Genetic Substrate, QTc Duration, and Arrhythmia Risk in LQTS

Study Questions:

What is the risk of life-threatening arrhythmic events (LAEs) based on the combination of genotype and phenotype in patients with the long QT syndrome (LQTS)?

Methods:

This was a retrospective analysis of 1,710 LQTS patients followed for a median of 7.1 years. The 5-year risk of LAEs was estimated based on QTc duration, genotype (LQT1, LQT2, or LQT3), and treatment with a beta-blocker.

Results:

The prevalence of LQT1, LQT2, and LQT3 was 56%, 32%, and 12%, respectively. The mean QTc interval in the overall cohort was 471 ms. The baseline QTc interval was ≤460 ms in 719 patients (42%) who had an annual LAE rate of 0.088. The annual rate of LAEs was 0.72 among the 991 patients (58%) with a baseline QTc >460 ms. Both genotype and baseline QTc were independently associated with LAE risk. The 5-year LAE risk increased by 15% for every 10 ms increment in QTc, regardless of genotype. At any QTc, the risk was higher by 130% and 157% in patients with LQT2 and LQT3 compared to LQT1. The only beta-blocker associated with a lower LAE risk in all genotypes was nadolol (hazard ratio 0.38 compared to no therapy).

Conclusions:

The risk of LAEs in LQTS can be individualized based on genotype and phenotype. The only beta-blocker associated with a lower risk is nadolol.

Perspective:

The simple scheme provided by this study for estimating the risk of LAEs will be very useful for guiding individualized recommendations for management in LQTS patients, particularly in patients who prove intolerant to nadolol. Based on LAE risk, an implantable cardioverter-defibrillator may or may not be recommended. The study provides important evidence that nadolol is superior to the other beta-blockers in LQTS.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Prevention, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Quality Improvement

Keywords: Arrhythmias, Cardiac, Adrenergic beta-Antagonists, Defibrillators, Implantable, Genotype, Long QT Syndrome, Nadolol, Phenotype, Risk, Secondary Prevention


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