The QUIDAM study: Hydroquinidine therapy for the management of Brugada syndrome patients at high arrhythmic risk

Heart Rhythm. 2017 Aug;14(8):1147-1154. doi: 10.1016/j.hrthm.2017.04.019. Epub 2017 Apr 12.

Abstract

Background: Although the implantable cardioverter-defibrillator (ICD) remains the main therapy for Brugada syndrome (BrS), it does not reduce life-threatening ventricular arrhythmia. Based on pathophysiologic mechanisms, hydroquinidine (HQ) has been suggested for effective prevention of arrhythmia.

Objective: The purpose of this study was to provide evidence-based data supporting HQ use to prevent life-threatening ventricular arrhythmia in high-risk patients with BrS.

Methods: We performed a prospective multicenter randomized (HQ vs placebo) double-blind study with two 18-month crossover phases in patients with BrS and implanted with an ICD.

Results: Among the 50 patients enrolled (mean age 47.0 ± 11.4 years, 42 [84%] male), 26 (52%) fully completed both phases. Thirty-four (68%) presented HQ-related side effects, mainly gastrointestinal, which led to discontinuation of the therapy in 13 (26%). HQ lengthened the QTc interval (409 ± 32 ms vs 433 ± 37 ms; P = .027) and increased repolarization dispersion as evaluated by Tpe max in precordial leads (89 ± 15 ms vs 108 ± 27 ms; P <.0001) with no significant changes in J-point elevation. During the 36-month follow-up, 1 appropriate ICD shock (0.97% event per year), 1 self-terminating ventricular fibrillation, and 1 inappropriate ICD shock occurred under placebo therapy. No arrhythmic events were reported under HQ therapy.

Conclusion: Although HQ seems to be effective in preventing life-threatening ventricular arrhythmia, it could not be an alternative for ICD implantation. Its frequent side effects greatly reduce its probable compliance and therefore do not reveal a significant effect. HQ increases repolarization dispersal with no changes in BrS pattern, which could indicate a more complex action of HQ than its Ito blocking effect alone.

Keywords: Arrhythmia; Brugada syndrome; Implantable cardioverter–defibrillator; Quinidine; Repolarization.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Arrhythmia Agents / therapeutic use
  • Brugada Syndrome / complications
  • Brugada Syndrome / physiopathology
  • Brugada Syndrome / therapy*
  • Cross-Over Studies
  • Defibrillators, Implantable*
  • Double-Blind Method
  • Electrocardiography*
  • Female
  • Follow-Up Studies
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Quinidine / analogs & derivatives*
  • Quinidine / therapeutic use
  • Risk Factors
  • Time Factors
  • Ventricular Fibrillation / etiology
  • Ventricular Fibrillation / physiopathology
  • Ventricular Fibrillation / prevention & control*

Substances

  • Anti-Arrhythmia Agents
  • hydroquinidine
  • Quinidine