Download Atrial arrhythmias in the young: early onset atrial arrhythmias

CLINICAL RESEARCH
Europace (2014) 16, 1814–1820
doi:10.1093/europace/euu141
Electrophysiology and ablation
Atrial arrhythmias in the young: early onset atrial
arrhythmias preceding a diagnosis of a primary
muscular dystrophy
Nik Stoyanov,1†, Jeffrey Winterfield 2†, Niraj Varma 3, and Michael H. Gollob1*
1
Arrhythmia Service, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada K1Y 4W7; 2Arrhythmia Service, Division of Cardiology, Loyola Center for Heart
and Vascular Medicine, Park Ridge, 60153 IL, USA; and 3Arrhythmia Service, Division of Cardiology, Cleveland Clinic Foundation, 44106 Cleveland, OH, USA
Received 25 February 2014; accepted after revision 7 May 2014; online publish-ahead-of-print 17 June 2014
Aims
The aetiology of atrial arrhythmias in the otherwise healthy and young is usually unrecognized. We hypothesized that rare
cases of atrial arrhythmias in the young may represent the initial manifestation of a muscular dystrophy syndrome.
.....................................................................................................................................................................................
Methods
We describe the clinical characteristics, disease progression, results of electrophysiological study, and genetic findings in
and results
four patients (age ,40 years) presenting with idiopathic atrial arrhythmias who subsequently received a diagnosis of a
muscular dystrophy syndrome. The mean age at presentation with atrial arrhythmias was 29.5 years (range, 21– 37
years), and the mean delay to diagnosis of muscular dystrophy was 3.6 years (range, 0.5 –6 years). Two patients received
a subsequent diagnosis of myotonic dystrophy type 1 and 2 a diagnosis of Emery –Dreifuss muscular dystrophy. Diseasecausing genetic defects were identified in all four patients. One patient underwent catheter ablation of atrial flutter,
experiencing improvement in arrhythmia symptoms. Two patients required device therapy, each receiving cardiac
resynchronization therapy-defibrillator implantation for progressive left ventricular dysfunction.
.....................................................................................................................................................................................
Conclusion
Early onset atrial arrhythmias may be the first clinical manifestation of a muscular dystrophy syndrome. Appropriate clinical assessment and surveillance may uncover this primary cause and provide an opportunity for timely genetic counselling
and family screening.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Genetics † Muscular dystrophy
Introduction
Atrial fibrillation (AF) and atrial flutter are common arrhythmias,
especially in the elderly population.1 Common secondary causes
of AF and atrial flutter include hypertension, coronary disease,
valvular disease, and other structural heart abnormalities. When
atrial arrhythmias occur in otherwise healthy, young individuals,
other recognized contributing factors may include a manifest or
concealed accessory atrioventricular (AV) pathway, excessive
alcohol consumption, sleep apnoea syndrome, or genetic-based
channelopathies.2 – 4 However, atrial arrhythmia as a first manifestation of a subclinical muscular dystrophy syndrome is not usually
considered.
In this paper, we describe four patients who presented with atrial
arrhythmias (AF, atrial flutter, or atrial standstill) at a young age. Their
unique clinical characteristics and progression subsequently led to a
diagnosis of a primary muscular dystrophy syndrome, with identification of the genetic aetiology in all four cases (Table 1).
Methods
We describe four young patients (age ,40 years), first presenting with an
atrial arrhythmia who later received a diagnosis of a muscular dystrophy
syndrome. Clinical records were reviewed, including 12-lead electrocardiograms (ECGs), invasive electrophysiological (EP) studies, clinical progression, and genetic testing results. Genetic testing was performed in
commercially available genetic testing centres following written informed
consent.
Results
We identified four patients presenting with an atrial arrhythmia prior
to a diagnosis of a muscular dystrophy syndrome. Two patients
* Corresponding author. Tel: 613 761 5016; Fax: 613 761 5060. E-mail address: [email protected]
†
These authors contributed equally.
