digoxin and Ventricular-Dysfunction--Left

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

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

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

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

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

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

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

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

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

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

Aldosterone blockade has been shown to be effective in reducing total mortality as well as hospitalization for heart failure in patients with systolic left ventricular dysfunction (SLVD) due to chronic heart failure and in patients with SLVD post acute myocardial infarction. The evidence for the effectiveness of aldosterone blockade in chronic heart failure comes from the randomized aldactone evaluation study (RALES) while that for patients post infarction from the eplerenone post acute myocardial infarction efficacy and survival study (EPHESUS). These studies suggest that mineralocorticoid receptor activation remains important despite the use of an angiotensin converting enzyme-inhibitor/angiotensin receptor blocking (ARB) agent and a beta blocker. Increasing evidence suggest that aldosterone blockade has important effects not only on the kidney but on ventricular remodeling, myocardial fibrosis, autonomic balance, fibrinolysis, oxidative stress, and activation of the NF-kappaB and AP-1 signaling pathways. The results of these studies in patients with SLVD has important implications not only for patients with chronic heart failure and post infarction but also for the therapy of patients with essential hypertension and other cardiovascular diseases.

Topics: Aldosterone; Angiotensin Receptor Antagonists; Digoxin; Enzyme Inhibitors; Eplerenone; Female; Humans; Male; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Randomized Controlled Trials as Topic; Spironolactone; Systole; Ventricular Dysfunction, Left

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

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

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

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

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adrenergic beta-Agonists; Calcium; Cardiotonic Agents; Cyclic Nucleotide Phosphodiesterases, Type 3; Digoxin; Dopamine Agonists; Drug Interactions; Humans; Phosphodiesterase Inhibitors; Triiodothyronine; Ventricular Dysfunction, Left

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

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

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Calcium Channel Blockers; Cardiotonic Agents; Digoxin; Humans; Severity of Illness Index; Systole; Ventricular Dysfunction, Left

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

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

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

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

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

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

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

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

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

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

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

A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction.. The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 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 <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1-10µg·kg(-1)·min(-1) according to the patient's condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively.. Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.

Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Flutter; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Morpholines; Prospective Studies; Tachycardia; Urea; Ventricular Dysfunction, Left

In patients with left ventricular systolic dysfunction (LVSD), peak oxygen uptake (pVO2) has strong predictive power for mortality, and can be used to guide management. However, many patients cannot tolerate standard test protocols. The 6-min walk test (6-MWT) is often used to estimate functional capacity due to its simplicity, cost effectiveness and familiarity to patients with LVSD. The relationship between 6-MWT performance and pVO2 is not certain, but if closely related could allow substitution of an expensive and cumbersome test for a cheaper and more familiar one.. 120 male patients with LVSD (LVEF <40%; (mean+/-S.D.) age 68+/-13 years; BMI 28+/-5) performed, in random order, a maximal incremental treadmill exercise test with metabolic gas exchange measurements to derive peak oxygen consumption (pVO2 = 19.8+/-5.8 mL.kg(-1).min(-1)), and a standardised 6-MWT (308+/-142 m; r = 0.44; P = 0.00001). In multivariate models including demographic data, resting blood pressure and heart rate, spirometry, routine blood samples, and walk distance, five variables were independently predictive of peak oxygen consumption. pVO2 = 11.92 + (1.48 x FEV1 (L)) + (1.12 x haemoglobin (g dl(-1))) + (0.016 x distance walked (m)) - (0.33 x BMI) - (0.11 x age (years)). This equation accounted for 48% of the variation in pVO2.. Using these five simple variables, peak oxygen consumption can be estimated with moderate accuracy. In clinical practice, however, when an estimate of peak oxygen consumption is required, incremental exercise testing with metabolic gas exchange measurements cannot be avoided in male patients with LVSD. Further work is needed to assess the relation between estimated pVO2 and outcome.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Digoxin; Diuretics; Exercise Test; Hemodynamics; Humans; Male; Middle Aged; Oxygen Consumption; Predictive Value of Tests; Regression Analysis; Ventricular Dysfunction, Left; Walking

