Left Atrial Function and Arrhythmias in Relation to Small Vessel Disease on Brain MRI: The Multi-Ethnic Study of Atherosclerosis

Thomas R. Austin, Paul N. Jensen, Ilya M. Nasrallah, Mohamad Habes, Tanweer Rashid, Jeffrey B. Ware, Lin Yee Chen, Philip Greenland, Timothy M. Hughes, Wendy S. Post, Steven J. Shea, Karol E. Watson, Colleen M. Sitlani, James S. Floyd, Richard A. Kronmal, W. T. Longstreth, Alain G. Bertoni, Sanjiv J. Shah, R. Nick Bryan, Susan R. Heckbert

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


BACKGROUND: Atrial fibrillation (AF) is associated with increased stroke risk and accelerated cognitive decline, but the association of early manifestations of left atrial (LA) impairment with subclinical changes in brain structure is unclear. We investigated whether abnormal LA structure and function, greater supraventricular ectopy, and intermittent AF are associated with small vessel disease on magnetic resonance imaging of the brain. METHODS AND RESULTS: In the Multi-Ethnic Study of Atherosclerosis, 967 participants completed 14-day ambulatory electrocardiographic monitoring, speckle tracking echocardiography and, a median 17 months later, magnetic resonance imaging of the brain. We assessed associations of LA volume index and reservoir strain, supraventricular ectopy, and prevalent AF with brain magnetic resonance imaging measures of small vessel disease and atrophy. The mean age of participants was 72 years; 53% were women. In multivariable models, LA enlargement was associated with lower white matter fractional anisotropy and greater prevalence of microbleeds; reduced LA strain, indicating worse LA function, was associated with more microbleeds. More premature atrial contractions were associated with lower total gray matter volume. Compared with no AF, intermittent AF (prevalent AF with <100% AF during electrocardiographic monitoring) was associated with lower white matter fractional anisotropy (−0.25 SDs [95% CI, −0.44 to −0.07]) and greater prevalence of microbleeds (prevalence ratio: 1.42 [95% CI, 1.12–1.79]). CONCLUSIONS: In individuals without a history of stroke or transient ischemic attack, alterations of LA structure and function, including enlargement, reduced strain, frequent premature atrial contractions, and intermittent AF, were associated with increased markers of small vessel disease. Detailed assessment of LA structure and function and extended ECG monitoring may enable early identification of individuals at greater risk of small vessel disease.

Original languageEnglish (US)
Article numbere026460
JournalJournal of the American Heart Association
Issue number20
StatePublished - Aug 16 2022

Bibliographical note

Funding Information:
National Heart, Lung, and Blood Institute Contracts: 75N92020D00001, HHSN268201500003I, N01HC95159, 75N92020D00005, N01HC95160, 75N92020D00002, N01HC95161, 75N92020D00003, N01HC95162, 75N92020D00006, N01HC95163, 75N92020D00004, N01HC95164, 75N92020D00007, N01HC95165, N01HC95166, N01HC95167, N01HC95168 and N01HC95169. National Heart, Lung, and Blood Institute Grant: R01HL127659. National Center for Advancing Translational Sciences Grants: UL1TR000040, UL1TR001079, and UL1TR001420. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
Dr Nasrallah was an educational speaker for Biogen. Dr Floyd has consulted for Shionogi Inc. Dr Shea has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfzer; and has served consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapeutics, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Cardiora, CVRx, Cytokinetics, Edwards, Eisai, Ionis, Ironwood, Merck, MyoKardia, Novartis, Prothena, Pfzer, Regeneron, Sanof, Shifamed, Tenax, and United Therapeutics. Dr Bryan reports nonfinancial support from Galileo CDS outside the submitted work; and has a patent licensed to Galileo CDS. The remaining authors have no disclosures to report.

Publisher Copyright:
© 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.


  • atrial fibrillation
  • brain magnetic resonance imaging
  • left atrium
  • white matter injury


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