Neurological Sciences

, Volume 35, Issue 6, pp 867–873 | Cite as

Prevalence of patent foramen ovale in ischemic stroke in Italy: the SISIFO study

  • Domenico Consoli
  • Maurizio Paciaroni
  • Marco Aguggia
  • Maurizio Melis
  • Giovanni Malferrari
  • Simone Vidale
  • Paolo Cerrato
  • Simona Sacco
  • Carlo Gandolfo
  • Paolo Bovi
  • Carlo Serrati
  • Massimo Del Sette
  • Anna Cavallini
  • Marina Diomedi
  • Paolo Postorino
  • Stefano Ricci
Original Article


Patent foramen ovale (PFO) is a common congenital anatomical defect in the general population with a mean prevalence of 20 %. Transcranial Doppler sonography and echocardiography, both with infusion of agitated saline as an echo contrast, have been introduced for the diagnosis of PFO. Transesophageal echocardiography is considered the gold standard. Several studies have suggested an association between cryptogenetic stroke and PFO, but the role of this condition as a risk factor for stroke is still debated. The aims of this prospective multicentre study are the evaluation of PFO prevalence in the whole ischemic stroke population and the identification of a stroke recurrence profile risk in patients with PFO. All consecutive patients admitted for acute ischemic stroke and with a confirmed diagnosis at discharge are eligible cases for the study. Demographic and vascular risk factors are registered. Clinical severity is summarized by the National Institute of Health stroke scale. Echocardiographic and transcranial studies are performed in each patient to detect the presence of PFO. Prevalence of PFO will be calculated with 95 % CIs. Univariate analysis will be performed to detect the correlation of PFO with different registered factors and multivariable analysis with PFO as independent variable. The present study should contribute to better identify the role of PFO in ischemic stroke risk and recurrence-related events. Qualifying findings of the study are represented by the high number of enrolled patients, the prospective methodology of the study and the presence of secondary instrumental endpoints.


Stroke Clinical trial Epidemiology Ischemic stroke Risk factors Ultrasound Patent foramen ovale Cardioembolic stroke 


