Prevalence of atrial arrhythmias in arrhythmogenic right

ventricular dysplasia/cardiomyopathy
Christian F. Camm, BM BCh,* Cynthia A. James, PhD, Crystal Tichnell, MGC, Brittney Murray, MS,
Aditya Bhonsale, MD, Anneline S.J.M. te Riele, MD, Daniel P. Judge, MD, Harikrishna Tandri, MD,
Hugh Calkins, MD, FHRS
From the *New College, University of Oxford, Oxford, United Kingdom, Department of Medicine, Division of Cardiology,
Johns Hopkins University School of Medicine, Baltimore, Maryland and, Department of Medicine, Division of Cardiology,
University Medical Center Utrecht, Utrecht, The Netherlands.
BACKGROUND Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy, characterized
by right ventricular dysfunction and ventricular arrhythmias.
Limited information is available concerning atrial arrhythmias in
ARVD/C.
OBJECTIVE The purpose of this study was to characterize spontaneous atrial arrhythmias in a large registry population of ARVD/C
patients.
METHODS Patients (n 248) from the Johns Hopkins ARVD/C
registry who met the diagnostic criteria and had undertaken
genotype analysis were included. Medical records of each were
reviewed to ascertain incidence and characteristics of atrial
arrhythmia episodes. Detailed demographic, phenotypic, and
structural information was obtained from registry data.
RESULTS Thirty-ve patients with ARVD/C (14%) experienced one
or more types of atrial arrhythmia during median follow-up of 5.78
(interquartile range 8.52) years. Atrial brillation was the most
common atrial arrhythmia, occurring in 80% of ARVD/C patients
with atrial arrhythmias. Patients developed atrial arrhythmias at a
mean age of 43.0 14.0 years. Atrial arrhythmia patients obtained
a total of 22 inappropriate implantable cardioverter-debrillator
shocks during follow-up. Older age at last follow-up (P o.001) and

Introduction
Arrhythmogenic right ventricular dysplasia/cardiomyopathy
(ARVD/C) is an inherited cardiomyopathy characterized by
right ventricular dysfunction, ventricular arrhythmias, and an
The authors received funding from the Alexandre Suerman Stipend (to
Dr. te Riele), the National Heart, Lung, and Blood Institute (K23HL093350
to Dr. Tandri), the St. Jude Medical Foundation, and Medtronic Inc. The
Johns Hopkins ARVD/C Program (ARVD.com) is supported by the Bogle
Foundation, the Healing Hearts Foundation, the Campanella family,
Wilmerding Endowments, and the Dr. Francis P. Chiaramonte Private
Foundation. Dr. Calkins receives research support from Medtronic and St.
Jude Medical. Address reprint requests and correspondence: Dr. Hugh
Calkins, Sheikh Zayed TowerRoom 7125R, The Johns Hopkins Hospital,
1800 Orleans Street, Baltimore, MD 21287. E-mail address: hcalkins@jhmi.
edu.

1547-5271/$-see front matter B 2013 Heart Rhythm Society. All rights reserved.

male gender (P .044) were associated with atrial arrhythmia

development. Patients with atrial arrhythmias had a higher
occurrence of death (P .028), heart failure (P o.001), and left
atrial enlargement on echocardiography (P .004).
CONCLUSION Atrial arrhythmias are common in ARVD/C and
present at a younger age than in the general population. They
are associated with male gender, increasing age, and left atrial
enlargement. Atrial arrhythmias are clinically important as they are
associated with inappropriate implantable cardioverter-debrillator
shocks and increased risk of both death and heart failure.
KEYWORDS Arrhythmogenic right ventricular dysplasia;
Arrhythmogenic right ventricular cardiomyopathy; Atrial
arrhythmia; Atrial brillation
ABBREVIATIONS AF atrial brillation; ARVD/C arrhythmogenic
right ventricular dysplasia/cardiomyopathy; ECG 12-lead
electrocardiogram; ICD implantable cardioverter-debrillator;
IQR interquartile range; PKP2 plakophilin-2; SVT
supraventricular tachycardia; TFC task force criteria; VF
ventricular brillation; VT ventricular tachycardia
(Heart Rhythm 2013;10:16611668)
All rights reserved.

