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CONTEMPORARY REVIEW
Arrhythmogenic right ventricular
dysplasia/cardiomyopathy: Screening, diagnosis, and
treatment
Philippine Kiès, MD, Marianne Bootsma, MD, PhD, Jeroen Bax, MD, PhD,
Martin J. Schalij, MD, PhD, Ernst E. van der Wall, MD, PhD
From the Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a heart muscle disorder
characterized pathologically by fatty or fibrofatty replacement and electrical instability of the right
ventricular myocardium. Clinical manifestations include structural and functional malformations (fatty
infiltration, dilatation, aneurysms) of the right ventricle, ECG abnormalities, and presentation with
ventricular tachycardias with left bundle branch block pattern or sudden death. The disease often is
familial with an autosomal inheritance. The typical hallmarks of ARVD/C are distributed in the
so-called “triangle of dysplasia.” The functional and morphologic characteristics are relevant to clinical
imaging approaches such as contrast angiography, echocardiography, radionuclide angiography, ultrafast computed tomography, and cardiovascular magnetic resonance imaging. Evident forms of the
disease are straightforward to diagnose based on a series of diagnostic criteria proposed by the
International Task Force for Cardiomyopathy. However, the diagnosis of early and mild forms of the
disease often is difficult. Treatment is directed toward preventing life-threatening ventricular arrhythmias in which radiofrequency ablation and implantable defibrillators play an increasing role. Despite
new diagnostic and therapeutic approaches in ARVD/C, uncertainties about the etiology of the disease,
the genetic basis, the appropriate diagnosis and therapy, and the clinical course of patients with
ARVD/C have resulted in several registries to increase our knowledge of this intriguing disease.
KEYWORDS Arrhythmogenic right ventricular dysplasia (ARVD/C); Screening; Diagnosis; Treatment
(Heart Rhythm 2006;3:225–234) © 2006 Heart Rhythm Society. All rights reserved.
The name arrhythmogenic right ventricular dysplasia
(ARVD) was coined for the first time in 1978 by Frank
and Fontaine.1 At that time, the disease was defined as
“total or partial replacement of right ventricular muscle
by adipose and fibrous tissue associated with arrhythmias
of left bundle branch block configuration.” In 1996, the
World Health Organization (WHO) and the International
Society and Federation of Cardiology (ISFC) decided
that ARVD had to be considered as a manifestation of a
cardiomyopathy (ARVD/C).
In recent years, ARVD/C has drawn considerable attention because of better understanding of the underlying
mechanisms, genetic background, improved diagnostic ca-
Address reprint requests and correspondence: Dr. Ernst E. van der
Wall, Department of Cardiology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
E-mail address: [email protected].
(Received July 20, 2005; accepted October 14, 2005.)
pabilities for early detection of ARVD/C, and use of more
advanced therapies.
Incidence/prevalence
ARVD/C occurs in young adults with a male-to-female ratio
of 2.7/1.0, but the true incidence is unknown. The prevalence of the disease in the general population is estimated at
0.02% to 0.1% (average 1:5,000) but is dependent on geographic circumstances.2 In certain regions of Italy (Padua,
Venice) and Greece (Island of Naxos), an increased prevalence of 0.4% to 0.8% for ARVD/C has been reported.2
Eighty percent of the disease is diagnosed in patients
younger than 40 years. ARVD/C should be suspected in all
young patients presenting with syncope, ventricular tachycardia, or cardiac arrest. Similar to the incidence, the true
prevalence of the disease is unknown because the diagnosis
may be missed in a substantial number of patients.
1547-5271/$ -see front matter © 2006 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2005.10.018
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Heart Rhythm, Vol 3, No 2, February 2006
Genetic factors
A familial predilection of ARVD/C has been recognized.
