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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“…no consen‐ sus regarding if patients with subclinical AF should be treated the same as those with symptomatic AF (Andrade et al., 2018; Gold, 2018) Several large clinical trials have demonstrated that subclin‐ ical AF carries an increased risk of stroke (Glotzer et al., 2009; Healey et al., 2012).”
Background
Thrombo-Embolism and Antithrombotic Therapy for Heart Failure in Sinus Rhythm. A Joint Consensus Document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis
Lip, G. Y. H., Ponikowski, P., Andreotti, F., Anker, S. D., Filippatos, G., Homma, S., Morais, J., Pullicino, P. M., Rasmussen, L. H., Marín, F. R., et al. (2012) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfs073 · Cited by 89
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Atrial Fibrillation Predictors: Importance of the Electrocardiogram
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Atrial fibrillation burden and atrial fibrillation type: Clinical significance and impact on the risk of stroke and decision making for long-term anticoagulation
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Left Atrial Dysfunction in the Pathogenesis of Cryptogenic Stroke: Novel Insights from Speckle-Tracking Echocardiography
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A Systematic Review on the Progression of Paroxysmal to Persistent Atrial Fibrillation
Proietti, R., Hadjis, A. E., AlTurki, A., Thanassoulis, G., Roux, J.-F., Verma, A., Healey, J. S., Bernier, M., Birnie, D. H., Nattel, S., et al. (2015) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2015.04.010 · Cited by 85
Consumer-Led Screening for Atrial Fibrillation: Frontier Review of the AF-SCREEN International Collaboration
Brandes, A., Stavrakis, S., Freedman, B., Antoniou, S., Boriani, G., Camm, A. J., Chow, C. K., Ding, E., Engdahl, J., Gibson, C. M., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.058911 · Cited by 88
Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation
Tandon, K., Tirschwell, D., Longstreth, W. T., Smith, B. M., & AKOUM, N. W. (2019) · Neurology · doi:10.1212/wnl.0000000000007827 · Cited by 82
Mobile health applications for the detection of atrial fibrillation: a systematic review
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“Atrial fibrillation manifestations can range from asymptomatic to highly symptomatic and can negatively affect patients’ quality of life if left untreated.(3) Early diagnosis of AF may have several benefits, including the potential for individualized risk factor evaluation and modification, ablation for symptomatic in…”
Background
Current and Future Use of Insertable Cardiac Monitors
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Venice Chart International Consensus Document on Atrial Fibrillation Ablation: 2011 Update
Raviele, A., Natale, A., Calkins, H. G., Camm, A. J., Cappato, R., Chen, S. A., Connolly, S. J., Damiano, R. J., Ponti, R. D., EDGERTON, J. R., et al. (2012) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2012.02381.x · Cited by 79
Long-term ECG monitoring using an implantable loop recorder for the detection of atrial fibrillation after cavotricuspid isthmus ablation in patients with atrial flutter
Mittal, S., Pokushalov, E. A., Romanov, A. B., Ferrara, M., Arshad, A., Musat, D. L., Preminger, M. W., Sichrovsky, T., & Steinberg, J. S. (2013) · Heart Rhythm · doi:10.1016/j.hrthm.2013.07.044 · Cited by 78
Arrhythmic Burden and the Risk of Cardiovascular Outcomes in Patients With Paroxysmal Atrial Fibrillation and Cardiac Implanted Electronic Devices
Chew, D. S., Li, Z., Steinberg, B. A., O’Brien, E. C., Pritchard, J. E., Bunch, T. J., Mark, D. B., Patel, M. R., Nabutovsky, Y., Greiner, M. A., et al. (2022) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.121.010304 · Cited by 79
Towards a new classification of atrial fibrillation detected after a stroke or a transient ischaemic attack
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Atrial Fibrillation or Flutter During Pregnancy in Patients With Structural Heart Disease
Salam, A. M., Ertekin, E., van Hagen, I. M., Al Suwaidi, J., Ruys, T. P. E., Johnson, M. R., Gumbiene, L., Frogoudaki, A. A., Sorour, K. A., Iserin, L., et al. (2015) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2015.04.013 · Cited by 79
Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke
Diamantopoulos, A., Sawyer, L., Lip, G. Y. H., Witte, K. K., Reynolds, M. R., Fauchier, L., Thijs, V., Brown, B., Angulo, M. E. Q., & Diener, H. (2016) · International Journal of Stroke · doi:10.1177/1747493015620803 · Cited by 78
Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial
Ntaios, G., Pearce, L. A., Veltkamp, R. C., Sharma, M., Kasner, S. E., Korompoki, E., Milionis, H. J., Mundl, H., Berkowitz, S. D., Connolly, S. J., et al. (2020) · Stroke · doi:10.1161/strokeaha.119.028669 · Cited by 76
Emerging Technologies for Identifying Atrial Fibrillation
Ding, E., Marcus, G. M., & McManus, D. D. (2020) · Circulation Research · doi:10.1161/circresaha.119.316342 · Cited by 77
Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation
Lópes, R. D., Granger, C. B., WOJDYLA, D. M., McIntyre, W. F., Alings, M., Mani, T., Ramasundarahettige, C. F., Rivard, L., Atar, D., Birnie, D. H., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.05.002 · Cited by 76
Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial
Diederichsen, S. Z., Haugan, K., Køber, L., Højberg, S., Brandes, A., Kronborg, C., Graff, C., Holst, A. G., Nielsen, J. B., Krieger, D. W., et al. (2017) · American Heart Journal · doi:10.1016/j.ahj.2017.02.017 · Cited by 74
2021 ISHNE/HRS/EHRA/APHRS Expert Collaborative Statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society
Varma, N., Cygankiewicz, I., Turakhia, M. P., Heidbuchel, H., Hu, Y.-F., Chen, L. Y., Couderc, J.-P., Cronin, E. M., Estep, J. D., Grieten, L., et al. (2021) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.120.009204 · Cited by 74
Intermittent short ECG recording is more effective than 24-hour Holter ECG in detection of arrhythmias
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Thromboembolism and antithrombotic therapy for heart failure in sinus rhythm
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Asymptomatic persistent atrial fibrillation and outcome: Results of the RACE study
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Self-monitoring for atrial fibrillation recurrence in the discharge period post-cardiac surgery using an iPhone electrocardiogram
Lowres, N., Mulcahy, G., Gallagher, R. D., Freedman, S. B., Marshman, D., Kirkness, A., Orchard, J. J., & Neubeck, L. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezv486 · Cited by 72
Automated detection of atrial fibrillation using R-R intervals and multivariate-based classification
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Continuous monitoring after atrial fibrillation ablation: the LINQ AF study
Wechselberger, S., Kronborg, M. B., Huo, Y., Piorkowski, J., Neudeck, S., Päßler, E., El‐Armouche, A., Richter, U., Mayer, J., Ulbrich, S., et al. (2018) · EP Europace · doi:10.1093/europace/euy038 · Cited by 73
Atrial high-rate episodes: prevalence, stroke risk, implications for management, and clinical gaps in evidence
Bertaglia, E., Blank, B., Blomström‐Lundqvist, C., Brandes, A., Cabanelas, N., Dan, G. A., Dichtl, W., Goette, A., de Groot, J. R., Lubiński, A., et al. (2019) · EP Europace · doi:10.1093/europace/euz172 · Cited by 72
Yield and consistency of arrhythmia detection with patch electrocardiographic monitoring: the Multi-Ethnic Study of Atherosclerosis
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“Our findings for AF/flutter detection with increased duration of monitoring are in agreement with previous studies using implanted or inserted devices [1,7,8] and noninvasive devices [2,9,10] conducted in clinical populations.”
Result
Cryoballoon versus Radiofrequency Catheter Ablation for Paroxysmal Atrial Fibrillation
Wasserlauf, J., Pelchovitz, D. J., Rhyner, J., Verma, N., Bohn, M., LI, Z., Arora, R., Chicos, A. B., Goldberger, J. J., Kim, S. S., et al. (2015) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12582 · Cited by 72
Predictive value of P wave terminal force in lead V1 for atrial fibrillation: A meta‐analysis
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“Atrial fibrillation (AF), one of the most common cardiac arrhythmias in adult medicine, is closely associated with stroke (Healey et al., 2012), heart failure (Ling, Kistler, Kalman, Schilling, & Hunter, 2016), cardiovascular mortality, and sudden cardiac death (Benjamin et al.”
