Background: Functional mitral regurgitation (FMR) is one of the most common heart valve diseases that is a sequel of left ventricular remodelling. Although mitral valve annuloplasty is a standard treatment of FMR, the recurrence of FMR is a major drawback and occurs in 10–50% of patients. The REFORM-MR registry aims to investigate the effectiveness of standardized papillary muscle relocation and ring annuloplasty and to identify the risk factors associated with recurrent FMR. Methods: REFORM-MR is a prospective, multicenter registry that enrols consecutive FMR patients across five sites in Germany. All patients with FMR and restricted movement of leaflets during systole (i.e., type IIIb mitral regurgitation) undergoing standardized subannular repair in combination with mitral valve annuloplasty are included in the study. The primary objective is to examine the effect of combined papillary muscle relocation and ring annuloplasty on the recurrence of FMR at 2 years postoperatively. The secondary objectives are MACCE rate, reinterventions on the mitral valve and cardiac-related mortality in the study cohort. Echocardiography core-lab and MRI core-lab will provide anonymized analysis of the imaging data in the REFORM-MR registry. Student’s t-test or Mann–Whitney U test for continuous variables and the Chi-Square or Fisher exact test for categorical variables are used for group comparisons. Kaplan–Meier analyses is performed for survival and safety outcomes. Results: As of May 2021, a total of 97 patients were enrolled across five sites in Germany. Conclusions: The results of this study will help define the outcomes of combined papillary muscle relocation and ring annuloplasty in the FMR treatment in a multicentre setting and to improve the understanding of the limitations of subannular repair procedures while treating patients with type III FMR. Trial registration clinicaltrials.gov Identifier: NCT03470155.

Pathological cardiac hypertrophy is a critical factor leading to cardiomyopathy and ultimately heart failure. While several signaling pathways controlling cardiac hypertrophy have been identified, the molecular mechanisms underlying their precise regulation remain incompletely understood. Strip1, a structural component of STRIPAK complexes, has been implicated in various cellular functions; however, its role in cardiomyocytes is uncharacterized. Here we identify Strip1 as a potent anti-hypertrophic factor, controlling cell size and the hypertrophic gene program in neonatal rat ventricular cardiomyocytes (NRVCMs). STRIP1 expression was found to be significantly reduced in human dilated and ischemic cardiomyopathies (DCM/ICM), as well as in murine stress model induced by transverse aortic constriction (TAC). In a knockdown model with morpholino-driven STRIP1 reduction in zebrafish in vivo, impaired cardiac function and heart failure–like features were observed. Interestingly, Strip1 localized to the nucleolus in NRVCMs, suggesting a putative nuclear/epigenetic role in cardiomyocytes. Furthermore, our data support association of Strip1 with cardiac STRIPAK complex, modulating kinase activities, including MST1/MST2 and MST4. Mechanistically, Strip1 appears to influence prohypertrophic signaling, including Hippo- and Calcineurin/NFAT-related pathways, which may contribute to pathological cardiac remodeling. Collectively, these findings establish Strip1 as an important modulator of cardiomyocyte hypertrophy and a potential therapeutic target for cardiomyopathy and heart failure.