• Inderjit Singh, OliveiraRudolf K FRKFDivision of Respiratory Diseases, Federal University of São Paulo-UNIFESP, São Paulo, Brazil., Paul M Heerdt, Rosa Pari, David M Systrom, and Aaron B Waxman.
• Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale New Haven Hospital and Yale School of Medicine, New Haven, CT.
• Chest. 2021 Jun 1; 159 (6): 2402-2416.

BackgroundRight ventricular (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Although female subjects are more likely to have HFpEF, male subjects have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary arterial (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known.Research QuestionThe goal of this study was to investigate the differential effects of sex on RV-PA coupling during maximum incremental exercise in patients with HFpEF.Study Design And MethodsThis study examined rest and exercise invasive pulmonary hemodynamics in 22 male patients with HFpEF and 27 female patients with HFpEF. To further investigate the discrepancy in RV-PA response between sex, 26 age-matched control subjects (11 male subjects and 15 female subjects) were included. Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance. RV-PA coupling was determined as the ratio of end-systolic elastance/PA elastance.ResultsBoth HFpEF groups experienced decreased peak VO2 (% predicted). However, male patients with HFpEF experienced a greater decrement in peak VO2 compared with female patients (58 ± 16% vs 70 ± 15%; P < .05). Male patients with HFpEF had a more pronounced increase in RV afterload, Ea (1.8 ± 0.6 mm Hg/mL/m2 vs 1.3 ± 0.4 mm Hg/mL/m2; P < .05) and failed to increase RV contractility during exercise, resulting in dynamic RV-PA uncoupling (0.9 ± 0.4 vs 1.2 ± 0.4; P < .05) and subsequent reduced stroke volume index augmentation. In contrast, female patients with HFpEF were able to augment RV contractility in the face of increasing afterload, preserving RV-PA coupling during exercise.InterpretationMale patients with HFpEF were more compromised regarding dynamic RV-PA uncoupling and reduced peak VO2 compared with female patients. This finding was driven by both RV contractile impairment and afterload mismatch. In contrast, female patients with HFpEF had preserved RV-PA coupling during exercise and better peak exercise VO2 compared with male patients with HFpEF.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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