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
484 C T (Q162X)
truncating mutation
EMD gene
RA + LA
standstill
AV block
EDMD**
EDMD
3
4
Atrial standstill
37
37
Elbow contracture
Elevated CK
Atrial standstill,
junctional escape
LVEF 35%; LVEDD
8.2 cm; LA + RA
dilated
Deletion mutation
(c.83-3_97) EMD
gene
RA standstill
CS fibrillation
LA flutter
AV block
N LV size, EF
55% 35%;
LA + RA dilated
Fine fibrillatory
activity, junctional
escape
Elbow contractures
Elevated CK
43
36
Normal
First-degree AV
block
27
21
Paroxysmal AF
DM1
2
RA standstill, CS
fibrillation
LA flutter
500 CTG repeats in
DMPK gene
250 CTG repeats in
DMPK gene
HV 65 ms
A flutter
(CTI) ablation
N/A
Normal
Normal
Myotonia; mild distal
weakness; ptosis; SCM
and temporalis wasting
Myotonia; mild distal
weakness; ptosis; SCM
and temporalis wasting
25
22
Paroxysmal AF,
AFL
Age at
diagnosis of
myopathy
Age at atrial
arrhythmia
Atrial
arrhythmia
Diagnosis
Patients
Table 1 Clinical characteristics of Patients 1 –4
Patient 1
A previously well 22-year-old female presented to her local emergency room complaining of an irregular heart rhythm and palpitations. Electrocardiogram confirmed the presence of AF (Figure 1A).
Despite the absence of atrioventricular nodal (AVN) blocking medications, her average ventricular rate was only in the range of 80 –
85b.p.m. Elective electrical cardioversion was performed revealing
a normal baseline ECG (Figure 1B), and outpatient referral to the
arrhythmia clinic requested. Echocardiography was normal in all
parameters, including LV function and atrial size. Cardiac examination
was normal. In light of only a single episode, the patient was commenced on daily aspirin.
At the age of 25, the patient presented with nausea, vomiting, and
headache. Imaging revealed a venous sinus thrombosis and a right
thalamic stroke. She completely recovered. However, neurological
examination elicited percussion myotonia of the thenar eminences.
Further inspection suggested atrophy of the temporalis muscles
and mild bilateral ptosis. In retrospect, the patient recalled myotonic
symptoms of both hands during hand grip activities over the previous
5–10 years. Electromyography studies demonstrated classical myotonic discharges and the patient received a diagnosis of myotonic dystrophy. No family history of muscular dystrophy or AF was present.
Genetic testing confirmed the presence of a heterozygous triplet
repeat expansion (250 CTG repeats) in the DMPK (Dystrophia Myotonica protein kinase) gene, consistent with the diagnosis of DM1.
At age 28, the patient perceived an increased symptom burden of
palpitations. Electrocardiogram documented typical atrial flutter,
again with a relative slow ventricular rate (75– 80 b.p.m.) in the
absence of AVN blocking agents (Figure 1B). The patient underwent
Muscle disease
Case details
DM1*
ECG
2D echo
received a diagnosis of myotonic dystrophy type 1 (DM1), and two
patients a diagnosis of Emery –Dreifuss muscular dystrophy (EDMD).
The mean age at presentation with atrial arrhythmias was 29.5 years
(range, 21– 37 years), and the mean delay to diagnosis of muscular
dystrophy was 3.6 years (range, 0.5 –6 years). Disease-causing
genetic defects were identified in four of four patients. Genetic counselling and cascade family screening have been initiated in each case.
Electrophysiological studies were performed in three of four patients
and demonstrated a range of abnormalities. One patient underwent
catheter ablation of atrial flutter and has remained minimally symptomatic of palpitations. Two patients required device therapy, each
receiving cardiac resynchronization therapy-defibrillator (CRT-D)
implantation for progressive left ventricular (LV) dysfunction.
.............................................................................................................................................................................................................................................
EP study
Genetic testing
† Atrial arrhythmias in the young may represent the first sign of a
systemic muscular dystrophy disorder.
† Unique electrocardiogram and electrophysiological observations may be a clue to an underlying subclinical muscular dystrophy syndrome.
† Recognition of this rare cause of atrial arrhythmias will lead to
appropriate genetic counselling and family screening.
1
What’s new?
AF, atrial fibrillation; AFL, atrial flutter; AV, atrioventricular; DM1, myotonic dystrophy type 1; EDMD, Emery –Dreifuss muscular dystrophy; RA, right atrium; LA, left atrium; SCM, sternocleidomastoid.