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

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

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

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

To investigate the effects of digoxin on left atrial (LA) function in patients with congestive heart failure and dilated left atria.. 30 patients with enlarged left atrium (maximum LA diameter > 4 mm) caused by heart failure (New York Heart Association functional class III or IV) were studied before and after treatment with digoxin (0.25 mg orally for 12 days). Digoxin was also administered to 30 normal participants who served as controls.. LA active (AEF) and passive emptying fractions (PEF), reservoir fraction (RF), kinetic energy (KE), and mean velocity of circumferential atrial fibre shortening (Vcf) were calculated from echocardiographic measurements of LA volumes and transmitral Doppler flow velocities at baseline and on the third, sixth, eighth, and 12th day after digoxin administration.. LA AEF, PEF, RF, KE, and Vcf were significantly lower in patients than in controls (p < 0.001). LA AEF, PEF, RF, KE, and Vcf increased significantly both in patients and controls after digoxin administration (p < 0.001). This increase was greater in patients than in controls (p < 0.001). KE was linearly correlated with LA volume at the onset of atrial systole in all participants. The slope and the intercept of this relation were significantly increased after digoxin both in patients and in controls (p < 0.001).. LA performance is impaired in patients with heart failure. Dilated atria manifest atrial failure. Digoxin improves LA performance and LA contractility both in dilated and in normal atria. The effects of digoxin on LA contractility are augmented in the failing atria compared with the normal atria.

Topics: Adult; Aged; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Echocardiography, Doppler; Heart Atria; Heart Function Tests; Humans; Middle Aged; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

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

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

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

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

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

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

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

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

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

Topics: Diabetes Mellitus, Type 2; Digoxin; Glucosides; Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left

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: Cardiotonic Agents; Digoxin; Heart Failure; Humans; Stroke Volume; Ventricular Dysfunction, Left

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

Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Cardiotonic Agents; Cohort Studies; Death, Sudden, Cardiac; Defibrillators, Implantable; Digitoxin; Digoxin; Diuretics; Exercise Test; Female; Heart Transplantation; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Oxygen Consumption; Prospective Studies; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Adrenergic beta-1 Receptor Antagonists; Anti-Arrhythmia Agents; Atrial Flutter; Digoxin; Female; Heart Rate; Humans; Male; Morpholines; Tachycardia; Urea; Ventricular Dysfunction, Left

Higher levels of resting heart rate (HR) have been associated with sudden cardiac death (SCD) but mechanisms are poorly understood. We hypothesized that severe left ventricular systolic dysfunction (LVSD) and HR-modulating drugs explain the HR-SCD relationship.. To evaluate the relationship between HR, severe LVSD, HR-modulating drugs, and SCD in the community by using a case-control approach.. From the ongoing Oregon Sudden Unexpected Death Study, SCD cases (n = 378) aged ≥35 years and with electrocardiogram-documented resting HR were compared to 378 age- and gender-matched control subjects with coronary artery disease (mean age 68 ± 13 years; 69% man). Associations with SCD were assessed by using multivariable logistic regression.. Mean resting HR was significantly higher among SCD cases compared to controls (7.5 beats/min difference; P < .0001). HR was a significant determinant of SCD after adjustment for significant comorbidities and medications (odds ratio for 10 beats/min increase 1.26; 95% confidence interval 1.14-1.38; P < .0001). After considering LVSD, resting HR was slightly attenuated but remained significantly associated with SCD (P = .005). In addition to diabetes and digoxin as well as pulmonary and renal disease, LVSD was also independently associated with SCD (odds ratio 1.79; 95% confidence interval 1.11-2.87; P = .02).. Contrary to expectations, the significant relationship between increased resting HR and SCD persisted even after adjustment for LVSD and HR-modulating drugs. These findings suggest a potential role for additional novel interventions/therapies that modulate autonomic tone.

