Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome

Christian Krijger Juárez; Virginnio M. Proost; Michael W. Tanck; Sven Dittmann; J. Martijn Bos; Lia Crotti; Julien Barc; Maarten P. van den Berg; Jasmin Mujkanovic; Corinna Rickert; Raquel Almeida Lopes Neves; Giulia Musu; Federica Dagradi; Fulvio L.F. Giovenzana; Aurélien Clédel; Aurélie Thollet; John R. Giudicessi; Jacob Tfelt-Hansen; Vincent Probst; Peter J. Schwartz; Michael J. Ackerman; Eric Schulze-Bahr; Connie R. Bezzina; Arthur A.M. Wilde

doi:10.1016/j.hrthm.2024.12.015

Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome

Christian Krijger Juárez, Virginnio M. Proost, Michael W. Tanck, Sven Dittmann, J. Martijn Bos, Lia Crotti, Julien Barc, Maarten P. van den Berg, Jasmin Mujkanovic, Corinna Rickert, Raquel Almeida Lopes Neves, Giulia Musu, Federica Dagradi, Fulvio L.F. Giovenzana, Aurélien Clédel, Aurélie Thollet, John R. Giudicessi, Jacob Tfelt-Hansen, Vincent Probst, Peter J. SchwartzMichael J. Ackerman, Eric Schulze-Bahr, Connie R. Bezzina, Arthur A.M. Wilde^*

^*Corresponding author for this work

Cardiovascular Centre (CVC)

Research output: Contribution to journal › Article › Academic › peer-review

1 Downloads (Pure)

Abstract

Background: Congenital long QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods.

Objective: We aimed to evaluate the potential utility of electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS.

Methods: The study, which considered patients with LQTS type 1 and LQTS type 2, comprised a discovery cohort of 695 and a validation cohort of 635 patients.

Results: The change in corrected QT (QTc) interval between rest and recovery (between rest and 3–4 minutes into the recovery period, called recovery-rest ΔQTc) was consistently greater in symptomatic patients. Sensitivity analyses performed on EST data obtained on and off β-blockers as well as upon distinguishing between patients with a baseline QTc interval below and those above 470 ms demonstrated consistent findings. The association of recovery-rest ΔQTc with cardiac events remained significant in a subanalysis focusing on future events (ie, occurring after the EST). An optimal recovery-rest ΔQTc cutoff was determined for LQTS type 1 (35 ms) and LQTS type 2 (16 ms) separately and was shown to be significantly associated with cardiac events.

Conclusion: Our findings suggest that in patients with LQTS, dynamic QT interval measures obtained during the EST are associated with lifetime arrhythmic events and events after the EST. Such measures can be helpful in identifying a higher-risk subset of patients with LQTS in order to optimize their management. Further research may confirm these findings in larger cohorts and explore the potential benefit of combining genetic and EST data for more precise risk stratification.

Original language	English
Journal	Heart Rhythm
DOIs	https://doi.org/10.1016/j.hrthm.2024.12.015
Publication status	E-pub ahead of print - 14-Dec-2024

Keywords

Arrhythmias
Exercise stress test
Genetics
Long QT syndrome
Risk stratification

Access to Document

10.1016/j.hrthm.2024.12.015Licence: CC BY

Novel risk predictor of arrhythmiasProof, 806 KBLicence: CC BY

Handle.net

Persistent link

Cite this

Krijger Juárez, C., Proost, V. M., Tanck, M. W., Dittmann, S., Bos, J. M., Crotti, L., Barc, J., van den Berg, M. P., Mujkanovic, J., Rickert, C., Lopes Neves, R. A., Musu, G., Dagradi, F., Giovenzana, F. L. F., Clédel, A., Thollet, A., Giudicessi, J. R., Tfelt-Hansen, J., Probst, V., ... Wilde, A. A. M. (2024). Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome. Heart Rhythm. Advance online publication. https://doi.org/10.1016/j.hrthm.2024.12.015

@article{985d97cc2b0e47ad85a3155fc90b65f3,

title = "Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome",

abstract = "Background: Congenital long QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods.Objective: We aimed to evaluate the potential utility of electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS.Methods: The study, which considered patients with LQTS type 1 and LQTS type 2, comprised a discovery cohort of 695 and a validation cohort of 635 patients.Results: The change in corrected QT (QTc) interval between rest and recovery (between rest and 3–4 minutes into the recovery period, called recovery-rest ΔQTc) was consistently greater in symptomatic patients. Sensitivity analyses performed on EST data obtained on and off β-blockers as well as upon distinguishing between patients with a baseline QTc interval below and those above 470 ms demonstrated consistent findings. The association of recovery-rest ΔQTc with cardiac events remained significant in a subanalysis focusing on future events (ie, occurring after the EST). An optimal recovery-rest ΔQTc cutoff was determined for LQTS type 1 (35 ms) and LQTS type 2 (16 ms) separately and was shown to be significantly associated with cardiac events.Conclusion: Our findings suggest that in patients with LQTS, dynamic QT interval measures obtained during the EST are associated with lifetime arrhythmic events and events after the EST. Such measures can be helpful in identifying a higher-risk subset of patients with LQTS in order to optimize their management. Further research may confirm these findings in larger cohorts and explore the potential benefit of combining genetic and EST data for more precise risk stratification.",

keywords = "Arrhythmias, Exercise stress test, Genetics, Long QT syndrome, Risk stratification",