  1. 1.
    Seib G (1934) Incidence of the patent foramen ovale cordis in adult American whites and America Negroes. Am J Anat 55:511–525CrossRefGoogle Scholar
  2. 2.
    Hagen et al (1984) Incidence and size of patent foramen ovale during the first 10 decades if life: an autopsy study of 965 normal hearts. Mayo Clin Proc 59:17–20CrossRefPubMedGoogle Scholar
  3. 3.
    Di Tullio M, Sacco RL, Venketasubramanian N, Sherman D, Mohr JP, Homma S (1993) Comparison of diagnostic techniques for the detection of a patent foramen ovale in stroke patients. Stroke 24:1020–1024CrossRefPubMedGoogle Scholar
  4. 4.
    Olivares-Reyes A, Chan S, Lazar EJ, Bandlamudi K, Narla V, Ong K (1997) Atrial septal aneurysm; a new classification in two hundred five adults. J Am Soc Echocardiogr 10:644–656CrossRefPubMedGoogle Scholar
  5. 5.
    Schneider B et al (1996) Diagnosis of patent foramen ovale by TEE and correlation with autopsy findings. Am J Cardiol 77:1202–1209CrossRefPubMedGoogle Scholar
  6. 6.
    Daniels C et al (2004) Second Harmonic TTE: the new reference screening method for the detection of patent foramen ovale. Eur J Echocardiogr 5:449–452CrossRefPubMedGoogle Scholar
  7. 7.
    Blersch WK, Draganski BM, Holmer SR, Koch HJ, Schlachetzki F, Bogdahn U, Hölscher T (2002) Transcranial duplex sonography in the detection of patient foramen ovale. Radiology 225:693–699CrossRefPubMedGoogle Scholar
  8. 8.
    Webster MW, Chancellor AM, Smith HJ, Sharpe DN, Bass NM, Glasgow GL (1988) Patent foramen ovale in young stroke patients. Lancet 2:11–12CrossRefPubMedGoogle Scholar
  9. 9.
    Lechat P, Mas JL, Lascault G, Loron P, Theard M, Klimczac M, Drobinski G, Thomas D, Grosgogeat Y (1988) Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 318:1148–1152CrossRefPubMedGoogle Scholar
  10. 10.
    Weimar C, Holle DN, Benemann J, Schmid E, Schminke U, Haberl RL, Diener HC, Goertler M (2009) Current management and risk of recurrent stroke in cerebrovascular patients with right-to-left cardiac shunt. Cerebrovasc Dis 28:349–356CrossRefPubMedGoogle Scholar
  11. 11.
    Fisher DC, Fisher EA, Budd JH, Rosen SE, Goldman ME (1995) The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study. Chest 107:1504–1509CrossRefPubMedGoogle Scholar
  12. 12.
    Lock JE (2000) Patent foramen ovale is indicated, but the case hasn’t gone to trial. Circulation 101:838CrossRefPubMedGoogle Scholar
  13. 13.
    Shuchlenz HW, WeihsW Horner S, Quehenberger F (2000) The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events. Am J Med 109:456–462CrossRefGoogle Scholar
  14. 14.
    de Castro S, Cartoni D, Fiorelli M, Rasura M, Anzini A, Zanette EM, Beccia M, Colonnese C, Fedele F, Fieschi C, Pandian NG (2000) Morphological and functional characteristics of patent foramen ovale and their embolic embolic implications. Stroke 31:2407–2413CrossRefPubMedGoogle Scholar
  15. 15.
    Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP, PFO in Cryptogenic Stroke Study (PICSS) Investigators (2002) Effect of medical treatment in stroke patients with patent foramen ovale. Patent foramen ovale in cryptogenic stroke study. Circulation 105:2625–2631CrossRefPubMedGoogle Scholar
  16. 16.
    Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, Coste J (2001) Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 345:1740–1746CrossRefPubMedGoogle Scholar
  17. 17.
    Messé SR, Silverman IE, Kizer JR, Homma S, Zahn C, Gronseth G, Kasner SE (2004) Recurrent stroke with patent foramen ovale and atrial septal aneurysm. Neurology 62:1042–1050CrossRefPubMedGoogle Scholar
  18. 18.
    Overell JR, Bone I, Less KR (2000) Interatrial septal abnormalities and stroke: a meta-analysis of case control studies. Neurology 55:1172–1179CrossRefPubMedGoogle Scholar
  19. 19.
    Almekhlafi MA, Wilton SB, Rabi DM, Ghali WA, Lorenzetti DL, Hill MD (2009) Recurrent cerebral ischemia in medically treated patent foramen ovale. Neurology 73:89–97CrossRefPubMedGoogle Scholar
