Cardiac Toxicity of Azole Antifungals

Abstract

Cardiac toxicity is an uncommon side effect of\ranti-fungal therapy. Until the recent reports of itraconazole (ITZ) associated cardiac failure, amphotericin was the\rantifungal most frequently reported with arrhythmias. We evaluated the cardiac\reffect of azole antifungals, specifically ITZ, and possible mechanisms of\rtoxicity. Ex vivo live-heart studies\rwere performed utilizing Sprague Dawley rats. Short exposure (25 (2 - 2.5 ug/mL)\rexposures, contractility decreased by 22.2% ± 15.7% and amplitude of left ventricular\rpressure decreased by 11% ± 0.17%. Electron\rmicrograph and alterations in mitochondrial\rrespiration suggest mitochondrial toxicity as an underlying mechanism. In conclusion, ITZ was associated with reductions in\rcontractility, possibly secondary to mitochondrial dysfunction and dilated cardiomyopathy.