Key result
Hydroxychloroquine exposure was associated with a modest but statistically significant median QTc increase from 413 ms to 421 ms, alongside rare but clinically significant cardiomyopathy or conduction abnormalities.
Why the study?
Hydroxychloroquine is commonly prescribed but its potential for cardiotoxicity remains under-recognized.
Does hydroxychloroquine therapy cause electrical abnormalities and cardiomyopathy in patients with autoimmune diseases and in preclinical cardiomyocyte models?
Cohort (n=261)
No
Does hydroxychloroquine therapy cause electrical abnormalities and cardiomyopathy in patients with autoimmune diseases and in preclinical cardiomyocyte models?
Absolute Event Rate: 421% vs 413%
p-value: p=0.003
Hydroxychloroquine use is associated with a modest but statistically significant prolongation of QTc and PR intervals and rare but severe cases of cardiomyopathy, effects that are biologically supported by human stem cell models demonstrating impaired autophagic degradation.
May warrant QTc monitoring in long-term users; leaves open cardiomyopathy risk magnitude pending prospective data.
AIMS: Hydroxychloroquine (HCQ) is commonly prescribed for malaria and autoimmune diseases, yet its potential for cardiotoxicity remains under-recognized. The objective of this study was to investigate the clinical and experimental features of HCQ-associated cardiotoxicity. METHODS AND RESULTS: We retrospectively analysed 261 HCQ-treated patients, assessing cardiac adverse events and electrocardiographic intervals. Endomyocardial biopsy specimens were examined via transmission electron microscopy. To explore potential pathophysiological correlates, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to HCQ, and electrophysiological, ultrastructural, contractile and autophagy-related responses were evaluated. Hydroxychloroquine was discontinued in 14 patients, including 3 patients with clinically significant cardiotoxicity manifesting as heart failure or an isolated conduction abnormality (1.1% of the cohort). QTc intervals increased from a median of 413 ms [interquartile range (IQR), 399-426 ms] pre-treatment to 421 ms (IQR, 407-440 ms) on-treatment (P = 0.003), indicating a modest but statistically significant change. PR interval also increased modestly from 148 ms (IQR, 140-163 ms) to 150 ms (IQR, 142-168 ms) (P = 0.041). In vitro, HCQ exposure in hiPSC-CMs prolonged corrected field potential duration (P = 0.013) and induced arrhythmic activity. Motion analysis demonstrated a reduced peak relaxation velocity (P < 0.01), with concomitant attenuation of contractile function. Transmission electron microscopy showed lamellar inclusions consistent with myelin-like bodies. Hydroxychloroquine exposure significantly increased autophagy-related protein levels, suggesting impaired autophagic degradation. These cellular phenotypes were consistent with clinical manifestations of HCQ-associated electrical abnormalities and cardiomyopathy. CONCLUSION: Hydroxychloroquine therapy was associated with electrical abnormalities and cardiomyopathy. Experimental findings in hiPSC-CMs recapitulated key clinical features and provided biological support for the clinical observations.
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Shiba et al. (2026) conducted a cohort in Autoimmune diseases (predominantly Systemic Lupus Erythematosus) (n=261). Hydroxychloroquine vs. Pre-treatment baseline was evaluated on QTc interval (ms) (p=0.003). Hydroxychloroquine exposure was associated with a modest but statistically significant median QTc increase from 413 ms to 421 ms, alongside rare but clinically significant cardiomyopathy or conduction abnormalities.
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