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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 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?

SUBMITTER: Tadros R 

PROVIDER: S-EPMC6769824 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Tadros Rafik R   Tan Hanno L HL   El Mathari Sulayman S   Kors Jan A JA   Postema Pieter G PG   Lahrouchi Najim N   Beekman Leander L   Radivojkov-Blagojevic Milena M   Amin Ahmad S AS   Meitinger Thomas T   Tanck Michael W MW   Wilde Arthur A AA   Bezzina Connie R CR  

European heart journal 20191001 37

<h4>Aims</h4>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).<h4>Methods and results</h4>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)  ...[more]

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