BACKGROUND/SIGNIFICANCE
Approximately 40% of cerebral infarctions cannot be classified as strokes of determined cause despite a complete diagnostic work-up and are labeled as "cryptogenic strokes". Patent foramen ovale (PFO), a hemodynamically insignificant inter-atrial communication, has been suggested as a potential conduit for paradoxical embolization in some patients with cryptogenic stroke. Among patients with stroke of undetermined origin aged under 40, 50, or 55 years, contrast echocardiography has identified a high prevalence of PFO. Most recently, we have found a several-fold higher prevalence of PFO in cryptogenic stroke patients, both in those aged below and above 55 years compared to those with a definable cause of stroke. Thus, the association of a PFO with cryptogenic stroke is significant not just for young but for all age groups. Since stroke is predominantly a disease of the elderly, association of PFO with cryptogenic stroke could have more public health consequences in terms of number of total patients, than if it were only associated with the young patients.
In order to assess the magnitude of the problem, the yearly incidence of cryptogenic strokeand the prevalence of PFO in both the general population and the population with cryptogenic stroke can be used to estimate the number of strokes attributable to PFO. The yearly incidence of stroke in the U.S. is estimated at 400,000 to 500,000, and approximately 40% are cryptogenic. If one uses Lechat et al's findings and assumes that the prevalence of PFO in the general population is 10% versus 40% in patients with cryptogenic stroke, then at least 48,000 strokes each year may be attributable to the presence of a PFO. Cryptogenic stroke has a death or recurrence rate at less than 30 days of approximately 3.0%, and one year death or recurrent stroke rate of approximately 16%. Therefore the national cost, as a result of recurrent stroke requiring hospitalizations and due to lost-work days is enormous.
Although warfarin or aspirin is often used, there is no consensus on the treatment of cryptogenic stroke patients with PFO. The rate of stroke recurrence on medical therapy is unknown, and there is no data on the additional risk the presence of a PFO imparts on cryptogenic stroke patients without a PFO. Some have advocated percutaneous closure of PFO, and reported on the preliminary results, but the role of such an invasive and potentially very costly procedure remains undefine.
At the present, treatment of patients with cryptogenic stroke and PFO is undefined due to
lack of any meaningful data. If percutaneous or surgical closure of PFO becomes widely accepted without the medical option tested, the resulting national cost may be extremely high. For percutaneous closure, with an assumed procedure cost of $15,000 (mean DRG cost of one-vessel angioplasty at our institution), the annual cost will be approximately $720 million for 48,000 patients with PFO related stroke. For surgical closure, with the cost at $35,000 each (mean DRG cost of atrial septal defect closure at our institution), the annual cost can be approximated at a staggering $1.68 billion.
Therefore, a study to assess the impact of warfarin or aspirin on stroke recurrence or systemic embolization in cryptogenic stroke patients with PFO would provide very important guidelines for the treatment of these patients. If one were to design such a trial, recruitment, neurological work-up, randomization, and follow-up need be carefully considered. At the same time, in order to assure adequate sample size, cooperation from a large number of centers experienced in stroke management will be necessary.
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