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

• Published in: Heart rhythm Vol. 14; no. 8; pp. 1147 - 1154
• Main Authors: Andorin, Antoine, Gourraud, Jean-Baptiste, Mansourati, Jacques, Fouchard, Swanny, le Marec, Hervé, Maury, Philippe, Mabo, Philippe, Hermida, Jean-Sylvain, Deharo, Jean-Claude, Delasalle, Béatrice, Esnault, Simon, Sadoul, Nicolas, Davy, Jean-Marc, Leenhardt, Antoine, Klug, Didier, Defaye, Pascal, Babuty, Dominique, Sacher, Frédéric, Probst, Vincent
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2017; Elsevier
• Subjects: Adult; Anti-Arrhythmia Agents - therapeutic use; Arrhythmia; Brugada syndrome; Brugada Syndrome - complications; Brugada Syndrome - physiopathology; Brugada Syndrome - therapy; Cardiology and cardiovascular system; Cardiovascular; Cross-Over Studies; Defibrillators, Implantable; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Heart Rate - drug effects; Human health and pathology; Humans; Implantable cardioverter–defibrillator; Life Sciences; Male; Middle Aged; Pharmaceutical sciences; Pharmacology; Prospective Studies; Quinidine; Quinidine - analogs & derivatives; Quinidine - therapeutic use; Repolarization; Risk Factors; Time Factors; Ventricular Fibrillation - etiology; Ventricular Fibrillation - physiopathology; Ventricular Fibrillation - prevention & control; Repolarization; Implantable cardioverter–defibrillator; Brugada syndrome; Arrhythmia; Quinidine
• ISSN: 1547-5271; 1556-3871; 1556-3871
• DOI: 10.1016/j.hrthm.2017.04.019

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. 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. 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. 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. 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.