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The pivotal role of echocardiography in cardiac sources of embolism

Bushra S. Rana , Mark J. Monaghan , Liam Ring , Len S. Shapiro , Petros Nihoyannopoulos
DOI: http://dx.doi.org/10.1093/ejechocard/jer122 i25-i31 First published online: 13 October 2011

Abstract

Stroke is a leading cause of morbidity and mortality and is the third commonest cause of death in Europe. Clinical history examination and basic investigations including an electrocardiogram may shed light on the potential cardiac cause. Echocardiography plays a pivotal role in the assessment of embolic stroke. The hierarchy of echocardiography investigations begins with a standard transthoracic echocardiography study and may be proceeded by a bubble contrast transthoracic and a transoesophageal echo study. This article discusses the crucial role echocardiography has assumed in the assessment of stroke patients and describes the cardiac sources responsible.

  • Transthoracic
  • Transesophogeal echocardiography
  • Embolic stroke

Introduction

Stroke is a leading cause of morbidity and mortality and is the third commonest cause of death in Europe. Stroke can be categorized into two major groups, ischaemic (85%) or haemorrhagic (15%). The former can be further classified by the presumed mechanism of focal brain injury and the type and localization of the vascular lesion. The TOAST1 criteria are frequently used and describe five groups: (i) large artery atherosclerotic disease (which can be extra- or intra-cranial) accounting for 20%; (ii) small-vessel disease, 25%; (iii) embolism from a cardiac source, 20%; (iv) other determined causes such as dissection, hypercoagulable state, and sickle cell disease, 5%; and (v) infarcts from undetermined cause (cryptogenic), 30%.

Brain imaging (CT or MRI) confirms the diagnosis, whereas the location and extent of any infarct lesion(s) will help guide the type of investigations necessary. In the absence of local arterial disease, more distant sources of potential embolism are sought. Certain characteristics seen during the imaging of the brain may suggest a (distant) cardiac source. If the infarct is large, particularly without preceding symptoms [such as transient ischaemic attacks (TIAs)], multiple sites (anterior and posterior circulation or bilateral) particularly if separated by time (infarcts of different age), more than one infarct within a territorial distribution, or if there are concomitant signs of systemic thrombo-embolism (such as splenic or renal infarcts, or peripheral limb ischaemia), then a cardioembolic stroke mechanism must be sought.2,3 It is worth noting that stroke from a cardiac source carries a poorer outcome compared with other sources, having a 50% mortality at 3 years.46 In this regard, echocardiography plays a pivotal role in determining cardiac sources.

Causes of cardiac sources of embolism

It is useful to categorize cardiac sources by the recommended therapy for that particular disease state, high risk for an embolic event, i.e. a propensity for thrombus formation and hence requiring formal anti-coagulation, and low risk (or undetermined risk) requiring anti-platelet therapy.7,8

High risk can be grouped into atrial fibrillation (AF), the leading cardiac cause, accounting for 50%; left ventricular (LV) dysfunction; valvular heart disease; and cardiac tumours. Low risk or uncertain risk includes certain valvular pathology and paradoxical embolism. The proximal aorta [assessed accurately with transoesophageal echocardiography (TEE) for aortic arch atheromatous plaque] is considered a potential risk and since it is related to the heart and imaged best by echocardiography, it is included in the list of causes (see Table 1).

View this table:
Table 1

Summarizes the two major groups of embolic stroke. (i) high risk sources and (ii) low or undetermined risk sources

Patent foramen ovale, if present, may be considered a potential source of cardiac embolism, through the mechanism of paradoxical embolism (thrombus within the venous system, which enters the right atrium and crosses into the left arterial circulation through a communication that allows right-to-left shunting for part or all of the cardiac cycle). This particular defect will not be discussed further in this article, since it featured in the last year’s' supplement.

When is echocardiography indicated in ischaemic stroke?

Echocardiography is indicated in the setting of a suspected cardiac mechanism for stroke or related symptoms of syncope and TIAs. Clinical history, examination, and basic investigations, including an electrocardiogram, may shed light on the potential cardiac cause.

