Embolism from the heart or the thoracic aorta often leads to clinically significant morbidity and mortality due to transient ischemic attack, stroke or occlusion of peripheral arteries. Transthoracic and transesophageal echocardiography are the key diagnostic modalities for evaluation, diagnosis, and management of stroke, systemic and pulmonary embolism. This document provides comprehensive American Society of Echocardiography guidelines on the use of echocardiography for evaluation of cardiac sources of embolism.
It describes general mechanisms of stroke and systemic embolism; the specific role of cardiac and aortic sources in stroke, and systemic and pulmonary embolism; the role of echocardiography in evaluation, diagnosis, and management of cardiac and aortic sources of emboli including the incremental value of contrast and 3D echocardiography; and a brief description of alternative imaging techniques and their role in the evaluation of cardiac sources of emboli.
Specific guidelines are provided for each category of embolic sources including the left atrium and left atrial appendage, left ventricle, heart valves, cardiac tumors, and thoracic aorta. In addition, there are recommendation regarding pulmonary embolism, and embolism related to cardiovascular surgery and percutaneous procedures. The guidelines also include a dedicated section on cardiac sources of embolism in pediatric populations.
Attention ASE Members:
The ASE has gone green! Visit www.aseuniversity.org to earn free continuing medical education credit through an online activity related to this article. Certificates are available for immediate access upon successful completion of the activity. Nonmembers will need to join the ASE to access this great member benefit!
Introduction
Embolism from the heart or the thoracic aorta often leads to clinically significant morbidity and mortality due to transient ischemic attacks (TIAs), strokes, or occlusions of peripheral arteries.
Stroke is the third leading cause of death in the United States and other industrialized countries. Echocardiography is essential for the evaluation, diagnosis, and management of stroke and systemic embolism.
Cardiac embolism accounts for approximately one third of all cases of ischemic stroke. Paradoxical embolism and embolism from the thoracic aorta, especially of its atheroma contents, are responsible for additional cases of stroke and systemic embolism.
This document provides the first set of guidelines of the American Society of Echocardiography (ASE) guidelines specific to this topic.
Introduction
Embolism from the heart or the thoracic aorta often leads to clinically significant morbidity and mortality due to transient ischemic attacks (TIAs), strokes, or occlusions of peripheral arteries.
Stroke is the third leading cause of death in the United States and other industrialized countries. Echocardiography is essential for the evaluation, diagnosis, and management of stroke and systemic embolism.
Cardiac embolism accounts for approximately one third of all cases of ischemic stroke. Paradoxical embolism and embolism from the thoracic aorta, especially of its atheroma contents, are responsible for additional cases of stroke and systemic embolism.
This document provides the first set of guidelines of the American Society of Echocardiography (ASE) guidelines specific to this topic.
Methodology
These guidelines are based on an extensive literature review including all other relevant guidelines from the ASE and other national and international medical societies. They provide primarily expert consensus opinions, because randomized trial data are lacking for many topics discussed in these guidelines. Throughout these guidelines, recommendations are provided in the same format for all topics. There are three levels of recommendations: echocardiography recommended, echocardiography potentially useful, and echocardiography not recommended. It is hoped that these guidelines will provide standardization in the echocardiographic evaluation of patients with cardiac sources of embolism and lead to improved patient care.
General Concepts of Stroke and Systemic Embolism
Stroke, probably embolic in origin, was first described by the Greek physician Hippocrates (circa 460–370 bc ). He also coined the term apoplexy (ἀποπληξία [apoplexia], “struck down with violence”) which was used for centuries to describe what we now refer to as strokes or cerebrovascular accidents. In 1847, the German pathologist Rudolf Virchow (1821–1902) provided initial evidence for the thromboembolic nature of some strokes.
Each year, >795,000 people in the United States experience new or recurrent strokes; 610,000 are first attacks and 185,000 are recurrent strokes. It is estimated that 6.9 million American aged >20 years have had strokes, which represents 2.7% of all men and 2.6% of all women in the United States. The prevalence of silent cerebral infarction is higher, estimated to range from 6% to 28%. Stroke is the third leading cause of death in Western countries (after cancer and heart disease); it accounts for one of every 19 deaths in the United States. In 2009, the direct and indirect cost of stroke in the United States was $36.5 billion.
Fifteen percent of all strokes are heralded by TIAs, defined as local neurologic deficits that last <24 hours.
Stroke Classification
It is estimated that 87% of all strokes are ischemic, and the remaining 13% are hemorrhagic. Using the Trial of Org 10172 in Acute Stroke Treatment criteria, ischemic strokes may be further subdivided into following types:
- 1.
Thrombosis or embolism associated with large vessel atherosclerosis
- 2.
Embolism of cardiac origin (cardioembolic stroke)
- 3.
Small blood vessel occlusion (lacunar stroke)
- 4.
Other determined cause
- 5.
Undetermined (cryptogenic) cause (no cause identified, more than one cause, or incomplete investigation)
The incidence of each cause is variable and depends on patient age, sex, race, geographic location, risk factors, clinical history, physical findings, and the results of various tests. This guidelines document deals primarily with cardioembolic strokes but also includes discussions of the role of echocardiography in evaluation of embolic strokes from the thoracic aorta (atheroembolism) and in cryptogenic strokes. Embolism of cardiac origin accounts for 15% to 40% of all ischemic strokes, while undetermined (cryptogenic) causes are responsible for 30% to 40% of such strokes.
Type and Relative Embolic Potential of Cardiac Sources of Embolism
In patients who are at risk for or have already had potentially embolic strokes, the primary role of echocardiography is to establish the existence of a source of embolism, determine the likelihood that such a source is a plausible cause of stroke or systemic embolism, and guide therapy in an individual patient.
