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Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults

Steven R Messé, MD
Naser M Ammash, MD
Section Editors
Scott E Kasner, MD
Heidi M Connolly, MD, FASE
Deputy Editors
John F Dashe, MD, PhD
Susan B Yeon, MD, JD, FACC


Stroke can be associated with abnormalities of the atrial septum, specifically patent foramen ovale (PFO), atrial septal defect (ASD), and atrial septal aneurysm (ASA).

The relationship between PFO, ASD, or ASA and ischemic neurologic complications will be reviewed here. Treatment is reviewed separately. (See "Treatment of patent foramen ovale (PFO) for secondary stroke prevention".)


The foramen ovale and its flap-like valve between the right and left atrium are important components of the fetal circulation. In the developing fetus, oxygenated blood from the umbilical vein enters the right atrium via the inferior vena cava and is shunted into the left atrium, circumventing the noninflated lungs. After birth, a relative increase in left atrial pressure closes the flap, and adhesions frequently result in a structurally intact atrial septum. However, in approximately 25 percent of adults, the foramen ovale remains patent and acts as a potential interatrial shunt (movie 1 and movie 2). (See "Patent foramen ovale".)

Less commonly, an open communication called an atrial septal defect (ASD) persists between the atria after septation. The majority of these are secundum ASD defects caused by deficiency in the septum primum. This may be visualized on transthoracic (movie 3 and movie 4) or transesophageal echocardiography (movie 5).

The pathophysiology and clinical features of PFOs and atrial septal defects are discussed in detail separately. (See "Clinical manifestations and diagnosis of atrial septal defects in adults", section on 'Classification' and "Clinical manifestations and diagnosis of atrial septal defects in adults", section on 'Embryology'.)

