Often, despite an extensive evaluation, an embolic fragment is not documented, and the diagnosis of cerebral embolism is made on circumstantial evidence. The most commonly recognized source for cerebral embolism is the heart. However, identification of a potential cardiac source does not prove embolism, especially if there is coexistent atherosclerosis or if the cardiac lesion is of uncertain clinical significance (Kittner et al 1992). Atheroembolism from the great vessels such as the aortic arch or carotid bifurcation is also a common cause of cerebral ischemia. Cardiac conditions predisposing to cerebral embolism include atrial fibrillation, valvular disorders, and the cardiomyopathies. Embolic stroke also occurs as a complication of cardiac catheterization, cardiac surgery, and cardiac transplant (Furlan and Breuer 1984).
Atrial fibrillation is found in up to 20% of all persons with ischemic stroke and in approximately 50% of all cardioembolic strokes. The risk of embolism in patients with atrial fibrillation is highest during the first months after the initial diagnosis. Longitudinal studies (eg, Framingham) reveal that certain causes of atrial fibrillation or underlying heart disease increase the risk of cerebral embolism. For example, the combination of atrial fibrillation with mitral stenosis increases the risk of cerebral embolism by a factor of 17, whereas atrial fibrillation not associated with rheumatic heart disease is associated with a 6-fold increased risk. The Stroke Prevention in Atrial Fibrillation trials identified hypertension, recent congestive heart failure, and prior embolism as factors associated with increased stroke risk in atrial fibrillation (Stroke Prevention in Atrial Fibrillation Investigators 1992a). The annual rate of embolism was 2.5% in patients with atrial fibrillation and none of these factors, 7.2% with 1 factor, and 17.6% with more than 1 factor. Lone atrial fibrillation in young patients without any other detectable cardiac disorder has a substantially lower rate of cerebral embolism, ranging between 0.4% and 1% per year (Kopecky et al 1987; Wolf et al 1991).
There has been increased research on genetic aspects of atrial fibrillation in recent years. Several genetic loci have been linked with atrial fibrillation (Tsai et al 2008). These loci are related to ionic channels, calcium handling proteins, conduction, and fibrosis. Another report described 11 members of a family with atrial fibrillation in which a frameshift mutation was detected in the gene encoding atrial natriuretic peptide (Hodgson-Zingman et al 2008). Larger genome-wide studies will likely be done in the future.
Myocardial infarction frequently is the source of emboli to the brain. The period of highest risk of cerebral embolism is within the first 4 weeks of acute myocardial infarction (Meltzer et al 1986). Embolism most frequently complicates transmural anterior wall infarcts; a secondary left ventricular thrombus is the usual substrate responsible for cerebral embolism (Asinger et al 1981; Kupper et al 1989; Vecchio et al 1991). Intracavitary stasis occurring during left ventricular dysfunction provides the milieu for the formation of left ventricular thrombus (Fuster and Halperin 1989). The majority of strokes occur within the first 2 weeks following an acute myocardial infarction, possibly reflecting the mobile nature of early thrombus formation. The rate of in-hospital stroke following MI was less than 1% in a large study from a myocardial infarction registry (Van de Graaff et al 2006). There was a lower rate of stroke in patients who received early cardiac revascularization procedures. The risk of cerebral embolism may persist at approximately 10% for patients with left ventricular thrombus followed for 2 years (Stratton and Resnick 1987).
Another cardiac condition that predisposes to cerebral embolism is dilated cardiomyopathy. The dilated cardiomyopathies are characterized by global ventricular dysfunction and are highly associated with arrhythmias. It is this combination that leads to chronic intracavitary stasis and is responsible for the conditions conducive to cerebral embolism (Ciaccheri et al 1989).
