U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL MEETING SUMMARY

June 8, 2021

The 292nd meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) convened virtually on Tuesday, June 8, 2021. The meeting began in closed session at 10:03 a.m. and was open to the public between 12:13 p.m. until adjournment at 3:45 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as chair.

NHLBAC Members Attending

Jennifer DeVoe, D.Phil., M.D.
Grace Anne Dorney Koppel, J.D.
Martha U. Gillette, Ph.D.
Garth Graham, M.D., M.P.H.
David H. Ingbar, M.D.
Monica Kraft, M.D.
Kiran Musunuru, M.D., Ph.D.
Mohandas Narla, D.Sc.
Richard S. Schofield, M.D. (Ex Officio)
Dean Sheppard, M.D.
Kevin L. Thomas, M.D.
Andrew S. Weyrich, Ph.D.
Zachariah P. Zachariah, M.D.

NHLBI Employees Attending

A number of NHLBI staff members were in attendance via Zoom.

NIH Employees and Public Attending

The total number watching/participating online was reported by NIH Videocast to be 267.

CLOSED SESSION

This portion of the meeting was closed to the public in accordance with the determination that it concerned matters exempt from mandatory disclosures under Sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended.

REVIEW OF APPLICATIONS

The session included a discussion of procedures and policies regarding voting and confidentiality of application materials, committee discussions and recommendations. Members absented themselves from the meeting during discussion of and voting on applications from their own institutions, or other applications in which there was a potential conflict of interest, real or apparent. Members were asked to sign a statement to this effect. The Council considered and recommended 3,559 applications requesting $7,746,820,630 in total costs. For the record, it is noted that secondary applications were also considered en bloc.

REVIEW OF INTRAMURAL RESEARCH

A report prepared by the Board of Scientific Counselors (BSC), NHLBI, on the NHLBI staff and intramural laboratories was presented to the Council by Dr. Donald M. Bers, BSC Chair.

OPEN SESSION

I. CALL TO ORDER

Dr. Gibbons reconvened the NHLBAC meeting at 12:13 p.m. in Open Session. He welcomed Council members, NHLBI staff and public attendees to the Open Session of the meeting.

II. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Laura K. Moen (Director, Division of Extramural Research Activities, NHLBI) provided guidance on participating, reminding Council members of conflict of interest requirements. She noted that the meeting would be publicly broadcast and archived on videocast.

III. REPORT OF THE DIRECTOR

Dr. Gibbons announced the recent appointment of Julie Panepinto, M.D., MSPH, as Deputy Director of the Division of Blood Diseases and Disorders.

Accountable Stewardship. Dr. Gibbons updated NHLBAC on NHLBI’s investments for fiscal year (FY) 2021 and early FY 22 funding prospects. He explained that the budget increase of $103 million dollars relative to FY 20 equated to just a 1% increase overall. However, NHLBI also received supplemental funds under the Coronavirus Aid, Relief, and Economic Security (CARES) Act. Current spending is aligned with NHLBI priorities:

• maintaining research project grants (RPGs) and investing in the future and continued commitment to investigator-initiated science in FY 21, particularly maintaining high success rates in the face of the challenge of the rising award costs of R01 (Research Project) funding over the past 5 years.
• continued commitment to nurturing the next generation of researchers by supporting career development (K) and fellowship awardees adversely affected by COVID-19.

NHLBI was invited to participate in the congressional hearings on FY 22 budget appropriations. Many of the congressional health care priorities for the upcoming year are aligned with the NHLBI mission.

NHLBI is actively fostering diversity, equity, and inclusion. The Institute has a policy of accountable stewardship. The Institute is aware that women and underrepresented minorities comprise a lower proportion of established researchers, although recipients of early career awards are more diverse. NHLBI is actively participating in the National Institutes of Health’s (NIH) UNITE Initiative, which addresses structural racism and reflects NIH’s commitment to diversity, equity, and inclusion.

Advancing Scientific Priorities. Dr. Gibbons highlighted specific areas of the mission upon which NHLBI has focused recent efforts:

• Advances in discovering novel therapeutics to cure sickle cell disease: The guiding principle of this initiative is that it is patient centered. In preliminary work, gene-based therapies are being assessed for safety and efficacy. Dr. Gibbons reported that genetic cell therapy trials are resuming after two cases of hematological cancers were found to be unrelated or misdiagnosed. A related effort is underway to investigate the background risk for hematological cancers in sickle cell disease, given the stress the disease places on bone marrow. This effort will require ancestrally diverse resources.
• Addressing the long-term public health impact of COVID-19: Goals of this undertaking include reducing severity, speeding recovery, and addressing health inequities. NHLBI has joined a trans-NIH research response that features adaptive clinical trials involving a variety of patient populations with a range of therapeutic goals.
• Disparate impact of COVID-19 on communities of color: It is recognized that this will require a multidimensional approach to address. The NIH Community Engagement Alliance (CEAL) is combating disparities by addressing mistrust and misinformation. Trends suggest that early disparities in vaccination are shrinking, but work is still needed in high-risk communities.
• Post-Acute Sequelae of COVID-19 (PASC): Initiative The NHLBI is at the forefront of this $1.1B effort. The challenges are to learn who is at risk and which therapeutic interventions prevent sequelae. PASC is characterizing infections with a meta-cohort that includes cohort studies and electronic health record interrogations.
• Catalyzing the transition from translational research to commercialization: NHLBI is committed to supporting the cycle of discovery and innovation that translates discoveries to precision prevention and new therapies. A major component of the overall effort is the NHLBI’s Catalyze program which provides flexible funding and key resources to bridge the gap in the translational pipeline.
• Understanding the molecular basis of heart failure and uncovering new therapeutic targets: To this end, researchers are leveraging genomic technologies for target discovery using diverse and inclusive genotype/phenotype resources. They are exploring heart failure at the level of the single cell to discover types of heart failure with different biological signatures. NHLBI’s Heart Share Initiative will promote discovery by leveraging NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program and public-private partnerships.