Topics: Aged; Cardiotonic Agents; Case-Control Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Diabetes Mellitus; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Risk Factors; Ventricular Dysfunction, Left

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

The importance of heart rate in the pathophysiology of heart failure with reduced LVEF has recently attracted attention. In particular, the findings of the Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial (SHIFT) have put special emphasis on heart rate reduction with ivabradine for improvement in clinical outcomes. Of course, there is a much older drug that reduces heart rate, i.e. digoxin.. In this short commentary, we retrospectively analyse the Digitalis Investigation Group (DIG) Trial looking at the primary composite endpoint used in SHIFT (i.e. cardiovascular death or hospital admission for worsening heart failure) and compare the effect of digoxin on this endpoint with that of ivabradine. A remarkably similar risk reduction in the composite outcome and in its components appears evident among patients receiving the active treatment in both studies (although ivabradine was added to a beta-blocker, whereas digoxin was not).. This raises the question of whether the Cardiological community dismissed digoxin too readily and if we should reappraise its potential role in the treatment of heart failure.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzazepines; Digoxin; Female; Heart Failure; Humans; Ivabradine; Kaplan-Meier Estimate; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

Left ventricular hypertrabeculation (LVHT), also known as noncompaction, has been previously reported in a female patient with Turner syndrome (TS) with X0-karyotype, but has not been described in a male patient with a Turner mosaic.. In a 45-year-old man with short stature, facial dysmorphism, cryptorchism, hypospadia, but normal intellectual performance, TS was diagnosed upon cytogenetic evaluation and fluorescence in-situ hybridization revealing the karyotype mos45,X(28)/46,X,+mar(21)/47,X, + 2 mar(1). During an episode of heart failure at age 41 LVHT was detected in the posterolateral region on echocardiography also showing a slightly dilated left ventricle, severely reduced systolic function, and a moderate mitral and tricuspid insufficiency. On cardiac MRI LVHT was additionally seen in the lateral and anterior regions. Under adequate therapy, heart failure completely resolved but LVHT persisted.. LVHT may also occur in association with a mosaic TS with male phenotype. In such patients LVHT may not be accompanied by other congenital cardiac abnormalities but may be associated with severe cardiomyopathy resulting in rhythm abnormalities and heart failure.

Topics: Adrenergic alpha-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Cardiomyopathy, Dilated; Cardiotonic Agents; Carvedilol; Digoxin; Diuretics; Echocardiography; Furosemide; Heart Ventricles; Humans; Lisinopril; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mosaicism; Phenotype; Propanolamines; Spironolactone; Turner Syndrome; Ventricular Dysfunction, Left

Chronic left heart failure is the result of the activation of pathophysiological mechanisms which over time lead to progressive deterioration of the cardiac function. As pharmacotherapy aims at these mechanisms and as treatment possibilities are increasing, we find it relevant to provide a survey. Treatment evidence is based mainly on systolic dysfunction. It consists of angiotensin-converting enzyme inhibitor, aldosterone antagonist, beta-blocker, digoxin and diuretics. Incorporation of evidence-based medicine and treatment of diastolic dysfunction should be focussed on in the future.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Evidence-Based Medicine; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Ventricular Dysfunction, Left

Topics: Cardiotonic Agents; Digoxin; Heart Failure; Heart Rate; Humans; Systole; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Digoxin; Female; Heart Failure; Humans; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sex Factors; Survival Analysis; Ventricular Dysfunction, Left

Heart failure is a leading cause of morbidity and mortality, but there are no reliable models based on readily available clinical variables to predict outcomes in patients taking angiotensin-converting enzyme (ACE) inhibitors.. A multivariate statistical model to predict mortality was developed in a random sample (n = 4277 patients [67%]) of the 6422 patients enrolled in the Digitalis Investigation Group trial who had a depressed ejection fraction (

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Models, Statistical; Multivariate Analysis; Proportional Hazards Models; Stroke Volume; Survival Rate; Systole; Ventricular Dysfunction, Left

Topics: Anti-Arrhythmia Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Ventricular Dysfunction, Left

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

Topics: Acute Disease; Aged; Anti-Arrhythmia Agents; Blood Pressure; Cardiac Surgical Procedures; Coronary Angiography; Coronary Disease; Digoxin; Electrocardiography; Female; Hospital Mortality; Humans; Incidence; Male; Middle Aged; Patient Admission; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Sex Factors; Stroke Volume; Syndrome; Thrombolytic Therapy; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

