Cardiac electronic implanted devices (CIEDs) readily detect atrial high-rate episodes (AHREs), which are fairly common and associated with an increased incidence of clinical atrial fibrillation, stroke, and systemic thromboembolism
Up to 20% of automatically detected AHREs reflect something other than an atrial arrhythmia, and inspection of the atrial electrogram is required for verification
The absolute risk of stroke associated with AHRE detection is lower than in patients with clinical atrial fibrillation who have similar clinical risk factors for stroke
The temporal relationship between AHREs and stroke is poor in most patients with a CIED who develop a stroke
In ∼15% of patients with stroke and a high AHRE burden, a close temporal relationship exists between the AHREs and stroke, which declines after 5 days
Two large clinical trials of anticoagulant drugs in CIED-detected AHREs are ongoing; their outcomes will inform future management
Cardiac implanted electronic devices (CIEDs), including pacemakers and implantable defibrillators that perform atrial sensing typically using an atrial electrode, frequently detect subclinical atrial high-rate episodes (AHREs). When the intracardiac electrograms are carefully examined, the majority of AHREs are atrial fibrillation (AF) or other atrial tachyarrhythmias, which have been shown to be associated with both an increased risk of stroke, and subsequent development of clinical AF. However, the absolute risk of stroke among patients with AHREs is less than might be expected for clinically diagnosed paroxysmal AF. In addition, a close temporal relationship between AHREs and stroke is seen in only 15% of strokes in patients with a CIED: the majority have either no AHREs before the stroke, or AHREs very distant from incident stroke, suggesting that AHREs might be more of a risk marker than a risk factor for stroke. Management of AHREs should not be the same as for clinical AF, and a degree of uncertainty underpins the rationale for much-needed, ongoing, randomized trials of oral anticoagulation in patients with CIED-detected AHREs. We propose a management algorithm that takes into account both the stroke risk and the AHRE burden, but highlights the current uncertainty and evidence gaps for this condition.
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Mond, H. G., Sloman, J. G. & Edwards, R. H. The first pacemaker. Pacing Clin. Electrophysiol. 5, 278–282 (1982).
Lidwill, M. C. in Transactions of the Third Session, Australasian Medical Congress (British Medical Association), Sydney, September 2 to 7, 1929. 160 (Government Printer, 1930).
Altman, L. K. Arne H. W. Larsson, 86; had first internal pacemaker. New York Times http://www.nytimes.com/2002/01/18/world/arne-h-w-larsson-86-had-first-internal-pacemaker.html (2002).
Kirchhof, P. et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 37, 2893–2962 (2016).
Katritsis, D. G. C. et al. European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE). Europace 19, 465–511 (2017).
Healey, J. S. et al. Subclinical atrial fibrillation and the risk of stroke. N. Engl. J. Med. 366, 120–129 (2012).
Glotzer, T. V. et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ. Arrhythm. Electrophysiol. 2, 474–480 (2009).
Vanassche, T. et al. Risk of ischaemic stroke according to pattern of atrial fibrillation: analysis of 6563 aspirin-treated patients in ACTIVE-A and AVERROES. Eur. Heart J. 36, 281–287a (2015).
Daoud, E. G. et al. Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. Heart Rhythm 8, 1416–1423 (2011).
Brambatti, M. et al. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation 129, 2094–2099 (2014).
Kaufman, E. S. et al. Positive predictive value of device-detected atrial high-rate episodes at different rates and durations: an analysis from ASSERT. Heart Rhythm 9, 1241–1246 (2012).
Sanna, T. et al. Cryptogenic stroke and underlying atrial fibrillation. N. Engl. J. Med. 370, 2478–2486 (2014).
Nolker, G. et al. Performance of an implantable cardiac monitor to detect atrial fibrillation: results of the DETECT AF study. J. Cardiovasc. Electrophysiol. 27, 1403–1410 (2016).
Mittal, S. et al. Real-world performance of an enhanced atrial fibrillation detection algorithm in an insertable cardiac monitor. Heart Rhythm 13, 1624–1630 (2016).
Gladstone, D. J. et al. Atrial fibrillation in patients with cryptogenic stroke. N. Engl. J. Med. 370, 2467–2477 (2014).
Defaye, P., Dournaux, F. & Mouton, E. Prevalence of supraventricular arrhythmias from the automated analysis of data stored in the DDD pacemakers of 617 patients: the AIDA study. The AIDA Multicenter Study Group. Automatic interpretation for diagnosis assistance. Pacing Clin. Electrophysiol. 21, 250–255 (1998).
