Embolism from the heart
- Coronary artery disease
- Mitral leaflet prolapse
- Paradoxical embolism
- Pulmonary arteriovenous fistula
- Sinoatrial disease
- Inter-atrial septal aneurysm
- Infective endocarditis
- Non-bacterial thrombotic
- Prosthetic heart valves
- Cardiac myxomas
- Valvular fibroelastoma
- Dilating cardiomyopathies
- Cardiac surgery
- Instrumentation of the coronary arteries and aorta
There is no doubt that emboli arising from within the heart, or passing through it from the venous system, can reach the brain and eye (and elsewhere) to cause ischaemic stroke, retinal infarction, and TIAs (Cerebral Embolism Task Force 1989; Hart 1992; Oppenheimer and Lima 1998). Increasingly sensitive imaging technology is throwing up more and more possible embolic sources, but so often of dubious relevance, such as mitral valve strands (Cohen et al. 1997).
Fortunately, although there are a large number of potential cardiac sources of embolism, the vast majority of relevance can be diagnosed easily enough using straightforward clinical examination, ECG, and chest radiography, along with non-invasive echocardiography. The much greater difficulty is in deciding whether an identified embolic source is the source, particularly when it is common in normal people (e.g. mitral leaflet prolapse, patent foramen ovale); or in an elderly person when significant atheroma affecting the cerebral circulation is so commonly found as well; or when the stroke is lacunar and rather unlikely to be caused by embolism from the heart or extracranial arteries (De Bono and Warlow 1981; Bogousslavsky et al. 1986a,b, 1990; Caplan 1995b). Moreover, some embolic sources are much more threatening (e.g. prosthetic valve, rheumatic atrial fibrillation) than others (e.g. mitral leaflet prolapse, patent foramen ovale).
In developed countries, about 20 per cent of ischaemic strokes and TIAs are probably due to embolism from the heart, the most common cause being non-rheumatic atrial fibrillation with presumed, but seldom proven, thrombus in the left atrium (Nishide et al. 1983; Kittner et al. 1990). Of course, emboli vary in their composition from mostly fibrin (atrial fibrillation) to mostly platelets (mitral leaflet prolapse) to calcium (mitral annulus calcification), tumour (myxoma), or infected vegetations (infective endocarditis). The emboli also vary in size so they may impact in a medium-sized artery to cause a substantial infarct (e.g. middle cerebral artery (MCA) origin, basilar artery) or in a smaller artery to cause merely a restricted defect (e.g. central retinal artery branch, cortical branch of MCA) (Castaigne et al. 1973; Caplan 1993). Some emboli, perhaps even most, like other causes of cerebral ischaemia, may be completely asymptomatic.
Although it is becoming much less common, rheumatic valvular disease, mitral far more often than aortic, is well recognized as an embolic source, either because of thrombus in the left atrium or valvular debris (Daley et al. 1951; Coulshed et al. 1970). Atrial fibrillation has already been discussed. Some other conditions are worth discussing in detail:
Coronary artery disease
Coronary artery disease: in the pre-thrombolytic era, left ventricular mural thrombus diagnosed echocardiographically occurred within days of an acute myocardial infarction (MI) in about 20 per cent of patients. Those with anterior infarcts are at higher risk than those with inferior infarcts; large infarcts and a dyskinetic wall segment are also risk factors (Meltzer et al. 1986).
These thrombi may embolize, particularly if protruding or mobile, and are associated with about a fivefold excess risk of stroke in the first few days and weeks after MI (Vaitkus and Barnathan 1993). But most seem to do little harm, since the frequency of clinically evident systemic embolism is well under 5 per cent (Fibrinolytic Therapy Trialists' (FTT) Collaborative Group 1994; Mooe et al. 1997).
Moreover, at least some, and maybe many, post-MI strokes must be due to hypotension and boundary zone infarction, atrial fibrillation with left atrial thrombus, paradoxical embolism in patients with right ventricular infarction and a patent foramen ovale, coronary and aortic instrumentation (see below), while others are primarily haemorrhagic as a consequence of the increasing use of antithrombotic and thrombolytic drugs (Sloan and Plotnick 1990; Maggioni et al. 1992).
Sometimes acute stroke and acute myocardial infarction appear to start simultaneously, making it difficult to know which was first, or whether there was some common underlying mechanism (Chin et al. 1977; von Arbin et al. 1982). Even more rarely, the same non-atheromatous disorder can cause both ischaemic stroke and acute MI (giant cell arteritis, aortic arch dissection, infective endocarditis).
