Hydroxychloroquine-associated cardiomyopathy with nondiagnostic noninvasive evaluation: diagnostic value of endomyocardial biopsy in a case-based review.

Hydroxychloroquine (HCQ) is a cornerstone in treating autoimmune diseases and is generally well-tolerated. Cardiotoxicity is a rare but serious adverse effect of prolonged HCQ therapy. The progression of cardiac dysfunction may evade early detection with standard noninvasive investigations. This case report was prepared in accordance with the CABARET guidelines from the EQUATOR Network. The patient underwent comprehensive clinical evaluation for diagnostic clarification. A 57-year-old woman with Sjogren's disease (SjD) who was treated with HCQ 400 mg daily for nearly 21 years (cumulative dose ~ 3,000 g). The patient started to develop symptoms of syncope, shortness of breath and lower extremity edema. Noninvasive evaluation including echocardiography, coronary angiography, and cardiac magnetic resonance imaging failed to identify a clear etiology, demonstrating preserved ventricular size and systolic function without evidence of infiltrative or inflammatory cardiomyopathy. Continued decline in the patient's clinical status in addition to lack of response to medical therapy, an endomyocardial biopsy (EMB) was performed and revealed findings consistent with HCQ induced cardiotoxicity. HCQ was stopped; however, the damage was beyond reversal, so the patient ended up having an orthotopic heart transplantation. This case sheds light on an irreversible HCQ-induced cardiotoxicity that ended up with a heart transplantation. Despite extensive cardiac workup this adverse effect remained undetected until advanced disease. Delayed diagnosis can lead to irreversible cardiac damage and EMB should be considered in patients on prolonged HCQ therapy with unexplained cardiac symptoms and nondiagnostic workup. This can prompt early discontinuation of HCQ with potentially reversible damage and more favorable outcomes.