Cardiac sources of embolism include blood clots, tumor fragments, infected and bland (noninfected) vegetations, calcified particles, and atherosclerotic debris. Conditions that are known to lead to systemic embolization are listed in Table 1 and subdivided into a high-risk and a low-risk risk group on the basis of their embolic potential. However, in many conditions more than one embolic source may be present (coexistence of embolic sources) or one cardioembolic condition may lead to another (interdependence of embolic sources). For instance, mitral stenosis is associated with spontaneous echocardiographic contrast (SEC), atrial fibrillation, left atrial (LA) clot, and even endocarditis.
| High embolic potential |
|---|
|
| Low embolic potential |
|
Diagnostic Workup in Patients with Potential Cardiac Sources of Emboli
Evaluation of suspected cardiac source of embolism requires rapid diagnostic efforts, which should include detailed history, comprehensive physical examination, blood workup, and imaging of the heart and the organs damaged by the embolus. Echocardiography should be the primary form of cardiac imaging, supplemented by chest x-ray, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging when necessary. CT or MRI as well as angiography may be indispensable in the evaluation of organs and tissues affected by cardiac sources of embolism.
Prevention and Treatment
Echocardiography plays an important role not only in the diagnosis but also in the treatment and prevention of cardiac sources of embolism. This aspect of echocardiography is beyond the scope of this guidelines document; references to appropriate treatment and prevention guidelines are given in individual sections of this document.
Role of Echocardiography in Evaluation of Sources of Embolism
Since its earliest days, echocardiography has been considered an important tool in the evaluation of possible cardiac source of embolism. Even the one-dimensional M-mode technique, which was first introduced in 1953 by Swedish cardiologist Inge Edler (1911–2001) and engineer Hellmuth Hertz (1920–1990), was capable of demonstrating conditions associated with embolic stroke and systemic emboli, such as mitral stenosis, LA dilatation, LA myxoma, and left ventricular (LV) systolic dysfunction.
The introduction of two-dimensional (2D) echocardiography in the early 1970’s further expanded the diagnostic capability and accuracy of ultrasound imaging in the evaluation of cardiac sources of embolism; wall motion abnormalities could be better defined, and various normal and abnormal cardiac structures could be better assessed.
The introduction of Doppler techniques in the 1970’s and transesophageal echocardiography (TEE) in the 1980’s allowed more precise quantification of normal and abnormal intracardiac structures and blood flows. Finally, the advent of real-time three-dimensional (3D) echocardiography at the turn of the 21st century has provided unprecedented anatomic and functional details of many cardiac structures implicated as cardiac sources of embolism and allowed guidance of percutaneous treatments of sources of cardiac embolism (e.g., percutaneous closure of LA appendage (LAA) in patients with atrial fibrillation).
The overall use of echocardiography in the evaluation of cardiac sources of emboli should follow established appropriate use criteria. Below is an excerpt from the appropriate use criteria guidelines, with entries relevant to cardiac sources of embolism.
Appropriate Use Criteria for Echocardiography in Evaluation of Cardiac Sources of Emboli
Appropriate Use: Transthoracic Echocardiography (TTE)
- •
Symptoms or conditions potentially related to suspected cardiac etiology, including but not limited to chest pain, shortness of breath, palpitations, TIA, stroke, or peripheral embolic event
- •
Suspected cardiac mass
- •
Suspected cardiovascular source of embolus
- •
Initial evaluation of suspected infective endocarditis (IE) with positive blood culture results or new murmur
- •
Reevaluation of IE at high risk for progression or complication or with a change in clinical status or cardiac examination results
- •
Known acute pulmonary embolism (PE) to guide therapy (e.g., thrombectomy and thrombolytic therapy)
- •
Reevaluation of known PE after thrombolysis or thrombectomy for assessment of change in right ventricular (RV) function and/or pulmonary artery pressure
Appropriate Use: TEE
- •
As initial or supplemental test for evaluation for cardiovascular source of embolus with no identified noncardiac source
- •
As initial or supplemental test to diagnose IE with a moderate or high pretest probability (e.g., staph bacteremia, fungemia, prosthetic heart valve, or intracardiac device)
- •
As initial test for evaluation to facilitate clinical decision making with regard to anticoagulation, cardioversion, and/or radiofrequency ablation
Uncertain Indication for Use: TEE
- •
Evaluation for cardiovascular source of embolus with a previously identified noncardiac source
Inappropriate Use: TTE
- •
Transient fever without evidence of bacteremia or new murmur
- •
Transient bacteremia with a pathogen not typically associated with IE and/or a documented nonendovascular source of infection
- •
Routine surveillance of uncomplicated IE when no change in management is contemplated
- •
Suspected PE to establish diagnosis
- •
Routine surveillance of prior PE with normal RV function and pulmonary artery systolic pressure
Inappropriate Use: TEE
- •
Evaluation for cardiovascular source of embolus with a known cardiac source in which TEE would not change management
- •
Routine use of TEE when diagnostic TTE is reasonably anticipated to resolve all diagnostic and management concerns
- •
Surveillance of prior transesophageal echocardiographic finding for interval change (e.g., resolution of thrombus after anticoagulation, resolution of vegetation after antibiotic therapy) when no change in therapy is anticipated
- •
To diagnose IE with low pretest probability (e.g., transient fever, known alternative source of infection, negative blood culture results or atypical pathogen for endocarditis)
- •
Evaluation when a decision has been made to anticoagulate and not to perform cardioversion
A Practical Perspective: Echocardiographic Techniques for Evaluation of Cardiac Sources of Embolism
Echocardiography plays an essential role in the evaluation, diagnosis, and management of cardiac and aortic sources of embolism. Standard TTE and TEE are useful but yield to better results when additional imaging techniques are performed as a part of the examination. These include, but are not limited to, high-frequency and fundamental imaging, off-axis and nonstandard views, thorough sweeps through chambers and multiple planes, multiplane and 3D imaging, and the use of contrast (both agitated saline and transpulmonary microbubble contrast agents). Such techniques are summarized in Table 2 . When assessing specific structures of the heart using 3D imaging, acquisition should be focused on the structure as outlined in the European Association of Echocardiography and ASE recommendations. Depending on the patient’s presentation and history, most or some of the imaging techniques previously mentioned in this section should be applied. Examples of various echocardiographic imaging techniques, including still images and video clips, are provided throughout this document in sections dealing with individual cardiac sources of embolism.
