Chloroquine- and Hydroxychloroquine–Induced Cardiomyopathy: A Case Report and Brief Literature Review

Abstract

Objectives To present an index case and review the histologic and electron microscopic findings in chloroquine (CQ) and hydroxychloroquine (HCQ) myopathy, focusing primarily on cardiomyopathy. CQ and HCQ are antimalarial drugs with disease-modifying activity in rheumatic diseases (DMARD) and now are among the most widely used DMARDs. Although they are rare, severe adverse effects caused mainly by deposition of intracellular metabolites in both cardiac and skeletal muscle have been described. Currently, both CQ and HCQ have been proposed to have efficacy for patients with coronavirus disease 2019, and several large centers in the United States and other countries have started clinical trials. Methods A case of HCQ cardiotoxicity diagnosed on an endomyocardial biopsy is presented. A review of the pathology archives was performed to identify additional cases of CQ or HCQ myopathy, and histologic changes were recorded. A brief literature review with an emphasis on pathologic findings in myopathies was performed. Results Including the index case, 4 cases of CQ or HCQ myopathy were identified. Light microscopic findings included vacuolated myopathy, and electron microscopic findings included myeloid bodies and curvilinear inclusion bodies. Conclusion CQ and HCQ myopathy can present following long-term administration of the drug. The pathologic findings are nonspecific and overlap with other vacuolated myopathies, necessitating careful correlation of the histologic changes with the patient’s medical history.

Rapid Onset and Resolution of Hydroxychloroquine Cardiomyopathy: A Case Report

“…Case Reports in Rheumatology mitochondria by decreasing oxidative phosphorylation, increasing mitochondrial DNA damage, and promoting apoptosis, leading to myonecrosis [9]. Another possible mechanism for HCQ cardiotoxicity is that HCQ binds directly to the myocyte membrane phospholipids, neutralizing phosphate groups and displacing calcium, leading to myofiber necrosis [9].…”

“…Hypokalemia and hyperthermia were found to increase the incidence of HCQ-induced proarrhythmia [ 8 ]. Moreover, HCQ's effect on the autophagy-lysosome pathway leads to cytosolic accumulation of toxic metabolite products in the phagosomes, inhibiting lysosomal function, affecting mitochondria by decreasing oxidative phosphorylation, increasing mitochondrial DNA damage, and promoting apoptosis, leading to myonecrosis [ 9 ]. Another possible mechanism for HCQ cardiotoxicity is that HCQ binds directly to the myocyte membrane phospholipids, neutralizing phosphate groups and displacing calcium, leading to myofiber necrosis [ 9 ].…”

“…Moreover, HCQ's effect on the autophagy-lysosome pathway leads to cytosolic accumulation of toxic metabolite products in the phagosomes, inhibiting lysosomal function, affecting mitochondria by decreasing oxidative phosphorylation, increasing mitochondrial DNA damage, and promoting apoptosis, leading to myonecrosis [ 9 ]. Another possible mechanism for HCQ cardiotoxicity is that HCQ binds directly to the myocyte membrane phospholipids, neutralizing phosphate groups and displacing calcium, leading to myofiber necrosis [ 9 ]. Risk factors for HCQ cardiotoxicity include long duration of therapy (more than 10 years), using higher doses per kilogram per day, female gender, older age, and previous cardiovascular or kidney disease [ 4 ].…”

The impact of SARS-CoV-2 treatment on the cardiovascular system: an updated review

“…These effects are attributable to the intracellular accumulation of toxic metabolites, necrosis of cardiomyocytes and mitochondrial damage. Examination by electron microscopy has shown curvilinear bodies and lamellar structures due to the accumulation of glycolipids and glycoproteins (Nadeem et al 2021;Chen et al 2006;Chatre et al 2018).…”

Review of Hydroxychloroquine Cardiotoxicity: Lessons From the COVID-19 Pandemic

“…Typically, the risk of cardiotoxicity is dose and time dependent, usually taking years to develop [ 17 ]. Some risk factors associated with increased adverse effects are female sex, older age, and renal dysfunction [ 17 ].

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