Download Atrial Arrhythmias in Arrhythmogenic Cardiomyopathy: At the

AUTHOR’S REPLY
Circulation Journal
Official Journal of the Japanese Circulation Society
http://www. j-circ.or.jp
Atrial Arrhythmias in Arrhythmogenic
Cardiomyopathy: At the Beginning or at
the End of the Disease Story? – Reply –
In a Letter to the Editor entitled “Atrial arrhythmias in arrhythmogenic cardiomyopathy – at the beginning or at the end of
the disease story?” S. Peters describes two middle-aged female patients with morphological and electrocardiographic
signs of arrhythmogenic right ventricular dysplasia (ARVD)
who presented with atrial fibrillation (AF) as their first arrhythmic event. The author points to the observation that AF is very
common in ARVD, with up to 40% of patients being affected,
and may often precede ventricular tachyarrhythmias. On the
other hand, Peters also indicates that in some patients AF may
be a late consequence of progressed disease with severe right
and left ventricular (LV) involvement,1 heart failure and atrial
dilatation, which typically occur during the late phases of
ARVD. Our study published in a previous issue of this Journal2 is in line with the letter by Peters showing that AF is
common in our ARVD population (20%). As ARVD is a
heterogeneous disease, the natural history may vary significantly among patients.3 Similar to the cases presented by
Peters, AF occurred at a rather early stage of the disease in a
minority of our study population. AF is common in patients
with Brugada syndrome who do not have structural heart disease at the macroscopic level.4 As some forms of ARVD may
overlap with the Brugada phenotype, and desmosomal mutations (plakophilin-2 and desmoglein-2) have been shown to
impair cardiac sodium current (INa), it is possible that associated changes in the electrophysiologic properties of atrial tissue
may predispose to AF in some patients at a rather early stage
of the disease.5,6 On the other hand, our ARVD cohort with AF
mainly comprised patients at later stages of the disease with
significant RV involvement, atrial dilatation, and some with
LV involvement. In line with the cases described by Peters,
AF was not associated with the presence of ventricular
tachyarrhythmias in our study. Reasons for this observation
have not been explored, but it may be speculated that, based
on genetic predisposition and epigenetic factors, some patients
with ARVD predominantly present with heart failure and
atrial dilatation rather than ventricular arrhythmias. Moreover,
in some patients, mutations within the desmosomal complex
may affect ion channels, signal transduction and fibrofatty
infiltration of the atria to a different extent than in the ventricles.7
AF in ARVD is a very interesting topic, and future basic
and clinical research is obviously necessary to better delineate
and understand the various aspects of atrial arrhythmias in this
challenging disease.
Disclosures
Sources of Funding: This work and the Zurich ARVC Program are supported by a grant from the Georg and Bertha Schwyzer-Winiker Foundation,
Zurich, Switzerland.
Conflict of Interest: None declared.
References
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disc. Circulation 2013; 128: 1381 – 1386.
2. Saguner AM, Ganahl S, Kraus A, Baldinger SH, Medeiros-Domingo
A, Saguner AR, et al. Clinical role of atrial arrhythmias in patients
with arrhythmogenic right ventricular dysplasia. Circ J 2014; 78:
2854 – 2861.
3. Hulot JS, Jouven X, Empana JP, Frank R, Fontaine G. Natural history
and risk stratification of arrhythmogenic right ventricular dysplasia/
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4. Giustetto C, Cerrato N, Gribaudo E, Scrocco C, Castagno D, Richiardi
E, et al. Atrial fibrillation in a large population with Brugada electrocardiographic pattern: Prevalence, management, and correlation with
prognosis. Heart Rhythm 2014; 11: 259 – 265.
5. Rizzo S, Lodder EM, Verkerk AO, Wolswinkel R, Beekman L,
Pilichou K, et al. Intercalated disc abnormalities, reduced Na(+) current density, and conduction slowing in desmoglein-2 mutant mice
prior to cardiomyopathic changes. Cardiovasc Res 2012; 95: 409 – 418.
6. Cerrone M, Lin X, Zhang M, Agullo-Pascual E, Pfenniger A, Chkourko
Gusky H, et al. Missense mutations in plakophilin-2 cause sodium
current deficit and associate with a brugada syndrome phenotype.
Circulation 2014; 129: 1092 – 1103.
7. Platonov PG, Christensen AH, Holmqvist F, Carlson J, Haunso S,
Svendsen JH. Abnormal atrial activation is common in patients with
arrhythmogenic right ventricular cardiomyopathy. J Electrocardiol
2011; 44: 237 – 241.
Circulation Journal Vol.79, February 2015
Ardan M. Saguner, MD
Corinna Brunckhorst, MD
Department of Cardiology,
University Heart Center Zurich, Switzerland
Firat Duru, MD
Department of Cardiology,
University Heart Center Zurich;
Center for Integrative Human Physiology,
University Zurich, Switzerland
(Released online December 8, 2014)