Grand Round Case www.jpgmonline.com Recurrent syncopal attacks in a lady with rheumatoid arthritis

Kubba S, Bali HK, Bahl A, Nand Kumar S

Department of Cardiol- 48-year-old lady presented with a history of frequent syncopal attacks since 7 days. There ogy, Postgraduate A was no history of seizure, headache, vomiting, breathlessness, chest pain, palpitations Institute of Medical or vertigo. She was a non-diabetic, non-smoker, non-hypertensive and had no significant family Education and Research, history of . She had a 16-year old history of seropositive rheumatoid arthritis Chandigarh, India. (RA) with intermittent relapses. Initially, she was on diclofenac but for the last 4 years her therapy Correspondence: had been changed to chloroquine 500 mg/day and indomethacin 75 mg/day. She had never re- Samir Kubba, ceived steroids, methotrexate or other disease-modifying anti-rheumatoid drugs in the past. She E-mail: had attained menopause 2 years back and was not on any hormone replacement therapy. At the [email protected] time of presentation, she had symmetrical fixed joint deformities of the hands and feet and no Received : 13-03-04 clinical features to suggest active disease. Examination revealed rate of 40 beats per minute, Review completed : 06-08-04 supine blood pressure of 120/80 mmHg, intermittent cannon waves in the jugular venous pulse Accepted : 29-09-04 and pallor. Cardiovascular examination revealed mild and a soft ejection systolic PubMed ID : 15623976 murmur grade 2/6 at the left sternal border. There was no hepatosplenomegaly. The chest was clear. J Postgrad Med 2004;50:291-2 She had with her a 4-day-old ECG (Figure 1). We repeated an ECG on her admission (Figure 2).

What do the ECGs show? c. Premature coronary artery disease due to accelerated The first ECG shows left anterior hemiblock, right bundle block atherosclerosis in patients with RA. Dyslipidaemia, inflam- and a PR interval of 0.18 seconds. This is suggestive of bifascicular matory milieu, raised homocysteine levels, use of block. The second ECG shows complete atrioventricular disso- corticosteroids and methotrexate and coronary vasculitis ciation with a broad QRS complex (QRS duration =0.14 sec- are some of the factors predisposing to the higher incidence onds) ventricular escape rhythm of 48 per minute. of coronary artery disease in these patients3,4 d. Chloroquine cardiotoxicity5 What are the likely factors predisposing to in pa- e. Focal due to RA1 tients with RA? f. Secondary (due to longstanding arthritis) in- Multiple factors can predispose to complete heart block in volving the conduction system1 patients with RA.1 These are: a. Rheumatoid nodule compressing the conduction tissue2 What are the various cardiovascular manifestations of RA? b. Coronary arteritis causing ischaemia to the conduction tissue1 The cardiovascular manifestations of RA include:1

Figure 1: 12 lead ECG showing bifascicular block Figure 2: 12 lead ECG showing complete atrioventricular dissociation with a wide QRS escape rythm

