Utility of tissue Doppler and strain rate imaging in the early detection of trastuzumab and anthracycline mediated cardiomyopathy.
J Am Soc Echocardiogr
; 22(4): 418-24, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19269133
BACKGROUND: Trastuzumab provides considerable therapeutic benefits in the adjuvant setting of breast cancer. However, its use is limited by an elevated incidence of cardiotoxicity when used in combination with doxorubicin. Although Myocet (liposomal encapsulated doxorubicin) is less cardiotoxic, its cardiac safety profile with trastuzumab is not well known. The aim of this study was to determine if sensitive indices of left ventricular (LV) dysfunction, specifically Doppler tissue imaging (DTI), would be useful for addressing the early detection of trastuzumab and anthracycline-mediated cardiotoxicity. METHODS: In an acute murine model, wild-type C57Bl/6 mice (n = 60) received one of the following drug regimens: (1) control, (2) doxorubicin, (3) Myocet, (4) trastuzumab, (5) doxorubicin plus trastuzumab, or (6) Myocet plus trastuzumab. DTI-derived peak endocardial systolic velocity, strain rate, and LV ejection fraction were measured serially for 5 days. On day 5, the hearts, lungs, and livers were removed for histopathologic and Western blot analyses. RESULTS: Mice treated with Myocet plus trastuzumab demonstrated minimal cardiotoxicity compared with those treated with doxorubicin plus trastuzumab. Progressive LV dilatation and LV systolic dysfunction were observed by day 4 of treatment with doxorubicin plus trastuzumab, compared with preserved LV ejection fraction in the remaining groups. DTI parameters decreased within 24 hours in the doxorubicin alone and doxorubicin plus trastuzumab groups and predicted early mortality. The survival rate was only 20% at day 5 of the experiment in the doxorubicin plus trastuzumab group, whereas 100% of mice receiving trastuzumab, Myocet, or Myocet plus trastuzumab survived the 5 days. CONCLUSION: DTI can detect early LV dysfunction prior to alterations in conventional echocardiographic indices and predicts early mortality in mice receiving doxorubicin plus trastuzumab.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ecocardiografia Doppler
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Protocolos de Quimioterapia Combinada Antineoplásica
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Doxorrubicina
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Disfunção Ventricular Esquerda
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Antraciclinas
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Técnicas de Imagem por Elasticidade
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Anticorpos Monoclonais
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article