Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure.

Background: Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V(1A) (vascular and myocardial effects) and V(2) receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure.

Methods And Results: A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V(1a)/V(2) vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo.

Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib.

Background: In comparing aspirin, nonselective nonsteroidal antiinflammatory agents (NSAIDs), and cyclooxygenase (COX)-2 inhibitors, variation in platelet inhibitory effects exists that may be associated with differential risks of cardiovascular (CV) thrombotic events. Among the randomized, controlled trials with the COX-2 inhibitor rofecoxib, one study demonstrated a significant difference between rofecoxib and its NSAID comparator (naproxen) in the risk of CV thrombotic events. A combined analysis of individual patient data was undertaken to determine whether there was an excess of CV thrombotic events in patients treated with rofecoxib compared with those treated with placebo or nonselective NSAIDs.

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.

Objectives: We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction.

Background: Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction.

Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis.

Background: Both metoprolol and carvedilol improve cardiac function and prolong survival in patients with heart failure. Carvedilol has broader antiadrenergic effects than metoprolol, but it is not clear whether this characteristic is associated with greater benefits on cardiac function during long-term treatment.

Study Design: We performed a meta-analysis of all 19 randomized controlled trials of carvedilol or metoprolol that measured left ventricular ejection fraction before and after an average of 8.

Economic impact of beta blockade in heart failure.

We reviewed the literature on clinical trials of beta-adrenergic blockade for treatment of heart failure, seeking evidence of reductions in hospital admissions. To analyze the economic implications of six clinical trials, we developed a stochastic cost model to generate estimates of total medical costs resulting from heart failure and related causes. The model includes inpatient, outpatient, and professional cost estimates based on Medicare claims data, and it is driven by traditional endpoint statistics reported in the clinical trial literature.

Cause and management of heart failure in patients with chronic renal disease.

Heart failure occurs in 40% of patients with end-stage renal disease and is a major determinant of mortality. Heart failure occurs in patients with left ventricular systolic dysfunction (dilated left ventricle) as well as those with a normal resting ejection fraction (nondilated left ventricle). This report describes the cause of heart failure among patients with end-stage renal disease and the effect of heart failure on survival.

Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation.

Objectives: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients.

Background: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown.

Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II.

Background: The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients, compared with captopril, an angiotensin-converting-enzyme (ACE) inhibitor. We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated.

Methods: We undertook a double-blind, randomised, controlled trial of 3,152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less.

Effects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction.

Background: A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction.

Methods: Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction.

Effects of losartan versus captopril on mortality in patients with symptomatic heart failure: rationale, design, and baseline characteristics of patients in the Losartan Heart Failure Survival Study--ELITE II.

Background: In the Evaluation of Losartan in the Elderly (ELITE) heart failure study, a survival benefit (primarily because of a reduction in sudden deaths) was observed in symptomatic patients treated with losartan compared with captopril.

Methods And Results: The Losartan Heart Failure Survival Study--ELITE II (currently ongoing) is a double-blind, randomized clinical trial being conducted in 45 countries at 288 sites. ELITE II formally tests the hypotheses that losartan, compared with captopril, will reduce all-cause mortality (primary end point) and sudden cardiac death and/or resuscitated cardiac arrest (secondary end point).

Factors influencing exercise performance in patients with left ventricular dysfunction. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

Background: The determinants of exercise performance are multifactorial and incompletely understood in patients with symptomatic left ventricular (LV) dysfunction, with much less information regarding asymptomatic LV dysfunction. This study assessed the hemodynamics and neurohormonal factors influencing exercise performance in patients with LV ejection fractions > or =0.35, both symptomatic and asymptomatic, enrolled in Studies of LV Dysfunction.

Treatment guidelines in heart failure.

The risk of heart failure increases with age. Prognosis is poor, with 82% of patients dying within 6 years of diagnosis. As the population ages, heart failure is becoming an increasing problem.

Ventricular remodeling and its prevention in the treatment of heart failure.

Ventricular remodeling refers to changes in left ventricular (LV) geometry, mass, and volume in response to myocardial injury or alterations in load. The extent of LV dilatation or remodeling after myocardial infarction (MI) or in patients with heart failure is a strong predictor of both morbidity and mortality. Based on these observations, it is clear that LV remodeling is a maladaptive process.

Ventricular remodeling in a mouse model of myocardial infarction.

We investigated the suitability of studying ventricular remodeling in a mouse model of myocardial infarction (MI). We performed left coronary ligation (n = 22) or a sham procedure (n = 21) on normal C57BL/6J mice. Six weeks later, animals underwent echocardiography and hemodynamic evaluation.