Gillis, A. M. & Morck, M. Atrial fibrillation after DDDR pacemaker implantation. J. Cardiovasc. Electrophysiol. 13, 542–547 (2002).
Glotzer, T. V. et al. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST). Circulation 107, 1614–1619 (2003).
Tse, H. F. & Lau, C. P. Prevalence and clinical implications of atrial fibrillation episodes detected by pacemaker in patients with sick sinus syndrome. Heart 91, 362–364 (2005).
Capucci, A. et al. Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. J. Am. Coll. Cardiol. 46, 1913–1920 (2005).
Orlov, M. V. et al. Asymptomatic atrial fibrillation in pacemaker recipients: incidence, progression, and determinants based on the atrial high rate trial. Pacing Clin. Electrophysiol. 30, 404–411 (2007).
Healey, J. S. et al. Pacemaker-detected atrial fibrillation in patients with pacemakers: prevalence, predictors, and current use of oral anticoagulation. Can. J. Cardiol. 29, 224–228 (2013).
Turakhia, M. P. et al. Atrial fibrillation burden and short-term risk of stroke: case-crossover analysis of continuously recorded heart rhythm from cardiac electronic implanted devices. Circ. Arrhythm. Electrophysiol. 8, 1040–1047 (2015).
Swiryn, S. et al. Clinical implications of brief device-detected atrial tachyarrhythmias in a cardiac rhythm management device population: results from the registry of atrial tachycardia and atrial fibrillation episodes. Circulation 134, 1130–1140 (2016).
Ziegler, P. D. et al. Incidence of newly detected atrial arrhythmias via implantable devices in patients with a history of thromboembolic events. Stroke 41, 256–260 (2010).
Ziegler, P. D. et al. Detection of previously undiagnosed atrial fibrillation in patients with stroke risk factors and usefulness of continuous monitoring in primary stroke prevention. Am. J. Cardiol. 110, 1309–1314 (2012).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT01694394 (2015).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT01727297 (2017).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT01461434 (2015).
US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT01851902 (2016).
Healey, J. et al. Prevalence of sub-clinical atrial fibrillation using an implantable cardiac monitor in patients with cardiovascular risk factors: ASSERT II. Circulation 134, e714 (2016).
Reiffel, J. A. et al. High incidence of previously unknown (“silent”) atrial fibrillation in patients at high risk for atrial fibrillation and stroke: primary results from the REVEAL AF study [abstract]. Heart Rhythm Scientific Sessions http://www.abstractsonline.com/pp8/#!/4227/presentation/12996 (2017).
Nasir, J. M. et al. PREdicting Determinants of Atrial fibrillation for Therapy Elucidation in patients at risk for thromboembolic events (PREDATE AF) study. Heart Rhythm http://dx.doi.org/10.1016/j.hrthm.2017.04.026 (2017).
Boriani, G. et al. Asymptomatic lone atrial fibrillation — how can we detect the arrhythmia? Curr. Pharm. Des. 21, 659–666 (2015).
Boriani, G. & Pettorelli, D. Atrial fibrillation burden and atrial fibrillation type: clinical significance and impact on the risk of stroke and decision making for long-term anticoagulation. Vascul. Pharmacol. 83, 26–35 (2016).
Freedman, B. et al. Screening for atrial fibrillation: a report of the AF-SCREEN International Collaboration. Circulation 135, 1851–1867 (2017).
Botto, G. L. et al. Presence and duration of atrial fibrillation detected by continuous monitoring: crucial implications for the risk of thromboembolic events. J. Cardiovasc. Electrophysiol. 20, 241–248 (2009).
Shanmugam, N. et al. Detection of atrial high-rate events by continuous home monitoring: clinical significance in the heart failure-cardiac resynchronization therapy population. Europace 14, 230–237 (2012).
Boriani, G. et al. Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices). Eur. Heart J. 35, 508–516 (2014).
Gonzalez, M. et al. Newly detected atrial high rate episodes predict long-term mortality outcomes in patients with permanent pacemakers. Heart Rhythm 11, 2214–2221 (2014).
Witt, C. T. et al. Early detection of atrial high rate episodes predicts atrial fibrillation and thromboembolic events in patients with cardiac resynchronization therapy. Heart Rhythm 12, 2368–2375 (2015).
Van Gelder, I. C. et al. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur. Heart J. 38, 1339–1344 (2017).
Boriani, G. et al. Improving stroke risk stratification using the CHADS2 and CHA2DS2-VASc risk scores in patients with paroxysmal atrial fibrillation by continuous arrhythmia burden monitoring. Stroke 42, 1768–1770 (2011).
