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. 2025 Apr;56(4):858-867.
doi: 10.1161/STROKEAHA.124.047747. Epub 2025 Mar 7.

Markers of Left Atrial Myopathy: Prognostic Usefulness for Ischemic Stroke and Dementia in People in Sinus Rhythm

Gabriele Masini  1 , Wendy Wang  2 , Yuekai Ji  3 , Anne Eaton  4 , Riccardo M Inciardi  5 , Elsayed Z Soliman  6 , Rod S Passman  7 , Scott D Solomon  8 , Amil M Shah  9 , Raffaele De Caterina  1 , Lin Yee Chen  10
Affiliations

Markers of Left Atrial Myopathy: Prognostic Usefulness for Ischemic Stroke and Dementia in People in Sinus Rhythm

Gabriele Masini et al. Stroke. 2025 Apr.

Abstract

Background: Various measures of abnormal left atrial (LA) structure or function (LA myopathy) are associated with a higher risk of ischemic stroke and dementia, independent of atrial fibrillation. However, limited data exist on their prognostic usefulness. Therefore, we aimed to assess the ability of markers of LA myopathy to improve the prediction of ischemic stroke and dementia.

Methods: The ARIC study (Atherosclerosis Risk in Communities) is a prospective community-based cohort study. For this analysis, we included participants who attended visit 5 (2011-2013) without a history of stroke or atrial fibrillation and had a 12-lead ECG and a transthoracic echocardiogram. Markers of LA myopathy included P wave abnormalities from 12-lead ECG, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and LA volume and strain parameters from the echocardiogram. The primary composite outcome comprised ischemic stroke and dementia, which were ascertained through hospital surveillance, cohort follow-up, and death registries. To determine improvement in risk prediction of the composite outcome, each marker was individually added to a model that included CHA2DS2-VASc variables, and Akaike information criterion, C statistic, and its change were computed. Cox proportional hazards models were used to assess the independent association of LA myopathy markers with the outcome.

Results: Among 4712 participants (59% female; mean age, 74 years), 193 ischemic strokes and 769 dementia cases were ascertained over a median follow-up of 8.3 years. Of LA myopathy markers, only LA reservoir strain and NT-proBNP significantly improved C statistic when added to the CHA2DS2-VASc model (base C statistic, 0.677) for the prediction of the composite outcome. Adding the LA reservoir yielded the highest increase in C statistic (0.010 [95% CI, 0.003-0.017]), and the model including the LA reservoir showed the lowest Akaike information criterion. In multivariable regression models, LA volume index, NT-proBNP, and LA strain parameters were significantly associated with the composite outcome.

Conclusions: Of various LA myopathy markers, LA reservoir yields the greatest improvement in the prediction of ischemic stroke and dementia, supporting its use to identify people at high risk of cerebrovascular events and dementia.

Keywords: atrial fibrillation; brain infarction; dementia; ischemic stroke; thrombosis.

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Conflict of interest statement

W. Wang is funded by the grant T32 HL007779. Dr Eaton is funded by grants R01 HL126637, R01 HL141288, and RF1 NS127266. Dr Passman has served on advisory boards for Medtronic, Abbott, and Janssen; received research support from Abbott, American Heart Association, and the National Institutes of Health (NIH); and royalties from UpToDate. Dr Solomon received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/National Heart, Lung, and Blood Institute, NeuroTronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProthera, Moderna, American Regent, and Sarepta. Dr Shah is funded by grants R01HL160025, R01HL148218, R01HL150342, R01HL143224, R01HL135008, and K24HL152008; received research grants from Novartis Pharma, Philips Ultrasound; and has consulted for Philips Ultrasound and Janssen Pharma. Dr De Caterina received research grants from Boehringer Ingelheim, Bayer, BMS/Pfizer, and Daiichi Sankyo; has consulted for Sanofi-Aventis, Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi Sankyo, Novartis, Merck, Portola, Roche, AstraZeneca, Menarini, Guidotti, Milestone, Amarin, and Noventure; received honoraria or lecture fees from Sanofi-Aventis, Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi Sankyo, Novartis, Merck, Portola, Roche, AstraZeneca, Menarini, Guidotti, Milestone, Amarin, and Noventure; received support for attending meetings and travels from Sanofi-Aventis, Bayer, BMS/Pfizer, Daiichi Sankyo, Menarini, and Amarin; and received fees for participating in the Advisory Boards from Sanofi-Aventis, Boehringer Ingelheim, Bayer, Janssen, Daiichi Sankyo, AstraZeneca, Menarini, Milestone, and Amarin. Dr Chen is funded by grants R01 HL126637, R01 HL 141288-04, RF1 NS127266, RF1 NS135615, K24 HL155813, R01 AG075883, and R01 HL158022. The other authors report no conflicts.

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