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 1. Saguner AM, Duru F, Brunckhorst CB. Arrhythmogenic right ventricular cardiomyopathy: A challenging disease of the intercalated 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/ cardiomyopathy. Circulation 2004; 110: 1879 – 1884. 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)
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 1. Saguner AM, Duru F, Brunckhorst CB. Arrhythmogenic right ventricular cardiomyopathy: A challenging disease of the intercalated 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/ cardiomyopathy. Circulation 2004; 110: 1879 – 1884. 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)
