High Plasma Levels of Exosomal Mir21 and Mir133a Are Associated with LV Reverse Remodelling after Surgical Mitral Valve Repair

Mitral valve regurgitation (MR) is the most common cardiac valvular disease associated with increased morbidity and mortality. Patients are characterized by volume overload and progressive increase of left ventricular (LV) end‐diastolic volume (EDV). Surgery is recommended for patients with substantial loss of global cardiac function (LV ejection fraction, LVEF). A correctly timed surgery for MR can reverse LV remodeling. Identification of patients at high risk of post‐operative LV remodeling may help to act with preventive strategies. In this scenario, microRNAs delivered by plasma exosomes (pEXOs), smallest extracellular nanovesicles, might have a predictive value. Primary MR patients (N=19; 45–71 y.o.) underwent implantation of a prosthetic mitral ring. LV remodeling was assessed by cadiac magnetic resonance imaging and pEXOs were isolated by optimized ultracentrifugation before surgery (T0) and six months after surgery (T1). Isolated pEXOs were quantified by nanoparticle tracking analysis (NanoSight) and miR‐1, miR‐21, miR‐133a and miR‐208a were measured by RT‐qPCR. The same analysis was performed healthy subjects with normal cardiac function (Control, N=8). pEXOs levels at T0 were lower (−32%, p=0.02) in patients with worst postoperative LV function, while they were higher at T1 (+31%, p=0.03) in patients with LV reverse remodeling after surgery. At T1, the increase in pEXOs levels was associated to decreased heart mass index (−13%, p=0.02) and higher levels of exosomal miR‐21 (+78%, p=0.02) and miR‐133a (+69%, p=0.05) were detected in patients with improved LV function. In conclusion, higher postoperative levels of pEXOs and exosomal miR‐21 and 133a mark LV reverse remodeling after mitral valve repair. Combined measurements of circulating exosomes and their microRNAs cargo might represent potential novel perioperative markers in patients with MR.