1815
Atrial arrhythmias in the young
1816
N. Stoyanov et al.
Figure 1 Electrocardiogram and EP tracings for Patient 1. (A) Electrocardiogram during AF with relatively slow ventricular rate response. (B) Electrocardiogram during sinus rhythm showing no evidence of overt conduction disease. (C ) Electrocardiogram during atrial flutter. (D) Intracardiac
electrograms (EGMs) during EP study demonstrating typical counterclockwise RA flutter. Halo positioning with Halo bipole 1 – 2 just lateral to
cavotricuspid isthmus, and Halo bipole 19– 20 at low interatrial septum.
an EP study confirming the presence of typical counter-clockwise,
cavotricuspid isthmus-dependent flutter (Figure 1D), and she underwent subsequent successful radiofrequency catheter ablation of the
cavotricuspid isthmus. Her HV interval was measured at 65 ms, but
no evidence of PR prolongation has been evident on ECG. The
patient has remained minimally symptomatic of palpitations and
remains solely on daily aspirin. Now aged 33, she has not shown progressive cardiac disease, experiences obstructive sleep apnoea, and
has mild myotonic symptoms.
Patient 2
A 21-year-old male was referred to the arrhythmia service following
presentation to his local hospital with symptomatic palpitations and
confirmed AF. Past medical history was remarkable only for a selfreported history of ‘tachycardia’ in early childhood. Presenting
ECG during AF was remarkable for a slow ventricular rate response
in the absence of medications (Figure 2A). Baseline ECG was abnormal
for the presence of a first-degree AV block (PR 280 ms) (Figure 2B).
Echocardiography was unremarkable, noting normal biventricular
function and chamber dimensions. In view of a minimum symptom
burden, the patient was treated conservatively with aspirin and
low-dose beta-blocker (metoprolol 12.5 mg twice daily) and was
followed annually for re-assessment of symptom burden.
During routine follow-up in the arrhythmia clinic, the patient was
noted to have moderate bilateral ptosis. The patient was requested
to perform hand grip and arm flexion isotonic exercises and displayed
delayed muscle relaxation. Myotonia was evident on percussion of
the deltoid. A diagnosis of DM1was suspected and genetic testing
was arranged. Genetic testing revealed a heterozygous triplet
repeat expansion of 500 CTG repeats in the DMPK gene, confirming
a diagnosis of DM1.
Patient 3
A previously well 36-year-old male physician, formerly a collegiate
distance runner, was referred for a new diagnosis of ‘atrial fibrillation’
following routine physical examination and 12-lead ECG. The patient
reported a long-standing history of asymptomatic, persistent slow
heart rate (40–50 b.p.m.). Initial referring ECG demonstrated no
visible P-waves, but later possibly flutter or fine fibrillatory activity,
and a ventricular rate of 42 b.p.m. with apparent regular R–R intervals (Figure 3A). Echocardiography revealed normal LV function but
severe bi-atrial enlargement. No intracardiac shunts were evident.
Doppler recordings across the AV valves showed complete
absence of A-waves, indicating loss of right and left atrial mechanical
activity.
The patient underwent an EP study.5 Regular flutter activity was
noted within the coronary sinus (CS) likely responsible for the evanescent fine electrical activity observed on ECG. This arrhythmia
could be pace-terminated (Figure 3B). Electroanatomical mapping
revealed extremely low voltage throughout the right atrium (RA)
with some sparing of the septum, and preserved voltage in the CS
(Figure 3C). Despite high output pacing from multiple sites, electrical
capture of the RA was not possible. Further mapping in the region of
the sinus node showed slow electrical activity (30 b.p.m.) that did not
depolarize adjacent tissue (Figure 3C). Direct mapping of the left
atrium was not attempted. Ventricular depolarization resulted
Atrial arrhythmias in the young
1817
Figure 2 Electrocardiogram tracings for Patient 2. (A) Monitor tracing of paroxysmal AF with slow ventricular rate response in the absence of AVN
blocking agents. (B) Sinus rhythm with baseline PR prolongation of 320 ms.
Figure 3 Electrocardiograms, intracardiac EGMs, and 3D electroanatomic mapping observations for Patient 3. (A) Presenting ECG showing
regular junctional escape rhythm and low amplitude baseline deflections suggestive of atrial fibrillatory or flutter activity. (B) Atrial flutter noted
in CS—terminated with overdrive pacing. (C) Bipolar voltage map of RA and CS showing extreme low voltage throughout RA and preserved CS
voltage. Silver dots indicate the region where sinus activity was explored. EGMs below show cyclic electrical activity in sinus node region
(3000 ms, black arrows). (D) EGM recordings during second EP study showing atrial flutter (CL 274 ms) within the CS. Fine flutter activity is
noted on surface ECG (arrows).
