OBJECTIVES Supplemental myocardial hypertrophy induced by insulin-like growth factor (IGF)-1 may prevent transition from hypertrophy to heart failure under chronic mechanical overload. BACKGROUND Several studies have ...
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OBJECTIVES Supplemental myocardial hypertrophy induced by insulin-like growth factor (IGF)-1 may prevent transition from hypertrophy to heart failure under chronic mechanical overload. BACKGROUND Several studies have suggested that IGF-1 treatment may be beneficial in chronic heart failure. In addition, recent studies indicated that the amount of cu-myosin heavy chain (MHC) plays a significant hemodynamic role in large animals including humans. METHODS We treated Dahl salt-sensitive hypertensive rats on a long-term basis with IGF-1. The effects were compared with those produced by treatment using a sub-antihypertensive dose of temocapril, an angiotensin-converting enzyme (ACE) inhibitor. At 11 weeks, when these rats displayed compensated left ventricular hypertrophy (LVH), they were randomized to three groups: 1) TGF group (3 mg/kg/day);2) temocapril group (1 mg/kg/day);and 3) vehicle (control) group. RESULTS After 15 weeks, the control rats showed left ventricular (LV) enlargement and severe LV dysfunction and rapidly died of pulmonary congestion (mean survival time: 16.8 +/- 0.5 weeks). The survival time was significantly shortened (15.6 +/- 0.3 weeks) in the IGF-1 group but significantly prolonged (19.5 +/- 0.6 weeks) in the temocapril group. The rats in the IGF-1 group showed accelerated LV dilation and dysfunction. Of the several parameters investigated, it was found that the relative amounts of MHC isoforms differed among the three groups. The alpha-MHC mRNA level was decreased by 52% (p < 0.01) in the IGF group, while it increased by 58% (p < 0.01) in the temocapril group compared with the control group. These changes were related to the progression of LV dysfunction. CONCLUSIONS Supplemental myocardial hypertrophy with long-term IGF-1 treatment may not be beneficial if concentric LVH already exists. Our data suggest that IGF-1 may not protect myocardial performance when its hypertrophic effect aggravates the reduction of alpha-MHC. By contrast, the ACE inhib
Background Our purpose was to evaluate the reliability, validity, and responsiveness of the 6-minute walk test (6MWT) in patients with heart failure (HF) enrolled in the Randomized Evaluation of Strategies for Left Ve...
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Background Our purpose was to evaluate the reliability, validity, and responsiveness of the 6-minute walk test (6MWT) in patients with heart failure (HF) enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study. Methods A total of 768 patients was enrolled in a multicenter randomized clinical trial evaluating the effect of candesartan, enalapril, and metoprolol on left ventricular ejection fraction (LVEF), 6MWT distance, neurohormones, and quality of life. The 6MWT was performed once at screening and twice at baseline, 18 weeks, and 43 weeks by a standardized method. Results Test-retest reliability at baseline (intraclass correlation coefficient [ICC] = 0.90), 18 weeks (ICC = 0.88), and 43 weeks (ICC = 0.91) was very good. Baseline 6MWT distance was weakly inversely correlated to the quality-of-life cumulative score (r = -0.26, P = .0001) and moderately inversely correlated to the New York Heart Association functional classification (NYHA-FC) (r = -0.43, P = .001). In the RESOLVD study, the 6MWT was not responsive to change when effect sizes and standardized response means were used. Disease-specific quality of life was responsive to change in patients treated with candesartan and enalapril and NYHA-FC was responsive to change in the candesartan and enalapril combination and for enalapril alone with small effect sizes. The 6MWT, NYHA-FC, and quality of life were not responsive to change during the metoprolol or placebo phase. Conclusions The 6MWT is highly reproducible in patients with symptoms of HF. It is somewhat correlated to NYHA-FC and quality of life. Overall, quality of life was most responsive to change, whereas 6MWT and NYHA-FC were comparable but less responsive to change in the RESOLVD study.
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