Catheterization and Cardiovascular Interventions 55:195–196 (2002) Editorial Comment The Case for Closing PFOs Jonathan Tobis, MD Interventional Cardiology Research, UCLA School of Medicine, Los Angeles, California The significance of a patent foramen ovale as the culprit pathway for a cryptogenic stroke is a fascinating concept that is gaining acceptance. When this idea was first proposed, it was greeted with skepticism in the scientific community. The likelihood that a blood clot from the lower extremities could enter the right atrium just at the moment when a patient produced a spontaneous valsalva maneuver to open a patent foramen ovale and push the embolus into the left atrium was thought to be extremely remote. However, there are two pieces of evidence that suggest this indeed may be the major physiologic mechanism of cryptogenic stroke. The first is that the incidence of a PFO (diagnosed by TEE) is present in only 10%–23% of the population, whereas the incidence of a PFO in patients who have had a cryptogenic stroke is estimated at40%–70% [1– 4]. The second finding is that recurrent stroke is nearly eliminated in patients who have the PFO closed [5]. In addition, isolated cases have been de-scribed by echocardiography, where a thrombus was seen straddling a foramen ovale. It is clear from these examples that thrombus can pass across a PFO. What is uncertain is how often this event occurs. Jim Lock, who pioneered PFO closure in 1989, has proposed an additional mechanism to explain how a PFO could be a causal factor in cryptogenic stroke. He suggests that the PFO acts more like a tunnel rather than a hole or flap. Since there is usually stasis within this tunnel, a thrombus may develop in situ within the PFO and subsequently is pushed into the left atrium when the patient bears down. This potential mechanism would address the concerns of those who are daunted by the probability of a venous thrombus spontaneously crossing the PFO on its voyage through the right side of the heart. A rough estimate of the magnitude of this problem is enlightening. The number quoted by the American Stroke Association for people suffering a symptomatic stroke each year in United States is 1 million. Of these, 80% are ischemic, 20% are hemorrhagic. The Stroke Center at UCLA estimates that 20% of these 800,000 ischemic strokes are cryptogenic. Of the estimated 160,000 cryptogenic strokes per year, approximately40%–70% have PFOs. The estimated number may de-pend on how aggressive the evaluation has been. This yields approximately 60,000 –110,000 strokes per year in which PFO is the leading identifiable cause. In addition, recent population studies using MRI screening suggest that there may be up to 11 million Americans per year who suffer a silent stroke. Since transesophageal echo-cardiogram studies were not performed in this patient population, we do not know what the incidence of PFO is in these patients with asymptomatic strokes. The potential volume of patients at risk is disturbing (Jeffrey Saver, UCLA Stroke Service, personal communication).With the availability of the CardioSEAL device used under the Humanitarian Device Exemption regulations of the FDA, percutaneous closure of PFOs in patients with cryptogenic stroke has increased. Approximately 4,000devices have been deployed in the past 3 years. It is unfortunate that no