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Observational Study
. 2024 Nov;10(11):2359-2370.
doi: 10.1016/j.jacep.2024.06.035. Epub 2024 Sep 4.

Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes

Majd A El-Harasis  1 , Zachary T Yoneda  1 , Katherine C Anderson  1 , Fei Ye  2 , Joseph A Quintana  1 , J Roberto Martinez-Parachini  1 , Gregory G Jackson  1 , Bibin T Varghese  1 , Diane M Crawford  3 , Lili Sun  2 , Hollie L Williams  1 , Matthew J O'Neill  4 , Giovanni E Davogustto  1 , James L Laws  1 , Brittany S Murphy  1 , Kelsey Tomasek  1 , Yan Ru Su  1 , Emily McQuillen  5 , Emma Metz  6 , Carly Smith  7 , Doug Stubbs  5 , Dakota D Grauherr  1 , Quinn S Wells  8 , Gregory F Michaud  9 , Pablo Saavedra  1 , Juan Carlos Estrada  1 , Travis D Richardson  1 , Sharon T Shen  1 , Arvindh N Kanagasundram  1 , Jay A Montgomery  1 , Harikrishna Tandri  1 , Christopher R Ellis  1 , George H Crossley  1 , Prince J Kannankeril  10 , Lynne W Stevenson  1 , William G Stevenson  1 , Steven A Lubitz  11 , Patrick T Ellinor  9 , Dan M Roden  8 , M Benjamin Shoemaker  12
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Free article
Observational Study

Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes

Majd A El-Harasis et al. JACC Clin Electrophysiol. 2024 Nov.
Free article

Abstract

Background: Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF). The efficacy of AF ablation in these patients is unknown.

Objective: This study tested the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have increased recurrence following AF ablation; and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, or a channelopathy) have increased recurrence.

Methods: We performed a prospective, observational, cohort study of patients who underwent AF catheter ablation and whole exome sequencing. The primary outcome measure was ≥30 seconds of any atrial tachyarrhythmia that occurred after a 90-day blanking period.

Results: Among 1,366 participants, 109 (8.0%) had a pathogenic or likely pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, the presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15; 95% CI 0.84-1.60; P = 0.53). P/LP variants in the ALVC gene group, predominantly LMNA, were associated with increased recurrence (n = 10; HR 3.75; 95% CI 1.84-7.63; P < 0.001), compared with those in the arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, and channelopathy gene groups. Participants with P/LP TTN variants (n = 46) had no difference in recurrence compared with genotype-negative-controls (HR 0.93; 95% CI 0.54-1.59; P = 0.78).

Conclusions: Our results support the use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including TTN. However, patients with ALVC variants, such as LMNA, may be at a significantly higher risk for arrhythmia recurrence.

Keywords: atrial fibrillation; catheter ablation; genetic testing.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by grants from the American Heart Association (AHA20SCG35540034 [Dr Shoemaker]) and the National Institutes of Health (R01HL155197 [Dr Shoemaker]). It was also supported by CTSA award (UL1TR000445) from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the AHA or NIH. Dr Shoemaker serves on the advisory board and has received sponsored research funds from Roche Diagnostics. Dr Kanagasundram has received speaking fees from Biosense Webster and Janssen. Dr Crossley has received consulting fees or honoraria from Bayer Healthcare, Boston Scientific, Janssen Pharmaceuticals, Medtronic, and Spectranetics. Dr Richardson has received research funding from Medtronic Inc, Abbott Inc and served as a consultant for Philips Inc and Biosense Webster. Dr Montgomery has received research funding from Medtronic Inc. Dr Ellis has received research funding from Boston Scientific, Medtronic, and Boehringer Ingelheim; and consulting fees from Medtronic, Boston Scientific, Abbott Medical, and Atricure. Dr Michaud has received consulting fees or honoraria from Boston Scientific, Medtronic, Biotronik, Abbott, and Biosense Webster. Vanderbilt receives fellowship support from Medtronic inc., Boston Scientific inc., Abbott Labs, Biotronik, and Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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