Arrhythmogenic Right Ventricular Dysplasia

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CHAPTER 65 Arrhythmogenic Right Ventricular Dysplasia

Aditya Jain, Harikrishna Tandri, Hugh Calkins, David A. Bluemke

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare, progressive genetic cardiomyopathy that is characterized clinically by ventricular arrhythmias and sudden death, and histologically by fibrofatty infiltration of the right ventricle. Although symptomatic ventricular arrhythmias and sudden death are the most common manifestations of the disease, either right ventricular or biventricular heart failure may be observed. This chapter discusses various aspects of ARVD including etiology and pathogenesis, clinical manifestations, differential diagnosis, and treatment options, with special focus on diagnostic imaging techniques, in particular MRI, which is the current noninvasive diagnostic modality of choice in ARVD.

DEFINITION

ARVD is a genetic cardiomyopathy principally involving the right ventricle that is characterized clinically by ventricular arrhythmias and progressive structural alterations in right ventricular size and function. Fibrofatty replacement of the right ventricular myocardium forms the histopathologic hallmark of this disease. There are three patterns of disease expression: (1) classic, characterized by disease limited to the right ventricle with either no or minimal involvement of the left ventricle, which appears late in the course of the disease; (2) left dominant, characterized by early or predominant left ventricular involvement; and (3) biventricular, characterized by parallel involvement of both ventricles from the beginning of disease process.¹

PREVALENCE AND EPIDEMIOLOGY

Although the exact incidence of ARVD is unknown, the prevalence has been estimated to be 0.02% of the general population.² ARVD reportedly is more prevalent (0.8%) in certain parts of northern Italy (Veneto) and Greece (Naxos Island).³^,⁴ ARVD most commonly manifests after puberty and before age 50 years.⁵^,⁶ ARVD is more common in highly athletic individuals. It is an important cause of sudden cardiac death in young individuals, particularly in athletes, accounting for 5% of sudden deaths in individuals younger than 35 years in the United States, and 25% of deaths in athletes in the Veneto region of Italy.⁷ ARVD is believed to be more common than reported because of its frequently asymptomatic clinical course, difficulty in diagnosis using conventional noninvasive methods, and frequent misdiagnosis.

ETIOLOGY AND PATHOPHYSIOLOGY

The exact pathogenesis of ARVD remains speculative, but it is most widely believed to be due to genetic abnormalities mainly affecting cardiac desmosomal structure and function. In the United States, the most common reported genetic abnormality in ARVD is a mutation in plakophillin-2 (PKP2), which is a desmosomal protein and is present in more than one third of patients. Desmosomal mutations are believed to disrupt cell-cell adhesion, which provokes myocyte detachment and death under conditions of high mechanical stress, as suggested by its frequent occurrence in athletics and the thinnest portions of the right ventricle, such as the inferior subtricuspid region, right ventricular apex, and right ventricular infundibulum—together termed the triangle of dysplasia (Fig. 65-1).⁸ This leads to a compensatory repair process characterized by inflammation and fibrofatty substitution. Familial ARVD accounts for 30% to 80% of cases, and most commonly shows an autosomal dominant inheritance, with age-dependent penetrance and variable clinical expression, which can be attributed to the complex interplay of age, gender effects, and environmental influences such as exposure to viruses and athletic activity with the underlying genetic background in the ultimate disease causation and progression. Mere inheritance of a genetic abnormality does not imply “disease” for the same reason. To date, at least 11 distinct subtypes of autosomal dominant ARVD are known, and at least seven genes have been implicated in ARVD (Table 65-1).⁹

FIGURE 65-1 Long-axis view of the right ventricle (RV), showing the triangle of dysplasia, which is formed by the inferior subtricuspid area (short arrow), apex (arrowhead), and infundibulum (long arrow). PA, pulmonary artery; RA, right atrium.

