Methods
Patient Population
We included 153 patients referred to our centre with atrial arrhythmias
for evaluation in the period between January 2015 and July 2018. We
excluded patients with structural heart disease, post-operative AF,
critically illness, significant dyselectrolytemias and patients with
conventional risk factors for AF.9 We also excluded
patients with ventricular arrhythmias. There were 45 patients without an
underlying cause for AF. We evaluated these 45 patients for evidence of
atrial inflammation. 18F FDG PET demonstrated atrial
uptake in 24 patients. Biopsy evidence of myocarditis was found in 15
out of these 24 patients. Atrial tachyarrhythmias with evidence of
atrial inflammation and mediastinal lymphadenopathy was observed in 15
patients (30%). In this study, we describe the clinical features of
these patients presenting with atrial arrhythmias with evidence of
inflammation on imaging and biopsy.
We evaluated the patient charts and reports for information on past
illness, procedures, and therapies. Informed consent was obtained from
all patients.
Diagnostic Evaluation
Detailed history and clinical examination were performed in all
patients. Laboratory tests for complete blood counts (CBC), erythrocyte
sedimentation rate (ESR), hs-CRP, Renal function, Liver function,
Thyroid function and electrolytes were performed in all patients.
Coronary artery disease was ruled out by stress testing and coronary
angiography when indicated. A 12-lead electrocardiogram at baseline and
during the tachyarrhythmia was evaluated in all patients. The diagnostic
evaluation protocol that was used has been summarized in the Figure 2.
The following imaging modalities were also used in all patients:
- Echocardiography – A detailed echocardiogram was conducted for
biventricular function, regional wall motion and valve dysfunction. We
also measured the left atrial (LA), right atrial (RA) volumes and the
left ventricular ejection fraction (LVEF). The American society of
Echocardiography (ASE) recommendations for chamber quantification were
used for these measurements.10 We used the 2012 WHF
echocardiographic criteria for rheumatic heart disease to rule out
rheumatic heart disease. We also ruled out acute rheumatic fever with
the modified Jones criteria.11
- Delayed gadolinium enhancement Cardiac Magnetic resonance (DE-CMR) –
A CMR was performed for ventricular function and delayed enhancement
in the ventricular myocardium in 6 of these patients.
- Positron Emission tomography (18 FDG PET-CT) - Was performed in all
the patients according to standard protocols with a 16-slice scanner
(Siemens). The 18F-FDG PET/CT images was obtained with patients on a
high fat, low carbohydrate diet for 24 hrs with an overnight fast of
12 – 16 hours prior to the imaging. The images were interpreted
visually for evidence of uptake in the atrial or ventricular
myocardium. We recorded the site of uptake in the atria and classified
it according to the following regions: 1. Right atrial appendage (RAA)
2. Right atrial free wall (RA) 3. Interatrial septum (IAS) 4. Left
atrial appendage (LAA) 5. Left atrial anterior wall (LAAW) and left
atrial posterior wall (LAPW)
- Computerized tomography and Magnetic resonance imaging of the brain
was performed in patients presenting with stroke.
- Evaluation of aetiology – A detailed physical examination for
evidence of rheumatic fever, sarcoidosis, and tuberculosis. A previous
history of tuberculosis was also sought. A tuberculin skin test was
performed in all patients with 5 tuberculin units of purified protein
derivative. An induration of greater than 10 mm at 48 hours was
interpreted as a positive test. An endomyocardial biopsy was performed
in 1 patient and a biopsy of enlarged lymph nodes was performed in all
the patients. The biopsy specimens were evaluated by histopathology
with Gram’s staining and haematoxylin and eosin staining. Staining and
cultures for mycobacterium and fungi were performed in all the biopsy
specimens. A polymerase chain reaction for tuberculosis was performed
in all the patients on tissue biopsy specimens. The diagnosis of
Cardiac Sarcoidosis was according to the Expert Consensus
Recommendation Criteria by Birnie et. al.12 The
diagnosis of Cardiac sarcoidosis was based on Histopathological or
clinical criteria and confirmed as definite with a histological
diagnosis from myocardial tissue or probable based on clinical
criteria and extracardiac biopsy diagnosis.
Management
Antiarrhythmic therapy
Initially all patients were treated with rate control medications such
as beta blockers, digoxin, and calcium channel antagonists. The rhythm
control medications used were sotalol, flecainide and amiodarone. Oral
anticoagulation was recommended in all patients with evidence of
myocarditis.
Electrophysiology study and Radiofrequency ablation
An EPS with ablation of atrial flutter was performed in 4 patients who
continued to have arrhythmias despite AADs. The ablation was performed
with three-dimensional mapping system (CARTO, Biosense Webster), a
Stockert radiofrequency generator (Stockert GmBh, Freiburg, Germany) and
an 8-F irrigated tip ablation catheter. The success of atrial flutter
ablation was defined as bidirectional block and AVNRT ablation was
defined as non-inducibility.
Management of underlying disease
Therapy of myocarditis in the form of either sarcoidosis or tuberculosis
was added to the management of patients after appropriate diagnosis. The
management protocol used is highlighted in Figure. Patients were treated
with oral corticosteroids (prednisolone 0.5mg/kg/day to a maximum dose
of 60 mg/day) for 8 weeks initially. Patients were evaluated at every
follow up visit by clinical evaluation, ECG, echocardiography, and18FDG-PET scans. After 8 weeks, the corticosteroids
were tapered, and oral methotrexate started concurrently at a dose of
7.5 mg/week. Methotrexate was continued for 2 years. The duration and
titration of therapy was guided by disease response. The response was
assessed by 18F-FDG-PETs and clinical evaluation.
After the initial phase, patients were followed up at 3- 6 monthly
intervals. In patients with evidence of tuberculosis, anti-tuberculosis
therapy was instituted according to standard recommendations.
Statistical Methods
Continuous variables were represented as mean and standard deviation
where data follows the normal distribution, otherwise as a median with
range. Categorical variables were represented as frequencies and
percentages. The paired t test was used to show the effect of treatment
on LA, RA dimensions, LVEF and inflammatory parameters.