The hierarchy of echocardiography investigations begins with a standard transthoracic echocardiography study (TTE). If the heart is deemed structurally normal without features listed in Table 1, a bubble contrast transthoracic study (cTTE) is performed to evaluate the presence of intra-cardiac shunting. TEE is indicated where transthoracic imaging is poor and so non-diagnostic; when a cardiac lesion is identified and requires further detailed assessment (e.g. mitral stenosis and suitability for percutaneous balloon mitral valvuloplasty or a positive cTTE requiring further detailed anatomical assessment of the atrial septum for risk stratification and suitability for device closure); or where no cardiac source for stroke has been identified and specific pathologies need to be excluded. TEE provides high resolution images from a (almost) non-invasive approach and has revolutionized the search for cardiac sources of embolism. Its good sensitivity and high specificity9,10 result from not only its excellent resolution but in its ability to image structures that are not seen well or not seen at all from the transthoracic approach, including the left atrial appendage, the atrial septum, and the thoracic aorta. TEE therefore has particular strengths in elucidating potential aetiology in cardiac sources of embolism.

Transthoracic echocardiography

The majority of stroke patients are likely to undergo TTE at some stage in their workup assessment. The cardiac conditions giving rise to embolism and stroke and the important echocardiographic findings are discussed; first, the high-risk states followed by the low-risk states.

High-risk sources

Atrial fibrillation

AF accounts for 50% of all cardiac sources of stroke. In one study, 26% of ischaemic stroke incidences were associated with intra-cardiac thrombus, of which 70% were located in the left atrial appendage; AF and LV dysfunction correlated with its presence.11 AF will not be discussed further as a separate article in this supplement issue focuses on this subject.

Left ventricular dysfunction

Acute myocardial infarction and left ventricular aneurysm

Thrombus within the LV is a recognized risk factor for stroke12 and 60% have been shown to be associated with acute myocardial infarction (AMI) within the first 2 weeks. LV thrombus occurs more often in anterior vs. inferior AMI, due to more extensive wall motion abnormalities, and an even greater percentage seen if the apex is involved. The incidence of embolism is highest in the first 3 months. However, this has decreased since the introduction of primary angioplasty and prompt revascularization. In the chronic phase, significant LV dysfunction and LV aneurysm formation are associated with a continued substantial embolic risk. The use of anti-coagulation duration remains controversial but a minimum of the first 3 months following an AMI is generally agreed.8

Left ventricular dysfunction and cardiomyopathies

With LV dysfunction, relative stasis of blood within the LV may increase the propensity of thrombus formation through the activation of the clotting cascade. Thus, cardiomyopathy of any cause resulting in significant LV dysfunction and heart failure may be associated with risk of embolic stroke.13 The worse the LV ejection fraction (EF), the greater the incidence of stroke (EF <29% stroke rate 1.7%/year vs. 0.8%/year with EF 29–35%14). No trial has established the superiority of warfarin over anti-platelet therapy in primary stroke prevention in the setting of LV dysfunction. However, if an LV thrombus is documented or if there is a history of stroke with significant LV impairment, then formal anticoagulation may be indicated.7,8

Thrombus seen in the LV on echocardiography is defined by the European Society of Echocardiography7 as a discrete echo dense mass (similar density to myocardium) in the LV with defined margins that are distinct from the endocardium and seen throughout systole and diastole. It should be located adjacent to a hypokinetic or akinetic segment of the LV and should be visible in at least two planes. Differential diagnosis includes false tendons (aberrant chordal attachments within the ventricle), trabeculae, papillary muscles, or artefacts. Thrombus can be flat, following the contour of the LV wall (mural), and immobile or extend into the LV cavity moving independently of the myocardium (helping distinguish it from an artefact) (Figure 1). It may have an organized homogeneous echogenic consistency or heterogeneous appearance with regions of translucency. Colour Doppler is a useful adjunct particularly in differentiating true mass from an artefact. Colour flow is seen over an artefact, but is absent and surrounds a true mass. Measurements are made at the maximum thickness of the thrombus in two dimensions.

Figure 1

Left ventricular thrombus: seen at the apex in an apical four-chamber view. The apex is thinned and akinetic. A large mobile mass is seen attached to the apex. Three frames are shown of the same movie clip (A), (B), and (C); the white arrow demonstrates the motion of the thrombus. Note the heterogeneous consistency of the thrombus.

