Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia-Reference-Cited by-同舟云学术

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Published:2023-12-19 Issue:25 Volume:148 Page:2029-2037
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Bergeman Auke T.¹²,Lieve Krystien V.V.¹²,Kallas Dania³,Bos J. Martijn⁴,Rosés i Noguer Ferran⁵⁶⁷,Denjoy Isabelle⁸⁷^ORCID,Zorio Esther⁹¹⁰¹¹^ORCID,Kammeraad Janneke A.E.¹²^ORCID,Peltenburg Puck J.¹²^ORCID,Tobert Katie⁴,Aiba Takeshi¹³^ORCID,Atallah Joseph¹⁴^ORCID,Drago Fabrizio¹⁵^ORCID,Batra Anjan S.¹⁶,Brugada Ramon¹⁷^ORCID,Borggrefe Martin¹⁸^ORCID,Clur Sally-Ann B.¹⁹⁷^ORCID,Cox Moniek G.P.J.²⁰^ORCID,Davis Andrew²¹^ORCID,Dhillon Santokh²²^ORCID,Etheridge Susan P.²³^ORCID,Fischbach Peter²⁴,Franciosi Sonia³,Haugaa Kristina²⁵^ORCID,Horie Minoru²⁶^ORCID,Johnsrude Christopher²⁷^ORCID,Kane Austin M.²⁸,Krause Ulrich²⁹^ORCID,Kwok Sit-Yee³⁰,LaPage Martin J.³¹^ORCID,Ohno Seiko¹³²⁶^ORCID,Probst Vincent⁷³²^ORCID,Roberts Jason D.³³^ORCID,Robyns Tomas⁷³⁴^ORCID,Sacher Frederic⁷³⁵^ORCID,Semsarian Christopher³⁶^ORCID,Skinner Jonathan R.³⁷^ORCID,Swan Heikki⁷³⁸,Tavacova Terezia⁷³⁹^ORCID,Tisma-Dupanovic Svjetlana⁴⁰^ORCID,Tfelt-Hansen Jacob⁷⁴¹⁴²^ORCID,Yap Sing-Chien⁴³^ORCID,Kannankeril Prince J.⁴⁴^ORCID,Leenhardt Antoine⁸⁷^ORCID,Till Janice⁵,Sanatani Shubhayan³^ORCID,Tanck Michael W.T.⁴⁵,Ackerman Michael J.⁴^ORCID,Wilde Arthur A.M.¹²⁷^ORCID,van der Werf Christian¹²⁷^ORCID

Affiliation:

1. Heart Centre, Department of Cardiology (A.T.B., K.V.V.L., P.J.P., A.A.M.W., C.v.d.W.), Amsterdam UMC Location AMC, University of Amsterdam, The Netherlands.

2. Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, The Netherlands (A.T.B., K.V.V.L., P.J.P., A.A.M.W., C.v.d.W.).

3. Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada (D.K., S.F., S.S.).

4. Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology & Experimental Therapeutics, Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Genetic Heart Rhythm Clinic and Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN (J.M.B., K.T., M.J.A.).

5. Department of Cardiology, Royal Brompton Hospital, London, United Kingdom (F.R.y.N., J.T.).

6. Department of Paediatric Cardiology, Vall d’Hebron University Hospital, Barcelona, Spain (F.R.y.N.).

7. European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart: ERN GUARD-Heart (F.R.y.N., I.D., F.D., S.-A.B.C., V.P., T.R., F.S., H.S., T.T., J.T.-H., A.L., A.A.M.W., C.v.d.W.).

8. Service de Cardiologie et CRMR Maladies Cardiaques Héréditaires et Rares, APHP, Hôpital Bichat, Université Paris Cité, France (I.D., A.L.).

9. Department of Cardiology, Hospital Universitario y Politécnico La Fe, Valencia, Spain (E.Z.).

10. Unidad de Cardiopatías Familiares, Muerte Súbita y Mecanismos de Enfermedad, Instituto de Investigación Sanitaria La Fe, Valencia, Spain (E.Z.).

