Heart failure with preserved ejection fraction in the elderly: scope of the problem

Abstract

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in older adults, particularly women, and is increasing in prevalence as the population ages. With morbidity and mortality on par with HF with reduced ejection fraction, it remains a most challenging clinical syndrome for the practicing clinician and basic research scientist. Originally considered to be predominantly caused by diastolic dysfunction, more recent insights indicate that HFpEF in older persons is typified by a broad range of cardiac and non-cardiac abnormalities and reduced reserve capacity in multiple organ systems. The globally reduced reserve capacity is driven by: 1) inherent age-related changes; 2) multiple, concomitant co-morbidities; 3) HFpEF itself, which is likely a systemic disorder. These insights help explain why: 1) co-morbidities are among the strongest predictors of outcomes; 2) approximately 50% of clinical events in HFpEF patients are non-cardiovascular; 3) clinical drug trials in HFpEF have been negative on their primary outcomes. Embracing HFpEF as a true geriatric syndrome, with complex, multi-factorial pathophysiology and clinical heterogeneity could provide new mechanistic insights and opportunities for progress in management. This article is part of a Special Issue entitled CV Aging.

Keywords: Aging; Heart failure with preserved ejection fraction; Review; Systemic disorder.

Figure 1

Systolic function by gender among participants with congestive heart failure Mild = mildly reduced systolic function; Mod-Sev = moderately to severely reduced systolic function.

Figure 2

Relationship of heart rate reserve (HRR) to peak exercise oxygen consumption (V̇O₂ peak) in older patients with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, with (○) and without (●) chronotropic incompetence (CI). There is a significant correlation between HRR and V̇o₂ peak in those with (R=0.39 P=0.04) and without CI (R=0.41 P=0.01).

Figure 3

Determinants of exercise intolerance in patients with HFpEF. ATP, adenosine triphosphate; LV, left ventricle; O₂, oxygen; RV, right ventricle.

Figure 4

Relationship between peak VO₂ (ml/min) and percent leg lean mass in heart failure with preserved ejection fraction (HFpEF) and healthy controls (HC) HFpEF (filled squares) and HC (filled circles)

Figure 5

Magnetic resonance imaging axial image of the mid-thigh in a patient with heart failure with preserved ejection fraction (HFpEF) and healthy controls (HC) Red = Skeletal muscle; green = Intermuscular fat (IMF); blue = Subcutaneous fat; purple = femoral cortex; yellow = femoral medulla. IMF (green) is substantially increased in the patient with HFpEF compared with the HC despite similar subcutaneous fat.

Figure 6

Relationship of capillary-to-fiber ratio (A) and percentage of type I muscle fibers (B) with peak O₂ uptake (VO₂) in older patients with heart failure with preserved ejection fraction (■) and age-matched healthy control subjects (▲).