2013 Heart Rhythm Society.

increased risk of sudden cardiac death.14 The severity and

progression of ARVD/C are highly variable, ranging from
asymptomatic disease to severe heart failure.5 Starting with
the seminal description of plakoglobin mutations,6 we now
know that ARVD/C is often a disease of the cardiac
desmosome.7 This structure is essential for cardiac integrity
and aids electromechanical coupling of cardiomyocytes.
A large number of studies have documented the high
incidence of life-threatening ventricular arrhythmias in
patients with ARVD/C.4,811 In contrast, relatively little
attention has been focused on supraventricular arrhythmias
in patients with ARVD/C,1214 and existing studies are
limited by sample size and a lack of genotype data. Although
unlikely to cause sudden death, atrial arrhythmias are nonetheless associated with increased risk of mortality15 and may
http://dx.doi.org/10.1016/j.hrthm.2013.08.032

1662

Heart Rhythm, Vol 10, No 11, November 2013

also be associated with an increased risk of morbidity.16

Therefore, the purpose of this study was to examine the
prevalence and characteristics of supraventricular arrhythmias in patients with ARVD/C. Particular attention is
focused on determining the relationship between the development of atrial arrhythmias, patient age, and the severity of
ARVD/C.

Methods
Study population
The Johns Hopkins ARVD/C Program was established in
1999 with a goal of studying ARVD/C and providing care
for patients with this condition. Patients with denite or
possible ARVD/C are enrolled in a prospective registry. The
study population was identied from this registry. Inclusion
criteria for this study were registry patients who had undertaken genotype analysis and met the 2010 Task Force
Criteria (TFC) for ARVD/C.17 All registry participants
provided written informed consent. The study protocol was
approved by the Johns Hopkins School of Medicine Institutional Review Board.

Clinical phenotype
Detailed clinical information regarding demographics, presentation, symptom onset, and noninvasive and invasive
studies was obtained for each patient. The medical history of
each subject was obtained through review of medical
records, clinical evaluation, and patient interview. A detailed
family history was obtained through patient interview by
genetic counselors with a special interest in ARVD/C.
Comprehensive mutation testing was performed, using
commercial or research genetic testing, on all patients
included in this study.18 Genetic testing included sequencing
of ve ARVD/C-associated desmosomal genes (PKP2,
DSC2, DSG2, DSP, JUP) and the PLN and TMEM43 genes.
The diagnosis of ARVD/C was based on the presence of
major and minor diagnostic criteria according to the revised
TFC 2010.17 The proband was dened as the rst person in a
family in whom ARVD/C diagnosis was conrmed (i.e.,
fullled TFC for ARVD/C irrespective of family history).
Severity and extent of structural abnormalities were
determined through review of echocardiography, cardiac
magnetic resonance imaging, and right ventricular angiography reports. Mitral and tricuspid regurgitation was
considered if rated as at least moderately severe on echocardiography reports. Enlargement of the right and left atria
Table 1

was dened as either present or absent based on the atrial

diameter (in millimeters) recorded.

