Notice of Special Interest (NOSI): Research Project Grants in Valvular Heart Disease (CAROL Act)

General FAQs

• What is the CAROL Act?
  The Cardiovascular Advances in Research and Opportunities Legacy (CAROL) Act was legislation introduced by U.S. Congressman Andy Barr (KY-06) in tribute to the life the legacy of his wife, Carol Leavell Barr, who tragically suffered sudden cardiac death at the age of 39 from mitral valve prolapse (MVP).
  
  The legislation authorizes NIH to spend $100 million dollars over five years to support or conduct research to address critical knowledge gaps in valvular heart disease (VHD).
   
• Where can I find potential areas of research encouraged under NOT-HL-23-078 and NOT-HL-23-079?
  The CAROL Act explicitly encourages research examining risk factors for sudden cardiac arrest/sudden cardiac death from valvular heart disease, most commonly associated with MVP. However, this funding opportunity also aims to expand research across the broader spectrum of valvular heart disease.
  
  Research opportunities on MVP are detailed in the report of the NHLBI Workshop on Research in the Treatment of Mitral Valve Prolapse, November 30 – December 2, 2021, and in Research Opportunities in the Treatment of Mitral Valve Prolapse: JACC Expert Panel. Delling et al. Journal of the American College of Cardiology. 2022 Dec 13;80(24):2331-2347. These include:
   
  • Open-access database opportunities, including registries, to collect de-identified comprehensive data on individuals with MVP and other valvular heart disease from diverse populations with the aim of leveraging imaging, -omics, biologic markers, electrophysiology, therapy, outcomes, and data derived from electronic health records and other repositories.
     
  • Genomic studies examining the clinical heterogeneity of MVP and other valvular heart disorders. Investigating regulatory mechanisms of genetic variants for valvular heart disease (i.e. using multiplex and high-throughput methods). Development of polygenic risk scores for MVP and sudden cardiac death.
     
  • Development of a molecular atlas of valvular heart disease.
    • Studies that use established NHLBI resources with large-scale human data sets, such as TOPMed, BioData Catalyst, and existing NHLBI-funded cohorts.
    • Assessing the impact of treatment and interventions on valvular heart disease outcomes is also an area of interest.
    • Data-driven approaches to develop advanced imaging approaches and artificial intelligence or machine learning techniques to improve phenotypic characterization and comprehensive risk assessment of individuals with MVP and valvular heart disease. 
    • Basic science studies to explore mechanisms of fibrosis, inflammation, and ventricular arrhythmia in MVP. The development of relevant animal and computational models to address current knowledge gaps in valvular heart disease and adverse tissue remodeling resulting from valvular heart interventions.
    • Clinical studies designed to identify optimal advanced imaging techniques and electrophysiology monitoring intervals to define key determinants of progression and clinical outcomes. Comparing mitral valve intervention to watchful waiting in asymptomatic individuals with MVP and other valvular heart disorders. 
    • Implementation studies addressing disparities in equitable access, referral, diagnosis, management, and treatment for individuals with MVP and valvular heart disease from diverse communities across the spectrum of socioeconomic status. Studies evaluating patient-reported outcomes, patient preferences for therapy and follow-up. Projects addressing the burden of valvular heart disease (including rheumatic heart disease) and its impact on global health disparities.
       

  Other research opportunities are described in:

  • Report of the NHLBI Working Group on Patient-Centered Research in Valvular Heart Disease, July 9 – 10, 2019, and in Priorities for Patient-Centered Research in Valvular Heart Disease: A Report From the National Heart, Lung, and Blood Institute Working Group. Lindman et al. Journal of the American Heart Association. 2020 April 24;9(9):e015975.
  • Report of the NHLBI Workshop on Eradication of Rheumatic Heart Disease, November 1 – 8, 2021.
  •  Valvular Heart Disease in Relation to Race and Ethnicity: JACC Focus Seminar 4/9. Lamprea-Montealegre et al. Journal of the American College of Cardiology. 2021 Dec 14;78(24):2493-2504.
  • 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Section 16 of Otto et al. Journal of the American College of Cardiology. 2021 Feb 2;77(4):e25-e197 and Circulation. 2021 Feb 2;143(5):e72-e227.

• Will all applications responsive to this NOSI be funded?
  This NOSI will be highly competitive. Therefore, no assurances of funding can be made even if the application is deemed meritorious and responsive.

FAQs Specific to Research Project Grant Opportunities

• What are the key requirements for submission under PA-20-183 and PA-20-185?
  Applicants must follow specific instructions contained in the SF424 (R&R) Application Guide and the funding opportunity announcement (FOA) used for submission.
  
  NOTE: To be considered for funding, applicants must include “NOT-HL-23-079” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 (R&R) form.  Applications without this information in box 4B will not be considered for this Notice.
  
  The NHLBI will accept applications to PA-20-183 – Research Project Grant (Parent R01 Clinical Trial Required)  only for mechanistic studies that meet the NIH’s definition of a clinical trial and address a primary goal of understanding how an intervention works per guidance in NOT-HL-19-690. Prior to submission, applicants are strongly encouraged to contact the listed program staff within the NOT-HL-23-079 to confirm that the clinical trial proposed meets these requirements.
   
• Are research projects using large animal models eligible for this notice?
  Yes, as long as the same animal models were proposed under the parent grant. (Please refer to What are the key requirements for submission under PA-20-183 and PA-20-185?)