Sex-Related Differences in Right Ventricle-Pulmonary Artery Coupling in HFpEF

pulmonary hypertension
Compared with women, men with HFpEF have been shown to be more compromised with respect to dynamic right ventricle-pulmonary artery uncoupling and reduced VO2.

In patients with heart failure with preserved ejection fraction (HFpEF), men have been shown to be more compromised with respect to dynamic right ventricle-pulmonary artery (RV-PA) uncoupling and reduced peak oxygen uptake (VO2) compared with women. A controlled analysis was conducted among patients from the Brigham and Women’s Hospital (BWH) Dyspnea Clinic, located in Boston, Massachusetts, and results were published in the journal CHEST.

Hypothesizing that women with HFpEF are more likely to have preserved RV-PA coupling while exercising, thus resulting in improved peak exercise aerobic capacity, the investigators sought to explore the differential effects of sex on RV-PA coupling during maximum incremental exercise in these individuals. Rest and exercise invasive pulmonary hemodynamics were evaluated in 22 men and 27 women with HFpEF. To further assess the discrepancy in RV-PA response between the 2 sexes, a total of 26 age-matched control individuals were included as well (11 men and 15 women).

The patients from the BWH Dyspnea Clinic were evaluated for unexplained exercise intolerance between March 2011 and January 2020, with resting supine right heart catheterization, followed by symptom-limited upright invasive cardiopulmonary exercise testing. End-systolic elastance (Ees) and pulmonary arterial elastance (Ea) were determined via use of single-beat analysis of RV pressure waveforms. Further, RV-PA coupling was established as the ratio of Ees/Ea.

Results of the study showed that both groups of HFpEF participants experienced decreased peak VO2 (percent predicted). Men with HFpEF, however, experienced a greater decrement in peak VO2 percent predicted compared with women (58%±16% vs 70%±15%, respectively; P =.05).

Men with HFpEF had more pronounced increases in RV afterload, peak Ea (1.8±0.6 mm Hg/mL/m2 vs 1.3±0.4 mm Hg/mL/m2, respectively; P <.05), and their RV contractility did not increase during exercise, which resulted in dynamic RV-PA uncoupling (0.9±0.4 vs 1.2±0.4, respectively; P <.05) and reduced stroke volume index augmentation. In contrast, women with HFpEF experienced augmentation in their RV contractile reserve in the face of increasing afterload, thus permitting better peak exercise RV-PA coupling and peak exercise aerobic capacity. 

The researchers concluded that additional studies are warranted to investigate the maladaptive mechanisms of RV-pulmonary vascular interaction between the sexes in patients with HFpEF.


Singh I, Oliveira RKF, Heerdt PM, Pari R, Systrom DM, Waxman AB. Sex-related differences in dynamic right ventricular-pulmonary vascular coupling in heart failure with preserved ejection fraction. CHEST. Published online December 31, 2020. doi:10.1016/j.chest.2020.12.028