Genetic Susceptibility to Atrial Fibrillation Is Associated With Atrial Electrical Remodeling and Adverse Post-Ablation Outcome

Wong, Geoffrey R. and Nalliah, Chrishan J. and Lee, Geoffrey and Voskoboinik, Aleksandr and Prabhu, Sandeep and Parameswaran, Ramanathan and Sugumar, Hariharan and Anderson, Robert D. and Ling, Liang-Han and McLellan, Alex and Johnson, Renee and Sanders, Prashanthan and Kistler, Peter M. and Fatkin, Diane and Kalman, Jonathan M. (2020) Genetic Susceptibility to Atrial Fibrillation Is Associated With Atrial Electrical Remodeling and Adverse Post-Ablation Outcome. JACC: Clinical Electrophysiology, 6 (12). pp.1509-1521. ISSN 2405500X

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OBJECTIVES: This study sought to assess the atrial electrophysiological properties and post-ablation outcomes in patients with atrial fibrillation (AF) with and without the rs2200733 single nucleotide variant. BACKGROUND: The phenotype associated with chromosome 4q25 of the AF-susceptibility locus remains unknown. METHODS: In this study, 102 consecutive patients (ages 61 +/- 9 years, 64% male) with paroxysmal or persistent AF were prospectively recruited prior to ablation. Patients were genotyped for rs2200733 and high-density left atrial (LA) electroanatomic maps were created using a multipolar catheter during distal coronary sinus (CS) pacing at 600 ms. Voltage, conduction velocity (CV), CV heterogeneity, and fractionated signals of 6 LA segments were determined. Arrhythmia recurrence was assessed by continuous device (51%) and Holter monitoring. RESULTS: Overall, 41 patients (40%) were single nucleotide variant carriers (38 heterozygous, 3 homozygous). A mean of 2,239 +/- 852 points per patient were collected. Carriers had relatively increased CV heterogeneity (45.7 +/- 7.5% vs. 35.9 +/- 2.3%; p < 0.001), complex signals (9.4 +/- 2.9% vs 6.0 +/- 1.2%; p = 0.008), regional LA slowing, or conduction block (31.7 +/- 8.2% vs. 17.9 +/- 1.9%; p = 0.013) particularly in the posterior and lateral walls. There were no differences in CV, voltage, atrial refractoriness, or sinus node function. At follow-up (median: 27 months; range 19 to 31 months), carriers had lower arrhythmia-free survival (51% vs. 80%; p = 0.003). On multivariable analysis, carrier status was independently associated with CV heterogeneity (p = 0.001), complex signals (p = 0.002), and arrhythmia recurrence (p = 0.019). CONCLUSIONS: These data provide the first evidence that the rs2200733-tagged haplotype alters LA electrical remodeling and is a determinant of long-term outcome following AF ablation. The molecular mechanisms underpinning these changes warrant further investigation.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 08 Nov 2021 02:31
Last Modified: 08 Nov 2021 02:31

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