Observational studyEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2026
Ventricular conduction is a marker for arrhythmic risk in SCN5A-E1784K overlap sodium channel disease.
Michael W T Tanck, Yanushi D Wijeyeratne, Julien Barc, Alison Muir, Takeshi Aiba, J Martijn Bos, Christian Veltmann, Joseph Galvin, Lia Crotti, Taisuke Ishikawa and 27 more
Abstract readMulticenter StudyObservational Study
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5 · Who and what moneyAuthors and funding
37 authors.
Michael W T TanckAmsterdam UMC, University of Amsterdam, Epidemiology and Data Science, Amsterdam Public Health, Meibergdreef 9, Amsterdam, Netherlands.ORCID 0000-0001-9828-4459 Yanushi D WijeyeratneCardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George's University of London, London SW17 0RE, UK.ORCID 0000-0003-0656-5769 Julien BarcDepartment of Medical Genetics, Nantes Université, CNRS, INSERM, L'institut du Thorax, Nantes F-44000, France.ORCID 0000-0003-4106-5946 Alison MuirBelfast Health and Social Care Trust, Belfast, UK.
Takeshi AibaDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.ORCID 0000-0003-1779-7282 J Martijn BosDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-3635-2003 Lia CrottiIstituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.ORCID 0000-0001-8739-6527 Taisuke IshikawaDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.ORCID 0000-0001-8195-4700 Seiko OhnoDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.ORCID 0000-0003-1209-8896 Stephen P PageLeeds Teaching Hospitals NHS Trust, Leeds, UK.
Isabelle DenjoyAP-HP Nord, Hôpital Bichat, Cardiology Department and Reference Center for Hereditary Arrhythmic Diseases, Paris Cité University, INSERM U1166, Paris, France.ORCID 0000-0002-1786-9461 David J TesterDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN, USA.
Martina MuggenthalerCardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George's University of London, London SW17 0RE, UK.
Hariharan RajuCardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George's University of London, London SW17 0RE, UK.ORCID 0000-0003-0000-7520 Jean Baptiste GourraudNantes Université, CHU Nantes, CNRS, INSERM, L'institut du Thorax, Nantes F-44000, France.ORCID 0000-0002-6961-2131 Richard RedonNantes Université, CHU Nantes, CNRS, INSERM, L'institut du Thorax, Nantes F-44000, France.ORCID 0000-0001-7751-2280 Jean-Jacques SchottNantes Université, CHU Nantes, CNRS, INSERM, L'institut du Thorax, Nantes F-44000, France.ORCID 0000-0002-9578-9475 Carla Haglund-TurnquistDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN, USA.
Matteo PedrazziniIstituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.ORCID 0000-0002-0675-4845 Chiara AlberioIstituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.ORCID 0000-0002-4727-0994 Federica DagradiIstituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.ORCID 0000-0002-1090-3292 Michael PapadakisCardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George's University of London, London SW17 0RE, UK.ORCID 0000-0003-0616-2353 Sanjay SharmaCardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George's University of London, London SW17 0RE, UK.ORCID 0000-0002-3630-6138 Peter J SchwartzIstituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.ORCID 0000-0003-0367-1048 Naomasa MakitaDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.ORCID 0000-0002-1807-672X Martin M BorggrefeDepartment of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Mannheim, Germany.ORCID 0000-0002-3206-934X Michael J AckermanDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN, USA.
Wataru ShimizuDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.ORCID 0000-0001-9941-8973 Pascal P McKeownBelfast Health and Social Care Trust, Belfast, UK.
Vincent ProbstNantes Université, CHU Nantes, CNRS, INSERM, L'institut du Thorax, Nantes F-44000, France.ORCID 0000-0002-5492-8619 Elijah R BehrCardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George's University of London, London SW17 0RE, UK.ORCID 0000-0002-8731-2853 Funding
ANR European Joint ProgrammeANR JCJCBritish Heart FoundationClinical Research Hospital ProgramFédération Française de CardiologieFrench Ministry of HealthHigher Education Funding Council for EnglandJames Lancaster Memorial FundLEARN R21006NNLEARN RPV21014NNALQTS-NEXTMayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death ProgramMcColl's RG LtdMedical Research CouncilNational Institute of Health Research
6 · The paper itselfAbstract
aimsSCN5A-E1784K (c.5350G>A) is the most common variant associated with the long QT (LQTS) and Brugada syndromes (BrS). It can manifest variably as LQTS, BrS, and/or conduction disorders. This presents a challenge for risk stratification. We aimed to describe clinical and ECG characteristics and identify risk markers that associate with arrhythmic events. METHODS AND
resultsWe undertook a retrospective observational multicentre study of a large cohort of 231 subjects with SCN5A-E1784K from Europe, USA, and Japan. Comprehensive demographic and clinical data, including initial presentation ECG and follow-up, were collected. 'Lethal events' were defined as sudden death, non-fatal cardiac arrest, and documented sustained VT or VF. 'Cardiac events' were defined as arrhythmic syncope plus any lethal events. Clinical characteristics and ECG parameters corrected for age were investigated for association with lethal and/or cardiac events. Fourteen (6%) subjects experienced a lethal event and 45 (19%) a cardiac event. PR interval and QRS duration were associated with lethal and cardiac events. In multivariable models, both PR interval and QRS duration were associated with lethal events, but only QRS duration was associated with cardiac events. Only age-corrected QRS (rQRS) was associated with lethal and cardiac event-free survival from birth after correction for multiple testing.
conclusionVentricular myocardial conduction appears likely to play a role in the risk of arrhythmic events in patients with SCN5A-E1784K. This provides an important opportunity for the personalization of management and has the potential to guide preventative therapies.
Indexed as
Brugada SyndromeHeart Conduction SystemLong QT SyndromeNAV1.5 Voltage-Gated Sodium ChannelTachycardia, VentricularVentricular FibrillationAction PotentialsAdultDeath, Sudden, CardiacElectrocardiographyEuropeFemaleGenetic Predisposition to DiseaseHumansJapanMaleNAV1.5 Voltage-Gated Sodium ChannelSCN5A protein, humanBrugada syndromeECGLong QT syndromepenetrancePhenotype
Identifiers
PMID42114100
PMCPMC13237868
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