Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome

Background: Congenital long QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods. Objective: We aimed to evaluate the potential utility of electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS. Methods: The study, which considered patients with LQTS type 1 and LQTS type 2, comprised a discovery cohort of 695 and a validation cohort of 635 patients. Results: The change in corrected QT (QTc) interval between rest and recovery (between rest and 3–4 minutes into the recovery period, called recovery-rest ΔQTc) was consistently greater in symptomatic patients. Sensitivity analyses performed on EST data obtained on and off β-blockers as well as upon distinguishing between patients with a baseline QTc interval below and those above 470 ms demonstrated consistent findings. The association of recovery-rest ΔQTc with cardiac events remained significant in a subanalysis focusing on future events (ie, occurring after the EST). An optimal recovery-rest ΔQTc cutoff was determined for LQTS type 1 (35 ms) and LQTS type 2 (16 ms) separately and was shown to be significantly associated with cardiac events. Conclusion: Our findings suggest that in patients with LQTS, dynamic QT interval measures obtained during the EST are associated with lifetime arrhythmic events and events after the EST. Such measures can be helpful in identifying a higher-risk subset of patients with LQTS in order to optimize their management. Further research may confirm these findings in larger cohorts and explore the potential benefit of combining genetic and EST data for more precise risk stratification.