There are now a number of guidelines outlining the diagnosis and management of patients with chronic heart failure (CHF). The extent to which these guidelines are used and the effects on patient outcomes are not well known. The aim of this study was to examine the implementation of a heart failure guideline among cardiologist and non-cardiologist physicians in a university hospital setting. Case record data were examined from 400 patients with a primary diagnosis of CHF. Management of these patients was assessed using a systolic heart failure guideline (Scottish Intercollegiate Guideline Network, number 35) as a benchmark. Hospital admission data were examined contemporaneously over a 17-month period to assess associations between adherence to drug therapies and number of admissions. Overall, there was poor adherence to the guideline, with relatively high use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) (80%), low use of beta-blockers (32%) and digoxin (36%), and very low use of spironolactone (13%). Cardiologists used more beta-blockers (37 vs. 21%, P=0.003) and digoxin in sinus rhythm (18 vs. 5%, P<0.001) than non-cardiologists. Hospital admission rate was individually associated with increasing age, NYHA status, beta-blocker, diuretic and spironolactone prescription (all P<0.001). At multivariable analysis, only age, NYHA status and increased diuretic prescription were associated with more frequent admission (P<0.001, R(2)=0.15). Despite carefully designed guidelines, the implementation of evidence-based therapies for CHF remains inadequate, even in a university hospital environment. This may reflect a lack of organisational developments to facilitate the increasingly complex management of patients with CHF.

Topics: Aged; Cardiology; Chronic Disease; Digoxin; Diuretics; Female; Guideline Adherence; Heart Failure; Hospitalization; Humans; Male; Practice Guidelines as Topic; Practice Patterns, Physicians'; Spironolactone; Ventricular Dysfunction, Left

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

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Black or African American; Digoxin; Diuretics; Drug Therapy, Combination; Ethnicity; Female; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Patient Selection; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Spironolactone; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Cross-Sectional Studies; Digoxin; Diuretics; Drug Interactions; Echocardiography; Europe; Heart Failure; Humans; Incidence; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Ventricular Dysfunction, Left

Much evidence has been accumulated that human plasma contains digitalis-like factor(s) with Na/K ATPase inhibitor properties. Increased concentrations of ouabain-like factor (OLF) have been reported in patients with moderate to severe hypertension and in patients with overt congestive heart failure due to dilated cardiomyopathy.. The presence of circulating OLF has not been investigated in borderline to mild hypertension or in the early stage of dilated cardiomyopathy.. The study population consisted of 18 normal volunteers, 24 patients with borderline to mild hypertension, 47 patients with asymptomatic left ventricular dysfunction (ALVD) due to dilated cardiomyopathy and 26 patients with cardiac arrhythmias but normal left ventricular function. OLF values (pM ouabain equivalent) were assayed in extracted plasma, using a radioimmunoassay for ouabain. OLF was, respectively, 29.4+/-20.6 pM in normal controls, 39.1+/-23.8 pM in hypertensives, 35+/-18 pM in patients with cardiac arrhythmias, 52.3+/-25.8 pM in ALVD patients not treated with digoxin and 64.6+/-29.6 pM in ALVD patients treated with digoxin. Patients with ALVD, both treated and not treated with digoxin, had OLF significantly higher (P<0.05) than all the other groups. In patients with ALVD no correlation between OLF and left ventricular ejection fraction was observed. In the hypertensive group no correlation between OLF and both diastolic and systolic pressure was found.. Increased concentrations of OLF were observed in patients with left ventricular dysfunction due to dilated cardiomyopathy, before the occurrence of overt heart failure, suggesting that OLF may be an early marker of the disease.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardenolides; Cardiomyopathy, Dilated; Digoxin; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Prognosis; Reference Values; Saponins; Ventricular Dysfunction, Left