Outcome measures
The primary outcome was presence of atrial arrhythmias,
ascertained from medical records, including records of ICD
interrogations. Atrial arrhythmias were dened as a narrow
complex tachycardias with at least one episode lasting Z30
seconds. Where available, traces were examined and adjudicated in addition to reports from the treating physician.
Atrial arrhythmias appearing only during electrophysiologic
studies were excluded. Type of arrhythmia, symptoms, and
detection method were recorded. Atrial arrhythmias were
categorized into three groups: atrial brillation (AF), atrial
utter, and all other supraventricular tachycardias (SVTs).
Secondary outcomes were the development of stage C heart
failure, a sustained ventricular arrhythmic event, ICD placement, and death. Stage C heart failure is dened as patients
with current or past symptoms of heart failure (e.g., dyspnea,
fatigue) associated with underlying structural heart disease.19
A sustained arrhythmic event is a composite measure of the
occurrence of sudden cardiac death, spontaneous sustained
VT/VF, or an appropriate ICD intervention for a sustained
ventricular arrhythmia.9 Echocardiographic reports were
reviewed for moderate-to-severe tricuspid regurgitation, mitral
regurgitation, and right and left atrial diameters.

Statistical analysis
Continuous variables are expressed as mean SD or median
(interquartile Range [IQR]) and compared across groups
using the independent Student t test or Mann-Whitney U test,
respectively. Categorical variables are reported as frequency
(percentage) and compared between groups using the 2 or
Fisher exact test. The cumulative probability of survival free
of an atrial arrhythmia was determined by the Kaplan-Meier
method, and differences in survival between groups was
evaluated with the log-rank test. Binary logistical regression
was used to control for age at last follow-up and sex. P o.05
was considered signicant. SPSS (version 19, IBM,
Chicago, IL) was used for all statistical analysis.

Results
Study population
Baseline demographic data of the 248 patients enrolled in
this study are listed in Table 1. Mean age at last follow-up
was 41.6 14.0 years, 131 patients (52.8%) were male, and

Baseline demographic data of the study population

Clinical value

Overall population (n 248)

Atrial arrhythmias (n 35)

No atrial arrhythmias (n 213)

P value

Male
Age at last follow-up (years)
Age at ARVD/C diagnosis
Length of ARVD/C follow-up
Desmosomal mutation carrier

131 (52.8%)
41.6 14.0
33.8 13.4
5.78 (IQR 8.52)
136 (54.8)

24 (68.6%)
49.7 14.6
39.4 15.7
6.15 (IQR 12.3)
14 (40.0)

107 (50.2%)
40.3 13.5
32.9 12.8
5.56 (IQR 8.11)
122 (57.3)

.044
o.001
.007
.047
.057

Values are given as n (%), mean SD, or median (interquartile range [IQR]).
ARVD/C arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Camm et al

Prevalence of Atrial Arrhythmias in ARVD/C

1663

136 (54.8%) had known ARVD/C-associated genetic mutations (77.9% PKP2). (See Online Supplement Table 1 for
additional clinical features).

Prevalence of supraventricular arrhythmias

Among the 248 patients, 35 (14.1%) experienced one or
more types of supraventricular arrhythmias (47 total arrhythmias) over a median follow-up period of 5.78 years (IQR
8.52). The distributions of supraventricular arrhythmias are
shown in Figure 1. AF was most common, observed in 28 of
35 patients (80%), followed by atrial utter (11, 31%) and
other SVTs (8, 23%). As shown in Figure 1, 11 patients
experienced more than one type of atrial arrhythmia, with
one patient experiencing all three types.
Mean age at time of rst atrial arrhythmia was 43 14
years. Thirty-two (68%) of the sentinel arrhythmic events
occurred while the patient was taking antiarrhythmic medications. Five of 47 sentinel atrial arrhythmic events (11%)
occurred prior to the rst documented ventricular event (4 AF,
1 atrial utter). There were a total of 22 inappropriate shocks
recorded for atrial arrhythmias in 10 patients; six for AF (four
patients), seven for atrial utter (three patients), and nine for
SVT (four patients). Diagnosis method used for these atrial
arrhythmias is shown in Figure 2. A comparison of the clinical
features of ARVD/C patients with AF, atrial utter, and other
types of supraventricular arrhythmias is shown in Table 2. No
difference was observed in the age at sentinel atrial arrhythmic
event, time since ARVD/C presentation, gender, gene carrier
status, proportion taking antiarrhythmic medication at time of
sentinel atrial arrhythmic event, or proportion with an ICD at
last follow-up between different types of atrial arrhythmias.
AF accounted for 28 of 47 supraventricular arrhythmias
(60%) experienced by our patient cohort. Twenty-seven of
28 arrhythmias (96%) were paroxysmal, with a single patient
suffering from persistent AF. The average CHADS2 score
was 0.68 (SD 0.84); 13 individuals had a CHADS2 score 40
(46%). Anticoagulation was prescribed in 18 patients (warfarin 11, aspirin 5, dabigatran 2). There were no recorded
adverse events related to anticoagulation in this patient
group. Thromboembolic events recorded in the AF group
included right ventricular thrombus (2), transient ischemic
attack (1), subclavian vein thrombosis (1), pulmonary

