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

Background: Women 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.Methods: PV 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 (PVA(iso)30), as the integrated metric of LV function. LV volume at an end-diastolic pressure of 30 mmHg (V30) indexed ventricular capacity.Results: 202 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 PVA(iso)30 (9094 vs 10,255 mmHg*mL/m(2), p = 0.02) driven by reduced ventricular capacitance (V30 54 vs 62 mL/m(2), p < 0.001). In multivariable linear regression indexed V30 was an independent predictor of exercise capacity.Conclusion: Impaired 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.