As outpatients with long-term chronic illness often show a high incidence of medication noncompliance, we investigated the influence of digoxin noncompliance on hospitalization, left ventricular ejection fraction, and mortality in outpatients in long-term therapy having congestive heart failure with tachycardia at a rate over 100 beats/min before starting digoxin therapy, but abnormal sinus rhythm.. Before starting this study, the digoxin compliance/noncompliance of patients was determined by measuring the serum digoxin concentration (SDC). SDC was determined once a month, followed for six consecutive months, and patients were defined as noncompliant if their SDC was zero (0.0 ng/ml) on at least three consecutive occasions. According to SDC data, 218 patients were assigned to the compliant group and 213 patients were assigned to the noncompliant group. All 431 patients received diuretics, angiotensin converting-enzyme inhibitors, or nitrates as well as conventional therapy with digoxin throughout the trial. The duration of follow-up was 72 months.. After 72 months of follow-up, the digoxin noncompliant patients showed significant increases in the number and duration of hospitalizations compared with the compliant patients. The digoxin noncompliant patients had a marked decrease in the left ventricular ejection fraction from 49.1% to 41.8%. The cumulative rate of mortality from any cause in noncompliant patients was twofold higher (15.0%) than in compliant patients (7.8%; risk ratio when noncompliant was compared with compliant: 1.95; 95% confidence interval 1.11, 3.45; P = 0.029) at the 72-month follow-up. The higher mortality in digoxin noncompliant patients was exclusively attributed to worsening heart failure rather than other cardiac and noncardiac causes (risk ratio 2.13; 95% confidence interval 1.12, 4.07; P = 0.033). In addition, multiple regression analyses demonstrated that patient noncompliance as well as lower left ventricular ejection fraction at baseline were significantly involved in increased mortality.. These results indicate that digoxin noncompliance, at least in part, increases the rate of both hospitalization and mortality due to worsening heart failure in outpatients who have congestive heart failure with tachycardia in long-term therapy.

Topics: Aged; Analysis of Variance; Cardiotonic Agents; Confidence Intervals; Digoxin; Female; Heart Failure; Hospitalization; Humans; Linear Models; Male; Middle Aged; Odds Ratio; Prospective Studies; Regression Analysis; Tachycardia, Supraventricular; Treatment Refusal; Ventricular Dysfunction, Left

Several large clinical trials conducted over the past decade have shown that pharmacologic interventions can dramatically reduce the morbidity and mortality associated with heart failure. These trials have modified and enhanced the therapeutic paradigm for heart failure and extended treatment goals beyond limiting congestive symptoms of volume overload. Part II of this two-part article presents treatment recommendations for patients with left ventricular systolic dysfunction. The authors recommend that, if tolerated and not contraindicated, the following agents be used in patients with left ventricular systolic dysfunction: an angiotensin-converting enzyme inhibitor in all patients; a beta blocker in all patients except those who have symptoms at rest; and spironolactone in patients who have symptoms at rest or who have had such symptoms within the past six months. Diuretics and digoxin should be reserved, as needed, for symptomatic management of heart failure. Other treatments or treatment programs may be necessary in individual patients.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiotonic Agents; Diet; Digoxin; Diuretics; Exercise; Heart Failure; Humans; Patient Education as Topic; Referral and Consultation; Systole; Ventricular Dysfunction, Left

OBJECTIVE - To describe clinical observations of marked improvement in ventricular dysfunction in a medical office environment under circumstances differing from those in study protocols and multicenter studies performed in hospital or with outpatient cohorts. METHODS - Eleven cardiac failure patients with marked ventricular dysfunction receiving treatment at a doctors office between 1994 and 1999 were studied. Their ages ranged from 20 and 66 years (mean 39.42+/-14.05 years); 7 patients were men, 4 were women. Cardiopathic etiologies were arterial hypertension in 5 patients, peripartum cardiomyopathy in 2, nondefined myocarditis in 2, and alcoholic cardiomyopathy in 4. Initial echocardiograms revealed left ventricular dilatation (average diastolic diameter, 69.45+/-8.15mm), reduced left ventricular ejection fraction (0.38+/-0.08) and left atrial dilatation (43.36+/-5.16mm). The therapeutic approach followed consisted of patient orientation, elimination of etiological or causal factors of cardiac failure, and prescription of digitalis, diuretics, and angiotensinconverting enzyme inhibitors. RESULTS - Following treatment, left ventricular ejection fraction changed to 0.63+/-0.09; left ventricular diameters changed to 57.18+/-8.13mm, and left atrium diameters changed to 37.27+/-8.05mm. Maximum improvement was noted after 16.9+/-8.63 (6 to 36) months. CONCLUSION - Patients with serious cardiac failure and ventricular dysfunction caused by hypertension, alcoholism, or myocarditis can experience marked improvement in ventricular dysfunction after undergoing appropriate therapy within the venue of the doctor's office.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Captopril; Digoxin; Diuretics; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Treatment Outcome; Ventricular Dysfunction, Left

