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Determining the genetic and social determinants of heart failure and mortality in patients with congenital heart disease (DEFINE)

Award Number: R01HL166217
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Determining the genetic and social determinants of heart failure and mortality in patients with congenital heart disease (DEFINE) - PROJECT SUMMARY/ABSTRACT Congenital heart defects (CHDs) affect nearly 1% of live births in the United States. CHDs are associated with high morbidity and are the most common birth defect-related cause of death. Rapid advancement in the early diagnosis, medical management, and treatment of CHD have led to tremendous gains in survival; however, heart failure (HF) is the leading cause of death in adults with CHD. This makes identifying the risk factors of HF across the lifespan critical so that individuals at the highest risk can be identified and managed. We have brought together a multi-disciplinary team with significant experience in population-based CHD outcomes, social determinants of health, and cardiovascular genetics to fill these critical knowledge gaps. Since 2008, our team has led the North Carolina Congenital Heart Disease Surveillance Network (NC-CHD) which links the 5 major academic centers in North Carolina in a surveillance network for the vast majority of patients with CHD in the state. NC-CHD links clinical records to a variety of robust, state, and national databases to conduct outcomes-based research on survivors of CHD across the lifespan. This puts our team in a unique position to establish a prospectively enrolled cohort of CHD survivors with rich clinical phenotyping for comprehensive genetic and outcomes-based research to determine the causes of HF in this population. The goal of our study is to develop a large, well- curated, population-based cohort of individuals with CHD in the state of North Carolina (NC-DEFINE) to identify social determinants of health and genetic factors which influence CHD outcomes, specifically HF. We hypothesize that social determinants of health and rare genetic variants localizing to sarcomeric genes are associated with HF development among survivors of CHD. To test this hypothesis, we propose 3 specific aims: 1) To identify the social determinants of health associated with the development of HF in cohort of 600 patients with CHD which will comprise NC-DEFINE. 2) To determine the coding genetic variants associated with the development of HF among patients with CHD in NC-DEFINE. 3) To determine the functional impact of candidate variants associated with HF in CHD using patient-derived cardiac myocytes. If we are successful, this project will allow for identification of CHD patients at heightened risk of HF based on either social or genetic risk, allowing for informed counseling at the time of surgical repair and early intervention to control reversible risk factors associated with HF. Further, NC-DEFINE will lay the foundation for a genomic medicine-based approach to predicting CHD prognosis and outcomes.


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 = $741,290 )
2026	2026	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	4	4/6/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$741,290
2026	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	000	3	4/2/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $741,290

Issue Date FY: 2025 ( Subtotal = $664,944 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	000	3	7/29/2025	NON-COMPETING CONTINUATION	$664,944
														Subtotal = $664,944

Issue Date FY: 2024 ( Subtotal = $667,938 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	000	2	5/13/2024	NON-COMPETING CONTINUATION	$667,938
														Subtotal = $667,938

Issue Date FY: 2023 ( Subtotal = $686,524 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	000	1	5/30/2023	NEW	$686,524
														Subtotal = $686,524

Grand Total All Awards = $2,760,696

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Determining the genetic and social determinants of heart failure and mortality in patients with congenital heart disease (DEFINE)

Award Number: R01HL166217

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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