| Cardioembolic source | TTE | TEE |
|---|---|---|
| Atrial arrhythmias |
|
|
|
|
|
| Endocarditis |
|
|
| Nonischemic and ischemic cardiomyopathies |
|
|
| Cardiac masses | ||
| Intracardiac thrombus, vegetations (marantic or infective) |
|
|
| Intracardiac tumors, fibroelastoma |
|
|
| Thromboembolism from the thoracic aorta |
|
|
| Aortic arch atheromatous plaque |
|
|
| Intracardiac shunt |
|
|
| Intrapulmonary shunt |
|
|
| Transcatheter devices |
|
|
Two-Dimensional High-Frequency and Fundamental Imaging
Most ultrasound systems are preset to image using harmonics, giving better endocardial definition while losing resolution on valvular structures and other structures compared with fundamental imaging. Tissue harmonics occur with transmission through tissue, so there is minimal harmonic effect in the near field. This is particularly important when evaluating for apical thrombus to differentiate the border of the thrombus from the endocardium. High-frequency and fundamental imaging, as mentioned in Table 2 , should be applied to highlight structures without increasing the thickness of the structure. Figure 1 displays an akinetic apex from an apex-focused view on TTE with harmonics on the left side and fundamental imaging on the right side of the image.
Three-Dimensional and Multiplane Imaging
Three-dimensional and multiplane imaging has opened up echocardiography to new ways of interrogating and assessing cardiac structure and function. Although standard 2D imaging is still used for the majority of an examination, 3D and multiplane imaging can highlight areas often missed or overlooked as well as specify areas of interest when it comes to sources of cardiac, aortic, and pulmonary emboli. Figure 2 and Videos 1 and 2 display standard 2D apical four-chamber, biplane, and 3D images. With each image, more information is gathered regarding the extent, mobility, and number of thrombi in the left ventricle.
Figure 3 illustrates a transesophageal echocardiographic examination of a patient with an LA myxoma. In the standard 2D image, the myxoma is shown moving through the mitral valve (MV) orifice, while the 3D image shows not only the LA myxoma as it moves in the left atrium and MV but also the point of attachment on the interatrial septum.
Saline and Transpulmonary Contrast
The appropriateness and use of transpulmonary contrast for endocardial border definition as well as Doppler enhancement is well defined in the 2014 ASE contrast guidelines. Additional uses of transpulmonary contrast can include border and structure definition of thrombi ( Figure 4 ) and masses as well as showing if a structure is vascularized, much like cardiac MRI.
Although color Doppler can sometimes detect intracardiac communication, the use of agitated saline contrast yields higher results or incidence of findings ( Figure 5 ).
Color Doppler, Off-Axis and Nonstandard Views and Sweeps
In addition to standard color Doppler imaging for valvular stenosis and regurgitation, routine imaging for intracardiac communication (with an appropriate Nyquist limit shift) should be performed in the setting of cardiac source of embolism. Color Doppler can illustrate new communication between cardiac chambers, paravalvular leaks, aneurysms and pseudoaneurysms, and abscesses. Figure 6 illustrates a prosthetic MV with endocarditis by 2D imaging, while the color Doppler image demonstrates the paravalvular leak from the infection.
As previously mentioned above in the section on 3D imaging, sources of cardiac, aortic, and pulmonary emboli can be missed or overlooked if only standard echocardiographic views are performed. The application of off-axis and nontraditional imaging can highlight pathology, enhance target definition by increasing specularity, and display regions of the heart in planes that are not appreciated by standard 2D images. The use of sweeps from multiple perspectives not only displays these additional planes of view but also highlights relational anatomy and gives spatial awareness of cardiac findings. Figure 7 shows an example of a sweep used to show an RV apical thrombus.
TTE versus TEE
The quality of TTE varies among patients and depends on body habitus, the size of the intercostal spaces, the presence of chest deformities, and lung disease such as emphysema. Even with the most advanced echocardiographic equipment, transthoracic imaging may still be suboptimal or even unobtainable.
Because the ultrasound beam loses energy as it travels through tissue, structures that are far from the chest wall may not be well imaged by TTE. Lower transducer frequency improves penetration but decreases image resolution. As a result, structures that may be important sources of embolism, such as the posteriorly located left atrium and its appendage, the interatrial septum, and the thoracic aorta, may be suboptimally visualized by TTE.
With the transducer in the esophagus during TEE, there is close proximity between the transducer and the posterior aspect of the heart. This shorter distance enables the use of higher frequency transducers. With TEE, the heart is not masked by extracardiac structures such as bones and lung tissue. As a result, TEE can provide images of higher resolution and disclose findings that may be responsible for cardiac and aortic sources of embolism. In many echocardiography laboratories, evaluation for a source of embolism is the most common indication for TEE.
