Background
Patent foramen ovale (PFO) is an anatomical interatrial communication with potential for right-to-left shunt. Foramen ovale has been known since the time of Galen. In 1564, Leonardi Botali, an Italian surgeon, was the first to describe the presence of foramen ovale at birth. However, the function of foramen ovale in utero was not known at that time. In 1877, Cohnheim described paradoxical embolism in relation to PFO.
Pathophysiology
PFO is a flaplike opening between the atrial septa primum and secundum at the location of the fossa ovalis that persists after age 1 year. In utero, the foramen ovale serves as a physiologic conduit for right-to-left shunting. Once the pulmonary circulation is established after birth, left atrial pressure increases, allowing functional closure of the foramen ovale. This is followed by anatomical closure of the septum primum and septum secundum by the age of 1 year.
The Mayo Clinic autopsy study revealed that the size of a PFO increases from a mean of 3.4 mm in the first decade to 5.8 mm in the 10th decade of life, as the valve of fossa ovalis stretches with age.[1]
With increasing evidence that PFO is the culprit in paradoxical embolic events, the relative importance of the anomaly is being reevaluated. James Lock, MD, postulated that PFO anatomy results in a cul-de-sac between the septa primum and secundum, predisposing individuals to hemostasis and clot formation. Any conditions that increase right atrial pressure more than left atrial pressure can induce paradoxical flow and may result in an embolic event.
This reasoning has greatly altered the previous conception of PFO and is changing current management of the condition.
Epidemiology
Frequency
United States
PFO is detected in 10-15% of the population by contrast transthoracic echocardiography. Autopsy studies show a 27% prevalence of probe-patent foramen ovale.[1] This difference is probably due to the ability to directly visualize PFO on autopsy study, while contrast echocardiography relies on detection of secondary physiologic phenomena.
Sex
The prevalence and size of probe-patent PFO is similar in males and females.
Age
The prevalence of PFO declines progressively with age — 34% up to age 30 years, 25% for age 30-80 years, and 20% older than 80 years.
Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. Jan 1984;59(1):17-20. [Medline].
Bonati LH, Wetzel SG, Kessel-Schaefer A, et al. Diffusion-weighted imaging findings differ between stroke attributable to spontaneous cervical artery dissection and patent foramen ovale. Eur J Neurol. Oct 23 2009;[Medline].
Agostoni P, Gasparini G, Destro G. Acute myocardial infarction probably caused by paradoxical embolus in a pregnant woman. Heart. Mar 2004;90(3):e12. [Medline]. [Full Text].
Diaz Castro O, Bueno H, Nebreda LA. Acute myocardial infarction caused by paradoxical tumorous embolism as a manifestation of hepatocarcinoma. Heart. May 2004;90(5):e29. [Medline]. [Full Text].
Carey HB, Boltax R, Dickey KW, Finkelstein FO. Bilateral renal infarction secondary to paradoxical embolism. Am J Kidney Dis. Oct 1999;34(4):752-5. [Medline].
Pell AC, Hughes D, Keating J, Christie J, Busuttil A, Sutherland GR. Brief report: fulminating fat embolism syndrome caused by paradoxical embolism through a patent foramen ovale. N Engl J Med. Sep 23 1993;329(13):926-9. [Medline].
Pellikka PA, Tajik AJ, Khandheria BK, Seward JB, Callahan JA, Pitot HC, et al. Carcinoid heart disease. Clinical and echocardiographic spectrum in 74 patients. Circulation. Apr 1993;87(4):1188-96. [Medline].
Schneider B, Hofmann T, Justen MH, Meinertz T. Chiari's network: normal anatomic variant or risk factor for arterial embolic events?. J Am Coll Cardiol. Jul 1995;26(1):203-10. [Medline].
Khositseth A, Cabalka AK, Sweeney JP, Fortuin FD, Reeder GS, Connolly HM, et al. Transcatheter Amplatzer device closure of atrial septal defect and patent foramen ovale in patients with presumed paradoxical embolism. Mayo Clin Proc. Jan 2004;79(1):35-41. [Medline].
Attenhofer Jost CH, Connolly HM, O'Leary PW, Warnes CA, Tajik AJ, Seward JB. Left heart lesions in patients with Ebstein anomaly. Mayo Clin Proc. Mar 2005;80(3):361-8. [Medline].
Maffe S, Dellavesa P, Zenone F, et al. Transthoracic second harmonic two- and three-dimensional echocardiography for detection of patent foramen ovale. Eur J Echocardiogr. Nov 12 2009;[Medline].
Steenblik MH, Mineau GP, Pimentel R, et al. Population-based assessment of familial inheritance and neurologic comorbidities among patients with an isolated atrial septal defect. Congenit Heart Dis. Nov 2009;4(6):459-63. [Medline].
Rigatelli G, Dell'avvocata F, Giordan M, et al. Transcatheter patent foramen ovale closure in spite of interatrial septum hypertrophy or lipomatosis: a case series. J Cardiovasc Med (Hagerstown). Oct 13 2009;[Medline].
Adams HP. Patent foramen ovale: paradoxical embolism and paradoxical data. Mayo Clin Proc. Jan 2004;79(1):15-20. [Medline].
Aslam F, Shirani J, Haque AA. Patent foramen ovale: assessment, clinical significance and therapeutic options. South Med J. Dec 2006;99(12):1367-72. [Medline].
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. May 1996;46(5):1301-5. [Medline].
Bridges ND, Hellenbrand W, Latson L, et al. Transcatheter closure of patent foramen ovale after presumed paradoxical embolism. Circulation. Dec 1992;86(6):1902-8. [Medline]. [Full Text].
