Exploring the prognostic value of myocardial inflammation in Fabry cardiomyopathy

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac involvement in Fabry Disease (FD) manifests as left ventricular hypertrophy (LVH) often complicated by myocardial fibrosis and/or inflammation. Indeed, glycosphingolipid storage does not explain the whole spectrum of FD pathophysiology. Lysosomal deposits of unmetabolized glycolipid substrates stimulate the activation of immunological pathways, taking to a chronic inflammatory process.1 In a subgroup of FD patients with late gadolinium enhancement (LGE), signs of myocardial inflammation can be detected by cardiac magnetic resonance (CMR) using T2-weighted (T2w) sequences and T2 mapping. T2 value in inferolateral wall (IL) has been described as the strongest predictor of increase in troponin level. 2 Aim The aims of the study were: 1) to compare CMR parameters in LVH and LGE positive FD patients with and without myocardial inflammation; 2) to verify if myocardial inflammation plays an incremental prognostic role in FD compared to LVH and LGE. Methods Among 190 consecutive FD patients referred for CMR, 47 patients with LVH and LGE were selected for this study. All patients underwent an extensive CMR protocol to provide a detailed evaluation of cardiac morphology and function, with multiparametric tissue characterization. Myocardial inflammation was detected by T2w and T2 mapping sequences. A comparison of CMR parameters between patients with and without inflammation was performed. A composite endpoint of cardiovascular (CV) events was used for survival analysis. Results No differences in age and Mainz Severity Score Index were found between LVH+/LGE+ FD patients with and without myocardial inflammation. Patients with inflammation showed significantly greater left ventricular mass index (LVMI) compared to patients without inflammation. Regarding tissue characterization, patients with myocardial inflammation had more extensive LGE and significantly higher ECV in IL wall. Native myocardial T1 was reduced in both groups without statistically significant difference. (Table 1) Myocardial inflammation always involved IL wall. During a median follow-up of 30 months, Kaplan-Meier curves showed similar event-free survival probability in patients with and without myocardial inflammation (Log-Rank p = 0,215, Figure 1). Conclusion In a population of LVH+/LGE+ FD patients, the presence of CMR signs of myocardial inflammation was associated with more severe LVH and more extensive LGE. However, the presence of myocardial inflammation did not showed an incremental prognostic value on CV outcomes on top of LVH and LGE. Larger studies are needed to verify this findings.