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. 2020 Mar;13(3):e007676.
doi: 10.1161/CIRCEP.119.007676. Epub 2020 Feb 14.

Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

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Free PMC article

Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation

M Benjamin Shoemaker et al. Circ Arrhythm Electrophysiol. .
Free PMC article

Abstract

Background: Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.

Methods: Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.

Results: Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13).

Conclusions: Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Keywords: atrial fibrillation; genetic variation; genetics; phenotype; pulmonary veins.

Conflict of interest statement

Disclosures: BEAT-AF: Kühne: Speaker for Boston Scientific, St. Jude Medical and Biotronik. Received lecture/consulting fees from Sorin, Boehringer Ingelheim, Bayer, Sanofi Aventis, Novartis, MSD, Pfizer-BMS and Daiichi-Sankyo. Received unrestricted grants from Bayer and Pfizer. Serves as a proctor for Medtronic (Cryoballoon). Blum, Aeschbacher, Thériault, Conen: No relevant financial disclosures or conflicts of interest. Cleveland Clinic: Sun, Zardkoohi, Barnard, Smith: Van Wagoner, Chung: No relevant financial disclosures or conflicts of interest. Groningen Genetics of Atrial Fibrillation (GGAF)/PREVEND: Al-Jazairi, Siland, Geelhoed,Van Gelder, Rienstra: No relevant financial disclosures or conflicts of interest. Heart Center Leipzig: Husser, Buettner, Hindricks, Bollman, Ueberham: No relevant financial disclosures or conflicts of interest. Intermountain Healthcare: Cutler: Serves as a consultant for Biosense Webster. Knight & Jacobs: No relevant financial disclosures or conflicts of interest. Johns Hopkins: Chrispin: No relevant financial disclosures or conflicts of interest. Calkins: Serves as a consultant and receives lecture honoraria from Medtronic, Boston Scientific, Abbott Medical, Biosense Webster, and Boehringer Ingelheim Nazarian: Serves as a scientific advisor to CardioSolv, Abbott Medical, Siemens Healthcare, ImriCor and Biosense Webster. Receives research support from Biosense Webster, Imricor, and Siemens. Massachusetts General Hospital: Lubitz: Receives research support from Bristol Myers Squibb / Pfizer, Bayer HealthCare, and Boehringer Ingelheim. Served as a consultant for Abbott, Quest Diagnostics, Bristol Myers Squibb / Pfizer. Roselli: No relevant financial disclosures or conflicts of interest. Ellinor: Receives sponsored research support from Bayer AG. Munich: Neumann, Freudling, Müller-Nurasyid, Kääb, Sinner: No relevant financial disclosures or conflicts of interest.: Texas Cardiac Arrhythmia Institute (TCAI): Mohanty: No relevant financial disclosures or conflicts of interest. Natale: BWI Consulting fee / Honoraria; Boston scientific Consulting fee / Honoraria; Medtronic Consulting fee / Honoraria; Abbott Consulting fee / Honoraria Vanderbilt AF Ablation Registry (VAFAR): Shoemaker, Roden, Shaffer, Rinke, Crawford, Montgomery, Yoneda, Well, Issa, No relevant financial disclosures or conflicts of interest. Michaud: Boston Scientific Consulting/Honoraria; Biosense Webster Consulting; Medtronic Honoraria; Biotronik Honoraria; Abbott Consulting/Honoraria.

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