Risk Assessment of Stroke in Patients with Atrial Fibrillation: Current Shortcomings and Future Directions

  • Daniel A. HymanEmail author
  • Vincent Siebert
  • Xiaoming Jia
  • Mahboob Alam
  • Glenn N. Levine
  • Salim S. Virani
  • Yochai Birnbaum


Atrial fibrillation is a well-known risk factor for cardioembolic stroke; a number of risk stratification scoring systems have been developed to help differentiate which patients would stand to benefit from anticoagulation. However, these scoring systems cannot be utilized in patients whose atrial fibrillation has not been diagnosed. As implantable cardiac monitors become more prevalent, it becomes possible to identify occult, subclinical atrial fibrillation. With this data, it is also possible to examine the relationship between episodes of paroxysmal atrial fibrillation and thromboembolism and the total burden of paroxysmal atrial fibrillation and thromboembolic risk. The data gleaned from these devices provides insight and raises questions regarding the underlying mechanism of thromboembolism in atrial fibrillation, and in doing so, exposes shortcomings in the present clinical use of current risk scoring systems, specifically, the inability to account for atrial fibrillation burden and to apply scores at all in subclinical atrial fibrillation.


Atrial fibrillation Stroke risk stratification Sub-clinical atrial fibrillation 



  1. 1.
    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. Vasc Pharmacol. 2016;83:26–35.CrossRefGoogle Scholar
  2. 2.
    Jia X, Levine GN, Birnbaum Y. The CHA2DS2 -VASc score: not as simple as it seems. Int J Cardiol. 2018;257:92–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Camm AJ, Kirchhof P, Lip GYH, et al. Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369–429.CrossRefPubMedGoogle Scholar
  4. 4.
    Watson T, Shantsila E, Lip GYH. Mechanisms of thrombogenesis in atrial fibrillation: Virchow’s triad revisited. Lancet. 2009;373(9658):155–66.CrossRefPubMedGoogle Scholar
  5. 5.
    Lip GY. Does atrial fibrillation confer a hypercoagulable state? Lancet (London, England). 1995;346(8986):1313–4 Accessed 12 Dec 2018.CrossRefGoogle Scholar
  6. 6.
    Lau C-P, Siu C-W, Yiu K-H, Lee KL-F, Chan Y-H, Tse H-F. Subclinical atrial fibrillation and stroke: insights from continuous monitoring by implanted cardiac electronic devices. EP Europace. 2015;17(Suppl 2):ii40–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology. 1978;28(10):973–7 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  8. 8.
    Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. 1994;154(13):1449–57 Accessed 12 Dec 2018.
  9. 9.
    Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The stroke prevention in atrial fibrillation (SPAF) Investigators. Stroke. 1999;30(6):1223–9 Accessed 12 Dec 2018.CrossRefGoogle Scholar
  10. 10.
    Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D’Agostino RB, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham heart study. JAMA. 2003;290(8):1049–56.CrossRefPubMedGoogle Scholar
  11. 11.
    Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of atrial fibrillation. JAMA. 2001;285(22):2864–70 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  12. 12.
    Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263–72.CrossRefGoogle Scholar
  13. 13.
    Aspberg S, Chang Y, Atterman A, Bottai M, Go AS, Singer DE. Comparison of the ATRIA, CHADS2, and CHA2DS2-VASc stroke risk scores in predicting ischaemic stroke in a large Swedish cohort of patients with atrial fibrillation. Eur Heart J. 2016;37(42):3203–10.CrossRefPubMedGoogle Scholar
  14. 14.
    Hijazi Z, Lindbäck J, Alexander JH, Hanna M, Held C, Hylek EM, et al. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur Heart J. 2016;37(20):1582–90.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Group SR in AFW. Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke. 2008;39(6):1901–10.CrossRefGoogle Scholar
  16. 16.
    Fang MC, Go AS, Chang Y, Borowsky L, Pomernacki NK, Singer DE. Comparison of risk stratification schemes to predict thromboembolism in people with Nonvalvular atrial fibrillation. J Am Coll Cardiol. 2008;51(8):810–5.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Olesen JB, Lip GYH, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ. 2011;342:d124 Accessed 12 Dec 2018.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation. J Am Coll Cardiol. 2014;64(21):e1–e76.CrossRefPubMedGoogle Scholar
  19. 19.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–962.CrossRefGoogle Scholar
  20. 20.