1818
from a regular junctional escape rhythm, with a normal HV interval
(50 ms). The patient underwent placement of a single chamber pacemaker (VVI with lower rate limit of 40 paces per minute) and was
commenced on warfarin. The patient continued endurance exercise
with no limitations.
Six years following initial presentation, the patient presented with
exercise-induced palpitations as well as a new complaint of increased
fatigue. A 7-day ambulatory monitor demonstrated frequent
ventricular ectopy and non-sustained ventricular tachycardia (VT),
including a 17 beat run of VT at 246 b.p.m. His average resting
heart rate measured 49 b.p.m. with bradycardia documented 92%
of time. He reported increased fatigue with his daily activities, and
he queried whether bradycardia might explain his symptoms. He
paced 40% of time with a setting of VVI 40.
Clinical examination revealed mild bilateral elbow contractures. In
hindsight, the patient recalled this abnormality since his late teens,
which were attributed to previous arm fractures in childhood.
Upon further questioning, he confirmed a history of elevated creatine
kinase (CK) levels in the past (as high as 1000 IU/L) attributed to endurance running. Echocardiography now revealed mild left and right
ventricular enlargement with LV ejection fraction of 50%, moderate
tricuspid regurgitation, and marked bi-atrial enlargement.
Invasive EP testing was repeated in view of the LV dilation and
documented symptomatic ventricular arrhythmias. Programmed
ventricular stimulation with up to triple extra-stimuli induced
repeated non-sustained polymorphic VT. As observed in the previous EP study, the RA remained electrically silent with left atrial
flutter (cycle length 251 ms) noted on the CS electrograms
(Figure 3D). Notably, AV block at the level of the AV node was
observed with spontaneous junctional rhythm (HV 51 ms) responsible for ventricular activity. Voltage mapping of left and right
ventricles demonstrated normal voltage with only patchy areas of
low voltage in the peri-valvular regions.
Taken together, the constellation of history, examination, imaging,
and EP findings suggested a diagnosis of EMDM. Following genetic
counselling, the patient underwent testing of the EMD gene, which
encodes the muscle-specific emerin protein, and of the LMNA
gene. Genetic testing revealed an 18 bp deletion mutation within
the EMD gene spanning over the latter sequence of intron 1, the
splice junction and initial region of exon 2 (c.83-3_97del18), resulting
in a frame-shift mutation and predicted premature truncation of the
emerin protein.
The patient underwent CRT-D implant, and he continued anticoagulation for left atrial flutter and RA standstill. With pacing set to VVI
60, he noted an initial functional improvement in symptoms of fatigue
and improved energy for daily activity.
Patient 4
A 37-year-old asymptomatic male was noted to have significant
bradycardia on routine physical examination and an abnormal
ECG, prompting referral to the arrhythmia clinic. Electrocardiogram
demonstrated no visible P-waves, regular R–R interval, and a heart
rate of 40 b.p.m. (Figure 4A). A Holter monitor again showed no evidence of atrial activity through 24 h monitoring, and noted a high
burden of premature ventricular contractions (PVCs), accounting
for 32% of QRS complexes. Echocardiogram was remarkable for
biventricular enlargement and an estimated LV ejection fraction of
N. Stoyanov et al.
30 –35% (global hypokinesis). Severe bi-atrial enlargement was also
apparent, and there was no significant valvular disease. Despite the
clinical findings and an active lifestyle, the patient had no complaints
of shortness of breath.
An invasive EP study was undertaken, and there was no evidence of
appreciable atrial electrograms in the RA free wall as well as within
the CS (Figure 4B). As observed in Patient 3, a junctional rhythm
was observed with an HV interval of 52 ms. Right atrial capture was
unsuccessful even at high output (20 mA, 9 ms). Voltage mapping
confirmed extreme low voltage throughout most of the RA
(,0.10 mV), further confirming electrical standstill (Figure 4C). Ventricular mapping indicated a PVC origin in the region of aortomitral
continuity; however, earliest activation measured 25 ms despite excellent pace map match. Mapping from the junction of the anterior
interventricular vein and great cardiac vein yielded earliest activation
of 0 ms with a poor pace map match. Application of radiofrequency
energy to the endocardial site resulted in thermal facilitation of the
PVC with acceleration to rapid VT of similar morphology;
however, the rhythm rapidly degenerated to ventricular fibrillation
requiring defibrillation. In the setting of marked LV dilation (7.2 cm
end-diastolic dimension), further ablation was abandoned. The
patient subsequently underwent implantation of a CRT-D device.
