Sex Differences in Cardiometabolic Traits and Determinants of Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Importance Sex differences in heart failure with preserved ejection fraction (HFpEF) have been established, but insights into the mechanistic drivers of these differences are limited. Objective To examine sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with HFpEF. Design, Setting, and Participants This cross-sectional study was conducted at a single-center tertiary care referral hospital from December 2006 to June 2017 and included 295 participants who met hemodynamic criteria for HFpEF based on invasive cardiopulmonary exercise testing results. We examined sex differences in distinct components of oxygen transport and utilization during exercise using linear and logistic regression models. The data were analyzed from June 2018 to May 2019. Main Outcomes and Measures Resting and exercise gas exchange and hemodynamic parameters obtained during cardiopulmonary exercise testing. Results Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years) and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men, women with HFpEF in this tertiary referral cohort had fewer comorbidities, including diabetes, insulin resistance, and hypertension, and a more favorable adipokine profile. Exercise capacity was similar in men and women (percent predicted peak oxygen [O-2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O-2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: Delta LVEF beta = -1.70; SE, 0.86; P < .05; Delta RVEF beta = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: beta = 0.63; SE, 0.31; P = .04), and peripheral O-2 extraction (C(a-v)O-2 beta=-0.90, SE=0.22; P < .001)). Conclusions and Relevance Despite a lower burden of cardiometabolic disease and a similar percent predicted exercise capacity, women with HFpEF demonstrated greater cardiac and extracardiac deficits, including systolic reserve, diastolic reserve, and peripheral O-2 extraction. These sex differences in cardiac and skeletal muscle responses to exercise may illuminate the pathophysiology underlying the development of HFpEF and should be investigated further. Question Are there differences in cardiometabolic profiles and exercise hemodynamic parameters in men and women with heart failure with preserved ejection fraction (HFpEF)? Findings In this cross-sectional study including 295 participants, compared with men, women with HFpEF demonstrated similar reductions in the percent predicted peak maximum level of oxygen consumption and greater deficits in oxygen delivery and utilization during exercise despite a lower burden of comorbidities in a cohort of rigorously defined HFpEF. Meaning The study's findings suggest that there are sex differences in the cardiac and skeletal muscle responses to exercise in HFpEF. This cross-sectional study examines sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with heart failure with preserved ejection fraction.