High HCQ Cumulative Doses Linked to Cardiac Conduction Disturbances in SLE

A higher cumulative dose was associated with the development of ECG conduction disturbances in patients with SLE.

In patients with systemic lupus erythematosus (SLE), treatment with high cumulative doses of hydroxychloroquine (HCQ) is linked to the development of new cardiac conduction abnormalities, according to study findings published in European Journal of Internal Medicine.

Researchers of a single-center study sought to evaluate the association between cumulative dose of HCQ and electrocardiogram (ECG) abnormalities in patients with SLE.

Participants were enrolled from the rheumatology department of a tertiary referral center located in northern Spain. 

Based on 2007 to 2009 American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Recommendations for Standardization and Interpretation of the Electrocardiogram, cardiac disturbances were divided into
2 categories:

  • Conduction disturbances
  • Atrioventricular block (AVB)
  • Left bundle branch block (LBBB)
  • Right bundle branch block (RBBB)
  • Long  QT
  • Short PR
  • Structural alterations
  • Atrial enlargement
  • Ventricular hypertrophy
[M]ore observational and prospective studies are needed to reach conclusive results on the medium long-term effect of HCQ in cardiac conduction and structural alterations in SLE populations.

The primary outcome variable was new cardiac conduction disturbances detected on ECG.

All participants were aged greater than 18 years and received a resting standard 12-lead ECG prior to initiation of HCQ, then another ECG during follow-up at 3 or more months after initiation of HCQ.

Cumulative dose of HCQ (cHCQ) was defined as “the total dose in grams taken by the patients from the beginning of the treatment to the date of the last follow-up visit.”

The study population, which included a total of 105 individuals, was divided into 2 groups: low-dose (ie, below the median cHCQ of 913 g) group and high-dose (ie, above the median cHCQ of 913 g) group.

The mean participant age at diagnosis of SLE was 46.1±16.3 years and 93 were women.

Overall, 11.4% (n=12/105) of the patients had conduction disturbances on ECG performed prior to initiation of HCQ treatment, including RBBB in 7 participants, AVB in 4 participants, and LBBB in 1 participant. Study participants were followed-up for a mean period of 16.3±10.3 years.

Results of the study revealed that a significantly higher number of conduction disturbances were reported in the high-dose cHCQ group (odds ratio [OR], 2.89; 95% CI, 1.01-8.23; P =.047).

According to multivariate analysis, following adjustment, the association between cHCQ and new conduction disturbances did not achieve statistical significance (OR, 1.06; 95% CI, 0.99-1.14; P =.09). Among the other covariates, age at diagnosis was the only variable to demonstrate a statistically significant association with conduction disturbances (OR, 1.06; 95% CI, 1.01-1.17; P =.03).

No statistically significant differences were reported in the tendency to develop more high-grade AVB or structural abnormalities.

The key limitations of the current study included its retrospective design and the lack of a control group of patients with SLE who did not receive HCQ.

“[M]ore observational and prospective studies are needed to reach conclusive results on the medium long-term effect of HCQ in cardiac conduction and structural alterations in SLE populations,” the researchers concluded.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Zubiaur J, Herrero-Morant A, Margarida de Castro A, et al. Association between cumulative dose of hydroxychloroquine and electrocardiographic abnormalities in patients with systemic lupus erythematosus. Eur J Intern Med. Published online March 20, 2023. doi:10.1016/j.ejim.2023.03.014