Martin, D. T. et al. Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices. Eur. Heart J. 36, 1660–1668 (2015).
Quinn, G. R., Severdija, O. N., Chang, Y. & Singer, D. E. Wide variation in reported rates of stroke across cohorts of patients with atrial fibrillation. Circulation 135, 208–219 (2017).
Boriani, G. & Padeletti, L. Management of atrial fibrillation in bradyarrhythmias. Nat. Rev. Cardiol. 12, 337–349 (2015).
Slotwiner, D. et al. HRS expert consensus statement on remote interrogation and monitoring for cardiovascular implantable electronic devices. Heart Rhythm 12, e69–e100 (2015).
Wolf, P. A. et al. Duration of atrial fibrillation and imminence of stroke: the Framingham study. Stroke 14, 664–667 (1983).
Sherman, D. G. et al. Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study. Arch. Intern. Med. 165, 1185–1191 (2005).
Freedman, B., Potpara, T. S. & Lip, G. Y. Stroke prevention in atrial fibrillation. Lancet 388, 806–817 (2016).
Freedman, B., Martinez, C., Katholing, A. & Rietbrock, S. Residual risk of stroke and death in anticoagulant-treated patients with atrial fibrillation. JAMA Cardiol. 1, 366–368 (2016).
Camm, A. J. et al. Atrial high-rate episodes and stroke prevention. Europace 19, 169–179 (2017).
Watson, T., Shantsila, E. & Lip, G. Y. Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet 373, 155–166 (2009).
Kottkamp, H. Human atrial fibrillation substrate: towards a specific fibrotic atrial cardiomyopathy. Eur. Heart J. 34, 2731–2738 (2013).
Goette, A. et al. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Europace 18, 1455–1490 (2016).
Kamel, H., Okin, P. M., Elkind, M. S. & Iadecola, C. Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke 47, 895–900 (2016).
Steinberg, B. A. et al. Higher risk of death and stroke in patients with persistent versus paroxysmal atrial fibrillation: results from the ROCKET-AF Trial. Eur. Heart J. 36, 288–296 (2015).
Hohnloser, S. H. et al. The effects of apixaban on hospitalizations in patients with different types of atrial fibrillation: insights from the AVERROES trial. Eur. Heart J. 34, 2752–2759 (2013).
Hindricks, G. et al. Perception of atrial fibrillation before and after radiofrequency catheter ablation: relevance of asymptomatic arrhythmia recurrence. Circulation 112, 307–313 (2005).
Ganesan, A. N. et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur. Heart J. 37, 1591–1602 (2016).
Jorgensen, H. S., Nakayama, H., Reith, J., Raaschou, H. O. & Olsen, T. S. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 27, 1765–1769 (1996).
January, C. T. et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 130, 2071–2104 (2014).
Camm, A. J. et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur. Heart J. 37, 1145–1153 (2016).
Carmo, J., Moscoso Costa, F., Ferreira, J. & Mendes, M. Dabigatran in real-world atrial fibrillation. Meta-analysis of observational comparison studies with vitamin K antagonists. Thromb. Haemost. 116, 754–763 (2016).
Potpara, T. S. Dabigatran in 'real-world' clinical practice for stroke prevention in patients with non-valvular atrial fibrillation. Thromb. Haemost. 114, 1093–1098 (2015).
Lopes, R. D. et al. Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial. Am. Heart J. 189, 137–145 (2017).
Kirchhof, P. et al. Probing oral anticoagulation in patients with atrial high rate episodes: rationale and design of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6) trial. Am. Heart J. 190, 12–18 (2017).
Grond, M. et al. Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study. Stroke 44, 3357–3364 (2013).
Sposato, L. A. et al. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol. 14, 377–387 (2015).
Wachter, R. et al. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial. Lancet Neurol. 16, 282–290 (2017).
Tayal, A. H. et al. Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke. Neurology 71, 1696–1701 (2008).
Elijovich, L., Josephson, S. A., Fung, G. L. & Smith, W. S. Intermittent atrial fibrillation may account for a large proportion of otherwise cryptogenic stroke: a study of 30-day cardiac event monitors. J. Stroke Cerebrovasc. Dis. 18, 185–189 (2009).
Gaillard, N. et al. Detection of paroxysmal atrial fibrillation with transtelephonic EKG in TIA or stroke patients. Neurology 74, 1666–1670 (2010).
