Overview

Atrium (> left)

• High risk causes: atrial fibrillation, atrial thrombi, atrial tumors.
• Low risk causes: patent foramen ovale, interatrial septal aneurysm, interatrial communication 

Ventricle (> left)

• High risk causes: ventricular thrombi and myocardial infarction, ventricular tumors, dilated cardiomyopathy.
• Low risk causes: myocardial contractility dysfunction, hypertrophic cardiomyopathy, interventricular communication.

Valvular heart disease

• High risk causes: endocarditis, prosthetic valves, mitral stenosis, papillary fibroelastoma.
• Low risk causes: annular calcification and prolapse.

Rare causes

• Left ventricular noncompaction cardiomyopathy
• Myocarditis
• Iatrogenic disease

Vascular disease

In this work, the key imaging cardiac findings (CT and MRI) responsible for cardiogenic stroke are revised.

In general terms, they are classified as follows:

- High risk causes:

• Thrombi in the left atrium and atrial fibrillation
• Thrombi in the left ventricle and myocardial infarction
• Cardiac tumors in the left heart (myxoma)
• Dilated cardiomyopathy
• Valvular vegetation

- Low risk or undetermined causes:

• Patent foramen ovale
• Interatrial and interventricular septal defects
• Interatrial septal aneurism

- Rare causes:

• Myocarditis
• Left ventricular noncompaction cardiomyopathy
• Iatrogenic causes

Dividing cardiac sources of emboli into high and low-risk categories is clinically useful, since major-risk causes carry a high risk of initial and recurrent stroke; consequently the diagnosis is of utmost importance.

Secondarily, potential causes of infarction (major and minor risk sources) are categorized based on the cardiac structure affected (Fig. 7):

- Atrium

- Ventricle

- Valves

Fig. 7: Potential causes of cardiogenic stroke.
References: Department of Radiology, Hospital del Mar. Barcelona

Finally, uncommon but potential cardiac sources of stroke, which are infrequently reported in the literature, are mentioned. They will be assembled as rare causes (Fig. 8). 

Fig. 8: Potential causes of cardiogenic stroke. Rare causes; infrequently reported.
References: Department of Radiology, Hospital del Mar. Barcelona.

HIGH RISK CAUSES:

• Atrial fibrillation

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia (5% of population older than 65 years old) and presents as the principal cause of cardioembolic strokes, especially in older patients. Irregular heartbeat induces motility dysfunction, which generates flow disturbance and blood stasis, which consequently generates a prothrombotic condition (high fibrinogen concentration, D-dimer, von-Willebrand factor). This state favours thrombi formation in the left atrium, generally more evident at the left atrial appendage (LAA) level.

Since thrombi of the left atrium and left atrial appendage (LAA) are common sources of stroke (AF-related strokes constitute about 60% of all cardioembolic cerebrovascular accidents) and they are treatable sources of embolism, their detection could markedly affect patient care.

AF has no obvious representation in imaging studies. However, its consequences can be appreciated through several techniques: atrial thrombi (view next section), motion artifact in CT, difficulties in cardiac gating synchronization in MRI and altered FDG uptake in PET-CT (Fig. 9).

Fig. 9: Motion artifact related to AF. Cardiac CT (A,B) show important motion artifact due to variable heart rate in a patient with AF. In PET-CT studies (C,D) artefactual FDG caption is observed at atrial level (arrows).
References: Department of Radiology, Hospital del Mar. Barcelona

• Atrial thrombi 

Atrial thrombi appear as oval or convex intraatrial filling defects (Fig. 10), most frequently located in the left atrial appendage. The LAA has the most turbulent flow inside the atrium, with higher predisposition to blood stasis and thrombi formation in case of AF.

Fig. 10: Atrial thrombi in the left atrium in a typical (A, B, C) and atypical (D, E, F) location. Thrombus (green circle) is observed as an hypodense, round or oval-shapped lesion in the left atrial appendage (LAA). Sagittal reconstruction, at the LAA long axis level (C), allows better visualization of thrombus distribution. A patient with a mechanic mitral prosthesis and atrial enlargement (D,E,F): LAA is permeable (D). An extense thrombus is adhered to the posterior atrial wall (E, F arrows) probably related to mitral insufficiency and regurgitation.
References: Department of Radiology, Hospital del Mar. Barcelona.

Echocardiographically, turbulent flow and circulatory stasis cause a spontaneous increase of echogenicity in the LAA interior, known as SEC (“spontaneous echo contrast) or LAS (“left atrial smoke”). In contrast enhanced-CT (CECT), SEC is equivalent to a filling defect in the LAA (Fig. 11). In black blood sequences in MRI (Double IR) artifacts are seen due to incomplete blood signal saturation (Fig. 12). SEC without AF is associated to low or undetermined stroke risk (Fig. 13). 

