Improved methodology for establishing a mitral regurgitation animal model guided by intracardiac echocardiography

Mitral regurgitation (MR) is the most common valvular heart disease in the general population. Establishing a reproducible and stable MR model is crucial for exploring the pathogenesis and treatment strategies of MR. This study optimized the entire modeling process based on the transcatheter method, aiming to provide a more reliable and stable strategy for constructing large animal models of MR. A total of 12 adult male Small-tailed Han sheep were randomly allocated using a random number table into 2 groups (n=6 each): an intracardiac echocardiography (ICE) group and a transthoracic echocardiography (TTE) group. MR models were established in both groups by severing mitral valve chordae tendineae using biopsy forceps under ICE and TTE guidance, respectively. Successful model establishment was defined as an intraoperative regurgitation area ≥4 cm2. Postoperative echocardiographic follow-up was conducted for three months. Paired t-tests were conducted for within-group comparisons against baseline, independent t-tests for intergroup comparisons, 2-way repeated measures analysis of variance (ANOVA) for evaluating regurgitation area changes over time between groups, Fisher's exact test for comparing the distribution of regurgitation severity (mild vs. moderate-severe) between groups, and at the conclusion of the follow-up period, the heart was dissected to evaluate the degree of chordal damage. One sheep in the ICE group succumbed to heart failure on the 65th day post-operation, whereas the remaining 11 sheep survived until the end of the observation period. Postoperative ultrasound follow-up at 7, 60, and 90 days revealed significantly larger regurgitant jet areas in the ICE group (7.7±3.1, 8.8±5.5, 6.9±2.7 cm2) compared with TTE group (2.6±2.6, 2.7±2.3, 2.5±1.1 cm2) (P=0.012, P=0.031, P=0.005, respectively). Both groups exhibited left atrial enlargement, with dilation being more pronounced in the ICE group. Postoperative left ventricular volume and systolic function were well preserved in both groups. Cardiac dissection confirmed that the chordal damage in the ICE group was located at the ideal position, whereas no significant chordal rupture was observed in the TTE group. The ICE-guided method for establishing an MR model is simple, minimally invasive, highly reproducible, and capable of producing significant and stable regurgitation. This model is applicable for preclinical evaluation of interventional devices and research on pathophysiology.