Transcatheter Closure of Patent Foramen Ovale

HomeCirculationVol. 143, No. 16Transcatheter Closure of Patent Foramen Ovale Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessArticle CommentaryPDF/EPUBTranscatheter Closure of Patent Foramen OvaleNot Always an "Open or Shut" Case Ashish H. Shah, MD, MD-Res, MRCP, Rishi Puri, MBBS, PhD and Richard A. Krasuski, MD Ashish H. ShahAshish H. Shah Ashish H. Shah, MD, MD-Res, Y-3006, St Boniface Hospital Winnipeg, Manitoba, R2H 2A6, Canada. Email E-mail Address: [email protected] https://orcid.org/0000-0002-9396-7178 St Boniface Hospital, Section of Cardiology, University of Manitoba, Winnipeg, Canada (A.H.S.). , Rishi PuriRishi Puri Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Ohio (R.P.). and Richard A. KrasuskiRichard A. Krasuski Division of Cardiology, Duke University Health System, Durham, NC (R.A.K.). Originally published19 Apr 2021https://doi.org/10.1161/CIRCULATIONAHA.120.050961Circulation. 2021;143:1539–1541Stroke or transient ischemic attack without an apparent cardiovascular source is often described as "cryptogenic" and is frequently caused by paradoxical embolization. Patent foramen ovale (PFO) is the most commonly identified source of right-to-left shunting (RLS) and hence actively searched for after cryptogenic stroke. If identified, transcatheter closure (TCC) is generally advised. However, the less commonly observed pulmonary arteriovenous malformation and atrial septal defect/septal fenestration also facilitate paradoxical embolism and can be eliminated through transcatheter intervention. Occasionally, these defects can coexist, making their identification even more challenging. Agitated saline contrast injection is the most commonly used method to screen for RLS and similarly to evaluate effectiveness after TCC of PFO.Recently published randomized trials have demonstrated the effectiveness of TCC of PFO in reducing recurrent cryptogenic stroke.1,2 Patients included in these trials were relatively young (18–60 years) with traditional cardiovascular risk factors and underwent thorough investigation to ensure that paradoxical embolization through a PFO was the most plausible stroke cause. Meta-analysis of the 5 large randomized trials included 3627 patients with a mean follow-up of 3.7 years demonstrated a significant reduction in ischemic stroke after device closure (absolute risk reduction, 2.11%; and relative risk reduction, 50.5%).3 New-onset atrial fibrillation was more common after TCC (odds ratio, 5.15; 95% CI, 2.18–12.15), although it resolved within 45 days of closure in 75%.3 Recently, the US Food and Drug Administration approved both the Amplatzer PFO Occluder and the Gore Cardioform Device for treating cryptogenic stroke believed to be caused by PFO.TCC of PFO in patients with paradoxical embolism is ideally intended to achieve complete elimination of RLS, as persistent RLS after closure can increase the risk of recurrent stroke or peripheral embolization.4 Despite recruiting highly selected patients in whom stroke was believed to be exclusively caused by paradoxical embolization through PFO, studies of TCC generally demonstrated a mere reduction and not total elimination of stroke recurrence at medium-term follow-up,1 with the exception of the CLOSE trial (Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence).2 The remaining questions after these trials include the following: Who are the patients who experience stroke recurrence, what are the underlying mechanisms of these events, and what is the significance of a positive RLS after PFO closure? Plausible explanations include (1) the PFO was merely a bystander in some patients, (2) an alternative pathology existed that may have facilitated RLS and paradoxical embolization (ie, a pulmonary arteriovenous malformation or small atrial septal defect/septal fenestration that was not occluded during TCC), (3) there was a residual shunt through the treated PFO, or (4) a left-sided thromboembolic process was previously missed or developed de novo (Figure).Download figureDownload PowerPointFigure. Recurrent stroke or persistent right-to-left shunt after patent foramen ovale (PFO) closure.A, Mechanisms responsible for persistent right-to-left shunt after PFO closure: (a) pulmonary arteriovenous malformation, (b) leak through the device, and (c) atrial septal fenestration. B, Various causes to be considered in the patients with recurrent stroke after PFO closure.Effectiveness of PFO closure is typically assessed using bubble contrast during transthoracic echocardiography. An abnormal RLS after PFO closure could be the result of incomplete PFO closure, inadequate device endothelization, or coexistence of additional defects. All 3 major trials demonstrating effectiveness of TCC of PFO had patients with moderate to strongly positive RLS at their latest follow-up echocardiograms: the RESPECT trial (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment trial; follow-up, 6 months; moderate to strong RLS, 6.5%); the