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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Background
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Bradyarrhythmias in the Elderly
Kumar, P., Kusumoto, F. M., & Goldschlager, N. (2012) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2012.08.004 · Cited by 31
Clinical predictors to identify paroxysmal atrial fibrillation after ischaemic stroke
Wohlfahrt, J., Stahrenberg, R., Weber-Krüger, M., Gröschel, S., Wasser, K., Edelmann, F., Seegers, J., Wachter, R., & Gröschel, K. (2013) · European Journal of Neurology · doi:10.1111/ene.12198 · Cited by 31
Mechanical closure of the left atrial appendage: Is it time to be more aggressive?
Cox, J. L. (2013) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2013.07.011 · Cited by 32
Does Preoperative Atrial Fibrillation Portend a Poorer Prognosis in Patients Undergoing Isolated Aortic Valve Replacement? A Multicentre Australian Study
Saxena, A., Dinh, D. T., Reid, C. M., Smith, J. A., Shardey, G. C., & Newcomb, A. E. (2012) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2012.08.016 · Cited by 31
Subclinical and Asymptomatic Atrial Fibrillation: Current Evidence and Unsolved Questions in Clinical Practice
Ballatore, A., Matta, M., Saglietto, A., Desalvo, P., Bocchino, P. P., Gaïta, F., Ferrari, G. M. D., & Anselmino, M. (2019) · Medicina · doi:10.3390/medicina55080497 · Cited by 33
“(2012) [18] AHRE: atrial rate ≥ 190 bpm lasting at least 6 min (detected by pacemaker or ICD) AHRE in the previous 3 months: 11/261 (4.”
BackgroundResultInfluential
Remote Patient Monitoring: What Have We Learned and Where Are We Going?
Vandenberk, B., & Raj, S. R. (2023) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-023-00720-7 · Cited by 30
Association between ventricular pacing and persistent atrial fibrillation in patients indicated to elective pacemaker replacement: Results of the Prefer for Elective Replacement MVP (PreFER MVP) randomized study
Ricci, R. P., Botto, G. L., Bénézet, J. M., Nielsen, J. C., Roy, L. D., Piot, O., Quesada, A., Quaglione, R., Vaccari, D., Mangoni, L., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.06.041 · Cited by 31
Symptom Representation and Treatment-Seeking Prior to Diagnosis of Atrial Fibrillation
McCabe, P. J., Chamberlain, A. M., Rhudy, L. M., & DeVon, H. A. (2015) · Western Journal of Nursing Research · doi:10.1177/0193945915570368 · Cited by 30
Anticoagulation in patients at high risk of stroke without documented atrial fibrillation. Time for a paradigm shift?
de Luna, A. B., Baranchuk, A. M., Martínez‐Sellés, M., & Platonov, P. G. (2016) · Annals of Noninvasive Electrocardiology · doi:10.1111/anec.12417 · Cited by 29
Atrial fibrillation and stroke: a practical guide
Best, J. G., Bell, R., Haque, M. M., Chandratheva, A., & Werring, D. J. (2019) · Practical Neurology · doi:10.1136/practneurol-2018-002089 · Cited by 31
Evaluation of a clinical score for predicting atrial fibrillation in cryptogenic stroke patients with insertable cardiac monitors: results from the CRYSTAL AF study
Zhao, S. X., Ziegler, P., Crawford, M. H., Kwong, C., Koehler, J. L., & PASSMAN, R. S. (2019) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286419842698 · Cited by 30
Comparison of Continuous ECG Monitoring by Wearable Patch Device and Conventional Telemonitoring Device
Choi, W., Kim, S., Lee, W., Kang, S., Yoon, C., Youn, T., & Chae, I. (2020) · Journal of Korean Medical Science · doi:10.3346/jkms.2020.35.e363 · Cited by 30
“5 Clinical diagnosis Acute myocardial infarction 5 (50) Heart failure 3 (30) Cardiac arrest 2 (20) Hypertension 4 (40) Diabetes mellitus 2 (20) Dyslipidemia 1 (10) Current smoker 4 (40) Baseline rhythma Sinus rhythm 8 (80) Atrial fibrillation 2 (20) Other tachy- or brady-arrhythmiab 0 (0) Values are presented as numbe…”
Background
Patent foramen ovale closure in the management of cryptogenic stroke: a review of current literature and guideline statements
Elzanaty, A., Patel, N., Sabbagh, E., & Eltahawy, E. A. (2021) · Current Medical Research and Opinion · doi:10.1080/03007995.2021.1876648 · Cited by 32
Is Atrial Fibrillation Always a Culprit of Stroke in Patients with Atrial Fibrillation plus Stroke?
