Atrial Premature Beats Predict Atrial Fibrillation in Cryptogenic Stroke: Results From the EMBRACE Trial

Background and Purpose— Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation (AF). We sought to identify those most likely to have subclinical AF. Methods— We prospectively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm, without known AF, enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) trial. Participants underwent baseline 24-hour Holter ECG poststroke; if AF was not detected, they were randomly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder. Multivariable logistic regression assessed the association between baseline variables (Holter-detected atrial premature beats [APBs], runs of atrial tachycardia, age, and left atrial enlargement) and subsequent AF detection. Results— Among 237 participants, the median baseline Holter APB count/24 h was 629 (interquartile range, 142–1973) among those who subsequently had AF detected versus 45 (interquartile range, 14–250) in those without AF (P<0.001). APB count was the only significant predictor of AF detection by 30-day ECG (P<0.0001), and at 90 days (P=0.0017) and 2 years (P=0.0027). Compared with the 16% overall 90-day AF detection rate, the probability of AF increased from <9% among patients with <100 APBs/24 h to 9% to 24% in those with 100 to 499 APBs/24 h, 25% to 37% with 500 to 999 APBs/24 h, 37% to 40% with 1000 to 1499 APBs/24 h, and 40% beyond 1500 APBs/24 h. Conclusions— Among older cryptogenic stroke or transient ischemic attack patients, the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent subclinical AF. Those with frequent APBs have a high probability of AF and represent ideal candidates for prolonged ECG monitoring for AF detection. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00846924.

David J. Gladstone | Muhammad Mamdani | S. Abootalebi | Melanie Spring | Paul Dorian | G. Saposnik | P. Christie | S. Verreault | A. Laupacis | P. Barber | J. Healey | D. Gladstone | G. Valencia | V. Hachinski | M. O’Donnell | M. Wright | M. Mamdani | D. Crisp | J. Spence | G. Klein | G. Saposnik | R. Cote | L. Durcan | M. Hill | K. Thorpe | D. Hackam | B. Menon | A. Woolfenden | D. Sahlas | G. Stotts | R. Aviv | S. Coutts | J. Ween | J. Blakely | P. Dorian | A. Haché | S. Verreault | A. Dhanani | D. Selchen | A. Shuaib | P. Teal | C. Jaigobin | M. Levitan | J. Minuk | Val Panzov | Jeff S. Healey | Kevin E. Thorpe | R. Aviv | K. Boyle | J. Blakely | R. Cote | J. Hall | M.K. Kapral | N. Kozlowski | A. Laupacis | M. O’Donnell | K. Sabihuddin | M. Sharma | A. Shuaib | H. Vaid | A. Pinter | R. Chan | S. Crann | L. Fleming | C. Frank | V. Hachinski | K. Hesser | B.S. Kumar | P. Soros | M. Wright | V. Basile | J. Hopyan | Y. Rajmohan | R. Swartz | G. Valencia | J. Ween | H. Aram | P.A. Barber | S. Coutts | A.M. Demchuk | K. Fischer | M.D. Hill | G. Klein | C. Kenney | B. Menon | M. McClelland | A. Russell | K. Ryckborst | P. Stys | E.E. Smith | T.W. Watson | S. Chacko | D. Sahlas | J. Sancan | R. Côté | L. Durcan | E. Ehrensperger | J. Minuk | T. Wein | L. Wadup | N. Asdaghi | J. Beckman | N. Esplana | P. Masigan | C. Murphy | E. Tang | P. Teal | K. Villaluna | A. Woolfenden | S. Yip | M. Bussière | D. Dowlatshahi | G. Stotts | S. Robert | K. Ford | D. Hackam | L. Miners | T. Mabb | J. D. Spence | B. Buck | T. Griffin-Stead | R. Jassal | M. Siddiqui | A. Hache | C. Lessard | F. Lebel | A. Mackey | C. Astorga | LK Casaubon | M. del Campo | C. Jaigobin | L. Kalman | FL Silver | L. Atkins | K. Coles | A. Penn | R. Sargent | C. Walter | Y. Gable | N. Kadribasic | B. Schwindt | P. Kostyrko | D. Selchen | A. Jin | D. Hicklin | D. Howse | E. Edwards | S. Jaspers | F. Sher | S. Stoger | D. Crisp | A. Dhanani | V. John | M. Levitan | M. Mehdiratta | D. Wong | P. Soros | P. Christie | T. Wein | B. Schwindt | K. Villaluna | Y. Rajmohan | E.E. Smith | M. Bussiére | M. Kapral | A. Jin | A. Pintér | M. Sharma | S. Jaspers | A. Mackey | F. Silver | Melanie Spring | Val Panzov | H. Vaid | S. Yip | A. Penn | D. Howse | M. Mehdiratta | K. Boyle | S. Crann | B. Kumar | A. Demchuk | K. Ryckborst | D. Dowlatshahi | C. Kenney | H. Aram | T. Watson | M. Siddiqui | L. Kalman | L. Casaubon | S. Robert | L. Fleming | K. Hesser | R. Chan | R. Swartz | J. Hopyan | P. Kostyrko | N. Asdaghi | R. Sargent | J. Beckman | D. Wong | L. Wadup | M. McClelland | F. Sher | C. Murphy | K. Fischer | S. Chacko | B. Buck | A. Russell | F. Lebel | C. Frank | E. Ehrensperger | C. Astorga | E. Tang | S. Abootalebi | L. Miners | J. Hall | N. Kozlowski | K. Sabihuddin | V. Basile | P. Stys | J. Sancan | N. Esplana | P. Masigan | K. Ford | T. Mabb | T. Griffin-Stead | R. Jassal | C. Lessard | M. del Campo | L. Atkins | K. Coles | C. Walter | Y. Gable | N. Kadribašić | D. Hicklin | E. Edwards | S. Stoger | V. John

[1]  Eleanor Rivoire,et al.  Kingston General Hospital , 2016 .

