Abstract 15339: Molecular Analysis of Epigenetic Modification Process in Distressed Cardiomyocytes May Explor Indication of Mitral Valve Surgery for Advanced Heart Failure Associated With Non-ischemic Dilated Cardiomyopath

Abstract

Introduction: Mitral valve (MV) surgery for functional mitral regurgitation (MR) associated with advanced heart failure (HF) is a surgical challenge with surgical indication not clearly established. It was recently reported that the epigenetic modification, such as methylation or acetylation of histone H3, is closely related to functional reversibility of cardiomyocytes in advanced HF. Hypothesis: We herein hypothesized that epigenetic profiles in the left ventricle (LV) may be associated with clinical outcome of MV surgery for non-ischemic dilated cardiomyopathy (NIDCM)-causing advanced HF. Methods: Thirteen patients diagnosed as having NIDCM underwent chordal sparing MV replacement for severe MR associated with low ejection fraction (EF) (<35%) between 2012 and 2015. Intraoperatively biopsied LV tissue was immunohistologically labeled by histone H3 lysine 9 tri-methylation (H3K9me3) and acetylation (H3K9ac), and then the scores ranging from 0 to 12 were assigned as intensity and percentage of positive staining cardiac cell nuclei. Results: Four patients (31%) necessitated left ventricular assist device (LVAD) implantation for persistent low output syndrome post-MV replacement, and one patient died of cardiac failure on day 260. Preoperative factors assessed by routine echocardiogram or right heart catheter study, such as LVEF (26±3 vs 24±6%, p=0.49), LV end-systolic dimension index (159±49 vs 188±58 ml/m2, p=0.42), or mean pulmonary arterial pressure (27±11 vs 22±9mmHg, p=0.42), were not a predictive factor of LVAD implantation post-MV surgery. In contrast, preoperative LV stroke work index (LVSWI) was significantly lower in the patients who had LVAD implantation (13±2 vs 22±7 g·m/m2/beat, p=0.02). In addition, the scores of H3K9me3 and H3K9ac were significantly lower in the patients with LVAD implantation (3.0±0.7 vs 6.5±1.9, p<0.01 and 4.1±0.7 vs 8.9±1.9, p<0.01, respectively) and closely correlated with preoperative LVSWI. Conclusions: Reduced H3K9 methylation and acetylation in cardiomyocytes was closely related to preoperative poor LV performance and represented poor clinical outcome after MV replacement in advanced NIDCM, suggesting that these parameters may be useful factors in determining the surgical indication.