Fig. 11: Patient with a very enlarged left atrium (LA) secondary to mitral insufficienty and AF. In thoracic CT (A,B) a linear filling defect is observed at LAA (*, B arrow) suggesting circulatory stasis. The oval or convex intraatrial filling defect suggests a thrombus (T).
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 12: Flow disturbances may cause artefactual hyperintensity in black blood MR sequences (B), similar to the filling defect seen in CT (A). White blood MRI sequences show absence of thrombi in the LA (C).
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 13: 63-year-old woman with heart failure and AF presenting aphasia. Initial brain CT (A) does not show significant findings. 12 hours later, similar clinical symptoms are observed. New brain CT and CT angiography (B) demonstrate occlusion of left MCA (arrow). Clinical suspicion of cardiac origin led to adquisition of thoracic CT (C), which exhibits a filling defect in the LAA (*) with no obvious evidence of thrombi.
References: Department of Radiology, Hospital del Mar. Barcelona.

On the contrary, atrial thrombi are linked to high risk of stroke, and thus have to be differentiated from slow mixing filling defects (Fig. 11). The following characteristics may be useful in cardiac CTA imaging:

• Filling defect morphology
• • Thrombi: oval or convex intraatrial filling defect (posterolateral in atrium, or most common in LAA)
  • Slow mixing: linear filling defect
• Hounsfield unit (HU)
• • Thrombi: low HU
  • Slow mixing: HU> 80 in LAA
• Delayed scans (CECT 70-90 seconds after contrast administration):
• • Thrombi: persistence of filling defect 
  • Slow mixing: homogeneous opacification in LAA
• Mean iodine concentration in dual-energy cardiac CT
• • Lately some authors state that dual-energy cardiac CT is a highly sensitive modality to distinguish thrombi from stasis, with significantly different mean iodine concentration between them (lower for thrombi than for circulatory stasis). 

Since flow disturbances induce thrombi formation, some patients with slow mixing filling defects in preliminary studies, may show thrombi in further ones (Fig. 14). 

Fig. 14: Thoracic CT in a patient with a cardiac pacemaker and toxic syndrome. Atrial enlargement of LA is observed (A) and a linear filling defect at LAA level (B, arrow). A thoracic CT 3 months after (C,D) shows pneumonia (P) and an oval and hypodense filling defect in the LAA surrounded by contrast (circle, T).
References: Department of Radiology, Hospital del Mar. Barcelona.

Pectiniform muscles have to be also included in the differential diagnosis from thrombi in the LAA, considering they can be mistaken for LAA filling defects (Fig. 15).

Fig. 15: Axial images of cardiac CT (A,B,C): several hypodense linear images in the LAA can be identified. Pectiniform muscles are generally located at the LAA and are better observed in sagital planes (D, arrows) and volumetric reconstructions (E, arrows).
References: Department of Radiology, Hospital del Mar. Barcelona.

In embolic stroke patients with chronic AF and increased risk for atrial thrombi formation, LAA percutaneous closure is a possible therapeutic approach (ie, with Amplatzer occlusion devices). Cardiac CT plays an important role in the treatment planning, allowing a morphologic assessment, and LAA diameter measurements.

• Atrial tumors

Myxomas are the most common of all primary heart neoplasms, the most frequent benign tumors (25-50%), generally located at the atria (60-75% in left atrium, followed by right atrium) (Fig. 16). They have been associated to embolic events in 30-40% of cases, displaying an important cause of cardioembolic cerebrovascular episodes.

Fig. 16: Big hypodense left intraatrial mass in contact with the interauricular septum, suggestive of atrial myxoma (M), incidentally diagnosed in a thoracic CT study (A, B, C). Cardiac CT (D, E) shows a well defined heterogeneous intraatrial lesion with irregular margins (E, *) contacting the interatrial septum (D, arrow). It prolapses towards the valvular plane (E, line). Cardiac MR perfusion image in a 4 chamber view shows dependence from the fossa ovalis (F, arrow).
References: Department of Radiology, Hospital del Mar. Barcelona.

The main differential diagnosis from myxoma are atrial thrombi. Several aspects of myxoma can help characterize myxomas:

• Location
• • Intracavitary mass originating from interatrial septum near fossa ovalis.
• Morphology
• • Size: bigger than thrombi (from 1-15 cm; mean 6 cm).
  • Shape: ovoid or round lesion with lobular contours (polypoid lesion).
  • • ~ 2/3 are smooth surfaced.
    • ~ 1/3 are villous and have irregular margins. They are more likely to develop embolic complications (Fig. 16 D,E).
• Calcification
• • In ~ 50% of right atrial myxomas.
• Hounsfield unit (HU) in CT
• •  Low HU (similar to thrombi).
• Contrast Enhanced CT (CECT)
• • Heterogeneous contrast enhancement. Inconstant.
• Retrospective ECG-gated cardiac CT or MR (Fig. 16 F)
• • May change position during cardiac cycle
  • May prolapse through the atrioventricular valve and occupy part of the ventricle 

LOW RISK CAUSES:

• Patent foramen ovale

In almost 30% of the population, interatrial septal fusion between the primum and secundum septae fails or is incomplete. When the foramen ovale is covered but not sealed, the resulting condition is a patent foramen ovale (PFO).

