Prolonged Antimalarial Exposure Increases Risk for Elevated Cardiac Biomarkers in SLE

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Prolonged antimalarial therapy and persistent creatine phosphokinase elevation resulted in an increased risk for abnormal brain natriuretic peptide and cardiac troponin.

Patients with systemic lupus erythematosus (SLE) who receive prolonged antimalarial therapy are at an increased risk for elevated cardiac biomarkers, such as brain natriuretic peptide (BNP) and cardiac troponin (cTnI), particularly when persistently elevated creatine phosphokinase (CPK) levels are present, according to data published in The Journal of Rheumatology.

The investigators sought to examine the prevalence and associated factors of specific heart biomarkers in patients with SLE who were seen at the University of Toronto Lupus Clinic between March and May 2016. They measured BNP and cTnI simultaneously in 151 consecutive patients with SLE and no history of heart disease or pulmonary arterial hypertension (PAH). None of the individuals exhibited electrocardiographic abnormalities indicative of acute coronary syndrome. Logistic regression analyses and cross-sectional comparisons were performed. Patients with abnormal biomarkers were observed to determine the specific cause.

Overall, 10.6% of the patients with no prior cardiac disease had elevated BNP, of whom 6% also had abnormal cTnI levels. Both tests were confirmed after 3 to 4 months. Patients with abnormal biomarkers were older and had longer disease duration, longer duration of antimalarial use, and more frequently persistent CPK elevation compared with those with normal biomarkers (n=135). Based on multivariable regression analysis, prolonged antimalarial treatment (>5.6 years), abnormal CPK level, and use of diuretics were all important predictors of elevated cardiac biomarkers, whereas normal estimated glomerular filtration rate was protective.

There were 6 patients who were diagnosed with definite or possible antimalarial-induced cardiomyopathy. Of these 6 patients, 5 were treated with hydrochloroquine and 1 with chloroquine. In 2 of these individuals, the diagnosis was confirmed using endomyocardial biopsy.

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The investigators concluded that approximately 10% of patients with SLE exhibit elevated myocardial biomarkers in the absence of PAH or prior cardiac disease, and approximately one-third of these individuals will be diagnosed with antimalarial-induced cardiomyopathy. Prolonged antimalarial treatment and persistent CPK elevation were associated with an increased risk for abnormal BNP and cTnI levels, which might be predictive of antimalarial-induced cardiomyopathy. The authors suggest that use of cardiac biomarkers could become a screening test for patients with SLE who receive antimalarial therapy for >5.6 years or who have persistently elevated CPK levels. Additional research is warranted to explore the toxicity of chloroquine and hydrochloroquine as treatments for these individuals.

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Tselios K, Gladman DD, Harvey P, Akhtari S, Su J, Urowitz MB. Abnormal cardiac biomarkers in patients with systemic lupus erythematosus and no prior heart disease: a consequence of antimalarials? [published online August 1, 2018]. J Rheumatol. doi:10.3899/jrheum.171436