Myocardial deformation imaging by 2D speckle tracking echocardiography for assessment of diastolic dysfunction in murine cardiopathology

Abstract

Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.

Mechanical loading reveals an intrinsic cardiomyocyte stiffness contribution to diastolic dysfunction in murine cardiometabolic disease

“…This dietary regime employed in this study has been well characterized as a model of diastolic dysfunction, with gradual development of metabolic disturbance (stable rate of weight gain and mild hyperglycemia), with maintained systolic function (ejection fraction and fractional shortening). As has been reported previously, over the time span of the dietary intervention differential fibrosis is not observed (Daniels et al, 2022;Wells et al, 2023;data not shown).The data presented here are consistent with clinical observations linking cardiometabolic disease and diastolic dysfunction.…”

“…4G). To evaluate possible influence of mechanical state on the Ca As we have reported previously, over the time span of the dietary intervention differential fibrosis is not observed (Daniels et al, 2022;Wells et al, 2023). The finding of increased stiffness in cardiometabolic disease is consistent with some aspects of prior experiments involving animal feeding of obesogenic diets, using other rodent preparation types -including permeabilized cardiomyocytes, tissue strips/papillary muscles, and non-paced cardiomyocytes (Leopoldo et al, 2010;Gonçalves et al, 2016;Sowers et al, 2020).…”

“…In diastolic dysfunction, the relaxation and filling phases of the cardiac cycle are impaired and the condition is generally described qualitatively as an increase in left ventricular wall ‘stiffness’ (or by decrease in compliance, the inverse of stiffness) (Daniels et al ., 2022; Janssens et al ., 2024). Clinically and experimentally, reduced compliance can be measured invasively as an elevation in left ventricular filling pressure or an increase in the gradient of the diastolic pressure-volume relationship.…”