Cheng TO. Transcatheter closure of patent foramen ovale: a definitive treatment for platypnea-orthodeoxia. Catheter Cardiovasc Interv. Sep 2000;51(1):120. [Medline].
Cujec B, Mainra R, Johnson DH. Prevention of recurrent cerebral ischemic events in patients with patent foramen ovale and cryptogenic strokes or transient ischemic attacks. Can J Cardiol. Jan 1999;15(1):57-64. [Medline].
Danzi GB, Sesana M, Capuano C, Baglini R. Percutaneous closure of patent foramen ovale: pathophysiology, indications, and technique. Neurol Sci. May 2003;24 Suppl 1:S17-9. [Medline].
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. Nov 1996;47(5):1162-6. [Medline].
Donnan GA, Davis SM. Patent foramen ovale and stroke: closure by further randomized trial is required!. Stroke. Mar 2004;35(3):806. [Medline].
Dubourg O, Bourdarias JP, Farcot JC, et al. Contrast echocardiographic visualization of cough-induced right to left shunt through a patent foramen ovale. J Am Coll Cardiol. Sep 1984;4(3):587-94. [Medline].
Fransson SG. The Botallo mystery. Clin Cardiol. Jun 1999;22(6):434-6. [Medline].
Furlan AJ. Patent foramen ovale and recurrent stroke: closure is the best option: yes. Stroke. Mar 2004;35(3):803-4. [Medline].
Guffi M, Bogousslavsky J, Jeanrenaud X, et al. Surgical prophylaxis of recurrent stroke in patients with patent foramen ovale: a pilot study. J Thorac Cardiovasc Surg. Aug 1996;112(2):260-3. [Medline].
Hara H, Virmani R, Ladich E, Mackey-Bojack S, Titus J, Reisman M. Patent foramen ovale: current pathology, pathophysiology, and clinical status. J Am Coll Cardiol. Nov 1 2005;46(9):1768-76. [Medline].
Hausmann D, Mugge A, Daniel WG. Identification of patent foramen ovale permitting paradoxic embolism. J Am Coll Cardiol. Oct 1995;26(4):1030-8. [Medline].
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. Jun 4 2002;105(22):2625-31. [Medline].
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. Sep 2001;38(3):613-23. [Medline].
Khairy P, O'Donnell CP, Landzberg MJ. Transcatheter closure versus medical therapy of patent foramen ovale and presumed paradoxical thromboemboli: a systematic review. Ann Intern Med. Nov 4 2003;139(9):753-60. [Medline].
Kizer JR, Devereux RB. Clinical practice. Patent foramen ovale in young adults with unexplained stroke. N Engl J Med. Dec 1 2005;353(22):2361-72. [Medline].
Landzberg MJ, Khairy P. Indications for the closure of patent foramen ovale. Heart. Feb 2004;90(2):219-24. [Medline].
Lechat P, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med. May 5 1988;318(18):1148-52. [Medline].
Lock JE. Patent foramen ovale is indicted, but the case hasn't gone to trial. Circulation. Feb 29 2000;101(8):838. [Medline].
Marie Valente A, Rhodes JF. Current indications and contraindications for transcatheter atrial septal defect and patent foramen ovale device closure. Am Heart J. Apr 2007;153(4 Suppl):81-4. [Medline].
Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic attack. French Study Group on Patent Foramen Ovale and Atrial Septal Aneurysm. Am Heart J. Nov 1995;130(5):1083-8. [Medline].
Meier B, Lock JE. Contemporary management of patent foramen ovale. Circulation. Jan 7 2003;107(1):5-9. [Medline].
Meissner I, Whisnant JP, Khandheria BK, Spittell PC, O'Fallon WM, Pascoe RD, 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. Sep 1999;74(9):862-9. [Medline].
Mohrs OK, Petersen SE, Erkapic D, et al. Diagnosis of patent foramen ovale using contrast-enhanced dynamic MRI: a pilot study. AJR Am J Roentgenol. Jan 2005;184(1):234-40. [Medline].
Ranoux D, Cohen A, Cabanes L, et al. Patent foramen ovale: is stroke due to paradoxical embolism?. Stroke. Jan 1993;24(1):31-4. [Medline].
Ruchat P, Bogousslavsky J, Hurni M, et al. Systematic surgical closure of patent foramen ovale in selected patients with cerebrovascular events due to paradoxical embolism. Early results of a preliminary study. Eur J Cardiothorac Surg. May 1997;11(5):824-7. [Medline].
Sievert H, Babic UU, Hausdorf G, et al. Transcatheter closure of atrial septal defect and patent foramen ovale with ASDOS device (a multi-institutional European trial). Am J Cardiol. Dec 1 1998;82(11):1405-13. [Medline].
Sievert H, Taaffe M. Patent foramen ovale: the jury is still out. Eur Heart J. Mar 2004;25(5):361-2. [Medline].
Siostrzonek P, Zangeneh M, Gossinger H, et al. Comparison of transesophageal and transthoracic contrast echocardiography for detection of a patent foramen ovale. Am J Cardiol. Nov 1 1991;68(11):1247-9. [Medline].
Slavin L, Tobis JM, Rangarajan K, Dao C, Krivokapich J, Liebeskind DS. Five-year experience with percutaneous closure of patent foramen ovale. Am J Cardiol. May 1 2007;99(9):1316-20. [Medline].
Somberg J. Patent foramen ovale closure devices: thoughts from the circulatory device advisory panel. Am J Cardiol. Sep 1 2007;100(5):905-6. [Medline].
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. Jan 1996;131(1):158-61. [Medline].
Windecker S, Wahl A, Chatterjee T, et al. Percutaneous closure of patent foramen ovale in patients with paradoxical embolism: long-term risk of recurrent thromboembolic events. Circulation. Feb 29 2000;101(8):893-8. [Medline].

