Cardiovascular (CV) injury leading to myocardial infarction (MI), cardiac death, stroke, and congestive heart failure (CHF) is a major impediment to the curative use of anthracycline-based chemotherapy for the treatment of adjuvant breast cancer, leukemia, and lymphoma. No clinically acceptable alternatives exist for children or adults that require this therapy. The assembled academic-industrial team will develop and optimize a cost-effective, automated, reproducible hardware/software platform that acquires, analyzes, and reports subclinical and clinical CV injury, identifies the mechanisms of this injury and forecasts CV event risks. This important information can be utilized for preclinical treatment protocols that, when administered to other high CV risk populations, reduce the rates of adverse CV events. This well-designed and powered pivotal clinical study to validate these technologies will: Collect within person longitudinal results before anthracycline exposure and at 3 and 24 months after exposure to determine if short-term results predict long-term subclinical disease that portends an adverse prognosis~ Determine the efficacy of this new platform in children and adults aged 10 to 80 years~ Derive population (age, gender, race, and cardiac risk factor-matched) predictive metrics for the platform compared against 6,000 individuals without known coronary artery disease from the existing Multi-Ethnic Study of Atherosclerosis (MESA)~ Standardize the automated platform to enable medical centers throughout the world with little MRI expertise to reliably and reproducibly perform the studies. This platform innovation is based on strong NCI funded preliminary data and provides a highly significant cost effective solution for a previously unsolved clinical problem that noninvasively defines early CV risk and enables targeted therapeutic interventions to dramatically reduce these risks. Reducing CV events in cancer survivors will reduce overall morbidity in patients with cancer and improve cancer-related survival.
We will translate a magnetic resonance imaging (MRI) solution to the neglected major problem of no effective clinical capacity to detect, treat, and monitor the risks of early subclinical cardiovascular injury secondary to cancer chemotherapy with anthracyclines. The assembled academic-industrial partner team will develop and optimize a MRI hardware and software platform to acquire, analyze, and report multiple measures of cardiac and aortic function, identify mechanisms of injury, and forecast cardiovascular event risks for individual adults and children in a highly time efficient, low operator dependent, reproducible, and cost effective upgrade for installed clinical MR scanners worldwide. This technical and methodologic solution for cancer investigations (PAR-10-169) will establish an innovative methodology to detect the risk for early cardiovascular disease, and thereby enable timely new preclinical therapy guidelines designed to reduce potential cardiovascular events and thus improve the overall survival in those treated for cancer.
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|Whitlock, Matthew C; Hundley, W Gregory (2015) Noninvasive Imaging of Flow and Vascular Function in Disease of the Aorta. JACC Cardiovasc Imaging 8:1094-1106|
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