Cardiac Embolism

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Chapter 4 Cardiac Embolism

Alejandro A. Rabinstein, Steven J. Resnick

Cardiac embolism represents one of the most common mechanisms of ischemic stroke. It is most common in the elderly as a consequence of the high incidence of atrial fibrillation, but it is also one of the most frequent causes of stroke in the young. Yet several factors often make the diagnosis of cardiac embolism complicated: (1) cardiac embolism can produce infarctions in any vascular distribution; (2) some of the potential sources of cardiac embolism are prevalent in the general population; (3) cardioembolic sources often coexist with atherosclerotic vascular lesions in the cerebral vasculature. Furthermore, even when the diagnosis of a cardioembolic stroke is typically followed by the initiation of anticoagulation for secondary prevention, this intervention has only been scientifically validated for atrial fibrillation and mechanical valve prosthesis. With these caveats in mind, Table 4-1 lists the potential causes of cardiac embolism divided according to the strength of the evidence supporting the pathophysiological association.

TABLE 4-1 Cardiac sources of embolism.

Definite

Atrial fibrillation (chronic and paroxysmal)^*

Mechanical valve prosthesis

Rheumatic valve disease

Infective endocarditis

Nonbacterial thrombotic endocarditis

Dilated cardiomyopathy with severely reduced left ventricular ejection fraction

Acute transmural myocardial infarction (especially of the anterior wall)

Mural thrombi

Apical aneurysm

Left atrial thrombus

Atrial myxoma

Probable

Patent foramen ovale with atrial septal aneurysm

Biological prosthetic valves (early after surgery)

Possible

Patent foramen ovale

Spontaneous echo contrast

Left atrial enlargement

Degenerative mitral or aortic valve disease

Valve strands

Mitral annular calcification

Valvular fibroelastoma

Nondilatated cardiomyopathies

Sick sinus syndrome

* Includes atrial flutter.

Brain infarctions caused by cardiac embolism tend to share similar radiological characteristics regardless of the type of cardiac disease responsible for the embolism. These general characteristics are listed in Table 4-2 and illustrated in Figure 4-1. The pattern of acute multiple bilateral infarctions on diffusion-weighted imaging (DWI), especially when involving the anterior and posterior circulation territories, is strongly associated with cardiac embolism.^1,² Infarctions with embolic appearance and acute multiple brain infarctions on DWI²^–⁴ should raise suspicion of a cardiac source but may also be produced by artery-to-artery embolism. In fact, it is essentially impossible solely on the basis of brain imaging to distinguish cardioembolic infarctions from infarctions due to aortic embolism. It is important to keep in mind that cardioembolic strokes can have atypical presentations, such as relatively small subcortical infarctions.⁵ Thus the presence of radiological features highly suggestive of cardiac embolism should prompt comprehensive cardiac assessment, but their absence does not exclude the possibility of a cardioembolic mechanism.

TABLE 4-2 Radiological characteristics of cardioembolic strokes.

Wedge-shaped infarctions based in the cortex

Concurrent acute bilateral infarctions

Concurrent acute infarctions in the anterior and posterior circulations

Multiple cortical infarctions in various vascular distributions (even if infarctions are of different ages)

Greater tendency to hemorrhagic transformation

Figure 4-1 Patterns of ischemic infarction from cardiac embolism. (A) Computed tomography (CT) scan shows infarctions in two vascular territories (bilateral middle cerebral artery strokes). (B) CT scan reveals anterior and posterior circulation strokes. (C) CT scan displays a typical wedge-shaped infarction based on the cortex. (D) CT scan shows a wedge-shaped cortical infarction associated with a hyperdense vessel sign in an M2 branch of the right middle cerebral artery (arrow). (E) Axial diffusion-weighted imaging magnetic resonance imaging (DWI MRI) revealing scattered areas of restricted diffusion indicative of acute ischemia within the left middle cerebral artery territory. (F) DWI MRI showing multiple small ischemic infarction in a pattern consistent with “embolic shower.”

The advent of echocardiography, particularly transesophageal echocardiography (TEE), has provided a wealth of information on various cardiac abnormalities that may increase the risk of ischemic stroke. Transthoracic echocardiography (TTE) provides better visualization of the left ventricle and mitral valve, but it typically adds little to TEE in the evaluation of stroke patients. TEE offers better visualization of the left atrium, left atrial appendage, interatrial septum, aortic valve, and aortic arch. The superiority of TEE for the study of the cardiac structures more commonly associated with embolism makes it the preferred choice for the evaluation of cardiac embolism in combination with electrocardiography (to detect myocardial ischemia and arrhythmias) and Holter monitoring (to recognized paroxysmal arrhythmias not apparent on the electrocardiogram [ECG]).⁶ TTE is justified when myocardial ischemia, areas of ventricular hypokinesis/akinesis, or dilatated cardiomyopathy are suspected by the history or the initial ECG. Although we strongly advocate the use of TEE for the study of cardiac sources of embolism after a transient ischemic attack (TIA) or stroke, in this chapter we present several examples of diagnostic TTE, because it was the institutional practice at Jackson Memorial Hospital’University of Miami to perform a transthoracic study first.