Based on similarities to the previous case, further questioning
revealed a family history of a skeletal muscular disorder in a male
first cousin (age 45) and in a maternal great uncle who required a permanent pacemaker and experienced sudden death at age 33 years.
Follow-up neurological assessment noted mild bilateral elbow
contractures. Blood work indicated an elevated CK of 1400 IU/L
and the patient received a diagnosis of EDMD. Genetic testing
demonstrated a 484C.T nucleotide change leading to a premature
stop codon mutation (Q162X) of the EMD gene and a predicted truncation of the emerin protein.
Discussion
Atrial arrhythmias in presumably healthy, young individuals (age ,40
years) occur in ,0.1% of the population.6,7 In isolation, episodes are
often attributed to a metabolic disturbance or alcohol excess. When
atrial arrhythmias occur in the young, secondary causes such as
previously unrecognized structural heat disease or familial, genetic-based primary arrhythmia syndromes may be considered but
are frequently unyielding. The association of atrial arrhythmias with
primary muscular dystrophy syndromes is well recognized, although
typically the natural course of these conditions begins with skeletal
muscle symptoms and onset of cardiac pathology in later years.8 In
this case series, we describe our experience and the clinical characteristics of four previously asymptomatic patients who first came
to medical attention for review of atrial arrhythmias, and who later
were recognized to have an underlying primary muscular dystrophy
syndrome.
Two patients in their early 20s were referred for management of
AF by family physicians following clinical presentation with symptomatic palpitations and documented AF. Uniquely, both patients presented with a controlled ventricular rate response in the context
of their arrhythmia and in the absence of any AVN blocking agents.
This observation, in hindsight, may have been a clinical clue to
their underlying condition, in light of the common association of
Atrial arrhythmias in the young
1819
Figure 4 Electrocardiograms, intracardiac EGMs, and 3D electroanatomic mapping observations for Patient 4. (A) Presenting ECG showing the
absence of atrial activity, regular junctional escape, and ventricular ectopy. (B) Intracardiac EGM during junctional rhythm with PVC; no atrial electrical activity is appreciated in the RA or CS poles of the duo-decapolar catheter. (C, D) Left anterior oblique and posteroanterior projections of
CARTO voltage map of RA showing diffuse low voltage with a small area of preserved voltage posteriorly. Yellow points denote location of His EGM.
conduction system disease in muscular dystrophy syndromes.8 In
Patient 1, a subsequent ablation procedure for atrial flutter noted a
prolonged HV interval of 65 ms, while Patient 2 was noted to have
a first-degree AV block on ECG. These patients had a delay of 3
and 6 years, respectively, to an ultimate diagnosis of DM1. Contributing to this delay was the absence of any significant functional limitations in both patients secondary to their underlying skeletal muscle
disorder. The absence of symptoms in DM1 may occur in individuals
who choose to live a more sedentary lifestyle, as was the case for
these patients. Despite the lack of physical complaints, the objective
findings of myotonia were evident on physical examination of both
patients. Although it is not usual to consider neurological assessment
during evaluation for AF management, simple examination observations and manoeuvres in the clinic may elicit findings consistent with
DM1 if clinical suspicion arises. Both patients had evidence of mild
bilateral ptosis, although a continuum of this phenotypic feature may
be a challenge for the unrefined in neurological examination. More
substantially, both patients exhibited the characteristic stiffness and
delay in release following a firm hand grip, an easily performed assessment. Gentle percussion to the thenar eminence (Case 1) or deltoid
muscle (Case 2) showed characteristic contraction and delayed
relaxation (myotonia). Genetic testing confirmed the diagnosis of
MD1 in both patients, allowing for a more focused clinical surveillance
and cascade family screening.