In most people there are no consequences from this persistent valvularlike connection, but in special clinical scenarios it gains significance. PFO is present in 1/3 of stroke patients (and 40% in patients younger than 55 years old) with a size between 2 to 8 mm, and with a pressure gradient that promotes a right-to-left shunt, may cause paradoxical embolism.

Transesophageal echocardiography (TEE) is considered the reference standard method for the detection of PFO (Fig. 17). Moreover, it can be visualized through cardiac and thoracic CT.

Fig. 17: Patient suffering from lymphoma presents with stroke. Basal brain CT evidences an hyperdense image at the sylvian fissure (A, arrow), that correlates to a filling defect in the angiographic study (B, arrow) at M1 level of MCA with adequate distal collaterallity. Extracranial vascular CT and further thoracic CT study (C,D) show filling defects in both principal pulmonary arteries, suggesting pulmonary embolism and concomitant stroke, suggesting a paradoxical embolism. Transthoracic Contrast Echocardiogram (E,F) with saline contrast in the right chambers (E), and inside the left chambers after Valsalva maneuvers (F), indicating a right-to-left shunt.
References: Department of Radiology, Hospital del Mar. Barcelona.

CT criteria for the diagnosis of PFO are:

• A left atrial flap in the expected location of the septum primum.
• A continuous column of contrast material connecting the flap to the right atrium
• A jet of contrast material from the left to the right atrium or from the column to the right atrium.

Using all three CT criteria together allows maximum specificity (100%) for the diagnosis (Fig. 18).

Fig. 18: Cardiac CT in a patient with effort angina. Axial image (A) demonstrates a left atrial flap at the expected location of the septum primum (A, arrow). Short axis images (B,C) confirm a continuous column of contrast material connecting the flap to the right atrium (B) and a jet of contrast material from the left to the right atrium (C), indicative of PFO. Transthoracic Contrast Echocardiogram (D,E) with saline contrast in the right chambers (D), with some bubbles in the left chambers after Valsalva maneuvers (E), a pressure gradient that promotes a right-to-left shunt in this patient with PFO.
References: Department of Radiology, Hospital del Mar. Barcelona.

• Interatrial septal aneurysm

Interatrial septal aneurysm or atrial septal aneurysm (IASA or ASA) is a sacular bulge of the interatrial septum, generally located at fossa ovalis level, that protrudes to right, left or both atria. ASA is a condition associated to cerebrovascular accident (sometimes linked to an interatrial shunt, usually a PFO).

Diagnostic is commonly incidental through echocardiography, CT or MRI.  In case of ASA, CT and MRI show:  

• A focal outpouching of the interatrial septum of at least 10 mm
• A bulge with at least 15mm long at its basis  (Fig. 19).

Fig. 19: Cardiac CT (A), Thoracic CT (D) and Cardiac MR (B,D) illustrate the typical morphology of IASA.
References: Department of Radiology, Hospital del Mar. Barcelona.

• Interatrial communication

Interatrial communication or atrial septal defects (ASD) represent approximately 30% of congenital cardiopathy in adults. Based on its location, they can be classified as:

• Ostium primum (15-20%)
• Ostium secundum (75%)
• Sinus venosus (5-10%)
• Coronary sinus (< 1%)

Usually asymptomatic in early life, ASD become symptomatic with advancing age. They are a potential source of paradoxical embolism, most prevalent in young patients with cryptogenic ischemic strokes (symptomatic cerebral infarcts of undetermined cause at initial diagnosis or with no probable cause identified after adequate diagnostic evaluation).

Typical CT and MRI findings are direct visualization of ASD (Fig. 20) and assessment of shunt. MRI perfusion sequences help determinate contrast redistribution in different heart chambers and thus determine shunt direction, even in cases where an ASD is not morphologically obvious (Fig. 21) .

Fig. 20: Cardiac MR depicts a wide interatrial communication (A, arrow). In the short axis image at the defect level (B), septal discontinuity (yellow arrow) and a flow artifact (red arrow) secondary to left-lo-right shunt are observed. Enlargement of right ventricle (C) and pulmonary artery (D) result from the pressure increase.
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 21: 44-year-old-patient with recent diagnosis of stroke. Echocardiography suggested unclear septal hypertrophy. Cardiac MR confirms a minimal posterior septal hypertrophy. Morphologic images do not confirm interatrial communication. In perfusion images (4 chamber view) a retrograde opacification of right chambers (1 to 4) is observed. This findings suggest interatrial communication, in absence of an anomalous pulmonary venous return.
References: Department of Radiology, Hospital del Mar. Barcelona.

