Author + information
- Geoffrey R. Wong, MBBS, PhDa,b,
- Chrishan J. Nalliah, MBBS, PhDa,b,
- Geoffrey Lee, MBChB, PhDa,
- Aleksandr Voskoboinik, MBBS, PhDc,d,
- Sandeep Prabhu, MBBS, PhDc,d,
- Ramanathan Parameswaran, MBBSa,b,
- Hariharan Sugumar, MBBSc,d,
- Robert D. Anderson, MBBSa,b,
- Liang-Han Ling, MBBS, PhDc,d,
- Alex McLellan, MBBS, PhDa,
- Renee Johnson, PhDf,
- Prashanthan Sanders, MBBS, PhDe,
- Peter M. Kistler, MBBS, PhDc,d,
- Diane Fatkin, MDf,g,h,∗∗∗ ( and )
- Jonathan M. Kalman, MBBS, PhDa,b,∗∗ ()
- aDepartment of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- bDepartment of Medicine, University of Melbourne, Melbourne, Victoria, Australia
- cBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- dHeart Centre, The Alfred Hospital, Melbourne, Victoria, Australia
- eCentre for Heart Rhythm Disorders, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- fMolecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
- gCardiology Department, St. Vincent’s Hospital, Darlinghurst, New South Wales, Australia
- hFaculty of Medicine, University of New South Wales Sydney, Kensington, New South Wales, Australia
- ↵∗Address for correspondence:
Dr. Jonathan M. Kalman, Department of Cardiology, Royal Melbourne Hospital, 300 Grattan Street, Parkville, Melbourne 3050, Victoria, Australia.
- ↵∗∗Dr. Diane Fatkin, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst 2010, New South Wales, Australia.
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.
- atrial fibrillation
- atrial fibrillation ablation outcomes
- atrial substrate
- electroanatomic mapping
- genetic predisposition
- single nucleotide variant
↵∗ Drs. Kalman and Fatkin contributed equally to this work and are joint senior authors.
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.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received April 16, 2020.
- Revision received May 19, 2020.
- Accepted May 27, 2020.
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