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PubMed2004

Apolipoprotein E epsilon4 allele is associated with left ventricular systolic dysfunction.

BACKGROUND: Apolipoprotein (APOE) epsilon4 allele has been associated with cardiac dysfunction in Alzheimer's disease and beta-thalassemia. We investigated the association between APOE genotypes and left ventricular dysfunction in a population of community-dwelling elderly subjects. METHODS: This study was performed in the Rotterdam Study, a population-based prospective cohort study among elderly subjects. For 2206 participants, a baseline echocardiogram and blood specimens for APOE typing were available. Cardiac dysfunction was considered present when fractional shortening was or=65 years. CONCLUSION: The APOE epsilon4 allele is an independent risk factor for cardiac dysfunction in elderly people. Besides well-known effects on atherosclerosis and cholesterol levels, there may be other mechanisms, such as apoptosis, through which this allele exerts negative effects on myocardial performance.

Age Factors↗
PubMed2006

Spironolactone treatment and clinical outcomes in patients with systolic dysfunction and mild heart failure symptoms: a retrospective analysis.

BACKGROUND: The effect of spironolactone on clinical outcomes in patients with mild heart failure is unclear. METHODS AND RESULTS: We performed a retrospective analysis of 482 consecutive patients with left ventricular ejection fraction < or =40% and New York Heart Association I-II symptoms. Major cardiac event (MCE) was defined as death, left ventricular assist device implantation, or United Network of Organ Sharing 1 cardiac transplantation. Proportional hazards analysis was used to determine predictors of MCE and to derive an adjusted hazard for spironolactone therapy. Spironolactone was prescribed to 279 (58%) patients and mean follow-up was 1029 days. After controlling for predictors of clinical events, spironolactone treatment was associated with a trend for lower risk of MCE or heart failure rehospitalization (HR, 0.68; 95% CI, 0.43-1.07; P = .095). Exploration of interaction terms between medications revealed that treatment with the combination of spironolactone and thiazide diuretics was associated with lower risk of clinical events (HR, 0.32; 95% CI, 0.12-0.89; P = .029). CONCLUSION: In subjects with mild heart failure treated with a thiazide diuretic, the use of spironolactone is associated with reduced risk of MCE or heart failure rehospitalization. A randomized controlled trial is necessary to accurately define the clinical effects of spironolactone in patients with mild heart failure.

Adult↗
PubMed2003

Systolic dysfunction is a predictor of long term mortality in men but not in women with heart failure.

AIMS: To evaluate possible gender differences in clinical profile and outcome of patients hospitalised with heart failure. METHODS AND RESULTS: During 1996 a total of 1065 hospital in-patients had confirmed heart failure, with follow-up data through 2002. Women (58%) were significantly older, had higher prevalence of hypertension and diabetes, and lower prevalence of ischaemic heart disease, chronic pulmonary disease and alcoholism. The proportion of patients with normal left ventricular ejection fraction (LVEF) increased with age, but in all age groups women had normal LVEF more frequently than men. Echocardiography was performed less frequently in females: 62% vs. 71% in men, P<0.01, and this finding was consistent in all age groups. During follow-up (median 19 months) 507 patients died (216 men [48.8%] and 291 women [46.8%]). Gender was not a predictor of survival when LVEF was included in the model (RH Male Gender 0.8, 95% CI 0.6 to 1.1, P=0.2). There was a significant interaction gender-LVEF (P=0.048): survival was similar in both genders with LVEF >0.3 but women with LVEF </=0.3 had a better prognosis than their male counterparts. CONCLUSIONS: Survival is similar in women irrespective of LVEF and in men with LVEF >0.3 while men with severely depressed LVEF have a worse prognosis.

Adolescent↗
PubMed2006

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction.

BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs. 1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.

Aged↗
PubMed2006

Lipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction.

BACKGROUND: Inflammation and oxidative stress have been implicated in the pathogenesis of atrial fibrillation (AF). Lipid-lowering drugs, particularly statins and fibrates, possess anti-inflammatory and antioxidant properties. OBJECTIVES: The purpose of this study was to assess the impact of lipid-lowering drug use on AF prevalence in patients with reduced left ventricular ejection fraction (LVEF). METHODS: Data were obtained from ADVANCENT(SM), a multicenter registry of patients with reduced LVEF (<or=40%). Demographic, clinical, and echocardiographic parameters were collected from interviews and medical records. Medications, including lipid-lowering drugs, were recorded. RESULTS: Of the 25,268 patients, 71.3% had hyperlipidemia, and 66.8% were prescribed lipid-lowering drugs. AF prevalence was 25.1% in patients taking lipid-lowering drugs compared with 32.6% in untreated hyperlipidemic patients and 32.8% in patients without hyperlipidemia (P <.001 for both comparisons). In multivariable analysis, lipid-lowering drug use remained significantly associated with reduced odds of AF (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.64-0.74), and this effect was larger than that of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (OR 0.85, 95% CI 0.79-0.92) or beta-blockers (OR 0.95, 95% CI 0.88-1.02). The beneficial impact of lipid-lowering drugs on AF risk was independent of their effects on the lipid profile. In patients in whom data on specific lipid-lowering drugs were available, 92% of the patients undergoing lipid-lowering therapy received statins, and 98% received statins and/or fibrates. CONCLUSION: Use of lipid-lowering drugs in patients with reduced LVEF is associated with a significant reduction in the prevalence of AF independent of the lipid profile and other known arrhythmia risk factors. This effect is larger than that of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or beta-blockers and may be the result of the antioxidant and anti-inflammatory effects of statins and fibrates.

