Clinical Aspects of Type 3 Long QT Syndrome

Study Questions:

What are the risk factors for cardiac events (CEs) and the response to treatment with beta-blockers in patients with type 3 long QT syndrome (LQT3)?


The subjects of this retrospective study were 391 genotype-positive patients with LQT3. Clinical data were collected prospectively after enrollment into a registry. The primary endpoint was the time from age 1 to the first CE, defined as syncope, aborted cardiac arrest (ACA), or sudden cardiac death (SCD).


A CE occurred in 30% of patients by age 40. Two-thirds of the CEs were ACA or SCD. The degree of corrected QT interval (QTc) prolongation was an independent predictor of CEs. There was a 19% increase in CEs for every 10 ms increase in QTc duration up to 500 ms. Beta-blockers were independently associated with an 83% reduction in the risk of a CE in women, but were not associated with a lower risk in men. A history of syncope doubled the risk of ACA/SCD.


A longer QTc and syncope are predictive of ACA/SCD in patients with LQT3. Beta-blockers substantially reduce this risk in women, but not men.


Approximately 5-10% of patients with long QT syndrome have LQT3, which is caused by a gain-of-function mutation in the SCN5A sodium channel gene. In LQT3, CEs often occur at rest instead of during periods of adrenergic activation. This has led to concerns that beta-blockers, which are effective in reducing CEs in LQT1/LQT2, could be proarrhythmic in LQT3. This study shows that this is not the case and that beta-blockers have either a neutral or positive effect on prognosis, depending on sex.

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

Keywords: Adrenergic beta-Antagonists, Arrhythmias, Cardiac, Death, Sudden, Cardiac, Genetic Testing, Genotype, Heart Arrest, Long QT Syndrome, Mutation, Primary Prevention, Risk Factors, Sodium Channels, Syncope

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