Histology of sudden death in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

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Guy Fontaine and Paul Fornes
Cardiomyopathy/Dysplasia
Histology of Sudden Death in Arrhythmogenic Right Ventricular
ISSN: 1524-4539
Copyright © 2004 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online
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doi: 10.1161/01.CIR.0000135590.37950.30
2004, 110:e20
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Letters to the Editor must not exceed 400 words in length and must be limited to three authors and five references. They should not have
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Histology of Sudden Death in Arrhythmogenic
Right Ventricular Cardiomyopathy/Dysplasia
To the Editor:
In a recent issue of Circulation, Tabib et al1reported the largest
ever published series of sudden cardiac deaths caused by arrhyth-
mogenic right ventricular cardiomyopathy (ARVC/D).
The authors addressed the controversial issue of the histologic
definition of ARVC/D. Fatty replacement of the right ventricular
myocardium is the salient feature in ARVC/D. “Fatty” and “fibro-
fatty” patterns have been distinguished, depending on the presence
of additional fibrosis.2Morphometric investigations performed by
Burke et al3suggested that fatty and fibrofatty patterns represented
2 distinct entities. We agree with Tabib et al1that disorganization or
isolation of myocardial cells within fat is necessary for the diagno-
sis, pure fat characterizing a different entity.
Asecondpointofcontroversyistheastonishingwiderange,from
5% up to 80% of cases, in which lymphocytic infiltrates have been
reported. Different methods of quantification of lymphocytes may
explain this range. We follow the opinion of the group of Padoua
considering that presence of a small number of lymphocytes may be
significant. A mild lymphocytic infiltrate can be arrhythmogenic as
suggested by our recent observation of increased C-reactive protein
in the acute phase of ventricular tachycardia in ARVD and not
ARVC.4Myocarditis may also explain replacement fibrosis in some
patients with a hypertrophied heart. This feature is more frequently
observed in males than in females, because of the protective effect
of female hormones on infection (S. Hüber, personal communica-
tion, 1996). We also agree with Tabib et al1that the presence of
lymphocytes is an “aggravating factor.” In our understanding of the
disease, inflammation explains the bimodal nature of left ventricular
ejection fraction in the most severe forms of ARVC.5
In the Tabib et al1study, almost 70% of hearts had abnormal
conduction tissue. To our knowledge, no other studies have reported
such a finding. All cardiovascular pathologists are aware of the
difficulty in interpreting findings involving the conduction tissue.
Lesions of the conduction tissue are often overestimated. Two
examples are illustrated in this paper. In our opinion, the micropho-
tographsarenotconvincing,becausenolow-magnificationviewhas
been provided to prove location of fibrosis/adipocytes. In our
clinical experience involving ?200 ARVC patients, ventricular
arrhythmias are frequent, and atrioventricular block is rare. Pace-
makers have been implanted in 12 patients because of bradycardias
that were mostly attributed to therapeutics used to control
tachycardias. In this context, we would like to have further expert
opinions from both clinical and pathology teams, to make sure that
findings reported in this paper are relevant.
Guy Fontaine, MD, PhD
Paul Fornes, MD, PhD
Institut de Cardiologie
Hôpital de la Pitié Salpe ˆtrière
Paris, France
1. Tabib A, Loire R, Chalabreysse L, et al. Circumstances of death and gross
and microscopic observations in a series of 200 cases of sudden death
associated with arrhythmogenic right ventricular cardiomyopathy and/or
dysplasia. Circulation. 2003;108:3000–3005.
2. Thiene G, Nava A, Corrado D, et al. Right ventricular cardiomyopathy and
sudden death in young people. N Engl J Med. 1988;318:129–133.
3. Burke AP, Farb A, Tashko G, et al. Right ventricular cardiomyopathy and
fatty infiltration of the right ventricular myocardium: are they different
diseases? Circulation. 1998;97:1571–1580.
4. Bonny A, Fontaine G, Hidden-Lucet F, et al. Role of inflammation in the
mechanism of onset of ventricular tachycardia in arrhythmogenic right ven-
tricular dysplasia. Abstract. Circulation 2003;108(suppl IV):IV-1032.
5. Fontaine G, Fontaliran F, Rosas Andrade F, et al. The arrhythmogenic right
ventricle. dysplasia versus cardiomyopathy. Heart Vessels 1995;10:227–235.
Response
We thank Drs Fontaine and Fornes for their comments. We
appreciate their agreement about the importance of disorganiza-
tion and isolation of myocardial fibers within fat as key elements
to distinguish arrhythmogenic right ventricular cardiomyopathy/
dysplasia (ARVC/D) from fatty replacement. It is difficult to
infer the role of lymphocyte infiltration in ARVC/D, and our
study does not bring any new elements to that issue.
Onthecontrary,oneofthenovelfindingsofourstudyiscertainly
the observation of frequent infiltration of conductive tissue by
fibrosis (54%), adipose tissue (8%) or both (6%) in hearts of
individuals who had unexpected sudden death associated with
ARVC/D. It is impossible to compare this high prevalence with
previous studies because conduction tissue was never systematically
scrutinized in ARVC/D. We have seen conduction tissue with
adipose infiltration and/or fibrosis in numerous ARVC/D cases as
convincing evidence of conduction tissue alteration.
Fontaine and Fornes raised an interesting point: how can conduc-
tive tissue infiltration in ARVC/D be so prevalent (?70%) when
atrioventricular (AV) block is so rare? In our series, among the 6
rare patients who had an ECG recording before death, 1 had an AV
block. Moreover, among the 50 patients with ARVC/D whose cases
were followed in our department, 2 have a pacemaker for complete
AV block. A third patient who suffered from ventricular tachycardia
had documented infrahisian block. Thus, AV block is not so
infrequent (about 6%) and appears as the tip of the iceberg of the
conduction tissue involvement. Clinicians should be aware of the
risk of AV block during antiarrhythmic drug prescription. Further-
more, our observations support the view that an invasive electro-
physiologic study is recommended to detect hidden intracardiac
conduction disturbances when antiarrhythmic drugs are indicated.
A. Tabib, MD, PhD
R. Loire, MD
L. Chalabreysse, MD
D. Meyronnet, MD
A. Miras, MD
D. Malicier, MD
F. Thivolet, MD, PhD
P. Chevalier, MD, PhD
P. Bouvagnet, MD, PhD
Services d’Anatomie-Pathologie,
Service de Cardiologie et Soins Intensifs
Service de Cardiologie Pédiatrique
Hôpital Louis Pradel
Hospices Civils de Lyon
Institut de Médecine Légale
CNRS FRE 2692
Faculté de Médecine
Université Claude Bernard
Lyon, France
e20
Correspondence
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