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

Andrea Mazzanti, Dmitri Guz, Alessandro Trancuccio, Eleonora Pagan, Deni Kukavica, Tekla Chargeishvili, Natalia Olivetti, Elżbieta Katarzyna Biernacka, Luciana Sacilotto, Georgia Sarquella-Brugada, Oscar Campuzano, Eyal Nof, Aristides Anastasakis, Valeria A. Sansone, Juan Jimenez-Jaimez, Fernando Cruz, Jessica Sánchez-Quiñones, Julio Hernandez-Afonso, Maria Eugenia Fuentes, Beata ŚredniawaAnastasia Garoufi, Irena Andršová, Maite Izquierdo, Rumen Marinov, Asaf Danon, Victor Expósito-García, Amaya Garcia-Fernandez, Carmen Muñoz-Esparza, Martín Ortíz, Agnieszka Zienciuk-Krajka, Elisa Tavazzani, Nicola Monteforte, Raffaella Bloise, Maira Marino, Mirella Memmi, Carlo Napolitano, Esther Zorio, Lorenzo Monserrat, Vincenzo Bagnardi, Silvia G. Priori

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1772-1784
Number of pages13
JournalJournal of the American College of Cardiology
Issue number15
Publication statusPublished - Apr 21 2020


  • genetics
  • inherited arrhythmias
  • KCNJ2
  • life-threatening arrhythmic events
  • sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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