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

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Standard

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia. / Bergeman, Auke T; Lieve, Krystien V V; Kallas, Dania; Bos, J Martijn; Rosés I Noguer, Ferran; Denjoy, Isabelle; Zorio, Esther; Kammeraad, Janneke A E; Peltenburg, Puck J; Tobert, Katie; Aiba, Takeshi; Atallah, Joseph; Drago, Fabrizio; Batra, Anjan S; Brugada, Ramon; Borggrefe, Martin; Clur, Sally-Ann B; Cox, Moniek G P J; Davis, Andrew; Dhillon, Santokh; Etheridge, Susan P; Fischbach, Peter; Franciosi, Sonia; Haugaa, Kristina; Horie, Minoru; Johnsrude, Christopher; Kane, Austin M; Krause, Ulrich; Kwok, Sit-Yee; LaPage, Martin J; Ohno, Seiko; Probst, Vincent; Roberts, Jason D; Robyns, Tomas; Sacher, Frederic; Semsarian, Christopher; Skinner, Jonathan R; Swan, Heikki; Tavacova, Terezia; Tisma-Dupanovic, Svjetlana; Tfelt-Hansen, Jacob; Yap, Sing-Chien; Kannankeril, Prince J; Leenhardt, Antoine; Till, Janice; Sanatani, Shubhayan; Tanck, Michael W T; Ackerman, Michael J; Wilde, Arthur A M; van der Werf, Christian.

In: Circulation, Vol. 148, No. 25, 2023, p. 2029-2037.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bergeman, AT, Lieve, KVV, Kallas, D, Bos, JM, Rosés I Noguer, F, Denjoy, I, Zorio, E, Kammeraad, JAE, Peltenburg, PJ, Tobert, K, Aiba, T, Atallah, J, Drago, F, Batra, AS, Brugada, R, Borggrefe, M, Clur, S-AB, Cox, MGPJ, Davis, A, Dhillon, S, Etheridge, SP, Fischbach, P, Franciosi, S, Haugaa, K, Horie, M, Johnsrude, C, Kane, AM, Krause, U, Kwok, S-Y, LaPage, MJ, Ohno, S, Probst, V, Roberts, JD, Robyns, T, Sacher, F, Semsarian, C, Skinner, JR, Swan, H, Tavacova, T, Tisma-Dupanovic, S, Tfelt-Hansen, J, Yap, S-C, Kannankeril, PJ, Leenhardt, A, Till, J, Sanatani, S, Tanck, MWT, Ackerman, MJ, Wilde, AAM & van der Werf, C 2023, 'Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia', Circulation, vol. 148, no. 25, pp. 2029-2037. https://doi.org/10.1161/CIRCULATIONAHA.123.064786

APA

Bergeman, A. T., Lieve, K. V. V., Kallas, D., Bos, J. M., Rosés I Noguer, F., Denjoy, I., Zorio, E., Kammeraad, J. A. E., Peltenburg, P. J., Tobert, K., Aiba, T., Atallah, J., Drago, F., Batra, A. S., Brugada, R., Borggrefe, M., Clur, S-A. B., Cox, M. G. P. J., Davis, A., ... van der Werf, C. (2023). Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia. Circulation, 148(25), 2029-2037. https://doi.org/10.1161/CIRCULATIONAHA.123.064786

Vancouver

Bergeman AT, Lieve KVV, Kallas D, Bos JM, Rosés I Noguer F, Denjoy I et al. Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia. Circulation. 2023;148(25):2029-2037. https://doi.org/10.1161/CIRCULATIONAHA.123.064786

Author

Bergeman, Auke T ; Lieve, Krystien V V ; Kallas, Dania ; Bos, J Martijn ; Rosés I Noguer, Ferran ; Denjoy, Isabelle ; Zorio, Esther ; Kammeraad, Janneke A E ; Peltenburg, Puck J ; Tobert, Katie ; Aiba, Takeshi ; Atallah, Joseph ; Drago, Fabrizio ; Batra, Anjan S ; Brugada, Ramon ; Borggrefe, Martin ; Clur, Sally-Ann B ; Cox, Moniek G P J ; Davis, Andrew ; Dhillon, Santokh ; Etheridge, Susan P ; Fischbach, Peter ; Franciosi, Sonia ; Haugaa, Kristina ; Horie, Minoru ; Johnsrude, Christopher ; Kane, Austin M ; Krause, Ulrich ; Kwok, Sit-Yee ; LaPage, Martin J ; Ohno, Seiko ; Probst, Vincent ; Roberts, Jason D ; Robyns, Tomas ; Sacher, Frederic ; Semsarian, Christopher ; Skinner, Jonathan R ; Swan, Heikki ; Tavacova, Terezia ; Tisma-Dupanovic, Svjetlana ; Tfelt-Hansen, Jacob ; Yap, Sing-Chien ; Kannankeril, Prince J ; Leenhardt, Antoine ; Till, Janice ; Sanatani, Shubhayan ; Tanck, Michael W T ; Ackerman, Michael J ; Wilde, Arthur A M ; van der Werf, Christian. / Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia. In: Circulation. 2023 ; Vol. 148, No. 25. pp. 2029-2037.

