214 Gene-specific effect of beta-adrenergic blockade on QT duration in the Long QT syndrome

Abstract

In the long QT syndrome (LQTS) the clinical efficacy of beta-blocker treatment differs according to the genotype. We aimed to asses the effect of beta-blocker treatment in LQT1 and LQT2 patients. 24-hour Holter ECG were recorded before and after beta-blocking therapy initiation in genotyped LQT1 (n = 30, 8 males, mean age 21 ± 17) and LQT2 patients (n = 16, 8 males, mean age 19 ± 15). QT duration was measured on consecutive 1-minute averaged QRS-T complexes leading to up to 1440 QT-RR pairs for each recording. Then, we computed subject- and condition-specific log/log QT/RR relationships which were used to calculate QT interval duration at RR = 1000 ms (QT1000 = 1000*). Before treatment, coefficients were higher in LQT2 than in LQT1 patients (0.53 ± 0.10 vs. 0.40 ± 0.11, p < 0.001) and QT1000 was longer in LQT2 than in LQT1 patients (521 ± 38 vs. 481 ± 39 ms, p < 0.01). Beta-blockers significantly prolonged the mean RR interval (RR = 827 ± 161 ms before treatment and 939 ± 197 ms on beta-blocker, p < 0.0001). The coefficients were not significantly modified by beta-blockers (0.41 ± 0.9 in LQT1 patients and 0.52 ± 0.12 LQT2 patients). Beta-blocker treatment was associated with a prolongation of the QT1000 interval (from 481 ± 39 to 498 ± 43 ms, p < 0.01) in LQT1 patients but with a shortening in LQT2 patients (from 521 ± 38 to 503 ± 32 ms, p < 0.01). Our results confirm the elevated coefficient of the QT/RR relationship in LQTS patients. LQT2 patients showed higher coefficient and longer QT1000 when compared to LQT1 patients. The effect of beta-adrenergic blockade on QT1000 duration was gene-specific. Given the demonstrated efficacy of beta-blockers in LQT1 and 2 patients, our data suggest that QT1000 might be a poor predictor of outcome under anti-adrenergic therapy.