Figure 2 Method used in the diagnosis of the sentinel atrial arrhythmic

event. No signicant difference was seen between atrial arrhythmia types in
the proportion of diagnosis made by any method. ECG 12-lead
electrocardiogram; ICD implantable cardioverter-debrillator; SVT
supraventricular tachycardia; ETT = exercise tolerance test.

embolism (1), and deep vein thrombosis (1). All but one of
these patients is currently anticoagulated.

Comparison of patients with and without

atrial arrhythmias
We compared clinical characteristics of ARVD/C patients
with and without at least one supraventricular arrhythmic
event at last follow-up (Table 1). Patients experiencing atrial
arrhythmias were older at the date of last follow-up (49.7
14.6 years vs 40.3 13.5 years respectively, P o.001) and
more likely to be male (68.6% and 50.2%, respectively, P
.044) than patients without atrial arrhythmias. In bivariate
analysis, older age at diagnosis and longer duration of
follow-up were also associated with having at least one
atrial arrhythmic event. However, binary logistic regression
controlling for age at last follow-up and gender showed no
signicant association with the remaining demographic
features, including duration of follow-up. Survival curves
outlining the development of atrial arrhythmias illustrate that
men have a lower lifetime survival free from atrial arrhythmias than do women (Figure 3).

Relationship between supraventricular arrhythmias

and markers of disease severity

Figure 1 Venn diagram illustrating the breakdown of atrial arrhythmia

types among the 35 patients experiencing at least one atrial arrhythmic event.
Circle area is proportional to total number of patients suffering from that
arrhythmia. Numbers within each section correspond to the number of
patient suffering from those arrhythmias. SVT supraventricular
tachycardia.

Echocardiographic reports were available for 210 study

participants (34 with atrial arrhythmias, 176 without).
Moderate or severe tricuspid regurgitation was signicantly
associated with the presence of atrial arrhythmias (29.4% vs.
13.6%, P .022). No association was seen between atrial
arrhythmias and moderate or severe mitral regurgitation
(Table 3). Binary logistical regression controlling for gender
and age at last follow-up removed the statistical signicance
of tricuspid regurgitation (B 0.750, SE 0.470, P
.110). Both right (52.9% vs. 27.8%, P .008) and left

1664
Table 2

Heart Rhythm, Vol 10, No 11, November 2013

Demographic features of atrial arrhythmias

Clinical value
Age at rst atrial arrhythmia (years)
Years from ARVD/C presentation
Proportion male
Desmosomal mutation carrier
Taking antiarrhythmic drug at sentinel
atrial arrhythmia
Implantable cardioverter-debrillator
at last follow-up

All atrial arrhythmias

(n 47)

AF (n 28)

Atrial utter
(n 11)

Other supraventricular
tachycardia (n 8)

P value

43.0 14.0
4.63 9.06
31 (66.0)
17 (36.2)
32 (68.1)

45.90 13.37
4.54 10.75
19 (67.9)
12 (42.9)
17 (60.7)

37.45 16.36
3.68 5.70
7 (63.6)
3 (27.3)
8 (72.7)

40.51 11.33
6.27 6.52
5 (62.5)
2 (25.0)
7 (87.5)

NS
NS
NS
NS
NS

41 (87.2)

25 (89.2)

9 (81.8)

7 (87.5)

NS

Values are given as mean SD or n (%).

