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patent foramen ovale (PFO)

Etiology: - occurs if the septum primum fails to fuse with the foramen ovale after birth - occurs frequently in association with an atrial septal aneurysm Epidemiology: - occurs in 25-30% of population [1] Pathology: - PFO associated with an increased risk of embolic stroke [3,4] a) PFO found in 40-63% of cryptogenic ischemic strokes in patients < 55-60 years of age & 39% in patients > 55 b) PFOis likely responsible for ~5% of all ischemic strokes & 10% of those occurring in young & middle-aged adults [17] c) atrial septal aneurysm increases likelihood of embolism through PFO d) possible mechanisms of embolic stroke 1] paradoxical embolism from the venous circulation 2] thrombosis with atrial septal aneurysm 3] atrial arrhythmias Clinical manifestations: - most patients are asymptomatic Special laboratory: - often discovered incidentally on transthoracic echocardiography - transthoracic echocardiography bubble study (diagnostic) - agitated saline is injected into a peripheral intravenous catheter to demonstrate right-to-left intracardiac shunt often enhanced by the Valsalva maneuver - electrocardiogram - normal with small PDA - with large PDA: - left ventricular hypertrophy - left atrial enlargement - with pulmonary hypertension, right ventricular hypertrophy Radiology: - chest X-ray - normal with small PDA - with large PDA: - cardiomegaly - increased pulmonary vascular markings - calcification of PDA (occasional) - with pulmonary hypertension - prominent central pulmonary arteries - reduced peripheral pulmomary vascularity Complications: - embolic stroke (see pathology) - recurrent strokes are uncommon & usually unrelated to the patent foramen ovale [5] - preoperatively diagnosed patent foramen ovale increases risk for perioperative stroke (3.2% vs 0.5% noncardiac surgery) [16] - evidence in support of causal link with migraines is insufficient - platypnea-orthodeoxia - may be associated with pneumonectomy [1] - endocarditis - heart failure (with large PDA) Management: - no treatment or follow-up needed for asymptomatic patients [1] - surgical closure - indications: - ACP (MKSAP19) endorses patent foramen ovale device closure after 1st cryptogenic stroke (reversal of prior recommendations) [1] - PFO occlusion device FDA approved 10/16 - formerly recurrent cryptogenic stroke despite medical therapy - may be of benefit, but the number needed to treat is ~50 [8]; 56 [12] - clinical trials do not support surgical closure to reduce risk of recurrent stroke or migraine [1] - PFO closure associated with lower rate of recurrent ischemic strokes than medical therapy [14] - younger patients < 60 years with larger shunts most likely to benefit [18] - PFO associated atrial septal aneurysm or large interatrial shunt may benefit from closure [14] - endovascular device closure of patent foramen ovale reduces stroke risk for patients with prior cryptogenic stroke (RR=0.03 in CLOSE trial - 0.23 in REDUCE trial) [13] - PFO closure associated with increased risk of atrial fibrillation (4% vs 1%) & device complications [14] - cryptogenic stroke (3.6% vs 6.3%) [15] - platypnea-orthodeoxia [1] - contraindications: - asymptomatic patients without history of stroke [1] - anti-platelet therapy recommended for cryptogenic stroke [1] - not recommended in the absence of cryptogenic stroke [1] - anticoagulation rcommended for recurrent stroke or initial stroke in a patient with a hypercoagulable state [1,18] - no benbefit of surgical closure if hypercoagulable state [18] Notes: - Reference [2] reports risk of recurrent stroke associated with both atrial septal aneurysm & patent foramen ovale, but not with either alone. Reference [3] found no such association.

Interactions

disease interactions

Related

atrial septal aneurysm foramen ovale patent foramen ovale (PFO) occlusion device (Amplatzer) septum primum