TABLE 65-1 Genetics of Arrhythmogenic Right Ventricular Dysplasia

Genetic mutations are also implicated in determining the ventricular predominance in ARVD. Chain-termination mutations causing truncation of the C-terminal domain of desmoplakin can disrupt cytoskeletal integrity, predisposing to predominant left ventricular involvement. Conversely, defects in the N-terminal domain of desmoplakin can result in a primary dysfunction of cell adhesion, leading to predominant right ventricular disease.⁸

In addition to genetic causes, other important proposed etiologic mechanisms of ARVD are (1) apoptosis (programmed cell death), (2) inherited metabolic or ultrastructural defects leading to myocardial dystrophy, and (3) secondary complication of a prior primary right ventricular myocarditis on the basis of frequently found myocardial inflammatory infiltrates and isolation of coxsackie B and enteroviral RNA viruses in some biopsy samples.¹⁰

Pathologically, ARVD is characterized by gradual myocyte loss and fibrofatty infiltration, which starts in the subepicardial region and gradually involves the endocardium, often sparing the trabecular myocardium. Plexiform arrangement of the residual myocardial fibers, separated by fat and fibrosis, leads to electrical instability and provides a conduit for a reentrant phenomenon. This situation explains the arrhythmogenic propensity characteristic of this disease, which can be worsened further by superimposed myocarditis that occurs frequently in ARVD because of the genetic susceptibility.¹¹ A myocardial dysplastic process and the associated loss of its strength and integrity are responsible for the varying degrees of structural derangement and functional disturbances of the heart seen in ARVD.

MANIFESTATIONS OF DISEASE

Clinical Presentation

ARVD usually manifests between the second and fifth decades (mean age at diagnosis approximately 30 years). Patients most commonly present with symptomatic ventricular arrhythmias or sudden cardiac death, or may remain asymptomatic, with ARVD discovered only incidentally on routine examination. The most common symptoms are palpitations, syncope, atypical chest pain, and dyspnea. Ventricular arrhythmias are often precipitated by exercise or stress, and range from isolated ventricular premature beats to sustained monomorphic or polymorphic ventricular tachycardia with left bundle branch block morphology, or abrupt ventricular fibrillation, which is the most common underlying cause of sudden cardiac death in ARVD.¹²

In addition to ventricular arrhythmias, about 25% of patients may also show supraventricular arrhythmias, which include atrial fibrillation, atrial tachycardia, and atrial flutter, in that order of frequency.¹³ Left ventricular involvement is associated with an increased incidence of arrhythmic events, more severe right ventricular wall thinning, and heart failure. Frank left-sided heart failure is rare. Figures 65-2, 65-4, and 65-6 illustrate left ventricular involvement in ARVD.

FIGURE 65-2 Contrast-enhanced, multidetector CT image in a patient with ARVD shows right ventricle (RV) (long arrow) and left ventricle (LV) (short arrow) thinning associated with fat replacement. Note also the dilation of the RV and epicardial pacing lead.

Diagnosis

Diagnosis of ARVD is challenging and is currently based on family history and morphofunctional, ECG, histopathologic, and clinical findings as proposed by the Task Force of Cardiomyopathies in 1994 (Table 65-2).¹⁴ The diagnosis is made in the presence of two major criteria, one major criterion and two minor criteria, or four minor criteria. Various modifications of the existing Task Force criteria are being increasingly proposed and emphasize the increment in the diagnostic sensitivity of these criteria for less severe forms of the disease and asymptomatic first-degree relatives of affected probands. These modifications include more comprehensive characterization of ECG and echocardiographic criteria, inclusion of mutation analysis, and descriptions of left ventricular involvement.¹⁵^,¹⁶

TABLE 65-2 Task Force Criteria for the Diagnosis of Arrhythmogenic Right Ventricular Dysplasia