Although TEE is usually safe, it is still considered a semi-invasive procedure. Complications are rare, but the most serious one is esophageal perforation (with a reported incidence ranging from 0.01% to 0.09% of all studies performed). Other complications include damage to the oral cavity, the teeth, the pharynx, and the trachea, as well as complications associated with topical anesthesia and sedation. Performance of TEE should follow appropriate ASE guidelines.
Unless there are clinical findings that suggest conditions that explain the embolic event, such as atrial fibrillation, mitral stenosis, or endocarditis, the results of TTE are often negative. It had been therefore suggested that TTE may be unnecessary in patients with cryptogenic stroke and negative clinical evaluation. TTE may also be unnecessary when TEE is already planned (e.g., for evaluation of intracardiac masses, prosthetic valves, and the thoracic aorta or when TEE is used to guide a percutaneous procedure related to cardiac source of embolism). Others believe that TTE may occasionally provide information not well seen on TEE (such as LV apical thrombi) or may even eliminate the need for the more invasive and expensive TEE.
Efforts to determine the cost-effectiveness of echocardiography as applied to patients with acute neurologic deficits have yielded conflicting results depending on the assumptions used to conduct the analyses. However, it is important to emphasize that these analyses do not take an individual patient into perspective but rather evaluate cost-effectiveness from a societal perspective.
In summary, TTE excels in imaging of anterior cardiac structures using lower frequency probes. In contrast, TEE uses higher frequency probes and excels in imaging of posterior cardiac structures and the thoracic aorta. In general, the sensitivity of TEE exceeds that of TTE. TEE is likely to be helpful if TTE is of poor quality, in young patients with stroke, those with stroke of unknown etiology, and those with nonlacunar strokes.
Pros and cons of TTE and TEE are listed in Table 3 .
| Potential source of embolism | TTE | TEE | |
|---|---|---|---|
| Favors TEE | LA/LAA thrombus or SEC | −/+ | ++++ |
| Aortic atheroma | −/+ | ++++ | |
| Prosthetic valve abnormalities | + | ++++ | |
| Native valve vegetation | ++ | ++++ | |
| Atrial septal anomalies | ++ | ++++ | |
| Cardiac tumors | +++ | ++++ | |
| Favors TTE | LV thrombus | ++++ | ++ |
Recommendations for Performance of Echocardiography in Patients with Potential Cardiac Source of Embolism
Echocardiography Recommended
- •
Echocardiography should be considered in all patients with suspected cardiac sources of embolism, especially in patients for whom clinical therapeutic decisions (such as anticoagulation or cardioversion) will depend on echocardiographic findings.
Echocardiography Potentially Useful
- •
Patients with neurologic events and concomitant intrinsic cerebrovascular disease.
Echocardiography Not Recommended
- •
Echocardiography is not recommended in patients for whom the results will not guide therapeutic decisions.
TTE versus TEE
- •
TEE is not indicated when transthoracic echocardiographic findings are diagnostic for a cardiac source of embolism.
- •
TTE may be unnecessary when TEE is already planned (e.g., for evaluation of intracardiac masses, prosthetic valves, and thoracic aorta or when TEE is used to guide a percutaneous procedure related to cardiac source of embolism).
Alternatives to Echocardiography in Imaging Cardiac Sources of Embolism
Radiologic nonechocardiographic techniques are used in imaging target organs affected by cardioembolism (primarily the brain) as well as for visualization of sources of embolism in the heart and large vessels.
Computed Tomographic or Magnetic Resonance Neuroimaging
Computed tomographic or magnetic resonance neuroimaging is essential for differentiating ischemic from hemorrhagic strokes. Neuroimaging findings that support cardioembolic stroke include simultaneous or sequential strokes in different arterial territories ( Figure 8 ). Because of their large size, cardiac emboli flow to the intracranial vessels in most cases and predominate in the distribution territories of the carotid and middle cerebral arteries. These brain findings are distinct from nonembolic stokes such as watershed infarcts and lacunar strokes ( Figure 9 ).
The presence of a potential major cardiac source of embolism in the absence of significant arterial disease remains the mainstay of clinical diagnosis of cardioembolic cerebral infarction. When cardiac and carotid arterial disease coexist, determining the etiology of the ischemic stroke becomes more difficult.
Transcranial Doppler (TCD)
TCD may be used to detect cerebral microemboli, which may consist of cholesterol crystals, fat, air, or calcium. TCD may also be used for the detection of intracranial emboli during surgical manipulation of the thoracic aorta. TCD may also allow noninvasive diagnosis of a right-to-left shunt caused by a patent foramen ovale (PFO) by detecting bubble signals in the middle cerebral artery after the injection of agitated saline in the antecubital vein.
The most important limitation of contrast TCD is the absence of a temporal bone window in 10% of patients who have strokes, especially in the older population. The temporal bone window is located just above the zygomatic arch; suitability of this window is defined as the ability to measure Doppler flow in the middle cerebral artery.
TCD also does not distinguish intracardiac shunts from extracardiac shunts, nor does it allow direct visualization of the shunt, as does echocardiography. TCD is a reliable, noninvasive alternative to TEE for the diagnosis of right-to-left shunting, with excellent sensitivity and specificity of 97% and 93%, respectively. Specificity can be further improved by increasing the bubble threshold for a positive result from one microbubble to 10 microbubbles, without compromising sensitivity.
Nuclear Cardiology
Assessment of myocardial perfusion and ventricular function may be useful in selected patients (e.g., in patients with ischemic heart disease).
