Novel risk predictor of arrhythmias for patients with potassium channel related congenital Long-QT Syndrome.

Abstract

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 exercise stress test (EST) electrocardiographic markers in identifying high-risk LQTS patients.

Methods: The study, which considered LQT1 and LQT2 patients, comprised a discovery cohort of 695 and a validation cohort of 635 patients.

Results: The change in QTc between rest and recovery (between rest and 3-4 minutes into recovery period, called Recovery-Rest ΔQTc) was consistently greater in symptomatic patients. Sensitivity analyses conducted on EST data obtained on and off BB as well as upon distinguishing between patients with a baseline QTC below or above 470 milliseconds (ms), demonstrated consistent findings. The association of Recovery-Rest ΔQTc with cardiac events remained significant in a sub-analysis focussing on future events (i.e. occurring after EST). An optimal Recovery-Rest ΔQTc cut-off was determined for LQT1 (35 ms) and LQT2 (16 ms) separately and was shown to be significantly associated with cardiac events.

Conclusion: Our findings suggest that in LQTS patients, dynamic QT interval measures obtained on EST are associated with lifetime arrhythmic events, and events following EST. Such measures can be helpful in identifying a higher-risk subset of LQTS patients 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.