Sex related differences in exercise performance in patients with hypertrophic cardiomyopathy: Hemodynamic insights through non-invasive pressure volume analysis

Abstract

BackgroundWomen with HCM have worse cardiopulmonary exercise performance compared to men. We used non-invasive pressure-volume (PV) analysis to delineate sex related hemodynamic differences in HCM. MethodsPV loops were constructed from echocardiograms using left ventricular (LV) volumes indexed to body surface area, Doppler estimates of LV end-diastolic pressure and blood pressure. The end-systolic PV relationship (ESPVR) and end-diastolic PV relationship (EDPVR) were derived from validated single-beat techniques. The area between the ESPVR and EDPVR (isovolumetric PV area), was indexed to an LV end-diastolic pressure of 30 mmHg (PVAiso30), as the integrated metric of LV function. LV volume at an end-diastolic pressure of 30 mmHg (V30) indexed ventricular capacity. Results202 patients were included, 56 women. Women were older (51 vs 44 years, p = 0.012) and had reduced exercise capacity (5.6 vs 6.9 METs, p < 0.001). Only 32 patients (16%) had a peak gradient >30 mmHg at rest with no sex differences. Women had significantly lower indexed PVAiso30 (9094 vs 10,255 mmHg*mL/m2, p = 0.02) driven by reduced ventricular capacitance (V30 54 vs 62 mL/m2, p < 0.001). In multivariable linear regression indexed V30 was an independent predictor of exercise capacity. ConclusionImpaired exercise capacity in women with HCM appears associated with abnormalities in passive diastolic properties, suggesting a unique pathophysiology compared to men, and a potential difference in viable therapeutic molecular targets.