  20. 20.
    Anzola GP, Zavarize P, Morandi E, Rozzini L, Parrinello G (2003) Transcranial Doppler and risk of recurrence in patient with stroke and patent foramen ovale. Eur J Neurol 10:129–135CrossRefPubMedGoogle Scholar
  21. 21.
    Roijer A, Lindgren A, Algotsson L, Norrving B, Olsson B, Eskilsson J (1997) Cardiac changes in stroke patients and controls evaluated with transoesophageal echocardiography. Scand Cardiovasc J 31:329–337CrossRefPubMedGoogle Scholar
  22. 22.
    Sastry S, Riding G, Morris J, Taberner D, Cherry N, Heagerty A, McCollum C (2006) Young Adult Myocardial Infarction and Ischemic Stroke: the role of paradoxical embolism and thrombophilia (The YAMIS Study). J Am Coll Cardiol 48:686–691CrossRefPubMedGoogle Scholar
  23. 23.
    Handke M, Harloff A, Olschewski M, Hetzel A, Geibel A (2007) Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 357:2262–2268CrossRefPubMedGoogle Scholar
  24. 24.
    Petty GW, Khandheria BK, Meissner I, Whisnant JP, Rocca WA, Christianson TJ, Sicks JD, O’Fallon WM, McClelland RL, Wiebers DO (2006) Population-based study of the relationship between patent foramen ovale and cerebrovascular ischemic events. Mayo Clin Proc 81:602–608CrossRefPubMedGoogle Scholar
  25. 25.
    Jones EF, Calafiore P, Donnan GA, Tonkin AM (1994) Evidence that patent foramen ovale is not a risk factor for cerebral ischemia in the elderly. Am J Cardiol 74:596–599CrossRefPubMedGoogle Scholar
  26. 26.
    Serena J, Segura T, Perez-Ayuso MJ, Bassaganyas J, Molins A, Davalos A (1998) The need to quantify right-to-left shunt in acute ischemic stroke: a case–control study. Stroke 29:1322–1328CrossRefPubMedGoogle Scholar
  27. 27.
    Force M, Massabuau P, Larrue V (2008) Prevalence of atrial septal abnormalities in older patients with cryptogenic ischemic stroke or transient ischemic attack. Clin Neurol Neurosurg 110:779–783CrossRefPubMedGoogle Scholar
  28. 28.
    Di Tullio M, Sacco RL, Gopal A, Mohr JP, Homma S (1992) Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 117:461–465CrossRefPubMedGoogle Scholar
  29. 29.
    Cabanes L, Mas JL, Cohen A, Amarenco P, Cabanes PA, Oubary P, Chedru F, Guerin F, Bousser MG, de Recondo J (1993) 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 24:1865–1873CrossRefPubMedGoogle Scholar
  30. 30.
    Negrao EM, Brandi IV, Nunes SV, Tavora DG, Nakayama M, Beraldo PS (2007) Patent foramen ovale and ischemic stroke in young people: statistical association or causal relation? Arq Bras Cardiol 88:514–520CrossRefPubMedGoogle Scholar
  31. 31.
    Cerrato P, Imperiale D, Priano L, Mangiardi L, Morello M, Marson AM, Carra F, Barberis G, Bergamasco B (2002) Transoesophageal echocardiography in patients without arterial and major cardiac sources of embolism: difference between stroke subtypes. Cerebrovasc Dis 13:174–183CrossRefPubMedGoogle Scholar
  32. 32.
    Rao S, Sila C (2013) PFO closure for cryptogenetic stroke: review of new data and results. Curr Treat Options Cardiovasc Med 15:360–371CrossRefPubMedGoogle Scholar
  33. 33.
    Del Sette M, Dinia L, Rizzi D et al (2007) Diagnosis of righ-to-left shunt with transcranial Doppler and vertebrobasilar recording. Stroke 38:2254–2256CrossRefPubMedGoogle Scholar
  34. 34.
    Angeli S, Del Sette M, Beelke M, Anzola GP, Zanette E (2001) Transcranial Doppler in the diagnosis of cardiac patent foramen ovale. Neurol Sci 22:353–356CrossRefPubMedGoogle Scholar
  35. 35.
    Sastry S, Daly K et al (2007) Is transcranial Doppler for the detection of venous-to-arterial circulation shunts reproducible? Cerebrovasc Dis 23:424–429CrossRefPubMedGoogle Scholar
  36. 36.
    Blersch W, Draganski BM, Holmer SR et al (2002) Transcranial duplex sonography in the detection of patent foramen ovale. Radiology 225:693–699CrossRefPubMedGoogle Scholar
  37. 37.
