Long-Term Frequency Gradients During Persistent Atrial Fibrillation in Sheep Are Associated With Stable Sources in the Left Atrium
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Background—: Dominant frequencies (DFs) of activation are higher in the atria of patients with persistent than paroxysmal atrial fibrillation (AF), and left atrial (LA)-to-right atrial (RA) DF gradients have been identified in both. However, whether such gradients are maintained as long-term persistent AF is established remains unexplored. We aimed at determining in vivo the time course in atrial DF values from paroxysmal to persistent AF in sheep and testing the hypothesis that an LA-to-RA DF difference is associated with LA drivers in persistent AF. Methods and Results—: AF was induced using RA tachypacing (n=8). Electrograms were obtained weekly from an RA lead and an implantable loop recorder implanted near the LA. DFs were determined for 5-second-long electrograms (QRST subtracted) during AF in vivo and in ex vivo optical mapping. Underlying structural changes were compared with weight-matched controls (n=4). After the first AF episode, DF increased gradually during a 2-week period (7±0.21 to 9.92±0.31 Hz; n=6; P <0.05). During 9 to 24 weeks of AF, the DF values on the implantable loop recorder were higher than the RA (10.6±0.08 versus 9.3±0.1 Hz, respectively; n=7; P <0.0001). Subsequent optical mapping confirmed a DF gradient from posterior LA-to-RA (9.1±1.0 to 6.9±0.9 Hz; P <0.05) and demonstrated patterns of activation compatible with drifting rotors in the posterior LA. Persistent AF sheep showed significant enlargement of the posterior LA compared with controls. Conclusions—: In the sheep, transition from paroxysmal to persistent AF shows continuous LA-to-RA DF gradients in vivo together with enlargement of the posterior LA, which harbors the highest frequency domains and patterns of activation compatible with drifting rotors.
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A number of observational studies have demonstrated the association between female sex and risk of AF-related stroke and thromboembolism.
“A number of observational studies have demonstrated the association between female sex and risk of AF-related stroke and thromboembolism (Supplementary Table S6).”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [74]
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- Authors
- Filgueiras-Rama, D., Price, N. F., Martins, R. P., Yamazaki, M., Avula, U. M. R., Kaur, K., Kalifa, J., Ennis, S. R., Hwang, E., Devabhaktuni, V., Jalife, J., & Berenfeld, O.
- Affiliations
- From the Center for Arrhythmia Research, Department of Internal Medicine (D.F.-R., N.F.P., R.P.M., M.Y., U.M.R.A., K.K., J.K., S.R.E., E.H., J.J., O.B.), Department of Molecular and Integrative Physiology (J.J.), and Department of Biomedical Engineering (O.B.), University of Michigan, Ann Arbor, MI; and Department of Electrical Engineering and Computer Science, College of Engineering, University of Toledo, Toledo, OH (N.F.P., V.D.).
- University of Michigan (US)
- Venue
- Circulation: Arrhythmia and Electrophysiology
- Published
- 2012-12
- Volume
- 5
- Issue
- 6
- Pages
- 1160-1167
- ISSN
- 1941-3084 (ISSN-L)
- 1941-3149
- PMC
- PMC4121987
- OpenAlex
- W2164665642
- Cited by
- 70
- References
- 28
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 9 · 2020: 2 · 2019: 8 · 2018: 2 · 2017: 11 · 2016: 11 · 2015: 9 · 2014: 6 · 2013: 4
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Arrhythmia and Electrophysiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL087226, P01HL039707, R01HL087055)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- persistent atrial fibrillation, paroxysmal atrial fibrillation, dominant frequency, left atrium, atrial rotors, atrial remodeling, left atrial enlargement, atrial activation patterns, optical mapping, implantable loop recorder, sheep model
- MeSH terms
- Animals, Atrial Fibrillation, Cardiac Pacing, Artificial, Disease Models, Animal, Heart Atria, Heart Conduction System, Sheep, Time Factors, Disease Progression, Electrophysiologic Techniques, Cardiac, Voltage-Sensitive Dye Imaging
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