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The Role of Cardiovascular Implantable Electronic Devices in the Detection and Treatment of Subclinical Atrial FibrillationA Review

Educational Objective
To understand the detection and treatment of subclinical atrial fibrillation (AF).
1 Credit CME
Abstract

Importance  Subclinical atrial fibrillation (AF) is associated with an increased risk for stroke.

Observations  Subclinical AF is asymptomatic, short in duration, and usually detected with long-term, continuous monitoring. Most prior studies have explored its consequences using cardiovascular implantable electronic devices (CIEDs). Although current prevalence estimates are derived from study populations with prior CIEDs, 3 trials will assess the time to a first AF diagnosis among patients receiving a CIED for purposes of AF detection. Stroke risk estimates are currently limited to patients with a prior CIED and vary widely, ranging from a hazard ratio of 0.87 (95% CI, 0.58-1.31) to 9.40 (95% CI, 1.80-47.00). Stroke risk pathogenesis may include factors that are proximately causal, upstream risk activators, and risk markers. The treatment of subclinical AF may be a useful stroke prevention strategy; however, no direct evidence of benefit from oral anticoagulation exists in this population. Two ongoing trials will assess the risk and benefit of non–vitamin K oral anticoagulants among patients at high risk for stroke with a previously placed implantable CIED, but without a prior diagnosis of clinical AF. If clinical benefit is proven, then the cost-effectiveness of screening for and the treatment of subclinical AF will require additional study.

Conclusions and Relevance  At present, no evidence suggests that implanting a CIED to detect AF or initiating oral anticoagulation therapy among those in whom AF is detected is beneficial. Ongoing and future studies will identify people at high risk for developing subclinical AF and will evaluate the efficacy, safety, and economic value of oral anticoagulation therapy in this population.

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Article Information

Corresponding Author: Renato D. Lopes, MD, PhD, MHS, Duke Clinical Research Institute, 2400 Pratt St, Room 0311 Terrace Level, Durham, NC 27705 (renato.lopes@duke.edu).

Accepted for Publication: November 8, 2016.

Published Online: January 11, 2017. doi:10.1001/jamacardio.2016.5167

Author Contributions: Drs Hess and Lopes had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Hess, Healey, Granger, Connolly, Ziegler, Alexander, Kowey, Flaker, Halperin, Lopes.

Acquisition, analysis, or interpretation of data: Connolly, Ruff, Halperin, Hart, Lopes.

Drafting of the manuscript: Hess, Granger, Lopes.

Critical revision of the manuscript for important intellectual content: All authors.

Obtained funding: Healey, Granger, Lopes.

Administrative, technical, or material support: Hess, Healey, Ziegler, Ruff, Flaker.

Study supervision: Healey, Connolly, Kowey, Ruff, Lopes.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Healey reports receiving research grants from Boehringer Ingelheim and from Canadian Stroke Prevention Intervention Network and Hamilton Health Sciences Foundation, which provide funding for ARTESiA, and serving as the chair of the Canadian Stroke Prevention Intervention Network. Dr Granger reports receiving consulting fees and/or honoraria from Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, AstraZeneca, Pfizer, The Medicines Company, Hoffman LaRoche, Takeda, Pfizer, Lilly, Sanofi Aventis, Boehringer Ingelheim, and Ross Medical Corporation; receiving research grants from Medtronic Foundation, Bristol-Myers Squibb, Sanofi Aventis, Boehringer Ingelheim, The Medicines Company, Takeda, GlaxoSmithKline, Pfizer, and Merck; and cochairing the think tank meeting to discuss the topic of subclinical atrial fibrillation (AF) and plan the ARTESiA trial. Dr Connolly reports receiving consulting fees and/or honoraria from Sanofi-Aventis, Bristol-Myers Squibb, Boehringer Ingelheim, Boston Scientific, St Jude Medical, Bayer, and Portola Pharmaceutical and receiving research grants from Sanofi-Aventis, Bristol-Myers Squibb, Boehringer Ingelheim, Boston Scientific, St Jude Medical, Portola Pharmaceutical, and Johnson & Johnson. Mr Ziegler reports being an employee and shareholder of Medtronic, Inc. Dr Alexander reports receiving consulting fees and/or honoraria from Pfizer, Daiichi Sankyo, Bristol-Myers Squibb, Boehringer Ingelheim, CSL Behring, Somahlution, Novartis, Regado Biosciences, Orexigen, Xoma Pharmaceuticals, Moerae Matrix, Bayer, and Ortho-McNeil-Janssen Pharmaceuticals and research grants from Regado Biosciences, the National Institutes of Health, Bristol-Myers Squibb, CSL, Pfizer, and Phyxius Pharmaceuticals. Dr Kowey reports receiving consulting fees and/or honoraria from Dendreon, AstraZeneca, Pfizer, Johnson & Johnson, Boehringer Ingelheim, Otsuka, Daiichi-Sankyo, Sanofi-Aventis, GlaxoSmithKline, Merck, Novartis, Portola, Bristol-Myers Squibb, Forest, Medtronic, Astellas, and AstraZeneca; serving as an officer or a director of Cardionet; and serving on the data safety monitoring board for Eli Lilly. Dr Ruff reports receiving consulting fees and/or honoraria from Beckman Coulter, Daiichi Sankyo, Bristol-Myers Squibb, and Boehringer Ingelheim and receiving research grants from AstraZeneca and Daiichi Sankyo. Dr Flaker reports receiving consulting fees and/or honoraria from Bristol-Myers Squibb, Boehringer Ingelheim, and Sanofi-Aventis and research grants from Boehringer Ingelheim and Sanofi-Aventis. Dr Halperin reports receiving consulting fees and/or honoraria from Boehringer Ingelheim, Sanofi-Aventis, Biotronik, Inc, AstraZeneca, Bayer HealthCare AG, Medtronic, Inc, Bristol-Myers Squibb, Daiichi Sankyo Pharma, Johnson & Johnson, Boston Scientific, OInc, Pfizer, Inc, and Ortho-McNeil-Janssen Pharmaceuticals, Inc. Dr Lopes reports receiving consulting fees and/or honoraria from Pfizer, Bristol-Myers Squibb, Bayer, and Boehringer Ingelheim; receiving research grants from Bristol-Myers Squibb and GlaxoSmithKline; and cochairing the think tank meeting to discuss the topic of subclinical AF and plan the ARTESiA trial. No other disclosures were reported.

Funding/Support: This study was supported by personnel award MC7450 from the Heart and Stroke Foundation, Ontario Provincial office (Dr Healey) and by an unrestricted grant that was used to cover the costs related to the logistics of the think tank meeting to discuss the topic of subclinical AF, including travel and food for the participants, from Medtronic, Inc.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Elizabeth Cook, BA, and Erin Hanley, MS, Duke Clinical Research Institute, made editorial contributions to this manuscript. Neither received compensation for their contributions apart from their employment.

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