Over the past two decades, evidence of a link between a patent foramen ovale and so called cryptogenic strokethat is, stroke with no other obvious causehas been accumulating, particularly in younger stroke patients. For example, the incidence of PFO in patients with cryptogenic stroke is about four times that expected in the general population. Presumed paradoxical embolism via the right-to-left shunt is the suspected mechanism of these strokes.

In these patients, lifelong anticoagulation with warfarin is standard, the researchers, with senior author Dr Donald J Hagler (Mayo Clinic College of Medicine, Rochester, MN), write. Surgical, and now percutaneous, closure of the PFO has also been undertaken to eliminate the shunt and hopefully avoid events.

In this study, Hagler and colleagues, with first author Dr Anant Khositseth, reviewed the records of patients with severe right-to-left shunt across the atrial septum and presumed paradoxical embolism who underwent closure of a PFO and/or ASD with use of either the Amplatzer^® PFO occluder or the Amplatzer^® septal occluder (AGA Medical, Golden Valley, MN). The septal occluder is approved by the FDA, Hagler told heartwire in an interview, but the PFO occluder is still available only under a Humanitarian Device Exemption that restricts its use. However, technically, it's possible to use the septal occluder for PFOs, he noted.

In this series of 103 patients, devices were deployed successfully in all cases. Procedural complications included atrial fibrillation in two patients, vessel injury in three, profound sinus node dysfunction in one, and device embolization with successful retrieval in one case. No patients died.

At three months, seven of 95 monitored patients had residual shunt; at 12 months, two of 23 had trivial residual shunt. At a mean follow-up of about eight months, there were three recurrent eventstwo transient ischemic attacks (TIA) and one retinal artery occlusionfor an average annual recurrence rate of 3.6% at 23 months, a number similar to most previous reports, Hagler noted.

Importantly, in those who had recurrent events, none had a residual shunt, "so we would have to postulate that the reason for their event was something other than an embolic event," he said.

In the second report, Hagler and colleagues, with first author Dr Michael G Earing, describe their experience to date using intracardiac echocardiography as an adjunct to PFO and ASD closure procedures.

In general, transesophageal echo has been used to guide these percutaneous procedures. However, intracardiac echo, where the ultrasound probe is threaded into the heart via femoral venous access, provides several potential advantages over TEE, Hagler said. First, there is no need for additional echo support staff. "We had complete control over the images that we were trying to generate, and we didn't have to rely on someone else to do the imaging," he said. Further, the heavy sedation or general anesthesia necessary to use TEE is not required with ICE, eliminating particularly problems with airway management. "So the recovery's faster, the patients feel better, and they can get out of the hospital the same day without any problems at all," Hagler said.

The recovery's faster, the patients feel better, and they can get out of the hospital the same day without any problems at all.

It's a fairly large probe, he noted, using an 11F sheath, so it can't be used in children younger than about five. The particular probe they use was developed by one of the coauthors, Dr James B Seward, at their institution. In this paper, they report outcomes in 94 patients undergoing PFO and ASD closure using ICE guidance. ICE identified a previously unrecognized anatomical diagnosis in 32 of the 94 patients; an additional ASD or PFO was found in 16. Complications included three cases of atrial fibrillation and one of supraventricular tachycardia; two of these episodes resolved spontaneously, and the other two responded to cardioversion with no recurrence.

"We believe that ICE should be considered the preferred imaging technique for guidance of transcatheter device closure of ASD/PFO in adults and larger pediatric patients," they conclude.

In an editorial accompanying the papers, neurologist Dr Harold P Adams (University of Iowa, Iowa City), urges some caution in the widespread adoption of PFO closure to reduce cryptogenic stroke.3

"The issue is that a patent foramen ovale is a common finding in patients with stroke, but it's also a common finding in healthy people," Adams told heartwire. "The cause-and-effect relationship between a PFO and stroke still has not been established with any degree of certainty. There probably are some patients with stroke who have paradoxical embolization, but it's probably not as many as are being diagnosed now."

The cause-and-effect relationship between a PFO and stroke still has not been established with any degree of certainty.

"These procedures are not extremely dangerous," he said, "but there are risks, and we need to know that the risks of placement of the device are more than compensated by superiority in preventing recurrent stroke, and right now, we don't have those data."

While the question of whether PFO closure can be done safely has been answered, the question remains of whether it should be done, Adams said. There is no reason that these devices cannot be tested with the same scientific rigor that has been brought to bear on other drugs, surgeries, or devices, he said. PFO closure "may be a spectacular treatment for this, but we need to find out, and cardiology and neurology need to work together on this to establish its efficacy."

Adams is an investigator in an ongoing randomized trial comparing the addition of PFO closure with best medical therapy in 1600 patients with stroke or TIA. Principal investigator on that trial, called CLOSURE I, is Dr Anthony Furlan (Cleveland Clinic Foundation, OH). The study is sponsored by NMT Corporation (Boston, MA), maker of the CardioSEAL^® and StarFlex^® occluders, the latter of which is being tested in the trial.

Competitor AGA Medical is running a trial of its own, called the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) trial. RESPECT is a prospective, randomized, multicenter trial comparing PFO closure with the Amplatzer PFO occluder with best medical management with antiplatelet or anticoagulant therapy.

Hagler acknowledges that these controlled studies will eventually provide more evidence needed about the efficacy of PFO closure, although he pointed out that recruitment for the studies is "difficult, because there aren't very many who want to be randomized to [warfarin] therapy for two years."

"The problem for many people right now is they've had a stroke, they're very anxious, they don't want to have another stroke, and for a variety of reasons, they can't or won't take chronic [warfarin] therapy, and they need something to provide closureotherwise, they would have surgical closure of their PFO," he said. "So we think there is a significant group of patients to whom we need to continue to offer ASD device closure since it's available."