This chapter summarizes information on the most commonly encountered sources of cardiac embolism. It presents various illustrations of the radiological pattern of the brain infarctions and echocardiographic appearance of the cardiac disorders. It concludes with a reference to aortic, embolism, which that is included here because its diagnosis hinges on the use of TEE and the neuroimaging features of strokes caused by aortic embolism are essentially indistinguishable from those due to cardiac embolism.

ATRIAL FIBRILLATION

Case Vignette

A 72-year-old man with history of hypertension, dyslipidemia, and coronary artery disease presented with sudden left-sided weakness. Examination revealed an irregularly irregular pulse, left visual field deficit, left hemiparesis, and left hemihypoesthesia with neglect. ECG confirmed the suspicion of atrial fibrillation, and brain imaging showed a right middle cerebral artery infarction (Figure 4-2). TEE was remarkable for left atrial enlargement but did not show any atrial thrombus or dense spontaneous echo contrast. The patient was initially treated with aspirin because of concerns about possible hemorrhagic transformation of the cerebral infarction. Beta-blockers were successful in maintaining the ventricular rate controlled. Warfarin was started 3 days after the stroke without complications. The patient evolved favorably and remained free of stroke recurrence 3 years later.

Figure 4-2 (A) Twelve-lead electrocardiogram showing irregular rhythm and absence of p waves, which characterize atrial fibrillation. Atrial activity is represented by fibrillatory or f waves, seen between QRS complexes. (B) Computed tomography scan of the brain shows two areas of infarction in the right hemisphere, an acute lesion in the right middle cerebral artery territory and a more chronic stroke in the border zone between the middle and posterior cerebral arteries. (C) Diffusion-weighted sequence of the brain magnetic resonance imaging confirms the area of acute ischemia in the right middle cerebral artery distribution.

♦ Stroke may be the presenting manifestation of atrial fibrillation.

♦ Paroxysmal atrial fibrillation carries a risk of thromboembolism similar to that associated with chronic atrial fibrillation.

♦ Atrial fibrillation is one of the most common causes of stroke in older patients. Moreover, the risk of thromboembolism from atrial fibrillation increases with age.

♦ Because of the high frequency of atrial fibrillation among elderly patients with ischemic strokes of embolic appearance, these patients must be exhaustively studied with serial electrocardiograms, Holter monitoring (24-48 hours), and probably prolonged ambulatory heart rhythm monitoring (several days to weeks).⁷^–⁹

♦ There are no distinctive radiological features to discriminate atrial fibrillation from other causes of cardiac embolism.

♦ TEE should always be performed before cardioversion in patients with atrial fibrillation lasting longer than 48 hours or of unknown duration.¹⁴

♦ Anticoagulation is clearly indicated for primary and secondary stroke prevention in patients with atrial fibrillation.¹⁵ Aspirin should only be used in patients with low risk of thromboembolic complications (i.e., young age, no cardiovascular risk factors, absence of echocardiographic markers of increased embolic risk).¹⁵ When anticoagulation is contraindicated by concurrent conditions, aspirin is prescribed and radiofrequency ablation procedures to restore sinus rhythm permanently are an option. Percutaneous occlusion of the left atrial appendage is being investigated as another alternative for these cases.¹⁶

♦ Sick-sinus rhythm (or tachycardia-bradycardia syndrome) is frequently associated with atrial fibrillation in older patients and may therefore increase the risk of stroke (Figure 4-5). This disorder is best treated with insertion of a pacemaker.

Figure 4-3 A 64-year-old man with history of hypertension and paroxysmal atrial fibrillation who had elected not to be treated with oral anticoagulation was transferred to our hospital with diagnosis of acute stroke. (A) Computed tomography scan of the brain showed areas of wedge-shaped cortical infarction in multiple territories, including the posterior division of the left middle cerebral artery, the anterior division of the right middle cerebral artery, and the external border-zone region between the right middle and posterior cerebral arteries. (B) Transesophageal echo view at the level of the midesophagus showing the left atrial appendage obliterated by a thrombus (arrowhead). AV, aortic valve. (C) Closer view of the thrombus (solid arrow) within the left atrial appendage also allows identification of spontaneous echo contrast in the left atrium (open arrow). LA, left atrium; LAA, left atrial appendage. (D) Detail view of the round echodensity located at the entrance of the left atrial appendage, consistent with a thrombus (solid arrow).

Figure 4-4 Echocardiographic predictors of increased stroke risk in patients with atrial fibrillation. (A) Spontaneous echo contrast or “smoke” (arrow) seen in the left atrium on transesophageal view. (B) Doppler flow velocities measured at the left atrium appendage entrance. Low-amplitude signals (slow velocities) represent decreased left atrial appendage blood flow and indicate predisposition for thrombus formation. (C) Left atrial enlargement seen on apical transthoracic echocardiogram view; the left atrial size in this patient approached that of the left ventricle. (D) Apical four-chamber transthoracic echo view revealing the presence of a left atrial thrombus (arrow). LA, left atrium; LAA, left atrial appendage; LV, left ventricle.