Kim, S. J., Ryoo, S., Kwon, S., Park, Y. K., Kim, J. P., Lee, G. Y., & Bang, O. Y. (2013) · Cerebrovascular Diseases · doi:10.1159/000355571 · Cited by 30
Clinical Efficacy and Safety of an Implantable Cardioverter‐Defibrillator Lead with a Floating Atrial Sensing Dipole
Şafak, E., Schmitz, D., Konorza, T. F. M., Wende, C., de Ros, J. O., & Schirdewan, A. (2013) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12171 · Cited by 30
CHA2DS2VASc score and adverse outcomes in middle-aged individuals without atrial fibrillation
Renda, G., Ricci, F., Patti, G., Aung, N., Petersen, S. E., Gallina, S., Hamrefors, V., Melander, O., Sutton, R., Engström, G., et al. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319868320 · Cited by 30
“The detection of asymptomatic AF provides an opportunity to prevent ischaemic stroke by instituting appropriate anticoagulation.(32) Opportunistic screening in all patients contacting the health system 65 years of age or older has been adopted in the European Society of Cardiology AF guidelines,(1) but might be more e…”
Method
Screen-detected atrial fibrillation predicts mortality in elderly subjects
Zink, M. D., Mischke, K., Keszei, A. P., Rummey, C., Freedman, B., Neumann, G., Tolksdorf, A., Frank, F., Wienströer, J., Kuth, N., et al. (2020) · EP Europace · doi:10.1093/europace/euaa190 · Cited by 29
“However, the prognosis of newly detected AF has been inferred from studies of incidentally detected AF registries,(10) retrospective studies,(11) or from the detection of subclinical AF using continuous recordings from implanted devices or patches.(12) There have been no studies to date to determine the prognosis of s…”
Background
Detection of Brief Episodes of Atrial Fibrillation Based on Electrocardiomatrix and Convolutional Neural Network
Salinas-Martínez, R., de Bie, J., Marzocchi, N., & Sandberg, F. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.673819 · Cited by 26
“arrhythmia for which even brief episodes could represent a risk factor for thrombus formation and stroke (Healey et al., 2012).”
Background
Stroke Prevention After Cryptogenic Stroke
Ibeh, C., & Elkind, M. S. V. (2021) · Current Cardiology Reports · doi:10.1007/s11886-021-01604-1 · Cited by 30
Prevalence of markers of atrial cardiomyopathy in embolic stroke of undetermined source: A systematic review
Stalikas, N., Doundoulakis, I., Karagiannidis, E., Κάρτας, Α., Gavriilaki, M., Sofidis, G., Panteris, E., Papazoglou, Α. S., Haidich, A., Sianos, G., et al. (2022) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2022.01.024 · Cited by 29
Atrial Cardiopathy and Cryptogenic Stroke
Kato, Y., & Takahashi, S. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.839398 · Cited by 31
“Although even brief subclinical episodes of AF are associated with the occurrence of stroke (9), the causal association between ischemic stroke and AF remains circumstantial (3).”