	Major Criteria	Minor Criteria
Global or regional dysfunction and structural alterations*	Severe dilation and reduction of right ventricular ejection fraction with no (or only mild) left ventricular impairment	Mild global right ventricular dilation or ejection fraction reduction with normal left ventricle
	Localized right ventricular aneurysms (akinetic or dyskinetic areas with diastolic bulging)	Mild segmental dilation of right ventricle
	Severe segmental dilation of right ventricle	Regional right ventricular hypokinesia
Tissue characterization of wall	Fibrofatty replacement of myocardium on endomyocardial biopsy specimen
Repolarization abnormalities		Inverted T waves in right precordial leads (V₂ and V₃) in individuals >12 yr old in absence of right bundle branch block
Depolarization or conduction abnormalities	Epsilon waves or localized prolongation (>110 ms) of the QRS complex in right precordial leads (V₁-V₃)	Late potentials (signal-averaged ECG)
Arrhythmias		Left bundle branch block ventricular tachycardia (sustained and nonsustained) by ECG, Holter, or exercise testing
		Frequent ventricular extrasystoles (>1000/24 hr) (Holter)
Family history	Familial disease confirmed at necropsy or surgery	Family history of premature sudden death (<35 yr old) owing to suspected right ventricular dysplasia
		Familial history (clinical diagnosis based on present criteria)

* Detected by echocardiography, angiography, MRI, or radionuclide scintigraphy.

As per the standard diagnostic algorithm for ARVD, all patients with clinical suspicion of ARVD first undergo noninvasive testing, which includes a 12-lead ECG, signal-averaged ECG, 24-hour Holter monitor, and cardiac imaging. If the results are consistent with a diagnosis or a high degree of suspicion of ARVD based on the Task Force criteria, at our institution we typically recommend patients to undergo further invasive testing, including right ventricular angiography, endomyocardial biopsy, and electrophysiology testing, for confirmation of the diagnosis and exclusion of other potential etiologies, such as sarcoidosis. The standard of reference for the diagnosis of ARVD has been the histopathologic demonstration of fibrofatty replacement of right ventricular myocardium either on an endomyocardial biopsy specimen or at autopsy. Endomyocardial biopsy carries the risk of perforation of right ventricular free wall, however, and has low sensitivity because of frequent sampling error owing to the segmental, patchy nature of the disease. One particularly important role of endomyocardial biopsy is to distinguish sarcoidosis from ARVD.

Electrocardiogram Evaluation

At least one ECG abnormality (Table 65-3) is detectable in more than 90% of patients with ARVD. A newly proposed marker of delayed right ventricular activation, prolonged S wave upstroke (≥55 ms) in V₁ to V₃, is the most prevalent ECG marker and correlates with disease severity and ventricular tachycardia induction on electrophysiology testing.¹⁷ Signal-averaged ECG is used to detect delayed ventricular activation owing to slowed propagation in the fibrofatty myocardium of ARVD. Late potentials on signal-averaged ECG (two or more of the following: filtered QRS duration ≥114 ms, duration of the low-amplitude signal <40 µV in the terminal portion of filtered QRS (LAS40) ≥38 ms, and root mean square voltage of the terminal 40 ms of filtered QRS (RMS40) <20 µV) form a minor diagnostic criterion for ARVD as per the Task Force criteria. Similar to extent of right precordial T wave inversion, late potentials on signal-averaged ECG are correlated with the extent of right ventricular involvement in ARVD. More recently, our group found that using filtered QRS 110 ms or greater identifies ARVD patients with inducible ventricular tachycardia more accurately than does conventional signal-averaged ECG criteria.¹⁸ T wave inversions and signal-averaged ECG abnormalities are more commonly seen in left-sided involvement in ARVD.

TABLE 65-3 Electrocardiogram Features of Arrhythmogenic Right Ventricular Dysplasia ^‡

* Minor Task Force criterion in the absence of right bundle branch block in individuals >12 yr old.

† Major Task Force criterion.

‡ These electrical abnormalities are believed to be caused by intraventricular myocardial defect (parietal block) rather than definite alteration of conduction in the bundle branch (septal block).