HIGH RISK CAUSES:

• Ventricular thrombi and myocardial infarction

Left ventricle (LV) mural thrombus is associated to myocardial infarction (MI), typically resulting from flow disturbance and wall motion abnormalities, which cause circulatory stasis. It is found in up to 40% of patients with anterior myocardial infarction, but in < 5% of them with inferior myocardial infarction.

The presence of severe left ventricular dysfunction, left ventricular aneurysm and arrhythmias increases the risk of thrombi formation and consequently increment the possibility of stroke and systemic emboli.

The best imaging tool to diagnose ventricular thrombi are echocardiography, CT and MR.

• Echocardiographic Findings
• • First-line imaging technique to identify LV thrombus
  • Transthoracic echocardiogram (TTE) most oftently used
  • Ventricular thrombi are usually anterior and apical
  • • TTE has some limitations in apical thrombi assessment, since interface between thrombus and myocardium may be difficult to observe.
• MR Findings
• • Contrast-enhanced MRI: Gold standard for evaluation of MI extension
  • Second-line imaging technique for intraventricular thrombi detection
  • • May be difficult to differentiate from other atrial or ventricular masses

• CT Findings
• Unlike cardiac MR and echocardiography, CTA has the added advantage of being able to depict the coronary arteries, in addition to ischemia and thrombi demonstration (Fig. 22)
• Thrombi assessment
• • Morphology: lamellate lesion that abuts the typically thinned myocardium
  • Mural thrombus may mimic normal thickness myocardium:
  • • HU: Thrombus appears slightly lower in attenuation (35-50 HU) compared to remote normal myocardium (80-100 HU)
    • Second delayed acquisition (60-70 seconds) or abdominal CT may help distinguish myocardium from thrombus.
  • Thoracic CT can also detect thrombi through underlying signs of MI and filling defects. Laminated mural thrombus may be a subtle finding (motion artifacts) (Fig. 23)  
•  Acute ischemia
• • Optimal windows help visualize hypoperfusion areas, otherwise difficult to detect (Fig. 24) 
  • Wall motion abnormality in underlying myocardium
• Chronic infarction
• • Underlying infarct may be evident from myocardial thinning, aneurysms, linear myocardial calcification or linear subendocardial fatty metaplasia (Fig. 25)
  • • Second delayed acquisition and abdominal CT are useful

Fig. 22: Patient with acute myocardial infarction (AMI). Cardiac MR (A) reveals an extensive apical myocardial infarction extending to the interventricular septum (A, arrows). Cardiac CT (B-E) evidences an apical thrombus (T) and a filling defect in the proximal portion of the Left Anterior Descending artery (arrows) responsible for the apical AMI.
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 23: 33-year-old patient with temporary loss of consciousness after cocaine consumption. Thoracic CT depicts an apical hypodense image, attached to the interventricular septum, suggestive of thrombus (*). Apical and septal myocardial hypoperfusion is uncertain (arrows). Echocardiography confirmed the diagnosis.
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 24: Patient with stroke secondary to basilar artery thrombosis. Thoracic CT performed after the clinical suspition of aortic dissection, depicted endocardial hypoperfusion at both apical and lateral cardiac levels (A, B, C) suggesting AMI. Utilization of narrow window settings enhances assessment of hypoperfusion (B, C; arrows), otherwise unnoticed in standard window (A). AMI was echocardiographically confirmed. No thrombi were identified.
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 25: Chronic apical infarction and history of stroke. Thoracic CT reveals an unclear apical hypodensity (A, red arrows). In the abdominal CT a more evident hypodensity is observed (B, C; brown arrows) suggestive of an extensive mural thrombus. Linear myocardial calcification (B, yellow arrow) indicates myocardial degeneration secondary to an old infarct.
References: Department of Radiology, Hospital del Mar. Barcelona.

The risk of acute ischemic stroke during the first 30 days after MI is approximately 2 %, and increases when ejection fraction is markedly reduced (<28%). Diagnosis of ventricular thrombi is crucial for adequate patient management and secondary prevention of new cerebrovascular accidents (Fig. 26).

Fig. 26: Brain CT (A) and angiographic intracranial CT (B) confirm occlusion of right MCA (brown arrow) and poor distal collaterallity in a patient with stroke suspicion. Some hours later presents a new stroke episode. Brain CT and angiographic CT (C,D) depict left MCA occlusion (D, blue arrow) poor collaterallity (blue circle) and reperfusion of previous occluded vessel. Thoracic CT evidences an intraventricular and hypodense lesion, congruent with a thrombus (E, yellow arrow).
References: Department of Radiology, Hospital del Mar. Barcelona.

