Patent foramen ovale: The never-ending story

  • Gérald Devuyst
  • Julien Bogousslavsky

Opinion statement

Several uncontrolled studies suggested a relationship between patent foramen ovale (PFO) and stroke. But recent data indicate that previous studies may overestimate the association between PFO and stroke. First, among patients who have had a cryptogenic stroke under treatment (with either warfarin or aspirin), the main data from the French PFO/atrial septal aneurysm (ASA) and PICSS (Patent Foramen Ovale in Cryptogenic Stroke Study), analyzed separately and in combination, indicate that PFO alone does not announce a significantly increased risk of recurrent stroke or death. But a small increase or decrease in risk cannot be excluded by this metaanalysis. Second, the data concerning the association between PFO and ASA are not clear and variable: the French PFO/ASA study found a significantly increased risk of recurrent stroke in patients with cryptogenic stroke and an association between PFO and ASA when treated medically. In contrast, PICSS found no association between the combined PFO-ASA with stroke or death, but the two populations had meaningful differences. Patients in the PICSS were much older than those in the French PFO/ASA study and had more risk factors for stroke, such as hypertension, diabetes, and history of prior stroke. Third, there were inadequate data to conclude about ASA alone. Possible practice recommendations could come from this meta-analysis: the evidence indicates that the risk of recurrent stroke or death is not different for patients with a PFO who underwent cryptogenic stroke compared to patients without a PFO who underwent a cryptogenic stroke under treatment with either aspirin or warfarin. But aspirin is more preferable (300 mg/d). However, it seems that the association between PFO and ASA confers an increased risk of recurrent stroke in medically treated patients who are less than 55 years of age. This subgroup of younger stroke patients may benefit from other treatments, such as the percutaneous closure of PFO or mini-invasive surgery to a lesser extent, but their efficacy and safety are not yet assessed by large randomized trials. However, we must also keep in mind that some stroke patients with PFO are psychologically attached to their PFO and prefer to close it.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Lechat P, Mas JL, Lascault G, et al.: Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988, 318:1148–1152.PubMedCrossRefGoogle Scholar
  2. 2.
    Overell JR, Bone I, Lees KR: Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 2000, 55:1172–1179.PubMedGoogle Scholar
  3. 3.
    Di Tullio M, Sacco RL, Gopal A, et al.: Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992, 117:461–465.PubMedGoogle Scholar
  4. 4.
    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, 345:1740–1746.PubMedCrossRefGoogle Scholar
  5. 5.
    Moon RE, Camporese EM, Kisslo JA: Patent foramen ovale and decompression sickness in divers. Lancet 1989, 1:513–514.PubMedCrossRefGoogle Scholar
  6. 6.
    Wilmshurst PT, Byrne JC, Webb-People MM: Relation between interatrial shunts and decompression sickness in divers. Lancet 1989, 2:1302–1306.PubMedCrossRefGoogle Scholar
  7. 7.
    Del Sette M, Angeli S, Leandri M: Migraine with aura and right-to-left shunt on transcranial Doppler: a case-control study. Cerebrovasc Dis 1998, 8:327–330.PubMedCrossRefGoogle Scholar
  8. 8.
    Anzola GP, Mangoni M, Guindani M, et al.: Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study. Neurology 1999, 52:1622–1625.PubMedGoogle Scholar
  9. 9.
    Forech C, Kessler KR, Steinmets H, et al.: “Economy class” stroke syndrome. Neurology 2004, 62:1026.Google Scholar
  10. 10.
    Conheim J: Thrombose und embolie. In Vorlesungen über Allgemein Pathologie, vol 1. Berlin: Hirschwald; 1877:134.Google Scholar
  11. 11.
    Zahn FW: Thrombose de plusieurs branches de la veine cave inférieure avec embolies consécutives dans les artéres pulmonaires, spléniques, rénales et iliaque droite. Rev Med Suisse Romande 1881, 1:227–237.Google Scholar
  12. 12.
    Hagen PT, Scholz DG, Edwards WD, et al.: Incidence and size of patent foramen ovale during the first ten decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc 1984, 59:17–20.PubMedGoogle Scholar
  13. 13.
