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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“21 25”
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BackgroundInfluential
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Recomendaciones preventivas cardiovasculares. Actualización PAPPS 2022
Orozco‐Beltrán, D., Cuixart, C. B., Banegas, J. R., Gil-Guillén, V. F., Cuenca, A. M. C., Rioboó, E. M., Baldó, A. J., Vicuña, J., & Pérez, J. N. (2022) · Atención Primaria · doi:10.1016/j.aprim.2022.102444 · Cited by 64
Challenges of Anticoagulant Therapy in Atrial Fibrillation—Focus on Gastrointestinal Bleeding
Scridon, A., & Balan, A. I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086879 · Cited by 17
“This risk is present regardless of whether the arrhythmia is paroxysmal, persistent, or permanent [7].”
Background
Electrocardiographic Morphology-Voltage-P-Wave-Duration (MVP) Score to Select Patients for Continuous Atrial Fibrillation Screening to Prevent Stroke
Xing, L. Y., Diederichsen, S. Z., Højberg, S., Krieger, D. W., Graff, C., Olesen, M. S., Nielsen, J. B., Brandes, A., Køber, L., Haugan, K., et al. (2023) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2023.08.042 · Cited by 17
Aromatase Inhibitor Therapy Increases the Risk of New-Onset Atrial Fibrillation in Patients With Breast Cancer
Ho, I., Wong, C., Wong, Y., Lam, T.-H., Leung, I. S. H., Lin, M., Lui, D. T. W., Kwok, W. C., Tam, C. C., Chan, Y., et al. (2023) · JACC Asia · doi:10.1016/j.jacasi.2023.09.014 · Cited by 17
JCS / JHRS 2022 Guideline on Diagnosis and Risk Assessment of Arrhythmia
Takase, B., Ikeda, T., Shimizu, W., Abe, H., Aiba, T., Chinushi, M., Koba, S., KUSANO, K. F., Niwano, S., Takahashi, N., et al. (2024) · Journal of Arrhythmia · doi:10.1002/joa3.13052 · Cited by 19
Long-Term Changes in Atrial Arrhythmia Burden After Renal Denervation Combined With Pulmonary Vein Isolation
Chinitz, L. A., Böhm, M., Evonich, R. F., Saba, S., Sangriogoli, R., Augostini, R. S., O’Neill, P. G., Fellows, C. L., Kim, M.-Y., Hettrick, D. A., et al. (2024) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2024.04.035 · Cited by 17
Clinically important atrial arrhythmia and stroke risk: a UK-wide online survey among stroke physicians and cardiologists
Rankin, A. J., Tran, R., Abdul‐Rahim, A. H., RANKIN, A. C., & Lees, K. R. (2014) · QJM · doi:10.1093/qjmed/hcu177 · Cited by 18
Diving to the foot of an iceberg: The SEARCH for undiagnosed atrial fibrillation
Lane, D. A., & Potpara, T. (2014) · Thrombosis and Haemostasis · doi:10.1160/th14-05-0437 · Cited by 17
Can we rely on machines? Device-detected atrial high rates correspond well with atrial arrhythmias in cardiac resynchronization recipients
Jędrzejczyk‐Patej, E., Lenarczyk, R., Mazurek, M., Liberska, A., Przybylska-Siedlecka, K., Podolecki, T., Kowalczyk, J. P., Sokal, A., Leopold-Jadczyk, A., Kowalski, O., et al. (2015) · EP Europace · doi:10.1093/europace/euv095 · Cited by 17
Characteristics and Prognosis of Pacemaker-Identified New-Onset Atrial Fibrillation in Japanese People
Ogino, Y., Ishikawa, T., Ishigami, T., Matsumoto, K., Hosoda, J., Iguchi, K., Matsushita, H., Taguchi, Y., Horiguchi, Y., & Kimura, K. (2017) · Circulation Journal · doi:10.1253/circj.cj-16-1018 · Cited by 17
Assessment of left atrial electro-mechanical delay to predict atrial fibrillation in hypertrophic cardiomyopathy
Tjahjadi, C., Hiemstra, Y. L., van der Bijl, P., Pio, S. M., Bootsma, M., Marsan, N. A., Delgado, V., & Bax, J. J. (2020) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jeaa174 · Cited by 17
Cardiac Ambulatory Monitoring: New Wireless Device Validated Against Conventional Holter Monitoring in a Case Series
Murali, S., Brugger, N., Rincón, F. J., Mashru, M. R., Cook, S., & Goy, J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.587945 · Cited by 17
“In addition, morbidity and mortality associated with subclinical AF are certainly underestimated and the conventional 24-h monitoring has a low sensitivity for the detection of such arrhythmia (8).”
