Interstitial fibrosis is associated with left atrial remodeling and adverse clinical outcomes in selected low-risk patients with hypertrophic cardiomyopathy

Background: Cardiovascular magnetic resonance (CMR) extracellular volume (ECV) allows non-invasive detection of myocardial interstitial fibrosis, which may be related to diastolic dysfunction and left atrial (LA) remodeling in hypertrophic cardiomyopathy (HCM). While the prognostic role of LGE is well-established, interstitial fibrosis and LA dysfunction are emerging novel markers in HCM. This study aimed to explore the interaction between interstitial fibrosis by ECV, LA morpho-functional parameters and adverse clinical outcomes in selected low-risk patients with HCM. Methods: 115 HCM patients and 61 matched controls underwent CMR to identify: i) interstitial fibrosis by ECV in hypertrophied left ventricular LGE-negative remote myocardium (r-ECV); ii) LA indexed maximum (LAVi max) and minimum (LAVi min) volumes, ejection fraction (LA-EF) and strain (reservoir epsilon s, conduit epsilon e and booster epsilon a), by CMR feature-tracking. 2D-echocardiographic assessment of diastolic function was also performed within 6 months from CMR. A composite endpoint including worsening NYHA class, heart failure hospitalization, atrial fibrillation and all-cause death was evaluated at 2.3 years follow-up. HCM patients were divided into two groups, according to r-ECV values of controls. Results: Patients with r-ECV >= 29% (n = 45) showed larger LA volumes (LAVimax 63 vs. 54 ml/m(2), p < 0.001; LAVimin 43 vs. 28 ml/m(2), p < 0001), worse LA function (epsilon s 16 vs. 28%, epsilon e 8 vs. 15%, epsilon a 8 vs. 14%, LA-EF 33 vs. 49%, all p < 0.001) and elevated Nt-proBNP (1115 vs. 382 pg/ml, p = 0.002). LA functional parameters inversely correlated with r-ECV (epsilon s r = -0.54; LA-EF r = -0.46; all p < 0.001) and E/e' (epsilon s r = -0.52, LA-EF r = -0.46; all p < 0.006). r-ECV >= 29% and LAVi min >30 ml/m(2) have been identified as possible independent factors associated with the endpoint. Conclusions: In HCM diffuse interstitial fibrosis detected by increased r-ECV is associated with LA remodeling and emerged as a potential independent predictor of adverse clinical outcomes, on top of the well-known prognostic impact of LGE.