Bibtex

@article{9e3a97bc0f7d420ebe01101d32892cc6,
title = "Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia",
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.",
keywords = "Female, Humans, Adolescent, Male, Flecainide/adverse effects, Incidence, Cross-Over Studies, Tachycardia, Ventricular/diagnosis, Adrenergic beta-Antagonists/adverse effects, Defibrillators, Implantable, Death, Sudden, Cardiac/epidemiology",
author = "Bergeman, {Auke T} and Lieve, {Krystien V V} and Dania Kallas and Bos, {J Martijn} and {Ros{\'e}s I Noguer}, Ferran and Isabelle Denjoy and Esther Zorio and Kammeraad, {Janneke A E} and Peltenburg, {Puck J} and Katie Tobert and Takeshi Aiba and Joseph Atallah and Fabrizio Drago and Batra, {Anjan S} and Ramon Brugada and Martin Borggrefe and Clur, {Sally-Ann B} and Cox, {Moniek G P J} and Andrew Davis and Santokh Dhillon and Etheridge, {Susan P} and Peter Fischbach and Sonia Franciosi and Kristina Haugaa and Minoru Horie and Christopher Johnsrude and Kane, {Austin M} and Ulrich Krause and Sit-Yee Kwok and LaPage, {Martin J} and Seiko Ohno and Vincent Probst and Roberts, {Jason D} and Tomas Robyns and Frederic Sacher and Christopher Semsarian and Skinner, {Jonathan R} and Heikki Swan and Terezia Tavacova and Svjetlana Tisma-Dupanovic and Jacob Tfelt-Hansen and Sing-Chien Yap and Kannankeril, {Prince J} and Antoine Leenhardt and Janice Till and Shubhayan Sanatani and Tanck, {Michael W T} and Ackerman, {Michael J} and Wilde, {Arthur A M} and {van der Werf}, Christian",
year = "2023",
doi = "10.1161/CIRCULATIONAHA.123.064786",
language = "English",
volume = "148",
pages = "2029--2037",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams & Wilkins",
number = "25",

}

RIS

TY - JOUR

T1 - Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

AU - Bergeman, Auke T

AU - Lieve, Krystien V V

AU - Kallas, Dania

AU - Bos, J Martijn

AU - Rosés I Noguer, Ferran

AU - Denjoy, Isabelle

AU - Zorio, Esther

AU - Kammeraad, Janneke A E

AU - Peltenburg, Puck J

AU - Tobert, Katie

AU - Aiba, Takeshi

AU - Atallah, Joseph

AU - Drago, Fabrizio

AU - Batra, Anjan S

AU - Brugada, Ramon

AU - Borggrefe, Martin

AU - Clur, Sally-Ann B

AU - Cox, Moniek G P J

AU - Davis, Andrew

AU - Dhillon, Santokh

AU - Etheridge, Susan P

AU - Fischbach, Peter

AU - Franciosi, Sonia

AU - Haugaa, Kristina

AU - Horie, Minoru

AU - Johnsrude, Christopher

AU - Kane, Austin M

AU - Krause, Ulrich

AU - Kwok, Sit-Yee

AU - LaPage, Martin J

AU - Ohno, Seiko

AU - Probst, Vincent

AU - Roberts, Jason D

AU - Robyns, Tomas

AU - Sacher, Frederic

AU - Semsarian, Christopher

AU - Skinner, Jonathan R

AU - Swan, Heikki

AU - Tavacova, Terezia

AU - Tisma-Dupanovic, Svjetlana

AU - Tfelt-Hansen, Jacob

AU - Yap, Sing-Chien

AU - Kannankeril, Prince J

AU - Leenhardt, Antoine

AU - Till, Janice

AU - Sanatani, Shubhayan

AU - Tanck, Michael W T

AU - Ackerman, Michael J

AU - Wilde, Arthur A M

AU - van der Werf, Christian

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Female

KW - Humans

KW - Adolescent

KW - Male

KW - Flecainide/adverse effects

KW - Incidence

KW - Cross-Over Studies

KW - Tachycardia, Ventricular/diagnosis

KW - Adrenergic beta-Antagonists/adverse effects

KW - Defibrillators, Implantable

KW - Death, Sudden, Cardiac/epidemiology

U2 - 10.1161/CIRCULATIONAHA.123.064786

DO - 10.1161/CIRCULATIONAHA.123.064786

M3 - Journal article

C2 - 37886885

VL - 148

SP - 2029

EP - 2037

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 25

ER -

ID: 378131081