Figure 4-5 Twenty-four-hour Holter monitor strip of a 63-year-old patient with recent ischemic stroke and sick-sinus syndrome. Note the presence of a fast supraventricular tachycardia (A) and sinus bradycardia (B), the diagnostic hallmark of the tachycardia-bradycardia syndrome.

DILATED CARDIOMYOPATHY

♦ Patients with dilated left ventricle and severely depressed left ventricular systolic function have considerably increased risk of stroke because of elevated incidence of ventricular thrombus formation (Figure 4-6) and higher risk of atrial fibrillation.

♦ The stroke risk is increased regardless of whether the cause of the dilated cardiomyopathy is ischemic or nonischemic.

♦ Peripartum cardiomyopathy should be considered in patients presenting with stroke during puerperium.

♦ Assessment of left ventricular function and evaluation for possible mural or apical clots are best accomplished using transthoracic echocardiography (see Figure 4-6).

♦ In patients with associated atrial fibrillation, it is also important to study the left atrial chamber and left atrial appendage (Figure 4-7).

♦ Anticoagulation is generally accepted as the optimal strategy for secondary prevention after a stroke attributed to dilated cardiomyopathy.¹⁷ For primary stroke prevention, anticoagulation is only indicated in patients with documented atrial fibrillation or left ventricular thrombus¹⁷ but might be useful in patients without these complicating conditions as well.¹⁸

Figure 4-6 Images illustrating a case of multiple embolic strokes secondary to left ventricular thrombus due to nonischemic dilatated cardiomyopathy. (A) Computed tomography scan of the brain showing bilateral infarctions. (B) Detail of a large left ventricular apical thrombus seen on transthoracic echocardiogram (arrow).

Figure 4-7 Another example of a patient with ischemic stroke secondary to dilatated cardiomyopathy, in this case associated with atrial fibrillation. (A) Parasternal long axis transthoracic echocardiogram view showing a dilated left ventricle filled with thrombus. Also note the presence of a thrombus attached to the left atrial wall (arrow). (B) Parasternal short axis transthoracic view at the level of the aorta. Two rounded echodensities are seen within the left atrium consistent with thrombi (arrows). AV, aortic valve; LA, left atrium; LV, left ventricle; MV, mitral valve.

MYOCARDIAL INFARCTION

♦ The risk of stroke is increased within the first 3 to 4 months after a myocardial infarction, with the highest embolic risk occurring during the first 2 weeks. The increased risk persists after this period in patients with depressed left ventricular function ¹⁹ or atrial fibrillation.

♦ Thus it is important to exclude concurrent myocardial ischemia in all patients presenting with acute ischemic stroke.

♦ Transmural anterior wall infarctions carry higher risk, but stroke may complicate inferior wall infarctions as well.

♦ TTE should be performed to determine whether left ventricular thrombus formation has occurred over dyskinetic wall segments (Figure 4-8). Thrombi with mobile or pedunculated components are most dangerous.

♦ Patients with left ventricular apical aneurysms are at particularly high risk of embolism (Figure 4-9).

♦ Anticoagulation for at least 3 to 6 months is recommended for patients with stroke due to acute myocardial infarction with documented left ventricular mural thrombus.²⁰ In patients with transmural myocardial infarction but without documented mural thrombus, short-term anticoagulation may be justified if the stroke was attributed to concurrent myocardial ischemia.

Figure 4-8 A 58-year-old man with history of hypertension and smoking presented to the emergency department with angina and fluent aphasia. (A) Computed tomography scan showed low attenuation changes in the territory of the posterior division of the left middle cerebral artery. (B) Acute left middle cerebral artery branch infarction was confirmed by magnetic resonance imaging (diffusion-weighted sequence shown). (C) Electrocardiogram in the emergency department showed ST elevation in the anterior leads with reciprocal ST depression in the inferior leads in a pattern typical for myocardial infarction of the anterior wall. (D) Detail of the anterior precordial leads showing significant ST elevation in V1 to V3 (E) Apical two-chamber transthoracic echocardiogram view showing a thrombus in the LV apex (arrow).

Figure 4-9 Echocardiographic predictors of increased risk of stroke after a myocardial infarction. (A) Large thrombus (arrow) protruding into the left ventricular cavity from the apex seen on transthoracic echocardiogram. (B) Detailed view showing the large echodensity within the left ventricle consistent with thrombus. (C) Left ventricle apical aneurysm (arrow) following extensive anterior wall myocardial infarction visualized on this apical two-chamber transthoracic echocardiogram view. (D) Transthoracic echocardiogram view after injection of echo contrast. Note the swirling of blood flow in the area corresponding to the left ventricle apical aneurysm (arrow). LA, left atrium; LV, left ventricle.

