Prognosis after percutaneous closure of patent foramen ovale for paradoxical embolism

Methods.

Percutaneous PFO closure was performed in 152 consecutive patients with PFO who had at least one embolic event, according to a study protocol approved by the local Ethics Committee. An embolic event was considered due to paradoxical embolism when the following conditions were fulfilled: 1) presence of PFO with or without ASA (defined as an abnormally redundant interatrial septum with an excursion of >10 mm into the right or left atrium) with spontaneous or provocable right-to-left shunt during contrast transesophageal echocardiography; 2) clinically and radiologically confirmed ischemic stroke, TIA, or peripheral embolism; and 3) exclusion of any other identifiable cardiac, aortic, or cerebrovascular cause. Contrast transesophageal echocardiography (TEE), color Doppler and Duplex examination of the extracranial carotid and vertebral arteries, transcranial Doppler, and an electrocardiogram were performed in all patients.

The procedure was performed under local anesthesia. Venous access was gained via the right femoral vein. The device was implanted under fluoroscopic guidance without echocardiographic monitoring. Patients were treated with 100 mg acetylsalicylic acid once daily for 6 months to provide an antithrombotic protection until full device endothelialization.

A contrast TEE study with aerated colloid solution injected into an antecubital vein was performed prior to device implantation and 6 months after percutaneous PFO closure to assess for a residual shunt following endothelial overgrowth. Spontaneous or provoked right-to-left shunt was semiquantitatively graded according to the amount of bubbles crossing the septum: grade 0 = none; grade 1 = minimal (1 to 5 bubbles); grade 2 = moderate (6 to 20 bubbles); and grade 3 = severe (>20 bubbles).5 Any recurrent embolic event, including TIA, ischemic stroke, or peripheral embolus was considered a primary endpoint. Patients were followed prospectively for up to 6.5 years and follow-up was complete in all but three patients. Patients with suspected embolic recurrence were examined by a neurologist, and an imaging study of the region of interest was obtained. The most recent contact consisted of a telephone interview, addressing recurrence of embolism, device related problems, and health status.

Results.

Patient demographics are summarized in table 1. Six different device types were utilized during the 6-year period (table 2). Device implantation was successful in 150 patients (99%). In one patient, the procedure was aborted prior to device delivery due to laceration of the femoral artery during venous puncture. This required surgical revision, at which time the PFO was closed surgically. In another patient with PFO and a large ASA, the device embolized into the pulmonary artery 12 hours after the procedure. It was retracted percutaneously into the femoral vein and removed from there by local incision. No procedural death was encountered. There were 10 procedural complications (7%) without long-term sequelae, consisting of embolization of the device or parts of it in four patients, cardiac tamponade requiring needle pericardiocentesis in one patient, symptomatic air embolism in three patients, and one additional arteriovenous fistula at the puncture site.

Complete PFO closure was achieved in 79% of patients, whereas a minimal, moderate, or large shunt persisted in 11%, 6%, or 4% of patients. During a mean follow-up period of 1.7 ± 1.6 years (median 1.1 years; range 0.1 to 6.5 years), nine recurrent embolic events were encountered in 150 patients with an implanted device. These comprised one minor ischemic stroke, six TIA, and two peripheral emboli. The actuarial freedom from recurrent embolism was 95.1% at 1 year and 90.6% at 2 and 6 years. A residual shunt was present in five of nine patients, with recurrence at follow-up contrast transesophageal echocardiography. The presence of a residual shunt after percutaneous PFO closure (RR 5.3; 95% CI 1.3 to 21.0; p = 0.02) was a predictor for recurrent embolism (table 3). In patients without residual shunt, the actuarial freedom from recurrence was 98.1% at 1 year and 94.2% at 2 and 6 years.

Discussion.

The current study confirms that percutaneous PFO closure can be performed safely with a high success and low morbidity rate using a variety of devices. There was no mortality, and all complications were without long-term sequelae. Most complications occurred in the early experience with older device types, and reflect, in part, a learning curve. Newer devices, specifically designed for PFO (as opposed to atrial septal occlusion) have been developed, with reduced risk of device dislodgement and embolization and improved closure mechanism.3 Similar morbidity has been observed in other studies of percutaneous PFO closure.2 Complications associated with surgical PFO closure have been as high as 21%.6

With respect to clinical efficacy, the long-term risk of recurrent embolic events after percutaneous closure in our patient population compares favorably with published data on medical7,8⇓ and surgical6,9,10⇓⇓ therapy. The actuarial freedom from recurrence was 95.1% at 1 year and 90.6% at 2 and 6 years in our study, compared with 93% at 1 year and 83% at 4 years following surgical PFO closure.6 The freedom from recurrence in our study was particularly high in patients without residual shunt, amounting to 98.1% at 1 year and 94.2% at 2 and 6 years. In contrast, patients with a residual shunt had an event-free survival of 86.7% at 1 year and 80.9% at 2 and 6 years, underscoring the importance of achieving complete PFO closure.

Older age (>55 years), an associated ASA, multiple prior events, or prior ischemic stroke were not associated with a worse prognosis in our study. However, this finding is preliminary due to the low number of recurrent events, and requires validation in future studies.

Randomized trials comparing medical treatment with interventional PFO closure will determine the best therapeutic strategy in this patient population. Until results from such trials become available, the implantation of PFO occlusion devices is feasible, but should be considered investigational.