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.

Public Health Relevance

Common cancer treatments such as anthracyclines and trastuzumab are associated with an increased risk of cardiovascular disease, which is responsible for significant mortality and morbidity in cancer survivors despite current prevention strategies. Current screening methods for identifying patients at high risk for cardiotoxicity are limited. Our proposed study will test the utility of pre-existing cardiac fibrosis to robustly idenify cancer patients at high risk for adverse cardiovascular outcomes. This innovative work will improve the overall cardiovascular and oncologic health and survival of a growing population.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL132011-04
Application #
9693287
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Scott, Jane
Project Start
2016-05-01
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Lin, Lucy Q; Kazmirczak, Felipe; Chen, Ko-Hsuan Amy et al. (2018) Impact of Cardiovascular Magnetic Resonance Imaging on Identifying the Etiology of Cardiomyopathy in Patients Undergoing Cardiac Transplantation. Sci Rep 8:16212
Weingärtner, Sebastian; Shenoy, Chetan; Rieger, Benedikt et al. (2018) Temporally resolved parametric assessment of Z-magnetization recovery (TOPAZ): Dynamic myocardial T1 mapping using a cine steady-state look-locker approach. Magn Reson Med 79:2087-2100
Reddy, Prajwal; Birkenbach, Mark; Shenoy, Chetan (2018) Chest Pain and a Very Abnormal Stress Echocardiogram. Circulation 138:1899-1903
Reichl, Kaitlyn; Kreykes, Sarah E; Martin, Cindy M et al. (2018) Desmoplakin Variant-Associated Arrhythmogenic Cardiomyopathy Presenting as Acute Myocarditis. Circ Genom Precis Med 11:e002373
Romano, Simone; Judd, Robert M; Kim, Raymond J et al. (2018) Feature-Tracking Global Longitudinal Strain Predicts Death in a Multicenter Population of Patients With Ischemic and Nonischemic Dilated Cardiomyopathy Incremental to Ejection Fraction and Late Gadolinium Enhancement. JACC Cardiovasc Imaging 11:1419-1429
Meiners, Becky; Shenoy, Chetan; Zordoky, Beshay N (2018) Clinical and preclinical evidence of sex-related differences in anthracycline-induced cardiotoxicity. Biol Sex Differ 9:38
Romano, Simone; Judd, Robert M; Kim, Raymond J et al. (2017) Association of Feature-Tracking Cardiac Magnetic Resonance Imaging Left Ventricular Global Longitudinal Strain With All-Cause Mortality in Patients With Reduced Left Ventricular Ejection Fraction. Circulation 135:2313-2315
Reddy, Prajwal; Shenoy, Chetan; Blaes, Anne H (2017) Cardio-oncology in the older adult. J Geriatr Oncol 8:308-314
Weingärtner, Sebastian; Moeller, Steen; Schmitter, Sebastian et al. (2017) Simultaneous multislice imaging for native myocardial T1 mapping: Improved spatial coverage in a single breath-hold. Magn Reson Med 78:462-471
Huang, Hans; Nijjar, Prabhjot S; Misialek, Jeffrey R et al. (2017) Accuracy of left ventricular ejection fraction by contemporary multiple gated acquisition scanning in patients with cancer: comparison with cardiovascular magnetic resonance. J Cardiovasc Magn Reson 19:34