• Ventricular tumors

Most of LV tumors are not positive cardioembolic sources, since they are located inside the myocardium and are not intracavitary. Cardiac lipoma, a benign encapsulated mass, may protrude into chamber lumen; althought emboli formation is still low.

Large masses based in the left atria, such as myxoma, may prolapse and become a possible stroke source (Fig. 27). Direct infiltration from adjacent tumors (ie, pulmonary) or invasion through LA or pulmonary veins may be a potential source of tumor emboli.

Fig. 27: Large mass in LA in contact with the interatrial septum (A, B), suggestive of myxoma, prolapses towards the left ventricle in systole (B).
References: Department of Radiology, Hospital del Mar. Barcelona.

• Dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a progressive disease of myocardium that is characterized by ventricular enlargement and contractile dysfunction with normal left ventricular (LV) wall thickness.

DCM is is a well-established risk factor for arrhythmias and mural thrombi, both of which are potential risk factors for brain infarction. The annual risk for embolic complications associated with dilated cardiomyopathy has been reported to be as high as 3.5% and correlates with the severity of systolic dysfunction. Recent literature considers major risk with severe LV dysfunction (ejection fraction <40%).

MR is gold standard for ventricular volumes and quantitative function (Fig. 28) and eventual ventricular thrombi (Fig. 29).

Fig. 28: Chest X-ray illustrates a severe cardiomegaly (A). MR confirms ventricular enlargement and difuse hypocontractility (B, diastole and D, sístole in short cardiac axis). Ejection Fraction (EF) was < 10%. Delayed enhancement sequence does not reveal neither intramyocardial fibrosis nor intraventricular thrombi (C).
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 29: Patient with history of DCM. Enlarged ventricular volume and apical akynesis is observed in long-axis view of cine SSFP cardiac MR (A, diastole; B, systole). Viability sequence shows gadolinium retention in apical and anterior walls (C, yellow arrows) secondary to previous myocardial infarction. Small apical hypointense image suggests intraventricular thrombus (T).
References: Department of Radiology, Hospital del Mar. Barcelona.

LOW RISK CAUSES:

• Myocardical contractility dysfunction

Isolated myocardic contractility dysfunction - such as hypo-, dys- or akinesis -, favor circulatory stasis, turbulent flow and low risk of thrombus formation and stroke.

Apical aneurysm is an akinetic or dyskinetic segment of thin and scarred myocardium resulting from transmural myocardial infarction that may promote LV thrombi formation (Fig. 30).

Fig. 30: Apical aneurysm in left ventricle (arrows) in Cardiac MR (A, B, C, D) and Thoracic CT (E, F) correlate to a low risk of stroke. Presence of thrombi inside the aneurysm increases the risk of cardioembolism.
References: Department of Radiology, Hospital del Mar. Barcelona.

• Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disease related to sarcomere gene mutations that is characterized by abnormal thickening of the LV myocardium. In most patients, a progressive process of cardiac remodelling with increasing myocardial fibrosis takes place, which induces complications: contractility dysfunction, arrhythmias and sudden cardiac death.

There is an obstructive phenotype of HCM, especially when the subaortic septal region is involved. The aforementioned arrangement leads to hypertrophic subaortic stenosis and a creation of a pathologic dynamic LV outflow tract (LVOT) gradient. Underlying structural abnormalities that include mitral valve anomalies, such as systolic anterior motion (SAM) of the mitral valve leaflet may also be identified. Thrombi formation responsible for ischemic stroke is in part secondary to turbulent flow development. 

Diagnosis of HCM traditionally relies on clinical assessment and transthoracic echocardiography. However recent studies have demonstrated increasing utility of CT and MR for both diagnosis and thrombi visualization (Fig. 31).

Fig. 31: Patient with HCM and history of stroke of undetermined cause. Cardiac MR depicts turbulent flow due to LVOT (yellow arrow) and important intramyocardial fibrosis (B, arrows). Revision of previous thoracic (C) and abdominal CT (D) reveals an obvious interventricular septal hypertrophy and a small hypodense lesion attached to the septum (brown arrow); a probable intraventricular thrombus.
References: Department of Radiology, Hospital del Mar. Barcelona.