REDUCE trial (GORE HELEX Septal Occluder/GORE CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging-Confirmed TIA in Patients With Patent Foramen Ovale [PFO] - The Gore REDUCE Clinical Study; follow-up, 12 months; abnormal RLS, 24.4%; severity not described), and the CLOSE trial (Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence trial; follow-up, 10.8 months; moderate to strong RLS, 7%). As we previously described, among 568 patients undergoing transthoracic echo bubble test at 12 months after PFO closure after cryptogenic stroke, a coexisting additional defect was found in 1.8% (10/568)—all of whom had moderate to strong RLS after TCC. Pulmonary arteriovenous malformation was most commonly identified (4/10), followed by leak through the device (3/10) and coexistent septal fenestration (2/10)5; each of these additional defects was successfully treated with TCC. A few additional points warrant further discussion:An additional source of RLS was chiefly identified in patients with a moderate to severe positive bubble test at 12 months after PFO closure, whereas no pathology was identified in patients with mildly positive RLS. In all 3 of the previously mentioned trials, patients were investigated with RLS 6 to 12 months after PFO closure. Although each of these studies reported a moderate to strongly positive bubble test in ≈7% of patients at this time point, no further investigations were performed to evaluate mechanisms of persistent RLS in these patients.More important, the relationship between stroke recurrence after PFO closure and presence of a persistently positive bubble test was not reported.A positive bubble test after PFO closure is not equivalent to the presence of a pulmonary arteriovenous malformation, because device endothelization may take up to 12 to 18 months, and leak through the device can persist; efforts should be made to better identify the source of shunt, especially in those patients with moderate to strongly positive RLS 12 to 18 months after closure.As we previously reported, all additional sources of residual RLS were amenable to further transcatheter interventions.5 This begs the following question: If each patient undergoing TCC of a PFO were to be followed up and investigated until either the bubble test became negative or no other cause was identified, would we observe even further reductions in stroke recurrence after closure, thus enhancing its clinical benefit? Although purely speculative at this time, a pragmatic, prospective investigator-initiated registry may be able to better shed further light on this interesting and important yet unresolved issue.AcknowledgmentsThe authors acknowledge Fuad Zain, MBBS, MFA (HeartStudio, Rochester, New York), for the graph work.Sources of FundingDr Shah is supported by the Establishment Grant from the Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.Disclosures None.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.https://www.ahajournals.org/journal/circAshish H. Shah, MD, MD-Res, Y-3006, St Boniface Hospital Winnipeg, Manitoba, R2H 2A6, Canada. Email [email protected]mb.caReferences1. Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, Tirschwell DL; RESPECT Investigators. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke.N Engl J Med. 2017; 377:1022–1032. doi: 10.1056/NEJMoa1610057CrossrefMedlineGoogle Scholar2. Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, Arquizan C, Béjot Y, Vuillier F, Detante O, et al.; CLOSE Investigators. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke.N Engl J Med. 2017; 377:1011–1021. doi: 10.1056/NEJMoa1705915CrossrefMedlineGoogle Scholar3. Ntaios G, Papavasileiou V, Sagris D, Makaritsis K, Vemmos K, Steiner T, Michel P. Closure of patent foramen ovale versus medical therapy in patients with cryptogenic stroke or transient ischemic attack: updated systematic review and meta-analysis.Stroke. 2018; 49:412–418. doi: 10.1161/STROKEAHA.117.020030LinkGoogle Scholar4. Windecker S, Wahl A, Chatterjee T, Garachemani A, Eberli FR, Seiler C, Meier B. Percutaneous closure of patent foramen ovale in patients with paradoxical embolism: long-term risk of recurrent thromboembolic events.Circulation. 2000; 101:893–898. doi: 10.1161/01.cir.101.8.893LinkGoogle Scholar5. Shah AH, Osten M, Benson L, Alnasser S, Bach Y, Vishwanath R, Van De Bruaene A, Shulman H, Navaranjan J, Khan R, et al.. Incidence and outcomes of positive bubble contrast study results after transcatheter closure of a patent foramen ovale.JACC Cardiovasc Interv. 2018; 11:1095–1104.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails April 20, 2021Vol 143, Issue 16Article InformationMetrics Download: 1,365 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.120.050961PMID: 33872078 Originally publishedApril 19, 2021 Keywordsarteriovenous malformationsheart septal defects, atrialechocardiographyforamen ovale, patentembolic strokePDF download Advertisement SubjectsCerebrovascular Disease/StrokeIschemic StrokeTransient Ischemic Attack (TIA)