General

congenital heart disease; congenital cyanotic heart disease

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2022
  2. Journal Watch 22(2):11, 2002 Mas JL et al Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 345:1740, 2001 PMID: 11742048
  3. Journal Watch 22(16):126-27, 2002 Homma S et al, Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke study Circulation 105:2565, 2002 PMID: 12045168 - Halperin JL & Fuster V, Patent foramen ovale and recurrent stroke: another paradoxical twist. Circulation 105:2580, 2002 PMID: 12045158
  4. Handke M et al, Patient foramen ovale and cryptogenic stroke in older patients. N Engl J Med 2007, 357:2262 PMID: 18046029
  5. Journal Watch, Massachusetts Medical Society, March 16, 2012 Furlan AJ et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012 Mar 15; 366:991. PMID: 22417252
  6. A.D.A.M. Medical Encyclopedia Patent foramen ovale http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002102/
  7. Shan SN eMedicine (Medscape): Patent foramen ovale http://emedicine.medscape.com/article/156863-overview
  8. Meier B et al. for the PC Trial investigators. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013 Mar 21; 368:1083 PMID: 23514285 http://www.nejm.org/doi/full/10.1056/NEJMoa1211716 - Carroll JD et al. for the RESPECT investigators. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013 Mar 21; 368:1092 PMID: 23514286 http://www.nejm.org/doi/full/10.1056/NEJMoa1301440
  9. Meier B, Lock JE. Contemporary management of patent foramen ovale. Circulation. 2003 Jan 7;107(1):5-9. PMID: 12515733
  10. Chen L, Luo S, Yan L, Zhao W A systematic review of closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and cryptogenic stroke or transient ischemic attack. J Neurol Sci. 2014 Feb 15;337(1-2):3-7 PMID: 24300230
  11. 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 Sep 24;128(13):1433-41. PMID: 23946264
  12. Messe SR et al. Practice advisory: Recurrent stroke with patent foramen ovale (update of practice parameter). Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2016 Jul 27 PMID: 27466464
  13. Phend C PFO Closure for Cryptogenic Stroke Prevents Recurrences - First overall stroke reduction with closure reported in two trials. MedPage Today. May 16, 2017 https://www.medpagetoday.com/Cardiology/Strokes/65348
  14. Mas JL et al Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. N Engl J Med 2017; 377:1011-1021. September 14, 2017 PMID: 28902593 http://www.nejm.org/doi/full/10.1056/NEJMoa1705915 - Saver JL et al Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke. N Engl J Med 2017; 377:1022-1032. September 14, 2017 PMID: 28902590 http://www.nejm.org/doi/full/10.1056/NEJMoa1610057 - Sondergaard L et al Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke. N Engl J Med 2017; 377:1033-1042. September 14, 2017 PMID: 28902580 http://www.nejm.org/doi/full/10.1056/NEJMoa1707404 - Farb A et al Patent Foramen Ovale after Cryptogenic Stroke - Assessing the Evidence for Closure. N Engl J Med 2017; 377:1006-1009. September 14, 2017 PMID: 28902595 http://www.nejm.org/doi/full/10.1056/NEJMp1700218 - Ropper AH. Tipping point for patent foramen ovale closure. N Engl J Med 2017 Sep 14; 377:1093 PMID: 28902592 http://www.nejm.org/doi/10.1056/NEJMe1709637
  15. De Rosa S, Sievert H, Sabatino J et al Percutaneous Closure Versus Medical Treatment in Stroke Patients With Patent Foramen Ovale: A Systematic Review and Meta-analysis. Ann Intern Med. 2018. Jan 9. PMID: 29310133 http://annals.org/aim/article-abstract/2668217/percutaneous-closure-versus-medical-treatment-stroke-patients-patent-foramen-ovale - Shah R, Nayyar M, Jovin IS Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis. Ann Intern Med. 2018. Jan 9. PMID: 29310136 http://annals.org/aim/article-abstract/2668216/device-closure-versus-medical-therapy-alone-patent-foramen-ovale-patients
  16. Ng PY, Ng AKy, MSubramaniam B et al Association of Preoperatively Diagnosed Patent Foramen Ovale With Perioperative Ischemic Stroke. JAMA. 2018;319(5):452-462 PMID: 29411032 https://jamanetwork.com/journals/jama/fullarticle/2671466 - Kasner SE, Messe SR Is Patent Foramen Ovale a Risk Factor for Perioperative Stroke? JAMA. 2018;319(5):446-447. PMID: 29411017 https://jamanetwork.com/journals/jama/article-abstract/2671449
  17. Elgendy AV, Saver JL, Amin Z et al Proposal for Updated Nomenclature and Classification of Potential Causative Mechanism in Patent Foramen Ovale-Associated Stroke. JAMA Neurol. Published online April 13, 2020 PMID: 32282016 https://jamanetwork.com/journals/jamaneurology/fullarticle/2763602
  18. Messe SR et al. Practice advisory update summary: Patent foramen ovale and secondary stroke prevention: Report of the Guideline Subcommittee of the American Academy of Neurology. Neurology 2020 May 19; 94:876. PMID: 32350058 https://n.neurology.org/content/94/20/876