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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-SBIB-U (57))
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Baker, Houston
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Wake Forest University Health Sciences
Internal Medicine/Medicine
Schools of Medicine
United States
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Stacey, R Brandon; Vera, Trinity; Morgan, Timothy M et al. (2018) Asymptomatic myocardial ischemia forecasts adverse events in cardiovascular magnetic resonance dobutamine stress testing of high-risk middle-aged and elderly individuals. J Cardiovasc Magn Reson 20:75
Jordan, Jennifer H; Todd, Ryan M; Vasu, Sujethra et al. (2018) Cardiovascular Magnetic Resonance in the Oncology Patient. JACC Cardiovasc Imaging 11:1150-1172
Jolly, Marie-Pierre; Jordan, Jennifer H; Meléndez, Giselle C et al. (2017) Automated assessments of circumferential strain from cine CMR correlate with LVEF declines in cancer patients early after receipt of cardio-toxic chemotherapy. J Cardiovasc Magn Reson 19:59
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Jordan, Jennifer H; Sukpraphrute, Bunyapon; Meléndez, Giselle C et al. (2017) Early Myocardial Strain Changes During Potentially Cardiotoxic Chemotherapy May Occur as a Result of Reductions in Left Ventricular End-Diastolic Volume: The Need to Interpret Left Ventricular Strain With Volumes. Circulation 135:2575-2577
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Vera, Trinity; D'Agostino Jr, Ralph B; Jordan, Jennifer H et al. (2015) Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection Fraction After Chemotherapy. Am J Cardiol 116:1752-5
Chotenimitkhun, Runyawan; D'Agostino Jr, Ralph; Lawrence, Julia A et al. (2015) Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function. Can J Cardiol 31:302-7
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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