Download Arrhythmogenic right ventricular dysplasia and sudden death

Rom J Leg Med 17 (2) 97 - 100 (2009)
© 2009 Romanian Society of Legal Medicine
Arrhythmogenic right ventricular dysplasia and sudden death.
Report of two cases
Ladislau Hecser*, Harald Jung, Katalin Palfi Siklodi, Dacian Biriş
Received: 18.02.2009/ Accepted in revised form: 9.04.2009
_____________________________________________________________________
Abstract: Arrhythmogenic right ventricular dysplasia or cardiomyopathy (ARVD or ARVC) is a heart
muscle disease, often familial, characterized by structural and functional abnormalities of the right ventricle due to
replacement of the myocardium by fatty and fibrous tissue. Clinical presentation of ARVD/ARVC usually consists of
arrhythmias of right ventricular origin that include isolated premature ventricular beats, sustained ventricular
tachycardia, and ventricular fibrillation that can lead to sudden death. The development of arrhythmogen right
ventricular dysplasia or cardiomiopathy appears to be related to the following two processes: (1) myocyte
degeneration (including apoptosis and transdifferentiation), which may be inherited, and (2) interstitial inflammation,
which may be infectious (probable postvital) or autoimmune in origin. Fatty infiltration, which is the hallmark of the
disorder, is considered to represent a secondary phenomen. Gene mutations have recently been identified and suggest
an underlying ion channel disorder. Fatty infiltration is nearly transmural and accompanied by thinning of the
muscular wall. Grossly, fatty infiltration generally spares the right ventricular trabeculations the ventricular septum
and the left ventricular free wall.
Authors present two cases, a 52-year-old and a 35-year-old women, previously healthy, with sudden death.
In both cases, marked fatty infiltration of the right ventricular myocardium was observed.
Key words: arrhythmogenic right ventricular dysplasia, sudden death
K
nowledge about the role of the right ventricle in health and disease historically
has lagged behind that of the left ventricle. Less muscular, restricted in its role to
pumping blood through a single organ, and less frequently or obviously involved than the left
ventricle in diseases of epidemic proportions such as myocardial ischemia, cardiomyopathy,
or valvulopathy, the right ventricle has generally been considered a mere bystander, a victim
of pathological processes affecting the cardiovascular system [1].
The right ventricle is affected by and contributes to a number of disease processes,
including perhaps most notably pulmonary hypertension caused by a variety of lung or
pulmonary vascular disease (cor pulmonale). Other diseases affect the right ventricle in different
ways, including global, left ventricular – or right ventricular – specific cardiomyopathy; right
ventricular ischemia or infarction; pulmonary or tricuspid valvular heart disease; and left-toright shunts [1].
Arrhythmogenic right ventricular dysplasia or cardiomyopathy [ARVD or ARVC] is a
heart muscle disease, often familial, characterized by structural and functional abnormalities of
the right ventricle due to replacement of the myocardium by fatty and fibrous tissue.
________________________
*) Corresponding author; Associate Professor L. Hecser, 540074 Tg.Mureş, str.Vulcan nr.10
Judet Mureş, Romania, tel./fax: 0265/215-240
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Hecser L et al
Arrhythmogenic right ventricular dysplasia and sudden death. Report of two cases
Clinical presentation of ARVD usually consists of arrhythmias of right ventricle origin
that include isolated premature ventricular beats, sustained ventricular tachycardia, and
ventricular fibrillation that can lead to sudden death [2, 3]. ARVD is an uncommon disorder
characterized by right ventricular dilatation and fibrofatty replacement of the right ventricular
myocardium (4]. Although it has been estimated that the disease afflicts about 1 in 5000 persons
in the United States, the exact prevalence is unknown [5].
In 80% the cases the initial manifestation occurs before the age of 40 years and includes
palpitations, presyncope or syncope, transient or sustained ventricular tachycardia, cardiac
arrest, congestive heart failure, or sudden unexpected death [5, 6, 7]. In many cases of sudden
death, there is no prior history of an underlying cardiac disorders [4].
Report of two cases
Case 1 A 35-yearold woman was hospitalized
in the Urological Clinic of
Tg. Mureş for a left kidney
calculus and hidronephrosis.
After the surgical intervention, the patient started
suddenly to complain of
thoracic pains, extreme
anxiety and dispnea and died
in less than 1 hour.
A forensic autopsy
was performed.
The right ventricle
was markedly dilated, and
very thin (the maximal
thickness of right ventricle
0,2 cm) with transmural
adipous invasion (Fig. 1, 2). Fig. 1 Heart. Right ventricle with adipose tissue (col. HE; x 40)
The heart weighted
280 g, maximum thickness
of left ventricle was 0.9 cm.
The right coronary artery
was markedly hypoplasic
(cir-cumference 0,3-0,4 cm).
