Cited by 2,100Atrial Fibrillation Management and OutcomesAcute Ischemic Stroke ManagementCardiac pacing and defibrillation studies

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Subclinical Atrial Fibrillation and the Risk of Stroke

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Healey, Jeff S., Connolly, Stuart J., Gold, Michael R., Israel, Carsten W., Van Gelder, Isabelle C., Capucci, Alessandro, Lau, C.P., Fain, Eric, Yang, Sean, Bailleul, Christophe, Morillo, Carlos A., Carlson, Mark, Themeles, Ellison, Kaufman, Elizabeth S., Hohnloser, Stefan H.·2012·New England Journal of Medicine

DOI 10.1056/nejmoa1105575

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Abstract

BACKGROUND: One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. METHODS: We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. RESULTS: By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. CONCLUSIONS: Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.).

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Method
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Background
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Comparison between left bundle branch area pacing and right ventricular pacing: ventricular electromechanical synchrony and risk of atrial high-rate episodes
Yang, W., Di, B., Peng, H., & Sun, Z.-J. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1267076 · Cited by 13
Performance of Atrial Fibrillation Burden Trends for Stroke Risk Stratification
Piccini, J. P., Stanelle, E. J., Johnson, C. C., Hylek, E. M., Kanwar, R., Lakkireddy, D., Mittal, S., Peacock, J. M., Russo, A. M., Soderlund, D. M., et al. (2024) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.123.012394 · Cited by 14
“Among AF burden trends, the trends with the highest mean variable importance after a prior history of stroke or TIA were the SMA of AF burden offset by the CMA over 2, 3, 5, 8, 13, or 21 days.”
Case 34-2013
Ning, M., & González, R. G. (2013) · New England Journal of Medicine · doi:10.1056/nejmcpc1302431 · Cited by 13
Stroke prevention in valvular heart disease: from the procedure to long-term management
Giustino, G., & Dangas, G. (2015) · EuroIntervention · doi:10.4244/eijv11swa7 · Cited by 13
Utility of Duranta, a wireless patch-type electrocardiographic monitoring system developed in Japan, in detecting covert atrial fibrillation in patients with cryptogenic stroke
Akiyama, H., Nukui, S., Araga, T., Hoshino, M., Tanaka, K., Kashima, S., Sasaki, R., Uchino, K., & Hasegawa, Y. (2017) · Medicine · doi:10.1097/md.0000000000005995 · Cited by 13
Impact of atrial fibrillation detected by extended monitoring—A population‐based cohort study
Busch, M., Groß, S., Alte, D., Kors, J. A., Völzke, H., Ittermann, T., Werner, A., Krüger, A., Busch, R., Dörr, M., et al. (2017) · Annals of Noninvasive Electrocardiology · doi:10.1111/anec.12453 · Cited by 13
Atrial fibrillation screening during automated blood pressure measurement—Comment on “Diagnostic accuracy of new algorithm to detect atrial fibrillation in a home blood pressure monitor”
Chen, Y., Lei, L., & Wang, J. (2017) · Journal of Clinical Hypertension · doi:10.1111/jch.13081 · Cited by 13
Telemonitoring with an implantable loop recorder in outpatient heart failure care
Kort, R. S. S., Tuininga, Y. S., Bosker, H. A., Janssen, M., & Tukkie, R. (2018) · Netherlands Heart Journal · doi:10.1007/s12471-018-1198-x · Cited by 13
Directly Acting Oral Anticoagulants for the Prevention of Stroke in Atrial Fibrillation in England and Wales: Cost-Effectiveness Model and Value of Information Analysis
Thom, H. H. Z., Hollingworth, W., Sofat, R., Wang, Z., Fang, W., Bodalia, P. N., Bryden, P. A., Davies, P. A., Caldwell, D. M., Dias, S., et al. (2019) · MDM Policy & Practice · doi:10.1177/2381468319866828 · Cited by 13
“Finally, we do not distinguish between types of AF despite increasing evidence that stroke risk increases as AF progresses from paroxysmal to persistent to permanent.(44,45) In addition to using RCTs to estimate relative effects, we also used their warfarin arms to estimate baseline event risks.”
Prevalence of undiagnosed atrial fibrillation in elderly individuals and potential cost-effectiveness of non-invasive ambulatory electrocardiographic screening: The ASSERT-III study
McIntyre, W. F., Yong, J. H. E., Sandhu, R. K., Gladstone, D. J., Simek, K. D., Liu, Y. Y., Quinn, F. R., Tytus, R. H., Zizzo, D., Henein, S., et al. (2019) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2019.11.040 · Cited by 13
Duration of atrial high-rate episodes and CHA2DS2-VASc score to predict cardiovascular and cerebrovascular events in patients with dual chamber permanent pacemakers
Chen, J., & Lu, W. (2020) · Journal of Cardiology · doi:10.1016/j.jjcc.2020.08.005 · Cited by 13