[2]  W. Stevenson,et al.  Predicting atrial fibrillation: can we shape the future? , 2015, European heart journal.

[3]  K. Aonuma,et al.  Prognostic impact of supraventricular premature complexes in community-based health checkups: the Ibaraki Prefectural Health Study. , 2015, European heart journal.

[4]  J. Healey,et al.  2014 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation. , 2014, The Canadian journal of cardiology.

[5]  J. Healey,et al.  Perioperative atrial fibrillation and the long-term risk of ischemic stroke. , 2014, JAMA.

[6]  Frank Beckers,et al.  Cryptogenic stroke and underlying atrial fibrillation. , 2014, The New England journal of medicine.

[7]  David J Gladstone,et al.  Atrial fibrillation in patients with cryptogenic stroke. , 2014, The New England journal of medicine.

[8]  C. Martinez,et al.  Adverse prognosis of incidentally detected ambulatory atrial fibrillation , 2014, Thrombosis and Haemostasis.

[9]  A. Capucci,et al.  Temporal Relationship Between Subclinical Atrial Fibrillation and Embolic Events , 2014, Circulation.

[10]  L. Wilkins Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation: Report of the Guideline Development Subcommittee of the American Academy of Neurology , 2014, Neurology.

[11]  S. Connolly,et al.  Embolic strokes of undetermined source: the case for a new clinical construct , 2014, The Lancet Neurology.

[12]  L. Eckardt,et al.  Supraventricular Premature Beats and Short Atrial Runs Predict Atrial Fibrillation in Continuously Monitored Patients With Cryptogenic Stroke , 2014, Stroke.

[13]  B. Hoit,et al.  Left atrial size and function: role in prognosis. , 2014, Journal of the American College of Cardiology.

[14]  Kennedy R. Lees,et al.  Detection of Atrial Fibrillation After Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis , 2014, Stroke.

[15]  V. Chair,et al.  Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. , 2014, Stroke.

[16]  E. Vittinghoff,et al.  Atrial Ectopy as a Predictor of Incident Atrial Fibrillation , 2013, Annals of Internal Medicine.

[17]  P. Zimetbaum,et al.  Ectopy and Expectations: Can We Predict Atrial Fibrillation, and Should We Try? , 2013, Annals of Internal Medicine.

[18]  T. Ohkubo,et al.  Long-Term Outcome of Healthy Participants with Atrial Premature Complex: A 15-Year Follow-Up of the NIPPON DATA 90 Cohort , 2013, PloS one.

[19]  P. Macfarlane,et al.  Noninvasive Cardiac Event Monitoring to Detect Atrial Fibrillation After Ischemic Stroke: A Randomized, Controlled Trial , 2013, Stroke.

[20]  T. Glotzer,et al.  Silent atrial fibrillation as a stroke risk factor and anticoagulation indication. , 2013, The Canadian journal of cardiology.

[21]  R. Wachter,et al.  Excessive Supraventricular Ectopic Activity Is Indicative of Paroxysmal Atrial Fibrillation in Patients with Cerebral Ischemia , 2013, PloS one.

[22]  T. Uejima,et al.  Usefulness of frequent supraventricular extrasystoles and a high CHADS2 score to predict first-time appearance of atrial fibrillation. , 2013, The American journal of cardiology.

[23]  Age-dependent yield of screening for undetected atrial fibrillation in stroke patients: the Find-AF study , 2013, Journal of Neurology.

[24]  Martin Adam,et al.  Premature Atrial Contractions in the General Population: Frequency and Risk Factors , 2012, Circulation.

[25]  Hung-Fat Tse,et al.  Frequent premature atrial complexes predict new occurrence of atrial fibrillation and adverse cardiovascular events. , 2012, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[26]  A. Capucci,et al.  Subclinical atrial fibrillation and the risk of stroke. , 2012, The New England journal of medicine.

[27]  Christopher E Hilker,et al.  Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. , 2011, Heart rhythm.

[28]  Raymond C S Seet,et al.  Prolonged Rhythm Monitoring for the Detection of Occult Paroxysmal Atrial Fibrillation in Ischemic Stroke of Unknown Cause , 2011, Circulation.

[29]  R Frank,et al.  Detection of paroxysmal atrial fibrillation with transtelephonic EKG in TIA or stroke patients , 2010, Neurology.

[30]  L. Køber,et al.  Excessive Supraventricular Ectopic Activity and Increased Risk of Atrial Fibrillation and Stroke , 2010, Circulation.

[31]  MBq 30mCi,et al.  University Health Network, , 2010 .

[32]  H. Mattle,et al.  Frequent Atrial Premature Beats Predict Paroxysmal Atrial Fibrillation in Stroke Patients: An Opportunity for a New Diagnostic Strategy , 2007, Stroke.

[33]  A. Sanabria,et al.  Randomized controlled trial. , 2005, World journal of surgery.

[34]  N. Kucher,et al.  Frequent atrial premature contractions as a surrogate marker for paroxysmal atrial fibrillation in patients with acute ischaemic stroke , 2003, Heart.

[35]  G. Lamas,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) , 2003, Circulation.

[36]  J B Seward,et al.  Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women. , 2001, Mayo Clinic proceedings.

[37]  B. Hedblad,et al.  Cardiac Arrhythmias and Stroke: Increased Risk in Men With High Frequency of Atrial Ectopic Beats , 2000, Stroke.