MItral VAlve prolapse Protocol (MIVAP): histological evidence of inflammatory clusters in patients undergoing surgical treatment of mitral valve

Abstract Mitral valve prolapse (MVP) is a prevalent valvular disease affecting 0.6-3.1% of the general population and can lead to serious complications, such as malignant ventricular arrhythmias (VA) and sudden cardiac death (SCD), which may be the first clinical presentation. Identifying high-risk patients is crucial for tailored diagnostic and therapeutic management. Moreover, in patients with MVP the incidence of new atrial fibrillation (AF) was 24% in patients initially in sinus rhythm during 10-year follow-up after MV surgery. This study prospectively investigates the correlation between sustained VA and AF at early follow-up and histopathologically identified inflammatory clusters in excised valves from patients undergoing surgical correction of MVP. Between October 2023 and April 2024, 38 patients at our institution underwent surgical correction of MVP. Clinical preoperative data and intraoperative samples were collected, including portions of the mitral leaflet and periannular tissue at the left atrioventricular junction, followed by histopathological examination. The primary endpoint of the study was the first occurrence of major adverse cardiovascular events (MACE) including sustained VA and AF, ventricular or atrial arrhythmic burden exceeding 20% as detected by 24-hour Holter ECG, in-hospital readmission or death from any cardiovascular cause. The aim of our study was to evaluate if the histopathological findings in surgical patients with MVP might be associated to increased risk of MACE at early postoperative follow-up. In the MIVAP study, 38 patients with MVP and surgical indication for mitral valve repair or replacement were enrolled. Based on the histopathological analysis, we divided the population into two groups: 17 patients (45%) with clear evidence of inflammatory infiltrate (Infl +) and 21 patients (55%) without inflammatory infiltrate (Infl -) at the level of the mitral valve. The inflammatory infiltrate was composed of macrophages, T lymphocytes, mast cells, and B lymphocytes. At the mean follow-up of 10 ± 4 months, the primary endpoint, after 2 months blanking period, occurred in 6 patients (16%) out of the overall population: 5 patients in Infl + group and 1 in Infl - group (p = 0.02). In patients undergoing cardiac surgery for MVP, the presence of local inflammatory infiltrate associated with LV fibrosis appears to act as a trigger for arrhythmias in the short-term following surgery. Currently, after evaluating risk factors as outlined by existing guidelines endomyocardial histological analysis of mitral valve specimens obtained during surgical intervention may aid in identifying MVP patients at high risk for developing sustained arrhythmias post-operatively. This approach could facilitate the development of novel therapeutic targets addressing inflammation and myocardial fibrosis in MVP, extending beyond patients with surgical indications.