive ones.

Topics: Aged; Atrial Fibrillation; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Practolol; Time Factors; Verapamil

Topics: Adult; Aged; Amiodarone; Atrial Fibrillation; Atrial Flutter; Benzofurans; Digoxin; Female; Humans; Male; Middle Aged; Myocardial Infarction; Pulmonary Heart Disease; Rheumatic Heart Disease

Topics: Ajmaline; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Heart Rate; Heart Ventricles; Humans; Lidocaine; Practolol; Procainamide

A patient with chronic atrial fibrillation developed hyperthyroidism. Increasing doses of digoxin were required to maintain satisfactor ventricular rate control. The systemic availability of oral digoxin was decreased in this patient. The metabolism of digoxin was studied in the hyperthyroid rats. The plasma digoxin concentrations were significantly decreased in the hyperthyroid rats. A threefold increase in digoxin excretion in the bile of the hyperthyroid rats was associated with these changes in plasma digoxin concentrations. Conversely, hypothyroid rats excreted less digoxin in the bile when compared with control and hyperthyroid rats. Thus, changes in digoxin absorption and its biliary excretion result, in part, in a decreased therapeutic effect of digoxin based on dose in hyperthyroidism.

Topics: Animals; Atrial Fibrillation; Bile; Digoxin; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Rats

Topics: Atrial Fibrillation; Digoxin; Heart Failure; Humans

Patient-controlled rapid atrial pacing was used to manage 12 cases of recurrent supraventricular tachycardia refractory to drug therapy. The pacing system consists of an implanted receiver-lead system and an external patient-activated transmitter. In each case, brief periods (5 to 20 seconds) of rapid atrial pacing were effective in terminating the supraventricular tachycardia and resulted in a return to normal sinus rhythm. In three patients, occasional transient episodes of atrial flutter or atrial fibrillation preceded a spontaneous return to normal sinus rhythm. The pacing system was removed in one patient 13 months postoperatively because of persistent pericarditis; one patient died of an unrelated cerebral hemorrhage 13 months postoperatively. Successful management of supraventricular tachycardia has been maintained in the 10 remaining patients for 15 to 36 months (average 26.4). In more than 6,000 patient applications of rapid atrial pacing, there has been only one failure to convert the tachycardia. Successful application of permanent rapid atrial pacing requires (1) prescreening of patients with temporary external rapid atrial pacing to verify susceptibility to conversion of supraventricular tachycardia and absence of anomalous conduction pathways that may permit conduction of rapid pacing rates to the ventricles, and (2) assessment of the patient's ability to use the transmitter properly.

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Heart Rate; Humans; Male; Middle Aged; Pacemaker, Artificial; Procainamide; Propranolol; Recurrence; Self-Help Devices; Tachycardia, Paroxysmal; Wolff-Parkinson-White Syndrome

The clinical course, through pregnancy and delivery, of a 30-year-old woman with rheumatic heart disease and a prosthetic mitral valve is presented. Despite maternal development of congestive cardiac failure and atrial fibrillation, the delivery of a healthy infant was achieved. The problems encountered during pregnancy and delivery in patients with rheumatic heart disease and prosthetic valves are discussed. These include the management of long-term anticoagulant therapy, prophylaxis against rheumatic fever and subacute bacterial endocarditis, impaired cardiac function, atrial fibrillation, breast feeding, and contraception as they relate both to the mother and the fetus and infant.

Topics: Adult; Atrial Fibrillation; Breast Feeding; Digoxin; Endocarditis, Subacute Bacterial; Female; Fetus; Heart Failure; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Penicillin G Benzathine; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Rheumatic Fever; Rheumatic Heart Disease; Sulfadiazine; Warfarin

Topics: Aged; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Middle Aged; Practolol; Time Factors

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Practolol

Clinical, electrocardiographic and laboratory data were found out in 52 patients with cardiac arrhythmias and conduction defects due to digoxin intoxication. Forty six nontoxic patients were also studied for comparison. Blood urea concentration was significantly higher in toxic patients as compared to nontoxic ones (P less than 0-01). Ventricular bigeminy and trigeminy (38.6%), multifocal ventricular premature beats (25%) and second or third degree A-V blocks (25%) were very much prevalent. Fairly good correlations have been observed between different cardiac arrhythmias and serum digoxin levels. Significantly higher mean serum digoxin levels were observed in patients with A-V block and multifocal ventricular premature beats as compared to patients with supraventricular arrhythmias.

Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Heart Block; Heart Failure; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia; Ventricular Fibrillation

The pharmacokinetic parameters for a two compartment open model were defined for six patients receiving a wide range of Digoxin doses. It was demonstrated that the two compartment model is a valid one to use for Digoxin pharmacokinetics. This model is an useful concept because it can explain the necessity to vary Digoxin dosage in patients with different body weights, the time course of the effect of Digoxin and certain causes of increased tolerance to Digoxin. There were no alterations in the parameters of this model or of the percent of an injected Digoxin dose excreted in the urine and stool in our patients in atrial fibrillation who appeared to require larger doses to control their ventricular rates. This also suggests that the kinetics of excretion of Digoxin are not influenced by altering the Digoxin dose.

Topics: Atrial Fibrillation; Digoxin; Feces; Female; Humans; Kinetics; Male; Middle Aged; Models, Biological; Time Factors

Topics: Atrial Fibrillation; Digoxin; Heart Rate; Humans; Nausea; Radioimmunoassay; Vomiting

Although therapeutic and toxic serum concentrations of digoxin have been established, there is sparse information permitting correlation of drug level with clinical effect. This study was undertaken to assess the radioimmunoassay serum digoxin levels in 30 patients with acute atrial fibrillation (38 determinations) and 30 patients with chronic atrial fibrillation (54 determinations). Those with chronic fibrillation were subdivided into those in clinically stable condition (14 patients), and those seriously ill and in clinically unstable condition (16 patients). Slowing of ventricular rate in patients with stable, chronic atrial fibrillation was accomplished in 10 of 16 instances by "therapeutic" and "subtherapeutic" levels of digoxin (less than 2 ng/ml). Ventricular rate was "controlled" (65 to 95 beats/min) with therapeutic levels of serum digoxin in only five instances of acute atrial fibrillation and seven of unstable chronic atrial fibrillation. In 43 studies (23 of acute atrial fibrillation, 20 of chronic atrial fibrillation), a rapid ventricular rate (95 to 140 beats/min) persisted in the presence of "therapeutic" or high levels of digoxin. Thirty-nine of these were in patients who were seriously ill with conditions such as infection, hypoxia or recent thoracotomy. Slowing of the ventricular rate required "toxic" concentrations of digoxin (2.5 to 6 ng/ml) in 15 instances. We conclude that sufficient amounts of digoxin to achieve "therapeutic" serum concentrations may fall to lower the ventricular rate in atrial fibrillation to less than 100 beats/min, especially when a serious, complicating illness coexists.

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Dose-Response Relationship, Drug; Drug Evaluation; Heart Rate; Heart Ventricles; Humans

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis Glycosides; Digoxin; Female; Humans; Male; Middle Aged; Tachycardia

Serum digoxin estimations were done in 98 patients receiving digoxin for heart failure of varied aetiology. Digoxin toxicity or the lack of it was determined on the basin of established electrocardiographic criteria. Fifty-two patients were classified as 'toxic' and 46 as 'non-toxic'. The difference is the mean digoxin levels between the two groups was highly significant (P less than 0.001). The mean serum digoxin level in 'non-toxic' patients was slightly higher than that found by other investigators. Fairly good correlations have been noted between different dosage schedules and various rhythm disturbances. Death was attributed to digoxin toxicity in only 2 patients who showed electrocardiographic evidence of intoxication at the time of death.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Radioimmunoassay

According to own experiences and after a review of the literature a survey of therapy of cardiac arrhythmias in infancy and childhood is given. In this age group most of the occurring cardiac arrhythmias are harmless and pass without serious circulatory disturbances. Therefore in these cases no specific treatment is necessary, except of course the treatment and management of the disease which is causing the arrythmia. This report is concerned more detailed with the therapy of rhythm disturbances which are life threatening or will become fatal if they continue untreated for a longer period. In spite of the therapeutic recommendations given we are aware of the fact that it is impossible to predict the success of therapy. This turned out to be so especially in the case of tachycardias. The difficulties in long-term management of postoperative heart block are mentioned. Antiarrhythmic drugs, their indications, efficacy, side-effects and contraindications are listed in separate tables ("FdM-Tabellen für die Praxis" Nr. 30/1975, Fortschr. Med. 93, 30: 1447, 1975).

