Original Research
3 December 2013

Atrial Ectopy as a Predictor of Incident Atrial Fibrillation: A Cohort Study

Publication: Annals of Internal Medicine
Volume 159, Number 11

Abstract

Background:

Atrial fibrillation (AF) prediction models have unclear clinical utility given the absence of AF prevention therapies and the immutability of many risk factors. Premature atrial contractions (PACs) play a critical role in AF pathogenesis and may be modifiable.

Objective:

To investigate whether PAC count improves model performance for AF risk.

Design:

Prospective cohort study.

Setting:

4 U.S. communities.

Patients:

A random subset of 1260 adults without prevalent AF enrolled in the Cardiovascular Health Study between 1989 and 1990.

Measurements:

The PAC count was quantified by 24-hour electrocardiography. Participants were followed for the diagnosis of incident AF or death. The Framingham AF risk algorithm was used as the comparator prediction model.

Results:

In adjusted analyses, doubling the hourly PAC count was associated with a significant increase in AF risk (hazard ratio, 1.17 [95% CI, 1.13 to 1.22]; P < 0.001) and overall mortality (hazard ratio, 1.06 [CI, 1.03 to 1.09]; P < 0.001). Compared with the Framingham model, PAC count alone resulted in similar AF risk discrimination at 5 and 10 years of follow-up and superior risk discrimination at 15 years. The addition of PAC count to the Framingham model resulted in significant 10-year AF risk discrimination improvement (c-statistic, 0.65 vs. 0.72; P < 0.001), net reclassification improvement (23.2% [CI, 12.8% to 33.6%]; P < 0.001), and integrated discrimination improvement (5.6% [CI, 4.2% to 7.0%]; P < 0.001). The specificity for predicting AF at 15 years exceeded 90% for PAC counts more than 32 beats/h.

Limitation:

This study does not establish a causal link between PACs and AF.

Conclusion:

The addition of PAC count to a validated AF risk algorithm provides superior AF risk discrimination and significantly improves risk reclassification. Further study is needed to determine whether PAC modification can prospectively reduce AF risk.

Primary Funding Source:

American Heart Association, Joseph Drown Foundation, and National Institutes of Health.

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References

1.
Naccarelli GVVarker HLin J, and Schulman KL. Increasing prevalence of atrial fibrillation and flutter in the United States. Am J Cardiol. 2009;104:1534-9. [PMID: 19932788]
2.
Lin HJWolf PAKelly-Hayes MBeiser ASKase CSBenjamin EJet al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke. 1996;27:1760-4. [PMID: 8841325]
3.
Benjamin EJWolf PAD'Agostino RBSilbershatz HKannel WB, and Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98:946-52. [PMID: 9737513]
4.
Wolowacz SESamuel MBrennan VKJasso-Mosqueda JG, and Van Gelder IC. The cost of illness of atrial fibrillation: a systematic review of the recent literature. Europace. 2011;13:1375-85. [PMID: 21757483]
5.
Schnabel RBAspelund TLi GSullivan LMSuchy-Dicey AHarris TBet al. Validation of an atrial fibrillation risk algorithm in whites and African Americans. Arch Intern Med. 2010;170:1909-17. [PMID: 21098350]
6.
Schnabel RBSullivan LMLevy DPencina MJMassaro JMD'Agostino RB Sret al. Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study. Lancet. 2009;373:739-45. [PMID: 19249635]
7.
Marcus GM. Predicting incident atrial fibrillation: an important step toward primary prevention [Editorial]. Arch Intern Med. 2010;170:1874-5. [PMID: 21098344]
8.
Haíssaguerre MJaís PShah DCTakahashi AHocini MQuiniou Get al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339:659-66. [PMID: 9725923]
9.
Kolb CNürnberger SNdrepepa GZrenner BSchömig A, and Schmitt C. Modes of initiation of paroxysmal atrial fibrillation from analysis of spontaneously occurring episodes using a 12-lead Holter monitoring system. Am J Cardiol. 2001;88:853-7. [PMID: 11676946]
10.
Wallmann DTüller DWustmann KMeier PIsenegger JArnold Met al. Frequent atrial premature beats predict paroxysmal atrial fibrillation in stroke patients: an opportunity for a new diagnostic strategy. Stroke. 2007;38:2292-4. [PMID: 17585079]
11.
Chong BHPong VLam KFLiu SZuo MLLau YFet al. Frequent premature atrial complexes predict new occurrence of atrial fibrillation and adverse cardiovascular events. Europace. 2012;14:942-7. [PMID: 22183750]
12.
Binici ZIntzilakis TNielsen OWKøber L, and Sajadieh A. Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke. Circulation. 2010;121:1904-11. [PMID: 20404258]
13.
Fried LPBorhani NOEnright PFurberg CDGardin JMKronmal RAet al. The Cardiovascular Health Study: design and rationale. Ann Epidemiol. 1991;1:263-76. [PMID: 1669507]
14.
Tell GSFried LPHermanson BManolio TANewman AB, and Borhani NO. Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol. 1993;3:358-66. [PMID: 8275211]
15.
Ives DGFitzpatrick ALBild DEPsaty BMKuller LHCrowley PMet al. Surveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study. Ann Epidemiol. 1995;5:278-85. [PMID: 8520709]
16.
Psaty BMKuller LHBild DBurke GLKittner SJMittelmark Met al. Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study. Ann Epidemiol. 1995;5:270-7. [PMID: 8520708]
17.
Fine JP and Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Amer Stat Assoc. 1999;94:496-509.
18.
Hlatky MAGreenland PArnett DKBallantyne CMCriqui MHElkind MSet alAmerican Heart Association Expert Panel on Subclinical Atherosclerotic Diseases and Emerging Risk Factors and the Stroke Council. Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009;119:2408-16. [PMID: 19364974]
19.
Wolbers MKoller MTWitteman JC, and Steyerberg EW. Prognostic models with competing risks: methods and application to coronary risk prediction. Epidemiology. 2009;20:555-61. [PMID: 19367167]
20.
Pencina MJD'Agostino RB Sr.D'Agostino RB Jr., and Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157-72. [PMID: 17569110]
21.
Cook NR and Paynter NP. Performance of reclassification statistics in comparing risk prediction models. Biom J. 2011;53:237-58. [PMID: 21294152]
22.
Calkins HKuck KHCappato RBrugada JCamm AJChen SAet alHeart Rhythm Society Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm. 2012;9:632-696.e21. [PMID: 22386883]
23.
Wilber DJPappone CNeuzil PDe Paola AMarchlinski FNatale Aet alThermoCool AF Trial Investigators. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010;303:333-40. [PMID: 20103757]

