@article{3104559,
    title = "Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1",
    author = "Mazzanti, A. and Guz, D. and Trancuccio, A. and Pagan, E. and Kukavica, D. and Chargeishvili, T. and Olivetti, N. and Biernacka, E.K. and Sacilotto, L. and Sarquella-Brugada, G. and Campuzano, O. and Nof, E. and Anastasakis, A. and Sansone, V.A. and Jimenez-Jaimez, J. and Cruz, F. and Sánchez-Quiñones, J. and Hernandez-Afonso, J. and Fuentes, M.E. and Średniawa, B. and Garoufi, A. and Andršová, I. and Izquierdo, M. and Marinov, R. and Danon, A. and Expósito-García, V. and Garcia-Fernandez, A. and Muñoz-Esparza, C. and Ortíz, M. and Zienciuk-Krajka, A. and Tavazzani, E. and Monteforte, N. and Bloise, R. and Marino, M. and Memmi, M. and Napolitano, C. and Zorio, E. and Monserrat, L. and Bagnardi, V. and Priori, S.G.",
    journal = "Journal of the American College of Cardiology",
    year = "2020",
    volume = "75",
    number = "15",
    pages = "1772-1784",
    publisher = "ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA",
    issn = "0735-1097, 1558-3597",
    doi = "10.1016/j.jacc.2020.02.033",
    keywords = "antiarrhythmic agent;  beta adrenergic receptor blocking agent;  amiodarone;  antiarrhythmic agent;  inwardly rectifying potassium channel;  KCNJ2 protein, human, adult;  Andersen Tawil syndrome type 1;  Andersen Tawil syndrome type 1;  Article;  cohort analysis;  disease association;  drug efficacy;  faintness;  female;  follow up;  hazard ratio;  heart arrhythmia;  heart ventricle tachycardia;  human;  Italy;  major clinical study;  male;  medical documentation;  medical history;  prediction;  priority journal;  risk assessment;  adolescent;  Andersen syndrome;  child;  complication;  electrocardiography;  factual database;  faintness;  genetic screening;  genetics;  heart arrhythmia;  heart ventricle tachycardia;  implantable cardioverter defibrillator;  infant;  middle aged;  muscle weakness;  mutation;  preschool child;  risk assessment;  sudden cardiac death;  young adult, Adolescent;  Adrenergic beta-Antagonists;  Adult;  Amiodarone;  Andersen Syndrome;  Anti-Arrhythmia Agents;  Arrhythmias, Cardiac;  Child;  Child, Preschool;  Databases, Factual;  Death, Sudden, Cardiac;  Defibrillators, Implantable;  Electrocardiography;  Female;  Genetic Testing;  Humans;  Infant;  Male;  Middle Aged;  Muscle Weakness;  Mutation;  Potassium Channels, Inwardly Rectifying;  Risk Assessment;  Syncope;  Tachycardia, Ventricular;  Young Adult",
    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. © 2020"
}