White Paper on Antimalarial Cardiac Toxicity

Desmarais J, Rosenbaum JT, Costenbader KH, et al.
American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity. Arthritis Rheumatol 2021;Oct 26:[Epub ahead of print].

The goals of this white paper by members of the American College of Rheumatology, the American College of Cardiology, and the American Academy of Dermatology were to review and summarize the current understanding of hydroxychloroquine (HCQ) and chloroquine (CQ) cardiac toxicity, including corrected QT interval (QTc) prolongation, cardiomyopathy, and conduction system abnormalities. The following are 10 key points to remember:

  1. HCQ and CQ are commonly used medications for the treatment of specific rheumatic and dermatologic diseases; notably systemic lupus erythematosus and rheumatoid arthritis.
  2. HCQ and CQ inhibit potassium efflux channels at the level of ventricular cardiomyocytes in a dose-dependent manner, potentially leading to QTc prolongation as early as 2 days after starting the medications.
  3. Both HCQ and CQ accumulate in lysosomes of various tissues including the eyes, adrenal, pituitary glands, kidney, bone marrow, lung, liver, and heart.
  4. The incidence of QTc prolongation after starting HCQ is estimated to range from 3.9-8.5%. Change in QTc associated with HCQ is, however, not associated with increased mortality.
  5. Concomitant use of HCQ/CQ and azithromycin significantly increases the risk of ventricular arrhythmias and other cardiac events.
  6. While electrocardiographic monitoring is not part of the current standard practice when HCQ or CQ is prescribed for the treatment of rheumatologic or dermatologic conditions, it should be considered in patients with ≥1 risk factor for QT prolongation. Concomitant use of QT-prolonging medications should be avoided.
  7. Other cardiac toxicities associated with HCQ/CQ include conduction defects (3.3% of reported adverse events) and cardiomyopathy (3.4% of reported adverse events), are dose dependent, and usually occur in the setting of prolonged use (mean treatment duration of 7-12 years).
  8. Cardiomyopathy associated with HCQ/CQ is typically restrictive, and endomyocardial biopsy is often necessary for diagnosis. The classic histologic findings of curvilinear bodies and lysosomal inclusions are similar to those in Fabry’s disease.
  9. Atrioventricular (AV) conduction defects are typically permanent. Cardiomyopathy, however, may improve with drug cessation and guideline-directed medical therapy.
  10. While rheumatologic diseases are strongly linked to an increased risk of atherosclerosis, how HCQ/CQ impacts that risk is unclear, with conflicting findings in the literature.

Keywords: Antimalarials, Arrhythmias, Cardiac, Arthritis, Rheumatoid, Atherosclerosis, Azithromycin, Cardiac Conduction System Disease, Cardiomyopathies, Cardiotoxicity, Chloroquine, Dermatology, Heart Failure, Hydroxychloroquine, Long QT Syndrome, Lupus Erythematosus, Systemic, Lysosomes, Myocytes, Cardiac, Primary Prevention, Rheumatology, Risk Factors

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