Targeting the Mitochondria in Heart Failure A Translational Perspective

The burden of heart failure (HF) in terms of health care expenditures, hospitalizations, and mortality is substantial and growing. The failing heart has been described as energy-deprived and mitochondrial dysfunction is a driving force associated with this energy supply-demand imbalance. Existing HF therapies provide symptomatic and longevity benefit by reducing cardiac workload through heart rate reduction and reduction of preload and aftertoad but do not address the underlying causes of abnormal myocardial energetic nor directly target mitochondria abnormalities. Numerous studies in animal models of HF as well as myocardial tissue from exptanted failed human hearts have shown that the failing heart manifests abnormalities of mitochondria' structure, dynamics, and function that lead to a marked increase in the formation of damaging reactive oxygen species and a marked reduction in on demand adenosine triphosphate synthesis. Correcting mitochondria dysfunction therefore offers considerable potential as a new therapeutic approach to improve overall cardiac function, quality of life, and survival for patients with HF. (C) 2020 The Author. Published by Elsevier on behalf of the American College of Cardiology Foundation.