Mitochondrial Dysfunction in Heart Failure With Preserved Ejection Fraction

Circulation. 2019 Mar 12;139(11):1435-1450. doi: 10.1161/CIRCULATIONAHA.118.036259.

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with an increasingly recognized heterogeneity in pathophysiology. Exercise intolerance is the hallmark of HFpEF and appears to be caused by both cardiac and peripheral abnormalities in the arterial tree and skeletal muscle. Mitochondrial abnormalities can significantly contribute to impaired oxygen utilization and the resulting exercise intolerance in HFpEF. We review key aspects of the complex biology of this organelle, the clinical relevance of mitochondrial function, the methods that are currently available to assess mitochondrial function in humans, and the evidence supporting a role for mitochondrial dysfunction in the pathophysiology of HFpEF. We also discuss the role of mitochondrial function as a therapeutic target, some key considerations for the design of early-phase clinical trials using agents that specifically target mitochondrial function to improve symptoms in patients with HFpEF, and ongoing trials with mitochondrial agents in HFpEF.

Keywords: MRI; exercise intolerance; heart failure with preserved ejection fraction; mitochondrial function.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Energy Metabolism*
  • Exercise Tolerance*
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Humans
  • Mitochondria, Heart / metabolism*
  • Mitochondria, Heart / pathology
  • Mitochondria, Muscle / metabolism*
  • Mitochondria, Muscle / pathology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Oxygen Consumption
  • Stroke Volume*
  • Ventricular Function, Left*

Substances

  • Adenosine Triphosphate