The long-term risk of stroke after acute MI is about 1.5 per cent per annum, 8 per cent in 5 years. Although some strokes may be due to embolization from thrombus in a chronic left ventricular aneurysm, many must be due atrial fibrillation, or coincidental arterial disease affecting the cerebral circulation (Meltzer et al. 1986; Martin et al. 1993; Loh et al. 1997).
Mitral leaflet prolapse
Mitral leaflet prolapse (MLP) is a common echocardiographic and even clinical finding in asymptomatic people, particularly if they are tall and thin, and it is sometimes familial (Levy and Savage 1987). It can be complicated by gross mitral regurgitation, infective endocarditis, atrial fibrillation and left atrial thrombus and so embolism to the brain. But although early case-control studies suggested that uncomplicated MLP was more common in ischaemic stroke and TIA patients than expected, this has not been confirmed. Moreover, there is no excess risk of first or recurrent stroke in patients with MLP and there is little pathological confirmation of significant thrombi on the abnormal valve cusps (Geyer and Franzini 1979; Chesler et al. 1983; Orencia et al. 1995a,b).
Therefore, if uncomplicated MLP is discovered in an ischaemic stroke patient, it is most unwise to assume a causal relationship (i.e. embolism from valvular vegetations to the brain) unless echocardiography reveals vegetations and no other cause is found, and even then keeping an open mind.
Calcification (and possibly sclerosis) of the aortic and mitral valves can, rarely, be a cause of embolism of calcific or complicating thrombotic material. However, these ‘degenerative’ (or perhaps rheumatic) disorders of heart valves are so common, particularly in the elderly, that it has been very difficult to associate them causally with stroke (De Bono and Warlow 1979; Benjamin et al. 1992; Boon et al. 1996). Unless calcific emboli are seen in the retina, or on CT of the brain, it is all but impossible to infer a causal relationship with ischaemic stroke in individuals (Brockmeier et al. 1981; Mouton et al. 1997; Shanmugam et al. 1997). Any associated atrial fibrillation, coronary heart disease, and carotid stenosis just compound the diagnostic problem.
Paradoxical embolism from the venous system (or exceptionally from thrombus in the right side of the heart) is a well-accepted mechanism of ischaemic stroke, based on a number of convincing cases described at post-mortem. However, definitive diagnosis during life is almost impossible because a patent foramen ovale can be found not only in about 25 per cent of unselected post-mortems but, with modern non-invasive technology (transoesophageal echocardiography with intravenous contrast), in about 15 per cent of normal people (Gautier et al. 1991; Jeanrenaud and Kappenberger 1991).
In an individual case of ischaemic stroke or TIA with a patent foramen ovale (or an atrial septal defect or ventricular septal defect), suggestive clues to paradoxical embolism are the presence, or high likelihood, of thrombosis in the leg or even pelvic veins, or pulmonary embolism, shortly before the stroke (afterwards it could be a result of the stroke); no other cause of stroke is identified; onset of stroke occurs during likely sustained or transitory elevation of right heart pressure (pulmonary hypertension, Valsalva manoeuvre, right ventricular myocardial infarction, etc.); and thrombus in the right atrium or ventricle is demonstrated or highly likely (Jeanrenaud and Kappenberger 1991). However, these clues are far from specific or sensitive (Petty et al. 1997). The risk of recurrent stroke is very uncertain but probably not particularly high (Bogousslavsky et al. 1996).
Pulmonary arteriovenous fistula
A pulmonary arteriovenous fistula (often visible on chest radiography and not necessarily only in patients with hereditary haemorrhagic telangiectasia) is a very rare route by which emboli may reach the brain from the venous system (Dennis 1985).
Sinoatrial disease (sick sinus syndrome) is associated with systemic embolism, particularly if there is bradycardia alternating with tachycardia, or atrial fibrillation (Bathen et al. 1978).
Inter-atrial septal aneurysm
Inter-atrial septal aneurysm is increasingly recognized with echocardiography, and some evidence is emerging that it may be complicated by thrombosis and then embolism to the brain (Silver and Dorsey 1978; Nater et al. 1992; Cabanes et al. 1993). However, it is often associated with other cardiac conditions which have embolic potential (particularly a patent foramen ovale) or which may be associated with atheromatous disease of the cerebral arteries (such as coronary heart disease).