    Szymanski FM, Lip GYH, Filipiak KJ, Platek AE, Hrynkiewicz-Szymanska A, Opolski G. Stroke risk factors beyond the CHA2DS2-VASc score: can we improve our identification of “high stroke risk” patients with atrial fibrillation? Am J Cardiol. 2015;116(11):1781–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, et al. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a randomized evaluation of long-term anticoagulation therapy (RE-LY) substudy. Circulation. 2012;125(13):1605–16.CrossRefPubMedGoogle Scholar
  22. 22.
    Zhao Y, Ji L, Liu J, Wu J, Wang Y, Shen S, et al. Intensity of left atrial spontaneous echo contrast as a correlate for stroke risk stratification in patients with nonvalvular atrial fibrillation. Sci Rep. 2016;6:27650.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Yaghi S, Moon YP, Mora-McLaughlin C, Willey JZ, Cheung K, di Tullio MR, et al. Left atrial enlargement and stroke recurrence: the northern Manhattan stroke study. Stroke. 2015;46(6):1488–93.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hijazi Z, Oldgren J, Siegbahn A, Granger CB, Wallentin L. Biomarkers in atrial fibrillation: a clinical review. Eur Heart J. 2013;34(20):1475–80.CrossRefPubMedGoogle Scholar
  25. 25.
    Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Hypertension. 2018;71(6):1269–324.CrossRefPubMedGoogle Scholar
  26. 26.
    Singer DE, Chang Y, Borowsky LH, et al. A new risk scheme to predict ischemic stroke and other thromboembolism in atrial fibrillation: the ATRIA Study Stroke Risk Score. J Am Hear Assoc Cardiovasc Cerebrovasc Dis. 2013;2(3).Google Scholar
  27. 27.
    van den Ham HA, Klungel OH, Singer DE, Leufkens HGM, van Staa TP. Comparative performance of ATRIA, CHADS2, and CHA2DS2-VASc risk scores predicting stroke in patients with atrial fibrillation: results from a National Primary Care Database. J Am Coll Cardiol. 2015;66(17):1851–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Hart RG, Pearce LA, Miller VT, Anderson DC, Rothrock JF, Albers GW, et al. Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies. Cerebrovasc Dis. 2000;10(1):39–43.CrossRefPubMedGoogle Scholar
  29. 29.
    Farmakis D, Parissis J, Filippatos G. Insights into onco-cardiology: atrial fibrillation in cancer. J Am Coll Cardiol. 2014;63(10):945–53.CrossRefPubMedGoogle Scholar
  30. 30.
    Sanfilippo AJ, Abascal VM, Sheehan M, Oertel LB, Harrigan P, Hughes RA, et al. Atrial enlargement as a consequence of atrial fibrillation. A prospective echocardiographic study. Circulation. 1990;82(3):792–7 Accessed 12 Dec 2018CrossRefPubMedGoogle Scholar
  31. 31.
    Black IW. Spontaneous echo contrast: where there’s smoke there’s fire. Echocardiography. 2000;17(4):373–82. Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  32. 32.
    Asinger RW, Koehler J, Pearce LA, Zabalgoitia M, Blackshear JL, Fenster PE, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: II. Dense spontaneous echocardiographic contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study). J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr. 1999;12(12):1088–96 Accessed 12 Dec 2018.CrossRefGoogle Scholar
  33. 33.
    Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Ann Intern Med. 1998;128(8):639–47 Accessed 12 Dec 2018.
  34. 34.
    Leung DY, Black IW, Cranney GB, Hopkins AP, Walsh WF. Prognostic implications of left atrial spontaneous echo contrast in nonvalvular atrial fibrillation. J Am Coll Cardiol. 1994;24(3):755–62 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  35. 35.
    Mügge A, Kühn H, Nikutta P, Grote J, Lopez JA, Daniel WG. Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: identification of a subgroup of patients at increased embolic risk. J Am Coll Cardiol. 1994;23(3):599–607 Accessed November 3, 2018.CrossRefPubMedGoogle Scholar
  36. 36.