Background
Clinical review of sick sinus syndrome and atrial fibrillation
Chang, W., & Li, G. (2021) · Herz · doi:10.1007/s00059-021-05046-x · Cited by 17
Randomized Trial of Surgical Left Atrial Appendage Closure: Protection Against Cerebrovascular Events
Madsen, C. V., Park-Hansen, J., Holme, S. J. V., Irmukhamedov, A., Carranza, C. L., Greve, A. M., Al-Farra, G. J., Riis, R., Nilsson, B., Clausen, J. S. R., et al. (2022) · Seminars in Thoracic and Cardiovascular Surgery · doi:10.1053/j.semtcvs.2022.06.012 · Cited by 17
Frequency and Outcomes of Postrandomization Atrial Tachyarrhythmias in the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial
Wilton, S. B., Exner, D. V., Wyse, D. G., Yetisir, E., Wells, G. A., TANG, A. S. L., & Healey, J. S. (2016) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.115.003807 · Cited by 17
Geographic and socio-demographic differences in uptake of population-based screening for atrial fibrillation: The STROKESTOP I study
Engdahl, J., Holmén, A., Svennberg, E., Friberg, L., Frykman, V., Al‐Khalili, F., Rosenqvist, M., & Strömberg, U. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.07.198 · Cited by 17
Sympathetic and Parasympathetic Coactivation Induces Perturbed Heart Rate Dynamics in Patients with Paroxysmal Atrial Fibrillation
Eickholt, C., Jungen, C., Drexel, T., Alken, F., Kuklik, P., Muehlsteff, J., Makimoto, H., Hoffmann, B. A., Kelm, M., Ziegler, D., et al. (2018) · Medical Science Monitor · doi:10.12659/msm.905209 · Cited by 19
Use of insertable cardiac monitors for the detection of atrial fibrillation in patients with cryptogenic stroke in the United States is cost-effective
Maervoet, J., Bossers, N., Borge, R. P., Hilpert, S. T., van Engen, A., & Smala, A. M. (2019) · Journal of Medical Economics · doi:10.1080/13696998.2019.1663355 · Cited by 17
When Low-Risk Atrial Fibrillation Is Not So Low Risk
Steinberg, B. A., & Piccini, J. P. (2018) · JAMA Cardiology · doi:10.1001/jamacardio.2018.1205 · Cited by 17
Left ventricular stiffness assessed by diastolic Wall strain predicts asymptomatic atrial high-rate episodes in patients with pacemaker implantation
Kishima, H., Mine, T., Fukuhara, E., & Ishihara, M. (2020) · Journal of Cardiology · doi:10.1016/j.jjcc.2020.08.002 · Cited by 16
The Role of Contemporary Wearable and Handheld Devices in the Diagnosis and Management of Cardiac Arrhythmias
Garikapati, K., Turnbull, S., Bennett, R. G., Campbell, T. G., Kanawati, J., Wong, M. S., Thomas, S. P., Chow, C. K., & Kumar, S. (2022) · Heart Lung and Circulation · doi:10.1016/j.hlc.2022.08.001 · Cited by 18
Current perspectives on the clinical management of cryptogenic stroke
Yang, D., & Elkind, M. S. V. (2023) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2023.2192403 · Cited by 17
Left atrial appendage strain predicts subclinical atrial fibrillation in embolic strokes of undetermined source
Saberniak, J., Skrebelyte-Strøm, L., Orstad, E. B., Hilde, J. M., Solberg, M. G., Rønning, O. M., Kjekshus, H., & Steine, K. (2023) · European Heart Journal Open · doi:10.1093/ehjopen/oead039 · Cited by 16
“The lack of consensus for cryptogenic stroke and transient ischemic attack (TIA) has prompted proposal of a new concept: ‘embolic strokes of undetermined source’ (ESUS),2 frequently associated with atrial cardiomyopathy.3 ESUS makes up to one-third of all ischemic strokes/TIA.4 Most cases of ESUS are thromboembolic,2…”
BackgroundInfluential
Atrial Fibrillation Detection and Load: Knowledge Gaps Related to Stroke Prevention
Smith, E. E., Yaghi, S. R., Sposato, L. A., Fisher, M., Broderick, J. P., Das, A. S., Elkind, M. S. V., Goldstein, L. B., Gurol, M. E., Kamel, H., et al. (2023) · Stroke · doi:10.1161/strokeaha.123.043665 · Cited by 17
Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease
Xu, Y., Ballew, S. H., Chang, A. R., Inker, L. A., Grams, M. E., & Shin, J. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.123.034641 · Cited by 16
Actualización detallada de las guías de la ESC para el manejo de la fibrilación auricular de 2012
Camm, A. J., Lip, G. Y. H., Caterina, R. D., Savelieva, I., Atar, D., Hohnloser, S. H., Hindricks, G., Kirchhof, P. F., Bax, J. J., Baumgartner, H., et al. (2012) · Revista Española de Cardiología · doi:10.1016/j.recesp.2012.11.001 · Cited by 16
Severity of Obstructive Sleep Apnea Influences the Effect of Genotype on Response to Anti-Arrhythmic Drug Therapy for Atrial Fibrillation
Goyal, S., Wang, L., Upender, R. P., Darbar, D., & Monahan, K. (2014) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.3696 · Cited by 16