INFECTIVE ENDOCARDITIS

Case Vignette

A 46-year-old man with recent community-acquired pneumonia and history of diabetes presented with worsening dyspnea. Examination revealed that the patient was confused and febrile, and careful cardiac auscultation denoted a new systolic murmur with characteristics suggestive of mitral regurgitation. Brain imaging showed scattered, small, acute ischemic infarctions in cortical locations. Echocardiography disclosed a vegetation attached to the mitral valve (Figure 4-10, F and G), and blood cultures grew Staphylococcus aureus. The patient was successfully treated with vancomycin and rifampin first and later switched to nafcillin with rifampin when susceptibilities proved that the organism was not methicillin-resistant. The patient did not have recurrent episodes of systemic or cerebral embolism, and repeat echocardiography 4 weeks later confirmed resolution of the vegetation.

Figure 4-10 Diffusion-weighted sequence of brain magnetic resonance imaging showing multiple small lesions (open arrows)

♦ Stroke complicates 10% to 40% of cases of infective endocarditis.²¹^–²³ Most strokes occur at presentation or within 48 hours of diagnosis.^23,²⁴ After adequate antibiotic therapy is instituted, the embolic risk falls substantially.^24,²⁵ The risk of stroke may be higher in patients with mitral valve endocarditis than in those with aortic vegetations (Figure 4-11).²³

♦ The possibility of infective endocarditis should always be investigated in a patient presenting with stroke and unexplained fever or other signs of systemic infection. Another clinical clue is that patients with infective endocarditis may present with a combination of focal deficits related to the embolic event and signs of more diffuse encephalopathy.

♦ TEE is the ideal method to diagnose valvular vegetations. No particular echocardiographic features serve to stratify the degree of embolic risk.

♦ Radiological acute ischemic stroke patterns in infective endocarditis are variable, including single cortical lesions, territorial infarctions, disseminated punctuate lesions (Figure 4-10), and infarctions of various sizes in multiple vascular distributions.²⁶

♦ The risk of intracranial hemorrhage is also considerably increased in patients with infective endocarditis (see Chapter 11). It may be caused by hemorrhagic conversion of an ischemic infarction or by rupture of a mycotic aneurysm. Small hemorrhagic components are commonly seen within ischemic infarctions on hemosiderin-sensitive sequences of magnetic resonance imaging (MRI). Mycotic aneurysms are typically small and located in the distal circulation; conventional angiography is necessary to exclude their presence because noninvasive angiographic techniques may not be sufficiently sensitive to detect them. When they rupture, they most often produce subarachnoid hemorrhage predominantly around the hemispheric convexity.

♦ Antibiotic therapy is the mainstay of treatment. Surgical excision of the vegetation is indicated in patients with recurrent embolic events. Use of anticoagulation is not favored because it does not appear to reduce the risk of embolism ^22,²⁷ and it increases the risk of hemorrhage.²⁸

Figure 4-11 Example of aortic valve endocarditis. (A) Parasternal long axis transthoracic echocardiogram view reveals the presence of a vegetation attached to the aortic valve protruding into the left ventricular cavity (arrow). (B) Detail of the echocardiogram showing the linear echodense vegetation (arrow) and its close association with the aortic valve cusps. AV, aortic valve; LA, left atrium; LV, left ventricle; RV, right ventricle.

PROSTHETIC VALVES

♦ The radiological patterns of brain infarction caused by embolism from prosthetic valves are quite variable. Multiple or recurrent strokes are not uncommon.

♦ TEE provides optimal sensitivity to visualize clots or vegetations over the prosthetic valve (Figure 4-12).

♦ The high risk of stroke in patients with mechanical prosthetic valves represents an absolute indication for chronic anticoagulation. An international normalized ratio target of 3.0 (2.5-3.5) is recommended for modern metallic prosthetic valves.²⁰ Addition of aspirin is reasonable in patients who had embolic events despite adequate anticoagulation.²⁰

♦ It is generally recommended that patients undergoing placement of bioprosthetic valves be anticoagulated for 3 months. Long-term anticoagulation may be justified in patients with a bioprosthetic valve who had an embolic infarction without other explanation.

♦ Patients with prosthetic valves should always receive antibiotic prophylaxis before procedures that may cause transient bacteriemia.

♦ In the event of endocarditis, anticoagulation should be continued in patients with metallic valves.

♦ In the event of intracranial hemorrhage, anticoagulation may be temporarily interrupted for 1 to 2 weeks with relatively safety.²⁹

Figure 4-12 A 42-year-old woman with history of mitral valve replacement presented with a right posterior cerebral artery infarction. Her international normalized ratio was subtherapeutic. (A) Transthoracic echocardiogram showed a vegetation attached to the prosthetic mitral valve on the atrial side (arrow). (B) Detail of the echocardiogram allows visualization of the previously noted vegetation but also discloses a smaller vegetation attached to the anterior leaflet of the prosthetic mitral valve (arrowhead). LA, left atrium; LV, left ventricle; MVal, anterior leaflet of the mitral valve; PMV, prosthetic mitral valve.