• MR Findings
• • Best imaging technique to assess LV wall thickness
  • • Septal thickness > 15 mm (most common diagnostic criterion)
  • Reference standard for noninvasive evaluation of fibrosis (Fig. 31).
  • Cine cardiac MR offers information about functional parameters and evaluate LVOT and SAM
• CT Findings:

• Interventricular communication

Interventricular communication or ventricular septal defects (VSD) are frequent congenital conditions, that generally associate a left-to-right shunt. In situations where temporary pressure gradient promotes a right-to-left shunt or in patients with reversed shunt direction (Eisenmenger Syndrome), cardioembolic paradoxical embolism may occur with a low or undetermined risk (Fig. 32).

Fig. 32: 35-year-old woman with a vagal reaction post partum. Brain CT (A) and brain MR (B) several months after reveal a right insular hypodense lesion in CT, that is periferically hyperintense and presents a hypointense center in FLAIR, concordant with a chronic isquemic lesion. Cine sequence SSFP in Cardiac MR (C) shows a millimetric interventricular discontinuity at subaortic level, compatible with a subaortic interventricular communication (arrow).
References: Department of Radiology, Hospital del Mar. Barcelona.

Ischemic stroke might be caused by several valvular heart diseases. Among them, endocarditis, the presence of prosthetic valves, stenosis of the mitral valve and valvular tumors (ie, fibroelastoma) represent major risk factors. In such pathologies, transesophageal echocardiography (TEE) is currently the gold standard and the technique of choice due to its elevated spatial resolution and relatively ease of access. CT and MR can be used to collect additional information and in some cases might diagnose these diseases incidentally.  

HIGH RISK CAUSES:

• Endocarditis

Endocarditis is an endocardial inflammation that most commonly affects valves. Both infective and non-infective endocarditis may cause cardioembolic stroke.

Tumors, lupus and the anti-phospholipid syndrome are associated to the non-infective form, which is difficult to diagnose because of the lack of infectious symptoms. Transoesophageal echocardiogram is required in most cases for the demonstration of vegetations.

Cardioembolic stroke affects a number of patients (approx 10%) with infective endocarditis in the early course of the disease. Emboli can be multiple, especially with aggressive agents or when prosthetic valves are infected. Vegetation size and mitral valve damage are well known embolic risk factors. TEE is the best diagnostic tool, useful for vegetation characterization (detailed anatomy and mobility).

CT or MR might also show valvular degeneration. Cardiac CT is useful for valvular lesion definition (soft tissue mass vs calcification), paravalvular involvement and prosthetic valve infection. CT can also visualize other systemic emboli at thoracoabdominal level.

• Prosthetic valves

Both aortic and mitral prosthetic valves can get infected and thus represent a focal point for infective endocarditis. In patients with prosthetic valves showing symptoms of ischemic stroke, TEE of the prosthesis is recommended to discard the presence of vegetation.

CT can be useful to analyse the morphology and performance of the prostheses. Moreover, not only sub-valvular calcifications (Fig. 33), but also atherosclerotic disease and vulnerable plaque in ascending aorta can be identified; both additional causes of stroke. In any case, TEE is the most adequate imaging technique to study valvular vegetation.  

Fig. 33: Cardiac CT allows morphologic and functional assessment of metallic valvular prosthesis. In this example, subvalvular calcifications can also be observed (arrows).
References: Department of Radiology, Hospital del Mar. Barcelona.

• Mitral stenosis

Mitral valve stenosis can be observed when there is an incomplete opening of the valve and subsequently a reduction in the valvular area. The most frequent cause is rheumatic valvulopathy. Echocardiography remains the method of choice for such diagnosis. CT or MR can provide information about the valvular area (functional repercussion commonly shows valvular areas below 2,5 cm²).

• Papillary fibroelastoma

Papillary fibroelastoma is the most common benign cardiac tumor after myxoma, and it is localized at the cardiac valvular level. It represents a lesion composed of fibrotic/elastic tissue adhered to the endothelium, in general of small size (< 1 cm). This tumor is usually asymptomatic. Symptoms are generally associated to thrombi embolization, which can be formed on the surface of the tumor and then embolize systemically. TEE is the technique with most sensitivity to detect these types of lesions.

CT and, in particular, MR (Fig. 34)  can confirm the presence of the lesion, establish its exact localization and its correlation with adjacent structures, discard the presence of other cardiac masses, and characterize the lesion in regards to its signal features.

Fig. 34: Cardiac MR: 3 chamber planes (A, D), cine SSFP (B, E), perfusion images (C, F) with viability assessment. A small hypointense lesion (approximately 5mm) attached to the anterior mitral valve protudes towards de LV outflow tract. No early contrast enhancement is detected (B). However, late gadolinium enhancement is observed, related to fibrosis (C). Signal intensities and location suggest papillary fibroelastoma.
References: Department of Radiology, Hospital del Mar. Barcelona.

