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Serial evaluation of cardioprotective effects of exercise training in heart failure using cardiac diffusion tensor MRI

Award Number: R01HL151704
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary / Abstract Heart failure (HF) is accounts for 1 in 9 deaths in the United States and currently affects ~6 million with a prevalence of 250,00-400,000 and incidence of 70,000-120,000. Current therapy does not address the underlying loss of functional heart muscle and adverse structural remodeling. One novel potential treatment of HF is exercise (aerobic) therapy that has demonstrated various cardioprotective properties to halt and potentially reverse adverse structural remodeling. However, dosing of exercise therapy remains a challenge due to each individual's inherent differences and consequentially, serial non-invasive monitoring of the therapy would be necessary to evaluate the change on structural remodeling. Furthermore, current non-invasive technologies characterize structural remodeling with surrogate measures and thus, there is no consensus on a single clinical gold-standard. Without a tool to monitor and characterize the degree of structural remodeling, the evaluation of the therapeutic potential of exercise therapy in HF patients cannot be fully realized representing an unmet need in ultimately improving therapy. The proposed project aims to improve the therapy monitoring of exercise training to cardioprotect against HF by revealing its effect on microstructural remodeling with cardiac diffusion tensor MRI (DT-MRI). DT-MRI is a unique, non-invasive technology capable of characterizing myocardial fiber orientation and directly reflecting microstructural remodeling. However, despite major advances, there are fundamental challenges that limit the capability of current cardiac DT-MRI methods to be applied robustly in a clinical setting. In this project, an innovative 5-min “push button” DT-MRI method will be developed that overcomes such limitations. We also leverage institutional strengths to further quantify the accuracy of in vivo DT-MRI in revealing myocardial microstructure using novel tissue cleared 3D histology. The central hypothesis is that addressing these major technical challenges will allow for clinical translation of cardiac DT-MRI to serve as a tool to monitor the therapeutic effects of HF on microstructural remodeling. This is achieved by extending previously developed technologies used for myocardial fibrosis detection with diffusion-weighted MRI. The proposed project is designed to systematically develop an innovative and robust clinical DT-MRI methodology and rigorously validate in a pre-clinical setting the effects of exercise therapy on the microstructural remodeling of HF thereby laying the groundwork for potential optimization of dosing exercise therapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	000	5	2/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $697,228 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	002	5	5/25/2023	NON-COMPETING CONTINUATION	$697,228
2023	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	3	11/3/2022	NON-COMPETING CONTINUATION	-$437,266
2023	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	001	4	11/4/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$437,266
														Subtotal = $697,228

Issue Date FY: 2022 ( Subtotal = $685,600 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	3	5/24/2022	NON-COMPETING CONTINUATION	$685,600
														Subtotal = $685,600

Issue Date FY: 2021 ( Subtotal = $673,600 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	6/3/2021	NON-COMPETING CONTINUATION	$673,600
														Subtotal = $673,600

Issue Date FY: 2020 ( Subtotal = $673,600 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	7/10/2020	NEW	$673,600
														Subtotal = $673,600

Grand Total All Awards = $2,730,028

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Serial evaluation of cardioprotective effects of exercise training in heart failure using cardiac diffusion tensor MRI

Award Number: R01HL151704

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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