    Bansal M, Kasliwal RR. Echocardiography for left atrial appendage structure and function. Indian Heart J. 2012;64(5):469–75.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lee JM, Shim J, Uhm J-S, Kim YJ, Lee HJ, Pak HN, et al. Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation. Am J Cardiol. 2014;113(6):963–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Di Tullio MR, Sacco RL, Sciacca RR, Homma S. Left atrial size and the risk of ischemic stroke in an ethnically mixed population. Stroke. 1999;30(10):2019–24 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  39. 39.
    Gupta DK, Shah AM, Giugliano RP, Ruff CT, Antman EM, Grip LT, et al. Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48. Eur Heart J. 2014;35(22):1457–65.CrossRefPubMedGoogle Scholar
  40. 40.
    Pollick C, Taylor D. Assessment of left atrial appendage function by transesophageal echocardiography. Implications for the development of thrombus. Circulation. 1991;84(1):223–31 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  41. 41.
    Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61(2):755–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Al-Saady N, Obel O, Camm A. Left atrial appendage: structure, function, and role in thromboembolism. Heart. 1999;82(5):547–54 Accessed 12 Dec 2018.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Masawa N, Yoshida Y, Yamada T, Joshita T, Ooneda G. Diagnosis of cardiac thrombosis in patients with atrial fibrillation in the absence of macroscopically visible thrombi. Virchows Arch A Pathol Anat Histopathol. 1993;422(1):67–71 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  44. 44.
    Boldt A, Wetzel U, Lauschke J, et al. Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease. Heart. 2004;90(4):400–5 Accessed 12 Dec 2018.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Goudis CA, Kallergis EM, Vardas PE. Extracellular matrix alterations in the atria: insights into the mechanisms and perpetuation of atrial fibrillation. EP Europace. 2012;14(5):623–30.CrossRefGoogle Scholar
  46. 46.
    Jalife J, Kaur K. Atrial remodeling, fibrosis, and atrial fibrillation. Trends Cardiovasc Med. 2015;25(6):475–84.CrossRefPubMedGoogle Scholar
  47. 47.
    Goette A, Kalman JM, Aguinaga L, Akar J, Cabrera JA, Chen SA, et al. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterisation, and clinical implication. J Arrhythmia. 2016;32(4):247–78.CrossRefGoogle Scholar
  48. 48.
    Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347(23):1834–40.CrossRefPubMedGoogle Scholar
  49. 49.
    Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825–33.CrossRefPubMedGoogle Scholar
  50. 50.
    Engelmann MDM, Svendsen JH. Inflammation in the genesis and perpetuation of atrial fibrillation. Eur Heart J. 2005;26(20):2083–92.CrossRefPubMedGoogle Scholar
  51. 51.
    Boos CJ, Anderson RA, Lip GYH. Is atrial fibrillation an inflammatory disorder? Eur Heart J. 2006;27(2):136–49.CrossRefPubMedGoogle Scholar
  52. 52.
    Conway DS, Buggins P, Hughes E, Lip GY. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J. 2004;148(3):462–6.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 2001;104(24):2886–91 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  54. 54.
    Lip GYH, Patel JV, Hughes E, Hart RG. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke. 2007;38(4):1229–37.CrossRefPubMedGoogle Scholar
  55. 55.
    Chung NAY, Belgore F, Li-Saw-Hee FL, Conway DSG, Blann AD, Lip GYH. Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor? Stroke. 2002;33(9):2187–91 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  56. 56.
    Morrissey JH. Tissue factor: an enzyme cofactor and a true receptor. Thromb Haemost. 2001;86(1):66–74 Accessed 12 Dec 2018.PubMedGoogle Scholar
  57. 57.
    Lijnen HR. Molecular interactions between the plasminogen/plasmin and matrix metalloproteinase systems. Fibrinolysis Proteol. 2000;14(2):175–81.CrossRefGoogle Scholar
  58. 58.
    Gramley F, Lorenzen J, Plisiene J, et al. Decreased plasminogen activator inhibitor and tissue metalloproteinase inhibitor expression may promote increased metalloproteinase activity with increasing duration of human atrial fibrillation. J Cardiovasc Electrophysiol. 2007;18(10):1076–82.CrossRefPubMedGoogle Scholar
  59. 59.