Adrenergic beta-Antagonists↗
PubMed2004

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction.

OBJECTIVES: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BACKGROUND: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. METHODS: The Survival And Ventricular Enlargement (SAVE) trial randomized 2231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. RESULTS: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. CONCLUSIONS: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.

Alcohol Drinking↗
PubMed2005

Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure.

OBJECTIVES: This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) < or =40% and clinical signs of heart failure. BACKGROUND: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p = 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF < or =40% and clinical signs of heart failure. METHODS: We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial. RESULTS: At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p = 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p = 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p = 0.003) and the risk of sudden cardiac death by 37% (p = 0.051). CONCLUSIONS: Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF < or =40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.

Aged↗
PubMed2006

Population-based analysis of sudden cardiac death with and without left ventricular systolic dysfunction: two-year findings from the Oregon Sudden Unexpected Death Study.

OBJECTIVES: We sought to evaluate the contribution of left ventricular (LV) dysfunction toward occurrence of sudden cardiac death (SCD) in the general population, and to identify distinguishing characteristics of SCD in the absence of LV dysfunction. BACKGROUND: Patients who manifest warning symptoms and signs are more likely to undergo evaluation before SCD. Although prevalence of LV dysfunction in this subgroup may overestimate the prevalence in overall SCD, this is the only means of assessment in the general population. METHODS: All cases of SCD in Multnomah County, Oregon (population 660,486; 2002 to 2004) were prospectively ascertained in the ongoing Oregon Sudden Unexpected Death Study. We retrospectively assessed LV ejection fraction (LVEF) among subjects who underwent evaluation of LV function before SCD (normal: > or =55%; mildly to moderately reduced: 36% to 54%; and severely reduced: < or =35%). Of a total of 714 SCD cases (annual incidence 54 per 100,000), LV function was assessed in 121 (17%). RESULTS: The LVEF was severely reduced in 36 patients (30%), mildly to moderately reduced in 27 (22%), and normal in 58 (48%). Patients with normal LVEF were distinguishable by younger age (66 +/- 15 years vs. 74 +/- 10 years; p = 0.001), higher proportion of females (47% vs. 27%; p = 0.025), higher prevalence of seizure disorder (14% vs. 0%; p = 0.002), and lower prevalence of established coronary artery disease (50% vs. 81%; p < 0.001). CONCLUSIONS: In this community-wide study, only one-third of the evaluated SCD cases had severe LV dysfunction meeting current criteria for prophylactic cardioverter-defibrillator implantation. The SCD cases with normal LV function had several distinguishing clinical characteristics. These findings support the aggressive development of alternative screening methods to enhance identification of patients at risk.

Aged↗
PubMed2006

Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program.

OBJECTIVES: We assessed the risk of adverse cardiovascular (CV) outcomes associated with atrial fibrillation (AF) in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program, which enrolled patients with chronic heart failure (CHF) and a broad range of ejection fractions (EFs). BACKGROUND: Atrial fibrillation is associated with an increased risk of adverse CV outcomes in patients with CHF and reduced EF. The risk of AF in patients with CHF and preserved left ventricular ejection fraction (PEF) is unknown. METHODS: A total of 7,599 patients with symptomatic CHF were randomized to candesartan or placebo. Patients were divided by baseline EF (< or =40% or >40%) in low or preserved EF groups. Major outcomes were cardiovascular death or hospitalization for worsening heart failure, and all-cause mortality. Median follow-up was 37.7 months. RESULTS: A total of 670 (17%) patients in the low EF group and 478 (19%) in the PEF group had AF at baseline. Atrial fibrillation predicted a high risk of cardiovascular morbidity and mortality regardless of baseline EF. Patients with AF and low EF had the highest absolute risk for adverse CV outcomes. However, AF was associated with greater relative increased risk of the major outcomes in patients with PEF than in patients with low EF: hazard ratio 1.72 (95% confidence interval [CI] 1.45 to 2.06) versus 1.29 (95% CI 1.14 to 1.46), respectively. The same was true for the risk of all-cause mortality. Candesartan was associated with similar treatment effects regardless of baseline rhythm. CONCLUSIONS: Atrial fibrillation is associated with an increased risk of CV outcomes in patients with CHF and either reduced EF or PEF. Candesartan improved outcomes similarly regardless of baseline rhythm.

Aged↗