If doubt remains, then the use of echo contrast agent may be indicated to help delineate the endocardium and LV cavity.15 It is useful to document the ventricle in the three long-axis planes (four, two, and three chamber) and then in short-axis beginning with the base at the mitral valve level and gradually scanning towards the apex. A thrombus is seen as a filling defect (black mass), with contrast surrounding it within the LV cavity and usually with some contrast uptake into the surrounding myocardium.

There is a limited role for TEE, as the LV is often foreshortened and the true apex poorly visualized (unless TTE windows are poor despite echo contrast agent). Other helpful alternatives include cardiac magnetic resonance imaging with gadolinium enhancement or computerized tomography; however, TTE with the addition of echo contrast is accessible, rapid, cheap, and safe, and is the first-line modality of choice. Three-dimensional (3D) echocardiography may assist in delineating the location and extent of thrombus.

Valvular pathology

Rheumatic mitral stenosis

Valvular heart disease is associated with risk of embolism. However, this is usually in association with AF. At greatest risk is rheumatic mitral stenosis, where potential for embolism is present whether in AF or not. Forward flow across the stenosed valve causes stasis of blood and risk of thrombus formation. Recurrent embolism is known to occur in 30–65% of such patients, with the greatest risk of recurrence in the proceeding 6 months and those with a history of paroxysmal or persistent AF. In sinus rhythm, the degree of left atrial enlargement and severity of mitral stenosis does not necessarily correlate with the risk of stroke.16,17 Oral anti-coagulation is therefore indicated in the setting of an ischaemic stroke or TIA whether in AF or sinus rhythm or in primary prevention if the patient is in AF.7,8

The diagnosis of mitral stenosis is made by TTE, which provides detailed information of the aetiology and mechanism as well as severity of the disease, including mean MV gradient, mitral valve area, pulmonary artery pressure estimation. It would be unnecessary to proceed to a TEE unless the images were non-diagnostic or percutaneous mitral balloon valvuloplasty was being considered. The latter would include a detailed assessment of valve anatomy for severity of calcification, leaflet mobility and thickness, and commissural fusion, in addition to the presence of thrombus within the left atrium and appendage. Three-dimensional TTE and TEE are important adjuncts both in terms of providing accurate planimetry of mitral valve orifice area and also valvular anatomy (Figure 2).

Figure 2

Mitral stenosis: transoesophageal echocardiographic three-dimensional live ‘zoom’ mode showing the surgical view (A) and the left ventricular view of mitral stenosis (B). The white arrow points to the fused commissure. The smooth funnel-shaped orifice is clearly depicted with three-dimensional imaging and gives important insights into the anatomy of the valve. LAA, left atrial appendage; AV, aortic valve; LVOT, left ventricular outflow tract.

Infective endocarditis

The risk of embolism from infective endocarditis (IE) may range from 10% but may be as high as 50%. True incidence is unknown and partly reflects a number that are clinically silent.18 Most often, the diagnosis of IE is based on the clinical presentation and confirmed by echocardiography. However, on occasion, suspicion is raised by a TTE study showing evidence of a mobile mass attached to a valve in a patient presenting with an unexplained embolic event.

Echocardiography is essential in confirming the diagnosis and risk stratification. A TTE must be performed in every case of suspected IE. Vegetations (infected tissue mass) appear as irregular echogenic masses usually attached to the atrial side of the atrioventricular valves or the ventricular side of the semilunar valves along the line of leaflet coaptation. The vegetations are seen to move independently to the underlying valve motion.

The echocardiographic features suggestive of increased embolic risk are size (>10 mm) and mobility of vegetations19; >15 mm and very mobile pose a very high risk of embolization particularly prior to the commencement and up to 2 weeks of starting antibiotic therapy.19,20

In the case of prosthetic valves, a TEE is recommended since acoustic shadowing from the prosthetic valve structure hampers adequate assessment of valve mechanism, presence of vegetations, and ring dehiscence. TEE has high sensitivity (86–94%) and specificity (88–100%) for the detection of vegetations.21,22 Differential diagnosis includes thrombus, sutures, or pledgets. Thus, the echocardiographic findings should be considered in the context of the clinical presentation.

TEE is recommended in cases where the TTE study is non-diagnostic or provides inadequate imaging in a patient with high clinical suspicion on IE, or suspected prosthetic valve endocarditis. Our preference is to proceed to a TEE at the initial diagnosis of IE to aid risk stratification, since confirmation of the degree of valve destruction and the early discovery of a root abscess will trigger timely discussions for surgical intervention planning.

