Published: 2017-01-18

Incidence of cardiac conduction disorders in patients with rheumatic disease receiving hydroxychloroquine

Vijaya Prasanna Parimi, Jitender Jain, Rajendra Varaprasad, Liza Rajasekhar


Background: Hydroxychloroquine (HCQ) used for long-term management of rheumatic diseases. Prolonged use of antimalarials has been implicated in the development of conduction disorders particularly with chloroquine. Since limited data are available with HCQ, we studied electrocardiograms (ECG’s) of 122 patients with rheumatic diseases treated with HCQ. This is the first study with large cohort evaluating conduction disorders in those receiving HCQ.

Methods: To evaluate cardiac conduction disorders in patients receiving HCQ as a part of their treatment, during 1-year follow-up and to note other related adverse reactions with a hypothesis to determine, how common are conduction disorders with HCQ. This is longitudinal prospective observational study over 1-year in the tertiary referral of south India. All patients who were started on HCQ (200-400 mg/day) as a part of their treatment were included. Patients with established cardiac diseases, electrolyte abnormalities and who were on drugs that cause conduction disorders were excluded. All ECG’s were cross-checked by a cardiologist.

Results: A total of 276 patients were screened at baseline and 270 patients were enrolled in the study. Patients of rheumatoid arthritis, lupus, Sjogren’s syndrome, undifferentiated connective tissue disease, palindromic rheumatism were included after satisfying respective classification criteria. The mean age is 38.85 (standard deviation [SD] 8.34) years. Females are 82.8% (n=101) and males are 17.2% (n=21). The baseline mean heart rate is 81.4 beats/min (SD=11.04), PR interval is 141.5 ms (SD=13.90), QRS is 84.8 ms (SD=13.90), QTc is 421.5 ms (SD=35.65). At 6 months, mean heart rate is 80.4 beats/min (SD=9.99), PR interval is 141.9 ms (SD=16-37), QRS is 81.5 ms (SD=11.82), QTc is 427.4 ms (SD=34.56). At the end of study period, mean heart rate is 81.8 beats/min (SD=9.49), PR interval is 140 ms (SD=21.33), QRS is 84.6 ms (SD=15.72), QTc is 422.7 ms (SD=36.2). During study period four events occurred. A young girl with lupus developed ventricular ectopics on hiking dose of HCQ from 200 mg to 400 mg with a cumulative drug intake of 9.8 g, which has resolved completely on stopping drug without any other intervention. A lupus patient died at home and the cause was not known. A 36-year-old male with rheumatoid arthritis of 4 years duration developed prolonged PR interval with 6 months of drug intake with cumulative was drug intake of 30.6 g with no available follow-up data. A 30-year-old female with undifferentiated arthritis developed skin rash which is pruritic, exfoliative with tiny blisters, 3 days after starting drug. The incidence of cardiac conduction defects in 1-year of follow-up in patients started on HCQ is 0.84.

Conclusion: This study highlights need for periodic cardiac evaluation of patients receiving long-term antimalarials. Reversibility of antimalarial toxicity is also highlighted in this study. Conduction disorders observed were similar to that expected in general population thus adding further evidence on safety of HCQ.


Hydroxychloroquine, Myopathy, Cardiomyopathy, Conduction disorders

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Veinot JP, Mai KT, Zarychanski R. Chloroquine related cardiac toxicity. J Rheumatol. 1998;25(6):1221-5.

Ratliff NB, Estes ML, McMahon JT, Myles JL. Chloroquine-induced cardiomyopathy. Arch Pathol Lab Med. 1988;112(6):578.

Baguet JP, Tremel F, Fabre M. Chloroquine cardiomyopathy with conduction disorders. Heart. 1999;81(2):221-3.

Reuss-Borst M, Berner B, Wulf G, Müller GA. Complete heart block as a rare complication of treatment with chloroquine. J Rheumatol. 1999;26(6):1394-5.

Felson DT, Anderson JJ, Meenan RF. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum. 1990;33(10):1449-61.

Keating RJ, Bhatia S, Amin S, Williams A, Sinak LJ, Edwards WD. Hydroxychloroquine-induced cardiotoxicity in a 39-year-old woman with systemic lupus erythematosus and systolic dysfunction. J Am Soc Echocardiogr. 2005;18(9):981.

Costedoat-Chalumeau N, Hulot JS, Amoura Z, Leroux G, Lechat P, Funck-Brentano C, et al. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology (Oxford). 2007;46(5):808-10.

Nord JE, Shah PK, Rinaldi RZ, Weisman MH. Hydroxychloroquine cardiotoxicity in systemic lupus erythematosus: a report of 2 cases and review of the literature. Semin Arthritis Rheum. 2004;33(5):336-51.

Aro AL, Anttonen O, Kerola T, Junttila MJ, Tikkanen JT, Rissanen HA, et al. Prognostic significance of prolonged PR interval in the general population. Eur Heart J. 2014;35(2):123-9.