Case 2 A 52 year old
woman collapsed suddenly
on a public side-way and died
before the arrival of an
ambulance. The personal
medical history provided no
relevant information. Postmortem toxicological investigation was negative for
common toxic substances
(including alcohol). The
autopsy revealed the presence
of moderately to markedly
dilated and thin (maximal Fig. 2 Heart. Right ventricle with adipose tissue (col. HE; x100)
thickness 0,3 cm) right ventricle. Transmural adipous invasion of the right ventricle wall was
present at various levels on serial sections. The heart weight was within the normal range (340 g).
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Vol. XVII, nr. 2, 2009
Low-power microscopic examination of right ventricular free wall revealed extensive
adiposity and small island of subendocardial myocytes (Fig. 3).
Discussion
Multiple theories
regarding the genesis of
ARVD has been described
[8]. In the dysontogenetic
theory, the absence of
myocardium is considered
to be the consequence of a
congenital aplasia or
hyperplasia of the right
ventricular wall, leading to
a parchment-like aspect.
The eponym Uhl anomaly
has been commonly used
in memory of the 8month-old infant described
by Uhl in 1952, with
“almost total absence of Fig. 3 Right ventricle with severe adiposity (col. VG; x 40)
the myocardium of the right ventricle” [8].
Only 27 years have elapsed from the time that the clinical profile of arrhythmogenic right
ventricular dysplasia/cardiomyopathy (ARVD/C) was first described [9]. Since then, this entity
has been found to have prevalence of about 1 in 5000 persons [10] and is well recognized in the
United States, Europe, and Asia. The usual clinical presentation of ARVD/C is that of palpations,
nonsustained ventricular tachycardia, and sustained ventricular arrhythmias. Uncommonly,
sudden cardiac death may be the first manifestation of the disease [11].
Arrhythmogenic right ventricular cardiomyopathy is characterized by myocyte loss due to
necrosis or apoptosis, as well as fatty or fibrofatty replacement. [5, 6, 7]. It primarily affects the
right ventricular free wall and may be focal or diffuse. The disease tends to progress from
subepicardium to subendocardium and is eventually associated with wall thinning, focal
aneurysm formation, and chamber dilatation.
Although ARVD may be diagnosed at any age, sudden deaths tend to occur between the
ages of 15 and 45 years, with a mean age of about 30 years [12, 13, 14]. Men are affected slightly
more often than women. In a series of 200 cases reported by Tabib et al. [14] the mean age was
34 years (range, 5-64 years), and 108 (54%) was male.
The development of ARVD appears to be related to the following 2 processes: [1]
myocyte degeneration (including apoptosis and transdifferentiation), which may be inherited, and
[2] interstitial inflammation, which may be infections (probably postviral) or autoimmune in
origin [5, 6, 7, 15, 16]. Both processes may be operative in some patients. Fatty infiltration, which
is the hallmark of the disorder, is considered to represent a secondary phenomenon. It has been
postulated that myocardial cell death in ARVD might represent a programmed death (“cell
suicide”) known as apoptosis [13]. This theory is very attractive because it offers a reasonable
explanation for the peculiar right ventricular involvement [17].
Link age analysis indicated that ARVD is a genetically heterogeneous disorder, but in
only about half of the patients can chromosomal defects be identified. For the autosomal
dominant form, defects have been localized to 1q42-q43 (ARVD2), 2q32 (ARVD4), 3q23
(ARVD5), 10q22 (ARVD7), 10p12-p14 (ARVD6), 14q12-q22 (ARVD3) and 14q23-q24
(ARVD1) [18,19]. Corresponding gene mutations have recently been identified and suggest an
underlying ion channel disorder [19]. A rare autosomal recessive form of ARDV, occurring with
Naxos disease (skin abnormalities and woolly hair), has been associated with defects at 6p24 and
17q21 [18, 19, 20]. Dalal et al. [21] and van Tintelen et al. [22] address the prevalence and
clinical expression of mutation in the plakophilin-2 gene (PKP2) in ARVD patient populations of
comparable size and fulfilling the task force diagnostic criteria [23].
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Hecser L et al
Arrhythmogenic right ventricular dysplasia and sudden death. Report of two cases
The ECG repolarization abnormalities are inverted T waves in right precordial leads (V2
and V3] in people aged >12 year and in absence of right bundle branch black. Fibro-fatty
replacement of myocardium on endomyocardial biopsy [23).
Annually in the United States, sudden unexpected death accounts for about half of all
cardiovascular deaths, or approximately 350 000 cases [24]. The underlying cases vary with age.
During the first 3 decades, myocarditis, cardiomyopathy, and coronary artery anomalies
predominate as causes of sudden unexpected death. However, for persons older than 30 years,
coronary atherosclerosis with ischemic heart disease is the most common cause [4]. Although
ARVD is considered a rare disorder, it accounted for 10% of all cases of sudden unexpected
cardiac death in the study of Tabib et al. [14]. However, in we cases of sudden or unexpected
deaths, the incidence of ARVD is very rare.
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