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Literature review current through: Dec 2017. | This topic last updated: Dec 15, 2017.
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  1. Cardiogenic brain embolism. Cerebral Embolism Task Force. Arch Neurol 1986; 43:71.
  2. CORRIN B. PARADOXICAL EMBOLISM. Br Heart J 1964; 26:549.
  3. Lamy C, Giannesini C, Zuber M, et al. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: the PFO-ASA Study. Atrial Septal Aneurysm. Stroke 2002; 33:706.
  4. Khositseth A, Cabalka AK, Sweeney JP, et al. Transcatheter Amplatzer device closure of atrial septal defect and patent foramen ovale in patients with presumed paradoxical embolism. Mayo Clin Proc 2004; 79:35.
  5. Kerut EK, Norfleet WT, Plotnick GD, Giles TD. Patent foramen ovale: a review of associated conditions and the impact of physiological size. J Am Coll Cardiol 2001; 38:613.
  6. Harvey JR, Teague SM, Anderson JL, et al. Clinically silent atrial septal defects with evidence for cerebral embolization. Ann Intern Med 1986; 105:695.
  7. Caes FL, Van Belleghem YV, Missault LH, et al. Surgical treatment of impending paradoxical embolism through patent foramen ovale. Ann Thorac Surg 1995; 59:1559.
  8. Falk V, Walther T, Krankenberg H, Mohr FW. Trapped thrombus in a patent foramen ovale. Thorac Cardiovasc Surg 1997; 45:90.
  9. Meacham RR 3rd, Headley AS, Bronze MS, et al. Impending paradoxical embolism. Arch Intern Med 1998; 158:438.
  10. Supple GE, Ren JF, Zado ES, Marchlinski FE. Mobile thrombus on device leads in patients undergoing ablation: identification, incidence, location, and association with increased pulmonary artery systolic pressure. Circulation 2011; 124:772.
  11. DeSimone CV, DeSimone DC, Patel NA, et al. Implantable cardiac devices with patent foramen ovale--a risk factor for cardioembolic stroke? J Interv Card Electrophysiol 2012; 35:159.
  12. DeSimone CV, DeSimone DC, Hagler DJ, et al. Cardioembolic stroke in patients with patent foramen ovale and implanted cardiac leads. Pacing Clin Electrophysiol 2013; 36:50.
  13. DeSimone CV, Friedman PA, Noheria A, et al. Stroke or transient ischemic attack in patients with transvenous pacemaker or defibrillator and echocardiographically detected patent foramen ovale. Circulation 2013; 128:1433.
  14. Langholz D, Louie EK, Konstadt SN, et al. Transesophageal echocardiographic demonstration of distinct mechanisms for right to left shunting across a patent foramen ovale in the absence of pulmonary hypertension. J Am Coll Cardiol 1991; 18:1112.
  15. Meissner I, Whisnant JP, Khandheria BK, et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study. Stroke Prevention: Assessment of Risk in a Community. Mayo Clin Proc 1999; 74:862.
  16. Pearson AC, Nagelhout D, Castello R, et al. Atrial septal aneurysm and stroke: a transesophageal echocardiographic study. J Am Coll Cardiol 1991; 18:1223.
  17. Cabanes L, Mas JL, Cohen A, et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography. Stroke 1993; 24:1865.
  18. Belkin RN, Kisslo J. Atrial septal aneurysm: recognition and clinical relevance. Am Heart J 1990; 120:948.
  19. Mügge A, Daniel WG, Angermann C, et al. Atrial septal aneurysm in adult patients. A multicenter study using transthoracic and transesophageal echocardiography. Circulation 1995; 91:2785.
  20. Silver MD, Dorsey JS. Aneurysms of the septum primum in adults. Arch Pathol Lab Med 1978; 102:62.
  21. Hanley PC, Tajik AJ, Hynes JK, et al. Diagnosis and classification of atrial septal aneurysm by two-dimensional echocardiography: report of 80 consecutive cases. J Am Coll Cardiol 1985; 6:1370.
  22. Olivares-Reyes A, Chan S, Lazar EJ, et al. Atrial septal aneurysm: a new classification in two hundred five adults. J Am Soc Echocardiogr 1997; 10:644.
  23. Agmon Y, Khandheria BK, Meissner I, et al. Frequency of atrial septal aneurysms in patients with cerebral ischemic events. Circulation 1999; 99:1942.
  24. Burger AJ, Sherman HB, Charlamb MJ. Low incidence of embolic strokes with atrial septal aneurysms: A prospective, long-term study. Am Heart J 2000; 139:149.
  25. Mattioli AV, Aquilina M, Oldani A, et al. Atrial septal aneurysm as a cardioembolic source in adult patients with stroke and normal carotid arteries. A multicentre study. Eur Heart J 2001; 22:261.
  26. Ewert P, Berger F, Vogel M, et al. Morphology of perforated atrial septal aneurysm suitable for closure by transcatheter device placement. Heart 2000; 84:327.
  27. Djaiani G, Phillips-Bute B, Podgoreanu M, et al. The association of patent foramen ovale and atrial fibrillation after coronary artery bypass graft surgery. Anesth Analg 2004; 98:585.
  28. Ilercil A, Meisner JS, Vijayaraman P, et al. Clinical significance of fossa ovalis membrane aneurysm in adults with cardioembolic cerebral ischemia. Am J Cardiol 1997; 80:96.
  29. Webster MW, Chancellor AM, Smith HJ, et al. Patent foramen ovale in young stroke patients. Lancet 1988; 2:11.
  30. Lechat P, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988; 318:1148.
  31. Di Tullio M, Sacco RL, Gopal A, et al. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992; 117:461.
  32. Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 2000; 55:1172.
  33. Handke M, Harloff A, Olschewski M, et al. Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 2007; 357:2262.
