TY - JOUR
TI - Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1
AU - Mazzanti, A.
AU - Guz, D.
AU - Trancuccio, A.
AU - Pagan, E.
AU - Kukavica, D.
AU - Chargeishvili, T.
AU - Olivetti, N.
AU - Biernacka, E.K.
AU - Sacilotto, L.
AU - Sarquella-Brugada, G.
AU - Campuzano, O.
AU - Nof, E.
AU - Anastasakis, A.
AU - Sansone, V.A.
AU - Jimenez-Jaimez, J.
AU - Cruz, F.
AU - Sánchez-Quiñones, J.
AU - Hernandez-Afonso, J.
AU - Fuentes, M.E.
AU - Średniawa, B.
AU - Garoufi, A.
AU - Andršová, I.
AU - Izquierdo, M.
AU - Marinov, R.
AU - Danon, A.
AU - Expósito-García, V.
AU - Garcia-Fernandez, A.
AU - Muñoz-Esparza, C.
AU - Ortíz, M.
AU - Zienciuk-Krajka, A.
AU - Tavazzani, E.
AU - Monteforte, N.
AU - Bloise, R.
AU - Marino, M.
AU - Memmi, M.
AU - Napolitano, C.
AU - Zorio, E.
AU - Monserrat, L.
AU - Bagnardi, V.
AU - Priori, S.G.
JO - Journal of the American College of Cardiology
PY - 2020
VL - 75
TODO - 15
SP - 1772-1784
PB - ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN - 0735-1097, 1558-3597
TODO - 10.1016/j.jacc.2020.02.033
TODO - 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
TODO - 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
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