author = "{Krijger Ju{\'a}rez}, Christian and Proost, {Virginnio M.} and Tanck, {Michael W.} and Sven Dittmann and Bos, {J. Martijn} and Lia Crotti and Julien Barc and {van den Berg}, {Maarten P.} and Jasmin Mujkanovic and Corinna Rickert and {Lopes Neves}, {Raquel Almeida} and Giulia Musu and Federica Dagradi and Giovenzana, {Fulvio L.F.} and Aur{\'e}lien Cl{\'e}del and Aur{\'e}lie Thollet and Giudicessi, {John R.} and Jacob Tfelt-Hansen and Vincent Probst and Schwartz, {Peter J.} and Ackerman, {Michael J.} and Eric Schulze-Bahr and Bezzina, {Connie R.} and Wilde, {Arthur A.M.}",

note = "Publisher Copyright: {\textcopyright} 2024 Heart Rhythm Society",

year = "2024",

month = dec,

day = "14",

doi = "10.1016/j.hrthm.2024.12.015",

language = "English",

journal = "Heart Rhythm",

issn = "1547-5271",

publisher = "ELSEVIER SCIENCE INC",

}

Krijger Juárez, C, Proost, VM, Tanck, MW, Dittmann, S, Bos, JM, Crotti, L, Barc, J, van den Berg, MP, Mujkanovic, J, Rickert, C, Lopes Neves, RA, Musu, G, Dagradi, F, Giovenzana, FLF, Clédel, A, Thollet, A, Giudicessi, JR, Tfelt-Hansen, J, Probst, V, Schwartz, PJ, Ackerman, MJ, Schulze-Bahr, E, Bezzina, CR & Wilde, AAM 2024, 'Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome', Heart Rhythm. https://doi.org/10.1016/j.hrthm.2024.12.015

TY - JOUR

T1 - Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome

AU - Krijger Juárez, Christian

AU - Proost, Virginnio M.

AU - Tanck, Michael W.

AU - Dittmann, Sven

AU - Bos, J. Martijn

AU - Crotti, Lia

AU - Barc, Julien

AU - van den Berg, Maarten P.

AU - Mujkanovic, Jasmin

AU - Rickert, Corinna

AU - Lopes Neves, Raquel Almeida

AU - Musu, Giulia

AU - Dagradi, Federica

AU - Giovenzana, Fulvio L.F.

AU - Clédel, Aurélien

AU - Thollet, Aurélie

AU - Giudicessi, John R.

AU - Tfelt-Hansen, Jacob

AU - Probst, Vincent

AU - Schwartz, Peter J.

AU - Ackerman, Michael J.

AU - Schulze-Bahr, Eric

AU - Bezzina, Connie R.

AU - Wilde, Arthur A.M.

PY - 2024/12/14

Y1 - 2024/12/14

N2 - Background: Congenital long QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods.Objective: We aimed to evaluate the potential utility of electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS.Methods: The study, which considered patients with LQTS type 1 and LQTS type 2, comprised a discovery cohort of 695 and a validation cohort of 635 patients.Results: The change in corrected QT (QTc) interval between rest and recovery (between rest and 3–4 minutes into the recovery period, called recovery-rest ΔQTc) was consistently greater in symptomatic patients. Sensitivity analyses performed on EST data obtained on and off β-blockers as well as upon distinguishing between patients with a baseline QTc interval below and those above 470 ms demonstrated consistent findings. The association of recovery-rest ΔQTc with cardiac events remained significant in a subanalysis focusing on future events (ie, occurring after the EST). An optimal recovery-rest ΔQTc cutoff was determined for LQTS type 1 (35 ms) and LQTS type 2 (16 ms) separately and was shown to be significantly associated with cardiac events.Conclusion: Our findings suggest that in patients with LQTS, dynamic QT interval measures obtained during the EST are associated with lifetime arrhythmic events and events after the EST. Such measures can be helpful in identifying a higher-risk subset of patients with LQTS in order to optimize their management. Further research may confirm these findings in larger cohorts and explore the potential benefit of combining genetic and EST data for more precise risk stratification.

AB - Background: Congenital long QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods.Objective: We aimed to evaluate the potential utility of electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS.Methods: The study, which considered patients with LQTS type 1 and LQTS type 2, comprised a discovery cohort of 695 and a validation cohort of 635 patients.Results: The change in corrected QT (QTc) interval between rest and recovery (between rest and 3–4 minutes into the recovery period, called recovery-rest ΔQTc) was consistently greater in symptomatic patients. Sensitivity analyses performed on EST data obtained on and off β-blockers as well as upon distinguishing between patients with a baseline QTc interval below and those above 470 ms demonstrated consistent findings. The association of recovery-rest ΔQTc with cardiac events remained significant in a subanalysis focusing on future events (ie, occurring after the EST). An optimal recovery-rest ΔQTc cutoff was determined for LQTS type 1 (35 ms) and LQTS type 2 (16 ms) separately and was shown to be significantly associated with cardiac events.Conclusion: Our findings suggest that in patients with LQTS, dynamic QT interval measures obtained during the EST are associated with lifetime arrhythmic events and events after the EST. Such measures can be helpful in identifying a higher-risk subset of patients with LQTS in order to optimize their management. Further research may confirm these findings in larger cohorts and explore the potential benefit of combining genetic and EST data for more precise risk stratification.

KW - Arrhythmias

KW - Exercise stress test

KW - Genetics

KW - Long QT syndrome

KW - Risk stratification

UR - http://www.scopus.com/inward/record.url?scp=85214504349&partnerID=8YFLogxK

U2 - 10.1016/j.hrthm.2024.12.015

DO - 10.1016/j.hrthm.2024.12.015

M3 - Article

C2 - 39675651

SN - 1547-5271

JO - Heart Rhythm

JF - Heart Rhythm

ER -

Novel risk predictor of arrhythmias for patients with potassium channel–related congenital long QT syndrome

Abstract

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Cite this