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Background Anderson Fabry disease (AFD) is a rare X-linked lysosomal storage disorder caused by deficient activity of α-galactosidase A bringing to intracellular accumulation of globotriaosylceramide (Gb3) in affected tissues, including heart. Progressive cardiac involvement has shown to cause electrocardiographic modifications in these patients. Treatment with enzyme replacement therapy (ERT) or chaperone therapy has demonstrated to decrease Gb3 levels in the heart, but little is known about its influence on ECG evolution. Purpose to gain new insights about ECG evolution in AFD patients on and off specific disease therapy and to assess its potential role in the diagnosis and the follow-up of these patients. Methods we analysed the ECG evolution of a multicentre study cohort of 170 patients with a diagnosis of AFD (64 males 38%, median age 46±15 years) for a median follow-up of 64±48 months, dividing them into patients off (group A, N=63) and on (group B, N= 107) specific therapy. Results the two groups did not differ as regard age at baseline (47±14 vs 44±12 years; p=0,171) but patients off specific disease therapy (group A) showed lower prevalence of male sex [13(21%) vs 51(48%); p= Conclusion We observed ECG progression despite specific disease therapy in 29% of patients of group B showing a potential role of ECG as a marker of cardiac specific response to therapy in these patients. Differently we detected ECG progression in 14% of patients off specific therapy, which is consistent with their less advanced cardiac involvement (lower prevalence of male sex, classic phenotype and lower maximum wall thickness), suggesting that ECG could be an important tool to detect an initial cardiac involvement in these patients even in absence of hypertrophy. The absence of left bundle branch blocks in the two groups compared with a significant prevalence of complete and incomplete right conduction delay could suggest a prevalent involvement of the right bundle branch in these patients and could represent a red flag for the diagnosis of AFD.

Background Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder that have gained attention due to the availability of therapeutic options. Disease specific therapy (DST), either by enzyme replacement therapy or oral pharmacological chaperone, is the mainstay for AFD treatment. Although its widespread use, few data are available on the electrocardiographic variations associated with DST. Purpose To evaluate ECG findings and variations in AFD according to time duration of DST, comparing patients under long-term therapy with naïve patients starting therapy during follow-up. Methods One-hundred-seventy-nine AFD patients, ≥18 years old, with 2 readable ECGs, were recruited in the present multicentre study cohort. Two patients were excluded due to pacemaker (PM) implantation. Only patients on DST (n=107) were considered for final cohort and divided into 2 groups according to therapy duration: Group A (n=42) included patients treated for ≥12 months at the time of first evaluation, whereas Group B patients (n=65) started therapy during follow-up. Results Group A and Group B had not significant difference in terms of age at presentation (48[39-60] vs 48[36-56]years; p=0.856) and maximal wall thickness (13[11-15] vs 13[11-18]mm; p=0.090) whereas they differed for male prevalence (61% vs 38%; p=0.029) and classic phenotype (86% vs 29%; p During the follow-up (57[60-28] months for Group A vs 70[37-85] months for Group B; p=0.152), both groups developed electrocardiographic alterations (38% vs 23%; p=0.127). Specifically, in GroupA, 4 (10%) patients presented AF, 1 (2%) AVB, 7 (17%) complete or incomplete RBBB, 4 (10%) LAFB, 1 (2%) LVH and 8 (19%) repolarization abnormalities. In Group B, 2 (3%) developed AF, 1 (2%) AVB, 7 (11%) complete or incomplete RBBB, 2(3%) LVH and 11(17%) repolarization abnormalities; none developed LAFB. Conclusions In this AFD cohort, both patients on chronic DST (Group A) and patients who started treatment during follow-up (Group B) developed ECG alterations. Treatment status didn't affect considerably the developing of ECG abnormalities and DST did not prevent ECG changes. ECG alterations during the follow-up were more frequent in Group A (38% vs 23%), mainly composed by classic phenotype and male patients, thus supporting a prompt start of therapy at an early stage.

Mitral valve prolapse is a relatively common disease with a good overall prognosis. However, in specific clinical and instrumental contexts, patients at high risk of ventricular arrhythmias and sudden cardiac death can be identified. Female sex, history of palpitations or syncope, bi-leaflet myxomatous valve, ECG repolarization abnormalities in the inferior leads, complex ventricular arrhythmias, left ventricular fibrosis detected by cardiac magnetic resonance correlate with a higher risk clinical profile. Additionally, morpho-functional abnormalities of the mitral valve annulus, particularly mitral annulus disjunction, may cause a mechanical stretch at the inferior basal ventricular wall and posterior papillary muscles, predisposing to myocardial fibrosis and arrhythmias. A risk stratification strategy is needed to identify patients with mitral valve prolapse and/or mitral annulus disjunction at high risk of arrhythmias; however, few data are available. Further prospective multicenter studies are warranted, focusing on medical therapy, the role of implantable cardioverter-defibrillators for primary prevention, efficacy of targeted catheter ablation or mitral valve surgery.