Spectrum and prevalence of side effects and complications with guideline-directed therapies for congenital long QT syndrome

Heart Rhythm. 2022 Oct;19(10):1666-1672. doi: 10.1016/j.hrthm.2022.06.008. Epub 2022 Jun 13.

Abstract

Background: β-Blockers (BBs), sodium channel blockers (SCBs), left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillators (ICDs) are used to prevent or counter long QT syndrome (LQTS)-triggered syncope, seizures, and sudden cardiac death. The spectrum and extent of side effects/complications associated with these guideline-directed therapies (GDTs) remain unknown.

Objective: The purpose of this study was to identify the types/prevalence of treatment-associated side effects/complications for patients with the most common LQTS subtypes after GDT.

Methods: Retrospective analysis was performed on 1310 patients with type 1, 2, or 3 LQTS evaluated in Mayo Clinic's Windland Smith Rice Genetic Heart Rhythm Clinic (average age at the time of diagnosis 22 ± 18 years; average length of follow-up 5 ± 5 years) and treated with ≥1 of the common GDTs for LQTS.

Results: BBs were used in 1102 (84%), SCBs in 104 (8%), LCSD in 197 (15%), and an ICD was used in 251 (19%) patients. Overall, 727 (55%) patients reported at least 1 treatment-associated side effect/complication. A total of 490 of 1102 patients treated with BBs (44%) reported side effects, with fatigue (381 [35%]) being the most common; 28 of 104 SCB-treated patients (27%) reported side effects, most common being gastrointestinal distress/vomiting (18 [17%]); 80 of 197 patients (41%) reported side effects after LCSD, most reporting neuropathic pain (57 [29%]); and 129 of 251 patients (51%) experienced ≥1 complication after ICD implantation, including inappropriate shocks (46 [18%]).

Conclusion: Although LQTS-triggered sudden cardiac death is uncommon in the properly treated patient, this study demonstrates that contemporary GDTs for LQTS are not innocuous. Their treatment-related side effects are not trivial and should compel an ongoing quest for new LQTS therapies.

Keywords: Complications; Guideline-directed therapies; LQTS; Side effects; β-Blocker.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Child
  • Child, Preschool
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology
  • Death, Sudden, Cardiac / prevention & control
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Iatrogenic Disease
  • Long QT Syndrome* / diagnosis
  • Prevalence
  • Retrospective Studies
  • Sodium Channel Blockers / therapeutic use
  • Young Adult

Substances

  • Adrenergic beta-Antagonists
  • Sodium Channel Blockers