Imaging Techniques and Findings

Echocardiography

Two-dimensional echocardiography is an important first-line imaging tool for diagnosis and follow-up in ARVD because of its noninvasiveness, low cost, wide availability, and ease of performance. Echocardiographic abnormalities associated with the Task Force criteria for ARVD are summarized in Table 65-5. A right ventricular outflow tract long-axis diameter greater than 30 mm on echocardiography has been found to have the highest sensitivity and specificity for the diagnosis of ARVD. Right ventricular dysfunction has been defined as a fractional area contraction less than 32%, or the presence of segmental right ventricular wall motion abnormalities (mostly observed in anterior and apical walls) for the purpose of echocardiographic diagnosis of ARVD.²¹

TABLE 65-5 Echocardiography Features Associated with Task Force Criteria for Arrhythmogenic Right Ventricular Dysplasia

Right ventricular regional wall motion abnormality

Right ventricular outflow tract dilation

Right ventricular dilation

Reduced right ventricular global function

Hyper-reflective moderator band

Exaggerated/abnormal trabeculations

Sacculations

We evaluated three-dimensional echocardiography, tissue Doppler echocardiography, and strain echocardiography, and found that these imaging modalities show high feasibility and reproducibility in ARVD. Three-dimensional echocardiography measurement of right ventricular volumes and ejection fraction showed close correlation with MRI, the current reference standard, and three-dimensional echocardiography may be potentially more useful in the assessment of right ventricular function and follow-up of patients with ARVD, in contrast to two-dimensional echocardiography. Tissue Doppler echocardiography and strain echocardiography showed higher sensitivity in detection of mild cases of ARVD with normal right ventricle on conventional echocardiography. In our opinion, these new echocardiographic modalities may have a potentially greater diagnostic utility in ARVD than conventional methods.²²^,²³ Contrast echocardiography using saline injections may outline the right ventricle better, enabling better evaluation of right ventricular volumes and regional and global function.¹¹

Computed Tomography

Electron-beam CT and multidetector CT can yield accurate and reliable qualitative and quantitative assessment of the right ventricle at an excellent spatial and temporal resolution. They can also provide tissue characterization of the myocardium and detect fatty changes, similar to MRI. Electron-beam CT can directly assess left ventricular adipose tissue changes and can even detect subclinical cases of ARVD without left ventricular wall motion abnormality.²⁴ Major abnormalities in ARVD reported on CT include (1) dilated right ventricle, (2) abundant epicardial fatty tissue, (3) intramyocardial fat deposits, (4) scalloped appearance (bulging) of the right ventricular free wall, and (5) conspicuous trabeculae with low attenuation (Figs. 65-2 and 65-3).

FIGURE 65-3 Contrast-enhanced, multidetector CT image in an ARVD patient shows extreme wall thinning and fat replacement of the right ventricle (RV) (arrow) and right ventricular dilation. Note the artifact caused by the ICD lead.

CT is less expensive, faster, technologically easier to perform, less operator-dependent, and more reliable in terms of image quality compared with MRI. It is less susceptible to artifacts resulting from respiratory motion and patient movement because of shorter image acquisition times on the order of milliseconds. CT is the diagnostic modality of choice in ARVD patients with claustrophobia and frequent arrhythmic events. Although the presence of an implantable cardioverter defibrillator (ICD) was previously considered to be an indication for a CT scan versus MRI, more recent studies have shown that MRI can be safely performed in patients with ICDs.²⁵ Limitations of CT include its fixed axial plane for image acquisition, requirement for ionizing radiation exposure, use of nephrotoxic contrast agent, and relatively lower temporal resolution compared with MRI.⁷

Magnetic Resonance Imaging

MRI has been increasingly recognized as the imaging technique of choice for ARVD. Its three-dimensional, multiplanar visualization of the heart along with excellent spatial and temporal resolution enables highly reproducible assessment of structural morphology and function of the right ventricle without using any geometric assumptions. The improved blood-myocardial image contrast allows optimal visualization of the right ventricle. For myocardial tissue characterization, MRI can specifically locate and quantify intramyocardial adipose infiltration, which forms the pathologic hallmark of the disease (Fig. 65-4).²⁶ MRI has the potential to visualize fibrous tissue replacement of right ventricular myocardium in ARVD by myocardial delayed enhancement (Fig. 65-5).²⁷

FIGURE 65-4 A, Axial black blood image from a patient with ARVD shows intramyocardial fat infiltration (seen as hyperintense T1 signal) of the right ventricle (arrows) and left ventricle (arrowheads). B, Axial fat-suppressed image from the same patient at the same slice level shows low signal intensity (owing to fat signal [arrows]) corresponding to the areas of high T1 signal in A. The fat suppression images are chemically selective for lipid signal.

