Relative Impairments in Hemodynamic Exercise Reserve Parameters in Heart Failure With Preserved Ejection Fraction: A Study-Level Pooled Analysis

Objectives: The aim of this study was to compare the relative impairment in different exercise hemodynamic reserve parameters in patients with heart failure with preserved ejection fraction (HFpEF) and control patients using a study-level meta-analysis. Background: A cardinal manifestation of chronic HFpEF is severely decreased exercise capacity. Developing effective therapies for exercise intolerance in HFpEF requires optimal understanding of the factors underlying exercise intolerance. Methods: Data were included from 17 unique cohorts that measured peak oxygen uptake and hemodynamic or echocardiographic parameters during exercise in patients with HFpEF and control subjects in this meta-analysis. Standardized mean differences (SMDs) in the exercise reserve (exercise − resting) measures of hemodynamic or echocardiographic parameters between the HFpEF and control groups were pooled in a random-effects meta-analysis. Results: The pooled analysis included 910 patients with HFpEF and 476 control subjects. In pooled analysis, patients with HFpEF had significantly lower peak oxygen uptake (SMD: −2.13; 95% confidence interval [CI]: −2.68 to −1.57). Among hemodynamic exercise reserve parameters, the largest impairment was observed in chronotropic response reserve (change in heart rate from rest to peak exercise; SMD: −1.87; 95% CI: −2.44 to −1.29), followed by exaggerated increase in pulmonary capillary wedge pressure with exercise (SMD: 1.78; 95% CI: 1.46 to 2.09). Significant abnormalities were also observed in the arteriovenous oxygen difference reserve and stroke volume reserve between the HFpEF and control groups. Conclusions: The most consistent and severe hemodynamic reserve abnormalities observed in patients with HFpEF were impairment in chronotropic reserve and exaggerated increase in pulmonary capillary wedge pressure with exercise. These may be important targets for therapeutic strategies to improve exercise tolerance in patients with HFpEF.