Chest CT
Electrocardiographically gated multidetector CT can be used to study the left heart and great vessels in patients suspected to have cardioembolic strokes. Multidetector CT allows extremely fast examination times combined with high spatial resolution (0.4–0.6 mm). Currently the main drawback is its relative lack of inherent soft-tissue contrast, which limits its assessment of the myocardium and identification of small thrombi. Other disadvantages are high radiation burden and exposure to potentially nephrotoxic iodinated contrast agents.
One advantage of chest CT and MRI compared with echocardiography is their ability to better visualize chest structures adjacent to the heart that may contribute to systemic embolism (e.g., cardiac invasion of a malignant tumor of a surrounding organ or tissue, visualization of the entire thoracic aorta).
Chest MRI
Routine cardiovascular MRI in the context of stroke does not currently form part of consensus guidelines, but there is an increasing body of literature to support its role, as an adjunct to echocardiography in selected cases (e.g., tissue characterization of cardiac tumors).
Recommendation for Alternative Imaging Techniques in Evaluation of Cardiac Sources of Embolism
Alternative Imaging Recommended
- •
Computed tomographic and magnetic resonance neuroimaging is essential in the evaluation of patients with neurologic symptoms attributable to a cardiac source of emboli.
- •
CT, MRI, or other radiologic imaging of the heart and the great vessels may be useful in selected patients with cardiac sources of embolism.
Alternative Imaging Not Recommended
- •
Alternative imaging of the heart and great vessels is not recommended when echocardiographic findings are diagnostic.
Thromboembolism from the Left Atrium and LAA
A thrombus located in the left atrium or, more precisely, the LAA is the most prevalent source of cardioembolic events and is typically associated with atrial arrhythmias such as atrial fibrillation and atrial flutter. TEE is the echocardiographic imaging modality of choice for the evaluation of LAA anatomy and function. The LAA may be unilobular or multilobular. Four different morphologies have been used to categorize the LAA: cactus, chicken wing, windsock, and cauliflower. Patients with chicken-wing LAA morphology may be less likely to have thromboembolic events compared with those with other LAA morphologies.
Pathogenesis of Atrial Thrombogenesis and Thromboembolism
Definite gaps remain in our knowledge regarding atrial thrombogenesis and thromboembolism and the most appropriate and clinically effective diagnostic and therapeutic options. The prevalence of atrial fibrillation is 0.4% to 1% of patients in the general population but increases to 9% in patients who are ≥80 years of age. The risk for stroke or embolism in patients with atrial fibrillation ranges from a low-risk value of 1% per year to a high-risk value of 15%. It is estimated that in approximately 75% of patients with cardioembolic episodes, emboli arise from the LAA and are thus presumed to be caused by atrial fibrillation. However, many of these patients are >75 years of age, with concomitant hypertension, diabetes mellitus, and carotid disease, all of which are independent predictors of stroke.
Although the fundamentals of thrombogenesis were proposed >150 years ago by the report of Virchow’s triad (blood stasis, endothelial injury, and hypercoagulability), the precise conditions under which thrombogenesis and thromboembolism occur in relation to the left atrium remain largely speculative. The tenets of this Virchow hypothesis have been extrapolated to the left atrium and atrial fibrillation. Thrombus formation occurs along a pathogenesis continuum that starts with SEC or “smoke” formation (erythrocyte rouleaux formation indicative of blood stasis), progresses to sludge formation (very dense smoke) and ends with complete thrombus formation ( Figure 10 , and Videos 3, 4, and 5 ). Persistent SEC in the left atrium on TEE has been associated with later thrombus formation and systemic embolization. Sludge has an echocardiographic appearance that is more viscid than smoke but less dense than thrombus.
The anatomic structure of the LAA and acquired enlargement and stretch of the left atrium or LAA in valvular and nonvalvular heart disease provide the milieu for blood stasis.
Microscopic endocardial changes in the LAA have been reported in atrial fibrillation as compared with sinus rhythm and mitral stenosis as compared with mitral regurgitation. Edema, fibrinous transformation, and endothelial denudation have been described in the LA tissue in patients with atrial fibrillation and thromboembolism. Additionally, impairment of extracellular matrix turnover has also been implicated as a factor contributing to structural changes that occur in the left atrium. Patients with LA fibrillation have abnormal amounts of collagen and degradation products as well as concentrations of matrix metalloproteinases.
Stasis of flow in the left atrium can occur not only during atrial fibrillation (because of the reduction of effective atrial contractile function, as evidenced by the presence of SEC) but may also occur during sinus rhythm given the appropriate associated pathology (i.e., significant LA enlargement and/or mitral stenosis).
Additional insights into the pathogenesis of thrombogenesis and thromboembolism have been obtained from studies that used TEE to study the effects of electrical cardioversion of atrial fibrillation to sinus rhythm. That thromboembolism could develop after electrical cardioversion of atrial fibrillation had been well described since the 1960’s and before the advent of TEE. However, clues to the underlying mechanisms came only with the use of TEE in this patient population.
The phenomenon of LAA “stunning” was demonstrated on TEE by an increase in the intensity of SEC ( Figure 11 ) and the decrease in LAA Doppler flow velocities ( Figure 12 ) immediately after cardioversion of atrial fibrillation to sinus rhythm. Before this transesophageal echocardiographic observation, the prevailing theory was that stroke in the postcardioversion period resulted solely from dislodgement of a preexisting thrombus (present before cardioversion and due to the underlying atrial fibrillation). Further evidence for the role of postcardioversion stunning in the genesis of thromboembolism came from a series of patients who had postcardioversion strokes despite the absence of LA or LAA thrombus on precardioversion TEE. These transesophageal echocardiographic studies formed the basis and rationale for the TEE-guided anticoagulation strategy used today when managing patients with atrial fibrillation undergoing electrical cardioversion.