AF atrial brillation; ARVD/C arrhythmogenic right ventricular dysplasia/cardiomyopathy.

(38.2% vs. 10.2%, P o.001) atrial enlargement were

signicantly associated with the presence of atrial arrhythmias; following binary logistical regression both right (B
0.929, SE 0.405, P .022) and left (B 1.352, SE
0.463, P .004) atrial enlargement remained signicant.
Left ventricular enlargement was present in ve patients with
atrial arrhythmias (14.3%). No statistically signicant difference was seen between the rate of left ventricular enlargement in those with left atrial enlargement (3/12 [25.0%]) and
those without (2/21 [9.5%]), (P .233). Left ventricular
ejection fractions were similar between those with left atrial
enlargement (54.7%, SD 8.1%, n 13) and those without
(54.7%, SD 10.8%, n 21) (P .994). The rate of
hypertension 4140 mm Hg systolic or 90 mm Hg diastolic

was not signicantly different between those with left atrial

enlargement (3/21 [14.3%]) and those without left atrial
enlargement (3/12 [25.0%]) (P .443).
The presence of atrial arrhythmias was associated with heart
failure (34.3% vs. 9.3% respectively, P o.001) and death
(11.4% vs. 2.8% respectively, P .037). Additionally, patients
with atrial arrhythmias were signicantly more likely to be
placed on antiarrhythmic therapies (82.9% vs. 41.3% respectively, P o.001). No other markers of disease severity were
signicantly associated (Table 4). Following binary logistical
regression analysis controlling for age at last follow-up and
gender, the presence of atrial arrhythmias were signicantly
associated with heart failure (B 1.646, SE 0.455, P o.001)
and death (B 1.576, SE 0.719, P .028).

Figure 3 Kaplan-Meier survival curves for the development of atrial arrhythmias. Left panel: Development of atrial arrhythmias based on age in years. Right
panel: Development of atrial arrhythmias based on length of follow-up. Four subjects were diagnosed on autopsy (time 0) and thus do not appear in the
numbers at risk. ARVD/C arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Camm et al
Table 3

Prevalence of Atrial Arrhythmias in ARVD/C

1665

Echocardiographic features associated with atrial arrhythmias

Clinical value

Overall population (n 210)

Atrial arrhythmias (n 34)

No atrial arrhythmias (n 176)

P value

Tricuspid regurgitation
Mitral regurgitation
Right atrial enlargement
Left atrial enlargement

34 (16.2)
9 (4.3)
67 (31.9)
31 (14.8)

10 (29.4)
2 (5.9)
18 (52.9)
13 (38.2)

24 (13.6)
7 (4.0)
49 (27.8)
18 (10.2)

.022
.64
.008
o.001

Values are given as n (%).

Discussion
Main ndings
The results of this study reveal that atrial arrhythmias are not
uncommon in patients with ARVD/C, occurring in 14% of
patients. ARVD/C patients who develop atrial arrhythmias
are, on average, older and more likely to be male. The
development of atrial arrhythmias was associated with
structural changes including left and right atrial enlargement.

