Patent foramen ovale diameter and embolic stroke: a part of the puzzle?

Abstract

Understanding the pathological basis of cerebral ischemia is critical when considering whether embolism is the cause of a transient ischemic attack or nonhemorrhagic stroke (1). Data from the Stroke Data Bank of the National Institutes of Health (NIH) suggest that cerebral emboli account for 60% of all ischemic strokes. To make the diagnosis, the other major causes of stroke—large vessel atherothrombotic disease (15%), small vessel lacunar stroke (25%), and other mechanisms, such as dissection or arteritis (3%)—must be excluded by determining that the stroke topology is not lacunar and that the parent vessels supplying the territory of the ischemic stroke are free of intrinsic atherosclerosis, dissection, or other causes of stenosis (2). It then becomes essential to identify the source of the embolus. The NIH Stroke Data Bank distinguishes two major categories of embolic stroke. About one-third are from a definite, clinically apparent, cardiac causes, such as atrial fibrillation, valvular heart disease (prosthetic or rheumatic), post-myocardial infarction, and infective endocarditis; the remainder have no clinically apparent cardiac cause (2). The advent of reliable transthoracic and transesophageal echocardiography has enabled a more clinically relevant and precise classification. We favor a classification scheme based on commonly accepted standards of preventive therapy (3), and classify the clinically apparent cardiac sources into those for which antithrombotic therapy is the standard of care—atrial fibrillation, valvular heart disease, and post-myocardial infarction— and those in which it is contraindicated, such as infectious endocarditis and myxomatous disease. We then classify the larger category of “unknown source” based on the echocardiographic findings as either a possible cardiac source (patent foramen ovale, mitral annular calcification, left ventricular dysfunction, left ventricular thrombus); a possible ascending aortic atheromatous source as diagnosed by transesophageal echocardiography; or a truly unknown source, when the transthoracic and transesophageal echocardiograms and cardiac monitoring are nondiagnostic. With the exception of the rate of secondary embolic strokes in patients with a 4 mm or greater plaque in the aorta, there are few data on the cumulative risk of stroke associated with these conditions (4), nor have there been any randomized trials to assess the efficacy of stroke prevention strategies in patients with these potential cardiac sources of embolism. Of all the possible cardiac causes of embolic stroke, a patent foramen ovale is perhaps the most clinically perplexing in terms of stroke prophylaxis. An anatomical marker of stroke risk in patients with a patent foramen ovale would allow the identification of a high-risk group of patients whose annual stroke risk would be high enough to warrant a randomized trial of preventive therapy. In this issue of The Green Journal, Schuchlenz and colleagues have been able to identify such an anatomical marker, just as Amarenco and colleagues accomplished in ascending aortic atheromatous disease (the .4 mm plaque) (5). If it can be confirmed that a mean diameter of a patent foramen ovale greater than 4 mm conveys an odds ratio of 12 for embolic stroke, this could well be the feature used in future clinical trials to identify high-risk patients. Homma and others have suggested that the size of a patent foramen ovale, as measured by agitated saline contrast, is important in determining stroke risk (6). Using a state-of-the-art 5 MHz multiplanar transesophageal probe, and excluding other stroke subtypes and other possible sources of embolism, the results of the study by Schuchlenz et al suggest that it is reasonable to conclude that a patent foramen ovale with a diameter .4 mm was the likely embolic source. Because computerized tomographic scans were the only imaging technique used to identify strokes in many patients, there may be a slight bias for supratentorial strokes. But the decision to include only patients with an infarct greater than 1.5 cm in diameter in an arterial territory with a patent arterial supply reliably assures an embolic cause for the stroke. Recently, Lock (personal communication, June 2000) suggested that the volume of a patent foramen ovale may be a determinant of “local thrombus” formation and thus may affect the rate of embolism. Rosenberg has advanced the concept that vascular bed-specific hemostasis is important in thrombus formation in atherothrombotic cardiovascular disease, as well as in venous thromboembolism (7). It may be that local cardiac endothelial factors, in relation to the size of the patent foramen ovale, influence the propensity to form an unstable thrombus and thus affect the risk of embolic stroke. In collaboration with Rosenberg and colleagues, we have determined that the level of activity of the hemostatic system increases with age in patients with atrial fibrillation (8). Moreover, the increased activity is reduced Am J Med. 2000:109:506 –507. From the Neurology Service, Massachusetts General Hospital, Boston, MA Requests for reprints should be addressed to J. Phillip Kistler, MD, Massachusetts General Hospital, Neurology Service, 32 Fruit Street, (VBK 802), Boston, MA, 05114-2695.