Download Cardiac arrhythmias and conduction

Rheumatology 2006;45:iv39–iv42
doi:10.1093/rheumatology/kel315
Cardiac arrhythmias and conduction disturbances
in autoimmune rheumatic diseases
P. M. Seferović, A. D. Ristić, R. Maksimović1, D. S. Simeunović, G. G. Ristić2,
G. Radovanović, D. Seferović3, B. Maisch4 and M. Matucci-Cerinic5
Rhythm and conduction disturbances and sudden cardiac death (SCD) are important manifestations of cardiac involvement in
autoimmune rheumatic diseases (ARDs). In patients with rheumatoid arthritis (RA), a major cause of SCD is atherosclerotic
coronary artery disease, leading to acute coronary syndrome and ventricular arrhythmias. In systemic lupus erythematosus
(SLE), sinus tachycardia, atrial fibrillation and atrial ectopic beats are the major cardiac arrhythmias. In some cases, sinus
tachycardia may be the only manifestation of cardiac involvement. The most frequent cardiac rhythm disturbances in systemic
sclerosis (SSc) are premature ventricular contractions (PVCs), often appearing as monomorphic, single PVCs, or rarely as
bigeminy, trigeminy or pairs. Transient atrial fibrillation, flutter or paroxysmal supraventricular tachycardia are also described
in 20–30% of SSc patients. Non-sustained ventricular tachycardia was described in 7–13%, while SCD is reported in 5–21% of
unselected patients with SSc. The conduction disorders are more frequent in ARD than the cardiac arrhythmias. In RA,
infiltration of the atrioventricular (AV) node can cause right bundle branch block in 35% of patients. AV block is rare in RA,
and is usually complete. In SLE small vessel vasculitis, the infiltration of the sinus or AV nodes, or active myocarditis can lead
to first-degree AV block in 34–70% of patients. In contrast to RA, conduction abnormalities may regress when the underlying
disease is controlled. In neonatal lupus, 3% of infants whose mothers are antibody positive develop complete heart block.
Conduction disturbances in SSc are due to fibrosis of sinoatrial node, presenting as abnormal ECG, bundle and fascicular
blocks and occur in 25–75% of patients.
Introduction
Several autoimmune rheumatic diseases (ARDs) impose an
increased risk for the development of cardiovascular comorbidities, either through their impact on progression of atherosclerosis,
thrombus formation, vasculitis or myocardial inflammation and/
or fibrosis. Rhythm and conduction disturbances and sudden
cardiac death (SCD) in ARD have higher incidence than in the
general population [1].
In addition to standard 12-lead ECG, 24-h Holter monitoring
is most widely applied for evaluation of patients with arrhythmias
and conduction abnormalities (Fig. 1). ECG signal averaging
can detect a substrate for malignant arrhythmias and identify
patients who warrant further investigation. Invasive electrophysiology studies are indicated when spontaneous arrhythmias
are infrequent and when a serious sustained arrhythmia is
suspected.
Cardiac arrhythmias in autoimmune rheumatic diseases
The nature and severity of underlying ARD is often of greater
prognostic
significance
than
the
arrhythmia
itself.
Pathophysiological substrate for rhythm disorders is related to
altered automaticity, re-entry or triggered automaticity. Serious
arrhythmias require additional diagnostic tests (Fig. 1), to define
its cause and exclude coronary, myocardial or arrhythmogenic
disorder. Fast supraventricular or ventricular tachyarrhythmias
can cause clinically significant haemodynamic compromise.
Cardiac arrhythmias in rheumatoid arthritis
Coronary artery disease (CAD) is a major contributor to the
increased risk of SCD in rheumatoid arthritis (RA), leading to
acute coronary syndrome and ventricular arrhythmias [2].
Accelerated coronary atherosclerosis, coronary vasculitis,
superimposed coronary thrombosis, myocarditis and pulmonary
hypertension also contribute to the rhythm disturbances.
Heart rate variability measurement is useful for the risk
assessment for ventricular arrhythmias. Significant correlation
was observed between RA activity and heart rate variability [3].
In patients with high activity of RA, the decrease of heart
rate variability reflects severity of inflammation. Decreased
heart rate variability in degree I-II RA activity, is predictor
for ventricular arrhythmias, SCD and acute myocardial
infarction (MI).