Prosthetic mechanical valves

Prosthetic mechanical valves, as with any foreign material in the heart, are a particular risk for embolic events for two reasons: first, risk of infection and endocarditis (see above) and, second, prosthetic valve thrombosis. Typically, the latter occurs during peri-operative periods, pregnancy, and episodes of inadequate anticoagulation for whatever reason. It is unusual for tissue (bioprosthetic) valves to present with an embolic stroke; however, in the absence of another cause may warrant anticoagulation.

Usually, the valve mechanism is affected and evidenced by an increase in transvalvular velocities, which should always be compared with baseline and serial values for that patient and the reference tables.23 There may be reduction in the effective orifice area and development of pathological regurgitation to varying degrees. TTE imaging resolution is often inadequate in clearly identifying thrombus. TEE, combined with 3D live imaging, is excellent in documenting valve anatomy, opening and closing disc motion, presence of any mobile masses (which may be thrombus, pannus, or vegetations), and sewing ring dehiscence (Figure 3). Three-dimensional colour flow imaging can accurately demonstrate the origin of any regurgitation and better differentiate transvalvular vs. paravalvular leaks.

Figure 3

Prosthetic valve function, bileaflet St Judes valve: transoesophageal echocardiographic three-dimensional live ‘zoom’ mode showing the surgical view; image (A) shows the delay in one disc opening (superior disc) and image (B) shows why. The arrow points to thrombus attached to valve mechanism causing one disc to stick.

Mitral valve prostheises are well visualized on TEE imaging since the valve is viewed from the left atrial aspect and the acoustic shadowing is therefore cast below the valve into the LV. Aortic valve (AV) prostheises are less well seen, but still more than adequate for diagnostic purposes. Although the presence of a mitral valve prosthesis can hamper AV prosthesis assessment due to acoustic shadowing.

Thrombus appears as a soft mobile structure seen within the valve ring and may extend into the left atrium. In the setting of an embolic stroke or progressive obstruction to prosthetic valve function, the discovery of thrombus may indicate the need for thrombolysis therapy. However, large thrombi (area ≥0.8 cm2), measured on TEE, pose a significant risk of embolism and death with this treatment.24 This may necessitate surgery in some instances.

Cardiac tumours

Cardiac tumours may be primary or secondary, benign or malignant. They can present with embolic events and stroke, which may be the first indication of their presence. Echocardiography is an excellent modality to assess their presence, location, extent, and haemodynamic consequences simultaneously. Two tumours most commonly associated with embolic stroke are myxomas and papillary fibroelastomas.

Myxoma

Myxoma is the commonest (approximately between 30 and 50%) primary tumour. The majority (90%) are found in the left atrium arising from the fossa ovalis. The typical clinical presentation is malaise, fever, embolic events with or without symptoms of mitral valve obstruction. Echocardiographic appearance is of an irregular and frond-like mass (polypoid), resembling a cluster of grapes attached via a narrow stalk. It is heterogeneous and may contain bright echodense regions of calcification (Figure 4). TTE (aided by 3D imaging) evaluation should assess the site of attachment, ensure valve leaflets are not involved, exclude other sites (right atrium 18%, left ventricle 4%, right ventricle 4%, multiple sites 5%), and assess haemodynamic effects (usually valve obstruction). If tumour attachment, margins, and suspicion of tumour infiltration cannot be confidently assessed, then TEE may be necessary. If diagnosis cannot be made with echocardiography, then further evaluation with CT or MRI may be needed.

Figure 4

Myxoma; non-homogeneous structure attached to the atrial septum in the region of the fossa ovalis (solid arrow). The stalk cannot be seen. Flecks of bright echos are seen and may represent calcification. A second potential source of embolism is also noted in this image, seen clearly on colour flow (image b). The white dotted arrow shows the opening of a patent foramen ovale on the left atrial side.

Papillary fibroelastomas

Papillary fibroelastomas are the most common valve-associated tumours. They usually arise from the LV side of the mitral valve and the aortic side of the AV, i.e. downstream side. They arise from a small pedicle, have an irregular surface, and are relatively small in size, measuring ∼0.5–2 cm. Their mobility determines the risk of stroke. If small and relatively immobile, close follow-up is advocated in an otherwise asymptomatic patient. Similar in appearance to Lambl's excrescences, it is debated whether they represent a spectrum of the same abnormality.7 The latter are smaller in size. Differential diagnosis includes vegetations.

