A number of cardiac conditions have been proposed as potential sources of embolism. The risk of embolism is heterogeneous. The more common high risk cardioembolic conditions are atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, dilated myocardiopathy, and mitral rheumatic stenosis. Other major sources of cardioembolism include infective endocarditis, marantic endocarditis, and atrial myxoma. Minor sources of cardioembolism are patent foramen ovale, atrial septal aneurysm, atrial or ventricular septal defects, calcific aortic stenosis, and mitral annular calcification [1
Atrial fibrillation is the most important cause of cardioembolic cerebral infarction [22
]. Atrial fibrillation is the commonest sustained cardiac arrhythmia. Prevalence of atrial fibrillation increases with age, reaching a peak of 5% in people over 65 years of age, and both its incidence and prevalence are increasing. The disorder is associated with valvular heart disease, thyroid disorders, hypertension, and recent heavy drinking of alcohol. In Western populations, most causes of atrial fibrillation are unrelated to mitral valve disease. Instead, atrial fibrillation is now mainly secondary to ischemic or hypertensive heart disease. The attributable risk of stroke due to atrial fibrillation rises from 1.5% at the age of 50 to 24% at the age of 80. The incidence of stroke in people with non-valvular atrial fibrillation is estimated to be 2 to 7 times higher than in people without atrial fibrillation and for those with valvular atrial fibrillation, the risk is 17 times higher than that in age-matched controls. Chronic and recurrent atrial fibrillation appears to carry very similar stroke risk. Atrial fibrillation in the absence of organic heart disease or risk factors (lone atrial fibrillation) appears to carry significantly lower risk especially in younger patients (approximately 1.3% per year). Atrial fibrillation causes stroke because it leads to inadequate contraction of, and leads to stasis that is most marked in the left atrial appendage. Stasis is associated with increased concentrations of fibrinogen, D-dimer, and von Willebrand factor, which are indicative of a prothrombotic state, which in turn predisposes to thrombus formation with consequent increased rate of cerebral embolization [2
]. In these patients, left ventricular dysfunction and left atrial size were independent echocardiographic predictors of later thromboembolism. Other factors associated with a particular high embolic risk are spontaneous echo contrast, left atrial thrombus or aortic plaque detected by transesophageal echocardiogram. Heart failure, hypertension, age > 75 years, and diabetes mellitus increase the risk of stroke in a more moderate but additive fashion [4
The bradycardia-tachycardia (sick sinus) syndrome can be associated with cerebral embolic events.
Approximately 2.5% of patients with acute myocardial infarction experience a stroke within 2 to 4 weeks of the infarction, and 8% of men and 11% of women will have an ischemic stroke within the next 6 years. Factors that enhance the risk of stroke include severe left ventricular dysfunction with low cardiac output, left ventricular aneurysm (Fig.
) or thrombus, and associated arrhythmias such as atrial fibrillation. Patients with an ejection fraction of less than 28% had a relative risk of stroke of 1.86 compared with patients with an ejection fraction greater than 35%. The incidence of early embolism is high, possibly up to 22% in the presence of a mural thrombus and is most likely when the thrombus is mobile or protrudes into the ventricle [6
Transthoracic echocardiography shows a left ventricular
aneurysm (VI) in a patient with history of acute myocardial infarction.
The annual rate of stroke in patients with congestive heart failure is 2%. The risk of stroke correlates with the severity of left ventricular dysfunction. Coexistent disease has a cumulative effect, and the combination of recent congestive heart failure and atrial fibrillation places the patient at particular high risk for cardioembolic stroke [7
Rheumatic valvular heart disease (Fig.