Asymptomatic atrial fibrillation in patients with atrial fibrillation and implanted pacemaker
Witkowski, M., Bissinger, A., Grycewicz, T., & Lubiński, A. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.10.097 · Cited by 16
Kommentar zu den 2016 Leitlinien der Europäischen Gesellschaft für Kardiologie (ESC) zum Management von Vorhofflimmern
Eckardt, L., Deneke, T., Diener, H., Hindricks, G., Hoffmeister, H. M., Hohnloser, S. H., Kirchhof, P. F., & Stellbrink, C. (2017) · Der Kardiologe · doi:10.1007/s12181-017-0141-5 · Cited by 16
The Impact of Atrial Fibrillation Clinical Subtype on Mortality
Leung, M., van Rosendael, P. J., Abou, R., Marsan, N. A., Leung, D. Y., Delgado, V., & Bax, J. J. (2017) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2017.09.002 · Cited by 16
Pacemaker-detected atrial fibrillation burden and risk of ischemic stroke or thromboembolic events—A cohort study
Chu, S., Jiang, J., Wang, Y., Sheng, Q., Zhou, J., & Ding, Y. (2019) · Heart & Lung · doi:10.1016/j.hrtlng.2019.07.007 · Cited by 16
PREventive left atrial appenDage resection for the predICtion of fuTure atrial fibrillation: design of the PREDICT AF study
van den Berg, N. W. E., Neefs, J., Berger, W. R., Boersma, L. V. A., van Boven, W. J., van Putte, B. P., Kaya, A., Kawasaki, M., Driessen, A. H. G., & de Groot, J. R. (2019) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000000868 · Cited by 16
Trends in utilization and spending on remote monitoring of pacemakers and implantable cardioverter–defibrillators among Medicare beneficiaries
Holtzman, J. N., Wadhera, R. K., Choi, E. H., Zhao, T., Secemsky, E. A., Fraiche, A. M., Shen, C., & Kramer, D. B. (2020) · Heart Rhythm · doi:10.1016/j.hrthm.2020.05.044 · Cited by 16
Altered Expression of Circadian Clock Genes in Patients with Atrial Fibrillation Is Associated with Atrial High-Rate Episodes and Left Atrial Remodeling
Chen, Y., Chuang, J., Wang, H., Chen, H., Liu, W., & Yang, M. (2021) · Diagnostics · doi:10.3390/diagnostics11010090 · Cited by 16
Subclinical Atrial Fibrillation and the Risk of Recurrent Ischemic Stroke
Wachter, R., & Freedman, B. (2021) · Thrombosis and Haemostasis · doi:10.1055/s-0041-1726403 · Cited by 16
Atrial High-Rate Episodes in Patients with Devices Without a History of Atrial Fibrillation: a Systematic Review and Meta-analysis
Doundoulakis, I., Gavriilaki, M., Tsiachris, D., Αρσένος, Π., Antoniou, C. K., Dimou, S., Σουλαϊδόπουλος, Σ., Farmakis, I. T., Akrivos, E., Stoiloudis, P., et al. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07209-8 · Cited by 16
ECG abnormalities and stroke incidence
Agarwal, S. K., & Soliman, E. Z. (2013) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.2013.811980 · Cited by 16
Remote monitoring as a key innovation in the management of cardiac patients including those with implantable electronic devices
Sutton, R. (2013) · EP Europace · doi:10.1093/europace/eut108 · Cited by 16
Diagnosis, prognosis, and management of cryptogenic stroke
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Cribado oportunista de fibrilación auricular frente a detección de pacientes sintomáticos de 65 años o más: ensayo clínico controlado por clúster
Blanco, V. G., de Torres, L. Á. P., Rioboó, E. M., Adell, M. Á. M., Rejano, J. M. P., González-Lama, J., Moruno, J. R., Álvarez, R. M., García, J., de Castroviejo, J. R., et al. (2016) · Medicina Clínica · doi:10.1016/j.medcli.2016.07.036 · Cited by 16
Incidence, Predictive Factors, and Prognostic Impact of Silent Atrial Fibrillation After Transcatheter Aortic Valve Implantation
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2021 ISHNE/HRS/EHRA/APHRS Collaborative Statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals
Varma, N., Cygankiewicz, I., Turakhia, M. P., Heidbuchel, H., Hu, Y., Chen, L. Y., Couderc, J.-P., Cronin, E. M., Estep, J. D., Grieten, L., et al. (2021) · Cardiovascular Digital Health Journal · doi:10.1016/j.cvdhj.2020.11.004 · Cited by 16
“Device-detected, “subclinical” atrial high-rate episodes (AHRE) lasting 6 minutes to 24 hours are associated with increased stroke risk, but the absolute risk is considerably lower than expected based on risk factors alone (Glotzer 2003, Healey 2012, van Gelder 2017).”
Background
Atrial Fibrillation Begets Myocardial Infarction
Dukes, J. W., & Marcus, G. M. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.11392 · Cited by 16

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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