ArticleEuropean heart journal. Cardiovascular pharmacotherapy2026
Clinical and experimental insights into hydroxychloroquine-associated electrical abnormalities and cardiomyopathy.
Article in European heart journal. Cardiovascular pharmacotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Universal evidence and contextual pharmacotherapy.European heart journal. Cardiovascular pharmacotherapy · 2026Article
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16 authors.
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Abstract
aimsHydroxychloroquine (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
resultsWe 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.
conclusionHydroxychloroquine 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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