Topics: Age Factors; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Child, Preschool; Digoxin; Electric Countershock; Heart Block; Humans; Infant; Metaproterenol; Pacemaker, Artificial; Tachycardia; Verapamil

Topics: Atrial Fibrillation; Bundle of His; Diagnostic Errors; Digoxin; Electrocardiography; Heart Rate; Humans; Male; Middle Aged; Sinoatrial Node

Topics: Atrial Fibrillation; Atrial Flutter; Atrioventricular Node; Child; Congenital Abnormalities; Delivery, Obstetric; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Infant; Infant, Newborn; Male; Pregnancy; Propranolol; Tachycardia, Paroxysmal; Wolff-Parkinson-White Syndrome

Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Humans; Male; Middle Aged; Prospective Studies

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis; Digoxin; Electric Countershock; Heart Block; Heart Ventricles; Humans; Lidocaine; Myocardial Infarction; Pacemaker, Artificial; Phenytoin; Phytotherapy; Plants, Medicinal; Plants, Toxic; Procainamide; Propranolol; Quinidine; Tachycardia; Tachycardia, Paroxysmal; Ventricular Fibrillation

Topics: Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Hemodynamics; Humans; Lidocaine; Male; Practolol; Procainamide; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Conduction System; Humans; Male; Pacemaker, Artificial; Tachycardia

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis Glycosides; Digoxin; Drug Synergism; Drug Therapy, Combination; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Lanatosides; Propranolol; Quinidine; Refractory Period, Electrophysiological; Tachycardia

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Diuretics; Electrocardiography; Exercise Test; Humans; Tachycardia

Topics: Aged; Atrial Fibrillation; Creatinine; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Radioimmunoassay; Urea

Topics: Aged; Atrial Fibrillation; Digitoxin; Digoxin; Electrocardiography; Female; Heart Arrest, Induced; Heart Conduction System; Humans; Ligation; Pacemaker, Artificial; Propranolol; Quinidine; Reserpine; Tachycardia

Topics: Atrial Fibrillation; Autopsy; Digoxin; Female; Heart Neoplasms; Humans; Immunoglobulin A; Middle Aged; Multiple Myeloma; Myocardium; Sinoatrial Node

Topics: Acidosis; Atrial Fibrillation; Bundle-Branch Block; Calcium; Colon, Sigmoid; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Humans; Hyperkalemia; Hypocalcemia; Hypokalemia; Infant; Potassium; Tachycardia; Urinary Diversion; Water-Electrolyte Balance

Topics: Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Heart Rate; Humans; Propranolol; Quinidine

Topics: Adult; Aged; Atrial Fibrillation; Bundle-Branch Block; Cardiac Complexes, Premature; Digoxin; Electrocardiography; Female; Heart Block; Heart Conduction System; Heart Diseases; Heart Failure; Humans; Male; Tachycardia

Topics: Adenocarcinoma; Aged; Atrial Fibrillation; Blood Transfusion; Cephalothin; Digoxin; Disseminated Intravascular Coagulation; Gangrene; Gastrointestinal Hemorrhage; Gentamicins; Heparin; Humans; Hydronephrosis; Hypothermia; Lymphatic Metastasis; Male; Prostatic Neoplasms; Pyelonephritis; Stomach Neoplasms; Vitamin K

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Myocardial Infarction; Pulse; Venous Pressure

Topics: Administration, Oral; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Electrocardiography; Heart Failure; Humans; Injections, Intravenous; Monitoring, Physiologic; Myocardial Infarction; Ouabain; Tachycardia, Paroxysmal