FIGURE 65-5 Delayed-enhancement axial image from a patient with ARVD shows high signal intensity (i.e., hyperenhancement) in the right ventricular free wall (arrow). The high signal intensity most commonly correlates with areas of fibrosis in these patients.

MRI can be uniquely applied for the identification of regional and diastolic dysfunction of the right ventricle and minor changes in right ventricular volume over time and other functional details, such as velocity mapping of the tricuspid flow and right ventricular strain measurements using myocardial tagging. MRI also has prognostic significance because of its ability to predict arrhythmia-free survival in ARVD.²⁸ MRI is noninvasive and devoid of radiation hazards. These features make MRI highly suited and superior to other imaging investigations for the detection and serial follow-up of patients with clinically suspected ARVD.

MRI findings in ARVD can be broadly divided into two groups: (1) morphologic abnormalities, including intramyocardial fat infiltration, right ventricular wall thinning (Fig. 65-6), trabecular hypertrophy (Fig. 65-7), and right ventricular outflow tract enlargement (Fig. 65-8), and (2) functional abnormalities, including right ventricular wall motion abnormalities, aneurysms (Fig. 65-9), right ventricular dilation (Fig. 65-10), and right atrial enlargement (Fig. 65-11). These findings are listed in Table 65-6.

FIGURE 65-6 Axial bright blood image from a patient with ARVD shows thinning of the right ventricular free wall (short arrow), and thinning (long arrow) and infiltration of fat (arrowhead) in the left ventricular lateral wall.

FIGURE 65-7 Short-axis bright blood image from a patient with ARVD shows trabecular hypertrophy and disarray of the right ventricle (arrows).

FIGURE 65-8 A, Axial bright blood image from a patient with ARVD shows enlarged right ventricular outflow tract (RVOT) (arrow) compared with aorta (arrowhead). B, Axial black blood image from another patient with ARVD shows enlarged and dysmorphic outflow tract (arrow).

FIGURE 65-9 A, Axial bright blood image from a patient with ARVD shows microaneurysms at the right ventricular free mid-wall (arrows). B, Axial bright blood image from a patient with ARVD shows a microaneurysm in the right ventricular outflow tract (arrow).

FIGURE 65-10 Axial bright blood image from a patient with ARVD shows dilation of the right ventricle (RV). The end-diastolic diameter of the RV is greater than that of the left ventricle (LV).

FIGURE 65-11 Axial bright blood image from a patient with ARVD shows enlargement of the right atrium (RA) (arrow). LA, left atrium; LV, left ventricle; RV, right ventricle.

TABLE 65-6 Magnetic Resonance Imaging Features of Arrhythmogenic Right Ventricular Dysplasia

Bright blood cine gradient MRI is the preferred modality for the functional evaluation of the right ventricle. ECG gated steady-state free precession (SSFP) imaging (e.g., FIESTA, true FISP, and balanced fast field echo) is preferred to segmented k-space cine gradient-echo imaging (e.g., fast low-angle shot [FLASH] and fast cardiac-gated gradient-echo [FASTCARD]) because of higher temporal resolution and excellent contrast between myocardium and blood pool, which make it better adapted for assessment of wall motion and volumetric measurement. Also, signal intensity in SSFP is not affected by reduction in blood flow velocity in instances of right ventricular dysfunction compared with gradient-echo imaging.