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: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiotonic Agents; Digoxin; Heart Failure; Humans; Myocarditis; Platelet Aggregation Inhibitors; Ventricular Dysfunction, Left

To assess whether implementation of guidelines increases the prescription of drugs, particularly beta blockers, recommended for secondary prevention after acute myocardial infarction.. Prescription patterns among 355 patients discharged from a public teaching hospital after recovery from myocardial infarction were prospectively monitored in a before-after trial. The implementation strategies included educational interventions (large group meetings), placement of guidelines in patients' records, and bimonthly general reminders sent to physicians.. Beta blockers were prescribed in 93 (38%) of 243 survivors of acute myocardial infarction before guideline implementation (12-month control period), as compared with 71 (63%) of 112 patients (P <0.001) after their implementation (6-month period). During the entire study period, the prescription of beta blockers at a neighboring public teaching hospital, used as a comparison, was unchanged. After adjusting for potential confounders, implementation of the guidelines remained significantly associated with prescription of beta blockers at discharge [odds ratio (OR) = 10; 95% confidence interval (CI), 3.2 to 33; P <0.001]. Other independent predictors of prescription of beta blockers were previous coronary artery bypass grafting (OR = 8.7; 95% CI, 2.5 to 31; P = 0.001), hypertension (OR = 2.5; 95% CI, 1.4 to 4.5; P = 0.003), age per 10-year increase (OR = 0.82; 95% CI, 0.67 to 0.99; P = 0.04), secular trend in prescription patterns expressed in months (OR = 0.9; 95% CI, 0.8 to 1.0; P = 0.02), a left ventricular ejection fraction < or = 40% (OR = 0.2; 95% CI, 0.1 to 0.4; P <0.001), the presence of atrioventricular block (OR = 0.1; 95% CI, 0.02 to 0.7; P = 0.02), and concomitant prescription of digoxin (OR = 0.2; 95% CI, 0.05 to 0.8; P = 0.02) or calcium antagonists (OR = 0.06; 95% CI, 0.01 to 0.3; P = 0.001).. When appropriately developed and implemented by local experts, literature-based guidelines may be effective in modifying use of recommended drugs for secondary prevention of coronary artery disease, such as prescription of beta blockers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Coronary Artery Bypass; Digoxin; Drug Prescriptions; Female; Heart Block; Humans; Hypertension; Male; Myocardial Infarction; Odds Ratio; Practice Guidelines as Topic; Severity of Illness Index; Stroke Volume; Switzerland; Ventricular Dysfunction, Left

We investigated whether patients with mild heart failure due to left ventricular systolic dysfunction were at risk of worsening during digoxin withdrawal.. Deterioration during digoxin withdrawal is often believed to be restricted to patients with moderate to severe clinical evidence of heart failure. To test this hypothesis, we studied the outcome of patients categorized by treatment assignment and a clinical signs and symptoms heart failure score in two rigorously designed clinical heart failure trials: the Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trial.. Potential differences in treatment failure, left ventricular ejection fraction and exercise capacity were evaluated in three groups of patients: those with mild heart failure (score < or = 2) who were withdrawn from digoxin (Dig WD Mild); those with moderate heart failure (score > 2) who were withdrawn from digoxin (Dig WD Moderate); and patients who continued receiving digoxin regardless of heart failure score (Dig Cont).. Heart failure score at randomization did not predict outcome during follow-up in Dig Cont-group patients. Dig WD Mild-group patients were at increased risk of treatment failure and had deterioration of exercise capacity and left ventricular ejection fraction compared with that in Dig Cont-group patients (all p < 0.01). Patients in the Dig WD Moderate group were significantly more likely to experience treatment failure than patients in either the Dig WD Mild or Dig Cont group (both p < 0.05).. Patients with systolic left ventricular dysfunction were at risk of clinical deterioration after digoxin withdrawal despite mild clinical evidence of congestive heart failure.

