Sex-related differences in dynamic right ventricular-pulmonary vascular coupling in heart failure with preserved ejection fraction.

BACKGROUND: Right ventricle (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Females are more likely to have HFpEF but males have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary artery (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known.

METHODS: We examined rest and exercise invasive pulmonary hemodynamics in 22 male HFpEF and 27 female HFpEF patients. In order to further investigate the discrepancy in RV-PA response between sex, we included 26 age matched control subjects (11 males and 15 females). Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance (Ea). Right ventricular-pulmonary artery (RV-PA) coupling was determined as the ratio of Ees/Ea.

RESULTS: Both HFpEF groups experienced decreased peak VO2 (%predicted). However, male HFpEF patients experienced greater decrement in peak VO2 compared to females (58±16 vs. 70±15%; p<0.05). Male HFpEF had more pronounce increase in RV afterload, Ea (1.8 ± 0.6 vs. 1.3 ± 0.4 mmHg/mL/m2 ; p<0.05) and failed to increase RV contractility during exercise, resulting in dynamic RV-PA uncoupling (0.9 ± 0.4 vs. 1.2 ± 0.4; p<0.05) and resulting reduced stroke volume index augmentation. In contrast, female HFpEF patients were able to augment RV contractility in face of increasing afterload, preserving RV-PA coupling during exercise.

CONCLUSION: Male HFpEF patients were more compromised with regards to dynamic RV-PA uncoupling and reduced peak VO2 compared to females. This was driven by both RV contractile impairment and afterload mismatch. In contrast, female HFpEF patients had preserved RV-PA coupling during exercise and better peak exercise VO2 compared to male HFpEF.