Low-risk sources

Mitral valve prolapse

Mitral valve prolapse (MVP) is reported as the most common valve lesion in adults, seen in 2% of the population.25,26 It follows a benign course in the majority, but a very small risk of thrombo-embolism and stroke has been documented (0.6%).27 Possible mechanisms include microthrombi formation on the myxomatous valve tissue, concurrent supraventricular arrhythmias, or an association with atrial septal aneurysms.28 However, prospective population-based studies have recently failed to identify any clear increase in risk of stroke.29,30 Current recommendations do not advocate the use of warfarin, unless there is another indication such as AF. Otherwise in the setting of stroke or TIA, aspirin is the first-line therapy.

Mitral annular calcification

Mitral annular calcification (MAC) is a marker of atherosclerosis and cardiovascular disease. It is a degenerative process and a common finding in the elderly population.31 Although postulated as a potential substrate for calcific debris or microemboli, no clear stroke risk has been established.

Calcific aortic stenosis

Aortic stenosis progression is associated with worsening calcification of the valve cusps and annulus. Risk of embolism is well known during procedures where cardiac catheters may disrupt larger emboli and cause TIA's or stroke. However, outside these situations, there is no clear evidence to suggest such patients are at increased risk.

Transoesophageal echocardiography

TEE may be indicated when TTE imaging is limited and non-diagnostic, but may also be necessary when no cause for embolism is found and specific conditions need to be excluded. The advantage of TEE is its ability to image structures not routinely assessed (due to limited resolution) by TTE. Its use has become pivotal in the search for cardiac sources of embolism. When comparing the diagnostic yield of TEE over TTE in patients with ischaemic stroke, in those with negative findings on TTE, TEE detected potential causes of embolism in 31% of patients altering management.32 TEE is superior in imaging the left atrial appendage for thrombus (and spontaneous echo contrast), interatrial septum anatomy (particularly patent foramen ovale (PFO) and paradoxical embolism), and the proximal aorta (aortic atheroma).32 Small cardiac tumours with a propensity for embolism may also be missed on TTE, and valvular anatomy and prosthetic valves are best assessed by TEE (see above).

Spontaneous echo contrast and LA appendage thrombus will be discussed in a separate article in the supplement and so will not be mentioned further.

PFO and assessment of the atrial septum by TEE was discussed in the preceding supplement and will similarly not be discussed further.

Aortic atheroma

Aortic atherosclerosis is a risk factor for stroke, independent of other factors including AF and carotid disease.33 Mobile thrombus superimposed on aortic atheroma poses a significant embolic risk.34 TTE gives useful information about atheroma within the aortic arch and its branches. However TEE is superior and the modality of choice in the detection and description of complex atheromatous disease.

Aortic atheroma is classified as either simple or complex (high risk). Echo assessment should include a measurement of the atheroma plaque thickness (high risk ≥4 mm), ulceration (high risk ≥2 mm), the extent of calcification (high risk, non-calcified plaques), and associated mobile thrombi (Figure 5). The discovery of complex plaque within the aortic arch may warrant anticoagulation and in some instances surgical removal.

Figure 5

Aortic atheroma; transoesophageal echocardiographic two-dimensional image seen of the aortic arch. Irregular echo bright atheroma measures over 8 mm at its widest diameter (red star). A mobile thrombus is seen attached to the endothelium (white arrow). Heavy calcification within the aortic wall cast bright echo shadows below the aorta.

Conclusion

Echocardiography plays a pivotal role in the assessment of embolic stroke. TTE is indicated in such cases, and high-risk findings, such as LV thrombus, myxoma, or mitral stenosis, may indicate the need for anticoagulation. Where no cause is found and the possibility of paradoxical embolism remains high, a bubble contrast study may be indicated to look for the presence of an intracardiac shunt. TEE should be considered in those where TTE study is normal to search for unidentified sources including LA appendage thrombus and spontaneous contrast, small cardiac tumours, atrial septum abnormalities, and complex aortic atheroma. TEE may also be necessary for further risk stratification or if an intervention is contemplated, such as LAA closure or percutaneous balloon mitral valvuloplasty.

Conflict of interest: none declared.

References

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