Background
New-Onset Atrial Fibrillation in Left Bundle Branch Area Pacing Compared With Right Ventricular Pacing
Ravi, V., Sharma, P. S., Patel, N. R., Dommaraju, S., Zalavadia, D. V., Garg, V., Larsen, T. R., Naperkowski, A. M., Wasserlauf, J., Krishnan, K., et al. (2022) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.121.010710 · Cited by 28
Asymptomatic versus symptomatic episodes in patients with paroxysmal atrial fibrillation via long-term monitoring with implantable loop recorders
SIMANTIRAKIS, E. N., Papakonstantinou, P. Ε., CHLOUVERAKIS, G. I., Kanoupakis, E. M., Mavrakis, H. E., Kallergis, E. M., Arkolaki, E. G., & Vardas, P. E. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.12.025 · Cited by 29
Detection of Subclinical Atrial Fibrillation in High-Risk Patients Using an Insertable Cardiac Monitor
Philippsen, T. J., Christensen, L. S., Hansen, M. G., Dahl, J. S., & Brandes, A. (2017) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2017.06.020 · Cited by 31
Effect of new-onset atrial fibrillation on cause-specific late mortality after coronary artery bypass grafting surgery†
Schwann, T. A., Al‐Shaar, L., Engoren, M., Bonnell, M. R., Goodwin, M. L., Schwann, A. N., & Habib, R. (2018) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezy028 · Cited by 28
Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial
Kronborg, M. B., Frausing, M. H. J. P., Malczynski, J., Riahi, S., Haarbo, J., Holm, K. F., Larroudé, C. E., Albertsen, A. E., Svendstrup, L., Hintze, U., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad564 · Cited by 28
“…significantly increased risk of thromboembolic events and identified as independent predictors of ischaemic stroke and clinical atrial fibrillation, 17 although a later study on the ASSERT population demonstrated that only episodes > 24 h were associated with an increased risk of stroke or…”
Background
Artificial intelligence–based electrocardiogram analysis improves atrial arrhythmia detection from a smartwatch electrocardiogram
Fiorina, L., Chemaly, P., Cellier, J., Saïd, M. A., Coquard, C., Younsi, S., Salerno, F., Horvilleur, J., Lacotte, J., Manenti, V., et al. (2024) · European Heart Journal - Digital Health · doi:10.1093/ehjdh/ztae047 · Cited by 31
“An early detection is essential to provide an appropriate treatment to reduce those risks and to manage associated comorbidities 2,4,5 and could enable the initiation of anticoagulation treatment.”
Background
Role of Atrial Fibrillation Burden in Assessing Thromboembolic Risk
ZIMETBAUM, P. J., Waks, J. W., Ellis, E. R., Glotzer, T. V., & PASSMAN, R. S. (2014) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.114.001356 · Cited by 28
Positionspapier „Schlafmedizin in der Kardiologie“
Oldenburg, O., Arzt, M. E., Bitter, T., Bonnemeier, H., Edelmann, F., Fietze, I., Podszus, T., Schäfer, T., Schöbel, C., Skobel, E. C., et al. (2015) · Der Kardiologe · doi:10.1007/s12181-015-0654-8 · Cited by 30
Physical Activity Measured by Implanted Devices Predicts Atrial Arrhythmias and Patient Outcome: Results of IMPLANTED (Italian Multicentre Observational Registry on Patients With Implantable Devices Remotely Monitored)
Palmisano, P., Guerra, F., Ammendola, E., Ziacchi, M., Pisanò, E., Dell’Era, G., Aspromonte, V., Zaccaria, M., Ubaldo, F. D., Capucci, A., et al. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.117.008146 · Cited by 28
“This cutoff was based on previous evidence, which defined 6-minute episodes as significantly associated with an increased risk of strokes and thromboembolic events.(16,17) Secondary end points were (1) time free from first AHRE ≥6 hours; (2) time free from first AHRE ≥48 hours; (3) time free from a predefined combined…”
Method
The role of cardiologists in stroke prevention and treatment: position paper of the European Society of Cardiology Council on Stroke
