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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The Accuracy of Atrial Fibrillation Detection from Wrist Photoplethysmography. A Study on Post-Operative Patients
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“Even if AF may display symptoms such as heart palpitations, shortness of breath, or lightheadedness [2], it is asymptomatic in at least one third of the cases [3].”
Background
Arrhythmic burden in patients with new-onset persistent left bundle branch block after transcatheter aortic valve replacement: 2-year results of the MARE study
Muntané‐Carol, G., Ureña, M., y, L. N.-F., Amat-Santos, I. J., Kleiman, N. S., Muñoz-García, A. J., Atienza, F., Serra, V., Deyell, M. W., Fernández, G. V., et al. (2020) · EP Europace · doi:10.1093/europace/euaa213 · Cited by 24
Prevalence and Predictors of Clinically Relevant Atrial High-Rate Episodes in Patients with Cardiac Implantable Electronic Devices
Kim, M. H., Kim, T., Yu, H. T., Choi, E., Park, H.-S., Park, J., Lee, Y. S., Kang, K., Uhm, J., Sung, J., et al. (2020) · Korean Circulation Journal · doi:10.4070/kcj.2020.0393 · Cited by 23
Incidence and Clinical Significance of New-Onset Device-Detected Atrial Tachyarrhythmia
Belkin, M. N., Soria, C. E., Waldo, A. L., Borleffs, C. J. W., Hayes, D. L., Tung, R. H., Singh, J. P., & Upadhyay, G. A. (2018) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.117.005393 · Cited by 23
Cost-Effectiveness of Extended and One-Time Screening Versus No Screening for Non-Valvular Atrial Fibrillation in the USA
Oguz, M., Lanitis, T., Li, X., Wygant, G. D., Singer, D. E., Friend, K. E., Hlavacek, P. R., Nikolaou, A., & Mattke, S. (2019) · Applied Health Economics and Health Policy · doi:10.1007/s40258-019-00542-y · Cited by 23
Cardiac monitoring for patients with palpitations
Pascual, J. F., Romero, J. C., Pérez‐Rodon, J., Benito, B., Santos‐Ortega, A., Maldonado, J., González, I. F., & Rivas‐Gándara, N. (2021) · World Journal of Cardiology · doi:10.4330/wjc.v13.i11.608 · Cited by 23
Hypertension and Arrhythmias: A Clinical Overview of the Pathophysiology-Driven Management of Cardiac Arrhythmias in Hypertensive Patients
Marazzato, J., Blasi, F., Golino, M., Verdecchia, P., Angeli, F., & Ponti, R. D. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9040110 · Cited by 23
Automated Atrial Fibrillation Detection with ECG
Wei, T.-R., Lu, S., & Yan, Y. (2022) · Bioengineering · doi:10.3390/bioengineering9100523 · Cited by 24
“Over 10% of patients with hypertension but no A-fib history were detected as having atrial tachyarrhythmias, which were associated with an increased risk of clinical atrial fibrillation [12].”
Background
Pathophysiology and clinical relevance of atrial myopathy
Tubeeckx, M., Keulenaer, G. W. D., Heidbüchel, H., & Segers, V. F. M. (2024) · Basic Research in Cardiology · doi:10.1007/s00395-024-01038-0 · Cited by 25
“Some studies suggest that atrial remodeling, rather than rhythm, is a significant stroke risk factor [246, 263] and therefore should guide initiation of anticoagulant therapy [97, 181].”
