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Anthracycline induced Cardiomyopathy

Anthracycline induced Cardiomyopathy

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Anthracycline induced Cardiomyopathy

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  1. Anthracycline induced Cardiomyopathy AM Report December 11 2009

  2. Chemotherapy and Cardiotoxicity • Anthracyclines • Herceptin • Antimetabolites • 5-fluorouracil - coronary vasospasm • Fludarabine - high dose for BMT conditioning • Vinca alkaloids - hypertension, myocardial ischemia • Taxanes - conduction abnormalities • Cyclophosphamide - cardiomyopathy • Bleomycin - pericarditis • Mitomycin C - heart failure • Monoclonal antibodies

  3. History of Anthracycline use • Fermentation product of Streptomyces peucetius • Daunomycin and doxorubicin devolped in 1960s • Clinical Uses • breast and esophageal carcinomas • osteosarcoma, • Kaposi's sarcoma and soft-tissue sarcomas • Hodgkin's and non-Hodgkin's lymphomas Doxorubicin

  4. Mechanism • Therapuetic • Intercalating between base pairs of the DNA/RNA • Inhibits topoiosomerase II enzyme • Cardiotoxicity • Production of toxic oxygenハfree radicals and an increase in oxidative stress • Loss of myofibrils and the vacuolization of cytoplasm

  5. Risk Factors - Cumulative dose

  6. Risk Factors • Age • <3 years of age and >70 years of age • Previous/Concurrent Radiation • Concomitant chemotherapy • Herceptin and taxols • Bone Marrow Transplant • Cardiac Risk Factors

  7. Clinical Manifestations • Acute - during infusion to 1 week • Arrhythmias • Ventricular dysfunction • Pericarditis/myocarditis • Early - < 1 year • Dose-related cardomyopathy • Late

  8. Monitoring • Serial noninvasive monitoring of LVEF • Radionuclide angiography (MUGA) • Echocardiography • Exercise stress radionuclide ventriculography • Biomarkers • Serum troponins • BNP/pro-BNP • Endomyocardial Biopsy

  9. Monitoring • Normal EF • Baseline (prior to 100 mg/m2) • 2nd study after 250 to 300 mg/m2 • 3rd at 400-450 mg/m2 • Sequential studies prior to each additional dose • EF 30-50% • EF study prior to each dose • EF < 30% - recommend against initiating • Discontinue doxorubicin for decrease in EF >10% or absolute < 30%

  10. Prevention • Altering infusion protocol • Alternate anthracycline derivatives • Liposomal preparations • Dexrazoxane - metal-chelating agent • Beta-blockers • ACE inhibitors

  11. Prognosis and Treatment • Prognosis • Mortality rates of > 30% in early studies • Treatment • ACE inhibitors • Traditional Heart failure Management • Heart Transplant

  12. Refrences • Up-to-Date • Cancer Medicine 6 • CHEST February 1999 vol. 115 no. 2 569-571 • Schwartz, RG, McKenzie, WB, Alexander, J, et al. Congestive heart failure and left ventricular dysfunction complication doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med 1987; 82:1109. • Jannazzo A, Hoffman J, Lutz M. Monitoring of anthracycline-induced cardiotoxicity. Ann Pharmacother. 2008 Jan;42(1):99-104. • Appel JM, Nielsen D, Zerahn B, Jensen BV, Skagen K. Anthracycline-induced chronic cardiotoxicity and heart failure. Acta Oncol. 2007;46(5):576-80. • Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998 Sep 24;339(13):900-5.