PMC4528786_01
Pathologic and echocardiographic manifestations of cyclophosphamide-induced cardiac toxicity.. (A) Hematoxylin and eosin staining of cardiac specimen with areas of necrotic and viable myocardium. (B) Contraction band necrosis, intravascular thrombosis, fibrin deposition, and interstitial edema are seen on high-power field. (C) Basal short axis echocardiographic view showing concentric left ventricular (LV) thickening and a moderate-sized circumferential pericardial effusion. The right ventricle (RV) is small and nearly obliterated. (D) Parasternal long-axis view that shows posterior wall thickening with a speckled appearance. A moderate pericardial effusion is noted with inversion of RV free wall consistent with increased intrapericardial pressures.
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Cardiac autopsy revealed diffuse geographic areas of ischemic necrosis and multifocal thrombosis involving capillaries and larger muscular arterial branches (Figure 1A and B). The coronary arteries were free from atherosclerosis and vasculitis, but microvascular thrombosis was evident (Figure 1B).
Pathophysiology and clinical manifestations of cyclophosphamide-induced cardiac toxicity.. (A) Carboxyphosphamide is an inactive metabolite. (B) Acrolein is associated with hemorrhagic cystitis. (C) Phosphamide mustard is the active cytotoxic metabolite.. Abbreviation: LV, left ventricular.
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Cyclophosphamide metabolites are believed to cause oxidative stress and direct endothelial capillary damage with resultant extravasation of proteins, erythrocytes, and toxic metabolites (Figure 2). The spectrum of clinical manifestations from cyclophosphamide-induced cardiac toxicity is variable in presentation and in severity (Figure 2).