    Thompson T, Evans W: Paradoxical embolism. Q J Med 1930, 23:135–150.Google Scholar
  14. 14.
    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, 74:862–869.PubMedGoogle Scholar
  15. 15.
    Agmon y, Khandheria BK, Messner I, et al.: Comparison of frequency of patent foramen ovale by transesophageal echocardiography in patients with cerebral ischemic events versus in subjects in the general population. Am J Cardiol 2001, 88:330–332.PubMedCrossRefGoogle Scholar
  16. 16.
    Hart RG, Albers GW, Koudstaal PJ: Cardioembolic stroke. In Cerebrovascular Disease: Pathophysiology, Diagnosis, and Management, vol 2. Edited by Ginsberg MD, Bogousslavsky J. Oxford: Blackwell Publishers; 1998:1392–1429.Google Scholar
  17. 17.
    Kerut EK, Norfleet WT, Plotnick GD, et al.: Patent foramen oval: a review of associated conditions and the impact of physiological size. J Am Coll Cardiol 2001, 38:613–623.PubMedCrossRefGoogle Scholar
  18. 18.
    Schneider B, Harath P, Vogel P, et al.: Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events. J Am Coll Cardiol 1990, 16:1000–1009.PubMedCrossRefGoogle Scholar
  19. 19.
    Homma S, Sacco RL, Di Tullio MR, et al.: Relationship of atrial septal aneurysm with patent foramen ovale: insights from PFO in Cryptogenic Stroke Study (PICSS). Circulation 2001, 104(suppl 2):670.Google Scholar
  20. 20.
    Fox ER, Picard MH, Chow CM, et al.: Interatrial septal mobility predicts larger shunts across patent foramen ovales: an analysis with transmitral Doppler scanning. Am Heart J 2003, 145:730–736.PubMedCrossRefGoogle Scholar
  21. 21.
    Homma S, Sacco RL, Di Tullio MR, et al.: Atrial anatomy in non-cardioembolic stroke patients. Effect of medical therapy. J Am Coll Cardiol 2003, 42:1066–1072.PubMedCrossRefGoogle Scholar
  22. 22.
    Webster MW, Chancellor AM, Smith HJ, et al.: Patent foramen ovale in young stroke patients. Lancet 1988, 2:1–12.Google Scholar
  23. 23.
    Pearson AC, Nagelhout D, Castello R, et al.: Atrial septal aneurysm and stroke: a transesophageal echocardiography. J Am Coll Cardiol 1991, 18:1223–1229.PubMedCrossRefGoogle Scholar
  24. 24.
    Cabanes L, Mas JL, Cohen A, et al.: Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patient with less than 55 years of age. A study using transesophageal echocardiography. Stroke 1993, 24:1865–1873.PubMedGoogle Scholar
  25. 25.
    Agmon Y, Khandhheria BK, Meissner I, et al.: Frequency of atrial septal aneurysms in patients with cerebral ischemic events. Circulation 1999, 99:1942–1944.PubMedGoogle Scholar
  26. 26.
    Mattioli AV, Aquilina M, Oldani A, et al.: Atrial septal aneurysm as a cardioembolic source in adults patients with stroke and normal arteries. A multicentric study. Eur Heart J 2001, 22:261–268.PubMedCrossRefGoogle Scholar
  27. 27.
    Chen WJ, Lin SL, Cheng JJ, et al.: The frequency of patent foramen ovale in patients with ischemic stroke: a transesophageal echocardiographic study. J Formos Med Assoc 1991, 90:744–748.PubMedGoogle Scholar
  28. 28.
    Job FP, Ringelstein EB, Grafen Y, et al.: Comparison of transcranial contrast Doppler sonography and transesophageal contrast echocardiography for the detection of patent foramen ovale in young stroke patients. Am J Cardiol 1994, 74:381–384.PubMedCrossRefGoogle Scholar
  29. 29.
    Jones HR, Caplan LR, Come PC, et al.: Cerebral emboli of paradoxical origin. Ann Neurol 1983, 13:314–319.PubMedCrossRefGoogle Scholar
  30. 30.
