Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction

Objectives: The purpose of this study was to determine the mechanisms responsible for reduced aerobic capacity (peak Vo(2)) in patients with heart failure with preserved ejection fraction (HFPEF).

Background: HFPEF is the predominant form of heart failure in older persons. Exercise intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with heart failure and reduced ejection fraction, the mechanism of exercise intolerance in HFPEF is less well understood.

Methods: Left ventricular volumes (2-dimensional echocardiography), cardiac output, Vo(2), and calculated arterial-venous oxygen content difference (A-Vo(2) Diff) were measured at rest and during incremental, exhaustive upright cycle exercise in 48 HFPEF patients (age 69 ± 6 years) and 25 healthy age-matched controls.

Results: In HFPEF patients compared with healthy controls, Vo(2) was reduced at peak exercise (14.3 ± 0.5 ml·kg·min(-1) vs. 20.4 ± 0.6 ml·kg·min(-1); p < 0.0001) and was associated with a reduced peak cardiac output (6.3 ± 0.2 l·min(-1) vs. 7.6 ± 0.2 l·min(-1); p < 0.0001) and A-Vo(2) Diff (17 ± 0.4 ml·dl(-1) vs. 19 ± 0.4 ml·dl(-1), p < 0.0007). The strongest independent predictor of peak Vo(2) was the change in A-Vo(2) Diff from rest to peak exercise (A-Vo(2) Diff reserve) for both HFPEF patients (partial correlate, 0.58; standardized β coefficient, 0.66; p = 0.0002) and healthy controls (partial correlate, 0.61; standardized β coefficient, 0.41; p = 0.005).

Conclusions: Both reduced cardiac output and A-Vo(2) Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-Vo(2) Diff reserve is an independent predictor of peak Vo(2) suggests that peripheral, noncardiac factors are important contributors to exercise intolerance in these patients.