Wislowska [4] revealed cardiac involvement more frequently
in nodular than in non-nodular RA and general population
(71.9 vs 42.9 vs 22.9%, respectively). A 24-h Holter monitoring
Department of Cardiology, Institute for Cardiovascular Diseases of the Clinical Center of Serbia, 1Institute of Radiology, Clinical Center of Serbia,
2
Department of Rheumatology and Clinical Immunology, Military Medical Academy, 3Institute for Rehabilitation ‘Dr Miroslav Zotovic’, Belgrade, Serbia,
4
Department of Internal Medicine-Cardiology, Philipps-University, Marburg, Germany and 5Department of Medicine, Division of Rheumatology, University
of Florence, Florence, Italy.
Submitted 12 July 2006; revised version accepted 17 July 2006.
Correspondence to: P. M. Seferović, Professor of Internal Medicine-Cardiology, Belgrade University Medical School and Institute for Cardiovascular
Diseases of the Clinical Center of Serbia, Koste Todorovica 8, 11000 Belgrade, Serbia. E-mail: [email protected]
iv39
ß The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
P. M. Seferović et al.
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Patients with rhythm and/or conduction
disorders in autoimmune rheumatic disease
History, ECG, Echocardiography
Patients with multiple daily
episodes of palpitations
or presyncope
Long-term
electrocardiographic
recording
24-h Holter
monitoring
Patients with infrequent,
anxiety- or exercise-induced
palpitations
Exercise
testing
Assessment of the
arrhythmogenic
potential
Event recording
➢ 30 days external ‘loop’ recorder
➢ Implantable loop recorder
➢ Heart rate variability analysis
➢ Baroreceptor reflex
sensitivity testing
➢ Signal-averaging techniques
(late potentials)
➢ Upright tilt-table testing
➢QT dispersion analysis
➢T wave alternans
Invasive assessment
➢ Invasive haemodynamics, coronary angiography
➢ Electrophysiological studies
FIG. 1. Diagnosis and management of patients with rhythm and conduction disorders in autoimmune rheumatic diseases.
did not demonstrate significant differences in frequency of rhythm
disorders between the RA patients and the controls.
Cardiac arrhythmias in systemic lupus erythematosus
Malignant ventricular arrhythmias are rarely reported in systemic
lupus erythematosus (SLE). Sinus tachycardia, atrial fibrillation
and atrial ectopic beats are most frequent. Supraventricular
arrhythmias are often transient, and may be related to myocarditis
and exacerbations of SLE. Sinus tachycardia occurs in 50% of
patients and may be the only cardiac manifestation of SLE,
resolving under corticosteroid treatment [5].
Anti-small cytoplasmic ribonucleoproteins (anti-Ro/SSA)associated sinus bradycardia and QT interval prolongation have
been described both in children and adults with ARD [6].
Abnormalities in the autonomic tone and ventricular late
excitability potentially indicate high risk of developing lifethreatening ventricular arrhythmias and SCD [7]. QT interval
prolongation and refractory ventricular arrhythmias could also be
associated with chronic hydroxychloroquine therapy for SLE [8].
Cardiac arrhythmias in systemic sclerosis
Atrial and ventricular arrhythmias are common among
asymptomatic patients with systemic sclerosis (SSc) and may be
associated with poor outcome. Transient atrial fibrillation, flutter,
or paroxysmal supraventricular tachycardia, may be present in
20–30% of SSc patients.
Patchy myocardial fibrosis provides an ideal substrate
for tachyarrhythmias, dependent on re-entrant circuits.
Ventricular arrhythmias have been demonstrated in 67% [9],
and non-sustained ventricular tachycardia (VT) in 7–13% of
unselected patients with SSc [10]. Patients with frequent
premature ventricular contractions (PVCs) had 50% mortality
during 33 months follow-up in contrast to 8% among
patients without frequent ectopy. Bulkley et al. [11] noted SCD
in 21% of patients with SSc in contrast to no SCD in 61/275
deaths of SSc patients in the study of Lee et al. [12]. In the study of
Follansbee et al. [13] SCD was confirmed in 5% of the
1258 patients with SSc. In patients with both skeletal and
myocardial involvement ventricular arrhythmias and SCD occur
more often.
Rhythm and conduction in rheumatic diseases
Management of cardiac arrhythmias in autoimmune
rheumatic diseases
In the management of arrhythmias, the understanding of the
aetiopathogenesis of ARD is very important. In patients with
a chronic disease, often related to significant disabilities,
arrhythmias may cause anxiety despite its clinical irrelevance
and reassurance is very important.
