PFO closure did not result in reduction in recurrent embolic events - Europe, Canada, Brazil & Australia

ORIGINAL ARTICLE

NEJM - online first

Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism

Bernhard Meier, M.D., Bindu Kalesan, Ph.D., Heinrich P. Mattle, M.D., Ahmed A. Khattab, M.D., David Hildick-Smith, M.D., Dariusz Dudek, M.D., Grethe Andersen, M.D., Reda Ibrahim, M.D., Gerhard Schuler, M.D., Antony S. Walton, M.D., Andreas Wahl, M.D., Stephan Windecker, M.D., and Peter Jüni, M.D. for the PC Trial Investigators

N Engl J Med 2013; 368:1083-1091March 21, 2013DOI: 10.1056/NEJMoa1211716

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BACKGROUND

The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy.

METHODS

We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population.

RESULTS

The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56).

CONCLUSIONS

Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number,NCT00166257.)

CLOSURE trial result (PFO closure for Stroke)

Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale

Anthony J. Furlan et al.

NEJM 2012;366:991-9

Results:
A total of 909 patients were enrolled in the trial. The cumulative incidence (Kaplan–Meier estimate) of the primary end point was 5.5% in the closure group (447 patients) as compared with 6.8% in the medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days in either group, and there were no deaths from neurologic causes during the 2-year follow-up period. A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events.

Conclusions:
In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA. (Funded by NMT Medical).

PFO morphology & Stroke (Infarct) size on MRI

Circulation: Cardiovascular Interventions. 2010

The Association of Patent Foramen Ovale Morphology and Stroke Size in Patients With Paradoxical Embolism
Andre Akhondi, MD; Rubine Gevorgyan, MD; Chi-Hong Tseng, PhD; Leo Slavin, MD; Catherine Dao, MD; David S. Liebeskind, MD and Jonathan M. Tobis, MD

Background Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke through paradoxical embolization to the cerebral circulation. This study evaluated the relationship between the morphological and functional size of the PFO by echocardiography compared with cerebral infarct volume identified on MRI.

Methods and Results Patients who were referred to interventional cardiology with the diagnosis of cryptogenic stroke were included and had either a transesophageal echocardiogram or an intracardiac echo and a brain MRI at the time of stroke. Transesophageal echocardiogram or intracardiac echo was used to obtain PFO measurements. MRI of the brain with 3 sequences (T2, diffusion-weighted imaging, and fluid-attenuated inversion recovery) was used to diagnose acute stroke and measure the infarct volume. In the 72 patients studied, the median measured stroke volume was 4.3 cm3 on diffusion-weighted imaging, 4.1 cm3 on T2, and 3.5 cm3 on fluid-attenuated inversion recovery. There was no significant correlation between the PFO height, length, septum secundum thickness, or echo bubble grade and the infarct volume measured from the 3 MRI sequences. There was a significant correlation between septal excursion distance and infarct volume (r=0.35; P=0.005), but the 12 patients with atrial septal aneurysm did not have the largest strokes.

Conclusions This analysis revealed that septal excursion distance correlates with stroke size by MRI. However, smaller PFO size without the presence of atrial septal aneurysm may still be associated with significant strokes. There was no significant association between PFO height, length by echo, or shunt grade by transcranial Doppler study and brain infarct volume. Therefore, PFO size or morphology should not be the only criteria to decide whether a PFO should be closed.

Stroke & PFO - New devices

J Am Coll Cardiol Intv, 2010; 3:963-967
Patent Foramen Ovale Closure With the SeptRx Device. Initial Experience With the First "In-Tunnel" Device.
Wibke J. Zimmermann, MD, Corinna Heinisch, MD, Nicolas Majunke, MD, Stephan Staubach, MD, Scott Russell, Nina Wunderlich, MD, Horst Sievert, MD*
CardioVascular Center, Sankt Katharinen, Frankfurt, Germany

Objectives: The purpose of this study was to evaluate the safety and effectiveness of the SeptRx patent foramen ovale (PFO) closure device (SeptRx, Inc., Fremont, California).