LOW RISK CAUSES:

• Annular calcification and prolapse

Calcification of various cardiovascular structures, such as aortic (Fig. 35) or mitral valves (Fig. 36) is associated with aging. The annular calcification may produce mobile projections, which can migrate and be a source of ischemic stroke. Calcium infiltration also reduces mobility, causing secondary valvular stenosis or insuficiency. While CT is more sensitive for calcification, both echocardiography and MR study finer the extent of stenosis.

Fig. 35: Patient with aortic stenosis and valvular calcification. Cardiac MR (A) depicts enlarged and irregular aortic valves (A, arrows). Thoracic CT (B) shows valvular calcification with motion artifact. ECG-Gated Cardiac CT manifests valvular, subaortic (C, black arrows) and ascending aorta calcifications (C, yellow arrow).
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 36: Cardiac CT may assess annular mitral calcification and its extension (A and B, brown arrows). Simultaneous studies of aortic valve and valvular planimetry are also possible. Prosthetic valves (A, B green and blue arrows) increase the thrombotic risk. Caseous calcification of the mitral valve is shown (C,D) as a laterally located nodular, calcified lesion (arrows).
References: Department of Radiology, Hospital del Mar. Barcelona.

Caseous calcification of the mitral valve is a rare form in which there is a prominent mass in the mitral ring with a liquid or gelatinous center - a mixture of calcium, fatty acid and colesterol-, which may be misdiagnosed as a cardiac tumor, vegetation or calcified thrombus. CT may help distinguish caseous calcification from tumor (Fig. 36). 

Another potential cause of cardiogenic ischemic stroke is represented by mitral prolapse, although the risk of ischemic stroke is low or undetermined. TEE is gold standard for accurately localizing the problem. Cardiac MR and CT are second-line imaging modalities if echocardiography is inconclusive.

This group includes, in our experience, potential and infrequently reported sources of cardiogenic stroke.

• Left ventricular noncompaction cardiomyopathy

Left ventricular noncompaction (LVNC) is a rare and recently described congenital cardiomyopathy also known as “spongy myocardium”, since it is characterized by prominent ventricular trabeculation and deep recesses, predominantly involving mid-lateral, mid-inferior and apex of left ventricle.

Thromboembolic events are related to development of thrombi within prominent ventricular recesses due to slow blood movement; impaired systolic function and AF have likewise been implicated to systemic emboli.

Although echocardiography remains primary diagnostic modality, cardiac MR represents the new gold standard to confirm LVNC (Fig. 37)  and it may also exclude intraventricular thrombi.

Fig. 37: LVNC. Echocardiography detects prominent apical trabecullation (A, arrow). Cardiac MR shows extensive trabecullation (arrows) and important ventricular enlargement. A delayed contrast enhanced MR to assess myocardial viability demonstrates an anteriorly located hypodense lesion; a thrombus suggestive image (C, arrow).
References: Department of Radiology, Hospital del Mar. Barcelona.

• MR findings
• • Extent of trabeculation at LV with delaminated appearance of myocardium 
  • Measurement of noncompacted vs. compacted myocardium
  • Fibrosis description. Late gadolinium enhancement may demonstrate subendocardial hyperenhancement corresponding to fibrosis
  • Thrombi exclusion

• Myocarditis

Myocarditis is an inflammatory disease of the myocardium, produced by different causes, mainly infectious. In developed countries, viral infection is the most frequently presumed cause of myocarditis.

The clinical presentation of myocarditis is variable and mimics other noninflammatory cardiac disorders. It may present similarly to acute myocardial injury with chest pain, electrocardiographic abnormalities, and elevated cardiac biomarkers (eg, troponin). Therefore, differential diagnosis with ischemic heart disease is relatively common. Diagnostic confirmation is not straightforward, since clinical presentation and first echocardiographic findings are non-specific.

A definitive diagnosis of myocarditis is based upon endomyocardial biopsy, only recommended for patients with fulminant heart failure or major clinical presentation. Usually, a combination of clinical manifestations and noninvasive diagnostic findings including typical cardiac MR findings can suggest the diagnosis:

• Presence inflammatory activity and injury. May be local or diffuse.
• Further cardiac MR study is suggested if non diagnostic findings after initial study and there is strong suspicion for myocarditis.

In our experience, myocarditis may be a cause of brain infarction, even if it is not generally reported in the literature. Myocarditis is accompanied by cardiac dysfunction, which may favor thrombi formation that can migrate to cerebral territory.

Retrospective evaluation of thoracic and abdominal CT findings in two patients with stroke of undetermined etiology, together with suggestive cardiac MR findings, allowed myocarditis diagnosis (Fig. 38 and Fig. 39). 