Black blood breath-hold fast spin-echo MRI (see Figs. 65-4A and 65-8B) with dual magnetization preparation pulse (double inversion recovery) is the preferred modality to detail cardiac morphology. Inversion recovery pulses are used to null (darken) the signal from a tissue of interest to highlight (enhance) the surrounding pathology. Breath-holding reduces motion artifacts and improves overall image quality of myocardial detail. Black blood single-shot spin-echo techniques (e.g., HASTE, turboFLASH, SSFSE) are ultrafast imaging modalities that substantially reduce image acquisition times and motion artifacts, but at the expense of blurring of detail. They are not recommended, unless a severe arrhythmia is present that results in failure of other black blood sequences. Incorporation of fat-suppressed sequences (see Fig. 65-4B) to conventional T1-weighted spin-echo imaging has been found to increase the interobserver agreement and confidence in the diagnosis of intramyocardial fat infiltration.²⁹^,³⁰ Table 65-7 presents a detailed MRI protocol recommended for ARVD.

TABLE 65-7 Magnetic Resonance Imaging Protocol for Arrhythmogenic Right Ventricular Dysplasia

Patient preparation: If the patient is known to have frequent ventricular ectopy, use oral metoprolol, 50 mg, 1 hr before the procedure, provided that the patient has no contraindications. If ventricular arrhythmias are frequent and would have a substantial impact on image quality, the examination should be terminated at this point.

1 Rapid three-plane image localizers

2 Axial black blood images: double inversion recovery fast/turbo spin-echo

3 Axial bright blood cine images: SSFP cine, temporal resolution ≤50 ms

4 Vertical and long-axis cine images (two- or four-chamber view) (same pulse sequence as step 3)

5 Short-axis black blood images (same pulse sequence as step 2)

6 Axial black blood images with fat suppression (optional sequence)

Administer intravenous gadolinium contrast agent, 0.1-0.2 mmol/kg per local protocols

7 Short-axis SSFP cine (same pulse sequence as step 3)

8 TI scout or other method to determine optimal blood suppression

9 Delayed gadolinium short-axis images (10-15 min delay after gadolinium administration)

10 Delayed gadolinium axial axis images

Right ventricular intramyocardial fat on MRI has a low sensitivity for detection of ARVD compared with other abnormalities, such as regional right ventricular dysfunction. Normal presence of epicardial fat, especially in areas such as the atrioventricular sulcus and anterolateral and apical portions of the right ventricle, sometimes makes distinction from pathologic fat difficult, particularly given the thinness of normal right ventricular wall and limited spatial and contrast resolution achievable by even state-of-the-art MRI protocols.³¹ Fat was also found to be the least specific and least reproducible of any of the other parameters in the MRI evaluation of ARVD.³²^,³³ High intramyocardial T1 signals are not specific for ARVD because isolated fatty infiltration of the right ventricle has also been reported in elderly individuals, obese individuals, patients on long-term steroid therapy, patients with alcohol abuse, patients with idiopathic right ventricular outflow tract tachycardia, and patients with inherited myopathies, and more recently as a separate disorder in itself, clinicopathologically distinct from ARVD.³⁴ False-positive high signal intensities potentially misconstrued as fat may be produced by various artifacts related to motion, respiration, blood flow, arrhythmia, or truncation band.

The ability of MRI stands out in the diagnosis of early and subtle cases of ARVD because of its potential to detect regional and diastolic ventricular dysfunction, which are thought to precede global and systolic dysfunction during the progressive course of the disease.³⁵ This capability of MRI can add to the overall sensitivity of diagnosis of ARVD because these patients may otherwise be clinically inapparent and less sensitive to diagnosis by Task Force criteria. In one of our studies, we found that despite preserved systolic function, 37% of patients with early or limited forms of ARVD show focal discoordinate contraction of right ventricular free basal wall on MRI, which was unique in its appearance as focal crinkling of the right ventricular wall in peak systole (Fig. 65-12).

FIGURE 65-12 A, End-diastolic axial bright blood image from a patient with ARVD. The right ventricular free wall (arrow) appears smooth and regular, with no aneurysms. B, End-systolic axial bright blood image from the same patient. Note the focal crinkling of the right ventricle owing to discoordinate contraction (arrows).