Novel Predictor for New-Onset Atrial High-Rate Episode in Patients With a Dual-Chamber Pacemaker
Nishinarita, R., Niwano, S., Oikawa, J., Saito, D., Sato, T., Matsuura, G., Arakawa, Y., Kobayashi, S., Shirakawa, Y., Horiguchi, A., et al. (2021) · Circulation Reports · doi:10.1253/circrep.cr-21-0096 · Cited by 13
Prognostic Impact of the Symptom of New-Onset Atrial Fibrillation in Acute Myocardial Infarction: Insights From the NOAFCAMI-SH Registry
Luo, J., Liu, B., Li, H., Xu, S., Gong, M., Li, Z., Qin, X., Shi, B., Hao, C., Zhang, J., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.677695 · Cited by 13
“Interestingly, we found that only the symptomatic NOAF during AMI was significantly associated with an increased risk of ischemic stroke, which was different from previous reports that patients with asymptomatic AF were at high risk of ischemic stroke due to suboptimal anticoagulation (8, 24).”
Result
Combined Effect of Homocysteine and Uric Acid to Identify Patients With High Risk for Subclinical Atrial Fibrillation
Wang, S., Wei, Y., Hidru, T. H., Li, D., Wang, N., Yang, Y., Wang, Y., Yang, X., & Xia, Y. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.121.021997 · Cited by 13
Multimodality Imaging Assessment of the Biatrial Remodeling of the Burden of Atrial High-Rate Episodes in Patients with Cardiac Implanted Electronic Devices
Huang, S., TSAO, H., Liao, C., Chen, Z., Chao, T., & Chen, S. (2022) · International Journal of Cardiology · doi:10.1016/j.ijcard.2022.10.007 · Cited by 13
“Although a recent study reported that device-detected SCAF > 6 min was associated with a 2.5-fold increased risk of stroke [3], the actual stroke incidence was lower in patients with AHRE than in those with clinical AF until SCAF lasted > 24 h [4,5].”
Influential
Serial 7-Day Electrocardiogram Patch Screening for AF in High-Risk Older Women by the CHARGE-AF Score
Lin, J. Y., Larson, J. C., Schoenberg, J., Sepulveda, A., Tinker, L., Wheeler, M. T., Albert, C. M., Manson, J. E., Wells, G., Martin, L. W., et al. (2022) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2022.08.024 · Cited by 13
Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole
Hindricks, G., Theuns, D. A. M. J., Bar-Lev, D. S., Anguera, I., Paredes, F. A., Arnold, M. B., Geller, J. C., Merkely, B. P., Dyrda, K., Perings, C. A., et al. (2023) · EP Europace · doi:10.1093/europace/euad061 · Cited by 13
“The new-onset AHRE (≥6 min) occurred in 119 patients (8.2%); in all cases, intracardiac electrogram showed AF.”
BackgroundInfluential
Atrial Fibrillation
Deshpande, S., Catanzaro, J. N., & Wann, S. (2014) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2013.10.006 · Cited by 13
Can oral anticoagulants be stopped safely after a successful atrial fibrillation ablation?
Chao, T., Lin, Y., Chang, S., Lo, L., Hu, Y., Chung, F., Liao, J., & Chen, S. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2072-1439.2015.01.18 · Cited by 13
Anticoagulation and population risk of stroke and death in incident atrial fibrillation: a population-based cohort study
Yu, A., Malo, S., Wilton, S. B., Parkash, R., Svenson, L. W., & Hill, M. D. (2016) · CMAJ Open · doi:10.9778/cmajo.20150096 · Cited by 13
Relevance of Monitoring Atrial Fibrillation in Clinical Practice
Lewalter, T., & Boriani, G. (2012) · Arrhythmia & Electrophysiology Review · doi:10.15420/aer.2012.1.54 · Cited by 13
The Role of Continuous Monitoring in Atrial Fibrillation Management
Camm, A. J. (2011) · Arrhythmia & Electrophysiology Review · doi:10.15420/aer.2011.3.1.48 · Cited by 15
Sensing and Detection With Cardiac Implantable Electronic Devices
Swerdlow, C. D., Brown, M. L., & Bordachar, P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-37804-8.00004-3 · Cited by 13
Diagnostic value of prehospital ECG in acute stroke patients
Bobinger, T., Kallmünzer, B., Kopp, M., Kurka, N., Arnold, M. B., Heider, S., Schwab, S., & Köhrmann, M. (2017) · Neurology · doi:10.1212/wnl.0000000000003940 · Cited by 13
Wearable and implantable diagnostic monitors in early assessment of atrial tachyarrhythmia burden
Healey, J. S., & Wong, J. A. (2018) · EP Europace · doi:10.1093/europace/euy246 · Cited by 14
Association between excessive supraventricular ectopy and subclinical cerebrovascular disease: a population‐based study
Hisamatsu, T., Miura, K., Fujiyoshi, A., Kunimura, A., Ito, T., Miyazawa, I., Torii, S., Shiino, A., Nozaki, K., Kanda, H., et al. (2019) · European Journal of Neurology · doi:10.1111/ene.13970 · Cited by 13
“Similarly, an independent relation between ESVEA and ischaemic stroke was shown in other studies using administrative claims data [21] or using implanted pacemaker or defibrillator recordings [22] for assessment of SVEB.”
Result
Infarto cerebral embólico de origen no determinado: más allá de la fibrilación auricular