Topics: Administration, Oral; Atrial Fibrillation; Digoxin; Electrocardiography; Exercise Test; Half-Life; Heart Rate; Heart Ventricles; Humans; Male; Methods; Middle Aged; Physical Exertion; Radioimmunoassay; Rest; Time Factors

Topics: Atrial Fibrillation; Biopharmaceutics; Digitoxin; Digoxin; Half-Life; Humans; Tablets; Time Factors

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Digoxin; Female; Heart; Humans; Injections, Intravenous; Intestinal Absorption; Male; Methylation; Middle Aged; Time Factors

Topics: Age Factors; Atrial Fibrillation; Digoxin; Electrocardiography; Humans; Infant; Male; Recurrence

Topics: Adolescent; Adult; Aged; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Bradycardia; Cardiac Catheterization; Digoxin; Dogs; Electrocardiography; Electrodes, Implanted; Female; Functional Laterality; Heart Atria; Heart Conduction System; Humans; Male; Middle Aged; Ouabain; Pacemaker, Artificial; Tachycardia; Vagotomy

Topics: Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Heart Conduction System; Humans; Male; Tachycardia

Topics: Atrial Fibrillation; Biopharmaceutics; Digoxin; Humans

Topics: Adrenergic beta-Agonists; Aged; Atrial Fibrillation; Bradycardia; Cerebrovascular Disorders; Digitalis Glycosides; Digoxin; Heart Block; Heart Failure; Humans

A daily infusion of 500-1,000 ml of 50% glucose containing 100-120 units of soluble insulin and 100-120 mEq of potassium chloride per litre was given to six patients suffering from hyponatraemia and congestive cardiac failure resistant to digoxin and diuretic therapy. In two patients there was no response, but four showed a striking improvement with a sodium and water diuresis, a rise in plasma sodium level, and in two cases a reversion from atrial fibrillation to sinus rhythm. It is suggested that insulin, glucose, and potassium given by the intravenous route in adequate dosage forms a useful adjunct to the management of severe congestive heart failure.

Topics: Adult; Aged; Atrial Fibrillation; Blood Pressure; Body Weight; Digoxin; Diuresis; Diuretics; Female; Glucose; Heart Failure; Humans; Hyponatremia; Injections, Intravenous; Insulin; Male; Middle Aged; Natriuresis; Potassium; Potassium Chloride; Sodium

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Pindolol; Tachycardia; Tachycardia, Paroxysmal

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Catheterization; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Male; Methods; Middle Aged; Phenytoin; Procainamide; Propranolol; Quinidine; Tachycardia, Paroxysmal; Time Factors; Wolff-Parkinson-White Syndrome

Topics: Atrial Fibrillation; Digoxin; Erythrocytes; Heart Rate; Humans; Radioimmunoassay; Radioisotopes; Rubidium

Topics: Atrial Fibrillation; Calcium; Creatinine; Digoxin; Drug Tolerance; Female; Heart Rate; Humans; Magnesium; Male; Middle Aged; Potassium; Radioisotopes; Rubidium

Topics: Adult; Aged; Aortic Valve; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Blood Urea Nitrogen; Digoxin; Female; Heart Block; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Prospective Studies; Tachycardia, Paroxysmal; Tricuspid Valve; Ventricular Fibrillation

Topics: Angina Pectoris; Atrial Fibrillation; Bradycardia; Cardiac Catheterization; Diagnosis, Differential; Diagnostic Errors; Digoxin; Electrocardiography; Humans; Hyperthyroidism; Lidocaine; Male; Middle Aged; Myocardial Infarction; Procainamide; Tachycardia; Tachycardia, Paroxysmal; Thyroxine

Topics: Aged; Atrial Fibrillation; Digoxin; Edrophonium; Female; Heart Arrest; Humans; Neuromuscular Nondepolarizing Agents; Quaternary Ammonium Compounds