The clinical findings related to ARVD/C suggested a familial occurrence of 30% to 50% with autosomal dominant
inheritance, various degrees of penetrance, and polymorphic
phenotypic expression. The diagnosis of ARVD/C may
have important consequences for direct relatives because
they have an increased chance of having the disease. Genetic screening for early detection of healthy carriers may
play a fundamental role in primary prevention, considering
that sudden death often occurs as a first manifestation of the
disease. The genes involved and the molecular defects are
not fully known, although several ARVD/C loci have been
identified. Genetic disorders have been identified on chromosomes 14q23-q24 (ARVD1), 1q42-q43 (ARVD2),
14q12-q22 (ARVD3), 2q32 (ARVD4), 3p23 (ARVD5),
10p12-14 (ARVD6), 10q22, 6p24 (ARVD8), and 12p11
(ARVD9).3 An autosomal recessive variant of ARVD/C
that is associated with palmoplantar keratosis and woolly
hair (Naxos disease) has been mapped on chromosome
17q21, whereby plakoglobin and desmoplakin have been
identified as the responsible genes. Plakoglobin participates
in cell-to-cell junctions, and it is postulated that inadequate
cell adherence injures the cardiac cell membranes, leading
to cell death and fibrofatty replacement. Mutations in the
desmosomal protein plakophilin-2 reportedly are common
in ARVD/C patients. In addition, the cardiac ryanodine
receptor gene may be involved in the disease. The ryanodine
receptor probably plays an important role in inducing catecholamine-related ventricular tachycardia. It has been suggested that the advent of genetic testing will provide the
gold standard for diagnosis.4 However, the findings of polymorphisms in ARVD/C and the fact that 50% of ARVD/C
families do not show any linkage with the identified chromosomal loci stress the need to exploit an ARVD/C registry
and to install tissue DNA banks.
Figure 1 Histologic specimen showing combination of fatty
deposits (white) and interstitial fibrosis (blue) incorporating atrophic myocytes (red) (azocarmine-aniline staining, magnification
⫻250). (Reproduced with permission from Van der Harst Tintelen
JP, Suurmeijer AJ, van Veldhuisen DJ. Arrhythmogenic rightventricular cardiomyopathy: different manifestations as precursors
of sudden death which might be prevented. Ned Tijdschr Geneesk
2004;149:2396 –2402.)
outflow tract, apex, and infundibulum. However, the fibrofatty
pattern of ARVD/C is limited not only to the right ventricle;
the disease also might migrate to the interventricular septum
and the left ventricular free wall, with a predilection for the
posteroseptal and posterolateral areas. Left ventricular involvement may even be the first manifestation of the disease. The
affected areas may form an “electricophysiologic hole” potentially constituting a substrate for reentrant arrhythmias.
Anatomy/histology
Etiology
The most striking morphologic feature of the disease is the
diffuse or segmental loss of right ventricular myocytes with
replacement by fibrofatty tissue and thinning of the right ventricular wall (Figure 1). Fatty infiltration of the right ventricle
per se probably is a different process that may not be considered synonymous with ARVD/C. Therefore, the diagnosis of
ARVD/C should only be made in the presence of fibrosis,
which probably is more arrhythmogenic than just fatty infiltration. Fibrofatty replacement usually begins in the subepicardium or mediomural layers and progresses to the subendocardium. Only the endocardium and the myocardium of the
trabeculae may be spared. Anatomic malformations of the right
ventricle consist of mild-to-severe global right ventricular dilation, right ventricular aneurysms, and segmental right ventricular hypokinesia. The sites of involvement are found in the
so-called “triangle of dysplasia,” namely, the right ventricular
The exact etiology of ARVD/C is not fully understood. Four
theories on the etiology of ARVD/C have been introduced:
dysontogenic, degenerative, inflammatory, and apoptotic.
D’Amati et al5 proposed a transdifferentiation theory, which
is based on the hypothesis that cells can change from muscle
to adipose tissue. A viral component also has been suggested in the pathogenesis of ARVD/C. Basso et al6 described a novel, genetically transmitted animal model in
boxer dogs, which may aid in understanding the pathogenic
mechanism in ARVD/C.
ECG findings
The anatomic damage present in ARVD/C may modify
electrical activation and repolarization. Generally, ECG ab-
Kiès et al
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
227
Figure 2 Precordial leads of an ECG from a 44-year-old woman recorded during regular sinus rhythm, with an epsilon wave (arrow) in
leads V1–V. The ECG shows a right bundle branch block pattern.