    Davis ME, Cai H, Drummond GR, Harrison DG. Shear stress regulates endothelial nitric oxide synthase expression through c-Src by divergent signaling pathways. Circ Res. 2001;89(11):1073–80 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  60. 60.
    Cai H, Li Z, Goette A, Mera F, Honeycutt C, Feterik K, et al. Downregulation of endocardial nitric oxide synthase expression and nitric oxide production in atrial fibrillation: potential mechanisms for atrial thrombosis and stroke. Circulation. 2002;106(22):2854–8 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  61. 61.
    Heppell RM, Berkin KE, McLenachan JM, Davies JA. Haemostatic and haemodynamic abnormalities associated with left atrial thrombosis in non-rheumatic atrial fibrillation. Heart. 1997;77(5):407–11.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Nakamura Y, Nakamura K, Fukushima-Kusano K, Ohta K, Matsubara H, Hamuro T, et al. Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis. Thromb Res. 2003;111(3):137–42 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  63. 63.
    Conway DSG, Heeringa J, Van Der Kuip DAM, et al. Atrial fibrillation and the prothrombotic state in the elderly: the Rotterdam Study. Stroke. 2003;34(2):413–7 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  64. 64.
    Conway DSG, Pearce LA, Chin BSP, Hart RG, Lip GYH. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation. 2003;107(25):3141–5.CrossRefPubMedGoogle Scholar
  65. 65.
    Lip GY, Lip PL, Zarifis J, et al. Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation. Effects of introducing ultra-low-dose warfarin and aspirin. Circulation. 1996;94(3):425–31 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  66. 66.
    Kamath S, Blann AD, Chin BSP, et al. A study of platelet activation in atrial fibrillation and the effects of antithrombotic therapy. Eur Heart J. 2002;23(22):1788–95 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  67. 67.
    Shinohara H, Fukuda N, Soeki T, et al. Relationship between flow dynamics in the left atrium and hemostatic abnormalities in patients with nonvalvular atrial fibrillation. Jpn Heart J. 1998;39(6):721–30 Accessed 12 Dec 2018.CrossRefPubMedGoogle Scholar
  68. 68.
    Stroke prevention in Atrial Fibrillation Study. Final results. Circulation. 1991;84(2):527–39 Accessed 12 Dec 2018.
  69. 69.
    Investigators AWG of the A, Connolly S, Pogue J, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet (London, England). 2006;367(9526):1903–12.CrossRefGoogle Scholar
  70. 70.
    Habara S, Dote K, Kato M, Sasaki S, Goto K, Takemoto H, et al. Prediction of left atrial appendage thrombi in non-valvular atrial fibrillation. Eur Heart J. 2007;28(18):2217–22.CrossRefPubMedGoogle Scholar
  71. 71.
    Turgut N, Akdemir O, Turgut B, Demir M, Ekuklu G, Vural Ö, et al. Hypercoagulopathy in stroke patients with nonvalvular atrial fibrillation: hematologic and cardiologic investigations. Clin Appl Thromb Off J Int Acad Clin Appl Thromb. 2006;12(1):15–20 Accessed 12 Dec 2018.CrossRefGoogle Scholar
  72. 72.
    January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):e199–267.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Israel CW, Neubauer H, Olbrich H-G, et al. Incidence of atrial tachyarrhythmias in pacemaker patients: results from the Balanced Evaluation of Atrial Tachyarrhythmias in Stimulated patients (BEATS) study. Pacing Clin Electrophysiol. 2006;29(6):582–8.CrossRefPubMedGoogle Scholar
  74. 74.
    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. 1998;21(1 Pt 2):250–5 Accessed September 29, 2018.CrossRefPubMedGoogle Scholar
  75. 75.
    Camm AJ, Corbucci G, Padeletti L. Usefulness of continuous electrocardiographic monitoring for atrial fibrillation. Am J Cardiol. 2012;110(2):270–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Quirino G, Giammaria M, Corbucci G, Pistelli P, Turri E, Mazza A, et al. Diagnosis of paroxysmal atrial fibrillation in patients with implanted pacemakers: relationship to symptoms and other variables. Pacing Clin Electrophysiol. 2009;32(1):91–8.CrossRefPubMedGoogle Scholar
  77. 77.
    Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak R, 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. 2003;107(12):1614–9.CrossRefPubMedGoogle Scholar
  78. 78.
    Ziegler PD, Koehler JL, Mehra R. Comparison of continuous versus intermittent monitoring of atrial arrhythmias. Heart Rhythm. 2006;3(12):1445–52.CrossRefPubMedGoogle Scholar
  79. 79.
    Hanke T, Charitos EI, Stierle U, et al. Twenty-four-hour Holter monitor follow-up does not provide accurate heart rhythm status after surgical atrial fibrillation ablation therapy: up to 12 months experience with a novel permanently implantable heart rhythm monitor device. Circulation. 2009;120(11_suppl_1):S177–84.CrossRefPubMedGoogle Scholar
  80. 80.
    Botto GL, Padeletti L, Santini M, et al. Presence and duration of atrial fibrillation detected by continuous monitoring: crucial implications for the risk of thromboembolic events. J Cardiovasc Electrophysiol. 2009;20(3):241–8.CrossRefPubMedGoogle Scholar
  81. 81.
    Wachter R, Gröschel K, Gelbrich G, Hamann GF, Kermer P, Liman J, et al. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AF RANDOMISED ): an open-label randomised controlled trial. Lancet Neurol. 2017;16(4):282–90.CrossRefPubMedGoogle Scholar
  82. 82.
    Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370(26):2467–77.CrossRefPubMedGoogle Scholar
  83. 83.
    Lowres N, Neubeck L, Salkeld G, Krass I, McLachlan AJ, Redfern J, et al. Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. Thromb Haemost. 2014;111(06):1167–76.CrossRefPubMedGoogle Scholar
  84. 84.
    Smartphone ECG Can Spot AF in Acute Stroke, Add to Holter Data. Medscape.Google Scholar
  85. 85.
    Halcox JPJ, Wareham K, Cardew A, Gilmore M, Barry JP, Phillips C, et al. Assessment of remote heart rhythm sampling using the AliveCor heart monitor to screen for atrial fibrillation. Circulation. 2017;136(19):1784–94.CrossRefPubMedGoogle Scholar
  86. 86.
    Healey JS, Connolly SJ, Gold MR, Israel CW, van Gelder IC, Capucci A, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120–9.CrossRefPubMedGoogle Scholar
  87. 87.
    Healey JS, Alings M, Ha A, Leong-Sit P, Birnie DH, de Graaf JJ, et al. Subclinical atrial fibrillation in older patients. Circulation. 2017;136(14):1276–83.CrossRefPubMedGoogle Scholar
  88. 88.
    Purerfellner H, Gillis AM, Holbrook R, Hettrick DA. Accuracy of atrial tachyarrhythmia detection in implantable devices with arrhythmia therapies. Pacing Clin Electrophysiol. 2004;27(7):983–92.CrossRefPubMedGoogle Scholar
  89. 89.
    Silveira I, Sousa MJ, Antunes N, et al. Efficacy and safety of implantable loop recorder: experience of a center. J Atr Fibrillation. 2016;9(2):1425.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Sanna T, Diener H-C, Passman RS, di Lazzaro V, Bernstein RA, Morillo CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370(26):2478–86.CrossRefPubMedGoogle Scholar
  91. 91.
    Brachmann J, Morillo CA, Sanna T, et al. Uncovering atrial fibrillation beyond short-term monitoring in cryptogenic stroke patients. Circ Arrhythm Electrophysiol. 2016;9(1).Google Scholar
  92. 92.
    Ziegler PD, Rogers JD, Ferreira SW, Nichols AJ, Sarkar S, Koehler JL, et al. Real-world experience with Insertable cardiac monitors to find atrial fibrillation in cryptogenic stroke. Cerebrovasc Dis. 2015;40(3–4):175–81.CrossRefPubMedGoogle Scholar
  93. 93.
    Ziegler PD, Rogers JD, Ferreira SW, Nichols AJ, Richards M, Koehler JL, et al. Long-term detection of atrial fibrillation with insertable cardiac monitors in a real-world cryptogenic stroke population. Int J Cardiol. 2017;244:175–9.CrossRefPubMedGoogle Scholar
  94. 94.
