Predicting cardiac electrical response to sodium-channel blockade and Brugada syndrome using polygenic risk scores

Abstract Aims Sodium-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 results In 1...

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Published in:European heart journal 2019-10, Vol.40 (37), p.3097-3107
Main Authors: Tadros, Rafik, Tan, Hanno L, el Mathari, Sulayman, Kors, Jan A, Postema, Pieter G, Lahrouchi, Najim, Beekman, Leander, Radivojkov-Blagojevic, Milena, Amin, Ahmad S, Meitinger, Thomas, Tanck, Michael W, Wilde, Arthur A, Bezzina, Connie R
Format: Article
Language:English
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Clinical Research
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Summary:Abstract Aims Sodium-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 results In 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 
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehz435