Background: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. Objectives: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. Methods: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. Results: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). Conclusions: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.

Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1 / A. Mazzanti, D. Guz, A. Trancuccio, E. Pagan, D. Kukavica, T. Chargeishvili, N. Olivetti, E. Biernacka, L. Sacilotto, G. Sarquella-Brugada, O. Campuzano, E. Nof, A. Anastasakis, V. Sansone, J. Jimenez-Jaimez, F. Cruz, J. Sánchez-Quiñones, J. Hernandez-Afonso, M. Fuentes, B. Średniawa, A. Garoufi, I. Andršová, M. Izquierdo, R. Marinov, A. Danon, V. Expósito-García, A. Garcia-Fernandez, C. Muñoz-Esparza, M. Ortíz, A. Zienciuk-Krajka, E. Tavazzani, N. Monteforte, R. Bloise, M. Marino, M. Memmi, C. Napolitano, E. Zorio, L. Monserrat, V. Bagnardi, S. Priori. - In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - ISSN 0735-1097. - 75:15(2020 Apr 21), pp. 1772-1784. [10.1016/j.jacc.2020.02.033]

Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1

V. Sansone;
2020

Abstract

Background: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. Objectives: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. Methods: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. Results: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). Conclusions: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.
genetics; inherited arrhythmias; KCNJ2; life-threatening arrhythmic events; sudden cardiac death;
Settore MED/26 - Neurologia
21-apr-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/795263
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