    Zahn R, Lehmkuhl S, Lotter R, et al.: Cardiac sources of cerebral ischemic events with special regard to a patent foramen ovale. Herz Kreislauf 1995, 27:279–284.Google Scholar
  31. 31.
    de Belder MA, Tourikis L, Leech G, et al.: Risk of patent foramen ovale for thromboembolic events in all age groups. Am J Cardiol 1992, 69:1316–1320.PubMedCrossRefGoogle Scholar
  32. 32.
    Meister SG, Grossman W, Dexter L, Dalen JE: Paradoxical embolism. Diagnosis during life. Am J Med 1972, 53:292–298.PubMedCrossRefGoogle Scholar
  33. 33.
    Holmes DR, Cohen H, Katz WE, et al.: Patent foramen oval, systemic embolization and closure. Cur Probl Cardiol 2004, 29:56–94.CrossRefGoogle Scholar
  34. 34.
    d’Audiffret A, Pillai L, Dryjski M, et al.: Paradoxical emboli: the relationship between patent foramen ovale, deep vein thrombosis and ischaemic stroke. Eur j Vasc Endovasc Surg 1999, 17:468–471.PubMedCrossRefGoogle Scholar
  35. 35.
    Mas JL: Specifics of patent foramen ovale. In Ischemic Stroke (Advances in Neurology), vol 92. Edited by Barnett et al. Philadelphia: Lippincott, Williams & Wilkins; 2003:197–202.Google Scholar
  36. 36.
    Stöllberger C, Slany J, Schuster I, et al.: The prevalence of deep venous thrombosis in patients with suspected paradoxical embolism. Ann Intern Med 1993, 119:461–465.PubMedGoogle Scholar
  37. 37.
    Stöllberger C, Finsterer J: Search for coagulopathy does not obviate search for venous thrombosis in suspected paradoxical embolism. Stroke 2003, 34:28–33.CrossRefGoogle Scholar
  38. 38.
    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, 80:1066–1069.PubMedCrossRefGoogle Scholar
  39. 39.
    Ranoux D, Cohen MD, Cabanes L, et al.: Patent foramen ovale: is stroke due to paradoxical embolism? Stroke 1993, 1:193–202.Google Scholar
  40. 40.
    Perrier A: Labeling the thrombus. The future of nuclear medicine for venous thromboembolism? Am J Respir Crit Care Med 2004, 169:977–981.PubMedCrossRefGoogle Scholar
  41. 41.
    Morris TA, Marsh JJ, Chiles PG, et al.: Single photon emission computed tomography of pulmonary emboli and venous thrombi using anti-D-Dimer. Am J Respir Crit Care Med 2004, 169:987–993.PubMedCrossRefGoogle Scholar
  42. 42.
    Reid JH: Multislice CT pulmonary angiography and CT venography. Br J Radiol 2004, 77:S39-S45.PubMedCrossRefGoogle Scholar
  43. 43.
    Morandi E, Anzola GP, Angeli S, et al.: Transcatheter closure of patent foramen ovale: a new migraine treatment? J Int Cardiol 2003, 16:39–42.CrossRefGoogle Scholar
  44. 44.
    Sztajzel R, Genoud D, Roth S, et al.: Patent foramen ovale, a possible cause of symptomatic migraine: a study of 74 patients with acute ischemic stroke. Cerebrovasc Dis 2002, 13:102–106.PubMedCrossRefGoogle Scholar
  45. 45.
    Hayashida K, Fukuchi K, Inubushi M, et al.: Embolic distribution through patent foramen ovale demonstrated by 99mTc-MAA brain SPECT after Valsalva radionuclide venography. J Nucl Med 2001, 42:859–863.PubMedGoogle Scholar
  46. 46.
    Gupta VK: Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology 2004, 63:1760–1761; author reply 1760–1.PubMedGoogle Scholar
  47. 47.
    Post MC, Thijs V, Herroelen L, et al.: Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Neurology 2004, 62:1439–1440.PubMedGoogle Scholar
  48. 48.
