Determinants of Exercise Intolerance in Elderly Heart Failure Patients With Preserved Ejection Fraction

Objectives To determine the mechanisms responsible for reduced aerobic capacity (peak VO2) in heart failure patients with preserved ejection fraction (HFPEF). Background HFPEF is the predominant form of HF 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 HF and reduced EF, the mechanism of exercise intolerance in HFPEF is less well understood. Methods Left ventricular volumes (2D echocardiography), cardiac output (CO), VO2 and calculated arterial-venous oxygen content difference (A-VO2 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 (HC). Results In HFPEF compared to HC, VO2 was reduced at peak exercise (mean±SE: 14.3±0.5 vs. 20.4±0.6 mL·kg min−1; p<0.0001) and was associated with a reduced peak CO (6.3±0.2 vs. 7.6±0.2 L·min−1, p<0.0001) and A-VO2 Diff (17±0.4 vs. 19±0.4 ml·dl−1, p<0.0007). The strongest independent predictor of peak VO2 was the change in A-VO2 Diff from rest to peak exercise (A-VO2 Diff reserve) for both HFPEF (partial correlant 0.58, standardized β coefficient 0.66; p=0.0002) and HC (partial correlant 0.61, standardized β coefficient 0.41; p=0.005) Conclusions Both reduced CO and A-VO2 Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-VO2 Diff reserve is an independent predictor of peak exercise VO2 suggests that peripheral, ‘non-cardiac’ factors are important contributors to exercise intolerance in these patients.