Non-Ischemic Fibrosis on Cardiac Magnetic Resonance Impacts Adverse Left Ventricular Remodeling and Mortality Among Patients with Functional Mitral Regurgitation

Introduction: Functional mitral regurgitation (FMR) alters left ventricular (LV) remodeling, providing a nidus for non-ischemic fibrosis (NIF). Cardiac magnetic resonance (CMR) can measure FMR and LV tissue properties. Prevalence, remodeling manifestations, and prognostic implications of NIF in patients with FMR are unknown. Hypothesis: Among post-myocardial infarction (MI) patients with FMR, NIF associates with advanced LV remodeling and predicts adverse prognosis. Methods: The population comprised post-MI patients with FMR undergoing CMR. CMR exams were retrieved from a single-center registry, reviewed for MR etiology (degenerative excluded) and analyzed for FMR severity, LV structure/function, and late gadolinium enhancement (LGE) including ischemic pattern MI and NIF, which was defined via established criteria (mid-myocardial or epicardial LGE). Follow-up was performed for all-cause mortality. Results: 467 consecutive FMR patients (74% male, 63±16 years old) were studied, of whom 14% had NIF. Prevalence of NIF increased stepwise with FMR severity (12% mild, 16% moderate, 21% severe; p=0.33). Patients with NIF had higher LV end-diastolic (241±72ml vs 194±64ml) and end-systolic volumes (174±70ml vs 120±63ml), paralleled by lower EF (31±13% vs 41±15%) and stroke volumes (67±20ml vs 74±24ml); all p<0.001. LV infarct size was similar between patients with and without NIF (13±8.6 vs 15±10, p=0.17). During follow-up (mean 3.0±2.5 years), overall mortality was 14% and was increased in patients with advanced (≥ moderate) FMR (HR 1.65 [CI 1.13-2.42], p=0.01) and NIF (HR 2.35 [CI 1.32-4.19], p=0.004: Figure). In multivariate analysis, NIF conferred over a 2-fold increase in risk for death (HR 2.15 [CI 1.20-3.85], p=0.01) independent of age and FMR severity. Conclusions: Among post-MI patients with FMR, NIF identifies an aggressive phenotype as evidenced by associations with adverse LV remodeling on CMR and increased mortality.