Cardiac magnetic resonance phenotypes and cardiovascular prognosis in classical vs cardiac variant of Fabry disease

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Fabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency/absence of alfa-galattosidase A enzyme activity. More than 1000 GLA gene mutations have been identified to be causative of classical or late-onset clinical phenotype. Cardiac variants (p.N215S, p.F113L and IVS4+919G>A) cause a predominant late-onset cardiac involvement with minimal systemic manifestations compared to classical phenotype.1 Cardiac magnetic resonance (CMR) is widely used to assess FD cardiac involvement, thanks to its accuracy in quantification of left ventricular mass and to the possibility to perform a non-invasive tissue characterization.2 Since cardiac involvement is the main cause of FD morbidity and mortality,3 CMR findings play a prognostic role in FD. Purpose the aims of this study were: 1) to compare CMR phenotypes of FD patients with classical and cardiac variant of the disease; 2) to compare the prognostic role of CMR parameters in these two groups of FD patients. Methods study population included 128 FD patients (classical variant: 69%, cardiac variant 31%). Clinical characteristics and CMR findings were compared between classical and cardiac variant. CV events during follow-up were abstracted from the patients’ records and only first event after CMR was used for survival analysis. The composite endpoint was defined as the development of one of the following events: a) sustained or non-sustained ventricular tachycardia, b) bradyarrhythmias requiring pacing, c) heart failure hospitalization, d) atrial fibrillation, e) myocardial infarction and f) all-cause mortality. Results compared to patients with cardiac variant, FD patients with classical mutations were younger (39 [26–53] vs 46 [37–57], p = 0,050), with a more severe systemic involvement according to Mainz Severity Score index (MSSI: 20,50 [9,25–27,00] vs 9,00 [2,00–23,00], p = 0,003). Overall, 37% (48/130) of patients assumed FD specific treatment, most of them exhibiting a classical mutation (43/48 patients, p<0,001).No significant differences in CMR parameters were observed comparing the two groups of patients. The percentage of patients with LVH, LGE and low T1 values were similar in classical and cardiac variants. During a median follow-up of 36 [17–57] months, Kaplan Meier curves shows a similar event-free survival probability (Log-rank p = 0,362) between the two phenotypes (Fig. 1). In addition, presence of LVH and LGE were both associated with composite CV endpoint in these two groups of patients. Conclusion patients with cardiac variants of FD showed similar CMR phenotype and CV prognosis compare to patients with classical mutations. The presence of LVH and LGE play the same prognostic impact in both the clinical phenotypes. CMR assessment of cardiac involvement represents a pivotal step in the evaluation of FD patients irrespective of patients’ genotype.