11. Center for Biomedical Network Research on Cardiovascular Diseases, Madrid, Spain (E.Z.).

12. Department of Pediatric Cardiology, Erasmus MC–Sophia, Rotterdam, The Netherlands (J.A.E.K.).

13. Medical Genome Center, National Cerebral and Cardiovascular Center, Suita, Japan (T.A., S.O.).

14. Department of Pediatrics, University of Alberta, Edmonton, Canada (J.A.).

15. Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children’s Hospital and Research Institute, Rome, Italy (F.D.).

16. Department of Pediatrics, University of California, Irvine (A.S.B.).

17. Cardiovascular Genetics Center, Institut d’Investigació Biomèdica Girona, Hospital Trueta, CIBERCV, University of Girona, Spain (R.B.).

18. Department of Medicine, University Medical Center Mannheim, Germany (M.B.).

19. Department of Pediatric Cardiology, Emma Children’s Hospital (S.-A.B.C.), Amsterdam UMC Location AMC, University of Amsterdam, The Netherlands.

20. Department of Cardiology, University of Groningen, University Medical Centre Groningen, The Netherlands (M.G.P.J.C.).

21. The Royal Children’s Hospital, Melbourne, Australia (A.D.).

22. IWK Health Center, Dalhousie University, Halifax, Canada (S.D.).

23. Division of Pediatric Cardiology, University of Utah, Salt Lake City (S.P.E.).

24. Sibley Heart Center, Children’s Healthcare of Atlanta, GA (P.F.).

25. ProCardio Center for Innovation, Heart, Vessel and Lung Clinic, Oslo University Hospital, Rikshospitalet, Norway (K.H.).

26. Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan (M.H., S.O.).

27. Division of Pediatric Cardiology, Department of Pediatrics, Norton Children’s Hospital, University of Louisville School of Medicine, KY (C.J.).

28. University of Alabama at Birmingham (A.M.K.).

29. Department of Pediatric Cardiology and Intensive Care Medicine, University Medical Center Göttingen, Georg-August-University, Germany (U.K.).

30. Department of Paediatrics, Hong Kong Children’s Hospital, China (S.-Y.K.).

31. University of Michigan Congenital Heart Center, Ann Arbor (M.J.L.).

32. Université de Nantes, CHU Nantes, CNRS, INSERM, L’institut du Thorax, France (V.P.).

33. Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Canada (J.D.R.).

34. Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium (T.R.).

35. LIRYC Institute, Bordeaux University Hospital, Bordeaux University, France (F.S.).

36. Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Australia (C.S.).

37. Cardiac Inherited Disease Group New Zealand, Green Lane Paediatric and Congenital Cardiac Services, Starship Children’s Hospital, Auckland (J.R.S.).

38. Heart and Lung Centre, Helsinki University Hospital and Helsinki University, Finland (H.S.).

39. Children’s Heart Centre, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic (T.T.).

40. Division of Cardiology, Children’s Mercy Hospital, Kansas City, MO (S.T.-D.).

41. Department of Cardiology, Rigshospitalet, Copenhagen, Denmark (J.T.-H.).

42. Section of Genetics, Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Denmark (J.T.-H.).

43. Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, The Netherlands (S.-C.Y.).

44. Department of Pediatrics, Monroe Carell Jr Children’s Hospital at Vanderbilt, Vanderbilt University Medical Centre, Nashville, TN (P.J.K.).

45. Epidemiology and Data Science, Amsterdam Public Health, Methodology (M.W.T.T.), Amsterdam UMC Location AMC, University of Amsterdam, The Netherlands.

Abstract

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14–29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7–3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4–7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0–6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38–0.83]; P =0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31–0.77]; P =0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14–0.45]; P <0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Reference32 articles.

1. Catecholaminergic Polymorphic Ventricular Tachycardia in Children

2. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

3. Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers

4. Therapeutic approach for patients with catecholaminergic polymorphic ventricular tachycardia: state of the art and future developments

5. Catecholaminergic Polymorphic Ventricular Tachycardia in Children

Cited by 5 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

2. Novel variants inTECRLleading to catecholaminergic polymorphic ventricular tachycardia;Life Science Alliance;2024-05-22

3. Zusätzliches Flecainid bei symptomatischen Patienten mit CPVT;Aktuelle Kardiologie;2024-04

4. Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies;Journal of Clinical Medicine;2024-03-20

5. Ion Channelopathy Genetics;Reference Module in Biomedical Sciences;2024