Gender differences in the evolution of echocardiographic HFpEF characteristics through age deciles: is menopause an inflection point?

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is more prevalent with advancing age and in females. Since sex hormones have trophic effects, menopause may be an inflection point in HFpEF gender characteristics. Aim To compare left ventricular (LV) echocardiographic parameters between gender, through age deciles. Methods A sequential "normal" outpatient cohort in sinus rhythm with Ejection Fraction (EF) >50%, ≤ mild valvular dysfunction, normal chamber sizes and tricuspid regurgitation (TR) gradient <39mmHg were included. Analysis was performed by Kruskal-Wallis and Mann-Whitney U tests. Results are median (quartiles) and p-values of <0.05 were considered significant. Results In 634 patients (65% females), EF tended be larger in females from the fifties decile; females EF 62% (59,65) versus males 60 (56,64) p= 0.013, sixties 62 (58,66) versus 61 (58,64), p=0.07, seventies 63 (59,67) versus 60 (55,64) p=0.009. Mitral inflow characteristics of HFpEF (E:A decreased and E;e’ increased) and TR gradient (increased) progressively evolved throughout the deciles, with no apparent gender difference (males and females all p<0.001). However, while body surface area (BSA) normalised LV diastolic diameters decreased in males (p<0.05) and females (p<0.01), LV systolic diameter (decrease, p<0.01) and left atrial size (increase, p<0.01) only changed in females. Conclusions Whilst age progressively alters hemodynamic echocardiographic characteristics of LV diastolic dysfunction in both sexes, females demonstrate larger LVEF from the fifties decade and left sided structural changes (smaller LV systolic diameter and larger left atrial size) not seen in males. This chronology supports a potential role of loss of sex hormones in HFpEF aetiology.