Electrocardiographic evolution in Anderson-Fabry disease: a valuable tool to detect progressive cardiac involvement

Abstract

Abstract Background Anderson-Fabry disease (AFD) is a multisystemic disorder caused by accumulation of glycosphingolipid in affected tissues and cardiac involvement can manifest with left ventricular hypertrophy (LVH), conduction delays, arrythmias and valvulopathies. Electrocardiogram (ECG) has proven to be useful for early detection of this condition, but there are only few datas on the association between ECG alterations and the progression of the disease. Purpose To evaluate the association between ECG anomalies and progressive cardiac involvement in AFD patients with different degrees of left ventricular hypertrophy. Methods We recruited 189 AFD patients > 18 years old (39% males, median age 47 years, 68% classical AFD) in a multicentre cohort and we divided them into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D ≥ 20 mm (n = 15, 8%). They underwent a complete clinical, ECG and echocardiographic evaluation and we analysed their ECG features in order to detect patterns suggestive of the different stages of AFD. Results A normal ECG was present in 87% of patients in group A, 54% in group B, 11% in group C, and 7% in group D. The most common conduction delay type was right bundle branch block (RBBB), mainly incomplete in groups B and C (respectively 20% and 22%) and complete RBBB in group D (53%), with p < 0.001; whereas none of the patients had LBBB. The prevalence of LVH criteria showed a statistically significant increase among the groups (p < 0.001) and also negative T waves and ST segment depression were more frequent in group C and D (p < 0.001), involving mainly lateral and inferior leads. Analysing these results we proposed ECG patterns representative of different AFD stages characterized by increasing LV thickness. In patients with normal LV thickness (group A) we noticed a high prevalence of normal ECG (87%) and minor anomalies like LVH criteria/giant positive T waves (8%) and delta wave/slurred QRS onset together with borderline PR (8%). Differently patients with intermediate LV thickness (group B and C) show more heterogeneous ECG alterations: LVH/giant positive T waves (17% and 7%); LVH+LV strain (9% and 17%); incomplete RBBB associated with repolarization abnormalities (8% and 9%) which were more frequently associated with LVH criteria in group C than B (8% and 15% respectively). In patients with severe LVH (group D) we detected more significant anomalies, like complete RBBB associated to LVH and repolarization abnormalities (40%), sometimes with QRS fragmentation (13%). Conclusions ECG represents an important tool for early detection and long-term monitoring of cardiac involvement in AFD with particular ECG features that evolve together with the natural history of the disease and with the progression of the LVH. Their potential association with clinical events remains unknown.