title: Acute cardiac toxicity associated with high-dose intravenous methotrexate therapy: case report and review of the literature.
abstract: A 36-year-old woman was hospitalized for preoperative chemotherapy for osteosarcoma. She received intravenous fluids for 12 hours for volume expansion, then methotrexate 24 g (12 g/m2) over 6 hours. This was followed by intravenous leucovorin 200 mg over 1 hour. Two hours after the methotrexate infusion the patient developed chest pain and bradycardia. An electrocardiogram revealed sinus pauses, and telemetry recordings indicated a 4-beat run of ventricular tachycardia. A cardiac work-up consisting of cardiac enzyme level determination, two-dimensional echocardiography, and an adenosine technetium-99m tetrofosmin stress test was negative for structural and ischemic heart disease. The patient recovered without treatment and, approximately 2 weeks later, received a second course of methotrexate at half the dose without complication. One month later the patient received treatment with doxorubicin and cisplatin; 2 days later she died unexpectedly at home. Clinicians should be aware that high-dose methotrexate can cause cardiac symptoms and arrhythmias in previously healthy adults. This complication warrants attention and needs additional clinical investigation.
authors.affiliation: Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Perez-Verdia
authors.forename: Freddy
authors.initials: F
authors.lastname: Angulo
authors.forename: Fred L
authors.initials: FL
authors.lastname: Hardwicke
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Nugent
mesh_terms: D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001919:Bradycardia / Q000139:chemically induced*; D004562:Electrocardiography; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy; D013125:Spinal Neoplasms / Q000188:drug therapy; D017180:Tachycardia, Ventricular / Q000139:chemically induced*; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D014803:Vitamin B Complex; D002955:Leucovorin; D008727:Methotrexate