    Schwerzmann M, Wiher S, Nedeltchev K, et al.: Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology 2004, 62:1399–1401.PubMedGoogle Scholar
  49. 49.
    Messé SR, Silverman IE, Kizer JR, et al.: Practice parameter: recurrent stroke with patent foramen ovale and atrial septal aneurysm. Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2004, 62:1042–1050. A meta-analysis of neurologic studies on stroke patients with PFO or PFO-ASA or ASA alone. It proposes recommendations for treatment in clinical practice, thus igniting the ongoing debate on the “best treatment.”PubMedGoogle Scholar
  50. 50.
    Bogousslavsky J, Garazi S, Jeanrenaud X, et al.: Stroke recurrence in patients with patent foramen ovale: the Lausanne Study. Lausanne Stroke with paradoxical embolism study group. Neurology 1996, 46:1301–1305.PubMedGoogle Scholar
  51. 51.
    De Castro S, Cartoni D, Fiorelli M, et al.: Morphological and functional characteristics of patent foramen ovale and their embolic implications. Stroke 2000, 31:2407–2413.PubMedGoogle Scholar
  52. 52.
    Homma S, De 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 (PICSS). Circulation 2002, 105:2625–2631. Investigated the stroke recurrence in stroke patients with PFO or PFO-ASA or ASA alone, which was crucial to provide treatment guidelines. Until now, the “best treatment” in these patients was unknown.PubMedCrossRefGoogle Scholar
  53. 53.
    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, 25:582–586.PubMedGoogle Scholar
  54. 54.
    Steiner MM, Di Tullio MR, Rundek T, et al.: Patent foramen ovale size and embolic brain imaging findings among patients with ischemic stroke. Stroke 1998, 29:944–948.PubMedGoogle Scholar
  55. 55.
    Serena J, Segura T, Perez-Ayuso MJ, et al.: The need to quantify right-to-left shunt in acute ischemic stroke: a case-control study. Stroke 1998, 29:1322–1328.PubMedGoogle Scholar
  56. 56.
    Anzola GP, Zavarize P, Morandi E, et al.: Transcranial Doppler and risk of recurrence in patients with stroke and patent foramen ovale. Eur J Neurol 2003, 10:129–135.PubMedCrossRefGoogle Scholar
  57. 57.
    Schuchlenz HW, Weihs W, Horner S, et al.: The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events. Am J Med 2000, 109:456–462.PubMedCrossRefGoogle Scholar
  58. 58.
    Devuyst G, Piechowski-Jozwiak B, Karapanayiotides T, et al.: Controlled contrast transcranial Doppler and arterial blood gas analysis to quantify shunt through patent foramen ovale. Stroke 2004, 35:859–863.PubMedCrossRefGoogle Scholar
  59. 59.
    Homma S, Di Tullio M, Sacco L, et al.: Age as a determinant of adverse events in medically treated cryptogenic stroke patients with patent foramen ovale. Stroke 2004, 35:2145–2149.PubMedCrossRefGoogle Scholar
  60. 60.
    Ringelstein EB, Droste DW, Babikian VL, et al.: Consensus on microembolus detection by TCD. Stroke 1998, 29:725–729.PubMedGoogle Scholar
  61. 61.
    Jauss M, Zanette E: Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography. Cerebrovasc Dis 2000, 10:490–496.PubMedCrossRefGoogle Scholar
  62. 62.
    Spencer MP, Moehring MA, Jesurum J, et al.: Power Mmode transcranial Doppler for diagnosis of patent foramen ovale and assessing transcatheter closure. J Neuroimaging 2004, 14:342–349.PubMedCrossRefGoogle Scholar
  63. 63.
    Furlan AJ: Patent foramen ovale and recurrent stroke: closure is the best option: yes. Stroke 2004, 35:803–804.PubMedCrossRefGoogle Scholar
  64. 64.
    Tong DC, Becker KJ: Patent foramen ovale and recurrent stroke: closure is the best option:no. Stroke 2004, 35:803–804.CrossRefGoogle Scholar
  65. 65.