NONBACTERIAL THROMBOTIC ENDOCARDITIS

Case Vignette

A 42-year-old woman without previous medical problems presented with acute left inferior quadrantanopsia, left hemiparesis, and diffuse petechiae in all limbs. Brain computed tomography (CT) showed high fronto-parietal hypodensities involving the cortex (Figure 4-13, A). Blood studies revealed thrombocytopenia (40,000 per mm³), leukocytosis (30,000 per mm³) and elevated lactate dehydrogenase (5060 U/L). An electrocardiogram disclosed inverted T waves in the inferior leads. Heparin and aspirin were started. Hours after admission, she developed excruciating left flank pain and became confused. Examination showed a pulseless and cold right foot. After four blood cultures were obtained, the patient was empirically started on antibiotics and high-dose dexamethasone. She improved over the following day, with less pain, improved foot temperature, and increasing platelet count. However, she remained confused and exhibited more ecchymotic lesions and subungual splinter hemorrhages (Figure 4-13, B and C). Chest CT revealed large mediastinal lymphadenopathy, and CT of abdomen showed multiple splenic and renal infarcts. Testing for cryoglobulins, antinuclear antibodies, antiphospholipid antibodies, complement levels, as well as serial blood cultures were negative. Transthoracic echocardiogram (TTE) (Figure 4-13, D) showed a large vegetation attached to the aortic valve, with moderate aortic regurgitation and moderate posterior and apical hypokinesis. The patient underwent aortic valve replacement, and pathological examination revealed marantic vegetations with myxoid degeneration of the removed valve. Stains and cultures of the vegetations were negative. After surgery, she developed bilateral leg ischemia, renal failure, and congestive heart failure due to global left ventricular hypokinesis documented by a new TTE that revealed acceptable function of the prosthetic aortic valve. She expired 7 days after the surgery. Necropsy findings included metastatic adenocarcinoma of unknown primary involving paratracheal nodes and pleura, bilateral kidney and splenic infarctions, congestive hepatomegaly, serosanguineous pleural effusions and ascites, large organizing right cerebral infarcts, and microscopic cerebellar infarcts. The prosthetic valve was covered by multiple vegetations that resulted in partial luminal occlusion.

Figure 4-13 Computed tomography scan of the brain showing low-attenuation changes consistent with acute infarction in the right frontal lobe (arrows) (A). Splinter hemorrhages were visible under the nails of multiple fingers (B). Areas of ecchymosis and distal ischemia from systemic embolism are illustrated on this picture of the patient’s right foot (C). Parasternal long-axis transthoracic echocardiogram view showing vegetation (arrow) attached to the aortic side of the aortic valve (D). LA, left atrium; LV, left ventricle.

♦ Nonbacterial thrombotic endocarditis should be suspected in patients with stroke and underlying malignancy or other conditions associated with thrombotic diathesis (such as antiphospholipid antibodies).

♦ Emboli may be occult, small and multiple presenting with encephalopathic features, or single and larger manifesting as territorial infarction.^30,³¹

♦ The pattern of acute ischemic lesions associated with nonbacterial thrombotic endocarditis as seen on DWI appears to be less variable than in infective cases. The typical pattern consists of numerous infarctions of various sizes distributed across multiple vascular territories.²⁶

♦ TEE is the diagnostic modality of choice to detect the sterile vegetations. However, there are no reliable features to distinguish them from septic vegetations.

♦ Anticoagulation is used to prevent embolism. Surgery is a reasonable alternative in patients with severe valvular dysfunction or recurrent embolic events despite anticoagulation.³²

MITRAL STENOSIS AND ANNULAR CALCIFICATION

♦ Mitral stenosis is often related to rheumatic heart disease (Figure 4-14, A) and may be associated with atrial fibrillation and left atrial thrombus formation.

♦ Risk of embolic infarction is elevated and recurrent strokes are not uncommon.

♦ Anticoagulation is indicated when atrial fibrillation or left atrial thrombus is documented; warfarin may also be used in the absence of these additional findings in patients with no other apparent causes for the infarction.

♦ Mitral annular calcification (Figure 4-14, B) has also been associated with higher incidence of ischemic stroke.³³ However, it is unclear whether mitral annular calcification directly increases the risk of stroke or represents a marker of other conditions with proven embolic potential (e.g., atrial arrhythmias).

♦ TEE is the ideal test to diagnose mitral stenosis and annular calcium deposits.

