The purpose of this proposal is to foster the clinical research skills and scientific development of Jamieson Bourque, M.D., M.H.S., to facilitate his transition to an independent clinical investigator. Dr. Bourque's training goal i to receive sufficient clinical research training to successfully pursue investigator-initiated R01 funding. The University of Virginia is an ideal venue to perform innovative research involving the noninvasive assessment of microvascular dysfunction and the application of exercise therapy to this disease process due to the strong research and clinical expertise of faculty in both CMR and exercise therapy and the strong institutional commitment to Dr. Bourque. His primary mentor, Christopher Kramer, M.D., is an internationally- respected thought leader in the application of cardiac magnetic resonance imaging to assess microvascular function. He has a long proven mentorship track record. Importantly, Dr. Bourque's career development plan includes advanced classes in vascular biology, advanced exercise physiology, image acquisition and processing, biostatistics, and research ethics that will strengthen his ability to pursue his long-term goal of developing a specialization in the noninvasive assessment of microvascular dysfunction and the application of exercise therapy and patient-centered outcomes clinical research to this morbid disease process. Dr. Bourque's research question is of paramount public health importance. Angina is a highly morbid condition but obstructive coronary artery disease (CAD) is seen in <50% of cases. These patients may have microvascular dysfunction, which can be assessed noninvasively by cardiac magnetic resonance imaging (CMR). The optimal treatment of this morbid population has not been sufficiently studied. Multiple medications and therapeutic exercise may improve microvascular function, aerobic capacity, and outcomes including anginal symptoms, quality of life, and cardiac events in this highly prevalent patient population.
The specific aims of Dr. Bourque's proposal are: 1) to determine the predictors of reduced myocardial perfusion reserve and patient- centered outcomes in patients with angina and no obstructive CAD; and 2) to compare changes in myocardial perfusion reserve, aerobic capacity, and patient centered outcomes between intensive medical therapy and intensive medical therapy plus exercise in patients with angina and no obstructive CAD. To address these aims, Dr. Bourque will perform a prospective study of patients with anginal symptoms and no obstructive disease on coronary angiography, who will undergo a clinical assessment followed by CMR perfusion imaging. Those with reduced perfusion reserve will be randomized to medical therapy versus medical therapy + exercise and changes in perfusion reserve, aerobic capacity, and patient-centered outcomes will be assessed. The invaluable training from this research project, robust mentorship, and didactic program will greatly assist Dr. Bourque in fulfilling his goal of becoming an independent clinical investigator.

Public Health Relevance

Cardiac chest pain affects more than 5% of the U.S. population, and many of the patients with cardiac chest pain but no large vessel obstruction may have dysfunction in the small coronary blood vessels. Identifying which patients with cardiac chest pain have this small vessel dysfunction and the effects of treatment with medicines and exercise on this dysfunction has the potential to reduce symptoms and cardiac events and improve quality of life in this population, and is thus of high public health importance.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL119620-03
Application #
8856333
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Scott, Jane
Project Start
2013-09-01
Project End
2016-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Schumann, Christopher; Bourque, Jamieson M (2018) Coronary microvascular dysfunction: Filling the research gaps with careful patient selection. J Nucl Cardiol :
Balfour Jr, Pelbreton C; Gonzalez, Jorge A; Shaw, Peter W et al. (2018) High-frequency QRS analysis to supplement ST evaluation in exercise stress electrocardiography: Incremental diagnostic accuracy and net reclassification. J Nucl Cardiol :
Ouellette, Michelle L; Löffler, Adrián I; Beller, George A et al. (2018) Clinical Characteristics, Sex Differences, and Outcomes in Patients With Normal or Near-Normal Coronary Arteries, Non-Obstructive or Obstructive Coronary Artery Disease. J Am Heart Assoc 7:
Robinson, Austin A; Bourque, Jamieson M (2018) Combined non-invasive imaging for predicting cardiovascular events : Is three a crowd? J Nucl Cardiol 25:842-844
Smith, LaVone; Myc, Lukasz; Watson, Denny et al. (2018) A high exercise workload of ? 10 METS predicts a low risk of significant ischemia and cardiac events in older adults. J Nucl Cardiol :
Löffler, Adrián I; Perez, Margarita V; Nketiah, Emmanuel O et al. (2018) Usefulness of Achieving ?10 METs With a Negative Stress Electrocardiogram to Screen for High-Risk Obstructive Coronary Artery Disease in Patients Referred for Coronary Angiography After Exercise Stress Testing. Am J Cardiol 121:289-293
Bourque, Jamieson M; Iskandrian, Ami E; Hage, Fadi G (2018) Screening pre-renal transplant: Risk factors appear key but important questions remain. J Nucl Cardiol 25:2069-2071
Zorach, Benjamin; Shaw, Peter W; Bourque, Jamieson et al. (2018) Quantitative cardiovascular magnetic resonance perfusion imaging identifies reduced flow reserve in microvascular coronary artery disease. J Cardiovasc Magn Reson 20:14
Ouellette, Michelle L; Beller, George A; Löffler, Adrián I et al. (2017) Appropriate Referrals of Angiography Despite High Prevalence of Normal Coronary Arteries or Nonobstructive CAD. J Am Coll Cardiol 69:2673-2675
Hamirani, Yasmin S; Kundu, Bijoy K; Zhong, Min et al. (2016) Noninvasive Detection of Early Metabolic Left Ventricular Remodeling in Systemic Hypertension. Cardiology 133:157-62

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