Myotonic dystrophy type 1 occurs in 1 of 8000 individuals and is the
most common adult-onset muscular dystrophy.9 Cardiac abnormalities may occur in up to 80% of affected cases, including dilated
cardiomyopathy and conduction disease. The most common manifestation is first-degree AV block although up to one-third of patients may
develop atrial arrhythmias later in life.9,10 Reports of AF preceding
overt symptoms of DM1 are rare. A single report by Bassez et al.11
describes two patients presenting with cardiac arrhythmia prior to
the recognition of DM1. One patient suffered a cardiac arrest due to
ventricular fibrillation, and another was symptomatic of atrial flutter.11
Interestingly, skeletal muscle symptoms in DM1 patients are commonly mild, although debilitating cases leading to progressive respiratory muscle weakness and death may occur.12 Management is
focused on education, genetic counselling, and regular monitoring
for heart rhythm disorders.8,9 Issues related to genetic counselling
are particularly relevant. Myotonic dystrophy type 1 is a trinucleotide
repeat genetic disease characterized by the genetic phenomenon of
‘anticipation’.12 This implies that offspring of affected individuals are at
risk of developing earlier onset and more severe features of the
disease. This results from trinucleotide repeat expansion within the
affected DMPK gene, which occurs during the repeated meiosis
events generating germ cells. Inheritance from an affected father is
generally less severe, likely related to the lack of viability of sperm
cells harbouring a large number of trinucleotide repeats.12 The
pathogenesis of muscle disease, both skeletal and cardiac, is believed
to be related to the toxic cellular effects of the DMPK mRNA containing high numbers of CTG repeats, leading to impairment in the gene
regulation and subsequent architecture of myofibril development.13
Histopathology in affected hearts commonly show myocyte hypertrophy, fatty infiltration, and interstitial fibrosis.14
1820
Emery– Dreifuss muscular dystrophy was subsequently diagnosed
in two additional patients who first presented with symptomatic palpitations and abnormal ECGs interpreted as AF. These patients
shared numerous clinical features, including age of onset (age 37
years), the absence of visible P-waves on ECG, severe bi-atrial
enlargement and mechanical standstill on echo, and invasive EP
evidence of atrial electrical standstill with the inability to pace atrial
myocardium. In both patients, there was evidence of AV block at
the level of the AV node with a junctional escape, a common
finding in certain inherited cardiomyopathies.15 Both patients developed LV impairment (indicating that the disease process is not limited
to the atria), and subsequently received CRT-D devices. Genetic
testing confirmed novel genetic defects in the EMD gene (encoding
the emerin protein), confirming a diagnosis of EDMD.
Emery– Dreifuss muscular dystrophy is a relatively rare muscle disorder affecting 1 of 100 000 individuals.16 Typically, clinical onset is
recognized in the second or third decade of life, characterized by
muscle weakness or wasting and development of contractures of
the elbows, ankles, or neck.16,17 Cardiac involvement is common,
with cardiomyopathy and the risk of sudden death a frequent sequelae in later years.8,16 Emery– Dreifuss muscular dystrophy may be
autosomal dominant in nature when caused by genetic defects in
the LMNA gene, or X-linked recessive in inheritance when caused
by mutations in the EMD gene. In the more common X-linked recessive form, as present in our patients, manifestation of the condition
typically skips females in the pedigree. However, rare reports of
cardiac involvement in female gene carriers of EMD mutations
exist, indicating that clinical and genetic screening should extend to
all family members.16
The specific mechanism of muscle disease related to emerin
defects remains unclear.18 Emerin is known to bind directly to
cardiac actin, and defective emerin proteins are suggested to
disrupt the normal molecular framework associated with myofibril
function, including impairment of integral membrane proteins and
junctional complexes.18 Histopathological description at autopsy
has described a marked loss of atrial myocardium and its replacement
by fibrous and fat tissue, as well as various degrees of interstitial
fibrosis in the ventricular myocardium.19
Conclusion
Early onset atrial arrhythmias may be the first clinical manifestation of
a muscular dystrophy syndrome, albeit rare in light of the low prevalence of these conditions and the uncommon scenario of early onset
N. Stoyanov et al.
atrial arrhythmias. Presenting clinical features may include atrial
arrhythmias with slow ventricular response in the absence of AVN
blocking agents, severe bi-atrial enlargement with mechanical/
electrical standstill or evidence of muscle weakness, myotonia, or
contractures on physical examination.
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