352. Case Report: The Culprit in the Pillbox – University of Kansas

CardioNerds (Dr. Amit Goyal) join Dr. Anureet Malhotra, Dr. John Fritzlen, and Dr. Tarun Dalia from the University of Kansas School of Medicine for some of Kansas City’s famous barbeque. They discuss a case of Hydroxychloroquine induced cardiomyopathy. Notes were drafted by Dr. Anureet Malhotra, Dr. John Fritzlen, and Dr. Tarun Dalia. Expert commentary was provided by Dr. Pradeep Mammen. The episode audio was edited by Dr. Akiva Rosenzveig.



Drug-induced cardiomyopathy remains an important and under-recognized etiology of cardiomyopathy and heart failure. Hydroxychloroquine is a disease-modifying antirheumatic drug used for various rheumatological conditions, and its long-term use is well-known to have toxic effects on cardiac muscle cells. Multiple cardiac manifestations of these drugs have been identified, the most prominent being electrophysiological disturbances.



In this episode, we discuss a biopsy-proven case of hydroxychloroquine-induced cardiotoxicity with detailed histopathological and imaging findings. We develop a roadmap for the diagnosis of hydroxychloroquine-induced cardiomyopathy and discuss the various differentials of drug-induced cardiomyopathy. We highlight the importance of clinical monitoring and early consideration of drug-induced toxicities as a culprit for heart failure.







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Case Media - Hydroxychloroquine induced cardiomyopathy

























Pearls - Hydroxychloroquine induced cardiomyopathy




Continued decline in left ventricular systolic function despite appropriate guideline directed medical therapy should prompt a thorough evaluation for unrecognized etiologies and warrants an early referral to advanced heart failure specialists.



Transthoracic echocardiogram is a valuable non-invasive screening tool for suspected pulmonary hypertension, but right heart catheterization is required for definitive diagnosis.



Cardiac MRI can be used for better characterization of myocardial tissue and can aid in the evaluation of patients with non-ischemic cardiomyopathy.



Hydroxychloroquine (HCQ) is a commonly used DMARD that remains an underrecognized etiology of cardiomyopathy and heart failure. In addition to ophthalmological screening, annual ECG, as well as echocardiography screening for patients on long-term HCQ therapy, should be considered in patients at risk for cardiovascular toxicity, including those with pre-existing cardiovascular disease, older age, female sex, longer duration of therapy, and renal impairment.



Management of hydroxychloroquine-associated cardiomyopathy consists of discontinuing hydroxychloroquine and standard guideline-directed medical therapy for heart failure.  HCQ cardiomyopathy may persist despite medical therapy, and advanced therapy options may have to be considered in those with refractory heart failure.




Show Notes - Hydroxychloroquine induced cardiomyopathy



What are the various cardiotoxic effects of hydroxychloroquine (HCQ) and the mechanism of HCQ-mediated cardiomyopathy?



One of the most frequently prescribed disease-modifying antirheumatic drugs (DMARDs), HCQ is an immunomodulatory and anti-inflammatory agent that remains an integral part of treatment for a myriad of rheumatological conditions. Its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions.8 The known cardiac manifestations of HCQ-induced toxicity include conduction abnormalities, ventricular hypertrophy, hypokinesia, and lastly, cardiomyopathy.




Conduction Abnormalities - by binding to and inhibiting the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel,