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Association Between Atrial Fibrillation and Silent Cerebral Infarctions: A Systematic Review and Meta-analysisAtrial Fibrillation and Silent Cerebral Infarctions

Shadi Kalantarian, MD, MPH; Hakan Ay, MD; Randy L. Gollub, MD, PhD; Hang Lee, PhD; Kallirroi Retzepi, MSc; Moussa Mansour, MD; and Jeremy N. Ruskin, MD
[+] Article, Author, and Disclosure Information

From the Institute for Heart Vascular and Stroke Care and Massachusetts General Hospital, Boston, Massachusetts.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health.

Acknowledgment: The authors thank W.T. Longstreth Jr., MD, MPH, from the University of Washington, Seattle, Washington, and Tsukasa Saito, MD, PhD, from Asahikawa Medical University, Hokkaido, Japan, for providing additional data from their published studies.

Grant Support: By the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and with support from Harvard Catalyst and the Harvard Clinical and Translational Science Center (National Institutes of Health Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers).

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0538.

Requests for Single Reprints: Jeremy N. Ruskin, MD, Cardiac Arrhythmia Service, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114; e-mail, jruskin@partners.org.

Current Author Addresses: Drs. Kalantarian, Mansour, and Ruskin: Cardiac Arrhythmia Service, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114.

Drs. Ay and Gollub and Ms. Retzepi: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 Thirteenth Street, Charlestown, MA 02129.

Dr. Lee: Department of Biostatistics, Massachusetts General Hospital, 50 Staniford Street, Boston MA 02114.

Author Contributions: Conception and design: S. Kalantarian, H. Ay, J.N. Ruskin.

Analysis and interpretation of the data: S. Kalantarian, H. Ay, R.L. Gollub, K. Retzepi, J.N. Ruskin.

Drafting of the article: S. Kalantarian, H. Ay, H. Lee, J.N. Ruskin.

Critical revision of the article for important intellectual content: S. Kalantarian, H. Ay, H. Lee, M. Mansour, J.N. Ruskin.

Final approval of the article: S. Kalantarian, H. Ay, R.L. Gollub, H. Lee, M. Mansour, J.N. Ruskin.

Provision of study materials or patients: S. Kalantarian.

Statistical expertise: H. Lee.

Administrative, technical, or logistic support: R.L. Gollub, J.N. Ruskin.

Collection and assembly of data: S. Kalantarian, K. Retzepi.


Ann Intern Med. 2014;161(9):650-658. doi:10.7326/M14-0538
Text Size: A A A

Background: Atrial fibrillation (AF) is a common cause of stroke. Silent cerebral infarctions (SCIs) are known to occur in the presence and absence of AF, but the association between these disorders has not been well-defined.

Purpose: To estimate the association between AF and SCIs and the prevalence of SCIs in stroke-free patients with AF.

Data Sources: Searches of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE from inception to 8 May 2014 without language restrictions and manual screening of article references.

Study Selection: Observational studies involving adults with AF and no clinical history of stroke or prosthetic valves who reported SCIs.

Data Extraction: Study characteristics and study quality were assessed in duplicate.

Data Synthesis: Eleven studies including 5317 patients with mean ages from 50.0 to 83.6 years reported on the association between AF and SCIs. Autopsy studies were heterogeneous and low-quality; therefore, they were excluded from the meta-analysis of the risk estimates. When computed tomography (CT) and magnetic resonance imaging (MRI) studies were combined, AF was associated with SCIs in patients with no history of symptomatic stroke (odds ratio, 2.62 [95% CI, 1.81 to 3.80]; I2 = 32.12%; P for heterogeneity = 0.118). This association was independent of AF type (paroxysmal vs. persistent). The results were not altered significantly when the analysis was restricted to studies that met at least 70% of the maximum possible quality score (odds ratio, 3.06 [CI, 2.24 to 4.19]). Seventeen studies reported the prevalence of SCIs. The overall prevalence of SCI lesions on MRI and CT among patients with AF was 40% and 22%, respectively.

Limitation: Most studies were cross-sectional, and autopsy studies were heterogeneous and not sufficiently sensitive to detect small lesions.

