TY - JOUR
T1 - Genetic Susceptibility to Atrial Fibrillation Is Associated With Atrial Electrical Remodeling and Adverse Post-Ablation Outcome
AU - Wong, Geoffrey R.
AU - Nalliah, Chrishan J.
AU - Lee, Geoffrey
AU - Voskoboinik, Aleksandr
AU - Prabhu, Sandeep
AU - Parameswaran, Ramanathan
AU - Sugumar, Hariharan
AU - Anderson, Robert D.
AU - Ling, Liang Han
AU - McLellan, Alex
AU - Johnson, Renee
AU - Sanders, Prashanthan
AU - Kistler, Peter M.
AU - Fatkin, Diane
AU - Kalman, Jonathan M.
N1 - Funding Information:
Dr. Wong has received support from co-funded National Health and Medical Research Council (NHMRC)/Heart Foundation post-graduate scholarships. Dr. Fatkin has received support from the NHMRC, Victor Chang Cardiac Research Institute, Estate of the Late RT Hall, and Simon Lee Foundation. Prof. Kalman has received support from an NHMRC practitioner fellowship; and has received research and fellowship support from Biosense Webster, Boston Scientific, St. Jude Medical, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Paul Zei, MD, served as Guest Editor for this paper. William Stevenson, MD, served as Guest Editor-in-Chief for this paper.
Publisher Copyright:
© 2020
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - atrial fibrillation
KW - atrial fibrillation ablation outcomes
KW - atrial substrate
KW - electroanatomic mapping
KW - genetic predisposition
KW - single nucleotide variant
UR - http://www.scopus.com/inward/record.url?scp=85090490900&partnerID=8YFLogxK
U2 - 10.1016/j.jacep.2020.05.031
DO - 10.1016/j.jacep.2020.05.031
M3 - Article
C2 - 33213811
AN - SCOPUS:85090490900
SN - 2405-500X
VL - 6
SP - 1509
EP - 1521
JO - JACC: Clinical Electrophysiology
JF - JACC: Clinical Electrophysiology
IS - 12
ER -