Atrial Fibrillation in Valvular Heart Disease
- 1Department of Medicine (Cardiovascular Division), University of California-San Francisco, San Francisco, California, USA
- 2Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Québec, Québec, Canada
- 3Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California, USA
Abstract
Background: Atrial fibrillation (AF) in valvular heart disease (VHD) is generally attributed to pressure or volume overload with atrial remodeling, but the independent contribution of genetic predisposition remains unclear.
Objectives: The authors evaluated the predictive value of a previously developed AF polygenic risk score (PRS) across VHD subtypes in the UK Biobank.
Methods: In this prospective cohort study (UK Biobank, 2000-2022), incident AF and VHD status were defined using ICD codes. VHD subtypes included mitral valve (MV) disease (MV prolapse [MVP], mitral regurgitation, mitral stenosis) and aortic valve (AV) disease (aortic stenosis, aortic regurgitation). PRS was categorized into quintiles and grouped as low, intermediate, and high.
Results: Among 452,841 participants with available PRS, 385 had MVP, 1,058 mitral regurgitation, 81 mitral stenosis, 421 aortic regurgitation, and 509 aortic stenosis. In Cox models, PRS was independently associated with incident AF in MV disease (HR: 1.7, P = 0.03 for intermediate PRS; HR: 2.3, P = 0.002 for high PRS), with the strongest effect in MVP (HR: 3.1, P = 0.03 for high PRS). In AV disease, PRS was not significantly associated with AF risk (P = 0.93 and P = 0.07 for intermediate and high PRS, respectively). Interaction analyses confirmed attenuation or absence of the PRS effect in AV disease (P = 0.04 and P = 0.004 for intermediate and high PRS, respectively), whereas no significant interaction was observed in MV disease (P = 0.80 and P = 0.11, respectively).
Conclusions: In VHD, AF PRS predicts AF risk, but the genetic impact differs by subtype. AV disease shows minimal genetic contribution, suggesting predominantly hemodynamic risk, while MV disease—particularly MVP—shows substantial genetic influence.
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BibTeX
@article{cristin2026atrial,
title = {{Atrial Fibrillation in Valvular Heart Disease}},
author = {Luca Cristin and Janet J. Tang and Lionel Tastet and Rohit Jhawar and David V. Glidden and Gregory M. Marcus and Francesca N. Delling},
journal = {JACC: Advances},
year = {2026},
month = oct,
doi = {10.1016/j.jacadv.2026.103355},
url = {https://doi.org/10.1016/j.jacadv.2026.103355},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Atrial Fibrillation in Valvular Heart Disease
AU - Luca Cristin
AU - Janet J. Tang
AU - Lionel Tastet
AU - Rohit Jhawar
AU - David V. Glidden
AU - Gregory M. Marcus
AU - Francesca N. Delling
PY - 2026
DA - 2026/10/20
JO - JACC: Advances
DO - 10.1016/j.jacadv.2026.103355
UR - https://doi.org/10.1016/j.jacadv.2026.103355
AB - Background: Atrial fibrillation (AF) in valvular heart disease (VHD) is generally attributed to pressure or volume overload with atrial remodeling, but the independent contribution of genetic predisposition remains unclear. Objectives: The authors evaluated the predictive value of a previously developed AF polygenic risk score (PRS) across VHD subtypes in the UK Biobank. Methods: In this prospective cohort study (UK Biobank, 2000-2022), incident AF and VHD status were defined using ICD codes. VHD subtypes included mitral valve (MV) disease (MV prolapse [MVP], mitral regurgitation, mitral stenosis) and aortic valve (AV) disease (aortic stenosis, aortic regurgitation). PRS was categorized into quintiles and grouped as low, intermediate, and high. Results: Among 452,841 participants with available PRS, 385 had MVP, 1,058 mitral regurgitation, 81 mitral stenosis, 421 aortic regurgitation, and 509 aortic stenosis. In Cox models, PRS was independently associated with incident AF in MV disease (HR: 1.7, P = 0.03 for intermediate PRS; HR: 2.3, P = 0.002 for high PRS), with the strongest effect in MVP (HR: 3.1, P = 0.03 for high PRS). In AV disease, PRS was not significantly associated with AF risk (P = 0.93 and P = 0.07 for intermediate and high PRS, respectively). Interaction analyses confirmed attenuation or absence of the PRS effect in AV disease (P = 0.04 and P = 0.004 for intermediate and high PRS, respectively), whereas no significant interaction was observed in MV disease (P = 0.80 and P = 0.11, respectively). Conclusions: In VHD, AF PRS predicts AF risk, but the genetic impact differs by subtype. AV disease shows minimal genetic contribution, suggesting predominantly hemodynamic risk, while MV disease—particularly MVP—shows substantial genetic influence.
SN - 2772-963X
ER -