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

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 a novel
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/6N 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. Conclusion: 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.