Topics: Aged; Digoxin; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Severity of Illness Index; Substance Withdrawal Syndrome; Systole; Ventricular Dysfunction, Left

To review the Agency for Health Care Policy and Research (AHCPR) clinical practice guideline for heart failure and comment on the guideline regarding pharmacotherapy from the perspective of the latest clinical trial data and the authors' clinical experience.. A MEDLINE search (1966 to June 1997) of English-language literature pertaining to the pharmacotherapy of heart failure was performed. Special emphasis was placed on literature published in the last 5 years. Additional literature was obtained from reference lists of key articles identified through the search.. Pertinent clinical trials were reviewed and considered along with information from the authors' database of over 800 patients with heart failure. Evidence concerning the use of angiotensin-converting enzyme inhibitors at appropriate dosages in all New York Heart Association classes of heart failure and the inclusion of digoxin as part of triple therapy in all symptomatic patients with left ventricular systolic dysfunction are reviewed. Strategies to circumvent clinical problems that may limit the proper application of standard therapeutic agents are considered, and the possible future role of beta-blockers as the therapeutic agents in patients with heart failure is discussed.. The AHCPR guideline provides the clinician with an excellent framework for treating the patient with heart failure. Building on the fundamentals of the guideline, the clinician can carefully apply current therapy at appropriate dosages and in the best combinations to individualize and thereby optimize pharmacologic therapy for this patient population.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Calcium Channel Blockers; Cardiac Output, Low; Digoxin; Diuretics; Female; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Ventricular Dysfunction, Left

This study evaluated the effect of digoxin on cardiac sympathetic activity in patients with congestive heart failure.. Digoxin favorably alters autonomic tone in heart failure. Whether it reduces cardiac sympathetic drive in the setting of heart failure is unknown.. Digoxin (0.25 mg intravenously) was administered to 12 patients with severe heart failure and elevated left ventricular end-diastolic pressure (> 14 mm Hg, Group A), 5 patients with less severe heart failure who had normal left ventricular end-diastolic pressure (> 14 mm Hg, Group B) and 6 patients with normal ventricular function. Seven additional patients with heart failure were studied as a time control group. Cardiac and total body norepinephrine spillover, systemic arterial pressure, left ventricular filling pressure and peak positive first derivative of left ventricular pressure were all assessed before and 30 min after administration of digoxin.. In Group A there were no changes in hemodynamic variables or total body norepinephrine spillover after digoxin administration; however, there was a significant reduction in cardiac norepinephrine spillover (263 +/- 70 to 218 +/- 62 pmol/min, mean +/- SEM, p < 0.001). In contrast, in Group B, digoxin caused a significant increase in cardiac norepinephrine spillover that was not associated with any hemodynamic changes or a change in total body spillover. There were no hemodynamic changes or a change in total body spillover. There were no hemodynamic or spillover changes in the time control or normal ventricular function group.. Digoxin, in the absence of detectable inotropic or hemodynamic effects, caused a reduction in cardiac norepinephrine spillover in patients with heart failure who had elevated filling pressures. This finding suggests a potentially beneficial primary autonomic action of digoxin in patients with severe heart failure.