Anti-arrhythmic drug therapy is the mainstay of management.
Drug selection is based upon their electrophysiological effects and
the type of arrhythmia. No randomized controlled trials have
evaluated any of these therapies specifically for use in patients
with rheumatological disease, and therefore, therapy should be
tailored to the individual patient. Verapamil-type calcium channel
blockers are preferred for the treatment of supraventricualar
arrhythmias. Digoxin can be used to decrease ventricular response
in atrial fibrillation and in end-stage heart failure. The treatment
of sinus tachycardia in SLE is generally carried out by -blockers.
Classic -blockers are contraindicated in patients with SSc and
conditions with vasculitis and pulmonary hypertension.
Ventricular fibrillation (except in the first few hours of acute
MI) and medically intractable life-threatening VT are indications
for treatment with implantable cardioverter defibrillators (ICDs)
[14]. Preventive ICD implantation was proven to decrease
mortality of patients with dilated cardiomyopathy and in
combination with resynchronization pacing is nowadays regarded
as a treatment of choice for patients with heart failure and
advanced left ventricular dysfunction. Importantly, defibrillators
do not prevent symptomatic arrhythmias and should be combined
with suppressive anti-arrhythmic therapy.
Radiofrequency (RF) ablation has revolutionized the approach
to many types of arrhythmias. Patients considered for RF catheter
ablation of VT are those with symptomatic, sustained, monomorphic VT when the tachycardia is drug resistant, when the
patient is drug intolerant or when the patient does not desire
long-term drug therapy; patients with bundle branch re-entrant
VT; and patients with sustained monomorphic VT and an ICD
who are receiving multiple shocks not manageable by
re-programming or concomitant drug therapy. Occasionally,
non-sustained VT or even severely symptomatic PVCs require
RF catheter ablation. Success rates >90% are expected for
accessory pathway tachycardias, para-atrioventricular (AV) nodal
re-entry tachycardia, atrial tachycardia and right ventricular
outflow tract tachycardia. AV node ablation (used for ventricular
rate control in atrial fibrillation) is possible in >99% of patients.
Success rates of 85% are reported for the cure of atrial flutter [15].
Conduction disorders
The conduction disorders occur in ARD mainly in the active
disease and are more frequent than rhythm disturbances. They
arise through abnormalities of intrinsic automaticity or impaired
conduction, principally within the AV node and the His–
Purkinje’s network.
Conduction disorders in rheumatoid arthritis
Primary infiltration of the AV node or other conducting tissue by
mononuclear cells or rheumatoid granulomas can be revealed in
patients with conduction disorders and RA. Other potential
mechanisms are vasculitis of the arterial supply to conductive
tissue, haemorrhage into a rheumatoid nodule or extension of an
inflammatory lesion from the aortic or mitral valve. Rarely, these
lesions may be due to amyloid deposition. Villecco et al. [16]
described right bundle branch block in 35% of 60 patients with
RA. Antibodies to cardiac conducting tissue were found
significantly more often in these patients than in those without
conduction abnormalities (76 vs 21%). AV block is rare in RA,
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usually complete, and does not respond to anti-inflammatory and
immunosuppressive therapy. Ahern et al. [17] described congenital
complete heart block (CHB) in 0.1% of patients with RA, mainly
in females, with sudden onset, and more prevalent in patients
with subcutaneous nodules. However, no major conduction
disorders were noted in anti-Ro/SSA positive RA patients [18].
Conduction disturbances in systemic lupus erythematosus
The small vessel vasculitis and the infiltration by fibrous or
granulation tissue are major causes of the dysfunction of sinus or
AV nodes in SLE. Correlation of autoimmunity-related destruction with conduction disorders has been documented. Conduction
defects may also represent a sequel of myocarditis in 34–70% of
patients with SLE [19]. First-degree heart block is often transient.
CHB in adults with SLE is extremely rare (11 cases described
so far), and is associated with appearance of anti-U1-RNP
(U1 nuclear ribonuclearprotein) antibodies, and not with antiRo/La antibodies as in newborns [7]. Myocarditis and conduction
defects occur more frequently in the anti-Ro-positive than in antiRo-negative SLE patients and healthy controls. In contrast to
RA, conduction abnormalities may regress when the underlying
disease is controlled.
