Myocardial remodeling assesed by cardiac MRI in patients receiving chemotherapy

• Grant number: 11/10481-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2012
• End date: January 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Otávio Rizzi Coelho
• Grantee: Otávio Rizzi Coelho
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• Associated researchers: Andrei Carvalho Sposito ; Fernando Cendes ; José Barreto Campello Carvalheira ; Otávio Rizzi Coelho-Filho

Abstract

Anthracyclines, such as doxorubicin, remain a key component of many chemotherapy regimens in pediatric and adult malignancies. Cardiovascular disease remains the leading cause of morbidity and mortality among patients treated with anthracycline. The mechanism of anthracycline -induced heart damage is incompletely understood, but consists, in part, of generation of reactive oxygen species, cell injury, and the development of pathological myocardial fibrosis. Methods for detection of Anthracyclines-induced cardiotoxicity are limited and improved detection of anthracycline -induced cardiac injury may improve outcomes. Detection and quantification of anthracycline -induced myocardial injury, myocardial fibrosis, and predicting the development of heart failure is currently limited by the latency period between injury and clinical presentation, and current methods employed. The gold-standard for detection of Anthracyclines -cardiotoxicity, cardiac biopsy, is invasive and prone to sampling error; while non-invasive measures for detection of anthracycline -induced cardiotoxicity are limited by some combination of insensitivity, variability, radiation exposure, or onerous sampling protocols. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a sensitive and reproducible technique for detection and quantification of myocardial injury, function, and myocardial fibrosis. However, current CMR techniques detect focal myocardial fibrosis, while cardiac diseases, such as that induced by anthracycline, generate diffuse myocardial fibrosis. Consequently, in anthracycline -induced cardiotoxicity, LGE is either absent, or provides a partial measure of the myocardial fibrosis burden.13 Preliminary work from our group has shown that serial measurements of myocardial T1 relaxation times after gadolinium (Gd) provide a robust measure of the extracellular volume fraction (ECVF). Our group has also shown that the measured expansion of ECVF is due to diffuse MF. It is a quantitative measure, a "fibrotic index", differentiating levels of MF on a continuous scale; from normal myocardium, through diffuse MF in viable myocardium, to non-viable fibrotic scar tissue. Therefore, the primary goal is to test the utility of the CMR-derived fibrotic index for detection of cardiac injury and myocardial fibrosis after administration of anthracycline in humans. (AU)