Do Family History of Sudden Cardiac Death, Syncope, Spontaneous Type 1 Brugada-ECG, Arrhythmia Inducibility and SCN5A Mutation Affect Onset of Arrhythmic Events in Brugada Patients?

Anat Milman ¹ Antoine Andorin ² Jean-Baptiste Gourraud ² Frederic Sacher ³ Philippe Mabo ⁴ Sung-Hwan Kim ⁵ Shingo Maeda ⁶ Yoshihide Takahashi ⁶ Tsukasa Kamakura ⁷ Takeshi Aiba ⁷ Giulio Conte ⁸ Eran Leshem ^1,9 Michael Rahkovich ^1,10 Yuka Mizusawa ¹¹ Pieter Postema ¹¹ Elena Arbelo ¹² Zhengrong Huang ¹³ Isabelle Denjoy ¹⁴ Carla Giustetto ¹⁵ Yanushi Wijeyeratne ¹⁶ Carlo Napolitano ¹⁷ Aviram Hochstadt ¹⁸ Yoav Michowitz ¹ Ramon Brugada ¹⁹ Ruben Casado-Arroyo ²⁰ Jean Champagne ²¹ Leonardo Calo ²² Jacob Tfelt-Hansen ²³ Silvia Priori ¹⁷ Masahiko Takagi ²⁴ Christian Veltmann ²⁵ Pietro Delise ²⁶ Domenico Corrado ²⁷ Elijah Behr ¹⁶ Fiorenzo Gaita ¹⁵ Gan-Xin Yan ²⁸ Josep Brugada ¹² Antoine Leenhardt ¹⁴ Arthur Wilde ¹¹ Pedro Brugada ⁸ Kengo Kusano ⁷ Kenzo Hirao ⁶ Gi-Byoung Nam ²⁹ Vincent Probst ² Bernard Belhassen ¹

¹Department of Cardiology, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University
²Service de Cardiologie, L'institut du Thorax, CHU de Nantes
³Service de Cardiologie, LIRYC Institute, INSERM 1045, Bordeaux University Hospital
⁴Cardiology and Vascular Disease Division, Rennes University Health Centre
⁵Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea
⁶Heart Rhythm Center, Tokyo Medical and Dental University
⁷Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
⁸Heart Rhythm Management Center, UZ-VUB
⁹Division of Cardiology, Beth Israel Deaconess Medical Center
¹⁰Arrhythmia Services, Sunnybrook Health Sciences Centre
¹¹Department of clinical and experimental Cardiology, Heart Center AMC, University of Amsterdam
¹²Cardiovascular Institute, Hospital Clínic Pediatric Arrhythmia Unit, Hospital of Peschiera del Garda
¹³Department of Cardiology, The First Affiliated Hospital of Xiamen University
¹⁴Service de Cardiologie et CNMR Maladies Cardiaques Héréditaires Rares, Hôpital Bichat
¹⁵Department of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital
¹⁶Cardiovascular Sciences, St. George's University of London
¹⁷Molecular Cardiology, Istituti Clinici Scientifici Maugeri IRCCS
¹⁸Department of Internal Medicine J,, Tel Aviv Medical Center
¹⁹Department of Cardiology, Institut d'Investigació Biomèdica Girona-IdIBGi
²⁰Department of Cardiology, Erasme University Hospital, Université Libre de Bruxelles
²¹Department of Cardiology, Quebec Heart and Lung Institute
²²Division of Cardiology, Policlinico Casilino
²³The Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, and Department of Medicine and Surgery, University of Copenhagen
²⁴Department of Cardiology, Osaka City University Graduate School of Medicine
²⁵Rhythmology and Electrophysiology, Department of Cardiology, Hannover Medical School
²⁶Division of Cardiology, Hospital of Peschiera del Garda
²⁷Department of Cardiac, Thoracic and Vascular Sciences, University of Padova
²⁸Division of Cardiology, Lankenau Medical Center
²⁹Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine

Background:
Various risk factors have been associated with arrhythmic events (AE) in Brugada syndrome (BrS).

Objectives:
To assess whether a family history of SCD, a history of prior syncope, presence of spontaneous type 1 Brugada ECG, arrhythmia inducibility and presence of SCN5A mutation affect the age of onset of AE in patients with BrS.

Methods:
Twenty one centers participated in this survey, collecting 628 BrS patients with their first AE documented either at the time of aborted cardiac arrest (Group A, n=383) or after prophylactic ICD implantation (Group B, n=245). There were 575 (91.6%) males, 355 (56.5%) Caucasians and 230 (36.6%) Asians. Age at time of first AE ranged from 0.27 to 84 (42.5 ± 14.1) years.

Results:
Of the 628 patients, 138 (22%) had a family history of SCD, 244 (38.9%) a history of syncope and 412 (65.6%) a spontaneous type 1 Brugada-ECG. Of the 373 (59.4%) patients who underwent EPS, VF was induced in 242 (64.8%). None of these 4 factors were shown to significantly influence the age of onset of AE. Of the 435 (69.3%) patients who underwent genetic testing 131 (30%) were positive for SCN5A mutation. The presence of SCN5A mutation was associated with a trend towards earlier onset of AE (p=0.094). Multivariate analysis showed a strong trend of the presence of SCN5A mutation as an independent risk factor for an earlier onset of AE (p=0.054).

Conclusion:
A family history of SCD, prior syncope, presence of spontaneous type 1 Brugada ECG, and arrhythmia inducibility do not affect age of first occurrence of AE in patients with BrS. The presence of SCN5A mutation was associated with a trend towards earlier occurrence of AE.

Anat Milman