Gene-specific effect of beta-adrenergic blockade on corrected QT interval in the long QT syndrome

Ann Noninvasive Electrocardiol. 2013 Jul;18(4):399-408. doi: 10.1111/anec.12048. Epub 2013 May 3.

Abstract

Background: In the long QT syndrome (LQTS) the effects of beta-blocker treatment on prevention of cardiac events differs according to the genotype. We aimed to assess the effect of beta-blocker treatment on QT/QTc duration in Type 1 LQTS (LQT1) and Type 2 LQTS (LQT2) patients.

Methods: 24-hour digital Holter ECG were recorded before and after beta-blocking therapy initiation in LQT1 (n = 30) and LQT2 patients (n = 16). QT duration was measured on consecutive 1-minute averaged QRS-T complexes leading to up to 1440 edited QT-RR pairs for each recording. We computed subject- and treatment-specific log/log QT/RR relationships which were used to correct the QT intervals. The QT duration was also evaluated at predefined heart rates and after correction using Bazett and Fridericia coefficients.

Results: At baseline, individual QT/RR 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 (from 827 ± 161 to 939 ± 197 ms, P < 0.0001). The individual QT/RR coefficients were not significantly modified by beta-blockers. 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).

Conclusions: The effect of beta-adrenergic blockade on QTc duration is different in LQT1 and LQT2 patients. Our data suggest that, in LQT1 patients, the well-known positive effect of beta-blockade might be associated with a prolongation of QTc duration. The mechanisms of beta-blockade protection may be different in LQT1 and in LQT2 patients.

Keywords: QT duration; beta-blocker; long QT syndrome.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adult
  • Analysis of Variance
  • Cohort Studies
  • Databases, Factual
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Electrocardiography / drug effects
  • Electrocardiography, Ambulatory / drug effects*
  • Electrocardiography, Ambulatory / methods
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Heart Rate / drug effects
  • Humans
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / drug therapy*
  • Long QT Syndrome / genetics*
  • Male
  • Middle Aged
  • Risk Assessment
  • Romano-Ward Syndrome / diagnosis
  • Romano-Ward Syndrome / drug therapy*
  • Romano-Ward Syndrome / genetics*
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists

Supplementary concepts

  • Long Qt Syndrome 2