Topics: Adult; Aged; Antibody Specificity; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Cholesterol; Dehydroepiandrosterone; Digitoxin; Digoxin; Electrocardiography; Estradiol; Female; Heart Block; Heart Failure; Humans; Hydrocortisone; Male; Mathematics; Methods; Middle Aged; Progesterone; Radioimmunoassay; Tachycardia; Testosterone; Tritium

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Coronary Care Units; Digoxin; Heart Block; Humans; Monitoring, Physiologic; Myocardial Infarction; Ouabain; Pacemaker, Artificial

Topics: Administration, Oral; Animals; Atrial Fibrillation; Cardiac Catheterization; Digitoxin; Digoxin; Dog Diseases; Dogs; Electrocardiography; Glycosides; Heart Failure; Heart Function Tests; Heart Ventricles; Injections, Intravenous; Intestinal Absorption; Ventricular Function

Topics: Adult; Atrial Fibrillation; Digoxin; Heart Atria; Heart Block; Humans; Male; Myocarditis; Pacemaker, Artificial; Physical Exertion; Propranolol; Radio Waves; Remission, Spontaneous; Tachycardia; Tachycardia, Paroxysmal

Topics: Atrial Fibrillation; Digoxin

Topics: Atrial Fibrillation; Atropine; Digoxin; Electric Countershock; Humans; Male; Middle Aged; Mitral Valve Stenosis; Myocardial Infarction; Ouabain; Warfarin

Topics: Aged; Atrial Fibrillation; Digoxin; Epinephrine; Humans; Hyperthyroidism; Isoproterenol; Male; Middle Aged; Propranolol; Quinidine; Ventricular Fibrillation

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Complexes, Premature; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Block; Humans; Middle Aged; Poisoning; Tachycardia

Topics: Administration, Oral; Atrial Fibrillation; Digoxin; Humans; Radioimmunoassay; Time Factors

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Glycosides; Digitoxin; Digoxin; Heart Rate; Humans; Mathematics; Strophanthins; Tachycardia

Topics: Animals; Atrial Fibrillation; Digoxin; Humans; Methods; Rabbits; Radioimmunoassay; Tritium

Topics: Aged; Antibodies; Atrial Fibrillation; Digoxin; Humans; Intestinal Absorption; Radioimmunoassay

Topics: Atrial Fibrillation; Creatinine; Digitoxin; Digoxin; Dosage Forms; Glycosides; Heart Rate; Humans; Intestinal Absorption; Kidney; Kinetics; Liver; Thyroid Gland; Time Factors; Water-Electrolyte Balance

Plasma digoxin concentrations were measured by radioimmunoassay in 116 patients with atrial fibrillation on long-term oral treatment with the drug, and in 23 patients with digoxin toxicity. The mean concentrations were 1.4 ng./ml. and 3.1 ng./ml., respectively. Though an overlap occurred between the therapeutic and toxic ranges, toxicity is unlikely to occur below a level of 2 ng./ml. Plasma concentration showed a poor correlation with resting heart rate during atrial fibrillation. In patients with good renal function, however, a significant correlation was found between oral dose and plasma concentration. No evidence was obtained for increased sensitivity to therapeutic concentrations of the drug in elderly subjects, but the doses required to achieve these concentrations tended to be less than in younger patients.

Topics: Administration, Oral; Adult; Age Factors; Aged; Atrial Fibrillation; Digoxin; Drug Hypersensitivity; Electrocardiography; Heart Rate; Humans; Kidney Function Tests; Middle Aged; Radioimmunoassay

Topics: Adult; Aged; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Atria; Heart Rate; Humans; Male; Middle Aged

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Computers; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Ventricular Fibrillation

Topics: Age Factors; Arteriosclerosis; Atrial Fibrillation; Body Weight; Digoxin; Edema; Female; Heart Failure; Heart Rate; Humans; Hypertension; Lung Diseases; Male; Middle Aged; Organ Size; Spirometry; Syphilis, Cardiovascular

Topics: Adult; Aged; Atrial Fibrillation; Atrial Flutter; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Block; Humans; Male; Tachycardia, Paroxysmal