Figure 4-14 Illustrations of mitral stenosis and mitral annular calcification. (A) Parasternal long-axis transthoracic echocardiogram view showing the typical findings of rheumatic mitral valve. Note the doming of the anterior leaflet (arrow) and the thickening of its tip (hockey stick appearance). (B) Mitral annular calcification seen as bright linear echodensity (arrow) at the margin of the mitral valve annulus in this apical four-chamber transthoracic echocardiogram view. AV, aortic valve; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

ATRIAL MYXOMA

♦ Ischemic stroke is the most common neurological presentation of atrial myxomas (Figure 4-15).³⁴ The proposed mechanism for the infarctions, which are often multiple, bilateral, and recurrent, is embolism of tumor fragments facilitated by the friable consistency of the mass.

♦ Strokes typically occur with myxomas of the left atrium but may also be caused by right atrial tumors in patients with patent foramen ovale.

♦ Diagnosis is based on echocardiographic visualization, which may also recognize other intracardiac tumors, such as fibroelastomas (Figure 4-16).

♦ Development of fusiform (“myxomatous”) intracranial aneurysms is an uncommon, delayed complication of embolization from a cardiac myxoma. These aneurysms tend to be multiple.³⁵ They may be diagnosed even years after surgical removal of the tumor.

♦ Treatment of atrial myxomas and other cardiac tumors is surgical excision.

Figure 4-15 Bilateral embolic strokes in a 54-year-old patient without prominent vascular risk factors whose echocardiogram showed a left atrial myxoma. (A) Diffusion-weighted imaging and (B) fluid-attenuated inversion recovery sequences showing the acute and early subacute ischemic infarctions in both frontal lobes. (C) Left atrial echodensity (arrow) seen in this parasternal long-axis transthoracic echocardiogram view. Differential diagnosis for this finding includes thrombus, tumor, and vegetation.

Figure 4-16 Example of patient presenting with sudden dysarthria and mild left hemiparesis who had two small cortical lesions on brain imaging. Echocardiography revealed the coexistent presence of an intracardiac myxoma and a fibroelastoma. (A and B) Apical four-chamber and parasternal long-axis transthoracic echocardiogram views showing a left atrial myxoma (arrows). (C and D) Small echodensity located in the anterior leaflet of mitral valve (arrows). Pathological examination confirmed that this lesion was a fibroelastoma. LA, left atrium; LV, left ventricle; MVal, mitral valve anterior leaflet; MVpl, mitral valve posterior leaflet.

PATENT FORAMEN OVALE

Case Vignette

A 44-year-old woman presented with sudden left-sided weakness and paresthesias and problems with speech articulation. Her symptoms had started after she had tried to lift a heavy box from the floor. Her only risk factors for atherosclerosis were obesity and smoking. Her medical history was otherwise significant for a previous episode of deep venous thrombosis in one leg 3 years before, which was considered spontaneous and had been treated with nearly 6 months of anticoagulation. Brain imaging revealed small cortical infarctions in the posterior right frontal lobe (Figure 4-17, A). Carotid ultrasound was unrevealing, and ECG showed sinus rhythm. Transthoratic echocardiogram with bubble study disclosed a patent foramen ovale (PFO) (Figure 4-17, B). The right-to-left shunt at rest and exacerbated with Valsalva was subsequently confirmed by transcranial Doppler (Figure 4-17, D–F). Venous Doppler of the lower extremities showed an acute deep venous thrombosis in the right leg (Figure 4-17, C). Hypercoagulability workup was positive for factorLeiden mutation (heterozygous). The patient was treated with oral anticoagulation and had no stroke recurrences at the last follow-up 32 months later.

Figure 4-17 (A) Diffusion-weighted magnetic resonance imaging showing small areas of acute cortical ischemia in the right hemisphere. (B) Apical four-chamber transthoracic echocardiogram view taken at the time of injection of aerated saline solution through a peripheral vein. Note the complete filling of the right ventricle (RV) and right atrium (RA) with the contrast (arrows) and the passage of microbubbles (arrowheads) to the left-sided chambers through the interatrial septum (IAS), indicating the presence of a patent foramen ovale (PFO). (C) Doppler ultrasound of the right lower extremity revealing a deep venous thrombosis. (D) Baseline transcranial Doppler (TCD) showing the flow in the right middle cerebral artery insonated through the transtemporal window. (E) TCD showing the presence of microembolic signals after the injection of agitated saline on a vein of the arm. (F) Degree of shunting becomes much more prominent when the patient is also asked to perform Valsalva maneuver at the time of the injection.

♦ PFO associated with atrial septal aneurysm (ASA) is associated with increased incidence of recurrent stroke in young patients (< 55 years old) with cryptogenic cerebral infarctions.³⁶^–³⁸ Even in the absence of concomitant ASA, PFO can be responsible for embolic brain infarctions, especially in young patients with deep venous thrombosis or thrombophilia (Figure 4-17).

