Gender differences in determinants of oxygen transport cascade in heart failure

BACKGROUND: In heart failure trials using cardiopulmonary exercise tests (CPET) the number of women has been small, thus the current cutoffs are representative of male patients. In this study we aimed to test the mechanisms for difference in peak VO2 between men and women in patients with heart failure and preserved ejection fraction (HFpEF), and heart failure with reduced ejection fraction (HFrEF) using combined stress echocardiography (SE) and CPET.

METHODS: We assessed 178 subjects by CPET-SE divided into 3 groups (control, HFpEF, HFrEF) stratified based on gender. Various echo parameters (LV volumes, RV area, ejection fraction, stroke volume, E/e`) and ventilatory parameters (peak oxygen consumption [VO2] and A-VO2 difference) were measured.

RESULTS: Female HFpEF subjects showed attenuated increases in end diastolic volume (P= 0.04 for gender x time interaction), significantly increased E/e` (p=0.03) and LVEDV: E/e (p=0.04) throughout the protocol and attenuated increases in A-VO2 difference (P= 0.003). Female HFrEF subjects showed attenuated increases in end diastolic volume (P= 0.05), mostly after the anaerobic threshold, resulting in attenuated increase in peak stroke volume index (P= 0.01) and cardiac output (P= 0.05).

CONCLUSIONS: Combined CPET-SE tests allows individual noninvasive evaluation of exercise physiology stratified by gender. Female HFpEF patients have lower exercise capacity due to poorer LV compliance and attenuated peripheral oxygen extraction. However, female HFrEF patients have lower exercise capacity due to diminished increases in LV volumes at the last stages of stress resulting in attenuated increase in peak stroke volume and cardiac output.