) and mechanical prosthetic valves are well recognized risk factors for stroke even in the absence of documented atrial fibrillation. The two most commonly cited rheumatic valve abnormalities are mitral stenosis and calcific aortic stenosis [1
Transthoracic echocardiography reveals a thrombus in the left atrium (T) in a patient with double rheumatic mitral valve lesion and
Two types of endocarditis, infective and non-infective, can cause stroke. Non-infective endocarditis can complicate systemic cancer, lupus, and the anti-phospholipid syndrome. Infective endocarditis is complicated by stroke in about 10% of cases. Most stroke happens early (before or during the first 2 weeks of appropriate antimicrobial therapy). Emboli can be multiple especially in the case of infection of prosthetic valves and in infections due to aggressive agents, such as Staphylococcus aureus
. Mycotic aneurysm is an uncommon (1−5%) complication of infective endocarditis. They may also enlarge and rupture, which is fatal in many cases (Fig.
Fig. (6) Right lobar hemorrhage (A) secondary to rupture of a mycotic aneurysm in the course of an infective bacterial endocarditis;
transthoracic echocardiography (B) shows an abscess in the posterolateral aortic root (a) between the aortic valve leaflets and (more ...)
Myxomas account for more than half of primary cardiac tumors and thromboembolism is the most common presenting symptom in patients with myxomas. Other primary cardiac tumors include papillary fibroelastoma [22
Patent foramen ovale, aortic arch atheroma and mitral annular calcification are emerging cardioembolic sources [26
A patent foramen ovale
is present in approximately 25% of the general population, and can be found in up to 40% of younger patients with otherwise cryptogenic stroke [47
]. There is a higher risk of stroke with patent foramen ovale, especially when combined with atrial septal aneurysm. In a meta-analysis of case control studies that examined the relative frequency of patent foramen ovale, atrial septal aneurysm, or both, in all patients with ischaemic stroke, cryptogenic stroke and known stroke cause, patent foramen ovale and atrial septal aneurysm were significantly associated with ischaemic stroke in patients younger than 55 years. It was concluded that further studies are needed to establish whether an association exists between patent foramen ovale and ischemic stroke in those older than 55 [48
]. There is insufficient evidence to recommend warfarin routinely in patients with cryptogenic stroke and patent foramen ovale. There was no difference of stroke recurrence in cryptogenic stroke between patients with and without massive right-left shunt [49
]. The American Heart Association, the American Stroke Association, the American Academy of Neurology [50
] and the European Stroke Organization [52
] recommend antiplatelet agents to prevent recurrent events whilst waiting for the results of ongoing clinical trials regarding closure of patent foramen ovale. In clinical practice, aspirin is the recommended treatment in stroke patients with a patent foramen ovale and indications of closure should be individualized and particularly considered only in young patients with recurrent stroke receiving medical treatment or when anticoagulant treatment is being considered.
Regarding complex aortic arch atheromatosis,
in a review of 500 necropsies of patients with neurological diseases, ulcerated aortic plaques were documented in 62 (26%) of 239 patients in whom stroke was the cause of death and only in 13 (5%) of 261 patients who died as a result of other neurological conditions. Likewise, ulcerated aortic plaques were observed in 17 (61%) of 28 patients with cerebral infarction of unknown aetiology as compared with 34 (22%) of 155 patients in whom a cerebral infarction-attributable aetiology was found [53
The main emboligenic risk criteria for atheromatous plaques of the aortic arch include plaque thickness ≥ 4 mm and the presence of mobile components [54
Complex atheromatosis of the aortic arch on echocardiogram. Main criteria of embolic risk associated with aortic atheromatosis are
plaque thickness ≥ 4 mm and the presence of mobile components.
It has been recently shown that complex atheromatous aortic plaques play a causative role in the recurrence of ischaemic stroke in the subgroup of cerebral infarctions of undetermined aetiology [55
]. The efficacy of anticoagulation versus
antiplatelet therapy in the prevention of stroke recurrence in patients with atherothrombosis of the aortic arch and a recent (< 6 months) cerebral or peripheral embolic event is the objective of the ongoing ARCH (Aortic Arch Related Cerebral Hazard Trial) study from France.