Left Atrial Appendage Exclusion for Atrial Fibrillation
Syed, F. F., DeSimone, C. V., Friedman, P. A., & Asirvatham, S. J. (2014) · Cardiology Clinics · doi:10.1016/j.ccl.2014.07.006 · Cited by 23
Ischemic Stroke Phenotype in Patients With Nonsustained Atrial Fibrillation
Arsava, E. M., Baş, D. F., Atalar, E., Has, A. C., Oğuz, K. K., & Topçuoğlu, M. A. (2015) · Stroke · doi:10.1161/strokeaha.114.006396 · Cited by 23
Untreated atrial fibrillation in the United Kingdom: Understanding the barriers and treatment options
Barra, S., & Fynn, S. P. (2014) · Journal of the Saudi Heart Association · doi:10.1016/j.jsha.2014.08.002 · Cited by 23
Subclinical atrial fibrillation and stroke: insights from continuous monitoring by implanted cardiac electronic devices
Lau, C., Siu, C.-W., Yiu, K., Lee, K. L., Chan, Y., & Tse, H. (2015) · EP Europace · doi:10.1093/europace/euv235 · Cited by 23
Performance of Atrial Fibrillation Detection in a New Single‐Chamber ICD
Deshmukh, A. J., BROWN, M. L., HIGGINS, E., SCHOUSEK, B., Abeyratne, A., Rovaris, G., & Friedman, P. A. (2016) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12918 · Cited by 23
P‐wave and interatrial block: New predictor for atrial high rate episodes in patients with cardiac implantable electronic devices
Campal, J. M. R., Benezet‐Mazuecos, J., Bravo, J. A. I., Borque, P. S., Blanco, Á. M., Alarcón, J. J. D. L. V., Mariscal, J. M., Baranchuk, A. M., & Farré, J. (2018) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.13268 · Cited by 23
Improving performance of 3D speckle tracking in arterial hypertension and paroxysmal atrial fibrillation by using novel strain parameters
Esposito, G., Piras, P., Evangelista, A., Nuzzi, V., Nardinocchi, P., Pannarale, G., Torromeo, C., & Puddu, P. E. (2019) · Scientific Reports · doi:10.1038/s41598-019-43855-7 · Cited by 22
Concomitant Use of Diltiazem With Direct Oral Anticoagulants and Bleeding Risk in Atrial Fibrillation
Xu, Y., Chang, A. R., Inker, L. A., McAdams‐DeMarco, M., Grams, M. E., & Shin, J. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.025723 · Cited by 22
Smartphone and wearable detected atrial arrhythmias in Older Adults: Results of a fully digital European Case finding study
Fabritz, L., Connolly, D. L., Czarnecki, E., Dudek, D., Guasch, E., Haase, D., Huebner, T. A., Złahoda-Huzior, A., Jolly, K. B., Kirchhof, P. F., et al. (2022) · European Heart Journal - Digital Health · doi:10.1093/ehjdh/ztac067 · Cited by 23
“Rare arrhythmias of 6 min duration or more, detected within three months of screening using an implanted device, are associated with an increased risk of stroke.(10,22) Six minutes of atrial arrhythmias are also sufficiently long to allow good differentiation of atrial arrhythmias from artefacts or other rhythm irregu…”
Background
Incidence of stroke in patients with hypertrophic cardiomyopathy in stable sinus rhythm during long-term monitoring
Fumagalli, C., Bonanni, F., Beltrami, M., Ruggieri, R., Zocchi, C., Tassetti, L., Maurizi, N., Berteotti, M., Zampieri, M., Argirò, A., et al. (2023) · International Journal of Cardiology · doi:10.1016/j.ijcard.2023.04.008 · Cited by 22
Predicting Future Incidences of Cardiac Arrhythmias Using Discrete Heartbeats from Normal Sinus Rhythm ECG Signals via Deep Learning Methods
Kim, Y.-H., Lee, M., Yoon, J., Kim, Y., Min, H., Cho, H., Park, J., & Shin, T. (2023) · Diagnostics · doi:10.3390/diagnostics13172849 · Cited by 22
Smartphone-based atrial fibrillation screening in the general population: feasibility and impact on medical treatment
Gruwez, H., Verbrugge, F. H., Proesmans, T., Evens, S., Vanacker, P., Rutgers, M. P., Vanhooren, G., Bertrand, P. B., Pison, L., Haemers, P., et al. (2023) · European Heart Journal - Digital Health · doi:10.1093/ehjdh/ztad054 · Cited by 23
Comprehensive atrial fibrillation burden and symptom reduction post-ablation: insights from DECAAF II
Noujaim, C., Assaf, A. Y. M., Lim, C., Feng, H., Younes, H., Mekhael, M., Chouman, N., Shamaileh, G., Hajjar, A. H. E., Ayoub, T. H., et al. (2024) · EP Europace · doi:10.1093/europace/euae104 · Cited by 24
Implantable Cardioverter Defibrillator System with Floating Atrial Sensing Dipole: A Single‐Center Experience
Iori, M., Giacopelli, D., Quartieri, F., Bottoni, N., & Manari, A. (2014) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12421 · Cited by 22
Position paper for management of elderly patients with pacemakers and implantable cardiac defibrillators: Groupe de Rythmologie et Stimulation Cardiaque de la Société Française de Cardiologie and Société Française de Gériatrie et Gérontologie
Fauchier, L., Alonso, C., Anselme, F., Blangy, H., Bordachar, P., Bovéda, S., Clémenty, N., Defaye, P., Deharo, J., Friocourt, P., et al. (2016) · Archives of cardiovascular diseases · doi:10.1016/j.acvd.2016.04.004 · Cited by 22
Refinement of detecting atrial fibrillation in stroke patients: results from the TRACK ‐ AF Study
Reinke, F., Bettin, M., Ross, L., Kochhäuser, S., Kleffner, I., Ritter, M., Minnerup, J., Dechering, D. G., Eckardt, L., & Dittrich, R. (2017) · European Journal of Neurology · doi:10.1111/ene.13538 · Cited by 22
“pAF increases stroke risk and is one of the main causes for “cryptogenic” stroke [5,6].”
Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source
Sanna, T., Ziegler, P., & Crea, F. (2018) · Clinical Cardiology · doi:10.1002/clc.22876 · Cited by 23
Remote monitoring: Doomed to let down or an attractive promise?
Lucà, F., Cipolletta, L., Fusco, S. A. D., Iorio, A., Pozzi, A., Rao, C. M., Ingianni, N., Benvenuto, M., Madeo, A., Fiscella, D., et al. (2019) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2019.100380 · Cited by 22
“Fabiana Lucà a,⁎, Laura Cipolletta b, Stefania Angela Di Fusco c, Annamaria Iorio d, Andrea Pozzi d, Carmelo Massimiliano Rao a, Nadia Ingianni e, Manuela Benvenuto f, Andrea Madeo g, Damiana Fiscella h, Daniela Benedetto i, Giuseppina Maura Francese h, Sandro Gelsomino j, Massimo Zecchin k, Domenico Gabrielli l, Mich…”
Background
Long-term Success and Follow-up After Atrial Fibrillation Ablation
Kircher, S., Hindricks, G., & Sommer, P. (2012) · Current Cardiology Reviews · doi:10.2174/157340312803760758 · Cited by 21
Comparison of 2 ambulatory patch ECG monitors: The benefit of the P-wave and signal clarity
Rho, R. W., Vossler, M. R., Blancher, S., & Poole, J. E. (2018) · American Heart Journal · doi:10.1016/j.ahj.2018.03.022 · Cited by 21
Bimodal classification algorithm for atrial fibrillation detection from m-health ECG recordings
Kruger, G. H., Latchamsetty, R., Langhals, N. B., Yokokawa, M., Chugh, A., Morady, F., Oral, H., & Berenfeld, O. (2018) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2018.11.016 · Cited by 21
Association between socioeconomic status and incident atrial fibrillation
Ramkumar, S., Ochi, A., Yang, H., Nerlekar, N., D’Elia, N. W., Potter, E. L., Murray, I. C., Nattraj, N., Wang, Y., & Marwick, T. H. (2018) · Internal Medicine Journal · doi:10.1111/imj.14214 · Cited by 21
Artificial intelligence predicts clinically relevant atrial high-rate episodes in patients with cardiac implantable electronic devices
Kim, M. H., Kang, Y., You, S. C., Park, H., Lee, S., Kim, T., Yu, H. T., Choi, E., Park, H., Park, J., et al. (2022) · Scientific Reports · doi:10.1038/s41598-021-03914-4 · Cited by 22
“The study population included patients (1) eligible for permanent pacemaker implantation according to the guidelines on cardiac pacemaker implantation for sick sinus syndrome (sinus bradycardia, sinus pause of ≥ 3 s, tachy-brady syndrome, sinus node dysfunction, and chronotropic incompetence) or atrioventricular block…”
Method
How should I treat patients with subclinical atrial fibrillation and atrial high-rate episodes? Current evidence and clinical importance
Kreimer, F., Mügge, A., & Gotzmann, M. (2022) · Clinical Research in Cardiology · doi:10.1007/s00392-022-02000-7 · Cited by 23
The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk
Madsen, C. L., Park-Hansen, J., Irmukhamedov, A., Carranza, C. L., Rafiq, S., Rodríguez-Lecoq, R., Palmer, N. E., Modrau, I. S., Hansson, E. C., Jeppsson, A., et al. (2023) · American Heart Journal · doi:10.1016/j.ahj.2023.06.003 · Cited by 21
Atrial Fibrillation and Dementia: Pathophysiological Mechanisms and Clinical Implications
Varrias, D., Saralidze, T., Borkowski, P., Pargaonkar, S., Spanos, M., Bazoukis, G., & Kokkinidis, D. G. (2024) · Biomolecules · doi:10.3390/biom14040455 · Cited by 23
“As highlighted by Healy et al., frequently silent infarcts are miss-characterized as “innocent, underestimating their clinical significance and the risk of developing into fatal strokes [34].”