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 159Number 113 December 2013
Pages: 721 - 728

History

Published online: 3 December 2013
Published in issue: 3 December 2013

Keywords

Authors

Affiliations

Thomas A. Dewland, MD
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Eric Vittinghoff, PhD, MPH
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Mala C. Mandyam, MD
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Susan R. Heckbert, MD, PhD
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
David S. Siscovick, MD, MPH
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Phyllis K. Stein, PhD
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Bruce M. Psaty, MD, PhD
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Nona Sotoodehnia, MD
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
John S. Gottdiener, MD
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Gregory M. Marcus, MD, MAS
From University of California, San Francisco, San Francisco, California; University of Washington and Group Health Research Institute, Seattle, Washington; Washington University School of Medicine, St. Louis, Missouri; and University of Maryland Medical Center, Baltimore, Maryland.
Disclaimer: Drs. Dewland and Marcus had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. A full list of principal Cardiovascular Health Study investigators and institutions can be found at www.chs-nhlbi.org. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
Grant Support: By grants 12POST11810036 (Dr. Dewland) and 12GRNT11780061 (Dr. Marcus) from the American Heart Association, the Joseph Drown Foundation (Dr. Marcus), and grant R01HL116747 (Dr. Sotoodehnia) from the National Heart, Lung, and Blood Institute; contracts HHSN268201200036C, N01HC85239, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke; and grant AG023629 from the National Institute on Aging.
Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Marcus (e-mail, [email protected]). Data set: Available through established CHS procedures for obtaining and analyzing data (see https://chs-nhlbi.org/).
Corresponding Author: Gregory M. Marcus, MD, MAS, 505 Parnassus Avenue, M-1180B, San Francisco, CA 94143; e-mail, [email protected].
Current Author Addresses: Drs. Dewland, Mandyam, and Marcus: University of California, San Francisco, 505 Parnassus Avenue, M-1180B, San Francisco, CA 94143.
Dr. Vittinghoff: University of California, San Francisco, 185 Berry Street, Suite 5700, San Francisco, CA 94107.
Drs. Heckbert, Siscovick, Psaty, and Sotoodehnia: University of Washington Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101.
Dr. Stein: Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8086, St. Louis, MO 63110.
Dr. Gottdiener: University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD 21201.
Author Contributions: Conception and design: T.A. Dewland, M.C. Mandyam, G.M. Marcus.
Analysis and interpretation of the data: T.A. Dewland, E. Vittinghoff, M.C. Mandyam, S.R. Heckbert, D.S. Siscovick, P.K. Stein, B.M. Psaty, N. Sotoodehnia, J.S. Gottdeiner, G.M. Marcus.
Drafting of the article: T.A. Dewland, E. Vittinghoff, M.C. Mandyam, G.M. Marcus.
Critical revision of the article for important intellectual content: T.A. Dewland, E. Vittinghoff, M.C. Mandyam, S.R. Heckbert, D.S. Siscovick, P.K. Stein, B.M. Psaty, N. Sotoodehnia, J.S. Gottdeiner, G.M. Marcus.
Final approval of the article: T.A. Dewland, E. Vittinghoff, M.C. Mandyam, S.R. Heckbert, D.S. Siscovick, P.K. Stein, B.M. Psaty, N. Sotoodehnia, J.S. Gottdiener, G.M. Marcus.
Provision of study materials or patients: S.R. Heckbert, D.S. Siscovick, P.K. Stein, B.M. Psaty, N. Sotoodehnia, J.S. Gottdeiner.
Statistical expertise: T.A. Dewland, E. Vittinghoff, G.M. Marcus.
Obtaining of funding: T.A. Dewland, G.M. Marcus.
Administrative, technical, or logistic support: T.A. Dewland, S.R. Heckbert, D.S. Siscovick, P.K. Stein, B.M. Psaty, N. Sotoodehnia, J.S. Gottdeiner, G.M. Marcus.
Collection and assembly of data: T.A. Dewland, M.C. Mandyam, S.R. Heckbert, D.S. Siscovick, P.K. Stein, B.M. Psaty, N. Sotoodehnia, J.S. Gottdeiner, G.M. Marcus.

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Thomas A. Dewland, Eric Vittinghoff, Mala C. Mandyam, et al. Atrial Ectopy as a Predictor of Incident Atrial Fibrillation: A Cohort Study. Ann Intern Med.2013;159:721-728. [Epub 3 December 2013]. doi:10.7326/0003-4819-159-11-201312030-00004

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