Author + information
- Hani N. Sabbah, PhD∗ ()
- ↵∗Address for correspondence:
Dr. Hani N. Sabbah, Henry Ford Health System, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202.
• Cardiac energy deprivation due to mitochondrial dysfunction is characteristic of heart failure.
• Mitochondrial dysfunction contributes to worsening of the heart failure state.
• Pharmacologic targeting of mitochondria in heart failure is an unmet need.
• Mitochondrial dysfunction in heart failure can be reversed with novel experimental drugs.
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 afterload but do not address the underlying causes of abnormal myocardial energetic nor directly target mitochondrial abnormalities. Numerous studies in animal models of HF as well as myocardial tissue from explanted failed human hearts have shown that the failing heart manifests abnormalities of mitochondrial 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 mitochondrial dysfunction therefore offers considerable potential as a new therapeutic approach to improve overall cardiac function, quality of life, and survival for patients with HF.
Supported in part by research grants from Stealth BioTherapeutics, Inc. and National Heart Lung and Blood Institute (1RO1HL132154-01A1). Dr. Sabbah has received research grants from Stealth BioTherapeutics, Inc.; and is a consultant for Stealth BioTherapeutics, Inc. and Bayer AG.
The author attests he is in compliance with human studies committees and animal welfare regulations of the author's institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received June 25, 2019.
- Revision received July 19, 2019.
- Accepted July 21, 2019.
- 2020 The Author
- Visual Abstract
- Abnormalities of Mitochondria in the Failing Heart
- Abnormalities of Skeletal Muscle in Heart Failure and Role of Mitochondria
- Aging Mitochondria as a Model of Mitochondrial Abnormalities in Heart Failure
- Potential Therapeutic Interventions