Imaging in Arrhythmogenic Right Ventricular Dysplasia (ARVD)

Arrhythmogenic right ventricular dysplasia (ARVD) is an unusual, often familial, condition characterized by the replacement of myocardial tissue by fat and fibrous tissue (as demonstrated in the image below). ARVD has a wide spectrum of clinical presentations, including mechanical dysfunction and various forms of ventricular arrhythmias. It is a cause of sudden death, mostly in young people and athletes.

Anatomic changes of the right ventricle consist of mild to severe global dilatation, aneurysms, and segmental hypokinesia. Sites of involvement of the right ventricle are found in the triangle of dysplasia, namely, the right ventricular outflow tract, the apex, and the infundibulum. Mutations have been identified in 5 desmosomal genes. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9]}

Electrocardiographically gated T1-weighted image shows arrhythmogenic right ventricular dysplasia (ARVD) with prominent epicardial fat in the right ventricular outflow tract.

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Preferred examination

The recognition of mild, forme fruste, and localized forms of ARVD remains a clinical challenge. Diagnosing ARVD in patients with minimal right ventricular abnormalities is difficult to accomplish using echocardiography, ultrafast computed tomography (CT) scanning, radionuclide angiography, multidetector computed tomography, and contrast-enhanced angiography. ^{[10, 11, 12, 13, 14, 15, 16, 17]}

Magnetic resonance imaging (MRI) is a promising technique for showing the anatomy and function of the right ventricle, as well as for characterizing the composition of the right ventricle's wall, especially with regard to adipose tissue. However, the diagnostic sensitivity and specificity of MRI remain to be defined, because the quality of images detected is observer dependent. Signal intensity suggesting the presence of fat in the right ventricle may be related to a latent form of the disease or to the dissociation of myocardial tissue by fat. Therefore, only the combination of MRI signs, including the size, function, and fat content in the free wall, is necessary to support the diagnosis. ^[18]

MRI has the advantage of offering methods that specifically eliminate or selectively include signal from only fat, which resonates at a different frequency than that of tissue or water. For example, a spatiospectral pulse sequence can be used to selectively image fat by using a gradient-echo technique, and a triple-inversion recovery sequence can be applied to nullify signals from fat. However, wall motion, gating abnormalities, or other artifacts can produce false-positive results, which must be eliminated by means of inspection and/or the acquisition of confirmatory views.

In some cases, endomyocardial biopsy may be necessary to confirm the diagnosis.

In 2010, a Task Force proposed revisions to the 1994 International Task Force criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), which facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. The Task Force elaborated on newer imaging techniques, such as contrast-enhanced echocardiography, 3-dimensional echocardiography, cardiovascular magnetic resonance with late enhancement, and electroanatomic voltage mapping. ^[19]

Chest radiographs may be normal, or they may demonstrate a wide variety of manifestations not specific for ARVD. These range from a completely normal cardiac silhouette to moderate or major cardiomegaly with a convexity between the aortic knob and the left ventricle without pulmonary vascular redistribution. Therefore, chest radiography is not a good tool for diagnosing ARVD, but it can help in assessing the patient's prognosis. The cardiothoracic index is less than 0.6 in most patients. In young athletes, this relative cardiomegaly may be incorrectly attributed to training.

The role of MRI in the diagnosis of ARVD has been established. In conjunction with electrophysiologic, electrocardiographic, and familial indicators, MRI results are specific. MRI is considered highly sensitive and highly specific. MRI can be an effective noninvasive examination for fatty infiltration of the myocardium. However, because fat is a normal component of the right ventricle in humans, it is necessary to interpret MRI results in light of all of the findings in the clinical context.

MRI enables clear visualization of morphology of the right ventricle, and it permits characterization of the composition of the wall, especially with regard to fatty tissue. ^[20] Typical MRI ARVD protocols include (1) bright-blood gradient-echo imaging in cine mode to assess wall motion, (2) dark-blood T1-weighted imaging to evaluate wall thickness, and (3) specific fat-sensitive or fat-suppressive imaging to confirm fatty infiltration or transdifferentiation on short-axis views spanning the entire right ventricle. ^{[21, 22, 23, 24]}

Use of orthogonal views, attention to gating, and/or alternative fat-sensitive methods help eliminate a false-positive signal dropout. ^{[10, 11, 13, 25, 26]}

Images derived from MRI techniques appear below.