normalities can be observed in almost 90% of patients with
ARVD/C. The ECG in patients with ARVD/C usually
shows sinus rhythm, QRS duration ⬎110 ms in lead V1, a
terminal deflection within or at the end of the QRS complex
(called epsilon wave) in leads V1–V3 (30% of patients), and
inversion of T waves in the right precordial leads (50%–
70% of patients) (Figure 2).7 Complete right bundle branch
block is found in approximately 15% of patients and incomplete right bundle branch block in 18% of patients with
ARVD/C. In the presence of right bundle branch block
pattern, selective prolongation of the QRS duration in leads
V1–V3 compared with lead V6 (⬎25 ms, parietal block) is
an important hallmark of ARVD/C. Additional ECG markers have been reported, such as the ratio of QRS duration in
leads V1⫹V2⫹V3 vs V4⫹V5⫹V6 ⱖ1.2 and a prolonged S
wave upstroke in V1–V3 ⱖ55 ms in the absence of right
bundle branch block.8 Several studies have shown a relation
between ARVD/C and the Brugada syndrome. This syndrome is associated with an ECG pattern of right bundle
branch block and right ventricular precordial ST-segment
elevation, which may be responsible for the sudden death of
young adults at rest or during sleep.
Exercise and ventricular arrhythmias
ARVD/C usually is characterized by the occurrence of
symptomatic right ventricular arrhythmias during exercise.
Islands of fibrofatty tissue may form the arrhythmogenic
substrate underlying these arrhythmias that typically are
induced by adrenergic stimulation. During exercise testing,
50% to 60% of patients with ARVD/C show ventricular
arrhythmias, which are characteristically monomorphic and
have a predominant left bundle branch block pattern in 96%
(Figure 3). An inferior QRS axis during ventricular tachycardia reflects the right ventricular outflow tract as site of
origin, whereas a superior axis reflects the right ventricular
inferior wall as site of origin. The occurrence of arrhythmic
cardiac arrest due to ARVD/C is significantly increased in
athletes. Particularly in certain regions in Italy, ARVD/C
has been shown to be the most frequent disease (22%)
leading to exercise-induced cardiac death in athletes. As a
result, a diagnosis of ARVD/C is considered incompatible
with competitive sports and/or moderate-to-high intensity
level recreational activities.9
Clinical presentation
The clinical presentation varies widely because ARVD/C
includes a spectrum of different conditions rather than a
single identity. Different pathologic processes may manifest
a diversity of symptoms, such as fatigue, atypical chest pain,
syncope, or acute coronary syndrome. ARVD/C is a disease
that may have a temporal progression, and the disease may
present differently according to the time of presentation.10
There may be (1) a symptomatic form with transient or
sustained ventricular tachycardia of left bundle branch
block configuration, although right bundle branch block
configuration also can be observed; (2) an asymptomatic
form consisting of ventricular ectopic beats (⬎1,000/24
hours); (3) right ventricular failure with or without arrhyth-
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Heart Rhythm, Vol 3, No 2, February 2006
Figure 3 Twelve-lead ECG from a 25-year-old man recorded during ventricular tachycardia with a left bundle branch block morphology
and a slight-to-moderate right axis, typically originating from the right ventricular outflow tract.
mias; and (4) a masked form in which sudden death, usually
during exercise, is the first clinical presentation. Overall,
judging the accurate position of the patient on the time scale
of the spectrum is difficult, and some patients may remain
stable for several decades.
Natural history
The natural history of ARVD/C is determined by both
cardiac electrical instability and progressive right ventricular dysfunction. In the major reported studies, mortality
rates ranged from 4% to 20% for similar follow-up periods.
In ARVD/C, both sexes have similar mortality risk, with a
peak of risk during the fourth decade. ARVD/C may account for up to 5% of sudden deaths in young adults in the
United States and 25% of exercise-related deaths in the
Veneto region of Italy. Unless sudden cardiac death occurs,
progressive impairment of cardiac function may result in
right or biventricular heart failure late in the evolution of
ARVD/C, usually in a time course of 4 to 8 years after
typical development of complete right bundle branch block.
Fontaine et al11 evaluated the natural history of 130
ARVD/C patients who were followed from 1977 to 2000.
The authors reported 21 cardiac deaths, of which 14 were
due to progressive heart failure and 7 to sudden cardiac
death, resulting in an annual mortality of 2.3%. In most
patients, the mechanism of sudden death in ARVD/C is
acceleration of ventricular tachycardia with ultimate degeneration into ventricular fibrillation. Generally, right ventric-
ular failure and left ventricular dysfunction were independently associated with cardiovascular mortality.
