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

Key Dates

Release Date:

March 7, 2023

First Available Due Date:
June 05, 2023
Expiration Date:
May 08, 2026

Related Announcements

NOT-HL-23-085 - NHLBI Notice of Availability of Frequently Asked Questions (FAQs) for NOT-HL-23-078 and NOT-HL-23-079 (CAROL Act).

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Issued by

National Heart, Lung, and Blood Institute (NHLBI)


As part of the National Heart, Lung, and Blood Institute’s implementation of the Cardiovascular Advances in Research and Opportunities Legacy (CAROL) Act, this Notice of Special Interest is seeking R01 applications that propose research in valvular heart disease.

Selected Research Examples

The CAROL Act explicitly encourages research using advanced imaging techniques and research on risk factors for sudden cardiac arrest or sudden cardiac death from valvular heart disease, most commonly associated with mitral valve prolapse (MVP). However, the Act also encourages research on valvular heart disease more broadly. Selected research examples may include, but are not limited to:

  • Registry activities. Collection of de-identified clinical data (e.g., imaging, omics, electrophysiology, therapy, outcomes, electronic health record data) on individuals with MVP from diverse populations.
  • Data science. Development of artificial intelligence or machine learning techniques for comprehensive risk assessment and improved phenotypic characterization of individuals with MVP. Development of approaches to enhance diagnostic imaging of individuals with MVP.
  • Basic. Studies of the mechanisms of fibrosis, inflammation, and ventricular arrhythmia in MVP and of persistent left ventricular dysfunction after mitral valve intervention. Development of relevant animal models and computational models.
  • Clinical. Comparing mitral valve intervention to watchful waiting in asymptomatic individuals with MVP. Studies to establish ideal intervals for imaging and electrophysiological monitoring and to identify key determinants of outcomes.
  • Omics. Genomic studies that span the clinical heterogeneity of MVP 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 (TOPMed, BioData Catalyst, existing HLBS cohorts).
  • Implementation. Studies that address the observed disparities across diverse communities and the spectrum of socioeconomic status in diagnosis, management, treatment, and referral of individuals with MVP. Studies of patient preferences for therapy and follow-up.

These and other research examples are detailed in the report of the NHLBI Workshop on Research in the Treatment of Mitral Valve Prolapse, November 30 December 2, 2021.

Applications that propose research on other anatomic valves (e.g., lymphatic valves, venous valves) will not be considered in response to this Notice.

Application and Submission Information

This notice applies to due dates on or after June 5, 2023, and subsequent receipt dates through May 7, 2026.

Applications for this initiative must be submitted using one of the following Notices of Funding Opportunity (NOFOs, formerly called Funding Opportunity Announcements or FOAs) or their subsequent reissued equivalents:

  • PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

NOTE: The NHLBI will only accept applications to PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required) that propose mechanistic studies which meet the NIH's definition of a clinical trial and that have the primary goal of understanding how an intervention works per guidance in NOT-HL-19-690. Applicants are strongly encouraged to consult the contact listed below prior to submission to confirm that the proposed clinical trial application meets these requirements.

All instructions in the SF424 (R&R) Application Guide and the NOFO used for submission must be followed, with the following addition:

  • For funding consideration, 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.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed funding opportunity announcements.

Scientific/Research Contact(s)

Frank Evans, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0510

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Francesca Hunter
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-3127