digoxin and Heart-Failure--Diastolic

To provide an overview of heart failure with preserved ejection fraction (HFPEF), as well as its pathophysiology, diagnosis, and clinical evidence regarding its pharmacologic management.. Peer-reviewed articles were identified from MEDLINE, International Pharmaceutical Abstracts, and Current Contents (all 1966-August 2010) using the search terms heart failure with preserved ejection fraction, diastolic dysfunction, diastolic heart failure, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), digoxin, β-blockers, calcium-channel blockers, and vasodilators. Citations from available articles were also reviewed for additional references.. Fourteen published manuscripts relating to pharmacologic management of HFPEF were identified.. The prevalence of HFPEF has continued to increase. Compared to heart failure with left ventricular systolic dysfunction, HFPEF has been largely understudied. Unlike in the management of heart failure with left ventricular systolic dysfunction, ACE inhibitors, ARBs, β-blockers, and aldosterone antagonists did not demonstrate mortality benefit in HFPEF, with the exception of one small study evaluating the use of propranolol. However, this study enrolled a small number of patients with recent history of myocardial infarction, which limited the generalizability of the results. Most of the current evidence centers on morbidity benefits and symptom reduction. One study showed that treatment with candesartan reduced hospital admissions in this population of patients. Management of HFPEF still focuses on optimally managing underlying diseases (eg, hypertension).. Much remains to be learned about the appropriate pharmacologic management of patients with HFPEF. Hypertension is in most cases the predominant contributor to its development and progression. For this reason, antihypertensive treatment, including ACE inhibitors, ARBs, β-blockers, and calcium-channel blockers, has been evaluated and is recommended to control the disease in this patient population, although these agents have not demonstrated significant benefit beyond blood pressure control. Further research into the pathophysiology of HFPEF may contribute to identifying the most optimal agent in managing this disease.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Clinical Trials as Topic; Digoxin; Heart Failure, Diastolic; Humans; Stroke Volume

Although women account for a significant proportion of the growing heart failure epidemic, they have been poorly represented in clinical trials. As emerging epidemiologic data reveal a growing prevalence and burden of disease among women, it is increasingly important that treating physicians and researchers recognize sex-based differences. Despite the overall incidence of heart failure being lower in women compared with men, the magnitude of improvement in survival over the last several decades has been less apparent in women. Women with heart failure are more likely to be older, have preserved systolic function and nonischemic cardiomyopathy. While clinical trials have demonstrated improved outcomes among heart failure patients, they have predominantly included men, yielding results that are sometimes inadequately powered to detect a benefit for women. Without adequate representation of women in clinical trials, one cannot assume that the same level of therapeutic evidence also applies to women. Nonetheless, it appears that beta-blockers and angiotensin-converting enzyme inhibitors provide the same survival benefits in women with systolic dysfunction as in men. In addition, some studies suggest that angiotensin-receptor blockers may lead to a better survival in women when compared with angiotensin-converting enzyme inhibitors. Focused research is needed to understand and guide the management of women with heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Comorbidity; Digoxin; Female; Heart Failure, Diastolic; Heart Failure, Systolic; Hormone Replacement Therapy; Humans; Male; Risk Factors; Sex Factors; United States

In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients.. In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin.. All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79).. In older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients.

Topics: Aged; Aged, 80 and over; Canada; Cardiotonic Agents; Cardiovascular Agents; Chronic Disease; Digoxin; Double-Blind Method; Female; Follow-Up Studies; Heart Failure, Diastolic; Humans; Kaplan-Meier Estimate; Male; Odds Ratio; Patient Admission; Patient Readmission; Proportional Hazards Models; Sample Size; Treatment Outcome; United States

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

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