Device Closure of Patent Foramen Ovale for Cryptogenic Stroke: Patient Selection and Outcomes According to New Randomized Trials

  • Adam M. Carroll
  • John D. CarrollEmail author
Structural Heart Disease (RJ Siegel and NC Wunderlich, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Structural Heart Disease


Purpose of Review

This review summarizes the most recent randomized clinical trials that studied the role of device-mediated patent foramen ovale (PFO) closure in patients after an ischemic stroke presumed to have been caused by a paradoxical embolism.

Recent Findings

Three major randomized trials published in 2017 studied the strategy of using PFO closure for secondary prevention in patients between the ages of 18 and 60 who presented with an index stroke having characteristics of an embolic mechanism. All patients had a PFO that potentially could have enabled paradoxical embolism and other causes of stroke were excluded by a thorough neurologic and cardiac evaluation. Patients were randomized to PFO closure versus medical therapy alone using a variety of guideline-recommended medications. After multiple years of follow-up, all three trials showed superiority in the device arm versus the medical arm with a relative risk reduction of recurrent stroke from 46 to 100% and an absolute recurrent stroke reduction from 0.49 to 1.32% per year. Complications related to the procedure and the device were infrequent and mostly transient.


These results have transformed the care of these patients, lead to FDA approval of two PFO closure devices, and started the process of updating guidelines. Patient selection is critically important since the presence of a PFO may be incidental. Therefore, both a neurologist and a cardiologist, who can also perform this procedure safely and effectively, should complete the initial evaluation and discuss their findings and recommendations with the patient as part of a shared decision-making process. There are remaining questions regarding how these trial results relate to older patients, patients with overt venothrombotic disease, and those with thrombophilia.


Patent foramen ovale Stroke Paradoxical embolism Septal closure Clinical trials Atrial septal aneurysm 


Compliance with Ethical Standards

Conflict of Interest

John D. Carroll has served on the national steering committee of the RESPECT trial and has received payments for activities related to the work performed by the steering committee. These payments were from the study sponsors over the duration of the trial including AGA Medical, St. Jude Medical, and Abbott Vascular.

Adam M. Carroll declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in the RESPECT trial involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012;366(11):991–9.CrossRefGoogle Scholar
  2. 2.
    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. InMayo Clinic Proceedings 1984 Jan 1 (vol. 59, No. 1, pp. 17-20). Elsevier.Google Scholar
  3. 3.
    Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368(12):1083–91.CrossRefGoogle Scholar
  4. 4.
    Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013;368(12):1092–100.CrossRefGoogle Scholar
  5. 5.
    Wiktor DM, Carroll JD. The case for selective patent foramen ovale closure after cryptogenic Stroke. Circ Cardiovasc Interv. 2018;11(3):e004152.CrossRefGoogle Scholar
  6. 6.
    Saver JL, Mattle HP, Thaler D. Patent foramen ovale closure versus medical therapy for cryptogenic ischemic stroke: a topical review. Stroke. 2018;49(6):1541–8.CrossRefGoogle Scholar
  7. 7.
    •• Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022–32 Multicenter RCT demonstrating superiority of PFO closure to medical therapy in preventing recurrent nonfatal stroke, fatal ischemic stroke, and/or early death for patients with prior cryptogenic stroke. CrossRefGoogle Scholar
  8. 8.
    •• Søndergaard L, Kasner SE, Rhodes JF, Andersen G, Iversen HK, Nielsen-Kudsk JE, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033–42 Multinational trial demonstrating superiority of PFO closure combined with antiplatelet therapy relative to antiplatelet therapy alone in preventing recurrent stroke in those with prior cryptogenic stroke, but with higher rates of device complication and atrial fibrillation. CrossRefGoogle Scholar
  9. 9.
    •• Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011–21 Multicenter trial demonstrating superiority of PFO closure with antiplatelet therapy relative to antiplatelet therapy alone in preventing stroke recurrence in those with prior cryptogenic stroke likely caused by PFO, but with higher rates of atrial fibrillation. CrossRefGoogle Scholar
  10. 10.
    Mirzada N, Ladenvall P, Hansson P, Eriksson P, Dellborg M. Multidisciplinary management of patent foramen ovale (PFO) and cryptogenic stroke/TIA. J Multidiscip Healthc. 2013;6:357–63.CrossRefGoogle Scholar
  11. 11.
    Kent DM, Ruthazer R, Weimar C, Mas JL, Serena J, Homma S, et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology. 2013;81(7):619–25.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.University of Colorado School of MedicineAuroraUSA
  2. 2.Interventional CardiologyUniversity of Colorado HospitalAuroraUSA

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