Impact of ischemia on left atrial remodeling and dysfunction in swine models of mitral regurgitation

BACKGROUND Left atrial (LA) dysfunction is one of the predictive factors of worse outcomes after mitral valve surgery for mitral regurgitation (MR). We aimed to investigate the effect of MR etiology on progression of LA remodeling in swine MR models. METHODS MR was induced in 14 Yorkshire pigs using catheter-based procedures. Seven pigs underwent simultaneous occlusions of the left circumflex artery and the diagonal branch, which resulted in ischemic MR (IMR group). The other seven pigs underwent chordal severing to induce leaflet prolapse simulating degenerative MR (DMR group). Changes in LA volume and function were assessed at baseline, 1 and 3 months using echocardiography and hemodynamic evaluations. Histopathological assessments were conducted to evaluate LA hypertrophy and fibrosis. RESULTS At 3 months, quantitative MR severity was comparable and severe in both groups. Despite the similar degree of MR, minimum LA volume index increased significantly more in the IMR group (IMR: 11.9±6.4 to 73.2±6.4, DMR: 10.7±6.4 to 29.5±6.4 ml/m2, pinteraction=0.004). Meanwhile, increase in maximum LA volume index was similar between the groups, resulting in lower LA emptying function in the IMR group (IMR: 60.1±3.1 to 29.4±3.1, DMR: 62.4±3.1 to 58.2±3.1%, pinteraction=0.0003). LA reservoir strain assessed by echocardiography was also significantly lower in the IMR group. Histological analyses revealed increased LA cellular hypertrophy and fibrosis in the IMR group. CONCLUSIONS Ischemic MR is associated with aggressive remodeling and reduced emptying function compared to MR due to leaflet prolapse. Earlier intervention might be necessary for ischemic MR to prevent LA remodeling.