Diagnosis
A definite diagnosis of ARVD/C is based on histologic
demonstration of transmural fibrofatty replacement of right
ventricular myocardium at either autopsy or surgery. Myocardial biopsy lacks sufficient sensitivity because, for safety
reasons, the biopsy is performed mostly in the interventricular septum, whereas the typical pathologic changes of
ARVD/C are more pronounced in the right ventricular free
wall. In 1994, McKenna et al7 established the criteria for
diagnosing ARVD/C in a Task Force report on ARVD/C.
The diagnosis of ARVD/C is based on several major and
minor criteria involving structural, histologic, ECG, arrhythmic, and genetic factors (Table 1). In 2002, Hamid et
al12 proposed a modification of the Task Force criteria for
diagnosing ARVD/C in first-degree relatives of patients
with proven ARVD/C. When standard criteria were applied,
28% of patients had ARVD/C, but when all cardiovascular
parameters were taken into account, 48% of relatives had
evidence of the disease. At variance with the Task Force
criteria, minor abnormalities of the current ECG, Holter, or
echocardiographic criteria may indicate familial involvement. As the Task Force criteria were reached by expert
consensus opinion, based primarily on tertiary center experience, the criteria are highly specific but lack sensitivity.
An additional drawback of the criteria is that the Task Force
did not specify the preferred order of imaging techniques to
Kiès et al
Table 1
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
229
Task Force diagnostic criteria for arrhythmogenic right ventricular dysplasia/cardiomyopathy
Major criteria
I
II
Global and/or regional dysfunction and
structural alterations
Tissue characterization of walls
Severe dilation and reduction of right
ventricular ejection fraction with no
(or only mild) left ventricular
impairment
Localized right ventricular aneurysms
(akinetic or dyskinetic areas with
diastolic bulging)
Severe segmental dilation of the right
ventricle
Fibrofatty replacement of myocardium
on endomyocardial biopsy
III Repolarization abnormalities
IV
Depolarization/conduction
abnormalities
V
Arrhythmias
VI
Family history
Epsilon waves or localized prolongation
(⬎110 ms) of the QRS complex in
right precordial leads (V1–V3)
Familial disease confirmed at necropsy
or surgery
Minor criteria
Mild global right ventricular dilation and/or
ejection fraction reduction with normal left
ventricle
Mild segmental dilation of the right ventricle
Regional right ventricular hypokinesia
Inverted T waves on right precordial leads (V2
and V3) (age ⬎12 years; in absence of
right bundle branch block)
Late potentials (signal-averaged ECG)
Left bundle branch block-type ventricular
tachycardia (sustained and nonsustained)
(ECG, Holter, exercise testing)
Frequent ventricular extrasystoles (⬎1,000/
24 hours) (Holter)
Familial history of premature sudden death
(⬍35 years) due to suspected right
ventricular dysplasia
Familial history (clinical diagnosis based on
present criteria)
To fulfill the appropriate criteria for arrhythmogenic right ventricular dysplasia/cardiomyopathy, patients must meet either two major criteria, one major
plus two minor criteria, or four minor criteria
Adapted from McKenna et al.7
ECG ⫽ electrocardiogram; LV ⫽ left ventricle; RV ⫽ right ventricle
examine and score right ventricular morphology and function. A standardized imaging protocol for the different imaging techniques and a quantification of the criteria were not
provided. Consequently, evident forms of the disease are
straightforward to diagnose, but diagnosis of early and mild
forms of the disease often is difficult. Based on our experience, serial reevaluation of Task Force-negative patients
suspected of having ARVD/C with minor ECG abnormalities is indicated because frequently functional/structural abnormalities only become apparent over time.13
Differential diagnosis
The most important differential diagnosis consists of Uhl
disease, which is characterized by a paper-thin right ventricle due to almost complete absence of myocardial muscle
fibers probably as a result of apoptotic destruction. Uhl
disease can be differentiated from ARVD/C by the absence
of a major gender difference (male-to-female ratio 1.3),
absence of a family history, and presentation in early childhood, usually with congestive heart failure as the first symptom. Also, the differentiation of ARVD/C from myocarditis
and biventricular cardiomyopathy may be difficult, particu-
larly when the left ventricular ejection fraction is slightly
below 50%.
Many patients with ARVD/C present with right ventricular outflow tract tachycardias as a first sign of the disease.
