Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT.

BACKGROUND: Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia. METHODS AND RESULTS: Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (P< or =0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions. CONCLUSIONS: Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them.

Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data.

OBJECTIVES: The objective of this study was to test the hypothesis that the severity of left ventricular remodeling predicts the response to treatment and outcomes in chronic heart failure. BACKGROUND: Reversal of remodeling should produce the most favorable outcome in patients with the most severe remodeling. METHODS: In 5010 heart failure patients on background therapy and randomized to valsartan and placebo, serial recordings of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were read at sites that had to meet qualifying standards before participating. Baseline LVIDd and EF were pooled across treatments and retrospectively grouped by quartiles Q1 to Q4, representing best to worst. Kaplan-Meier survival curves were obtained by the log-rank test. Q1 was compared with Q4 for mortality and combined mortality and morbidity (M + M) from Cox regression risk ratios (RRs). Valsartan versus placebo changes from baseline in LVIDd and EF were analyzed by quartiles from analysis of covariance. Valsartan and placebo were compared by RRs for M + M. RESULTS: Survival rates were greater in the better quartiles for LVIDd and EF (p < 0.00001). The RR for Q1 versus Q4 in events approached 0.5 for both LVIDd and EF (p < 0.0001). An LVIDd decrease and EF increase were quartile-dependent and greater with valsartan than placebo at virtually all time points. The RR for M + M outcomes favored valsartan in the worse quartiles. CONCLUSIONS: Stratification by baseline severity of remodeling showed that patients with worse LVIDd and EF are at highest risk for an event, yet appear to gain the most anti-remodeling effect and clinical benefit with valsartan treatment.

Comparison of treatment benefit and outcome in women versus men with chronic heart failure (from the Valsartan Heart Failure Trial).

The comparison of treatment effect and co-morbidity between the genders in the Valsartan Heart Failure Trial showed equal benefit of treatment in men and women. Co-morbidities, such as diabetes and coronary artery disease, increased nonfatal cardiac morbidity more in women than in men.

Morbidity, mortality, physiologic and functional parameters in elderly and non-elderly patients in the Valsartan Heart Failure Trial (Val-HeFT).

BACKGROUND: The Valsartan Heart Failure Trial (Val-HeFT) demonstrated the favorable effects of the addition of valsartan to prescribed heart failure (HF) therapy on HF hospitalization, and functional and physiological parameters. As the prevalence of HF morbidity and mortality are increased in the elderly, the effect of valsartan in the elderly is of clinical significance. METHODS: In this post-hoc analysis, morbidity, mortality, left ventricular (LV) size and function, brain natriuretic peptide (BNP), aldosterone, norepinephrine (NE), quality of life, and treatment effect with valsartan were examined by subgroups of 2350 elderly (>or= 65 years) and 2660 non-elderly (< 65 years) patients enrolled in Val-HeFT. RESULTS: While the overall incidence of morbidity and mortality was higher in the elderly, valsartan produced beneficial effects in reducing risk of morbidity in the elderly by 11.8% (P = .07), and the non-elderly by 14.6% (P = .09). Valsartan had no effect on mortality compared to placebo in the non-elderly, 15.2% vs 15.0% (P = .87), and elderly, 25.1% vs 24.0%, (P = .64). Valsartan had statistically significant beneficial effects in both the elderly and non-elderly on LV size and function, BNP, aldosterone and quality of life. Beneficial effects on NE were also observed with valsartan in both subgroups with statistically significant reductions produced in the non-elderly. CONCLUSIONS: Val-HeFT demonstrated that elderly patients present with more advanced HF as evidenced by higher morbidity and mortality along with greater neurohormonal activation. In Val-HeFT, valsartan produced a consistent beneficial effect on morbidity, LV function and size, quality of life, and neurohormonal levels in both the elderly and non-elderly.

Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val-HeFT.

AIMS: To investigate the effect of valsartan in the Valsartan-Heart Failure Trial (Val-HeFT) when added to angiotensin-converting enzyme inhibitor (ACEi) alone in patients with heart failure (HF). METHODS: Subjects in Val-HeFT receiving ACEi but not beta-blocker at baseline were analysed; 1532 were assigned to valsartan and 1502 assigned to placebo. Primary outcome events (all-cause mortality, hospitalisation for adjudicated heart failure, sudden death with resuscitation and need for >4 h of parenteral therapy for worsening heart failure) were monitored. RESULTS: Mortality was not affected by valsartan but morbidity endpoints were significantly reduced (36.3% in placebo, 31.0% in valsartan, p=0.002) in patients receiving an ACEi but no beta-blocker. Quality of life (QOL) was significantly improved, ejection fraction (EF) significantly increased, left ventricular (LV) diameter significantly reduced and plasma B-type natriuretic peptide, norepinephrine and aldosterone levels significantly reduced with valsartan compared to placebo. The morbidity benefit was significant in patients on ACEi doses below the median (22% reduction, p=0.003) and not statistically significant in those receiving ACEi doses above the median (14% reduction, p=0.143). CONCLUSION: Valsartan reduces heart failure hospitalisations and slows LV remodelling in patients treated with an ACEi in the absence of beta-blockade, particularly in those on lower doses of ACEi.