Myocardial Edema, Myocyte Injury, and Disease Severity in Fabry Disease

Background: Cardiovascular magnetic resonance can demonstrate myocardial processes in Fabry disease (FD), such as low native T1 (sphingolipid storage) and late gadolinium enhancement (LGE, scar). Recently, high T2 (edema) has been observed in the basal inferolateral wall along with troponin elevation. We hypothesized that edema and myocyte injury would be chronically associated and have electrical, mechanical, and disease associations in FD. Methods: A prospective international multicenter study was conducted on 186 consecutive FD patients (45.2 +/- 1.1 years, 58% females). Additionally, 28 patients with hypertrophic cardiomyopathy, 30 with chronic myocardial infarction and 59 healthy volunteers were included. All study participants underwent comprehensive cardiovascular magnetic resonance with T1 and T2 mapping, cines, and LGE imaging. Results: LGE in the basal inferolateral wall in FD had T2 elevation (FD 58.2 +/- 5.0 ms versus hypertrophic cardiomyopathy 55.6 +/- 4.3 ms, chronic myocardial infarction 53.7 +/- 3.4 ms and healthy volunteers 48.9 +/- 2.5 ms, P<0.001), but when LGE was present there was also global T2 elevation (53.1 +/- 2.9 versus 50.6 +/- 2.2 ms, P<0.001). Thirty-eight percent of FD patients had high troponin. The strongest predictor of increased troponin was high basal inferolateral wall T2 (odds ratio, 18.2 [95% CI, 3.7-90.9], P<0.0001). Both T2 and troponin elevations were chronic over 1 year. High basal inferolateral wall T2 was associated with baseline global longitudinal strain impairment (P=0.005) and electrocardiographic abnormalities (long PR, complete bundle branch block, left ventricular hypertrophy voltage criteria, long QTc, and T-wave inversion, all P<0.05) and predicted clinical worsening after 1 year (Fabry stabilization index >20%, P=0.034). Conclusions: LGE in Fabry has chronic local T2 elevation that is strongly associated with chronic troponin elevation. In addition, there is slight global T2 elevation. Both are associated with ECG and mechanical changes and clinical worsening over 1 year.