Infective endocarditis, acute or subacute, is complicated by ischaemic stroke or TIA as a result of embolism of infected vegetations in about 20 per cent of cases. Stroke can be the first symptom but more often occurs at about the time of hospitalization and the diagnosis of the cardiac pathology. Mycotic aneurysms may form at sites of embolic occlusion (usually on distal branches of the middle cerebral artery) and some rupture to cause intracerebral or subarachnoid haemorrhage, usually during the acute illness and rarely a few weeks later. Intracranial haemorrhage is also caused by pyogenic necrosis of the arterial wall (Jones and Siekert 1989; Hart et al. 1990; Kanter and Hart 1991; Salgado 1991; Masuda et al. 1992).
Non-bacterial thrombotic (marantic) endocarditis: small, friable, and sterile vegetations made of fibrin and platelets can be found on the heart valves of cachectic and debilitated patients, and in the antiphospholipid antibody syndrome, systemic lupus erythematosus, and possibly protein C deficiency (Section 27.4.6). Mostly they are too small to be diagnosed during life, although some can now be picked up on transoesophageal echocardiography (Lopez et al. 1987; Walz et al. 1998).
Prosthetic heart valves
Prosthetic heart valves, particularly mechanical ones, have long been known to be complicated by thrombosis with embolic potential, and infective endocarditis. There seems to be little difference in this respect between the different mechanical valves, but those in the mitral position are most prone to thrombosis. The overall risk of clinically evident embolism is 1–2 per cent per annum, even on anticoagulants (Vongpatanasin et al. 1996). The very frequent signals on transcranial Doppler probably mostly represent gas cavitation bubbles forming on prosthetic valves, particular mechanical ones, rather than formed emboli, and do not seem to be clinically relevant (Sliwka and Georgiadis 1998).
Cardiac myxomas are rare, occasionally familial, and arise in any heart chamber, but 75 per cent are found in the left atrium (Markel et al. 1987; Reynen 1995). Tumour material, or complicating thrombus, may embolize to the brain, eye, and elsewhere, and very often, but not always, there are additional features of intracardiac obstruction (dyspnoea, cardiac failure, syncope) and constitutional upset (malaise, weight loss, fever, rash, arthralgia, myalgia, anaemia, raised ESR, hypergammaglobulinaemia) (Sandok et al. 1980). Myxomatous emboli impacted in cerebral arteries may also cause aneurysmal dilatation with subsequent intracerebral or subarachnoid haemorrhage (Roeltgen et al. 1981).
Valvular fibroelastoma is an even rarer embologenic cardiac tumour (Giannesini et al. 1999). Other very rare primary and secondary cardiac tumours may embolize (Joynt et al. 1965; Chalmers and Campbell 1987; Reynen 1995).
Dilating cardiomyopathies are well recognized to be complicated by intracardiac thrombus, but this seems to be a remarkably rare cause of embolic stroke. Any atrial fibrillation is likely to exacerbate the tendency (Dec and Fuster 1994).
Cardiac surgery is complicated by stroke or retinal/optic nerve infarction in about 2 per cent of cases, the risk being greater for valve than coronary artery surgery (Lancet 1989; Roach et al. 1996). Early post-operative confusion is much more common, and although cognitive deficits may persist for some weeks or longer, they seldom seem to cause much persistent functional impairment (Shaw et al. 1989; Walzer et al. 1997). Possible mechanisms include embolization during surgery (of platelet aggregates, fibrin, calcific debris from valves, atheromatous debris, fat, air, silicone or particulate matter from the pump-oxygenerator system); embolism after surgery (from thrombus on suture lines, prosthetic material, complicating myocardial infarction, endocarditis, or atrial fibrillation); hypotension during or after surgery, causing boundary zone ischaemia; haemodilution during surgery; the cholesterol embolization syndrome; a simultaneous carotid endarterectomy; thrombosis associated with heparin-induced thrombocytopenia; and intracranial haemorrhage due to anticoagulation or thrombocytopenia. The neurological complications are not very clearly related to any particular risk factors, even carotid stenosis, perhaps because studies have been too small to demonstrate them reliably and no systematic reviews have been done.
Instrumentation of the coronary arteries and aorta
Instrumentation of the coronary arteries and aorta may be associated with similar neurological complications by dislodging valvular or atheromatous debris (Ayas and Wijdicks 1995) and the cholesterol embolization syndrome (27.4.2).