Postoperative plasma exosomal miR-21 and miR-133a signature in patients with left ventricular reverse remodelling after surgical mitral valve repair

introduction: Patients with mitral valve regurgitation(MR) show volume overload and progressive heart remodelling with increased left ventricular (LV) end-diastolic volume (EDV). Surgery is recommended for patients with substantial decay of global cardiac function (LV ejection fraction, LVEF) in order to reverse LV remodelling. However, approximately 10% patients show poor recovery. Identification of patients at high risk of post-operative LV remodelling may help preventive strategies. In this scenario, microRNAs delivered by plasma exosomes (pEXOs) might have a predictive value as well as complement the routine clinical measures of surgical outcome. Methods: Primary MR patients (N = 19; 45–71 y.o.)underwent implantation of a prosthetic mitral ring. LV remodelling was assessed by cardiac 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 and miR-1, miR-21, miR-133a, and miR-208a were measured by RT-qPCR. The same analysis was performed on healthy subjects with normal cardiac function (N = 8). Local ethical committee approved the study (EMIGRATEstudy, approval n°1529) and informed consent was obtained from all patients. Results: 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 reversed LV remodelling 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. Summary/Conclusion: Higher postoperative levels of pEXOs delivering miR-21 and 133a depict LV reverse remodelling after surgical mitral valve repair. Monitoring of exosomal microRNAs cargo might predict postoperative outcome in patients with MR.