Araúz, A., Arteaga, C., Zapata-Gómez, C., Ramos-Ventura, C., Méndez, B., Otiniano-Sifuentes, R. D., Haseeb, S., González-Oscoy, R., & Baranchuk, A. M. (2019) · Neurología · doi:10.1016/j.nrl.2019.03.008 · Cited by 15
Long-term (>10-year) clinical follow-up after young embolic stroke/TIA of undetermined source
Nassif, M., Annink, M. E., Yang, H., Rettig, T. C. D., Roos, Y. B. W. E. M., van den Brink, R., Tijssen, J. G. P., Mulder, B. J. M., de Winter, R. J., & Bouma, B. J. (2019) · International Journal of Stroke · doi:10.1177/1747493019884520 · Cited by 13
Differences in Thromboembolic Complications Between Paroxysmal and Persistent Atrial Fibrillation Patients Following Electrical Cardioversion (From the ENSURE-AF Study)
Goette, A., Lip, G. Y. H., Jin, J., Heidbüchel, H., Cohen, A.-A., Ezekowitz, M. D., & Merino, J. L. (2020) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2020.06.046 · Cited by 13
Diagnostic yield of chest and thumb ECG after cryptogenic stroke, Transient ECG Assessment in Stroke Evaluation (TEASE): an observational trial
Magnusson, P., Lyren, A., & Mattsson, G. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-037573 · Cited by 14
Electrodes for Long-Term Esophageal Electrocardiography
Niederhäuser, T., Haeberlin, A., Marisa, T., Jungo, M., Goette, J., Jacomet, M., Abächerli, R., & Vogel, R. (2013) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2013.2261067 · Cited by 13
Distribution of thromboembolism in valvular versus non-valvular atrial fibrillation
Blustin, J. M., McBane, R. D., Ketha, S. S., & Wysokiński, W. E. (2014) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.2014.960851 · Cited by 13
Atrial fibrillation in patients with cardiac implantable electronic devices: new perspectives with important clinical implications
Boriani, G., & Vitolo, M. (2019) · Kardiologia Polska · doi:10.33963/kp.15110 · Cited by 13
What Lies beneath the Surface — Treatment of Subclinical Atrial Fibrillation
Svennberg, E. (2023) · New England Journal of Medicine · doi:10.1056/nejme2311558 · Cited by 13
Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes
Adabag, S., Chen, J., & Karim, R. (2023) · New England Journal of Medicine · doi:10.1056/nejmc2312837 · Cited by 13
Subclinical Atrial Fibrillation and Anticoagulation: Weighing the Absolute Risks and Benefits
Patel, S. M., & Ruff, C. T. (2024) · Circulation · doi:10.1161/circulationaha.123.067919 · Cited by 14
Detection of Atrial Fibrillation in Holter ECG Recordings by ECHOView Images: A Deep Transfer Learning Study
Krasteva, V., Stoyanov, T., Naydenov, S., Schmid, R., & Jekova, I. I. (2025) · Diagnostics · doi:10.3390/diagnostics15070865 · Cited by 12
“In this context, the following dissimilarities between IRIDIA-AF [64], MITBIH-AF [94,95], MITBIH-Arrhythmia [95,96], and CinC Challenge 2017 [97] datasets could be outlined:”
Influential
Ablation of atrial fibrillation
Wright, M. J., & Narayan, S. M. (2014) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2014.11.009 · Cited by 12
The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation
Kawabata, M., Goya, M., Takagi, T., Yamashita, S., Iwai, S., Suzuki, M., Takamiya, T., Nakamura, T., Hayashi, T., Yagishita, A., et al. (2016) · Journal of Cardiology · doi:10.1016/j.jjcc.2016.01.007 · Cited by 12
Implantable Loop Recorders for Cryptogenic Stroke (Plus Real-World Atrial Fibrillation Detection Rate with Implantable Loop Recorders)
Musat, D. L., Milstein, N. S., & Mittal, S. (2018) · Cardiac Electrophysiology Clinics · doi:10.1016/j.ccep.2017.11.011 · Cited by 12
Incidence of subclinical atrial fibrillation in a South Asian population
O’Neill, J., Jegodzinski, L., & Tayebjee, M. H. (2018) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.13516 · Cited by 12
The Guideline-Policy Gap in Direct-Acting Oral Anticoagulants Usage in Atrial Fibrillation: Evidence, Practice, and Public Policy Considerations
Wan, D., Healey, J. S., & Simpson, C. S. (2018) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2018.07.476 · Cited by 12
Neuro-arrhythmology: a challenging field of action and research: a review from the Task Force of Neuro-arrhythmology of Italian Association of Arrhythmias and Cardiac Pacing
Strano, S., Toni, D., Ammirati, F., Sanna, T., Tomaino, M., Brignole, M., Mazza, A., Nguyen, B. L., Bonaventura, C. D., Ricci, R. P., et al. (2019) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000000866 · Cited by 12
A New Vision at the Interface of Atrial Fibrillation and Stroke
Ronsoni, R. D. M., Saffi, M. A. L., Gonçalves, M. V. M., Nakayama, I. H., & Leiria, T. L. L. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.689313 · Cited by 12
“Therefore, these data question the clear biological gradient between stroke and AF; this suggests the occurrence of other associated mechanisms in the elderly population (14, 15).”
Background