Conclusion: Atrial fibrillation is associated with more than a 2-fold increase in the odds for SCI.

Primary Funding Source: Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital.

Figures

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Appendix Figure.

Summary of evidence search and selection.

AF = atrial fibrillation; SCI = silent cerebral infarction.

* Once relevant papers were identified through electronic search, their reference lists were manually searched to identify any additional relevant papers. Twenty-nine full-text articles were reviewed from reference lists, and 1 was found to be relevant.

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Figure 1.

Association between AF and SCIs according to the method of SCI diagnosis in 9 studies.

AF = atrial fibrillation; CT = computed tomography; MRI = magnetic resonance imaging; SCI = silent cerebral infarction.

* Studies that used an acceptable method to control for ≥5 of the following 6 variables were considered to be at minimal risk of bias: age, sex, hypertension, hyperlipidemia, diabetes mellitus, and presence of significant carotid stenosis. Studies that did not control for ≥2 variables were considered at moderate risk of bias.

† For the purpose of this meta-analysis, we used the reported odds ratio for the association between AF and SCI lesions >5 mm.

‡ Paroxysmal AF.

§ Persistent AF.

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Figure 2.

Prevalence of SCIs in patients with AF according to the method of SCI diagnosis.

AF = atrial fibrillation; CT = computed tomography; MRI = magnetic resonance imaging; SCI = silent cerebral infarction.

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Tables

References

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Comments

Submit a Comment/Letter
Silent cerebral infarction in patients with atrial fibrillation should not be kept “silent”
Posted on November 7, 2014
Gauranga Dhar
Bangladesh Institute of Family Medicine and Research
Conflict of Interest: None Declared
Very good message. It is a well established fact that atrial fibrillation (AF) leads to increased risk of stroke but silent phenomenon “silent cerebral infarction (SCI)” should also be considered. Patients with AF, both persistent and paroxysmal, should be screened for SCI by MRI as a preventive measure for the development of cognitive impairment, overt stroke and death. In addition to this, rate and rhythm control and proper use of anti-coagulants to this population is important.
Protect the diabetic brain from silent cerebral infarction by hearing the heart
Posted on November 9, 2014
Raffaele Marfella, Maria Rosaria Rizzo, Michelangela Barbieri, Giuseppe Paolisso.
Department of Geriatrics and Metabolic Diseases Second University of Naples, Italy.
Conflict of Interest: None Declared
The evidence by Shadi Kalantarian and coworkers (1) that atrial fibrillation is associated with more than a 2-fold increase in the odds for silent cerebral infarct (SCI), is an important message, especially in the diabetic population, in which the SCI prevalence reaches 40% (2). Our recent data (3) found SCI prevalence in 41% the of diabetic patients, being these data comparable to the previous observations (approximately 42%) (2). As background for such association, the asymptomatic episodes of AF seem to have a pivotal role. It seems likely that SCI exists more frequently in type 2 diabetic patients with asymptomatic episodes of AF than in subjects without, since a frequency of SCI was reported to be 61% in diabetic patients with asymptomatic episodes of AF and 29% in diabetic patients without asymptomatic episodes of AF. Moreover, the results of our study suggested that silent episodes of AF was an independent determinant of SCI, since the OR in our population was 4.46. Therefore, the data Shadi Kalantarian and coworkers strengthen our hypothesis and suggest that the heart rhythm surveillance in the SCI high risk population, such as diabetic people, should be recommended to protect the brain.

References
1. Kalantarian S, Ay H, Gollub RL, Lee H, Retzepi K, Mansour M, Ruskin JN. Association Between Atrial Fibrillation and Silent Cerebral Infarctions: A Systematic Review and Meta-analysis. Ann Intern Med. 2014;161:650-658.
2. Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MMB. Silent brain infarcts and white-matter lesions increase stroke risk in the general population: the Rotterdam Scan study. Stroke. 2003; 34: 1126–29.
3. Marfella R, Sasso FC, Siniscalchi M, Cirillo M, Paolisso P, Sardu C, Barbieri M, Rizzo MR, Mauro C, Paolisso G. Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients. J Am Coll Cardiol. 2013;62:525-30.
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