Antoine Andorin1, Jean-Baptiste Gourraud2, Jacques Mansourati3, Swanny Fouchard1, Hervé le Marec1, Philippe Maury4, Philippe Mabo5, Jean-Sylvain Hermida6, Jean-Claude Deharo7, Béatrice Delasalle1, Simon Esnault1, Nicolas Sadoul8, Jean-Marc Davy9, Antoine Leenhardt10, Didier Klug11, Pascal Defaye12, Dominique Babuty13, Frédéric Sacher14, Vincent Probst1. 1. L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France. 2. L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France. Electronic address: jeanbaptiste.gourraud@chu-nantes.fr. 3. CHU Brest, Service de Cardiologie, Brest, France. 4. CHU Toulouse, Service de Cardiologie, Toulouse, France. 5. CHU Rennes, Service de Cardiologie, Rennes, France. 6. CHU Amiens, Service de Cardiologie, Amiens, France. 7. CHU Marseille, Service de Cardiologie, Marseille, France. 8. CHU Nancy, Service de Cardiologie, Nancy, France. 9. CHU Montpellier, Service de Cardiologie, Montpellier, France. 10. CNMR Maladies Cardiaques Héréditaires Rares, Hôpital Bichat, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Service de Cardiologie, Hôpital Bichat, Paris, France. 11. CHU Lille, Service de Cardiologie, Lille, France. 12. CHU Grenoble, Service de Cardiologie, Grenoble, France. 13. CHU Tours, Service de Cardiologie, Tours, France. 14. CHU Bordeaux, IHU LIRYC, INSERM 1045, Université de Bordeaux, Bordeaux, France.
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.
RCT Entities:
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.
Authors: Edmond M Cronin; Frank M Bogun; Philippe Maury; Petr Peichl; Minglong Chen; Narayanan Namboodiri; Luis Aguinaga; Luiz Roberto Leite; Sana M Al-Khatib; Elad Anter; Antonio Berruezo; David J Callans; Mina K Chung; Phillip Cuculich; Andre d'Avila; Barbara J Deal; Paolo Della Bella; Thomas Deneke; Timm-Michael Dickfeld; Claudio Hadid; Haris M Haqqani; G Neal Kay; Rakesh Latchamsetty; Francis Marchlinski; John M Miller; Akihiko Nogami; Akash R Patel; Rajeev Kumar Pathak; Luis C Saenz Morales; Pasquale Santangeli; John L Sapp; Andrea Sarkozy; Kyoko Soejima; William G Stevenson; Usha B Tedrow; Wendy S Tzou; Niraj Varma; Katja Zeppenfeld Journal: J Interv Card Electrophysiol Date: 2020-10 Impact factor: 1.900
Authors: Edmond M Cronin; Frank M Bogun; Philippe Maury; Petr Peichl; Minglong Chen; Narayanan Namboodiri; Luis Aguinaga; Luiz Roberto Leite; Sana M Al-Khatib; Elad Anter; Antonio Berruezo; David J Callans; Mina K Chung; Phillip Cuculich; Andre d'Avila; Barbara J Deal; Paolo Della Bella; Thomas Deneke; Timm-Michael Dickfeld; Claudio Hadid; Haris M Haqqani; G Neal Kay; Rakesh Latchamsetty; Francis Marchlinski; John M Miller; Akihiko Nogami; Akash R Patel; Rajeev Kumar Pathak; Luis C Sáenz Morales; Pasquale Santangeli; John L Sapp; Andrea Sarkozy; Kyoko Soejima; William G Stevenson; Usha B Tedrow; Wendy S Tzou; Niraj Varma; Katja Zeppenfeld Journal: Europace Date: 2019-08-01 Impact factor: 5.214
Authors: Bence Hegyi; Ye Chen-Izu; Leighton T Izu; Sridharan Rajamani; Luiz Belardinelli; Donald M Bers; Tamás Bányász Journal: Circ Arrhythm Electrophysiol Date: 2020-03-23