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atropine; Bradycardia; Cardiac Complexes, Premature; Digoxin; Drug Hypersensitivity; Dyspnea; Heart Rate; Humans; Male; Middle Aged; Propranolol; Tachycardia; Uremia

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitoxin; Digoxin; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Postoperative Complications

Topics: Atrial Fibrillation; Cardiac Catheterization; Chronic Disease; Digoxin; Electric Countershock; Heart Atria; Humans; Male; Methods; Middle Aged; Tachycardia

Topics: Anemia; Atrial Fibrillation; Black People; Blood Pressure; Cardiac Catheterization; Cardiac Output; Digoxin; Electrocardiography; Endomyocardial Fibrosis; Heart Rate; Heart Ventricles; Hemodynamics; Hemoglobinometry; Humans; Oxygen; Pericarditis, Constrictive; Strophanthins; Uganda

Topics: Adult; Aortic Valve; Atrial Fibrillation; Digoxin; Female; Heart Failure; Heart Rate; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Stenosis; Propranolol; Rheumatic Heart Disease; Sympatholytics

Topics: Atrial Fibrillation; Cardiac Glycosides; Chromatography, Thin Layer; Digoxin; Humans; Male; Middle Aged; Mitral Valve Stenosis; Rheumatic Heart Disease; Tritium

Topics: Adolescent; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Heart Ventricles; Humans; Male; Middle Aged; Pulmonary Edema; Quinidine; Thromboembolism

Topics: Acute Kidney Injury; Aged; Aortic Aneurysm; Atrial Fibrillation; Atrial Flutter; Digoxin; Humans; Male; Middle Aged; Postoperative Complications; Tachycardia

Topics: Adult; Aged; Atrial Fibrillation; Atrial Flutter; Digoxin; Electric Countershock; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Coronary Disease; Digoxin; Female; Heart Defects, Congenital; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia, Paroxysmal

Topics: Adult; Atrial Fibrillation; Atrial Flutter; Cardiac Surgical Procedures; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Ouabain; Postoperative Complications; Propranolol; Quinidine

Topics: Adult; Atrial Fibrillation; Digoxin; Electrocardiography; Humans; Male; Middle Aged; Monitoring, Physiologic; Myocardial Infarction; Physical Exertion; Propranolol; Radio; Telemetry

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Child, Preschool; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Block; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Postoperative Complications; Quinidine

Topics: Atrial Fibrillation; Chronic Disease; Digoxin; Electrocardiography; Heart Ventricles; Humans; Hydrochlorothiazide; Male; Middle Aged; Pacemaker, Artificial; Phenytoin; Procainamide; Propranolol; Quinidine; Tachycardia, Paroxysmal

Topics: Animals; Atrial Fibrillation; Chlorothiazide; Digoxin; Dirofilariasis; Dog Diseases; Dogs; Electrocardiography; Heart Failure; Male; Quinidine

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Humans; Vertigo

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Electric Countershock; Electric Stimulation Therapy; Electrocardiography; Humans; Phenindione; Quinidine; Tachycardia

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis Glycosides; Digoxin; Drug Therapy; Electric Countershock; Electric Stimulation Therapy; Potassium; Procaine; Quinidine; Tachycardia; Toxicology

Topics: Adrenergic Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Digoxin; Electrocardiography; Ethanolamines; Geriatrics; Heart Block; Heart Failure; Hypotension; Myocardial Infarction; Nausea; Paresthesia; Sympatholytics; Toxicology; Vertigo; Vomiting

Topics: Atrial Fibrillation; Diagnosis, Differential; Digoxin; Electrocardiography; Humans; Procainamide; Prognosis; Quinidine; Tachycardia; Tachycardia, Ventricular; Wolff-Parkinson-White Syndrome

Topics: Atrial Fibrillation; Blood Pressure Determination; Digoxin; Hemodynamics; Humans

Topics: Atrial Fibrillation; Digitalis; Digitalis Glycosides; Digoxin; Plant Extracts

Topics: Atrial Fibrillation; Digitalis; Digitalis Glycosides; Digoxin; Glycols; Humans; Plant Extracts; Propylene Glycol