In addition to the anatomic and hemodynamic changes contributing to the propensity of the left atrium to thrombogenesis, abnormalities of coagulation cascade proteins and platelets may also play a role. Increased fibrin turnover and prothrombin fragments 1 and 2 have been associated with atrial fibrillation in patients with stroke. Furthermore this prothrombotic state has been correlated with LAA dysfunction and SEC. d -dimer levels also appear associated with thromboembolism events in patients with nonvalvular atrial fibrillation and may be useful in determining hypercoagulability. Serum levels of von Willebrand factor, a marker of endothelial damage and dysfunction, have also been found to be elevated in the presence of LAA thrombus and atrial fibrillation. Although many studies have suggested a potential role for platelets and thrombogenesis in atrial fibrillation, the precise involvement and link of platelet function to the hypercoagulable state have yet to be defined.
Echocardiographic Evaluation of the Left Atrium and LAA
The basis of imaging in atrial fibrillation centers on identifying one of the many underlying cardiac causes of atrial fibrillation, such as valvular heart disease, ventricular dysfunction, and hypertension. Once an associated etiology of atrial fibrillation has been identified or ruled out, attention turns to details of LA anatomy, specifically whether the left atrium is enlarged and, if so, how severely.
LA enlargement has significance relative to thromboembolic risk, maintenance of sinus rhythm, and prognosis. Although thrombus can be identified by TTE and the specificity is high, the sensitivity of TTE is unacceptably low, in part because most atrial thrombi are located in the LAA rather than the main LA cavity. The LAA is best viewed by TEE.
LA size can be expressed as either the anterior-posterior LA diameter or LA area and measured according to the ASE guidelines on chamber quantification. Investigation has demonstrated the superiority of LA volume measurements and more precisely LA volume indexed to body size as a more accurate measurement. In addition, atrial volumes have significant prognostic value relative to stroke risk, mortality, atrial fibrillation recurrence after electrical cardioversion, ablation, and cardiac surgery. It is believed that LA volumes obtained by 3D echocardiography may provide the ultimate quantification. However, this has not been routinely adopted in clinical practice at this time.
Because of its portability, relatively low cost, and noninvasive nature, TTE is recommended for evaluation of the left atrium, cardiac structure, and function in atrial fibrillation by these guidelines as well as the European Association of Echocardiography consensus guidelines, the American College of Cardiology, American Heart Association, and Heart Rhythm Society document on management of patients with atrial fibrillation, and the American College of Cardiology, American Heart Association, and ASE appropriate use criteria for echocardiography.
Because of its location immediately adjacent to the esophagus, the left atrium is the structure best suited to the strengths of TEE and its ability to visualize cardiac structures with high spatial resolution and good temporal resolution, all in real time. More specifically, TEE enables optimal visualization of LAA anatomy as well as interrogation of its function and physiology with Doppler interrogation. The introduction and addition of 3D imaging have added to our ability to interrogate the LAA, providing perspective relative to LAA anatomy as well as an added ability to visualize real or artifactual masses within the cavity.
Cardioversion
In a substudy of the Stroke Prevention in Atrial Fibrillation trial, in which patients with atrial fibrillation were randomized to warfarin versus aspirin for primary stroke prophylaxis, the LAA data obtained by TEE were found to be independent predictors of thromboembolism. The presence of LAA clot (relative risk, 3.5), LAA peak flow velocity ≤ 27 cm/sec (relative risk, 1.7), and aortic plaque (relative risk, 2.1) were all associated with thromboembolic events.
In addition to evaluating patients with stroke and/or atrial fibrillation for the presence of thrombus, TEE is commonly used in the management of patients with atrial fibrillation in whom maintenance of sinus rhythm is desired either by using chemical or electrical cardioversion or pulmonary vein isolation. TEE has been demonstrated to be useful in guiding anticoagulation management around the time of cardioversion, such that if the results of TEE are negative for the presence of thrombus, one can proceed directly to cardioversion, provided the patient has been therapeutically anticoagulated before the procedure.
The Assessment of Cardioversion Using Transesophageal Echocardiography trial was a prospective randomized multicenter trial that compared a conventional anticoagulation strategy with a TEE-guided anticoagulation management strategy in patients undergoing cardioversion for atrial fibrillation. Conventional anticoagulation management consisted of 3 weeks of therapeutic anticoagulation with warfarin before cardioversion and 4 weeks of anticoagulation after cardioversion. Patients randomized to the TEE-guided arm could proceed directly to cardioversion provided they were anticoagulated to therapeutic levels and had no evidence of thrombus on TEE. Low embolic event rates (0.65%) were found in both arms, with no difference between the conventional (0.5%) and TEE (0.8%) arms relative to embolic stroke as well as a composite end point that included mortality, embolic stroke, and bleeding. Bleeding was significantly lower in patients undergoing TEE-guided cardioversion, and the time to cardioversion was shorter compared with the conventional arm. Therefore, the primary advantage to the TEE-guided strategy is that a 3-week course of precardioversion anticoagulation can be avoided, provided the results of TEE are negative for thrombus.
Pulmonary Vein Isolation
Echocardiography, primarily TEE, has been studied and used in patients undergoing pulmonary vein isolation to assess for thrombus before instrumenting the left atrium. Intracardiac echocardiography can also be useful in detecting atrial thrombus and is commonly used during the procedure by the electrophysiologist to assist in monitoring and guidance of the pulmonary vein isolation procedure.
TTE has been reported to be useful in assessing return of LA function after pulmonary vein isolation, while TEE can be useful in identifying pulmonary vein stenosis after the procedure. The significant reduction in incidence of pulmonary vein stenosis as the procedure has matured as well as the excellent diagnostic accuracy of multidetector CT and cardiac MRI in this setting has reduced the prominence of TEE for this indication.
