This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Cancer survivals are at risk of developing heart failure if they have been treated with cytotoxic chemotherapeutic agents such as anthracyclines/anthraquinones, high-dose alkylating agents or antimetabolites, and other newer monoclonal antibodies and tyrosine kinase inhibitors. However, the prevalence, characteristics, and risk factors of developing late (>2 years) subclinical cardiomyopathy have not been well described and current clinical practice do not include heart failure screening. The main objective of this proposed project is to assess the cardiac status of long-term cancer survivors, and to evaluate screening and monitoring strategies to detect subclinical cardiac dysfunction induced by cardiotoxic chemotherapy. Be identifying cancer survivors via a screening protocol involving venous blood sample collection to measure natriuretic peptides and mycloperoxidase, autonomic testing for heart rate variability, and portable echocardiography screening for cardiac structure and performance abnormalities, we aim to determine the prevalence of late subclinical cardiac and autonomic dysfunction and to construct and validate prediction rules for detecting subclinical cardiac dysfunction in this population of cancer survivors. Diagnostic predictive accuracies of single and multi-biomarkers in detecting subclinical cardiomyopathy will be determined by standard decision statistics, and novel metabolic and oxidative biomarkers will be developed to better screen for subclinical cardiac dysfunction in cancer survivors. The long-term goal of this project is to develop a multimarker-echocardiography screening strategy that can identify and monitor cancer survivors in the most cost-effective and practical manner. Our ultimate goal is to establish a large cohort of asymptomatic (or minimally symptomatic) cancer survivors with early heart failure and to provide longitudinal follow-up for future mechanistic research opportunities (particularly in relation to the roles of oxidative stress and metabolic derangements).
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