Hemodynamic Sex‐differences in Diastolic Function

Abstract

BackgroundIn the past decade, cardiac research has focused on the emerging crisis of diastolic dysfunction, commonly observed in patients with heart failure with preserved ejection fraction (HFpEF) — a disorder with ineffective management strategies. Diastolic dysfunction is abnormal active relaxation and/or passive stiffness of the ventricle. Because echocardiography is non‐invasive and accessible to more specialities, it remains widely used in the diagnosis and prognostic gradation of diastolic dysfunction. However, echocardiography provides indirect estimations of diastolic indices because diastolic measures were calibrated based on direct measures of end diastolic filling pressure (the gold standard for diastolic assessment). As it is increasingly evident that the manifestation of heart failure in men/males and women/females is not the same, a focus on sex‐specific mechanisms and physiology of diastole is warranted.Experimental ApproachThe primary objective of this work is to perform a comprehensive hemodynamic analysis of diastolic function in males and females to highlight sex‐differences that exist in diastolic physiology and provide implications in cardiac pathology. Male and female Wistar rats were anesthetized with isoflurane and a pressure catheter was inserted into the right carotid artery and advanced into the left ventricle. Pressure measurements were sampled at 2kHz and digitized using custom software. Diastolic parameters – end diastolic pressure (EDP), maximum relaxation rate (dP/dtmin), isovolumetric relaxation time constant (Tau Weiss, Glantz, Logistic) – were analyzed to evaluate diastolic function.Results and ConclusionsDiastolic function in healthy males and females is not equal, suggesting there are sex‐specific differences in diastolic physiology. In a pathological state, each of the diastolic parameters follows its own unique time course until severe dysfunction is present, suggesting that diastole cannot be reconciled by any one parameter. EDP, dP/dtmin and Tau Logistic should be used together to stratify dysfunction as diastole is a dynamic process and each parameter captures a specific nuance.Support or Funding InformationCanadian Institutes of Health Research