Fig. 38: 46-year-old woman presents with stroke compatible symptoms. Angiographic brain CT depicts a complete occlusion of distal right internal carotid artery and right MCA (A, B, arrows). Extracranial angiography illustrates a filling defect in the braquiocephalic artery (C, arrow). Clinical history revealed chest pain and a viral infection. Minor anterior chest wall and mediastinic fat hyperdensities were observed in the revision of extracranial angiographic CT (C, blue rectangle). Cardiac MR 25 days after demonstrates heterogeneous signal intensity in infero-lateral wall and epicardial gadolinium enhancement, suggesting myocarditis (D, E, F yellow arrows).
References: Department of Radiology, Hospital del Mar. Barcelona.

Fig. 39: 58 year-old man with history of stroke of undetermined cause. Cardiac MR for heart insufficiency assessment was performed. MR show moderate enlargement of LV (A), mild signal enhancement in lateral ventricular wall (B, arrows). Delayed contrast enhancement sequence to assess viability presents a mild epicardical enhancement (C, arrows). Since the stroke episode, patient presents chest pain and mild fever, features compatible with of a possible myocarditis. Posterior revision of a previous thoraco-abdominal study (one week before stroke) reveal moderate lateral LV wall hyperdensity (D) - probably secondary to edema or increased myocardial permeability- and an image consistent with thrombus (D, E arrows).
References: Department of Radiology, Hospital del Mar. Barcelona.

• Iatrogenic disease

Invasive procedures in the cardiac chambers can favor atrial thrombi formation and their systemic embolization. Thromboembolism is an eventual complication in catheter ablation, an everyday increasing procedure. Left atrium is most commonly accessed through interatrial septal perforation from a venous catheterization (eg, femoral access). Intracavitary thrombi formed during prolonged catheter manipulation in LA may cause stroke during or after the procedure and represents the third cause of death related to the ablation.

Spontaneous closure of the interatrial communication is expected in some days. Meanwhile or when closure does not occur (Fig. 40) when the auricular thrombus formation risk is increased.  

Fig. 40: Cardiac MR performed before atrial fibrillation catheter ablation (A). Cardiac MR after ablation shows an interatrial discontinuity and a contrast jet, suggesting spontaneous iatrogenic interatrial communication did not occur.
References: Department of Radiology, Hospital del Mar. Barcelona.

Esophageal injury due to tissue heating at the posterior wall of the left atrium ranges from mild ulceration to exceptional left atrio-esophageal fistula (Fig. 41).  It may appear as a subacute or late complication (between 3 to 38 days after the procedure) with passage of esophageal content to the LA (air, food and bacterial flora) and further systemic embolization, with fatal consequences. Neurologic symptoms such as meningitis, transient ischemic attacks after meal and neurologic deficit may suggest the diagnosis. Oral endoscopy or nasogastric tube placement are contraindicated, since they may increase the slit size of the fistula. Surgical repair is the therapy of choice.

Fig. 41: 31-year-old man with atrial fibrillation catheter ablation presents with an ictal episode and fever (39ºC). Brain CT exhibits left frontal hypodense lesion (A, circle). Similar symptoms develop one day after. New brain CT images show enlargement of previous lesion (B, circle) and appearance of 3 new lesions in different vascular territories (C, circles). Septic embolism is suspected. Thoraco-abdominal CT (D, E, F) reveals a hypodense image in LA posterior wall with air (brown arrows), contiguous to esophagus. Multiplanar reconstructions better depict the location of the atrio-esophageal fistula. Surgical repair failed and patient died some days after.
References: Department of Radiology, Hospital del Mar. Barcelona.

Thrombi are the major sources of embolism, but emboli of air, fat and tumor tissue have also been reported. Cerebral air embolism can happen through central venous catheters in patients with a PFO and a right-to-left shunt (Fig. 42).  Air emboli absorb quickly and are best depicted in an early stage at CT.

Fig. 42: Patient with a central venous catheter presents with stroke syptoms after catheter manipulation. Early brain CT show multiple air emboli (A, B, arrows). Subcutaneous emphysema was observed in thoracic CT (C). Further studies revealed a permanent foramen ovale.
References: Department of Radiology, Hospital del Mar. Barcelona.

Imaging findings of cardioembolic complications in the brain are probably similar for different types of embolism, and the clinical history is important for final diagnosis.

Is also important to take into account that embolus may not always have a cardiac origin, but a vascular one. Many centers perform CT angiography from the aortic arch to the vertex in patients with stroke in order to depict aortic dissections (Fig. 43) and to examine the extent of extra- and intracranial atherosclerotic disease. CT angiography can provide useful information about vascular stenosis and plaque vulnerability; predicted by morphology (ie, ulceration) and composition (extensive calcification has a protective effect).

Fig. 43: Patient with acute brain infarction symptoms. Angiographic brain CT images demonstrate abscence of right carotid circulation (A, B arrows) and an aortic dissection with aortic arch involvement (C, *).
References: Department of Radiology, Hospital del Mar. Barcelona.