♦ The association of cryptogenic stroke with PFO in older patients (> 55 years of age) is more controversial, but supported by the results of one large study revealed older patients with cryptogenic strokes were 3 times more likely to have a PFO on TEE than patients with stroke of known cause.³⁹

♦ It is important to remember that PFO is a common finding in healthy individuals (prevalence of 25% in a population study).⁴⁰ In fact, PFO is not an independent risk factor for cerebrovascular events in the general population,^41,⁴² and it has not been consistently found to be associated with increased risk of recurrent stroke among unselected patients with cryptogenic strokes.⁴³

♦ Hence, the influence of PFO on the risk of recurrent stroke remains to be fully defined. In our opinion, it is most reasonable to be cautious when ascribing a stroke to PFO, particularly in older patients among whom paroxysmal atrial fibrillation may be difficult to diagnose in the absence of prolonged ambulatory monitoring.

♦ The diagnosis of PFO and ASA hinges on the use of echocardiography, particularly TEE (see Figures 4-17, 4-18, 4-19). TEE allows visualization of the PFO, recognition and grading of right-to-left shunt (defined by the appearance of microbubbles in the left atrium within 3 to 5 cardiac cycles following injection of 5 to 10 ml of agitated saline solution into a peripheral vein), and detection of ASA (bulging of the region of the fossa ovalis extending 15 mm or more beyond the plane of the atrial septum). Contrast echocardiography may enhance the sensitivity of the technique.

♦ Transcranial Doppler (TCD) is also an effective method to diagnose the presence of a right-to-left shunt (Figure 4-17). The shunt is demonstrated by detecting microembolic signals’corresponding to microbubbles’in an intracranial vessel (typically one of the middle cerebral arteries) after infusion of agitated saline in a peripheral vein of the arm. The sensitivity of TCD is comparable that of TEE.⁴⁵ In fact, we have seen patients with PFO diagnosed by TCD after being missed by TEE because the patients had been too sedated during TEE to perform adequate Valsalva. However, TCD can only prove the existence of a right-to-left shunt rather than a PFO. The degree of shunting can be quantified by TCD,⁴⁶ but this method does not allow assessment of the characteristics of the PFO itself or presence of an ASA. Hence, TCD and TEE should be considered complementary techniques.⁴⁷ Use of contrast TCD, and performing the test twice using two provocation maneuvers (e.g., coughing and standard Valsalva) may increase the diagnostic sensitivity of the method.⁴⁸

♦ Larger PFOs may be associated with higher risk of cryptogenic strokes than smaller ones.^43,⁴⁹ Presence of right-to left shunt at rest (as opposed to only with Valsalva maneuver) may also increase the risk for recurrent brain embolism.⁵⁰ In addition, presence of concomitant ASA correlates with the occurrence of multiple acute DWI lesions, even after controlling for PFO size and degree of right-to-left shunt.⁵¹

♦ The optimal treatment of patients with ischemic stroke ascribed to PFO and ASA remains to be established.³⁶ Although there is insufficient evidence to support the use of anticoagulation, most experts favor this approach over antiplatelet therapy. Ongoing trials are testing the value of endovascular closure of PFO.

Figure 4-19 Illustration of a patent foramen ovale (PFO) associated with an atrial septal aneurysm (ASA). (A and B) Transesophageal echocardiogram views of an ASA. Note the doming of the septum (arrows) toward the left atrium (LA). A channel can be identified into the intrarterial septum (IAS) consistent with a PFO (arrowhead). Microbubbles from injection of aerated saline are seen crossing from the RA to the LA.

Figure 4-18 Illustration of atrial septal aneurysm (ASA). (A and B) Apical four-chamber transthoracic echocardiogram views in different parts of the cardiac cycle showing an aneurysmal interatrial septum (IAS). Note the long excursion of the septum, which protrudes into the left atrium (LA) in part A and the right atrium (RA) in part B. LV, left ventricle; RV, right ventricle.

PROXIMAL AORTIC ATHEROSCLEROTIC PLAQUE

Case Vignette

A 76-year-old man with history of hypertension, hyperlipidemia, smoking, coronary artery disease, peripheral vascular disease with claudication, and previous right carotid endarterectomy for severe, asymptomatic stenosis presented with acute right sided weakness. Examination confirmed the presence of right hemiparesis but also disclosed a left visual field deficit. CT scan of the brain showed cortical infarctions in the left frontal and right occipital lobes (Figure 4-20, A and B). Carotid duplex showed moderate stenosis on the left internal carotid origin and no significant restenosis on the right side. Electrocardiography and cardiac telemetry proved that the patient was in sinus rhythm. TEE showed extensive aortic arch atherosclerosis including a thick focal plaque with an area of small ulceration on its surface. Although there was no mobile component in the aortic plaque, the patient was treated with oral anticoagulation for 3 months along with low-dose aspirin, high-dose statin, and adjustment in the doses of his antihypertensive agents. The patient recovered favorably with help from rehabilitation services, and repeat TEE 3 months later showed reduction in the size of the larger aortic arch plaque. Warfarin was stopped, and he was continued on aspirin without stroke recurrence.