Prior studies of atrial arrhythmias in patients

with ARVD/C
The presence of atrial arrhythmias in ARVD/C was highlighted soon after the initial recognition of this cardiomyopathy and has been conrmed in prior cases studies and case
series.1214,20,21 Tonet et al14 were the rst group to assess
the presence of atrial arrhythmias in patients with ARVD/C.
Evaluation of 72 ARVD/C patients presenting with ventricular arrhythmias demonstrated a 24% prevalence rate, with
AF the most common arrhythmia (59%). The presence of
right atrial enlargement and tricuspid regurgitation were both
suggested by this group as factors in the development of
atrial arrhythmias. In a similar population of 47 patients,
Brembilla-Perrot et al13 demonstrated a 15% prevalence rate
and an increased susceptibility to the development of atrial
arrhythmias under programmed electrical stimulation.
Jaoude et al22 assessed the progression of ECG tracings
during follow-up of 74 patients with ARVD/C. This yielded
a 4% prevalence of atrial arrhythmias (three patients).
However, this study did not further categorize the arrhythmias or the patients presenting with these arrhythmias.
Recently, Chu et al12 highlighted a prevalence rate of 42%
in a retrospective analysis of 36 ARVD/C patients undergoing ablation for ventricular arrhythmias. There was a
nonsignicant trend toward older age in the atrial arrhythmia
group; however, there was no difference in gender. Tricuspid
Table 4

regurgitation was signicantly associated with the development of atrial arrhythmias; in contrast, association with right
atrial enlargement was not signicant.

Atrial arrhythmias in the Johns Hopkins

ARVD/C Registry
The results of the present study conrm and extend the ndings
of prior studies of atrial arrhythmias in patients with ARVD/C.
This is the rst study directly assessing the presence and nature
of atrial arrhythmias in a large research database. Previous
studies characterizing atrial arrhythmia type and prevalence
have focused on particular subpopulations of ARVD/C patients
those diagnosed with ventricular arrhythmias14 or patients
undergoing ventricular ablation.12 The current study provides
novel insights using data from a large, specialist registry and
highlights key features important to the practicing physician
regarding the development of atrial arrhythmias in this group.

Overall prevalence
The rst important nding of this study is the prevalence of
atrial arrhythmias (AF, atrial utter, and other SVTs) in
patients with ARVD/C was 14%. This rate is similar to the
14.9% reported by Brembilla-Perrot et al.13 The lower
prevalence in this study compared with the 42% reported
by Chu et al12 and the 25% reported by Tonet et al14 may be
related to population selection. In these prior studies, patients
were limited to those undergoing ventricular ablation therapy
and those presenting with ventricular arrhythmias, respectively, both markers of more severe disease. Given the high
proportion of paroxysmal AF in our current study (27/28
[96%]), the low rate of atrial arrhythmias (4.1%) demonstrated by Jaoude et al22 likely reects the lack of comprehensive assessment of patient records examining for atrial
arrhythmias, which were instead identied solely through
ECG assessment.

Association of disease severity markers with atrial arrhythmias.

Clinical value

Overall population
(n 248)

Atrial arrhythmias
(n 35)

No atrial arrhythmias
(n 213)

P value

Dead
10 (4.0)
4 (11.4)
6 (2.8)
.038
ICD
239 (92.3)
32 (91.4)
197 (92.5)
.738
Sustained arrhythmic event
164 (66.1)
25 (71.4)
139 (65.3)
.565
Premature ventricular complex count (n 179) 2430 (IQR 4620) 2530 (IQR 4820) (n 21) 2380 (IQR 4650) (n 157)
.790
Heart failure
32 (12.9)
12 (34.3)
20 (9.4)
o.001
Antiarrhythmic therapy at last follow-up
117 (47.2%)
29 (82.9%)
88 (41.3%)
o.001
Values are given as n (%), n/N (%), or median (interquartile range [IQR]).
A sustained arrhythmic event is a composite measure of the occurrence of sudden cardiac death, spontaneous sustained ventricular tachycardia/ventricular
brillation, or an appropriate implantable cardioverter-debrillator (ICD) intervention for a sustained ventricular arrhythmia.