Widimský, P., Doehner, W., Diener, H., Gelder, I. C. V., Halliday, A. W., & Mazighi, M. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx478 · Cited by 28
Recomendaciones preventivas cardiovasculares. Actualización PAPPS 2018
Cuixart, C. B., Sánchez, J. J. A., Banegas, J. R., León, C. F., Lobos-Bejarano, J. M., Rioboó, E. M., Pérez, J. N., Orozco‐Beltrán, D., & Álvarez, F. V. (2018) · Atención Primaria · doi:10.1016/s0212-6567(18)30360-3 · Cited by 29
Atrial high-rate episodes and thromboembolism in patients without atrial fibrillation: The West Birmingham Atrial Fibrillation Project
Li, Y., Miyazawa, K., Pastori, D., Székely, O., Shahid, F., & Lip, G. Y. H. (2019) · International Journal of Cardiology · doi:10.1016/j.ijcard.2019.04.055 · Cited by 30
Atrial fibrillation burden during the coronavirus disease 2019 pandemic
O’Shea, C., Middeldorp, M. E., Thomas, G., Harper, C., Elliott, A. D., Ray, N., Campbell, K. R., Lau, D. H., & Sanders, P. (2021) · EP Europace · doi:10.1093/europace/euab099 · Cited by 31
“Device-detected AF is highly prevalent amongst patients with a cardiac implantable electronic device (CIED),(5) and infers a significant stroke risk.(6) Remote monitoring of CIEDs allows for the timely assessment of device-detected arrhythmic events.”
Background
Characteristics of patients with atrial high rate episodes detected by implanted defibrillator and resynchronization devices
Miyazawa, K., Pastori, D., Martin, D. T., Choucair, W. K., Halperin, J. L., Lip, G. Y. H., & the IMPACT Study Investigators (2021) · EP Europace · doi:10.1093/europace/euab186 · Cited by 28
“An increased risk of adverse outcomes such as ischaemic stroke or systemic embolismhas been associated with AHRE >5–6 min.(4) Whether AHRE have the same implications for antithrombotic prophylaxis as overt AF remains unclear.”
Background
Anticoagulation in heart failure: current status and future direction
Gheorghiade, M., Vaduganathan, M., Fonarow, G. C., Greene, S. J., Greenberg, B., Liu, P. P., Massie, B. M., Mehra, M. R., Metra, M., Zannad, F. M., et al. (2012) · Heart Failure Reviews · doi:10.1007/s10741-012-9343-x · Cited by 28
Risk of arterial and venous thromboembolism in patients with atrial fibrillation or flutter: A nationwide population-based cohort study
Sundbøll, J., Horváth–Puhó, E., Adelborg, K., Ording, A. G., Schmidt, M., Bøtker, H. E., & Sørensen, H. T. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.04.081 · Cited by 28
Silent Atrial Fibrillation: A Critical Review.
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What every clinician should know about Bayés syndrome
Bayés‐Genís, A., Martínez‐Sellés, M., Bayés‐Genís, A., Elosúa, R., & Baranchuk, A. M. (2020) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2020.04.026 · Cited by 28
Primary Aldosteronism: Cardiovascular Outcomes Pre- and Post-treatment
Hundemer, G. L. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1185-x · Cited by 27
Remote Patient Monitoring in Chronic Heart Failure
Palaniswamy, C., Mishkin, A. D., Aronow, W. S., Kalra, A., & Frishman, W. H. (2012) · Cardiology in Review · doi:10.1097/crd.0b013e318276198b · Cited by 26
Prevalence of atrial fibrillation in an urban population in India: the Nagpur pilot study
Saggu, D. K., Sundar, G., Nair, S. G., Bhargava, V., Lalukota, K., Chennapragada, S., Narasimhan, C., & Chugh, S. S. (2016) · Heart Asia · doi:10.1136/heartasia-2015-010674 · Cited by 28
Mechanical dyssynchrony of the left atrium during sinus rhythm is associated with history of stroke in patients with atrial fibrillation
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Remote monitoring of heart failure: benefits for therapeutic decision making
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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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