However, right ventricular outflow tract tachycardias with a
left bundle branch block pattern and inferior QRS axis
represent a broad clinical spectrum. These tachycardias are
not only observed in ARVD/C patients; they may be of
idiopathic origin and can be seen in patients with coronary
artery disease, right or biventricular cardiomyopathy, sarcoidosis, and congenital heart disease. Based on electrophysiologic characteristics such as inducibility of ventricular tachycardia, the mechanism underlying the ventricular
tachycardia (reentry vs triggered automaticity), presence of
more than one ECG morphology, and fragmented potentials, usually one can distinguish between idiopathic right
ventricular outflow tract arrhythmias and arrhythmias due to
ARVD/C.14
Myocardial imaging
In addition to the Task Force criteria, imaging modalities
such as contrast angiography, echocardiography, radioiso-
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Heart Rhythm, Vol 3, No 2, February 2006
is akinesis/dyskinesis of the inferior wall and the right
ventricular apex.15 Due to its restricted acoustic window in
obese patients and in patients with pulmonary emphysema,
transthoracic echocardiography is not always the optimal
imaging technique for visualizing the right ventricle; in
these patients, transesophageal echocardiography is the preferred approach. Peters et al16 compared intracardiac ultrasound with contrast angiography in 25 patients with
ARVD/C and showed additional details in 12 patients with
the ultrasound technique. In the near future, contrast echocardiography may help in diagnosing ARVD/C because of
improved endocardial border delineation and enhanced right
ventricular opacification (Figure 5). In clinical practice,
echocardiography will remain the initial diagnostic approach in patients suspected of having ARVD/C.
Figure 4 Right ventricular angiogram of a patient with arrhythmogenic right ventricular dysplasia/cardiomyopathy showing
prominent trabeculations and akinetic aneurysmatic bulges of the
right ventricular outflow tract (arrow).
tope techniques, computed tomography, and cardiovascular
magnetic resonance imaging may play a specific and unique
role in establishing and affirming the diagnosis of ARVD/
C.7 However, one should realize that imaging techniques
are always dependent upon technical aspects of the study,
focusing on the right side of the heart, the expertise of the
technician, the type of equipment used, and the expertise of
the interpreter. Whenever possible, an abnormality observed
with one imaging technique should be verified using another
imaging modality.
Right ventricular contrast angiography
Right ventricular contrast angiography usually is regarded
as the reference standard for the diagnosis of ARVD/C.
Angiographic evidence of ARVD/C consists of akinesis/
dyskinetic bulgings localized in the anatomic triangle of
dysplasia and the presence of hypertrophic trabeculae (Figure 4). However, the invasive nature of the angiographic
technique, x-ray exposure, common occurrence of ventricular extrasystoles during contrast injection, and considerable interobserver variability regarding the visual assessment of right ventricular motion abnormalities preclude the
use of right ventricular angiography as a primary diagnostic
technique.
Radioisotope techniques
Radionuclide angiography, by showing abnormal right ventricular function with left ventricular involvement, is useful
for predicting subsequent cardiac death in ARVD/C. Myocardial perfusion scintigraphy allows noninvasive assessment of right ventricular damage in patients with arrhythmias due to ARVD/C. This technique may distinguish
patients with ARVD/C from those with idiopathic right
ventricular outflow tract tachycardias.
Use of radioisotopes with specific affinity for the betaadrenoceptor allows investigation of the neuronal mechanisms of the heart. In patients with ARVD/C, cardiac sympathetic innervation is diminished, which may have
implications for early recognition and treatment of arrhythmias.17 Current limitations of radioisotope imaging, such as
suboptimal spatial resolution and inherent radiation burden,
prohibit the use of radionuclide imaging as a first-line approach in patients with ARVD/C.
Echocardiography
Echocardiography is the most widely used noninvasive
technique for assessing cardiac performance in patients with
ARVD/C. The most conspicuous findings by echocardiography are right ventricular dilation, enlargement of the right
atrium, isolated dilatation of the right ventricular outflow
tract, increased reflectivity of the moderator band, localized
aneurysms, and decreased fractional area change. There also
Figure 5 Echocardiographic image with contrast of the right
ventricle (RV) of a 25-year-old man of a severely dilated right
ventricle clearly showing enhanced border delineation with a localized aneurysm (asterisk) of the right ventricular outflow tract.