Topics: Cardiotonic Agents; Case-Control Studies; Depression, Chemical; Digoxin; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Stroke Volume; Sympathetic Nervous System; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

The present study examined left ventricular (LV) and myocyte contractile performance and electrophysiologic variables after long-term digoxin treatment in a model of LV failure.. A fundamental therapeutic agent for patients with chronic LV dysfunction is the cardiac glycoside digoxin. However, whether digoxin has direct effects on myocyte contractile function and electrophysiologic properties in the setting of chronic LV dysfunction remains unexplored.. Left ventricular and isolated myocyte function and electrophysiologic variables were examined in five control dogs, five dogs after the development of long-term rapid pacing (rapid pacing, 220 beats/min, 4 weeks) and five dogs with rapid pacing given digoxin (0.25 mg/day) during the pacing period (rapid pacing and digoxin).. Left ventricular ejection fraction decreased in the dogs with rapid pacing compared with that in control dogs (30 +/- 2% vs. 68 +/- 3%, p < 0.05) and was higher with digoxin than that in the rapid pacing group (38 +/- 3%, p = 0.038). Left ventricular end-diastolic volume increased in the rapid pacing group compared with the control group (84 +/- 6 ml vs. 59 +/- 7 ml, p < 0.05) and remained increased with digoxin (79 +/- 6 ml). Isolated myocyte shortening velocity decreased in the rapid pacing group compared with the control group (37 +/- 1 microns/s vs. 59 +/- 1 microns/s, p < 0.05) and increased with digoxin compared with rapid pacing (46 +/- 1 microns/s, p < 0.05). Action potential maximal upstroke velocity was diminished in the rapid pacing group compared with the control group (135 +/- 6 V/s vs. 163 +/- 9 V/s, p < 0.05) and increased with digoxin compared with rapid pacing (155 +/- 12 V/s, p < 0.05). Action potential duration increased in the rapid pacing group compared with the control group (247 +/- 10 vs. 216 +/- 6 ms, p < 0.05) and decreased with digoxin compared with rapid pacing (219 +/- 12 ms, p < 0.05).. In this model of rapid pacing-induced LV failure, digoxin treatment improved LV pump function, enhanced isolated myocyte contractile performance and normalized myocyte action potential characteristics. This study provides unique evidence to suggest that the cellular basis for improved LV pump function with digoxin treatment in the setting of LV failure has a direct and beneficial effect on myocyte contractile function and electrophysiologic measures.

Topics: Action Potentials; Animals; Cardiac Pacing, Artificial; Cardiotonic Agents; Digoxin; Dogs; Female; Heart Failure; Male; Myocardial Contraction; Stroke Volume; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Three cases of chronic atrial tachycardia associated with ventricular dysfunction and severe exercise intolerance markedly improved within a few weeks when ventricular rate was slowed. Slowing ventricular rate may improve symptoms and ejection fraction despite possible changes in myocyte and tissue structure.

Topics: Adult; Cardiotonic Agents; Chronic Disease; Digoxin; Exercise Tolerance; Female; Heart Atria; Heart Rate; Humans; Male; Stroke Volume; Tachycardia; Ventricular Dysfunction, Left

This study sought to evaluate the changes in direct medical costs and life-years gained or lost by adding enalapril to conventional treatment (digoxin and diuretics) for heart failure (HF). The published results of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial, and a decision analytical model developed by the University of Pennsylvania, were used in combination with New Zealand data to undertake the evaluation. All costs were measured in 1993 New Zealand dollars ($NZ) [$NZ1 = $US0.5509, September 1993]. Potential net cost savings per patient treated over a 4-year period were $NZ652 together with an additional 2 months of life gained. If these individual potential cost savings are extended to the New Zealand population who have HF (but are at present not receiving an ACE inhibitor) then $NZ6 517 000 in discounted health sector costs could be avoided. The model was sensitive to changes in the price of enalapril, to estimates of the population with HF, the percentage of the population with HF treated with enalapril, and to hospital unit costs for nonfatal cases of HF. The study demonstrated that the addition of enalapril to the conventional treatment of HF was cost effective when compared with conventional medical therapy alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Costs and Cost Analysis; Decision Support Techniques; Digoxin; Diuretics; Enalapril; Female; Heart Failure; Humans; Male; New Zealand; Ventricular Dysfunction, Left