Guidance of LAA Percutaneous Procedures
TEE in general and real-time 3D TEE in particular are useful for guiding percutaneous closure of the LAA using closure devices such as the recently US Food and Drug Administration–approved Watchman device (Boston Scientific, Marlborough, MA) or others still in investigational stages.
Recommendations for Performance of Echocardiography in Patients with Suspected LA and LAA Thrombus
Echocardiography Recommended
- •
TTE is recommended in patients with suspected LA or LAA thrombus to assess LA size and LV size and function, as well to assess for underlying etiologies of atrial fibrillation and additional risk factors for stroke.
- •
TEE is superior to TTE in assessment of anatomy and function of LAA in a variety of clinical contexts, such as before cardioversion, ablation of atrial arrhythmias, and percutaneous procedures for LAA closure.
Echocardiography Potentially Useful
- •
Contrast echocardiography using microbubble agents (such as perflutren) may aid in detecting LA and LAA thrombi and may help differentiate avascular thrombi from vascular tumors.
- •
Three-dimensional echocardiography may provide more precise assessment of LA and LAA size and morphology.
Echocardiography Not Recommended
- •
Echocardiography is not recommended in patients for whom the results will not guide therapeutic decisions.
Thromboembolism from the Left Ventricle
Acute Coronary Syndromes
Regional wall motion abnormalities along with subendocardial injury in the setting of an acute myocardial infarction result in blood stasis and nidus for LV thrombus formation. Furthermore, there is a hypercoagulable state with increased procoagulants and a decrease in concentration of physiologic anticoagulants during an acute coronary event, thus creating a perfect milieu for formation of LV thrombus. These thrombi, composed of fibrin, red blood cells, and platelets, can occur as early as 24 hours after an acute myocardial infarction, with the majority (90%) of thrombi forming within 14 days of a myocardial infarction.
The incidence of LV thrombus in the setting of an acute coronary event varies significantly depending on different studies, ranging from as low as 7% to as high as 46%. Current reperfusion therapies such as thrombolysis and aggressive medical management, including aggressive use of antiplatelet and anticoagulant agents, have shown a trend toward reducing the incidence of LV thrombosis. Patients with acute anterior myocardial infarction and/or apical infarction are more likely to have LV apical thrombus. The prevalence may be as high as 50% in chronic LV aneurysm.
Data on the incidence of LV thrombus in the current era of aggressive interventions in the setting of acute myocardial infarction are limited and retrospective in nature; the incidence is reported to be about 5% to 15%. These data are further compounded by many other factors, including time frame when the imaging study is done to identify an LV thrombus. Echocardiographic studies performed early are likely to miss the presence of LV thrombus.
The presence of LV thrombus from 2 to 11 days after myocardial infarction is reported to be as high as 40% in patients with acute anterior myocardial infarction. Despite the higher incidence of thrombus formation, the incidence of a thromboembolic event leading to stroke is relatively low. The prevalence of LV thrombus is more likely to be present in patients with advanced systolic dysfunction, previous myocardial infarction, and large scar burden identified by delayed enhanced MRI. In a study of 8,000 patients with ST-segment elevation myocardial infarction, LV thrombus was present in approximately 5% of cases.
Patients with anterior wall infarction were more likely to have LV thrombus (11.5% vs 2.3% in other regions). Furthermore, LV thrombus was more likely in patients with ejection fractions of <40% and anterior wall myocardial infarction (17.8%). LV thrombus is not located exclusively within the LV apex; it can occur in other regions of the left ventricle, specifically the inferoposterior and septal walls in a small percentage of patients.
Studies have consistently shown that LV thrombus is more likely to be present in the setting of large infarct size, anterior myocardial infarction, severe apical wall motion abnormality, and LV aneurysm.
Cardiomyopathy
Patients with significant LV dilation and dysfunction, whether ischemic or nonischemic, are at increased risk for developing LV thrombus. It is unusual to have the presence of LV thrombus in the setting of normal wall motion, with the exception of endomyocardial fibrosis, in which thrombus can occur in either the left or right ventricle within normally contracting regions of the heart. The incidence of LV thrombus in patients with cardiomyopathies also varies depending on studies, which also are predominantly retrospective in nature. In patients with dilated cardiomyopathy, thromboembolic events are reported to be in the range of 1.7% to 18%.
Risk factors that predispose patients with cardiomyopathies to thromboembolic events include extensive regional wall motion abnormalities, very dilated left ventricles, low cardiac output with the stagnation of blood within the ventricle, significant slow swirling streaks of blood within the left ventricle (SEC) and the presence of atrial fibrillation. Additionally, the presence of advanced apical hypertrophy cardiomyopathy with apical outpouching can also be a risk for clot formation.
LV Thrombus Morphology
There are three main types of thrombi that can be identified within the left ventricle:
- 1.
Mural thrombus (only one surface exposed to the blood pool; flat and parallel to the endocardial surface)
- 2.
Protruding thrombus (more than one surface exposed to the blood pool and protruding into the LV cavity)
- 3.
Mobile thrombus with independent motion (either in parts of the thrombus or in its entirety)
Studies have shown that patients with LV thrombi that are mobile and/or protrude into the LV cavity have a higher incidence of embolization. However, 40% of embolic events occur in patients who do not have protruding and/or mobile thrombi.
The incidence of embolization is lowest for a mural thrombus and highest for a mobile thrombus. However, serial echocardiographic studies have shown variability of thrombus morphology in the first several months after acute myocardial infarction, with 41% of thrombi changing shape and 29% changing mobility. Other characteristics of thrombus that have been shown to be associated with increased risk for embolization include central lack of lucency, hyperkinesis of adjacent myocardial segments around the thrombus, and thrombus size (controversial).