Conduction disturbances in neonatal lupus
Neonatal lupus is a rare syndrome related to the transplacental
passage of autoantibodies from mothers positive for anti-Ro/SSA
(and/or anti-La/SSB) to their newborns. Approximately 3% of
infants whose mothers are antibody-positive develop CHB [20].
The risk of recurrence is 10 times higher in the following
pregnancies [21]. CHB is usually permanent (despite steroid
therapy), and can be isolated or associated with other structural
heart diseases. Incomplete heart block is often reversible, but may
also progress to CHB despite therapy. Rarely, CHB can be
associated with VT [22].
Direct arrhythmogenic activity of anti-Ro/SSA antibodies,
immunoglobulin and complement deposition in cardiac tissues
were demonstrated in several studies. Inhibition of L- and T-type
calcium channels, seems to play an important role in the pathophysiology of the syndrome [23]. Fetal susceptibility may be influenced
by specific human leukocyte antigen complex (HLA) alleles [24].
However, the discordance of CHB in identical twins suggests that an
in utero factor plays a more important role than genetic differences
[25]. Maternal–fetal microchimerism may be important in neonatal
lupus, as demonstrated by finding of female (maternal) cells in the
myocardium of the males who died of CHB [26].
Women with elevated levels of anti-Ro/SSA and anti-La/SSB
could be treated with glucocorticoids for prevention of CHB
during pregnancy. CHB did not develop in any of 26 infants
born to mothers undergoing such a treatment before 16 weeks’
gestation [27]. However, such a preventive approach exposes 80%
of expectant mothers and fetuses to the risks of unnecessary
glucocorticosteroid treatment.
Immunoadsorption was recently suggested by Hickstein et al.
[28] as a possible treatment for pregnant women with high titers
of SSA-antibodies and clinical complications. Infants with CHB
may require a cardiac pacemaker, especially if the heart rate
before delivery is <50 beats/min [20].
Conduction disturbances in systemic sclerosis
Conduction disturbances in SSc are mostly due to the fibrosis of
the sinoatrial node, but direct involvement of the cardiac
conduction tissue and its arterial blood supply has also been
reported. In the study of Volta et al. [29] 25% of the patients with
progressive SSc had antibodies against cardiac conducting tissue.
Abnormal ECG, bundle and fascicular blocks occur in 25–75% of
patients with SSc, sometimes even preceding cutaneous lesions,
and are independent predictors of mortality. Fortunately, second
and third degree AV block, are rare (<2%) [30].
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P. M. Seferović et al.
Conduction disturbances in polymyositis and
dermatomyositis
Polymyositis and dermatomyositis (PM/DM) are frequently
complicated by conduction disturbances either by direct lesion
of the conduction system or by myositis with contraction band
necrosis and/or focal myocardial fibrosis. The block is localized
distally to the His bundle, with no alterations in sinus node
and AV nodal function. Cardiac involvement is mainly subclinical, but up to 23% of patients have conduction block in
ECG that can occur in the absence of cardiomyopathy and may be
progressive [7].
Management of conduction disturbances
in autoimmune rheumatic diseases
Pacemaker implantation is the method of choice for the treatment
of CHB and other serious conduction abnormalities.
Sophisticated pacing modalities and programmability as well as
low-energy circuitry and new battery designs have increased
device longevity and enabled wide clinical application. A simple
VVI pacemaker (paces and senses the ventricle and is inhibited by
a sensed ventricular event) may be adequate for transient or
infrequent bradyarrhythmia. For frequent or persistent bradyarrhythmia, prolonged dependence on ventricular pacing may
warrant use of a rate-responsive demand unit or, if no atrial or
sinus node abnormalities are present, a dual-chamber system
(DDD—both chambers are capable of being sensed and paced).
New devices enable resynchronization therapy in patients with
dilated cardiomyopathy and severely impaired contractility, with
beneficial effect on haemodynamics and long-term survival.
Acknowledgements
This work is part of the project supported by the Ministry of
science and environmental protection, Republic of Serbia,
‘Uncovering etiopathogenesis of heart muscle disease, pericardial
disease, and congestive heart failure as a comprehensive background for diagnosis and treatment: application of neuronal
network and artificial intelligence’, (No. 145063) and Joint
European Project, Tempus (No. 19046-2004), ‘Restructuring
of postgraduate studies and training in medicine in Serbia’.
The authors have declared no conflicts of interest.
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