Syncope Triggers and Long QT Syndrome Risk

Quick Takes

  • Adrenergic triggered syncope in long QT syndrome (LQTS) type 1 increases risk of future life-threatening events (LTE) by eightfold.
  • Both adrenergic and nonadrenergic syncope increase risk of future LTE in LQTS type 2.
  • Nonselective beta-blockade is a critical treatment for optimal protection in LQTS.

Study Questions:

What is the association between syncope trigger type and risk of future life-threatening event(s) (LTE) in long QT syndrome (LQTS)?


This is a retrospective cohort study of patients from five international LQTS registries with single variant genotype positive LQTS. Excluded were those: with a history of aborted cardiac arrest/death, lost to follow-up, and without data on triggers or treatment. The primary outcome was occurrence of LTE, defined as defibrillated ventricular arrhythmia, aborted cardiac arrest, or LQTS-related sudden death, up to a follow-up point of 40 years of age. Risk of LTE was assessed based on syncope trigger type—adrenergic (exercise, arousal such as loud noise, emotion) or nonadrenergic (rest and other nonspecific triggers)—and treatment.


There were 2,938 patients included in the study, age 29 ± 7 years. For the 45% of the cohort with LQTS type 1 (LQT1), 27% had experienced syncope, more commonly with adrenergic triggers. An adrenergic triggered syncope event increased the risk of future LTE (hazard ratio [HR], 7.6; p > 0.001). Nonadrenergic triggered syncope was an insignificant factor. Beta-blocker therapy reduced risk of LTE in LQT1 by 70%; however, selective beta-blocker use was associated with the highest rate of LTE versus nonselective beta-blocker use, which was associated with a low rate of LTE. For the 38% of the cohort with LQTS type 2 (LQT2), syncope had occurred in 26%, more commonly with nonadrenergic triggers. Both trigger types significantly increased the risk of subsequent LTE (HR, approximately 3-3.5; p < 0.001). Beta-blocker treatment reduced risk in LQT2 by 53%; again, subsequent LTE was highest when selective beta-blockers were used. Few of the 501 patients with LQTS type 3 experienced syncope. LTE occurred in 11% of this group and was the sentinel event for 88% of those patients.


Trigger-specific syncope in LQTS is associated with a differential risk of subsequent LTE. Beta-blocker type impacts risk of future LTE.


This large cohort study suggests that a less aggressive treatment approach to nonadrenergic syncope in patients with LQT1 may be reasonable. Syncope was associated with a risk of future events in LQT2 and adrenergically triggered LQT1 events and should be weighed into overall risk considerations. The study reinforces the importance of using nonselective beta-blockers (nadolol or propranolol), and not selective beta-blockers.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, 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 Prevention, CHD and Pediatrics and Quality Improvement, Exercise

Keywords: Arrhythmias, Cardiac, Adrenergic Agents, Adrenergic beta-Antagonists, Death, Sudden, Death, Sudden, Cardiac, Emotions, Exercise, Genotype, Heart Arrest, Long QT Syndrome, Nadolol, Propranolol, Risk, Romano-Ward Syndrome, Syncope, Young Adult

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