Background: A PFO is a relatively common remnant of the fetal circulation that can be associated with cryptogenic stroke, transient ischemic attack, migraine, or decompression sickness. Percutaneous PFO closure with different devices has been performed for many years. However, most of the common devices leave a relatively large amount of material in the left and right atria. The SeptRx PFO device (SeptRx, Inc.) is the first PFO closure device designed to fit directly into the pocket of the PFO.

Methods: From July 2006 to May 2007, 13 patients between 18 and 65 years of age with a history of cryptogenic stroke or transient ischemic attack were included into this first-in-man trial. All patients received 100 mg aspirin and 75 mg clopidogrel for 6 months. Follow-up was done at 1 and 6 months after procedure with transesophageal echocardiography and transcranial Doppler.

Results: In 11 of 13 patients, PFO closure with the SeptRx device was successfully performed. In 2 patients, PFO closure with this device was not possible due to the anatomy of the PFO; 1 device was retrieved before release, and the other was recaptured with a snare. After 30 days, 6 of the 11 PFOs were closed; after 6 months, all were closed. No adverse events occurred.

Conclusions: The SeptRx PFO closure device appears to be safe and effective. The advantage of this occluder is that there is only minimal foreign material on the left and right sides of the interatrial septum. This is the first such "in-tunnel" PFO closure device.

The longer anchors are on the left atrial side and are designed to uncoil to accommodate a range of patent foramen ovale (PFO) tunnel lengths. The interior of the device contains a fine-wire braided Nitinol mesh, which provides an immediate barrier to the conduction of emboli and is intended to stimulate the body‘s natural adhesion response for permanent closure of the PFO.

J Am Coll Cardiol Intv, 2010; 3:968-973
Patent Foramen Ovale Closure Using a Bioabsorbable Closure Device
Safety and Efficacy at 6-Month Follow-Up
Ben J. Van den Branden, MD*, Martijn C. Post, MD, PhD, Herbert W. Plokker, MD, PhD, Jurriën M. ten Berg, MD, PhD, Maarten J. Suttorp, MD, PhD
Department of Interventional Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands

Objectives: The aim of this study was to assess the mid-term safety and efficacy of percutaneous patent foramen ovale (PFO) closure using a bioabsorbable device (BioSTAR, NMT Medical, Boston, Massachusetts).

Background: Closure of PFO in patients with cryptogenic stroke has proven to be safe and effective using different types of permanent devices.

Methods: All consecutive patients who underwent percutaneous PFO closure with the bioabsorbable closure device between November 2007 and January 2009 were included. Residual shunt was assessed using contrast transthoracic echocardiography.

Results: Sixty-two patients (55% women, mean age 47.7 ± 11.8 years) underwent PFO closure. The in-hospital complications were a surgical device retrieval in 2 patients (3.2%), device reposition in 1 (1.6%), and a minimal groin hematoma in 6 patients (9.7%). The short-term complications at 1-month follow-up (n = 60) were a transient ischemic attack in the presence of a residual shunt in 1 patient and new supraventricular tachycardia in 7 patients (11.3%). At 6-month follow-up (n = 60), 1 patient without residual shunt developed a transient ischemic attack and 1 developed atrial fibrillation. A mild or moderate residual shunt was noted in 51.7%, 33.9%, and 23.7% after 1-day, 1-month, and 6-month follow-up, respectively. A large shunt was present in 8.3%, 3.4%, and 0% after 1-day, 1-month, and 6-month follow-up.

Conclusions: Closure of PFO using the bioabsorbable device is associated with a low complication rate and a low recurrence rate of embolic events. However, a relatively high percentage of mild or moderate residual shunting is still present at 6-month follow-up.

The biodegradable matrix is mounted on the MP35N STARFlex "double-umbrella" framework. The left and right atrial umbrellas are connected by microsprings, serving as a self-centering mechanism.