Role of myocardial inflammation in the progression of Fabry cardiomyopathy: a multicentre cardiac magnetic resonance study

Background Inflammation plays a central role in the pathophysiology of Fabry Disease (FD) and can be assessed by cardiac magnetic resonance (CMR) using T2 mapping. However, its significance in the progression of cardiomyopathy remains unclear. Purpose To evaluate the relationship between CMR T2 values and the progression of tissue alterations, namely late gadolinium enhancement (LGE), in patients with FD. Methods 185 pairs of CMR examinations, derived from 105 FD patients, were retrospectively analysed and categorized into four groups based on LGE status: A) absence of LGE on both examinations; B) absence of LGE on the first CMR, with new LGE appearance at follow-up; C) presence of LGE on the first CMR that remained unchanged at follow-up; D) presence of LGE on the first CMR that increased at follow-up. T2 was measured in the basal inferolateral segment and, for LGE positive patients, in the LGE area (ROI:LGE) and it was reported as Z-score. Comparative analyses between groups were performed, and the predictive value of the T2 z-score for the occurrence/extent of LGE was tested. Additionally, the correlation between T2 values and LGE extent was explored. Results Among LGE-negative patients at baseline, T2 Z-score at the first CMR of each pair was significantly higher in patients who developed LGE at follow up (Group B) compared to those who did not (Group A) (1.67 [0.33; 2.00] vs. 0.00 [-0.67; 1.00], p=0.0004). Among LGE-positive patients at baseline, T2 Z-score at the first CMR was significantly higher in Group D (LGE increased at the next exam) compared to Group C (LGE unchanged at follow up) (4.33 [2.83; 5.50] vs. 3.00 [2.67; 3.67], p=0.036). (Figure 1). No significant differences were observed in other clinical, demographic and CMR parameters. High T2 Z-scores at baseline were identified as predictive factors for the appearance (odds ratio [OR] 4.74, p=0.0008) or extension (OR 1.57, p=0.02) of LGE, independently of other CMR parameters. Finally, the correlation between T2 Z-score and LGE extension was assessed, showing a significant, almost linear, relationship for LGE percentages >10% (figure 2). Conclusions Myocardial inflammation, quantified by T2-mapping, is a predictive factor for the progression of Fabry cardiomyopathy in terms of the occurrence and progression of LGE. These data suggest that inflammation plays an active role in the onset and progression of myocardial damage and may represent a potential therapeutic target.