Abstract 11237: Dose Response and Long QT Genotype During Exercise Stress Testing in Children

Abstract

Introduction: Beta-blockers (BB) are first-line therapy for long QT syndrome (LQTS). Many physicians rely on repeated exercise stress tests (ESTs) to establish the optimal dose in each patient. Hypothesis: Increased BB dose is associated with a decrease in maximum heart rate, influenced by precision-medicine factors including genotype. Methods: Retrospective chart review of treadmill ESTs with the outcome variable “% predicted heart rate (HR)” = (maximum HR achieved/(220-age))*100. Genotype positive patients had pathogenic or likely pathogenic variants, re-adjudicated in 2022. Doses of BB other than nadolol were converted to nadolol equivalents using an established methodology. Results: We evaluated 345 ESTs in 132 LQTS patients (58% genotype positive) from 2003-21. The mean age at first EST was 12.5 years (standard deviation 4.0 years). Most patients were prescribed nadolol (59%) or atenolol (28%). When controlled for person-level fixed effects, we observed an inverse relationship between BB dose and % predicted HR. The dose-response slope was steeper in genotype positive patients than genotype negative patients (-4.8 vs. -3.3, Figure , p<0.01). We observed mild decreases in blood pressure as BB dose increased, (mean 5 mmHg decrease in systolic blood pressure per 1 mg/kg increase in BB). However, neither maximum VO2 nor maximum respiratory exchange ratio were affected by increased BB dose (the slope of each was indistinguishable from 0 in person-level fixed effects models). Conclusion: In children with LQTS, genotype positive patients were more sensitive to BB than genotype negative patients. We developed a multivariate model to predict the dose of BB required to achieve therapeutic beta-blockade, conditional on individual patient demographics and genotype. The model may decrease the need for serial ESTs. BB dose did not affect maximum VO2 or respiratory exchange ratio, which is reassuring for children and adolescents with LQTS who exercise.