Long-term fate of long QT syndrome patients diagnosed in childhood and differential effects of beta-blockers.

Background and aims: Congenital long QT syndrome (LQTS) is associated with the risk of major arrhythmic events (MAEs), which can be modified by beta-blocker (BB) administration. We aimed to evaluate the effects of selective vs. non-selective BBs on the cumulative burden of MAEs by performing a retrospective analysis of a cohort of LQTS patients diagnosed during childhood. Methods: All pediatric patients (N = 179, female 54.7%) without structural heart disease diagnosed with LQTS (Schwartz score ≥3.5 points and/or presence of a pathogenic or likely pathogenic genetic variant) between 1985 and 2022, with a median presentation age of 10.8 and a median follow-up of 8.5 years, were included. Data were obtained from medical records, structured patient phone calls, and the National Death Registry. Results: Mean QTc and median Schwartz score were 501.20 ms and 4.0 points, respectively. Pathogenic or likely pathogenic variants were identified in 124 of 143 tested patients (86.7%). BBs were administered to 156 patients (87.2%). Eleven patients died (6.1%), yielding survival probabilities at 5/10/20 years of 97.7%/94.0%/90.2%. Freedom from MAEs was 93.9%/89.4%/79.3% at 5/10/20 years. MAE was independently predicted by early presentation [hazard ratio (HR): 6.92, p < 0.001], Schwartz score (HR: 1.87, p < 0.002), QTc (HR: 1.13, p < 0.001), and the presence of LQTS type 3 (HR: 7.91, p < 0.001). MAE burden was significantly lower in patients treated with non-selective vs. selective BBs, independent of other risk-determining variables (Poisson regression model p = 0.011). Conclusions: The 20-year survival probability of patients with LQTS diagnosed during childhood was 90.2% in the BB treatment era. Non-selective BBs were significantly more effective in decreasing the cumulative MAE burden.