Prognostic role of ECG patterns in Anderson Fabry disease

Abstract Background Anderson Fabry disease (AFD) is an X-linked lysosomal storage disorder leading to a deficiency in α-galactosidase A and globotriasylceramide (Gb3) deposition in different organs. Cardiac involvement is extremely common. It has been shown that the ECG abnormalities are directly correlated with the progressive accumulation of glycosphingolipids in the myocardium and cardiac conduction system. However, it is still unclear whether the ECG alterations are correlated with clinical events. Purpose To evaluate the prognostic role of ECG patterns in an unselected population of patients with AFD. Methods We conducted a retrospective multicenter study enrolling 215 consecutive patients. Based on the baseline ECG the study population was divided into the following five groups: 1) normal ECG or minimal alterations; 2) left ventricular hypertrophy (LVH) without signs of overload; 3) isolated negative T waves in the inferior and/or lateral leads; 4) LVH with signs of overload with or without incomplete right bundle branch block (RBBB); 5) complete RBBB. The primary endpoint was the composite of sudden cardiac death, resuscitated cardiac arrest, sustained ventricular tachycardia, and heart failure. Results Median age of study population was 45 years (32-57), and 86 patients (40%) were men. The rate of classic phenotype was 68%. Patients with ECG patterns 3 and 4 were older at baseline, more frequently affected by arterial hypertension, mostly male and showed greater left ventricular thickening, At a median follow up of 60 months (25-83) the overall Kaplan-Meier survival free from the primary endpoint was 57%: the Kaplan-Meier survival estimates of ECG groups were 66%, 75%, 68%, 27% e 52% respectively (log Rank 0.0026). On multivariable analysis patients belonging to either 3 or 4 group showed an increased risk of primary endpoint (HR= 2.45; 95% CI 1.04-5.78, p=0.040) compared to other groups. Conclusion ECG at baseline may be a useful tool to predict the risk of cardiovascular events in Anderson-Fabry Disease. Future studies should investigate if ECG may be useful also to evaluate the clinical response to specific therapy.