    Davis D, Gregson J, Willeit P, Stephan B, Salman RAS, Brayne C (2013) Patent foramen ovale, ischemic stroke and migraine: systematic review and stratified meta-analysis of association studies. Neuroepidemiology 40:56–67CrossRefPubMedGoogle Scholar
  38. 38.
    Homma S, Di Tullio MR, Sacco RL, Mihalatos D, Li Mandri G, Mohr JP (1994) Characteristics of patent foramen ovale associated with cryptogenetic stroke. A biplane transesophageal echocardiography study. Stroke 25:582–586CrossRefPubMedGoogle Scholar
  39. 39.
    Goel SS, Tuzcu EM, Shishehbor MH, de Oliveira EI, Borek PP, Krasuski RA, Rodriguez LL, Kapadia SR (2009) Morphology of patent foramen ovale in asymptomatic versus symptomatic (stroke or transient ischemic attack) patients. Am J Cardiol 103:124–129CrossRefPubMedGoogle Scholar
  40. 40.
    Homma S, Di Tullio MR (2010) Patent foramen ovale and stroke. J Cardiol 56:134–141CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Stöllberger C, Slany J, Schuster I, Leitner H, Winkler WB, Karnik R (1993) The prevalence of deep venous thrombosis in patients with suspected paradoxical embolism. Ann Intern Med 119:461–465CrossRefPubMedGoogle Scholar
  42. 42.
    Ranoux D, Cohen A, Cabanes L, Amarenco P, Bousser MG, Mas JL (1993) Patent foramen ovale: is stroke due to paradoxical embolism? Stroke 24:31–34CrossRefPubMedGoogle Scholar
  43. 43.
    Pezzini A, Del Zotto E, Magoni M, Costa A, Archetti S, Grassi M, Akkawi NM, Albertini A, Assanelli D, Vignolo LA, Padovani A (2003) Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke 34:28–33CrossRefPubMedGoogle Scholar
  44. 44.
    Karttunen V, Hiltunen L, Rasi V, Vahtera E, Hillbom M (2003) Factor V Leiden and prothrombotic gene mutation may predispose to paradoxical embolism in patients with foramen ovale. Blood Coagul Fibrinolysis 14:261–268PubMedGoogle Scholar
  45. 45.
    Botto N, Spadoni I, Giusti S, Ait-Ali L, Sicari R, Andreassi MG (2007) Prothrombotic mutations and risk factors for cryptogenetic ischemic cerebrovascular events in young subjects with patent foramen ovale. Stroke 38:2070–2073CrossRefPubMedGoogle Scholar
  46. 46.
    Meacham RR 3rd, Headley AS, Bronze MS, Lewis JB, Rester MM (1998) Impending paradoxical embolism. Arch Intern Med 158:438–448CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • Domenico Consoli
    • 1
    • 11
  • Maurizio Paciaroni
    • 6
    • 11
  • Marco Aguggia
    • 7
    • 11
  • Maurizio Melis
    • 8
    • 11
  • Giovanni Malferrari
    • 9
    • 11
  • Simone Vidale
    • 10
    • 11
  • Paolo Cerrato
    • 10
    • 11
  • Simona Sacco
    • 13
    • 11
  • Carlo Gandolfo
    • 3
    • 11
  • Paolo Bovi
    • 12
    • 11
  • Carlo Serrati
    • 14
    • 11
  • Massimo Del Sette
    • 5
    • 11
  • Anna Cavallini
    • 2
    • 11
  • Marina Diomedi
    • 15
  • Paolo Postorino
    • 1
    • 11
  • Stefano Ricci
    • 4
    • 11
  1. 1.UO Neurologia Ospedale “G. Jazzolino” Piazzale FlemingVibo ValentiaItaly
  2. 2.UC Malattie Cerebrovascolari/Stroke Unit IRCCS INN CPaviaItaly
  3. 3.DINOGMI, Stroke-UnitUniversity of GenoaGenoaItaly
  4. 4.UO Neurologia ASL 1 dell’ Umbria OspedaleCittà di Castello (PG)Italy
  5. 5.Neurology Unit S. Andrea HospitalLa SpeziaItaly
  6. 6.Stroke UnitPerugia UniversityPerugiaItaly
  7. 7.Neurologia e Stroke Unit Ospedale Cardinal Massaja AstiAstiItaly
  8. 8.SC Neurologia-Stroke Unit Azienda Ospedaliera G.BrotzuCagliariItaly
  9. 9.Neurology Unit, Stroke Unit, Department of Neuromotor PhysiologyArcispedale Santa Maria Nuova IRCCSReggio EmiliaItaly
  10. 10.Azienda Ospedaliera S. AnnaComoItaly
  11. 11.AOU “Molinette”TurinItaly
  12. 12.SSO Stroke Unit UO Neurologia DAI di NeuroscienzeAOU Integrata VeronaVeronaItaly
  13. 13.Department of NeurologyUniversity of L’AquilaL’AquilaItaly
  14. 14.AO “S. Martino”GenovaItaly
  15. 15.Uoc Stroke Unit, Dipartimento di NeuroscienzeUniversita’ Degli Studi di Roma tor VergataRomeItaly

Personalised recommendations