    Devuyst G, Bogousslavsky J, Ruchat P, et al.: Prognosis after stroke followed by surgical closure of patent foramen ovale a prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler ultrasound. Neurology 1996, 47:1162–1166.PubMedGoogle Scholar
  66. 66.
    Homma MR, Di Tullio RL, Sacco RR, et al.: Surgical closure of patent foramen ovale in cryptogenic stroke patients. Stroke 1997, 28:2376–2381.PubMedGoogle Scholar
  67. 67.
    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-II175.PubMedGoogle Scholar
  68. 68.
    Caes FL, Van Belleghem YV, Missault LH: Surgical treatment of impending paradoxical embolism through patent foramen ovale. Ann Thorac Surg 1995, 59:1559–1561.PubMedCrossRefGoogle Scholar
  69. 69.
    Levi DS, Moore JW: Embolization and retrieval of the Amplatzer septal occluder. Catheter Cardiovasc Interv 2004, 61:543–547.PubMedCrossRefGoogle Scholar
  70. 70.
    Windecker S, Wahl A, Chatterjee T, et al.: Percutaneous closure of PFO in patients with paradoxical embolism: long-term risk of recurrent thromboembolic events. Circulation 2000, 101:893–898.PubMedGoogle Scholar
  71. 71.
    Braun MU, Fassbender D, Schoen SP, et al.: Transcatheter closure of patent foramen ovale in patients with cerebral ischemia. J Am Coll Cardiol 2002, 39:2019–2025.PubMedCrossRefGoogle Scholar
  72. 72.
    Onorato E, Melzi G, Casilli F, et al.: Patent foramen ovale with paradoxical embolism: mid-term results of transcatheter closure of 256 patients. J Int Cardiol 2003, 16:43–50.CrossRefGoogle Scholar
  73. 73.
    Sievert H, Horvath K, Zadan E, et al.: Patent foramen ovale closure in patients with transient ischemia attack/stroke. J Int Cardiol 2001, 14:261–266.Google Scholar
  74. 74.
    Bruch L, Parsi A, Grad MO, et al.: Transcatheter closure of interatrial communications for secondary prevention of paradoxical embolism: single-center experience. Circulation 2002, 105:2845–2848.PubMedCrossRefGoogle Scholar
  75. 75.
    Hung J, Landzberg MJ, Jenkins KJ, et al.: Closure of patent foramen ovale for paradoxical emboli: intermediateterm risk of recurrent neurological events following transcatheter device placement. J Am Coll Cardiol 2000, 35:1311–1316.PubMedCrossRefGoogle Scholar
  76. 76.
    Martin F, Sanchez PL, Doherty E, et al.: Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Circulation 2002, 106:1121–1126.PubMedCrossRefGoogle Scholar
  77. 77.
    Schwerzmann M, Windecker S, Wahl A, et al.: Percutaneous closure of patent foramen ovale: impact of device design on safety and efficacy. Heart 2004, 90:186–190.PubMedCrossRefGoogle Scholar
  78. 78.
    Ferrari J, Baumgartner H, Tentschert S, et al.: Cerebral microembolism during transcatheter closure of patent foramen ovale. J Neurol 2004, 251:825–829.PubMedCrossRefGoogle Scholar
  79. 79.
    Khositseth A, Calabra 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, 79:35–41.PubMedCrossRefGoogle Scholar
  80. 80.
    Hildick-Smith DJ, O’Sullivan M, Wisbey CR, et al.: Amplatzer device closure of atrial septal defects in mature adults: analysis of 76 cases. Heart 2004, 90:334–335.PubMedCrossRefGoogle Scholar
  81. 81.
    Anzola GP, Morandi E, Casilli F, et al.: Does transcatheter closure of patent foramen ovale really “shut the door?” A prospective study with transcranial Doppler. Stroke 2004, 35:2140–2144.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Gérald Devuyst
    • 1
  • Julien Bogousslavsky
    • 1
  1. 1.Department of Neurology, Academic of VaudCentre Hospitalier Universitaire VaudoisLausanneSwitzerland

Personalised recommendations