Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice

Abstract Background: Transthoracic echocardiography remains the primary non-invasive method for assessing cardiac function in clinical practice. However, technical challenges in acquiring accurate apical 4-chamber-long-axis (A4CLAX) views have historically limited mouse studies to left ventricle (LV...

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Main Authors: Ege Kacira, Mariam F. Oueis, Nawal H. Tamimi, Sarah L. Sturgill, Xianyao Xu, Thomas J. Hund, Mark T. Ziolo, Yuchi Han, Isabelle Deschênes, Ji-dong Fu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-025-01036-w
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author Ege Kacira
Mariam F. Oueis
Nawal H. Tamimi
Sarah L. Sturgill
Xianyao Xu
Thomas J. Hund
Mark T. Ziolo
Yuchi Han
Isabelle Deschênes
Ji-dong Fu
author_facet Ege Kacira
Mariam F. Oueis
Nawal H. Tamimi
Sarah L. Sturgill
Xianyao Xu
Thomas J. Hund
Mark T. Ziolo
Yuchi Han
Isabelle Deschênes
Ji-dong Fu
author_sort Ege Kacira
collection DOAJ
description Abstract Background: Transthoracic echocardiography remains the primary non-invasive method for assessing cardiac function in clinical practice. However, technical challenges in acquiring accurate apical 4-chamber-long-axis (A4CLAX) views have historically limited mouse studies to left ventricle (LV) assessment using parasternal short-axis (SAX) M-mode imaging. Methods: To overcome this limitation, we developed an A4CLAX imaging approach for mice and performed a comparative analysis with established echocardiographic methods to assess cardiac function in healthy mouse hearts. To evaluate the utility of A4CLAX in detecting disease progression, we longitudinally monitored cardiac function of C57BL/6 N mice (male and female) following severe transverse aortic constriction (TAC), using both long-axis biplane (LAX-BP) and conventional SAX M-mode assays. Results: Here we show that LAX-BP echocardiography demonstrates volumetric accuracy comparable to cardiac magnetic resonance (CMR) and detects significant LV functional decline within the first week post-TAC–changes that are not clearly captured by M-mode imaging. Importantly, A4CLAX further enables clinically relevant Doppler assessments, allowing detection of mitral valve regurgitation, restrictive filling patterns, and desynchronized valve motion. It also facilitates right ventricle (RV) functional evaluation and improved atrial visualization, revealing progressive enlargement of the left atrial (LA) and left atrial appendage (LAA) associated with worsening diastolic function. Conclusions: The A4CLAX imaging approach provides clinically comparable, comprehensive echocardiographic evaluation in murine models and offers improved sensitivity for detecting subtle changes in cardiac performance during disease progression.
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spelling doaj-art-3c75b95ebf6140b698272dba2edeed0b2025-08-20T04:03:07ZengNature PortfolioCommunications Medicine2730-664X2025-07-015111210.1038/s43856-025-01036-wAdvanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in miceEge Kacira0Mariam F. Oueis1Nawal H. Tamimi2Sarah L. Sturgill3Xianyao Xu4Thomas J. Hund5Mark T. Ziolo6Yuchi Han7Isabelle Deschênes8Ji-dong Fu9Department of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, The Ohio State UniversityDepartment of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, The Ohio State UniversityDepartment of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, The Ohio State UniversityDepartment of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, The Ohio State UniversityDepartments of Internal Medicine and Biomedical Engineering, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, Wexner Medical Center, The Ohio State UniversityDepartments of Internal Medicine and Biomedical Engineering, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, Wexner Medical Center, The Ohio State UniversityDepartment of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, The Ohio State UniversityCardiovascular Division, Department of Internal Medicine, The Dorothy M. Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State UniversityDepartment of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, The Ohio State UniversityDepartment of Physiology and Cell Biology, The Dorothy M. Davis Heart and Lung Research Institute, Frick Center for Heart Failure and Arrhythmia, The Ohio State UniversityAbstract Background: Transthoracic echocardiography remains the primary non-invasive method for assessing cardiac function in clinical practice. However, technical challenges in acquiring accurate apical 4-chamber-long-axis (A4CLAX) views have historically limited mouse studies to left ventricle (LV) assessment using parasternal short-axis (SAX) M-mode imaging. Methods: To overcome this limitation, we developed an A4CLAX imaging approach for mice and performed a comparative analysis with established echocardiographic methods to assess cardiac function in healthy mouse hearts. To evaluate the utility of A4CLAX in detecting disease progression, we longitudinally monitored cardiac function of C57BL/6 N mice (male and female) following severe transverse aortic constriction (TAC), using both long-axis biplane (LAX-BP) and conventional SAX M-mode assays. Results: Here we show that LAX-BP echocardiography demonstrates volumetric accuracy comparable to cardiac magnetic resonance (CMR) and detects significant LV functional decline within the first week post-TAC–changes that are not clearly captured by M-mode imaging. Importantly, A4CLAX further enables clinically relevant Doppler assessments, allowing detection of mitral valve regurgitation, restrictive filling patterns, and desynchronized valve motion. It also facilitates right ventricle (RV) functional evaluation and improved atrial visualization, revealing progressive enlargement of the left atrial (LA) and left atrial appendage (LAA) associated with worsening diastolic function. Conclusions: The A4CLAX imaging approach provides clinically comparable, comprehensive echocardiographic evaluation in murine models and offers improved sensitivity for detecting subtle changes in cardiac performance during disease progression.https://doi.org/10.1038/s43856-025-01036-w
spellingShingle Ege Kacira
Mariam F. Oueis
Nawal H. Tamimi
Sarah L. Sturgill
Xianyao Xu
Thomas J. Hund
Mark T. Ziolo
Yuchi Han
Isabelle Deschênes
Ji-dong Fu
Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice
Communications Medicine
title Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice
title_full Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice
title_fullStr Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice
title_full_unstemmed Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice
title_short Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice
title_sort advanced 4 chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice
url https://doi.org/10.1038/s43856-025-01036-w
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