Patients at highest risk for embolization include patients with atrial fibrillation, severe congestive heart failure, markedly dilated left ventricles with severe systolic dysfunction, previous thromboembolic events, and advanced age. Thrombi within LV aneurysm are less likely to embolize, probably because of the absence of LV contraction in the aneurysm.
Role of Echocardiography in the Detection of LV Thrombus
TTE is the technique of choice and most widely used clinically for the evaluation of regional and global LV and RV function, assessment of valves, and LV thrombus. TTE has excellent sensitivity (95%) and specificity (85%–90%) in detecting LV thrombus. Echocardiographically LV thrombus is identified as a discrete echocardiographic mass seen in the left ventricle with well-defined margins that are distinct from the endocardium and seen throughout systole and diastole in an area with corresponding significant LV, regional, or global wall motion abnormalities ( Figure 13 and Videos 6, 7, and 8 ).
To confirm the diagnosis of a thrombus, it must be seen in at least two orthogonal (apical and short-axis) views. It is important to exclude artifacts, including near-field clutter, false tendons, LV trabeculations, and apical foreshortenings, to accurately diagnose a thrombus. Simple steps can be used to overcome these artifacts, including moving the focal zone to the apex, using a higher frequency transducer, and using low-aliasing color flow velocities to define any filling defects. If the diagnosis is still uncertain, echocardiographic contrast agents should be used.
In technically limited studies (30%–35%), especially when the apex is not clearly visualized, the use of myocardial echocardiographic contrast agents has significantly affected the accurate diagnosis of ruling in or out an LV thrombus.
TEE has a limited role in the detection of LV thrombus, because the apex is farthest from the transducer, and the apex is often foreshortened and/or not well visualized. In contrast, the transthoracic echocardiographic probe is in close proximity to the left ventricle and apex, making them easier to image in multiple planes.
Three-dimensional echocardiography may further enhance identification of LV thrombus by more detailed evaluation of the LV apex (more segments and regions evaluated). However, the limitations of 3D echocardiography remain, as it has low frame rates and poor resolution.
Recommendations for Performance of Echocardiography in Patients with Suspected LV Thrombus
Echocardiography Recommended
- •
TTE is recommended for the evaluation of patients with underlying cardiac disease known to predispose to LV thrombus formation (such as myocardial infarction or nonischemic cardiomyopathy).
- •
TTE is typically superior to TEE in the assessment of LV apical thrombus.
Echocardiography Potentially Useful
- •
Contrast echocardiography using microbubble agents (such as perflutren) may aid in detecting LV thrombi and may help differentiate avascular thrombi from vascular tumors.
- •
Three-dimensional echocardiography may provide more precise assessment of LV thrombus.
Echocardiography Not Recommended
- •
Echocardiography is not recommended in patients for whom the results will not guide therapeutic decisions.
Valve Disease
Native cardiac valves can be a source of both systemic and PE in the form of thrombi, infective and noninfective vegetations, and calcific debris. In addition, both biologic and mechanical valvular prostheses may become embolic sources of thrombi and/or vegetations and also represent a common underlying substrate for cardioembolic stroke. Both TTE and TEE play a central role in diagnosis, prognostication, and management and decision making for these patients.
Several specific valvular entities have been associated with embolism, including IE, nonbacterial thrombotic endocarditis (NBTE), valvular papillary fibroelastoma (PFE), mitral annular calcification (MAC), and biologic or mechanical prosthetic valve endocarditis and thrombosis. Other conditions remain controversial as embolic sources, including degenerative native valve strands and mechanical valve platelet thrombi. Each condition will be addressed separately with emphasis on its echocardiographic recognition, the diagnostic and prognostic value of echocardiography, as well as appropriate use and indications of each echocardiographic modality.
Infective Endocarditis
Diagnosis
In the great majority of cases, positive blood culture results and evidence of endocardial involvement constitute the definition of IE, so echocardiographic exploration for endocardial infection is not only accepted but mandatory in the evaluation of a patient with possible IE. Although a “valvular vegetation” is the hallmark of endocardial infection, cardiac abscess or fistula, new partial prosthetic valve dehiscence, and the presence of new valvular regurgitation all represent endocardial infection in the correct clinical setting, even in the absence of vegetation.
Knowledge of the patient’s clinical history is critical because maximal diagnostic benefit of echocardiography will be obtained in those patients with intermediate pretest probability, and interpretation and reporting of imaging findings must be done in light of the clinical history because echocardiography does not provide substantial tissue characterization or pathologic information ( Table 4 ).
|
Therefore, awareness of the echocardiographic features that characterize vegetations ( Table 5 , Figure 14 and Video 9 ) and paravalvular complications is key ( Figure 15 and Video 10 ). Native valvular findings that may be confused with infective vegetations are PFE, valvular strands and Lambl’s excrescences, MAC with mobile components, redundant chordae tendineae, and NBTE.
|
Prosthetic findings that may be confused with vegetation include prosthetic strands, thrombosis, mitral subvalvular tissue remnants ( Figure 16 and Videos 11 and 12 ), and microcavitations. An experienced echocardiographer should readily recognize microcavitations and their benign nature ( Figure 17 and Video 13 ). Microcavitations are high-velocity, tiny, bright echoes that occur at the inflow zone of mechanical valves (both aortic and mitral, more frequent mitral) at the time of valve closure, when flow velocity and pressure drop abruptly. They represent a normal phenomenon and in fact may disappear with valve obstruction or thrombosis, only to return after thrombolysis.