Bhatt, A. et al. Predictors of occult paroxysmal atrial fibrillation in cryptogenic strokes detected by long-term noninvasive cardiac monitoring. Stroke Res. Treat. 2011, 172074 (2011).
Flint, A. C., Banki, N. M., Ren, X., Rao, V. A. & Go, A. S. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke: the Stroke and Monitoring for PAF in Real Time (SMART) Registry. Stroke 43, 2788–2790 (2012).
Kamel, H. et al. Pilot randomized trial of outpatient cardiac monitoring after cryptogenic stroke. Stroke 44, 528–530 (2013).
Miller, D. J. et al. Outpatient cardiac telemetry detects a high rate of atrial fibrillation in cryptogenic stroke. J. Neurol. Sci. 324, 57–61 (2013).
Cotter, P. E. et al. Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology 80, 1546–1550 (2013).
Ritter, M. A. et al. Occult atrial fibrillation in cryptogenic stroke: detection by 7-day electrocardiogram versus implantable cardiac monitors. Stroke 44, 1449–1452 (2013).
Etgen, T., Hochreiter, M., Mundel, M. & Freudenberger, T. Insertable cardiac event recorder in detection of atrial fibrillation after cryptogenic stroke: an audit report. Stroke 44, 2007–2009 (2013).
Rojo-Martinez, E. et al. High performance of an implantable Holter monitor in the detection of concealed paroxysmal atrial fibrillation in patients with cryptogenic stroke and a suspected embolic mechanism [Spanish]. Rev. Neurol. 57, 251–257 (2013).
Christensen, L. M. et al. Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study. Eur. J. Neurol. 21, 884–889 (2014).
Brachmann, J. et al. Uncovering atrial fibrillation beyond short-term monitoring in cryptogenic stroke patients: three-year results from the Cryptogenic Stroke and Underlying Atrial Fibrillation Trial. Circ. Arrhythm. Electrophysiol. 9, e003333 (2016).
Haeusler, K. G. et al. Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): rationale and design of a prospective randomized multicenter study. Am. Heart J. 172, 19–25 (2016).
Frontera, A. et al. Demographic and clinical characteristics to predict paroxysmal atrial fibrillation: insights from an implantable loop recorder population. Pacing Clin. Electrophysiol. 38, 1217–1222 (2015).
Favilla, C. G. et al. Predictors of finding occult atrial fibrillation after cryptogenic stroke. Stroke 46, 1210–1215 (2015).
Thijs, V. N. et al. Predictors for atrial fibrillation detection after cryptogenic stroke: results from CRYSTAL AF. Neurology 86, 261–269 (2016).
Poli, S. et al. Insertable cardiac monitors after cryptogenic stroke — a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation. Eur. J. Neurol. 23, 375–381 (2016).
Cheung, J. W. et al. Newly detected atrial fibrillation following dual chamber pacemaker implantation. J. Cardiovasc. Electrophysiol. 17, 1323–1328 (2006).
Mittal, S. et al. Frequency, duration, and predictors of newly-diagnosed atrial fibrillation following dual-chamber pacemaker implantation in patients without a previous history of atrial fibrillation. Am. J. Cardiol. 102, 450–453 (2008).
Dion, F. et al. Unexpected low prevalence of atrial fibrillation in cryptogenic ischemic stroke: a prospective study. J. Interv. Card. Electrophysiol. 28, 101–107 (2010).
P.K. has received grants from several public funding bodies, including EU grant agreement No. 633196 (CATCH ME), British Heart Foundation (FS/13/43/30324), and Leducq Foundation.
B.F. declares that he has received speakers' fees and advisory board honoraria from Bayer Pharma AG, BMS/Pfizer, and Boehringer Ingelheim. G.B. declares that he has received honoraria (as speakers' fees) from Boston Scientific and Medtronic. T.V.G. declares that she has received a speaking honorarium from Medtronic. J.H. declares that he has received grants from Bayer, Boehringer Ingelheim, Bristol-Meyers-Squibb, and Medtronic. P.K. declares that he has received grants and personal fees from several industry companies involved in producing AF therapies (including Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Medtronic, Pfizer, and Servier); grants and personal fees from AFNET, ESC, and other professional societies and academic organizations; and has patents on 'AF therapy' and 'Markers for AF' pending to the University of Birmingham, UK. T.S.P. declares no competing interests.
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Freedman, B., Boriani, G., Glotzer, T. et al. Management of atrial high-rate episodes detected by cardiac implanted electronic devices. Nat Rev Cardiol 14, 701–714 (2017). https://doi.org/10.1038/nrcardio.2017.94
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