ArticleEuropean heart journal2019
Predicting cardiac electrical response to sodium-channel blockade and Brugada syndrome using polygenic risk scores.
Article in European heart journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- The diagnostic role of pharmacological provocation testing in cardiac electrophysiology: a clinical consensus statement of the European Heart Rhythm Association and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, the ESC Working Group on Cardiovascular Pharmacotherapy, the Association of European Paediatric and Congenital Cardiology (AEPC), the Paediatric & Congenital Electrophysiology Society (PACES), the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS).Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Guideline
- Brugada Syndrome: an exemplar for the genomic basis of sudden death.European journal of human genetics : EJHG · 2026Review
- Further mystification of SCN5A phenotypes: sodium channel blockade in individuals with loss-of-function sodium channel mutations dangerous or helpful?Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Contemporary Perspectives on J-Wave Syndromes: An Expert Consensus Statement.Journal of arrhythmia · 2026Article
- Genetics of Sudden Cardiac Death.Diseases (Basel, Switzerland) · 2025Review
- The Utility of Genome-Wide Association Studies in Inherited Arrhythmias and Cardiomyopathies.Genes · 2025Review
- Genome-Wide Association Study for Resting Electrocardiogram in the Qatari Population Identifies 6 Novel Genes and Validates Novel Polygenic Risk Scores.Journal of the American Heart Association · 2025Article
- Causal Relationship Between Electrocardiogram Parameters and Brugada Syndrome: A Bidirectional Mendelian Randomization Study.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2025Article
- Genetics of Sudden Cardiac Arrest: Overview of Genetic Risk Factors and Aetiologies.Arrhythmia & electrophysiology review · 2025Review
- Type 1 Brugada Pattern May Be Provoked by Ajmaline in Some Healthy Subjects: Results From a Clinical Trial.Circulation · 2024Article
- Applying polygenic risk score methods to pharmacogenomics GWAS: challenges and opportunities.Briefings in bioinformatics · 2023Article
- Deep learning unmasks the ECG signature of Brugada syndrome.PNAS nexus · 2023Article
- The Role of Genetics in the Management of Heart Failure Patients.International journal of molecular sciences · 2023Review
- Unravelling NovelInternational journal of molecular sciences · 2023Article
- Use, misuse, and pitfalls of the drug challenge test in the diagnosis of the Brugada syndrome.European heart journal · 2023Review
- Subepicardial Cardiomyopathy: A Disease Underlying J-Wave Syndromes and Idiopathic Ventricular Fibrillation.Circulation · 2023Article
- Management of Inherited Arrhythmia Syndromes: A HiRO Consensus Handbook on Process of Care.CJC open · 2023Review
- Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification.International journal of molecular sciences · 2023Review
- The Utility of Sodium Channel Provocation in Unexplained Cardiac Arrest Survivors and Electrocardiographic Predictors of Ventricular Fibrillation Recurrence.Circulation. Arrhythmia and electrophysiology · 2022Article
- European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsSodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors of ajmaline-induced PR and QRS changes and Type I Brugada syndrome (BrS) electrocardiogram (ECG). METHODS AND
resultsIn 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements of 26 721 ECGs, dose-response mixed modelling and genotyping. We calculated polygenic risk scores (PRS) for PR interval (PRSPR), QRS duration (PRSQRS), and Brugada syndrome (PRSBrS) derived from published genome-wide association studies and used regression analysis to identify predictors of ajmaline dose related PR change (slope) and QRS slope. We derived and validated using bootstrapping a predictive model for ajmaline-induced Type I BrS ECG. Higher PRSPR, baseline PR, and female sex are associated with more pronounced PR slope, while PRSQRS and age are positively associated with QRS slope (P < 0.01 for all). PRSBrS, baseline QRS duration, presence of Type II or III BrS ECG at baseline, and family history of BrS are independently associated with the occurrence of a Type I BrS ECG, with good predictive accuracy (optimism-corrected C-statistic 0.74).
conclusionWe show for the first time that genetic factors underlie the variability of cardiac electrical response to SCB. PRSBrS, family history, and a baseline ECG can predict the development of a diagnostic drug-induced Type I BrS ECG with clinically relevant accuracy. These findings could lead to the use of PRS in the diagnosis of BrS and, if confirmed in population studies, to identify patients at risk for toxicity when given SCB.
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