Mitral regurgitation is a serious complication of acute myocardial infarction (AMI) as it impairs cardiac performance and confers increased risk for adverse outcomes such as heart failure and death. Despite advances in treatment of AMI, mitral regurgitation remains common and has been reported in over 50% of post-AMI patients. Papillary muscle infarction - which can be a consequence of AMI - provides a mechanism for mitral regurgitation, whereby myocyte necrosis produces papillary muscle dysfunction, impaired tethering of the mitral valve leaflets, and regurgitant flow. The goal of this research proposal is to identify incidence, predictors, and functional consequences of papillary infarction following AMI. Central to this proposal is the hypothesis that papillary infarction will confer increased risk for development of post-AMI mitral regurgitation. To investigate this, I will employ multimodality imaging to study papillary infarction a broad post-AMI population. Delayed enhancement magnetic resonance imaging (MRI) will be used to detect sub-clinical papillary infarction;This technique enables in-vivo detection of papillary myocyte necrosis in a manner never before possible in humans, providing non-invasive infarct assessment that closely replicates histopathology. Two delayed enhancement MRI techniques - breath-held two dimensional (2D) and free-breathing three dimensional (3D) imaging - will be used to assess incidence of papillary infarction;The techniques will be compared to determine whether incidence is greater with 3D vs. 2D imaging. Comprehensive clinical, angiographic, and imaging variables will be obtained and analyzed to identify predictors of papillary infarction. Serial follow-up echocardiography will be used to assess whether papillary muscle infarction independently predicts long-term risk for post-AMI mitral regurgitation after controlling for traditional clinical and imaging predictors. Analysis will also be performed to assess the relationship between papillary muscle infarction and left atrial remodeling. The results of this study may provide important insights regarding papillary muscle infarction as a predictor of mitral regurgitation and cardiac chamber remodeling in the post-AMI setting. Through this project, which integrates my interests in cardiovascular imaging and outcomes research, I will receive valuable mentorship and attain critical skills within the context of a 5 year career development award. I will obtain formal training in principles of clinical research and statistical analysis through a Master's degree in clinical investigation. I will receive didactic and hands-on training in advanced cardiac MRI techniques, with specific focus on free breathing MRI. I will implement my research study with mentorship provided by two leading investigators in cardiac imaging and epidemiologic research. This career development plan will enhance my capabilities as a physician-scientist and will enable me to develop future independent projects that employ cardiac imaging as a tool to study cardiac pathophysiology and improve patient care.

Public Health Relevance

Mitral regurgitation is a serious complication of acute myocardial infarction (AMI) as it impairs cardiac performance and confers increased risk for adverse outcomes such as heart failure and death. Papillary muscle infarction, which provides a mechanism for mitral regurgitation, can be identified using cardiac magnetic resonance imaging (MRI) - a powerful imaging tool that enables detection of papillary infarcts never before seen. This study will use cardiac MRI to study incidence, predictors, and functional consequences of papillary muscle infarction following AMI.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL102249-05
Application #
8677953
Study Section
Special Emphasis Panel (ZHL1-CSR-R (F1))
Program Officer
Scott, Jane
Project Start
2010-08-20
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
$136,080
Indirect Cost
$10,080
Name
Weill Medical College of Cornell University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Kim, Jiwon; Medicherla, Chaitanya B; Ma, Claudia L et al. (2016) Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance. PLoS One 11:e0147349
Kim, Jiwon; Srinivasan, Aparna; Seoane, Tania et al. (2016) Echocardiographic Linear Dimensions for Assessment of Right Ventricular Chamber Volume as Demonstrated by Cardiac Magnetic Resonance. J Am Soc Echocardiogr 29:861-70
Weinsaft, Jonathan W; Kim, Jiwon; Medicherla, Chaitanya B et al. (2016) Echocardiographic Algorithm for Post-Myocardial Infarction LV Thrombus: A Gatekeeper for Thrombus Evaluation by Delayed Enhancement CMR. JACC Cardiovasc Imaging 9:505-15
Kochav, Jonathan; Simprini, Lauren; Weinsaft, Jonathan W (2015) Imaging of the right heart--CT and CMR. Echocardiography 32 Suppl 1:S53-68
Goyal, Parag; Kim, Jiwon; Feher, Attila et al. (2015) Myocardial perfusion pattern for stratification of ischemic mitral regurgitation response to percutaneous coronary intervention. Coron Artery Dis 26:642-50
Kim, Jiwon; Kochav, Jonathan D; Gurevich, Sergey et al. (2014) Left ventricular geometric remodeling in relation to non-ischemic scar pattern on cardiac magnetic resonance imaging. Int J Cardiovasc Imaging 30:1559-67
Weinsaft, Jonathan W; Kochav, Jonathan D; Kim, Jiwon et al. (2014) P wave area for quantitative electrocardiographic assessment of left atrial remodeling. PLoS One 9:e99178
Weinsaft, Jonathan W; Kochav, Jonathan D; Afroz, Anika et al. (2014) Q wave area for stratification of global left ventricular infarct size: comparison to conventional ECG assessment using Selvester QRS-score. Coron Artery Dis 25:138-44
Volo, Samuel C; Kim, Jiwon; Gurevich, Sergey et al. (2014) Effect of myocardial perfusion pattern on frequency and severity of mitral regurgitation in patients with known or suspected coronary artery disease. Am J Cardiol 114:355-61
Simprini, Lauren A; Afroz, Anika; Cooper, Mitchell A et al. (2014) Routine cine-CMR for prosthesis-associated mitral regurgitation: a multicenter comparison to echocardiography. J Heart Valve Dis 23:575-82

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