1666

Age and gender

AF and other atrial arrhythmias are age dependent and more
likely to be seen in male patients.23,24 AF has a population
prevalence of 21% by age 80.23 Atrial arrhythmias were
shown to be similarly age and gender dependent within our
ARVD/C population. Additionally, the mean age of 43.0
14.0 years illustrates a high disease burden in an age group
that normally has a AF prevalence o0.5%.25 Furthermore,
our study has shown that older ARVD/C patients were more
likely to have experienced an atrial arrhythmia, which
supports the earlier ndings of Chu et al.12 The mean age
of 43 years in this population is lower than the 51 and 52
years seen in previous studies.12,13 The lower age range seen
in our population may, in part, represent increased recognition of ARVD/C as a condition over the past decade with
better diagnostic clarication following publication of
improved TFC in 2010. Increased use of genetic screening
in family members,7 as suggested by Heart Rhythm Society
guidelines,26 following proband diagnosis (and hence their
meeting TFC at an earlier stage of disease) may explain the
signicant association with negative genetic screening
results and atrial arrhythmias (due to the potential diagnosis
of such individuals at an earlier stage of disease progression),
an association that was not maintained when regression
controlled for age at last follow-up and gender. Unlike age,
gender has not been shown to be a signicant predisposing
factor in previous studies in this area.12 These results suggest
the possibility that atrial arrhythmias are occurring in older
individuals with a predisposition to AF that is triggered by
the presence of ARVD/C.

Diagnosis method and ICD

A large proportion of atrial arrhythmias were diagnosed in
this study using ICDs (both during routine follow-up and as a
result of inappropriate shocks) and Holter monitors. This
suggests that many atrial arrhythmias in this population may
be concealed, with only 34.0% of all atrial arrhythmias being
rst demonstrated using an ECG tracing. This is consistent
among different atrial arrhythmia types and has not been
shown previously. Tonet et al14 showed that the majority of
their atrial arrhythmias (82%) were diagnosed using a
standard 12-lead ECG tracing. The increased diagnostic
prevalence of other techniques likely results from their
increased utilization in the diagnosis and management of
ARVD/C over the past 2 decades. However, the fact that
17% of all atrial arrhythmias were initially diagnosed
following an inappropriate ICD shock and the presence of
22 inappropriate shocks within our atrial arrhythmia population highlights the need for better awareness and control
of these arrhythmias.

Disease severity
It has been previously suggested that atrial arrhythmias may
be associated with the presence or development of more
severe disease.12,14 In this study, the presence of atrial
arrhythmias showed a variable association with factors

Heart Rhythm, Vol 10, No 11, November 2013

suggestive of disease severity. Death and heart failure both
were more prevalent in the atrial arrhythmia group. However, it is not clear whether either atrial arrhythmias or heart
failure played a causative role in the development of the
other. Although statistically signicant, the small number of
deaths in our study population suggests that the clinical
signicance of this nding is less clear. The increased
utilization of antiarrhythmic agents in the atrial arrhythmia
group is potentially a result of the atrial arrhythmia burden
rather than suggestive of increased ventricular arrhythmia
burden. Although atrial arrhythmias in general, and AF in
particular, are associated with an increased mortality rate
in the general population,15 the increased rate of heart failure
in this population likely added to this.