Kiès et al
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
231
Computed tomography
Computed tomography is capable of diagnosing patients
with ARVD/C. Electron-beam computed tomography provides superior resolution, enabling improved visualization
of the right and left ventricles because of its ability to
acquire cardiac images in cross-section. Dery et al18 were
the first to demonstrate a dilated hypokinetic right ventricle
in a patient with ARVD/C. Specific findings of ARVD/C on
electron-beam computed tomography are the presence of
epicardial fat, intramyocardial fat deposits, conspicuous trabeculations with low attenuation, dilated hypokinetic right
ventricle, and scalloped appearance of the right ventricular
wall. At present, there are no reports on the use of multislice
computed tomography in ARVD/C patients. In the near
future, this advanced modality may improve the capability
to detect the disease by virtue of its enhanced temporal and
spatial resolution. In addition, computed tomography may
be of value in serially evaluating ARVD/C patients with an
implantable cardioverter-defibrillator. Because the radiation
burden is high, multislice computed tomography currently
is not the optional imaging modality for initial screening of
patients suspected of having ARVD/C.
Cardiovascular magnetic resonance imaging
Theoretically, cardiovascular magnetic resonance imaging
offers the optimal noninvasive imaging approach in patients
with right and left ventricular dysfunction, in view of its
high spatial resolution and unlimited field of view.19 This
modality allows visualization of the right ventricle, not only
anatomically and morphologically but also in functional and
flow dynamic terms. Anatomic and morphologic abnormalities in patients with ARVD/C include intramyocardial fat
deposits, focal wall thinning, wall hypertrophy, trabecular
disarray, and right ventricular outflow tract enlargement.
The ability of this technique to characterize adipose infiltration by showing myocardial areas with high signal intensity is unique in diagnosing ARVD/C.20,21 Functional abnormalities consist of right ventricular aneurysms, regional
thinning, right ventricular dilation, failure of systolic thickening, and impaired global and diastolic right ventricular
function. In addition, cardiovascular magnetic resonance
imaging allows velocity mapping of tricuspid flow, which
may be an early but nonspecific sign of the disease. Cardiovascular magnetic resonance imaging is more accurate in
analyzing right ventricular function than most other imaging
modalities because it allows a truly three-dimensional calculation of ventricular volumes.
Midiri et al22 used the following five anatomic, morphologic, and functional cardiovascular magnetic resonance
criteria for diagnosis of ARVD/C: (1) presence of highsignal intensity areas indicating the substitution of myocardium by fat, (2) ectasia of right ventricular outflow tract, (3)
dyskinetic bulges, (4) right ventricular dilation, and (5) right
atrial enlargement (Figure 6).22 However, much experience
Figure 6 Axial T1-weighted black blood spin-echo cardiovascular magnetic resonance image showing extensive transmural
fatty replacement of the right ventricular (RV) myocardium (arrow). (Reproduced with permission from Kayser HW, van der
Wall EE, Sivananthan MU, Plein S, Bloomer TN, de Roos A.
Diagnosis of arrhythmogenic right ventricular dysplasia: a review.
Radiographics 2002;22:639 – 648.)
in interpretation of cardiovascular magnetic resonance imaging is required because of the normal variants of the right
ventricle, which in general are greater than for the left
ventricle. Of interest, studies revealed that focal wall-motion abnormalities are much more reliable indicators than
intramyocardial fat infiltration, which appears to have a
poor interreader agreement. Bomma et al23 demonstrated
that the diagnosis of ARVD/C cannot rely solely upon
qualitative features noted by cardiovascular magnetic resonance imaging as 77% of patients with initial abnormal
cardiovascular magnetic resonance imaging findings of intramyocardial fat/wall thinning could not be confirmed at
reevaluation.
Consequently, there was a high rate of misdiagnosis of
ARVD/C based of the supposed finding of adipose infiltration by cardiovascular magnetic resonance. Because fibrosis
may be more specific than intramyocardial fat, Tandri et al24
used an improved imaging approach to visualize the intramyocardial fibrotic process. The authors showed for the
first time that contrast-enhanced cardiovascular magnetic
resonance imaging allowed identification of myocardial fibrosis by increased signal enhancement in the majority of
patients with ARVD/C.
Several studies have addressed the value of cardiovascular magnetic resonance imaging in patients showing right
ventricular outflow tract tachycardias as a first manifestation
of ARVD/C. Patients with idiopathic right ventricular outflow tract tachycardias were shown to be morphologically
indistinguishable from healthy individuals. Kayser et al25
232
showed a high diagnostic accuracy for detecting ARVD/C
in patients with ventricular tachycardia with a left bundle
branch block pattern.
