Prognostic role of myocardial storage, hypertrophy, and inflammation/fibrosis in Fabry cardiomyopathy: a new predictive score including T1 values

AIMS: Limited data exist about the prognostic significance of the processes underlying Fabry Disease (FD) cardiomyopathy (storage, hypertrophy, inflammation/fibrosis) as detected by cardiac magnetic resonance (CMR). Notably, T1 mapping has had limited prognostic application primarily due to poor reproducibility across different sequences and vendors. This CMR study aimed to identify the prognostic weight of the different mechanisms of FD cardiomyopathy and to develop a predictive score of adverse cardiovascular (CV) events. METHODS AND RESULTS: This prospective, observational study enrolled 167 FD patients, who underwent CMR at baseline. The study endpoint was the composite of all-cause death, heart failure hospitalization, new-onset atrial fibrillation/flutter, non-sustained/sustained ventricular tachycardia, major bradyarrhythmias, and myocardial infarction with non-obstructive coronary arteries. Over a median follow-up of 40 months, 27 patients (16%) experienced the primary endpoint. Left ventricle mass index (LVMI) [HR 1.02 (1.02-1.03), P < 0.001], presence of late gadolinium enhancement (LGE) [HR 20.12 (6.02-67.24), P < 0.001] and its extent [number of LGE + segments: HR 1.51 (1.33-1.71), P < 0001], and septal T1 [HR 0.98 (0.97-0.99), <0.001], measured in both ShMOLLI and MOLLI sequences, were associated with the composite endpoint. None of the patients with normal T1 experienced adverse CV events. A multivariable model including age, LVMI, number of LGE+ segments, and T1 value showed a good performance in predicting the composite endpoint. CONCLUSION: We propose a 3-year prognostic score to predict CV outcome in FD, including age, LVMI, number of LGE+ segments, and septal T1. Normal T1 has a negative predictive value for adverse CV events irrespective of the acquisition setting.