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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BackgroundInfluential
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Self-citation
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Result
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BackgroundMethodInfluential
Accurate detection of atrial fibrillation from 12-lead ECG using deep neural network
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Atrial fibrillation ablation patients have long-term stroke rates similar to patients without atrial fibrillation regardless of CHADS2 score
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Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1
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Monitoring and detecting atrial fibrillation using wearable technology
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Usefulness of CHADS2 and CHA2DS2-VASc Scores in the Prediction of New-Onset Atrial Fibrillation: A Population-Based Study
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Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial
Boriani, G., Tukkie, R., Manolis, A. S., Mont, L., Pürerfellner, H., Santini, M., Inama, G., Serra, P., de Sousa, J., Botto, G. L., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu165 · Cited by 145
ESC Guidelines on cardiac pacing and cardiac resynchronization therapy
Nielsen, J. C., Petersen, H. H., Karlsen, F. M., Chri, L. S., & Haarbo, J. (2014) · Cited by 146
Usefulness of Continuous Electrocardiographic Monitoring for Atrial Fibrillation
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Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference
Kirchhof, P., Breithardt, G., Aliot, E., Al Khatib, S., Apostolakis, S., Auricchio, A., Bailleul, C., Bax, J., Benninger, G., Blomstrom-Lundqvist, C., et al. (2013) · Europace · doi:10.1093/europace/eut232 · Cited by 141
Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis
Welton, N. J., McAleenan, A., Thom, H. H. Z., Davies, P. A., Hollingworth, W., Higgins, J. P. T., Okoli, G. N., Sterne, J. A. C., Feder, G. S., Eaton, D., et al. (2017) · Health Technology Assessment · doi:10.3310/hta21290 · Cited by 142
Pathophysiology of atrial fibrillation and chronic kidney disease
Ding, W. Y., Gupta, D., Wong, C. F., & Lip, G. Y. H. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa258 · Cited by 144
Validation and clinical use of a novel diagnostic device for screening of atrial fibrillation
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Cognitive dysfunction in atrial fibrillation
Madhavan, M., Graff‐Radford, J., Piccini, J. P., & Gersh, B. J. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0075-z · Cited by 146
Atrial fibrillation and stroke: State-of-the-art and future directions
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Omega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation
Macchia, A., Grancelli, H., Varini, S. D., Nul, D. R., Laffaye, N., Mariani, J. A., Ferrante, D., Badra, R., Figal, J. C., Ramos, S., et al. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.11.021 · Cited by 140
Atrial fibrillation burden in clinical practice, research, and technology development: a clinical consensus statement of the European Society of Cardiology Council on Stroke and the European Heart Rhythm Association
Doehner, W., Boriani, G., Potpara, T., Blomström‐Lundqvist, C., PASSMAN, R. S., Sposato, L. A., Dobrev, D., Freedman, B., Gelder, I. C. V., Glotzer, T. V., et al. (2025) · EP Europace · doi:10.1093/europace/euaf019 · Cited by 157
“3,52 Hence, combining AF burden with individual risk factors, such as the CHA 2 DS 2 -VASc score, may offer superior prognostic precision compared with each aspect in isolation ( Figure 4 ).”
Atrial fibrillation among Medicare beneficiaries hospitalized with sepsis: Incidence and risk factors
Walkey, A. J., Greiner, M. A., Heckbert, S. R., Jensen, P. N., Piccini, J. P., Sinner, M. F., Curtis, L. H., & Benjamin, E. J. (2013) · American Heart Journal · doi:10.1016/j.ahj.2013.03.020 · Cited by 136
Electrocardiographic left atrial abnormality and stroke subtype in the atherosclerosis risk in communities study
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Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL)
Shanafelt, T. D., Parikh, S. A., Noseworthy, P. A., Goede, V., Rabe, K. G., Bahlo, J., Call, T. G., Schwager, S. M., Ding, W., Eichhorst, B. F., et al. (2016) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2016.1257795 · Cited by 136
European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin
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Stepwise mass screening for atrial fibrillation using N-terminal B-type natriuretic peptide: the STROKESTOP II study
Gudmundsdottir, K. K., Fredriksson, T., Svennberg, E., Al‐Khalili, F., Friberg, L., Frykman, V., Hijazi, Z., Rosenqvist, M., & Engdahl, J. (2019) · EP Europace · doi:10.1093/europace/euz255 · Cited by 131
JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias
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Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial
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Atrial fibrillation and stroke
Choi, S. E., Sagris, D., Hill, A. M., Lip, G. Y. H., & Abdul‐Rahim, A. H. (2022) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2023.2160319 · Cited by 142
Screening for Atrial Fibrillation in Older Adults at Primary Care Visits: VITAL-AF Randomized Controlled Trial
Lubitz, S. A., Atlas, S. J., Ashburner, J. M., Lipsanopoulos, A. T. T., Borowsky, L. H., Guan, W., Khurshid, S. S., Ellinor, P. T., Chang, Y., McManus, D. D., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.057014 · Cited by 128
“Three patient samples were established for the analyses: (1) Intention-to-treat (group assignment was based on the patients’ first visit to a study practice during the study period); (2) per protocol (patients with a first visit to an intervention practice and screened at least once during the study period were assign…”
BackgroundMethod
Adverse prognosis of incidentally detected ambulatory atrial fibrillation
Martínez, C., Katholing, A., & Freedman, S. B. (2014) · Thrombosis and Haemostasis · doi:10.1160/th4-04-0383 · Cited by 130
Noninvasive Cardiac Event Monitoring to Detect Atrial Fibrillation After Ischemic Stroke
Higgins, P., Macfarlane, P. W., Dawson, J., McInnes, G. T., Langhorne, P., & Lees, K. R. (2013) · Stroke · doi:10.1161/strokeaha.113.001927 · Cited by 127
EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA)
Savelieva, I., Fumagalli, S., Kenny, R. A., Anker, S. D., Bénétos, A., Boriani, G., Bunch, T. J., Dagres, N., Dubner, S., Fauchier, L., et al. (2022) · EP Europace · doi:10.1093/europace/euac123 · Cited by 137
“183 An analysis of all the data from the literature reveals that that AHREs with a duration > 5–6 min are common in patients implanted with CIEDs, with an incidence between 10 and 68%.”
Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation
Sarvari, S. I., Haugaa, K. H., Stokke, T. M., Ansari, H. Z., Leren, I. S., Hegbom, F., Smiseth, O. A., & Edvardsen, T. (2015) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jev185 · Cited by 127
Etiologic classification of ischemic stroke: Where do we stand?
Radu, R. A., Terecoasă, E., Bajenaru, O. A., & Tiu, C. (2017) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2017.05.019 · Cited by 129
Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals
Lowres, N., Olivier, J., Chao, T., Chen, S.-A., Chen, Y., Diederichsen, A. C. P., Fitzmaurice, D. A., Gómez‐Doblas, J. J., Harbison, J. A., Healey, J. S., et al. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1002903 · Cited by 124
Thirty-Second Gold Standard Definition of Atrial Fibrillation and Its Relationship With Subsequent Arrhythmia Patterns
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Tailoring the Approach to Embolic Stroke of Undetermined Source
Kamel, H., Merkler, A. E., Iadecola, C., Gupta, A. K., & Navi, B. B. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.0591 · Cited by 126
Sleep apnoea and the heart
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Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial
Traaen, G. M., Aakerøy, L., Hunt, T.-E., Øverland, B., Bendz, C., Sande, L. Ø., Aakhus, S., Fagerland, M. W., Steinshamn, S., Anfinsen, O., et al. (2021) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202011-4133oc · Cited by 127
Detection of new atrial fibrillation in patients with cardiac implanted electronic devices and factors associated with transition to higher device-detected atrial fibrillation burden
Boriani, G., Glotzer, T. V., Ziegler, P., Melis, M. D., Stefano, L. M. D. S., Sepši, M., Landolina, M., Lunati, M., Lewalter, T., & Camm, A. J. (2017) · Heart Rhythm · doi:10.1016/j.hrthm.2017.11.007 · Cited by 120
Diagnostic assessment of a deep learning system for detecting atrial fibrillation in pulse waveforms
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The dialysis procedure as a trigger for atrial fibrillation: New insights in the development of atrial fibrillation in dialysis patients
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Paroxysmal Supraventricular Tachycardia and the Risk of Ischemic Stroke
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Management of atrial high-rate episodes detected by cardiac implanted electronic devices
Freedman, B., Boriani, G., Glotzer, T. V., Healey, J. S., Kirchhof, P. F., & Potpara, T. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.94 · Cited by 120
Risk of Thromboembolism Associated With Atrial Fibrillation Following Noncardiac Surgery
Butt, J. H., Olesen, J. B., Havers‐Borgersen, E., Gundlund, A., Andersson, C., Gislason, G., Torp-Pedersen, C. T., Køber, L., & Fosbøl, E. L. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.07.088 · Cited by 122
“Interestingly, in a study including patients without a history of AF with recently implanted pacemakers or defibrillators, short episodes of subclinical AF were associated with a significantly increased risk of subsequent ischemic stroke or systemic embolism (32).”
Background
P-wave evidence as a method for improving algorithm to detect atrial fibrillation in insertable cardiac monitors
Pürerfellner, H., Pokushalov, E. A., Sarkar, S., Koehler, J. L., Zhou, R. J., Urban, Ľ., & Hindricks, G. (2014) · Heart Rhythm · doi:10.1016/j.hrthm.2014.06.006 · Cited by 118
Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study
Christensen, L. M., Krieger, D. W., Højberg, S., Pedersen, O. D., Karlsen, F. M., Jacobsen, M. D., Worck, R. H., Nielsen, H., Ægidius, K. L., Jeppesen, L. L., et al. (2014) · European Journal of Neurology · doi:10.1111/ene.12400 · Cited by 118
Left Atrial Mechanical Function and Incident Ischemic Cerebrovascular Events Independent of AF
Habibi, M., Zareian, M., Ambale‐Venkatesh, B., Samiei, S., Imai, M., Wu, C. O., Launer, L. J., Shea, S., Gottesman, R. F., Heckbert, S. R., et al. (2019) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2019.02.021 · Cited by 121

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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