Background
Genetic Polymorphisms for Estimating Risk of Atrial Fibrillation in the General Population: A Prospective Study
Newton‐Cheh, C. (2012) · Archives of Internal Medicine · doi:10.1001/archinternmed.2012.786 · Cited by 21
Detecting the Elusive P-Wave: A New ECG Lead to Improve the Recording of Atrial Activity
Kennedy, A., Finlay, D., Guldenring, D., Bond, R., & McLaughlin, J. A. (2015) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2015.2450212 · Cited by 21
Predictors and long-term clinical outcomes of newly developed atrial fibrillation in patients with cardiac implantable electronic devices
Kim, B. S., Chun, K. J., Hwang, J. K., Park, S., Park, K., Kim, J. S., & On, Y. K. (2016) · Medicine · doi:10.1097/md.0000000000004181 · Cited by 21
Relevance of supraventricular runs detected after cerebral ischemia
Weber-Krüger, M., Lutz, C., Zapf, A., Stahrenberg, R., Seegers, J., Witzenhausen, J., Wasser, K., Hasenfuss, G. P., Gröschel, K., & Wachter, R. (2017) · Neurology · doi:10.1212/wnl.0000000000004487 · Cited by 21
Screening of older patients for atrial fibrillation in general practice: Current evidence and its implications for future practice
Fay, M., Fitzmaurice, D. A., & Freedman, B. (2017) · European Journal of General Practice · doi:10.1080/13814788.2017.1374366 · Cited by 21
“A major diagnostic challenge relates to those with paroxysmal or asymptomatic (silent) AF, particularly given the results of the ASSERT and Copenhagen Holter studies, which clearly indicate that even short episodes of ‘silent’ AF are associated with an increased risk of stroke [15,16].”
Result
Clinical significance of atrial high-rate episodes for thromboembolic events in Japanese population
Kawakami, H., Nagai, T., Saito, M., Inaba, S., Seike, F., Nishimura, K., Inoue, K., Okura, T., Sumimoto, T., Uemura, S., et al. (2017) · Heart Asia · doi:10.1136/heartasia-2017-010954 · Cited by 22
Extended ECG monitoring with an implantable loop recorder in patients with cryptogenic stroke: time schedule, reasons for explantation and incidental findings (results from the TRACK-AF trial)
Bettin, M., Dechering, D. G., Kochhäuser, S., Bode, N., Eckardt, L., Frommeyer, G., & Reinke, F. (2018) · Clinical Research in Cardiology · doi:10.1007/s00392-018-1358-4 · Cited by 21
Stroke Prevention in Atrial Fibrillation
Mtwesi, V., & Amit, G. (2019) · Medical Clinics of North America · doi:10.1016/j.mcna.2019.05.006 · Cited by 21
Resource Use and Economic Implications of Remote Monitoring With Subcutaneous Cardiac Rhythm Monitors
Afzal, M. R., Nadkarni, A., Niemet, L., Houmsse, M. M., Devgun, J. K., Koppert, T. L., Ferguson, K., Mease, J., Okabe, T., Houmsse, M., et al. (2021) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2020.10.014 · Cited by 21
Frequency of cardiac arrhythmias in older adults: Findings from the Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study
Mannina, C. M., Jin, Z., Matsumoto, K., Ito, K., BIVIANO, A. B., Elkind, M. S. V., Rundek, T., Homma, S., Sacco, R. L., & Tullio, M. R. D. (2021) · International Journal of Cardiology · doi:10.1016/j.ijcard.2021.05.006 · Cited by 21

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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