An Innovative Apical-4-Chamber-long-axis Imaging Approach Precisely Tracks Progressive Deterioration of Mouse Ventricles, Atria, and Atrioventricular Valves
Authors: Kacira Ege , Oueis Mariam , Sturgill Sarah , Xu Xianyao , Hund Thomas , Ziolo Mark , Han Yuchi 
Published: May 2024

Transthoracic echocardiography stands as the primary non-invasive method for cardiac function evaluation in clinical settings. It’s widely used to assess chamber sizes, heart wall integrity, as well as the hemodynamic performance of the left ventricle (LV), right ventricle (RV), atria, and valves. However, applying comprehensive echocardiography assessments to mice has been challenging, primarily due to diffculties in obtaining on-axis apical 4-chamber views; most mouse studies have thus been restricted to evaluating the LV using short-axis M-mode assays. To overcome this limitation, we’ve recently developed a novel methodology to consistently obtain high-quality apical 4-chamber-long-axis (A4CLAX) view images of mouse heart. This advancement permits a range of clinically relevant functional assessments, including Long Axis Biplane (LAX-BP) assay, which has been shown to surpasses M-mode in estimating LV function. In this study, we delve into the breadth of comprehensive echocardiography assessments made possible for mice through the A4CLAX imaging approach. We performed a severe transverse aortic constriction (TAC) surgery on mice and monitored the pathological development in their hearts post-surgery. Alongside the expected hypertrophy, the LAX-BP assay revealed LV volumetric dilation as early as 1-week after TAC surgery Indicative of decompensated heart failure; however, m-mode was not able to pick up on this early dilation due to its lack of longitudinal assessment and inconsistent measurements of EDV and ESV. The apical 4 chamber view significantly improved the consistency and reliability of trans mitral and pulmonary vein doppler recordings and enabled us to reliably estimate the pressure relationships of the LV and Left Atrial (LA) pressure, which is consistent with the LAX-BP detected LV decompensation. Additionally, the high clarity of the 4 chamber images achieved improved visualization of both mitral and tricuspid valve leaflets. This allowed more precise characterization of valvular issues, including mitral regurgitation caused by LV dilatation, as well as identification of less common pathological occurrences like desynchronization of the tricuspid and mitral valve opening. A speckle tracking assay of the Right ventricle (RV) showed that a delayed contraction of the lateral apical RV wall caused the tricuspid valve to not open during the early filling phase, but rather at the atrial kick, leading to this valve desynchrony. This delayed contraction indicates a possible elevation of pulmonary pressure, as evidenced by pulmonary vein doppler indices and the analysis of pulmonary congestion. In conclusion, the innovative A4CLAX imaging technique revolutionizes murine heart analysis, bringing it in line with clinical echocardiography standards allowing for a whole heart analysis approach. It sensitively identifies subtle anomalies, providing a precise characterization of cardiac remodeling and disease progression in mouse hearts. This study has been supported by grants NIH-R01HL139006 and R21OD031965. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.