Transcript Anthracycline induced Cardiomyopathy

Anthracycline induced
Cardiomyopathy
AM Report
December 11 2009
Chemotherapy and
Cardiotoxicity
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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
History of Anthracycline use
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Fermentation product of
Streptomyces peucetius
Daunomycin and
doxorubicin devolped in
1960s
Clinical Uses
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breast and esophageal
carcinomas
osteosarcoma,
Kaposi's sarcoma and softtissue sarcomas
Hodgkin's and nonHodgkin's lymphomas
Doxorubicin
Mechanism
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Therapuetic
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Intercalating between base
pairs of the DNA/RNA
Inhibits topoiosomerase II
enzyme
Cardiotoxicity
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Production of toxic oxygen
ﾊfree radicals and an
increase in oxidative stress
Loss of myofibrils and the
vacuolization of cytoplasm
Risk Factors - Cumulative dose
Incidence of CHF as a Function of
Cumulative Doxorubicin Dose
Incidence of CHF (%)
100
80
60
40
20
0
< 350 550
600
700
Cumulative Dose (mg/m2)
Risk Factors
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Age
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Previous/Concurrent Radiation
Concomitant chemotherapy
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<3 years of age and >70 years of age
Herceptin and taxols
Bone Marrow Transplant
Cardiac Risk Factors
Clinical Manifestations
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Acute - during infusion to 1 week
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Early - < 1 year
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Arrhythmias
Ventricular dysfunction
Pericarditis/myocarditis
Dose-related cardomyopathy
Late
Monitoring
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Serial noninvasive monitoring of LVEF
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Exercise stress radionuclide ventriculography
Biomarkers
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Radionuclide angiography (MUGA)
Echocardiography
Serum troponins
BNP/pro-BNP
Endomyocardial Biopsy
Monitoring
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Normal EF
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EF 30-50%
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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 study prior to each dose
EF < 30% - recommend against initiating
Discontinue doxorubicin for decrease in EF
>10% or absolute < 30%
Prevention
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Altering infusion protocol
Alternate anthracycline derivatives
Liposomal preparations
Dexrazoxane - metal-chelating agent
Beta-blockers
ACE inhibitors
Prognosis and Treatment
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Prognosis
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Mortality rates of > 30% in early studies
Treatment
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ACE inhibitors
Traditional Heart failure Management
Heart Transplant
Refrences
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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.