Andrea Mazzanti1, Dmitri Guz2, Alessandro Trancuccio3, Eleonora Pagan4, Deni Kukavica5, Tekla Chargeishvili5, Natalia Olivetti2, Elżbieta Katarzyna Biernacka6, Luciana Sacilotto7, Georgia Sarquella-Brugada8, Oscar Campuzano9, Eyal Nof10, Aristides Anastasakis11, Valeria A Sansone12, Juan Jimenez-Jaimez13, Fernando Cruz14, Jessica Sánchez-Quiñones15, Julio Hernandez-Afonso16, Maria Eugenia Fuentes17, Beata Średniawa18, Anastasia Garoufi19, Irena Andršová20, Maite Izquierdo21, Rumen Marinov22, Asaf Danon23, Victor Expósito-García24, Amaya Garcia-Fernandez25, Carmen Muñoz-Esparza26, Martín Ortíz27, Agnieszka Zienciuk-Krajka28, Elisa Tavazzani3, Nicola Monteforte2, Raffaella Bloise2, Maira Marino2, Mirella Memmi2, Carlo Napolitano1, Esther Zorio29, Lorenzo Monserrat27, Vincenzo Bagnardi4, Silvia G Priori30. 1. 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. 2. Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy. 3. Department of Molecular Medicine, University of Pavia, Pavia, Italy. 4. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 5. Molecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy. 6. Department of Congenital Heart Diseases, National Institute of Cardiology, Warsaw, Poland. 7. Department of Cardiology, Hospital das Clinicas Faculdade de Medicina Universidade de São Paulo (HCFMUSP), São Paulo, Brazil. 8. Arrhythmia Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Barcelona, Spain. 9. Cardiovascular Genetics Center-Gencardio, IdIBGi Medical Sciences Department, Medical School, University of Girona, Girona, Spain. 10. Leviev Heart Center, Chaim Sheba Medical Center Affiliated to Sackler Medical School, Tel-Aviv University, Tel Hashomer, Israel. 11. Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. 12. NEMO Center, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, Milan, Italy. 13. Department of Cardiology, Virgen de las Nieves University Hospital, Granada, Spain. 14. Arrhythmia and Electrophysiology Unit, Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil. 15. Department of Cardiology, Hospital de Vinalopó, Elche, Spain. 16. Department of Cardiology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain. 17. Department of Cardiology, Hospital Infanta Cristina, Badajoz, Spain. 18. Department of Cardiology, Medical University of Silesia, Katowice, Poland. 19. Second Department of Pediatrics, National and Kapodistrian University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece. 20. Department of Internal Medicine and Cardiology, University Hospital Brno and Faculty of Medicine of Masaryk University, Brno, Czech Republic. 21. Department of Cardiology, Hospital Clinico Universitario, Valencia, Spain. 22. Department of Pediatrics, University of Medicine Hospital, Stara Zagora, Bulgaria. 23. Department of Cardiology, Hillel Yaffe Medical Center, Hadera, Israel. 24. Department of Cardiology, Marqués de Valdecilla University Hospital, Santander, Spain. 25. Department of Cardiology, Hospital General Universitario de Alicante, Alicante, Spain. 26. Department of Cardiology, Hospital Clinico Universitario Virgen de La Arrixaca, Murcia, Spain. 27. Health in Code, La Coruña, Spain. 28. Department of Cardiology and Electrotherapy, Medical University of Gdansk, Gdansk, Poland. 29. Department of Cardiology, Hospital Universitario y Politécnico La Fe,Valencia, Spain and Center for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Madrid, Spain. 30. 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. Electronic address: silvia.priori@icsmaugeri.it.
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.
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.
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Back Sternick Eduardo; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong-Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti Mac Intyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Pablo Ochoa Juan; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: J Arrhythm Date: 2022-05-31
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Eduardo Back Sternick; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti MacIntyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Juan Pablo Ochoa; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: Europace Date: 2022-09-01 Impact factor: 5.486
Authors: Michael G Klein; Mori J Krantz; Naheed Fatima; Ashlie Watters; Dayan Colon-Sanchez; Robert M Geiger; Robert E Goldstein; Soroosh Solhjoo; Philip S Mehler; Thomas P Flagg; Mark C Haigney Journal: J Am Heart Assoc Date: 2022-06-06 Impact factor: 6.106
Authors: Estefanía Martínez-Barrios; Sergi Cesar; José Cruzalegui; Clara Hernandez; Elena Arbelo; Victoria Fiol; Josep Brugada; Ramon Brugada; Oscar Campuzano; Georgia Sarquella-Brugada Journal: Biomedicines Date: 2022-01-05