Background
2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation
Tzeis, S. E., Gerstenfeld, E. P., Kalman, J. M., Saad, E., Shamloo, A. S., Andrade, J. G., Barbhaiya, C. R., Baykaner, T., Bovéda, S., Calkins, H. G., et al. (2024) · Journal of Arrhythmia · doi:10.1002/joa3.13082 · Cited by 76
Prevalence of unknown atrial fibrillation in patients with risk factors
Samol, A., Masin, M., Gellner, R., Otte, B., Pavenstädt, H.-J., Ringelstein, E. B., Reinecke, H., Waltenberger, J. L., & Kirchhof, P. F. (2012) · EP Europace · doi:10.1093/europace/eus366 · Cited by 72
Left atrial remodelling assessed by 2D and 3D echocardiography identifies paroxysmal atrial fibrillation
Schaaf, M., André, P., Altman, M., Maucort‐Boulch, D., Placide, J., Chevalier, P., Bergerot, C., & Thibault, H. (2016) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jew028 · Cited by 70
Atrial Fibrillation Detection During Sepsis: Study on MIMIC III ICU Data
Bashar, S. K., Hossain, M.-B., Ding, E., Walkey, A. J., McManus, D. D., & Chon, K. H. (2020) · IEEE Journal of Biomedical and Health Informatics · doi:10.1109/jbhi.2020.2995139 · Cited by 72
“The 6 minute rule for subject-wise AF decision is derived based on the clinical studies which focused on the relation of AF and risk of stroke [47], [48]; further insights can also be explored to find out what may be the best criteria for subject-wise AF decision.”
BackgroundMethod
Early detection of atrial high rate episodes predicts atrial fibrillation and thromboembolic events in patients with cardiac resynchronization therapy
Witt, C. T., Kronborg, M. B., Nohr, E. A., Mortensen, P. T., Gerdes, C., & Nielsen, J. C. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.07.007 · Cited by 72
Prevalence, risk factors, and type of sleep apnea in patients with paroxysmal atrial fibrillation
Traaen, G. M., Øverland, B., Aakerøy, L., Hunt, T. E., Bendz, C., Sande, L., Aakhus, S., Zaré, H., Steinshamn, S., Anfinsen, O. G., et al. (2020) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2019.100447 · Cited by 71
Reducing Stroke Risk in Atrial Fibrillation: Adherence to Guidelines Has Improved, but Patient Persistence with Anticoagulant Therapy Remains Suboptimal
Lowres, N., Giskes, K., Hespe, C. M., & Freedman, B. (2019) · Korean Circulation Journal · doi:10.4070/kcj.2019.0234 · Cited by 74
The Atrium and Embolic Stroke
Sajeev, J., Kalman, J. M., Dewey, H. M., Cooke, J. C., & Teh, A. W. (2020) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2019.12.013 · Cited by 72
Rate versus rhythm control for management of atrial fibrillation in clinical practice: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry
Steinberg, B. A., Holmes, D. N., Ezekowitz, M. D., Fonarow, G. C., Kowey, P. R., Mahaffey, K. W., Naccarelli, G. V., Reiffel, J. A., Chang, P., Peterson, E. D., et al. (2013) · American Heart Journal · doi:10.1016/j.ahj.2012.12.019 · Cited by 71
Ambulatory Atrial Fibrillation Monitoring Using Wearable Photoplethysmography with Deep Learning
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“Silent AF results in a quarter of all ischemic strokes [13].”
Background
Pilot Randomized Trial of Outpatient Cardiac Monitoring After Cryptogenic Stroke
Kamel, H., Navi, B. B., Elijovich, L., Josephson, S. A., Yee, A., Fung, G. L., Johnston, S. C., & Smith, W. S. (2012) · Stroke · doi:10.1161/strokeaha.112.679100 · Cited by 68
Research Priorities in Atrial Fibrillation Screening
Benjamin, E. J., Go, A. S., Desvigne-Nickens, P. M., Anderson, C. D., Casadei, B., Chen, L. Y., Crijns, H. J. G. M., Freedman, B., Hills, M. T., Healey, J. S., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.047633 · Cited by 71

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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