  34. Alsheikh-Ali AA, Thaler DE, Kent DM. Patent foramen ovale in cryptogenic stroke: incidental or pathogenic? Stroke 2009; 40:2349.
  35. Wu LA, Malouf JF, Dearani JA, et al. Patent foramen ovale in cryptogenic stroke: current understanding and management options. Arch Intern Med 2004; 164:950.
  36. Dearani JA, Ugurlu BS, Danielson GK, et al. Surgical patent foramen ovale closure for prevention of paradoxical embolism-related cerebrovascular ischemic events. Circulation 1999; 100:II171.
  37. Bogousslavsky J, Garazi S, Jeanrenaud X, et al. Stroke recurrence in patients with patent foramen ovale: the Lausanne Study. Lausanne Stroke with Paradoxal Embolism Study Group. Neurology 1996; 46:1301.
  38. Pezzini A, Grassi M, Zotto ED, et al. Do common prothrombotic mutations influence the risk of cerebral ischaemia in patients with patent foramen ovale? Systematic review and meta-analysis. Thromb Haemost 2009; 101:813.
  39. Kitsios GD, Lasker A, Singh J, Thaler DE. Recurrent stroke on imaging and presumed paradoxical embolism: a cross-sectional analysis. Neurology 2012; 78:993.
  40. Schuchlenz HW, Weihs W, Horner S, Quehenberger F. The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events. Am J Med 2000; 109:456.
  41. Homma S, Di Tullio MR, Sacco RL, et al. Characteristics of patent foramen ovale associated with cryptogenic stroke. A biplane transesophageal echocardiographic study. Stroke 1994; 25:582.
  42. De Castro S, Cartoni D, Fiorelli M, et al. Morphological and functional characteristics of patent foramen ovale and their embolic implications. Stroke 2000; 31:2407.
  43. Stone DA, Godard J, Corretti MC, et al. Patent foramen ovale: association between the degree of shunt by contrast transesophageal echocardiography and the risk of future ischemic neurologic events. Am Heart J 1996; 131:158.
  44. Hanna JP, Sun JP, Furlan AJ, et al. Patent foramen ovale and brain infarct. Echocardiographic predictors, recurrence, and prevention. Stroke 1994; 25:782.
  45. Rigatelli G, Dell'avvocata F, Braggion G, et al. Persistent venous valves correlate with increased shunt and multiple preceding cryptogenic embolic events in patients with patent foramen ovale: an intracardiac echocardiographic study. Catheter Cardiovasc Interv 2008; 72:973.
  46. Serena J, Marti-Fàbregas J, Santamarina E, et al. Recurrent stroke and massive right-to-left shunt: results from the prospective Spanish multicenter (CODICIA) study. Stroke 2008; 39:3131.
  47. Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001; 345:1740.
  48. Homma S, Sacco RL, Di Tullio MR, et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation 2002; 105:2625.
  49. Di Tullio MR, Sacco RL, Sciacca RR, et al. Patent foramen ovale and the risk of ischemic stroke in a multiethnic population. J Am Coll Cardiol 2007; 49:797.
  50. Meissner I, Khandheria BK, Heit JA, et al. Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study. J Am Coll Cardiol 2006; 47:440.
  51. Petty GW, Khandheria BK, Meissner I, et al. Population-based study of the relationship between patent foramen ovale and cerebrovascular ischemic events. Mayo Clin Proc 2006; 81:602.
  52. Kent DM, Ruthazer R, Weimar C, et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology 2013; 81:619.
  53. Thaler DE, Ruthazer R, Weimar C, et al. Recurrent stroke predictors differ in medically treated patients with pathogenic vs. other PFOs. Neurology 2014; 83:221.
  54. Katsanos AH, Spence JD, Bogiatzi C, et al. Recurrent stroke and patent foramen ovale: a systematic review and meta-analysis. Stroke 2014; 45:3352.
  55. Weimar C, Holle DN, Benemann J, et al. Current management and risk of recurrent stroke in cerebrovascular patients with right-to-left cardiac shunt. Cerebrovasc Dis 2009; 28:349.
  56. Adams HP Jr. Cardiac disease and stroke: will history repeat itself? Mayo Clin Proc 2006; 81:597.
  57. Thaler DE, Ruthazer R, Di Angelantonio E, et al. Neuroimaging findings in cryptogenic stroke patients with and without patent foramen ovale. Stroke 2013; 44:675.
  58. Hamann GF, Schätzer-Klotz D, Fröhlig G, et al. Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale. Neurology 1998; 50:1423.
  59. Droste DW, Schmidt-Rimpler C, Wichter T, et al. Right-to-left-shunts detected by transesophageal echocardiography and transcranial Doppler sonography. Cerebrovasc Dis 2004; 17:191.
  60. Katsanos AH, Psaltopoulou T, Sergentanis TN, et al. Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta-analysis. Ann Neurol 2016; 79:625.
  61. Lethen H, Flachskampf FA, Schneider R, et al. Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack. Am J Cardiol 1997; 80:1066.
  62. Stöllberger C, Slany J, Schuster I, et al. The prevalence of deep venous thrombosis in patients with suspected paradoxical embolism. Ann Intern Med 1993; 119:461.
  63. Cramer SC, Rordorf G, Maki JH, et al. Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study. Stroke 2004; 35:46.
  64. Meier B, Lock JE. Contemporary management of patent foramen ovale. Circulation 2003; 107:5.
  65. Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e576S.
  66. Krasuski RA, Hart SA, Allen D, et al. Prevalence and repair of intraoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival. JAMA 2009; 302:290.