In summary, cardiovascular magnetic resonance imaging
provides important anatomic, morphologic, functional, and
flow-dynamic criteria for diagnosing ARVD/C. Although
fatty infiltration has been shown to have less diagnostic
accuracy than wall-motion abnormalities, cardiovascular
magnetic resonance imaging is an important technique for
detecting structural abnormalities suggestive of ARVD/C,
but the imaging findings should be confirmed by other
imaging modalities such as echocardiography and/or angiography.19 Accordingly, the diagnosis of ARVD/C must
be made based on Task Force criteria and not on structural
abnormalities alone. As a result, echocardiography will be
the initial diagnostic approach in most centers.
Treatment
There are five therapeutic options in patients with ARVD/C:
(1) antiarrhythmic agents, (2) radiofrequency ablation, (3)
implantable cardioverter-defibrillator therapy, (4) heart failure treatment, and (5) surgical treatment.
1. The effects of antiarrhythmic drug therapy are difficult to
assess because of small series of patients and limited
time to follow-up. Wichter et al26 found sotalol was more
effective than beta-blocking agents or amiodarone both
in patients with inducible ventricular tachycardia and
those with noninducible ventricular tachycardia. However, it is not known whether sotalol is able to prevent
sudden death, even in patients tested by programmed
electrical stimulation.
2. Catheter ablation can be considered in case of drug
intolerance or ineffectiveness.27 To guide radiofrequency ablation, electroanatomic mapping constitutes a
suitable way to visualize the myocardium in patients
with ARVD/C. Boulos et al28 were the first to describe
three-dimensional electroanatomic mapping using the
CARTO technique. By studying spatial association of
endocardial electrograms, significant loss of myocytes
was shown to result in the recording of low-amplitude,
fractionated endocardial ECGs with a prolonged duration (Figure 7). There was an excellent concordance with
echocardiography and cardiovascular magnetic resonance imaging in detecting the pathologic substrate.
Success of the ablation procedure may be affected by
the progressive and diffuse nature of the disease, resulting in multiple arrhythmogenic foci, which are difficult
to abolish. Fontaine et al29 studied 50 patients who were
followed for a mean of 5.4 years, and the authors reported success rates of 32%, 45%, and 66% after one,
two, and three ablations, respectively. Most of these
patients had not responded to pharmacologic therapy.29
In our institution, radiofrequency ablation proved to be
successful in 32 patients with ARVD/C and drug-refrac-
Heart Rhythm, Vol 3, No 2, February 2006
Figure 7 Recording during electrophysiologic study of a 45year-old female displaying surface ECG leads I, II, aVF, V1, and
V6 and endocardial electrograms recorded in the high right atrium
(HRA), His bundle (His tip), and right ventricular apex (RVa)
during RV apex pacing. Note the highly fragmented prolonged
signal (arrow) reflecting diminished local endocardial conduction
velocity.
tory ventricular tachycardia, with an initial success rate
of 88%. However, we observed procedure-related complications, such as myocardial perforation, in two patients. In addition, one patient required pericardiocentesis for pericardial effusion. In line with previous studies,
we observed recurrences in 7 (29%) patients during follow-up (Figure 8).30
3. Implantable cardioverter-defibrillator therapy is indicated in case of serious risk of sudden death.31 Patients
at highest risk are those who have been resuscitated,
those who are unresponsive or intolerant of antiarrhythmic therapy (secondary prevention), and those with the
disease who have a family history of cardiac arrest in
first-degree relatives (primary prevention). There is no
evidence that patients who have a positive family history
but no evidence of the disease are at exceptional high
risk. Although an implantable cardioverter-defibrillator
has been shown to be the most effective safeguard
against sudden arrhythmic death in large patient populations with ARVD/C, its precise role still needs to be
defined.32,33 Programming the implantable cardioverterdefibrillator is difficult in ARVD/C patients because they
may develop supraventricular and ventricular tachyarrhythmias with similar rates. In addition, the fibrofatty
nature of the right ventricle may preclude proper sensing
of the implantable cardioverter-defibrillator. Wichter et
al32 showed a high incidence of lead-related adverse
events in 60 patients with ARVD/C who received implantable cardioverter-defibrillator therapy because of
resuscitated cardiac arrest or sustained ventricular tachycardia. In a series of 132 patients, Corrado et al33 showed
that five patients required placement of an additional
septal lead due to loss of ventricular sensing and/or
pacing, and that four patients had an increase in defibrillation threshold. Overall, the major clinical question remains whether it would be possible to identify those
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Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
233
5. More than 20 years ago, surgical treatment was introduced, initially consisting of right ventriculotomy. Total
disconnection of the right free wall then was tried. This
approach was abandoned because of the risk of developing right ventricular failure, the increased availability
of cardiac transplantation, and the improvement in the
technology of implantable cardioverter-defibrillators.
