Key result
Women with HFpEF had similar exercise capacity to men (66% vs 68% predicted peak O2 consumption; P=.38) but worse biventricular systolic and diastolic reserve and peripheral O2 extraction.
Why the study?
Sex differences in HFpEF are established, but insights into the mechanistic drivers of these differences remain limited.
Does female sex affect resting and exercise gas exchange and hemodynamic parameters in patients with HFpEF?
Cross-Sectional (n=295)
No
Does female sex affect resting and exercise gas exchange and hemodynamic parameters in patients with HFpEF?
Absolute Event Rate: 66% vs 68%
p-value: p=.38
Women with HFpEF demonstrate distinct cardiac and extracardiac deficits during exercise compared to men, highlighting sex-specific pathophysiological mechanisms despite similar percent predicted exercise capacity.
Suggests sex-specific exercise pathophysiology in HFpEF; hypothesis-generating for targeted trials.
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 [O2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70; SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2 β=-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 O2 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.
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Lau et al. (2019) conducted a cross-sectional in Heart failure with preserved ejection fraction (HFpEF) (n=295). Female sex vs. Male sex was evaluated on Percent predicted peak oxygen [O2] consumption (p=.38). Women with HFpEF had similar exercise capacity to men (66% vs 68% predicted peak O2 consumption; P=.38) but worse biventricular systolic and diastolic reserve and peripheral O2 extraction.
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