Dose response to nadolol in congenital long QT syndrome

Heart Rhythm. 2021 Aug;18(8):1377-1383. doi: 10.1016/j.hrthm.2021.04.021. Epub 2021 Apr 24.

Abstract

Background: Beta-blocker therapy is the cornerstone of treatment for patients with long QT syndrome (LQTS). Few details on the dose to be used are available. As the response is variable between patients, we systematically evaluated the effect of treatment by performing an exercise test.

Objective: The purpose of this study was to explore dose response to nadolol on exercise test in LQTS patients in order to propose a more personalized therapeutic approach.

Methods: LQTS patients followed at the Reference Centre for Hereditary Arrhythmic Diseases of Nantes with at least 1 exercise test under nadolol were included retrospectively between 1993 and 2017. All patients underwent gradual cycle exercise tests. Doses adjusted to weight and response to treatment were recorded and evaluated by the percentage of age-predicted maximum heart rate reached on exercise test.

Results: Ninety-five patients were included in the study, and 337 stress tests under nadolol were analyzed. No correlation existed between dose and percentage of age-predicted maximum heart rate on exercise tests. Twenty-one patients were overresponders, mostly LQTS1, and 20 were underresponders, mainly LQTS2 (P = .0229). Forty-two patients had at least 3 stress tests under nadolol. We found a negative correlation between dose change and percentage of age-predicted maximum heart rate change (P <.0001). We then proposed a table to adapt dose according to exercise test response.

Conclusion: Our study demonstrated a major variability of dose response to nadolol in patients with LQTS, thus underlining the need for a tailored dosage for each patient. Intraindividual analysis showed a relatively constant dose-response relationship, allowing guided dose adaptation after the first exercise test.

Keywords: Beta-blocker; Dosage; Exercise test; Long QT syndrome; Nadolol.

MeSH terms

  • Adaptation, Physiological / physiology*
  • Adolescent
  • Adult
  • Anti-Arrhythmia Agents / administration & dosage
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Electrocardiography / drug effects*
  • Exercise Test
  • Female
  • Follow-Up Studies
  • Heart Rate / physiology*
  • Humans
  • Infant
  • Injections, Intravenous
  • Long QT Syndrome / drug therapy*
  • Long QT Syndrome / physiopathology
  • Male
  • Middle Aged
  • Nadolol / administration & dosage*
  • Prospective Studies
  • Young Adult

Substances

  • Anti-Arrhythmia Agents
  • Nadolol