Mitral valve stenosis is usually a sequela of rheumatic fever, which afflicts approximately 1.5 million Americans. Mitral stenosis causes the left atrium to dilate and is a frequent cause of atrial fibrillation. A left atrial thrombus forms in a large number of affected patients and provides the substrate for cerebral embolism (Coulshed et al 1970). Embolism may also occur in mixed lesions of the mitral valve (stenosis-regurgitation), but isolated mitral regurgitation is not a common cause of cerebral embolism. Mitral valve prolapse is pathologically characterized by fibromyxomatous degeneration of the leaflets and the chordae tendinea. Mitral valve prolapse is a common finding in young adults and is typically associated with a benign course. Overall, the stroke risk for patients with mitral valve prolapse is low, with an estimated yearly incidence of 0.02%. It should be considered a potential cause of stroke or transient ischemic attack when all other causes have been excluded. Mitral annular calcification also is linked with embolic stroke, especially when there is associated atrial fibrillation. However, mitral annular calcification is prevalent in elderly people and may be a marker of concomitant atherosclerosis in most patients rather than a source of embolism.
Aortic stenosis is a rare cause of cerebral emboli, which are usually calcific.
Cerebral embolism is a major cause of morbidity and mortality associated with prosthetic cardiac valves. Rates of embolism vary depending on the position of the valve and whether the valve is mechanical or bioprosthetic. The rate of embolism in patients with mechanical mitral valves who are not treated with anticoagulants averages 3% to 4% per patient year. In the aortic position for patients not receiving anticoagulants, the rate of embolism averages 2% to 4% per year (Levine et al 1989). Oral anticoagulants cut the risk of embolism by one half. The embolism rate in patients with bioprosthetic valves is similar to the rate in patients with mechanical valves who are on anticoagulation.
In a significant proportion of embolic strokes, the source is cryptic (Mohr et al 1978). Transesophageal echocardiography can reveal previously unrecognized potential mechanisms of cardioembolic strokes (Lee et al 1991). The most common occult cardiac source of embolism is patent foramen ovale, which is present in approximately 20% of the normal population. Because it is so prevalent in the normal population, caution should be exercised before attributing a stroke to a patent foramen ovale. The mechanism of stroke is presumably paradoxical embolism of venous thrombi across the patent foramen ovale via a right-to-left shunt when the pressure in the right heart exceeds that in the left heart. This may occur transiently during a Valsalva maneuver or pathologically when pulmonary hypertension exists (Jeanrenaud and Kappenberger 1991). A single center review of 1689 patients with stroke or TIA identified several factors associated with patent foramen ovale (Ozdemir et al 2008). These included a history of deep venous thrombosis or pulmonary embolism, prolonged travel, migraine, preceding Valsalva maneuver, and waking up with stroke.
Transesophageal echocardiography has also provided evidence that the aortic arch is a common source of embolic material. The risk of cerebral embolism appears to be directly related to the size of atherosclerotic plaques visualized (Amarenco et al 1994).
Cerebral embolism is a common complication of infectious endocarditis but accounted for less than 1% of all causes of cerebral embolism in the Cerebral Embolism Stroke Registry (Cerebral Embolism Task Force 1986; 1989). Infectious emboli from valvular vegetations, usually mitral, occur in 30% to 40% of endocarditis cases. The manifestations of septic cerebral emboli vary from subtle protean symptomatology, such as encephalopathy and headache, to catastrophic intracranial hemorrhage and death. Intracranial hemorrhage in endocarditis is due to either mycotic aneurysm rupture or septic arteritis (Salgado et al 1987). The clinical presentation depends on the size and number of emboli. Large emboli may lead to obstruction of major vessels producing cerebral ischemia or suppuration leading to abscess formation (Mugge et al 1989). Multiple microemboli often lead to an encephalopathic clinical presentation. It is not uncommon to have a clinical picture involving both mechanisms. In a 15-year review of 707 endocarditis cases from an academic medical center, stroke occurred in 68 patients (9.6%) (Anderson et al 2003). Stroke was more common with mitral (17%) compared to aortic valve (9%) endocarditis. The risk of embolization is highest during the first week of antimicrobial therapy and in patients with mobile vegetations or vegetations greater than 10 mm on the anterior mitral leaflet (Derex 2010). The 1-year death rate for patients with stroke and endocarditis was 52%. Cerebral embolization is rare in right-sided infectious endocarditis but can occur via paradoxical embolization through a patent foramen ovale.