(P122) WHY IS HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) MORE COMMON IN WOMEN THAN MEN? EXPLORING ABNORMALITIES IN PULSITILE ARTERIAL LOAD AS DISTINCT FEATURE OF THE HFPEF SYNDROME IN WOMEN

Background: Heart failure with preserved ejection fraction (HFpEF) is more common in women than men, but the bases for these sex differences are incompletely understood. Abnormalities in pulsatile arterial load can negatively affect cardiovascular performance, contributing to HFpEF development. Further, although elevated left ventricular (LV) filling pressures and coronary microvascular dysfunction (CMVD) are key features of HFpEF, the interplay between arterial hemodynamics and these key HFpEF features in men and women is unknown. To understand how hemodynamic abnormalities may contribute to the greater prevalence of HFpEF in women, we sought to: (1) assess arterial hemodynamic differences between men and women with HFpEF, compared to age- and sex-matched controls, and (2) determine whether alterations in arterial hemodynamics correlated with elevated LV filling pressures and CMVD in men and women.

METHODS AND RESULTS: We performed a cross-sectional study of 32 HFpEF participants and 26 age- and sex-matched controls. HFpEF was defined according to ESC Guidelines. Arterial hemodynamics were non-invasively assessed with validated methodology combining arterial tonometry with transthoracic echocardiography (TTE). LV filling pressures were assessed with TTE, using the mitral E/e’ ratio as per ASE guidelines. After excluding epicardial coronary artery disease, CMVD was assessed by 82Rb positron emission tomography (PET) as the myocardial flow reserve (MFR). We divided the sample based on sex and performed multivariable linear regression to determine whether the presence of HFpEF was associated with altered arterial hemodynamics in men and women. We then assessed the association of abnormal arterial hemodynamics with mitral E/e’ and PET-MFR in men and women, using multivariable linear regression. Men and women did not differ with respect to underlying characteristics (Table). HFpEF participants had significantly higher E/e’ ratio, RVSP and lower MFR than controls (p < 0.05 for each). Among women, HFpEF was associated with higher pulsatile arterial load (Image) as compared to age- and sex-matched controls without HFpEF. This association was not observed in men. Furthermore, among women only, higher aortic characteristic impedance (Zc) and lower proximal arterial compliance (PAC) were associated with higher E/e’ and lower MFR (Image).

Conclusion: Although both men and women with HFpEF exhibit cardiac abnormalities (higher E/e’, RVSP and greater CMVD) compared to controls, our findings suggest a distinct arterial phenotype unique to older women with HFpEF, which independently correlates with key pathophysiological abnormalities of the HFpEF syndrome. This highlights assessment of pulsatile arterial load as a potential tool for early detection and therapeutic targeting of HFpEF in women.