Improving quality of life in patients with chronic heart failure: Overcoming exercise intolerance

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Conference Proceeding

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Heart failure (HF) is characterized by poor survival and poor quality of life (QOL); the latter reflected by “exercise intolerance”. Over the past 3 decades, considerable research efforts and treasure were expended toward understanding the pathophysiology of HF and toward the development of new drugs and devices for its treatment. These efforts paid dividends in terms of improved survival but did little to improve QOL. Over the years, most attempts to establish a direct correlation between cardiac function and exercise intolerance in HF failed suggesting a source, other than cardiac output, may be responsible for this maladaptation. These findings were substantiated by an observed lack of appreciable improvement in exercise tolerance in CHF patients who benefited from drugs that extended survival. In recent years, focused research identified abnormalities of skeletal muscle (SM) in patients with HF as potential causes of exercise intolerance. These abnormalities include 1) a reduction in the number of aerobic Type-I, slow-twitch, fatigue-resistant fibers; 2) an increase in the number of glycolytic Type-II, fast-twitch, fibers; 3) functional abnormalities of SM mitochondria (MITO) and 4) a reduced ability of SM MITO to generate ATP commensurate with the demands of working SM. Interestingly, these abnormalities are present in HF despite appropriate SM blood perfusion, normal SM capillary density and SM fiber size. Recent studies in animals with HF showed that elamipretide (ELAM), a mitochondria-targeting peptide, can normalize SM fiber type distribution along with SM MITO abnormalities and maximum rate of ATP synthesis. ELAM also improved SM response to exercise in elderly humans with MITO dysfunction. In a Phase-IIa clinical trial, ELAM improved exercise tolerance in patients with genetic MITO diseases manifesting SM myopathies. These findings, viewed cumulatively, auger well for the use of novel, MITO-targeting drugs, to overcome exercise intolerance and improve overall QOL in patients with chronic HF.





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