    Christensen LM, Krieger DW, Højberg S, Pedersen OD, Karlsen FM, Jacobsen MD, et al. Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study. Eur J Neurol. 2014;21(6):884–9.CrossRefPubMedGoogle Scholar
  95. 95.
    Israel C, Kitsiou A, Kalyani M, Deelawar S, Ejangue LE, Rogalewski A, et al. Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders. Thromb Haemost. 2017;117(10):1962–9.CrossRefPubMedGoogle Scholar
  96. 96.
    Katz JM, Eng MS, Carrazco C, Patel AV, Jadonath R, Gribko M, et al. Occult paroxysmal atrial fibrillation in non-cryptogenic ischemic stroke. J Neurol. 2018;265(10):2237–42.CrossRefPubMedGoogle Scholar
  97. 97.
    Glotzer TV, Daoud EG, Wyse DG, Singer DE, Ezekowitz MD, Hilker C, et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk. Circ Arrhythm Electrophysiol. 2009;2(5):474–80.CrossRefPubMedGoogle Scholar
  98. 98.
    Kirchhof P, Blank BF, Calvert M, Camm AJ, Chlouverakis G, Diener HC, 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. 2017;190:12–8.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Lopes RD, Alings M, Connolly SJ, Beresh H, Granger CB, Mazuecos JB, 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. 2017;189:137–45.CrossRefPubMedGoogle Scholar
  100. 100.
    Daoud EG, Glotzer TV, Wyse DG, Ezekowitz MD, Hilker C, Koehler J, et al. Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. Heart Rhythm. 2011;8(9):1416–23.CrossRefPubMedGoogle Scholar
  101. 101.
    Brambatti M, Connolly SJ, Gold MR, Morillo CA, Capucci A, Muto C, et al. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation. 2014;129(21):2094–9.CrossRefPubMedGoogle Scholar
  102. 102.
    Martin DT, Bersohn MM, Waldo AL, Wathen MS, Choucair WK, Lip GYH, et al. Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices. Eur Heart J. 2015;36(26):1660–8.CrossRefPubMedGoogle Scholar
  103. 103.
    Turakhia MP, Ziegler PD, Schmitt SK, Chang Y, Fan J, Than CT, et al. Atrial fibrillation burden and short-term risk of stroke. Circ Arrhythm Electrophysiol. 2015;8(5):1040–7.CrossRefPubMedGoogle Scholar
  104. 104.
    Graves KG, Jacobs V, May HT, Cutler MJ, Day JD, Bunch TJ. Atrial fibrillation ablation and its impact on stroke. Curr Treat Options Cardiovasc Med. 2018;20(1):2.CrossRefPubMedGoogle Scholar
  105. 105.
    Friberg L, Tabrizi F, Englund A. Catheter ablation for atrial fibrillation is associated with lower incidence of stroke and death: data from Swedish health registries. Eur Heart J. 2016;37(31):2478–87.CrossRefPubMedGoogle Scholar
  106. 106.
    Nielsen JC, Gerdes JC. Does catheter ablation reduce mortality and stroke in patients with atrial fibrillation? Patient selection or causality? Eur Heart J. 2016;37(31):2488–9.CrossRefPubMedGoogle Scholar
  107. 107.
    Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Hear Rhythm. 2017;14(10):e275–444.Google Scholar
  108. 108.
    Hagens VE, Van Gelder IC, Crijns HJGM. RAte control versus electrical cardioversion of persistent atrial fibrillation (RACE) study group. The RACE study in perspective of randomized studies on management of persistent atrial fibrillation. Card Electrophysiol Rev. 2003;7(2):118–21 Accessed October 30, 2018.CrossRefPubMedGoogle Scholar
  109. 109.
    Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation. Circulation. 2004;110(9):1042–6.CrossRefPubMedGoogle Scholar
  110. 110.
    Heeringa J, van der Kuip DAM, Hofman A, Kors JA, van Herpen G, Stricker BHC, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27(8):949–53.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MedicineBaylor College of MedicineHoustonUSA
  2. 2.Section of Cardiology, Department of MedicineBaylor College of MedicineHoustonUSA
  3. 3.Michael E. Debakey VA Medical CenterHoustonUSA

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