Authors: Healey, J. S., Connolly, S. J., Gold, M. R., Israel, C. W., Van Gelder, I. C., Capucci, A., Lau, C. P., Fain, E., Yang, S., Bailleul, C., Morillo, C. A., Carlson, M., Themeles, E., Kaufman, E. S., & Hohnloser, S. H.
Affiliations: Population Health Research Institute (CA)
Medical University of South Carolina (US)
Goethe University Frankfurt (DE)
Marche Polytechnic University (IT)
Queen Mary Hospital (CN)
MetroHealth (US)
ORCID: Healey, Jeff S.
Connolly, Stuart J.
Gold, Michael R.
Israel, Carsten W.
Capucci, Alessandro
Fain, Eric
Bailleul, Christophe
Morillo, Carlos A.
Kaufman, Elizabeth S.
Hohnloser, Stefan H.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2012-01-12
Volume: 366
Issue: 2
Pages: 120-129
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1105575
OpenAlex: W2154658516
Cited by: 2,100
References: 37
Citations by year: 2026: 87 · 2025: 104 · 2024: 137 · 2023: 116 · 2022: 134 · 2021: 153 · 2020: 148 · 2019: 162 · 2018: 154 · 2017: 154 · 2016: 162 · 2015: 146 · 2014: 181 · 2013: 133 · 2012: 124
FWCI: 120.21
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
Keywords: subclinical atrial fibrillation, atrial tachyarrhythmia, ischemic stroke, systemic embolism, atrial overdrive pacing, atrial fibrillation risk, hypertension, elderly patients, population attributable risk, stroke prevention, cardiac implantable electronic devices, atrial fibrillation detection, atrial fibrillation prevention
MeSH terms: Aged, Aged, 80 and over, Atrial Fibrillation, Cardiac Pacing, Artificial, Embolism, Female, Humans, Hypertension, Male, Pacemaker, Artificial, Prospective Studies, Risk, Defibrillators, Implantable, Stroke

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Subclinical Atrial Fibrillation and the Risk of Stroke

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