The protective effect of statin theraphy on the incidence of stroke and other embolic events in patients with severe thoracic aortic plaque was reported in a matched-paired analysis [57
Mitral annular calcification
is a chronic degenerative process characterized by calcium and lipid deposition in the fibrous support of the mitral valve. Mitral annular calcification has been cited as a possible source of cerebral embolism with a relative risk of stroke of 2.1 in the Framingham Study independent of traditional risk factors for stroke [58
]. In a recent study in patients with ischaemic stroke of uncertain etiology, dense mitral annular calcification was an important marker of aortic arch atherosclerosis with high risk of embolism [46
Spontaneous echo contrast is an independent echocardiographic risk factor for left atrial thrombus and its appendage and cardiac thromboembolic events.
Cardiological substrate and pathophysiological mechanisms presumptively involved in cardioembolic stroke in the Sagrat Cor Hospital of Barcelona Stroke Registry [59
] are shown in (Table
). Atrial dysrhythmia without structural cardiac disease was documented in 89 (22%) patients, with a mean (SD) age of 75 (4) years (range 63–90 years). All these patients had normal electrocardiographic findings and 90% were asymptomatic. The cardiac condition associated with cardiogenic stroke was atrial fibrillation in 88 patients (chronic 67, paroxysmal 18, persistent 3) and atrial flutter in 1. A previous diagnosis of atrial dysrhythmia had been established in the outpatient setting in 51% of patients but none of the patients received anticoagulation.
Cardiac Disorders and Pathophysiological Mechanisms Presumptively Associated with Cardioembolic Stroke in 402 Patients. Distribution by Cardiac Source Risk Groups. Sagrat Cor Hospital of Barcelona Stroke Registry
Structural cardiac disease with sustained sinus rhythm was diagnosed in 81 (20%) of patients. Left ventricular systolic dysfunction was documented in 59 patients (ischemic heart disease in 35 and dilated cardiomyopathy in 24) associated with intraventricular thrombosis in 13. Other less frequent cardiac disorders included mitral annular calcification, cardiac tumors, aortic prosthetic valve, endocarditis, atrial septal aneurysm with patent foramen ovale, rheumatic mitral valve disease, mitral valve prolapse, calcified aortic stenosis with embolism during catheterization, and moderate mitral valve regurgitation [59
In the remaining 232 (58%) patients, structural cardiac disorders were associated with atrial fibrillation in 230 cases and atrial flutter in 2. Hypertensive left ventricular hypertrophy was documented in 120 cases followed by rheumatic mitral valve disease in 49 cases and left ventricular dysfunction in 32 cases (ischemic heart disease in 19 and dilated cardiomyopathy in 13). Other less frequent cardiac disorders complicated with atrial fibrillation included mitral valve prolapse, mitral prosthesis, hypertrophic cardiomyopathy, lipomatous hypertrophy of the atrial septum, severe mitral regurgitation, and atrial septal aneurysm with patent foramen ovale [59
The frequency of the different cardiac disorders in the overall series of 402 patients with cardioembolic stroke is shown in (Table
). Atrial fibrillation was documented in 79.1% of patients (in association with structural cardiac disease in 72% of cases) followed by hypertensive left ventricular hypertrophy in 29.8% of patients, left ventricular dysfunction in 22.6%, rheumatic mitral valve disease in 12.4%, and mitral annular calcification in 9.9%. Mitral valve prolapse, atrial septal aneurysm with patent foramen ovale and degenerative heart valve disease were observed in only 1% of the patients. In the group of 118 patients with hypertensive left ventricular hypertrophy associated with atrial fibrillation, anteroposterior diameter of the left atrium was significantly larger than in the group of 88 patients with lone atrial fibrillation (45 ± 3 mm vs.
41 ± 3 mm, P
< 0.001). On the other hand, 80.6% of these patients were asymptomatic, 50.5% had other vascular risk factor (cigarette smoking, diabetes mellitus, hyperlipidemia) besides hypertensive disease, and although a previous diagnosis of atrial dysrhythmia had been established in the outpatient setting in 43.7% of patients, none of the patients received anticoagulation at the time of stroke onset [59
Frequency of the Different Cardiological Substrate in 402 Patients with Cardioembolic Stroke in the Sagrat Cor Hospital of Barcelona Stroke Registry