Pathophysiology
The pathophysiology behind the development of atrial
arrhythmias in ARVD/C is far from clear. Atrial enlargement
is a known risk factor for atrial arrhythmias, especially AF.27
Several groups have previously suggested a role for the right
atrial dilation often seen in ARVD/C in the development of
atrial arrhythmias.12,14 The limited availability of cardiac
magnetic resonance imaging data within this population
makes structural analysis of the atria difcult. However, we
demonstrated a correlation between atrial arrhythmias and
tricuspid regurgitation using echocardiographic imagining,
in support of previous studies.12 However, this nding
cannot fully explain the prevalence of atrial arrhythmias
within the ARVD/C population. Although a correlation with
both left and right atrial enlargement and atrial arrhythmias
was also identied, the known limitations of echocardiography when viewing the atria limit the validity of these
results. Left atrial enlargement is a known effect of AF,28
which suggests that the structural changes seen both in this
study and by previous groups may be a result of the atrial
arrhythmias rather than a causative factor.
Desmosome mutations and the resulting dysfunction are
known to be a major pathologic mechanism in ARVD/C.
Desmosomes are found throughout the cardiac system,
including the atria. Evidence for a pathologic role of the
atria in ARVD/C remains limited; however, support for a
desmosomal basis to atrial arrhythmias in this population is
multifactorial. A small autopsy case series (two patients with
ARVD/C) by Morimoto et al29 showed the presence of fatty
tissue within the sinoatrial node of both patients. Direct atrial
involvement with ARVD/C is further suggested by the
nding of atrial involvement in 17% of cats in an ARVD/
C model.30 Additionally, the postnatal loss of desmoplakin
within the cardiac conduction system has been shown to lead
to sinoatrial node dysfunction in mice.31 Furthermore, work
by Platonov et al32 has demonstrated evidence for altered
electrical conduction within the atria of ARVD/C patients.
Despite this suggestive evidence, data directly relating to
atrial involvement in patients with ARVD/C are lacking. The
thin-walled nature of the atria makes biopsy unwise.
Furthermore, despite cardiac magnetic resonance imaging

Camm et al

Prevalence of Atrial Arrhythmias in ARVD/C

proving itself to be an excellent imaging modality for

ventricular involvement,33 resolution of the atria remains
poor. Without further evidence relating to a direct role of the
atria in ARVD/C, it remains uncertain whether atrial
arrhythmias are due to desmosomal dysfunction within the
atria, right atrial enlargement as a result of right ventricular
dysfunction, or a combination of both mechanisms.

Clinical implications
An atrial arrhythmia prevalence of 14% in this ARVD/C
population highlights the need for vigilance among treating
clinicians. This is further supported by the increased mortality and heart failure prevalence associated with these
patients. Furthermore, our study demonstrates that atrial
arrhythmias are a common cause of inappropriate shocks in
patients with ARVD/C. This nding has important implications for programming of ICDs to minimize the risk of
inappropriate shocks should an atrial arrhythmia occur. The
association with male gender and increasing age suggests
that these factors should guide clinicians when considering
evaluation of ARVD/C patients for atrial arrhythmias.
However, the lack of additional association with length of
follow-up suggests that clinical vigilance should not depend
on this factor.

Study limitations
This study has a number of limitations. First, data were
obtained retrospectively as part of a large registry; as such,
there is likely to be variability in the completeness of data
records and the standard of evaluation each patient received
both in regard to their ARVD/C as a whole and any atrial
arrhythmias in particular. Although this does provide some
limitations to the data, it also highlights a situation similar to
that encountered by many practicing physicians who may
lack complete data regarding a patient. Second, the use of
echocardiographic report data to rate valvular regurgitation
and atrial size is a potential limitation because echocardiograms are notorious for poor imaging of the right atrium, and
the quality of the data contained within reports is likely to be
affected by examiner experience. This limitation may be
compounded by the lack of corroborating imaging. Additionally, length of time between echocardiogram and last
follow-up or sentinel atrial arrhythmia was variable. This
may have resulted in some related factors being missed.

Conclusion
The results of this study demonstrate that atrial arrhythmias
are common in patients with ARVD/C and, when seen, occur
at a signicantly younger age when compared to the general
population. Other associated factors include male gender,
presence of heart failure, and right atrial enlargement. We
suggest that clinicians caring for patients with ARVD/C
should consider the presence of atrial arrhythmias in such
patients, particularly bearing in mind the above associations.

1667

Acknowledgments
We are grateful to the ARVD/C patients and their families
who made this work possible.

Appendix
Supplementary data
Supplementary data associated with this article can be found
in the online version at http://dx.doi.org/10.1016/j.hrthm.
2013.08.032.

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