Occasionally, disconnection surgery or right ventricular
cardiomyoplasty is a useful therapeutic option.
Conclusion
Figure 8 Catheter ablation of a drug-refractory ventricular
tachycardia in a 26-year-old man with arrhythmogenic right ventricular dysplasia/cardiomyopathy using a three-dimensional mapping system to determine the location of the ablation catheter.
After induction of ventricular tachycardia, an anatomic model of
the right ventricular (RV) outflow tract is constructed by dragging
the ablation catheter over the endocardium of the RV outflow tract.
Simultaneously, electrograms are recorded sequentially at multiple
sites, and the local activation time (relative to the surface ECG) is
marked automatically, superimposing a color-coded activation
map on the RV outflow tract model. Activation maps are used to
identify the site of earliest endocardial activity. At these sites,
small areas of electrograms consisting of multiple small deflections (fragmented electrograms) are often found. In this threedimensional model, the endocardial position of an area with fragmented electrograms (2 ⫻ 3 cm2) could be delineated accurately
using the RV outflow tract model (white dots). This entire area was
ablated and resulted in termination and noninducibility of the
ventricular tachycardia. TV ⫽ tricuspid valve. (Reproduced with
permission from de Groot NM, Schalij MJ, van der Wall EE. Area
ablation of ventricular tachycardia in a patient with arrhythmogenic right ventricular cardiomyopathy. Heart 2003;89:703.)
patients with ARVD/C who could benefit most from
implantable cardioverter-defibrillator placement based
on anticipated knowledge such as genetic screening.34 In
our institution, placement of an implantable cardioverterdefibrillator is indicated in patients with ventricular arrhythmias and a positive family history, ventricular
tachycardia/fibrillation prone to collapse, hemodynamically unstable ventricular tachycardias, or frequently occurring stable ventricular tachycardias that are difficult
to abolish by radiofrequency catheter ablation. In all
other patient categories, we prefer to start with sotalol as
the primary drug of choice.
4. When the disease has progressed to right ventricular or
biventricular failure, treatment consists of the current
therapy for heart failure, including diuretics, beta-blocking agents, angiotensin-converting enzyme inhibitors,
and anticoagulants. In case of intractable right ventricular failure, cardiac transplantation may be the only remaining alternative.
ARVD/C is a heart muscle disorder of unknown course that
is characterized pathologically by fibrofatty replacement of
the right ventricular myocardium and electrical instability.
Clinical manifestations include structural and functional
malformations of the right ventricle, ECG abnormalities,
and presentation with ventricular tachycardia with left bundle branch block pattern or sudden death. Although in most
centers echocardiography will remain the initial screening
approach for patients suspected of having ARVD/C, cardiovascular magnetic resonance imaging provides important
anatomic, morphologic, functional, and flow-dynamic criteria to aid in the diagnosis of ARVD/C. Nevertheless, the
diagnosis of ARVD/C consists of a combination of ECG
and morphologic abnormalities as well as evidence of familial disease. Genetic evaluation is becoming increasingly
important in confirming the diagnosis in probands and family members. Pharmacologic treatment remains useful, but
radiofrequency ablation and implantable cardioverter-defibrillator therapy are increasingly important therapeutic approaches in patients with ARVD/C. However, remaining
uncertainties about the etiology of the disease, the genetic
basis, the appropriate diagnosis and therapy, and the clinical
course of patients with ARVD/C have resulted in initiation
of several registries to increase our knowledge of this intriguing disease.4,35,36 Currently, large clinical trials of
ARVD/C patients are in progress, such as the European
ARVD Registry and the Multidisciplinary Study of Right
Ventricular Dysplasia (US ARVD Study).4,35,36 Hopefully
these registries will improve our knowledge of ARVD/C.
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