Heart failure (HF) is a common, disabling, and costly disease. Despite major advances in medical therapy, morbidity and mortality remain high, in part because current pharmacological regimens may not fully address some unique requirements of the heart for energy. The heart requires a continuous supply of energy-providing substrates and amino acids in order to maintain its function. In HF, defects in substrate metabolism and cardiac energy and substrate utilization may contribute to contractile dysfunction. HF is often accompanied by a deficiency in key micronutrients required for unimpeded energy transfer. Correcting these deficits has been proposed as a method to limit or even reverse the progressive myocyte dysfunction and/or necrosis in HF. This review summarizes the existing HF literature with respect to supplementation trials of key micronutrients involved in cardiac metabolism: coenzyme Q10, l-carnitine, thiamine, and amino acids, including taurine. Studies using a broader approach to supplementation are also considered. Although some of the results are promising, none are conclusive. There is a need for a prospective trial to examine the effects of micronutrient supplementation on morbidity and mortality in patients with HF.
Exercise training (ET) in heart failure (HF), as demonstrated in the HF-ACTION trial, was associated with improved exercise tolerance and health status, and a trend towards reduced mortality or hospitalizations. This analysis of the HF-ACTION cohort examines the effect of ET in overweight and obese compared to normal HF subjects. 2,314 of 2,331 systolic HF subjects randomized to aerobic ET vs. usual care in HF-ACTION were analyzed to determine the effect of ET on all cause mortality, hospitalizations, exercise parameters, quality of life (QOL), and body weight changes by subgroups of body mass index (BMI). Strata included normal weight (BMI 18.5 – 24.9 kg/m2), overweight (BMI 25.0 – 29.9 kg/m2), obese I (BMI 30 – 34.9 kg/m2), obese II (BMI 35-39.9 kg/m2), and obese III (BMI ≥ 40 kg/m2). At enrollment, 19.4% of subjects were normal weight, 31.3% overweight, and 49.4% obese. Higher BMI was associated with a non-significant increase in all cause mortality or hospitalization. ET was associated with non-significant reductions in all cause mortality or hospitalization in each weight category (HR 0.98, 0.95, 0.92, 0.89, and 0.86 in normal weight, overweight, obese I, obese II, and obese III categories, respectively [all p>0.05]). Modeled improvement in exercise capacity (peak oxygen consumption) and QOL in the ET group was seen in all BMI categories. In conclusion, aerobic ET in HF was associated with a non-significant trend towards decreased mortality and hospitalizations and a significant improvement in QOL across the range of BMI categories.
Chronotropic incompetence (CI) is common in heart failure with preserved ejection fraction (HFpEF), and may be a key reason underlying exercise intolerance in these patients. However, the determinants of CI in HFpEF are unknown. We prospectively studied 157 consecutive HFpEF patients undergoing cardiopulmonary exercise testing (CPET), and defined CI according to specific thresholds of the percent heart rate reserve (%HRR). CI was diagnosed as present if %HRR < 80 if not taking a β-blocker and < 62 if taking β-blockers. Participants who achieved inadequate exercise effort (respiratory exchange ratio ≤ 1.05) on CPET were excluded. Multivariable-adjusted logistic regression was used to determine the factors associated with CI. Of the 157 participants, 108 (69%) achieved a respiratory exchange ratio > 1.05 and were included in the final analysis. Of these 108 participants, 70% were women, 62% were taking β-blockers, and 38% had chronic kidney disease (CKD). The majority of HFpEF patients met criteria for CI (81/108; 75%). Lower estimated glomerular filtration rate (GFR), higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure were each associated with CI. A 1-standard deviation decrease in GFR was independently associated with CI after multivariable adjustment (adjusted odds ratio 2.2, 95% confidence interval 1.1-4.4; P = 0.02). The association between reduced GFR and CI persisted when considering a variety of measures of chronotropic response. In conclusion, reduced GFR is the major clinical correlate of CI in patients with HFpEF, and further study of the relationship between CKD and CI may provide insight into the pathophysiology of CI in HFpEF.
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