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Graft Stiffness as a Substrate for Adverse Cardiovascular Remodeling and Clinical Outcomes in Genetically Triggered Aortic Aneurysms

Award Number: K23HL177257
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/05/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2030

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Graft Stiffness as a Substrate for Adverse Cardiovascular Remodeling and Clinical Outcomes in Genetically Triggered Aortic Aneurysms - PROJECT SUMMARY / ABSTRACT This K23 will provide Dr. Nupoor Narula with new skills critical for her to attain academic independence as an investigator focused on novel profiling approaches to improve therapy, risk stratification, and outcomes for patients with genetically triggered thoracic aortic aneurysms (gTAA). Extending logically on her prior track record, an integrated training plan has been developed focused on two key areas – cardiac magnetic resonance imaging (CMR) and advanced cardiovascular genetics. Applied training will be attained by leveraging an established R01, which will provide a rigorous framework in which to study impact of prosthetic aortic grafts (a cornerstone of therapy for gTAA known to be stiffer than native aortic tissue) on left ventricular (LV) and distal aortic remodeling, and whether gTAA etiology modifies impact of grafts. To test these concepts, at least 150 gTAA patients undergoing prosthetic graft replacement of the proximal aorta will be prospectively studied using cutting edge CMR methods pre- and (1 year) post-operatively, together with rigorous genotyping. LV tissue characterization will be performed using high resolution navigator and parametric mapping CMR technologies, and both 4D flow and dynamic (cine) CMR will be employed to quantify aortic vessel wall properties. In parallel, tailored genetic analyses will be performed to test if CMR-evidenced response to grafts is modified by genotypic characteristics of TAA, and validated survey methods will be used to assess outcomes. Aim 1 will test impact of native and graft-induced alterations of aortic stiffness on LV performance in gTAA, with focus on whether pre- and post-operative LV function and tissue characteristics (fibrosis) vary in relation to gTAA etiology; Aim 2 will employ innovative CMR approaches to assess distal aortic response to proximal graft implantation – including tortuosity, 4D flow derived wall shear stress, and pulse wave velocity; Aim 3 will explore phenotypic and genotypic modifiers of LV and distal aortic remodeling after proximal graft replacement, with focus on type and mechanism of pathogenic variants. Applied training will be complemented by didactic training enabled by graduate coursework in CMR physics, genetics, and translational research/statistics. K23 research and training will be attained at a leading institution for gTAA, and guided by mentors with complementary multidisciplinary expertise: Dr. Weinsaft is the principal investigator of the R01 to which this K23 is paired and has extensive experience in use of CMR in gTAA focused longitudinal outcomes studies; Dr. Wang is a co-mentor with an established track record in CMR pulse sequence development – including high resolution 3D CMR, as will be employed in the proposed research plan; Dr. Devereux is a co-mentor with longstanding expertise in gTAA related to translational genetics and LV remodeling. Findings from this K23 will address key knowledge gaps of broad significance to gTAA patients – including mechanism and patient profiles at greatest risk for adverse remodeling after prosthetic aortic graft implantation. Study results will directly inform future R01s focused on use of integrated genotype/CMR profiling to improve prediction of therapeutic response and clinical outcomes in gTAA.


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: 2026 ( Subtotal = $173,032 )
2026	2026	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Cardiovascular Diseases Research	001	2	9/8/2026	NON-COMPETING CONTINUATION	$173,032
2026	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Cardiovascular Diseases Research	000	1	1/27/2026	NEW	$0
														Subtotal = $173,032

Issue Date FY: 2025 ( Subtotal = $174,389 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Cardiovascular Diseases Research	000	1	9/4/2025	NEW	$174,389
														Subtotal = $174,389

Grand Total All Awards = $347,421

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Graft Stiffness as a Substrate for Adverse Cardiovascular Remodeling and Clinical Outcomes in Genetically Triggered Aortic Aneurysms

Award Number: K23HL177257

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/05/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2030

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