Cardiac Fibrosis and Risk Prediction in Cancer Treatment-Related Cardiotoxicity

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 DESCRIPTION (provided by applicant): This Mentored Clinical Scientist Research Career Development Award proposal describes a five-year career development and training plan for Dr. Chetan Shenoy, a cardiovascular physician investigator at the University of Minnesota. His long-term goal is to be an independent, patient-oriented physician investigator who will make significant contributions in the field of preventive onco-cardiology. His career development plan encompasses the following: protected research time, focused didactic coursework within a Masters in Clinical Research degree program, hands-on training in cardiovascular prevention and advanced clinical research methodology, a highly structured cohesive mentoring program designed with a multidisciplinary team of accomplished clinical investigators, first-hand experience in patient-oriented research through the design and execution of a prospective cohort study initiated by Dr. Shenoy, and ultimately, successful application for independent research funding. Common cancer treatments such as anthracyclines and trastuzumab are associated with an increased risk of cardiotoxicity, which is responsible for significant mortality and morbidity in cancer survivors despite current preventive strategies. Identification of patients at risk for cancer treatment-related cardiotoxicity would allow us to intervene and prevent cardiovascular morbidity and mortality and improve the overall outcomes of patients with cancer. The overall objective of the proposed research is to establish the role of pre-existing cardiac fibrosis detected by magnetic resonance imaging to predict cardiotoxicity from cardiotoxic medications. In a prospective cohort study, Dr. Shenoy will first determine the prevalence and predictors of cardiac fibrosis in cancer patients before treatment with anthracyclines and/or trastuzumab. Next, he will determine the association between pre-existing cardiac fibrosis and cardiotoxicity at 24 months after initiation of anthracyclines and/or trastuzumab. Finally, he will determine the association between pre-existing cardiac fibrosis and cardiac troponin levels after initiation of anthracyclines and/or trastuzumab. This research will provide the first systematic data on the role of pre- existing cardiac fibrosis for the prediction f cardiotoxicity, laying the foundation for Dr. Shenoy's long-term goal of developing new interventions to prevent cardiovascular disease in patients with cancer. In summary, a comprehensive career development plan in the context of a well-defined training, research and mentorship structure will allow Dr. Shenoy to emerge as a highly successful, independent physician investigator in preventive onco-cardiology.