Cardiotoxicity following cyclophosphamide therapy: a case report

Abstract

IntroductionCardiac toxicity is one of the life-threatening complications of cancer therapy. Systemic anticancer treatments may exert their own toxic effects or can aggravate adverse effects of other drugs. We report a case of cyclophosphamide-induced cardiotoxicity in a patient with normal cardiac functions before chemotherapy.Case presentationA 66-year-old Caucasian woman with a mediastinal mass diagnosed with Burkitt lymphoma underwent chemotherapy with rituximab-hyperfractionated-cyclophosphamide-vincristine-doxorubicin-dexamethasone. On the seventh day of chemotherapy, she developed dyspnea. An electrocardiogram demonstrated low voltage in the limb and precordial leads. It also showed diffusely increased myocardial echogenicity, mild pericardial and pleural effusion, generally impaired biventricular systolic functions with a left ventricular ejection fraction of 31%, and right ventricular mid-apical akinesia, even though she had normal biventricular functions before chemotherapy. Cyclophosphamide-induced cardiotoxicity was suspected and she was given treatment for congestive heart failure. Her dyspnea decreased and she was discharged on the tenth day with a left ventricular ejection fraction of 37% and normal right ventricular function. After 1 month, echocardiography showed normal biventricular functions with a left ventricular ejection fraction of 60%.ConclusionsDrug-induced cardiotoxicity, therefore, should be taken into consideration when using cyclophosphamide therapy, especially when anthracyclines are co-administered. Close communication between hematologists and cardiologists is required.

Acute and fatal cardiotoxicity following high-dose cyclophosphamide in a patient undergoing autologous stem cell transplantation for systemic sclerosis despite satisfactory cardiopulmonary screening

“…[4][5][6] In one reported case of a patient treated for non-Hodgkin lymphoma, post-mortem examination showed normal arteries, myocardial hemorrhage and necrosis, without inflammatory cells or fibrosis, a picture similar to our findings. 5 Pathogenesis of acute CYC toxicity is thought to be related to toxic endothelial damage leading to extravasation of active CYC metabolites and increased free oxygen radicals, with consequent cardiomyocyte apoptosis, interstitial hemorrhage and edema. 6 Elderly patients, history of mediastinal irradiation and prior anthracycline exposure may confer a higher risk of acute CYC cardiotoxicity.…”

“…Acute CYC-related cardiotoxicity has been previously reported in cancer patients who received simultaneous cardiotoxic drugs such as anthracyclines. 4,5 Post-mortem examinations, the only means of confirming direct CYC causality, are rare. CYC-related cardiotoxicity usually occurs in the first 3 weeks after drug administration.…”

“…A micro-voltage with sinus tachycardia is commonly observed as well as increased serum levels of troponin Ic. 4,5,7 Echocardiography constantly reveals severe biventricular failure and global hypokinesia. Pericardial effusion can be observed.…”

Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity

“…The delayed toxicity of doxorubicin, in combination with the direct cytotoxic effects and apoptosis seen with cyclophosphamide, led to her initial drop in LVEF. 4,15 Subsequent exposure to cisplatin in May 2014 further damaged DNA repair mechanisms and quickly depressed our patient's LVEF to 25%. Upon discontinuation of cisplatin, her LVEF rapidly improved to 35-40%.…”

The analysis of the parameters of 24‐hr ECG Holter monitoring in patients with blood neoplasms undergoing high‐dose chemotherapy and stem cell transplantation

“…Generally in comment to the influence of chemotherapy on ECG changes there are not many reports in the group of patients undergoing HSCT and especially using 24‐hr Holter monitoring taking the influence of a single agent into consideration. In cases when cyclophosphamide treatment was used in an early period after it there were some changes in standard ECG including low voltage of QRS, QT dispersion and systolic dysfunction of the left ventricle with ejection fraction about 30% as well as dysfunction of the right ventricle, and troponin elevation, however, the changes recovered after 1 month of treatment and only in few patients the diffuse myocardial thickening due to hemorrhagic myopericarditis was present with pericardial effusion leading to tamponade resulting in death (Atalay, Gulmez, & Ozsancak Ugurlu, ; Auner et al., ; Birchall, Lalani, Venner, & Hugh, ; Gottdiener, Appelbaum, Ferrans, Deisseroth, & Ziegler, ; Morandi et al., ; Nakamae, Tsumura, Hino, Hayashi, & Tatsumi, ; Wadia, ). Cardiotoxicity induced by cyclophosphamide is well‐known, with symptoms occurring usually within 1–3 weeks, resolving in some patients without late consequences, with the high mortality rate to 43%, however, no such cases were described in HSCT treatment so this is a novel finding that cyclophosphamide may increase less severe ECG changes at first that should be monitored (Goldberg, Antin, Guinan, & Rappeport, ; Morandi, Ruffini, Benvenuto, Raimondi, & Fosser, ; Slordal & Spigset, ; Yeh et al., ).…”