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CMYK 291  Kubba et al: Recurrent syncopal attacks in a lady a. Pericardial disease-chronic asymptomatic effusive pericar- in patients with severe rheumatoid disease, often with dial disease, acute , pericardial calcification, con- extraarticular manifestations or high titers of rheumatoid fac- strictive pericarditis tor.6 However, the clinical profile, supplemented with the rel- b. Coronary artery disease (CAD) which may be due to sys- evant investigations ruled out the presence of active disease in temic inflammation, corticosteroid use, methotrexate our patient. So these factors are unlikely to cause the conduc- therapy raising homocysteine levels and coronary arteritis tion disturbance in this patient. Though coronary artery dis- c. Myocarditis ease is more common in patients with RA our patient did not d. Restrictive due to secondary amyloidosis have coronary lesions severe enough to explain the conduc- complicating longstanding RA tion block. And although long-term chloroquine therapy caus- e. Conduction disturbances due to active disease, secondary ing complete heart block (CHB) has been described (due to amyloidosis, focal myocarditis, rheumatoid nodule or per- the quinidine-like action of the drug), the absence of any other manent damage to the conduction tissue by fibrosis and side-effect of chloroquine therapy such as myopathy, pigmen- inflammation secondary to disease remissions and relapses tation or visual disturbance (fundus examination was normal f. Rheumatoid aortitis and aortic valvulitis in our patient) make chloroquine toxicity unlikely to be the g. Secondary pulmonary artery hypertension due to lung disease cause for CHB in our patient. However, the possibility of chlo- roquine causing or contributing to the heart block cannot be How would you investigate this patient? completely ruled out. Secondary amyloidosis as the cause for a. Complete haemogram with peripheral smear and ESR the conduction disturbance was ruled out by relevant investi- b. Iron studies gations. c. Renal functions d. Urine routine and microscopy CHB can rarely occur in the well-controlled phase of the dis- e. Liver functions ease even in the absence of the above mentioned complicat- f. Serum electrolytes ing factors.7 As the disease typically has remissions and relapses, g. Lipid profile repeated episodes of inflammation interrupted by the quies- h. Blood glucose cent phases of the disease can cause permanent damage to the i. Cardiac enzymes including creatinine phosphokinase (to- conduction system leading to heart blocks.7 This could have tal and MB) and troponin T been the likely cause for CHB in our patient though other fac- j. C reactive protein tors like long-term chloroquine therapy and CAD could have k. Antinuclear antibodies contributed as well. l. Chest X-ray m. X-rays of the hand and foot and How would you manage this patient? n. Echocardiography As the disease is not in its active phase the focus should be on the conduction disturbance which is producing symptoms of Since the patient was experiencing frequent syncopal attacks, cerebral ischaemia. Since conduction blocks once established a temporary pacemaker was inserted. Investigations revealed in the disease do not respond to anti-inflammatory treatment,1 haemoglobin of 9g%, Total leuckocyte count of 5400/mm3 with the patient should undergo permanent pacemaker implanta- 70% polymorphs 30% lymphocytes, ESR 16mm/1st hour, plate- tion. Our patient received a single chamber VVI permanent let count 2,00,000/mm3. Peripheral smear revealed a micro- pacemaker implantation. She was also started on 10 mg cytic hypochromomic picture and the iron studies were con- leflunomide, a relatively new disease modifying anti-rheumatic sistent with iron deficiency anaemia. The renal functions, liver drug. Though the drug may not benefit the permanent joint functions, serum electrolytes, urine examination, lipid profile deformities it will decrease the relapses and the overall inflam- and blood glucose were normal. Cardiac enzymes were not el- matory milieu thereby reducing the progression of CAD and evated at baseline and on serial follow-up. C-reactive protein cerebrovascular disease. For the CAD, she was started on 150 was not elevated. Antinuclear antibodies were negative. The mg aspirin, 20 mg atorvastatin and 25 mg bid metoprolol. She chest X-ray revealed mild cardiomegaly and the lung fields were has been discharged and is symptom-free at 6 months of fol- clear. X-rays of the hand and foot revealed juxta-articular low-up. osteopenia. Echocardiography showed normal left ventricular systolic and diastolic function, without regional wall motion References abnormality or pulmonary artery hypertension. Coronary an- 1. Mandell BF, Hoffman GS. Rheumatic Diseases and the Cardiovascular System. In: giography done to rule out coronary artery disease as the cause Heart Disease, A Text Book of Cardiovascular Medicine 6th Ed. Braunwald E, Zipes for the conduction block, revealed significant disease in the DP, Libby P, editors. WB Saunders Company; 2001. p. 2199-210. 2. Okada Y, Nakanishi I, Kajikawa K, Kawasaki S. An autopsy case of rheumatoid ar- first diagonal branch of the left anterior descending artery thritis with an involvement of the cardiac conduction system. Jpn Circ J 1983;47:671-6. which was a small vessel; other coronary arteries were normal. 3. Van Doornum S, McColl G, Wicks IP. Accelerated Atherosclerosis: An Extraarticular Feature of Rheumatoid Arthritis? Arthritis Rheum 2002;46:862-73. 4. Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how high grade systemic What could be the most likely cause for the complete heart inflammation accelerates vascular risk in RA. Circulation 2003;108:2957-63. block in this patient after the analysis of the above-mentioned 5. Reuss-Borst M, Berner B, Wulf G, Muller GA. Complete heart block as a rare com- plication of treatment with chloroquine. J Rheumatol 1999;26:1394-5. investigations? 6. Athern M, Lever JV, Cosh J. Complete heart block in rheumatoid arthritis. Ann Rheum Dis 1983;42:389-97. Rheumatoid nodule compressing the conduction system, coro- 7. Sigal LH, Friedman HD. Rheumatoid pancarditis in a patient with well controlled nary arteritis and rheumatoid myocarditis are more often seen rheumatoid arthritis. J Rheumatol 1989;16:368-73.

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