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  • Review Article
  • Published:

The pathophysiology of heart failure with preserved ejection fraction

Nature Reviews Cardiology volume 11, pages 507–515 (2014)Cite this article

Subjects

Key Points

  • Heart failure with preserved ejection fraction (HFpEF) is an increasingly common form of cardiac disease associated with ageing, obesity, and hypertension, for which no treatment has proven effective

  • HFpEF is characterized by increased left ventricular (LV) filling pressure secondary to diastolic dysfunction; this pressure elevation can be observed at rest or during exercise and causes secondary pulmonary hypertension

  • Despite normal ejection fraction, HFpEF is characterized by mild systolic dysfunction and dramatic limitations in systolic reserve capacity during stress, with blunted increases in ejection fraction

  • Chronotropic incompetence, left atrial dysfunction, atrial fibrillation, arterial stiffening, autonomic imbalance, and endothelial dysfunction contribute to diastolic and systolic dysfunction to limit cardiac output reserve and increase LV filling pressures

  • Peripheral impairments, including abnormalities in endothelial function, body composition, and skeletal muscle function, also have an important role in HFpEF

  • These impairments in cardiac, vascular, and peripheral reserve can be caused by common risk factors for HFpEF, such as ageing, adiposity, hypertension, and metabolic stress

Abstract

Approximately half of all patients with heart failure have preserved ejection fraction (HFpEF) and, as life expectancies continue to increase in western societies, the prevalence of HFpEF will continue to grow. In contrast to heart failure with reduced ejection fraction (HFrEF), no treatment has been proven in pivotal clinical trials to be effective for HFpEF, largely because of the pathophysiological heterogeneity that exists within the broad spectrum of HFpEF. This syndrome was historically considered to be caused exclusively by left ventricular diastolic dysfunction, but research has identified several other contributory factors, including limitations in left ventricular systolic reserve, systemic and pulmonary vascular function, nitric oxide bioavailability, chronotropic reserve, right heart function, autonomic tone, left atrial function, and peripheral impairments. Multiple individual mechanisms frequently coexist within the same patient to cause symptomatic heart failure, but between patients with HFpEF the extent to which each component is operative can differ widely, confounding treatment approaches. This Review focuses on our current understanding of the pathophysiological mechanisms underlying HFpEF, and how they might be mechanistically related to typical risk factors for HFpEF, including ageing, obesity, and hypertension.

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Figure 1: LV diastolic function in health and in HFpEF.
Figure 2: Depiction of short-axis views of the left ventricle at end diastole and end systole.
Figure 3: The pathophysiology of heart failure with preserved ejection fraction.
Figure 4: The interaction between risk factors, cardiac ageing, and loss of cardiovascular reserve, which results in the development of symptomatic HFpEF.

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  1. The Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, 55905, MN, USA

    Barry A. Borlaug

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The author has acted as a consultant for: Amgen, Cardiokinetix, DC Devices (unpaid), GlaxoSmithKline, and Merck. He has received research support from AtCor Medical.

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Borlaug, B. The pathophysiology of heart failure with preserved ejection fraction. Nat Rev Cardiol 11, 507–515 (2014). https://doi.org/10.1038/nrcardio.2014.83

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