Heart Failure With Preserved Ejection Fraction In Perspective

Abstract

Approximately half of the patients with signs and symptoms of heart failure have a left ventricular ejection fraction that is not markedly abnormal. Despite the historically initial surprise, heightened risks for heart failure specific major adverse events occur across the broad range of ejection fraction, including normal. The recognition of the magnitude of the problem of heart failure with preserved ejection fraction in the past 20 years has spurred an explosion of clinical investigation and growing intensity of informative outcome trials. This article addresses the historic development of this component of the heart failure syndrome, including the epidemiology, pathophysiology, and existing and planned therapeutic studies. Looking forward, more specific phenotyping and even genotyping of subpopulations should lead to improvements in outcomes from future trials.

Keywords: clinical trials, phase III; epidemiology; heart failure; heart failure, diastolic.

Figure 1

PubMed citations for heart failure with preserved ejection fraction from 1986 to 2018.

Figure 2

The Pathophysiologic Progression of HFpEF. By cellular mechanisms that are as yet not completely understood, established risk factors alter cell and tissue function, impairing cardiac diastolic and systolic reserve, leading to abnormal hemodynamics and secondary organ dysfunction. Note that this constellation may be seen with any pattern of cardiac geometry and remodeling, contrast to historical preconceptions that concentric left ventricular (LV) hypertrophy was requisite. See text for further details.

Figure 3

[A] As compared to controls (black), patients with HFpEF (red) display greater elevation in pulmonary capillary wedge pressure (PCWP) during exercise. [B] In tandem with abnormalities in pulmonary vasodilation and vascular recruitment, this promotes greater increases in mean pulmonary artery pressure (mPAP) as cardiac output increases during exercise. These hemodynamic perturbations are correlated with abnormalities in ventilatory drive [C] and the perception of dyspnea [D], reductions in peak aerobic capacity (peak oxygen consumption, VO₂) [E], and increased mortality [F]. *Hazard ratio (HR) 2.37, 95% confidence interval (CI) 1.09–5.17, p=0.029; **HR 3.14, 95% CI 1.22–8.01; € HR 4.75, 95% CI 1.90–11.84, p<0.001. Adapted with permission from references 100, 104, 105, 106, and 118.