Electrocardiographically gated T1-weighted image shows arrhythmogenic right ventricular dysplasia (ARVD) with prominent epicardial fat in the right ventricular outflow tract.

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Electrocardiographically gated axial spin-echo T1-weighted image demonstrates diffuse high signal intensity in the myocardium of the right ventricular anterior free wall. This finding corresponds to fatty infiltration.

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Electrocardiographically gated axial spin-echo T1-weighted image shows the high signal intensity due to fatty infiltration of the right ventricular free wall.

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Four-chamber electrocardiographically gated cine gradient-echo images show an abnormality in right ventricular wall motion during systole or a systolic aneurysm.

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In ARVD, MRI findings consist of abnormalities in signal intensity, which usually affect the right ventricular free wall and/or the previously mentioned triangle of dysplasia. Fibrofatty deposition in these regions of the right ventricle may be found on T1- and T2-weighted images, where they appear as areas of either focal or diffuse high signal intensity. Other relatively nonspecific signal-intensity abnormalities in the right ventricle may be due to fibrosis or inflammation.

Regardless of the MRI findings obtained, myocardial biopsy is often warranted. In terms of morphology, diffuse or focal dilatation of the chamber of the right ventricle is a key finding in ARVD. Often, the free wall of the right ventricle is noticeably thinned. Motion abnormalities depend on the extent of the underlying fibrofatty infiltration and vary from a focal bulge to a low ejection fraction due to disease that is more diffuse.

MRI may be indicated in (1) young athletes with frequent simple arrhythmias, even in the absence of echocardiographic abnormalities; (2) patients with ventricular tachyarrhythmias in a left bundle-branch-block pattern; (3) patients with palpitations, syncopal episodes, or echocardiographic abnormalities of the right ventricle; and (4) patients with a familial occurrence of ARVD or sudden death syndrome.

Echocardiography is sensitive for ARVD, but it is not specific, because it does not allow for an assessment of the adipose substitution of the myocardium, which is a hallmark of ARVD. Echocardiography is less sensitive than MRI, because it may fail to depict focal right ventricular wall thickening, and it does not reliably help in distinguishing fat from muscle. The last limitation also decreases the specificity of echocardiography. Right ventricular hypertrophy, right ventricular infarct, and prominent pericardial fat contribute to false-positive results. Limitation of views and focality of thickening of the right ventricular wall contribute to false-negative findings.

Echocardiography may show morphologic abnormalities, such as dilatation of the right ventricle and outflow tract, segmental wall bulging or aneurysms in the predominantly affected portions during diastole, and hypokinetic or dyskinetic areas in the inferobasal region. ^{[27, 28]} However, in most cases of ARVD, the structural abnormalities are moderate, and they may be difficult to detect. The posterior and inferior walls of the right ventricular inflow tract under the tricuspid valve are the most important regions that must be visualized because they are most frequently affected.

Contrast-enhanced echocardiography with injections of sodium chloride solution may aid in evaluating the outline of the right ventricle to permit an analysis of right ventricular volume.

The use of three-dimensional (3D) echocardiography, particularly in combination with the transesophageal approach, is being investigated as a means to enhance the diagnostic accuracy of this technique.

Although nuclear ventriculoscintigraphy is accurate in the quantitative evaluation of right ventricular function, it does not provide specific information. Nuclear ventriculoscintigraphy provides data concerning the size, ejection fraction, and contraction pattern of the ventricles. In most cases of ARVD, the size of the right ventricle is increased, but it can also be within normal limits. Wall motion during contraction is not uniform, as a result of dyskinetic areas of fat replacement in the free wall of the right ventricle. Specific isotopic markers have demonstrated regional sympathetic denervation of these areas. ^[29]  With nuclear ventriculoscintigraphy, ARVD should be in the differential diagnosis for any condition that results in a large right ventricle, a diminished ejection fraction, or an alternating contraction pattern in the right ventricle.

Because MRI and 3D echocardiography are noninvasive and repeatable examinations, they are preferred over angiography for the evaluation of the right ventricle's structure and function. The angiographic features of ARVD include global and/or regional function and morphologic abnormalities of the right ventricle. Such features include localized akinetic or dyskinetic bulges, outpouchings, dilatation of the infundibulum, trabecular hypertrophy, and/or disarray with deep fissures. ^[12]