MRI can also have a role in screening of first-degree relatives of ARVD cases. In one of our previous studies, we found that MRI frequently detects mild qualitative and regional functional abnormalities in first-degree relatives of ARVD probands with overall normal chamber sizes and volumes. We also noted focal discoordinate contraction of the right ventricular basal free wall on MRI was found to represent an early phenotypic expression of desmosomal mutation–positive (especially PKP2), asymptomatic first-degree relatives of ARVD probands. This finding showed good correlation with repolarization abnormalities on ECG and inducibility for ventricular arrhythmias.

Despite the diagnostic utility of MRI in ARVD, its specificity and reliability remain in question because of the subjectivity in the interpretation of its findings, dependence on image quality, over-reliance on intramyocardial fat and wall thinning, and lack of standardized protocol and technical and clinical expertise in cardiovascular MRI. Observers without extensive experience in MRI for ARVD can overdiagnose this condition, particularly when the only abnormalities observed are with MRI. MRI can be a low-yield test for the diagnosis of ARVD in children compared with adults. MRI should be considered as only a part of the multidisciplinary diagnostic work-up of the patient, and the final diagnosis of ARVD should be based on an integrated assessment of all noninvasive and invasive testing in reference to Task Force criteria.³⁵ Follow-up studies, in probands and suspected relatives, can be advantageous—keeping in mind the progressive and evolving nature of the disease.

DIFFERENTIAL DIAGNOSIS

Numerous clinically diverse conditions can mimic ARVD because of related histologic picture, ventricular tachycardia of right ventricular origin, or right ventricular enlargement and distorted right ventricular anatomy, and must be appropriately excluded (Table 65-8).¹¹^,³⁶ Right ventricular outflow tract tachycardia is one of the most important differential diagnoses from the clinical standpoint (Table 65-9).³⁷ A few other important conditions are discussed next.

TABLE 65-8 Differential Diagnosis of Arrhythmogenic Right Ventricular Dysplasia

* Whether right ventricular outflow tract tachycardia represents a form of arrhythmogenic right ventricular cardiomyopathies is still debated.

From Corrado D, Basso C, Thiene G. Arrhythmogenic right ventricular cardiomyopathy: diagnosis, prognosis, and treatment. Heart 2000; 83:588.

TABLE 65-9 Differences Between Right Ventricular Outflow Tract (RVOT) Tachycardia and Arrhythmogenic Right Ventricular Dysplasia

Features	RVOT Tachycardia	ARVD
Clinical Presentation
Family history	No	Frequently yes
Arrhythmias	Premature ventricular contractions, nonsustained ventricular tachycardia, or sustained ventricular tachycardia at rest or with exercise	Same
Sudden cardiac death	Rare	1%/yr
ECG Features
T wave morphology	T wave upright V₂-V₅	T wave inverted beyond V₁
Parietal block	QRS duration <110 ms in V₁-V₃	QRS duration >110 ms
Epsilon wave V₁-V₃	Absent	Present in one third of cases
Prolonged S wave upstroke	Rarely seen	Usually present
Signal-averaged ECG	Normal	Usually abnormal
Electrophysiology Study
Presence of more than one ECG morphology during tachycardia	Absent	Seen frequently
Fractionated diastolic potentials during ventricular tachycardia	Absent	Seen frequently
Programmed premature stimulation–induced ventricular tachycardia	Absent	Seen frequently
Imaging Features
Echocardiogram	Normal	Usually abnormal
Right ventricular ventriculogram	Usually normal	Usually abnormal
MRI	Usually normal	Usually abnormal

From Prakasa KR, Calkins H. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. Curr Treat Options Cardiovasc Med 2005; 7:467.

Sarcoidosis

Involvement of the ventricle in cardiac sarcoidosis often can mimic the ECG and structural changes in ARVD.³⁸ Presence of hilar lymphadenopathy should alert the physician to consider this diagnosis. MRI may reveal patchy left ventricular delayed hyperenhancement in a noncoronary distribution. Finally, an endomyocardial biopsy specimen of an affected region often reveals noncaseating granulomas, confirming the diagnosis of sarcoidosis.