Flail Leaflets and Papillary Muscle Fibrosis: Potential Substrate for Ventricular Arrhythmias in Valvular Mitral Regurgitation

Objectives Ventricular arrhythmias have been associated with mitral valve prolapse, but the mechanisms behind this association remain poorly defined. In our experimental model of mitral regurgitation (MR), we observed spontaneous arrhythmias and aimed to characterize their anatomical and electrophysiological substrates. Methods Fourteen canines (24±4kg) underwent 24-hour Holter and LGE-MRI at baseline. Endovascular chordal avulsion was performed in 8 animals. Severe MR was created under echocardiographic guidance with evidence of a flail leaflet, an eccentric wall-impinging jet or jet to LA area ratio greater than 70%. After 6 months of survival, baseline imaging was repeated for MR animals and cardiac tissue samples were collected for histology. Results Following chordae avulsion, the median regurgitant fraction was 76% [76%, 80%]. Six MR animals survived 6.0 [5.8, 6.0] months. The median increase in LA volume was 87%[62%, 114%] ( P =.020) and LV end-diastolic volume increased by 23%[5%, 50%]( P =.141) from baseline. LGE in the left atrium increased non-significantly from 1.0%[0.6%, 1.0%] to 1.9% [1.0%, 2.9%]( P =.125). One animal experienced spontaneous arrhythmias on repeat Holter, which included a 36-second episode of sustained ventricular tachycardia and a 126-second episode of atrial fibrillation. The sustained VT morphology was consistent with a right bundle branch block and left inferior axis pattern, suggesting a left ventricular origin. This subject exhibited visible LGE in bilateral papillary muscles on the terminal scan. Histology confirmed patchy replacement fibrosis and lymphocytic infiltration in the mid-papillary muscles, which was not present in any other animals. Conclusions In our experimental model of mitral regurgitation, volume overload led to chamber enlargement and hypertrophy In the only animal with spontaneous atrial and ventricular arrhythmias, there was marked atrial and papillary muscle fibrosis, suggesting an association with arrhythmogenicity.