International PFO Consortium

Background

The prevalence of patent foramen ovale (PFO) is about 25% in the general population and
approximately 40% in patients who have ischemic stroke of unknown cause (cryptogenic stroke).
Given the large number of asymptomatic patients, no primary prevention is currently
recommended. On the contrary, secondary prevention is very important. Prospective studies
have shown that antithrombotic treatment (ATT) with aspirin or warfarin appears to negate the
risk of recurrent stroke associated with a PFO. Patients with spontaneous or large
right-to-left shunts (RLS), those with a coinciding atrial septal aneurysm (ASA) or multiple
ischemic events prior to the PFO diagnosis may still be at increased risk of stroke
recurrence despite ATT. Percutaneous device closure (PDC) is a challenging alternative to
ATT. Several studies reported 0% to 3.4% annual recurrence rates of stroke or TIA in patients
treated by PDC. To date, there is no data from randomized controlled trials (RCT) comparing
the risk of stroke recurrence after PDC with that under ATT only. The results from ongoing
RCTs are not to be awaited in the near future, mainly due to low enrolment and event rates.
Even if RCTs are completed successfully, statistical differences may remain undetected with
the planned sample sizes. Alternative data-gathering strategies such as multicenter
registries are needed to overcome the low recruitment rates.

Objective

1) To compare the risk of recurrent stroke and TIA in patients aged ≤ 55 years with PFO and
otherwise unexplained stroke who undergo PDC or receive ATT only; 2) To assess the
etiological role of PFO for stroke/TIA in patients aged > 55 years; 3) To assess the risk of
recurrent stroke/TIA in "high-risk" PFO patients (i.e. those with spontaneous (at rest) or
large RLS, coinciding ASA, or multiple previous cerebrovascular events).

Methods

Multicenter prospective non-randomized study with scheduled 3-years follow-up of patients
with PFO and ischemic stroke or TIA. Participating centers: Swiss University Hospitals of
Basel, Bern, Geneva, Lausanne and Zurich, the Cantonal Hospital of Aarau, the Triemli
Hospital, the Alfried-Krupp Krankenhaus of Essen, the University Hospital of Essen, the
Klinikum Worms gGmbH, Tufts Medical Center, Baystate Medical Center, the East Medical Center
Tyler, and the University Hospital of Leuven.

Inclusion Criteria:

- Age > 18 years

- Diagnosis of PFO established by transesophageal echocardiography (TEE)

- Ischemic stroke or transient ischemic attack within the previous 6 months

Exclusion Criteria

- Non-vascular origin of the neurological symptoms after brain imaging (CT scan or MRI)

- Comorbid condition that would interfere with the study

- Pregnancy

- History of intracranial bleeding, confirmed arterio-venous malformation, aneurysm or
uncontrolled coagulopathy

- Contraindications for TEE, echocardiographic or iodine contrast media