Figure 4-20 (A and B) Computed tomography scans of the brain showing bilateral cortical infarctions in the left frontal and right occipital lobes. This combination of infarctions in various arterial territories is a hallmark of embolism from a proximal source. (C) Large atheromatous plaque (5′6 mm in maximal thickness) seen in the aortic arch in this transesophageal echocardiogram view (arrow). (D) Another transesophageal echocardiogram view of the aortic arch revealing diffuse atherosclerotic disease (arrows).

♦ Complex atherosclerotic plaques (defined by thickness > 4 mm, presence of ulceration, and/or mobile component) in the proximal aorta (ascending or arch) are associated with an increased risk of embolic stroke (Figure 4-20). This association has been consistently found in several case-control studies.^52,⁵³ Among stroke patients referred for evaluation with TEE, the prevalence of complex proximal aortic plaques is 14% to 21%, and the 1-year incidence of stroke is 10% to 12%.^54,⁵⁵

♦ In a population-based study the rate of complex proximal aortic plaques was much lower (2.4%) than in selected populations of stroke patients.⁵⁶ In this community-based study free of referral bias, there was no association between the presence of complex proximal aortic plaques and the occurrence of embolic strokes over a 5-year follow-up. In the same population, the presence of complex atherosclerotic debris was not associated with the occurrence of cryptogenic strokes.⁵⁷ However, the low number of patients with complex proximal aortic plaques may have undermined the power of the study to test the likelihood of these associations.

♦ Aortic atherosclerosis is associated with many other stroke risk factors including hypertension, hyperlipidemia, smoking, hyperhomocysteinemia, elevated serum inflammatory markers, carotid stenosis, coronary artery disease, valvular disease (aortic stenosis, mitral annular calcification), left ventricular hypertrophy, and atrial fibrillation.⁵⁸

♦ There is some persistent debate in regards to whether proximal aortic debris represents an independent risk of factor for stroke or just a marker for generalized atherosclerosis and cardiovascular disease. Although the lack of association with cryptogenic strokes in the community favors the latter position,⁵⁹ clinical experience (including iatrogenic cases during invasive procedures), pathological data, and the strikingly increased prevalence of the condition among patients undergoing TEE for stroke of unclear cause strongly support the notion that aortic embolism is responsible for embolic strokes.⁵⁸

♦ TEE is the diagnostic technique of choice to detect and characterize proximal aortic plaques. Although there is a small portion of the ascending aorta near the origin of the innominate artery that may be obscured by the tracheal air column, the rest of the proximal aorta, including the entire arch, is visualized on TEE in great detail.

♦ The following ultrasonographic characteristics of the plaque have been shown to correlate with stroke risk: thickness (odds ratio for stroke 13.8 for plaques > 4 mm thick), mobile elements (usually thrombus), ulceration, and large hypoechoic core (rich lipid content).⁵² Conversely, plaque calcification (hyperechogenicity) reduced the risk of embolism.

♦ The neuroimaging characteristics of strokes caused by aortic embolism are not distinguishable from those of cardioembolic infarction.

♦ Before attributing a stroke to aortic embolism, it is important to define the location of the aortic plaque in relation to the main aortic branches. For example, an aortic plaque distal to the takeoff of the innominate branch should not be considered responsible for an infarction in the right middle cerebral artery distribution.

♦ Most aortoembolic events are presumed to be caused by atherothrombosis. Embolization of cholesterol crystals from a highly unstable aortic plaque (known as atheroembolism) is a much less common complication, which typically results in ischemia of multiple organs and is often fatal.

♦ The optimal regimen for secondary stroke prevention in patients with severe aortic arch atheroma has not been firmly established. Aggressive statin therapy should be prescribed on the basis of the benefits documented in a large observational study (59% relative risk reduction in the rate of embolic events)⁶⁰ and evidence of plaque regression in treated patients.⁶¹ There is limited evidence that anticoagulation may be preferable to antiplatelet therapy in these patients;⁶² a randomized, controlled trial is ongoing.

♦ Iatrogenic strokes from aortic embolism (through thromboembolism or atheroembolism) may complicate cardiac catheterization and cardiac bypass surgery. Scraping of a plaque during catheterization, manipulation of the aorta during graft anastomosis, crashing of a plaque during cross-clamping, and direct damage of the plaque and endothelium during cannulation and from the cannula jet flow are possible mechanisms. It is not feasible in practice to discriminate between these mechanisms and air embolism, except when air emboli are seen on acute brain imaging.

♦ Careful study of the aortic arch using TEE or intraoperative epiaortic ultrasound is helpful in reducing the risk of perioperative aortoembolic complications.^63,⁶⁴ The option of off-pump bypass surgery in patients with high aortic plaque burden should be considered.⁶⁵ Prophylactic aortic arch endarterectomy should not be performed because it has been shown to increase the risk of serious embolization.⁶⁶

References

1 Wessels T, Wessels C, Ellsiepen A, Reuter I, Trittmacher S, Stolz E, et al. Contribution of diffusion-weighted imaging in determination of stroke etiology. AJNR Am J Neuroradiol. 2006;27:35-39.