Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1
Por:
Mazzanti A, Guz D, Trancuccio A, Pagan E, Kukavica D, Chargeishvili T, Olivetti N, Biernacka EK, Sacilotto L, Sarquella-Brugada G, Campuzano O, Nof E, Anastasakis A, Sansone VA, Jimenez-Jaimez J, Cruz F, Sánchez-Quiñones J, Hernandez-Afonso J, Fuentes ME, Sredniawa B, Garoufi A, Andršová I, Izquierdo M, Marinov R, Danon A, Expósito-García V, Garcia-Fernandez A, Muñoz-Esparza C, Ortíz M, Zienciuk-Krajka A, Tavazzani E, Monteforte N, Bloise R, Marino M, Memmi M, Napolitano C, Zorio E, Monserrat L, Bagnardi V and Priori SG
Publicada:
21 abr 2020
Categoría:
Cardiology and cardiovascular medicine
Resumen:
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. (C) 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.
Filiaciones:
Mazzanti A:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Department of Molecular Medicine, University of Pavia, Pavia, Italy
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Guz D:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Trancuccio A:
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Pagan E:
Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
Kukavica D:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Chargeishvili T:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Olivetti N:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Biernacka EK:
Department of Congenital Heart Diseases, National Institute of Cardiology, Warsaw, Poland
Sacilotto L:
Department of Cardiology, Hospital das Clinicas Faculdade de Medicina Universidade de São Paulo (HCFMUSP), São Paulo, Brazil
Sarquella-Brugada G:
Arrhythmia Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Barcelona, Spain
Campuzano O:
Cardiovascular Genetics Center-Gencardio, IdIBGi Medical Sciences Department, Medical School, University of Girona, Girona, Spain
Nof E:
Leviev Heart Center, Chaim Sheba Medical Center Affiliated to Sackler Medical School, Tel-Aviv University, Tel Hashomer, Israel
Anastasakis A:
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece
Sansone VA:
NEMO Center, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, Milan, Italy
Jimenez-Jaimez J:
Department of Cardiology, Virgen de las Nieves University Hospital, Granada, Spain
Cruz F:
Arrhythmia and Electrophysiology Unit, Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil
Sánchez-Quiñones J:
Department of Cardiology, Hospital de Vinalopó, Elche, Spain
Hernandez-Afonso J:
Department of Cardiology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain
Fuentes ME:
Department of Cardiology, Hospital Infanta Cristina, Badajoz, Spain
Sredniawa B:
Department of Cardiology, Medical University of Silesia, Katowice, Poland
Garoufi A:
Second Department of Pediatrics, National and Kapodistrian University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
Andršová I:
Department of Internal Medicine and Cardiology, University Hospital Brno and Faculty of Medicine of Masaryk University, Brno, Czech Republic
Izquierdo M:
Department of Cardiology, Hospital Clinico Universitario, Valencia, Spain
Marinov R:
Department of Pediatrics, University of Medicine Hospital, Stara Zagora, Bulgaria
Danon A:
Department of Cardiology, Hillel Yaffe Medical Center, Hadera, Israel
Expósito-García V:
Department of Cardiology, Marqués de Valdecilla University Hospital, Santander, Spain
Garcia-Fernandez A:
Department of Cardiology, Hospital General Universitario de Alicante, Alicante, Spain
Muñoz-Esparza C:
Department of Cardiology, Hospital Clinico Universitario Virgen de La Arrixaca, Murcia, Spain
Ortíz M:
Health in Code, La Coruña, Spain
Zienciuk-Krajka A:
Department of Cardiology and Electrotherapy, Medical University of Gdansk, Gdansk, Poland
Tavazzani E:
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Monteforte N:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Bloise R:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Marino M:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Memmi M:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Napolitano C:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Department of Molecular Medicine, University of Pavia, Pavia, Italy
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Zorio E:
Department of Cardiology, Hospital Universitario y Politécnico La Fe,Valencia, Spain and Center for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Madrid, Spain
Monserrat L:
Health in Code, La Coruña, Spain
Bagnardi V:
Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
Priori SG:
Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
Department of Molecular Medicine, University of Pavia, Pavia, Italy
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Molecular Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
Green Submitted
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