IV. THE NIH UNITE INITIATIVE TO STRENGTHEN DIVERSITY, EQUITY, AND INCLUSION: TOGETHER, WE’RE STRONGER

Dr. Marie A. Bernard (Chief Officer for Scientific Workforce Diversity, NIH) provided NHLBAC with an overview of the NIH UNITE Initiative. She noted that the past year’s events have brought ongoing racial injustice in our country into sharp relief. In June 2020, Institute and Center (IC) directors met to identify initial issues related to structural racism and diversity, equity, and inclusion at NIH. Two self-assembled affinity groups also met with NIH leadership. Together, these groups and NIH leadership arrived at a shared commitment to address structural racism, recognizing that we must not let this pivotal moment pass. The UNITE Initiative was unveiled at the February 26, 2021, meeting of the Advisory Committee to the Director.

The UNITE Initiative identified initial issues to address. Biomedical research and its supporting administrative system must be devoid of hostility grounded in race, sex, and other federally protected characteristics. NIH must look within to delineate elements that perpetuate structural racism in biomedical research. All ideas must be given an equal and fair review regardless of who presents them, and regardless of the current dogma. Fundamental causes of health disparities and inequities must be redressed.

The UNITE Initiative comprises five intersecting committees:

• The U Committee’s charge is to evaluate elements that perpetuate structural racism and lead to a lack of diversity, equity, and inclusion within NIH and the external scientific community.
• The N Committee’s charge is to ensure NIH-wide transparency, accountability, and sustainability in marshaling resources for health equity research.
• The charge of the I Committee is to change NIH organizational culture and structure to promote diversity, equity, and inclusion throughout the NIH workforce.
• The charge of the T Committee is to ensure the transparency, accountability, and sustainability of all UNITE efforts.
• The E committee’s charge is to identify and change NIH extramural policies and processes that perpetuate a lack of inclusivity and diversity.

Dr. Bernard pointed out that NIH has made substantial progress toward initiating and implementing the initiative’s recommendations under UNITE. Actions taken include:

1. Dr. Francis S. Collins’ (Director, NIH) apology to those disadvantaged by structural racism. In his statement, he affirmed NIH’s commitment to supporting diversity, equity, and inclusion through dismantling structurally racist policies and practices.
2. NIH has launched a Common Fund initiative addressing health disparities and advancing health equity with a commitment of up to $24M. A request for applications (RFA) on understanding the impact of structural racism and discrimination on minority health and health disparities has been issued with a $30.8M commitment from 25 Institutes, Centers, and Offices.
3. NIH workforce data by race/ethnicity and disability status is now available online.
4. NIH has convened an Anti-Racism Steering Committee open to all members of the NIH workforce.

Dr. Bernard also described two other Institute-sponsored actions of potential interest to the Council. The National Institute of General Medical Sciences issued a Notice of Special Interest (NOSI) on understanding structural racism’s effects on biomedical careers and research. The BRAIN Initiative is the first NIH funding opportunity announcement that will be using a plan to enhance diverse perspectives as a consideration for scoring. She concluded with a quotation from Dr. Martin Luther King, “Injustice anywhere is a threat to justice everywhere.”

V. DIR SCIENTIFIC PRESENTATION: “OPPORTUNITIES IN CARDIOPULMONARY IMAGING USING A HIGH-PERFORMANCE 0.55T MRI SYSTEM”

Dr. Adrienne E. Campbell-Washburn (Stadtman Tenure Track Investigator, NHLBI) told the Council about new translational opportunities offered by a high-performance 0.55T MRI 6 system. This system allows more accessible cardiac MRI, comprehensive lung MRI, and safer MRI-guided cardiac procedures.

Current MRI clinical technologies primarily are used for imaging the brain, spine, and joints. These systems have a large magnetic field (1.5T or 3T)—50,000 times stronger than the earth’s magnetic field. Magnetic field strength has increased since the 1990s to improve the image resolution and signal-to-noise ratio, but these higher-field systems have disadvantages, including higher costs.

The innovation of the 0.55T system is that it combines low-field strength with high-performance hardware and technology. The image acquisition and reconstruction methods shift the financial burden of enhanced technology from expensive magnets to cheap computing. The system has advanced data sampling that uses efficient spiral sampling. The image-reconstruction algorithms take advantage of the power of cloud computing. Clinical cardiac MRI allows imaging of anatomy, function, and physiology. Cardiac MRI has been underutilized because of system cost and complexity, but lower-field systems could increase accessibility. Savings are derived from decreased magnet strength, a lighter system, less shielding, and less helium. Other benefits of 0.55T are increased patient safety and comfort. A 0.55T system potentially could provide a lower-cost radiology system capable of meeting 90 percent of radiology needs.

Dr. Campbell then demonstrated the capabilities of the lower-field system for heart and lung imaging. Comparing 0.55T and 1.5T systems for imaging the heart, she showed that measurement concordance is high, and interpretation is consistent. Dr. Campbell noted that MRI of the lung presents challenges. The lung has low water content, and the air-tissue interfaces distort the magnetic field. At 0.55T, however, distortions are reduced at the air-tissue interface. Low-field MRI can also use oxygen as a contrast agent which works well in determining lung function. Dr. Campbell showed the Council how oxygen signal enhancement maps were able to accurately contrast healthy volunteers with patients with lymphangioleiomyomatosis (LAM).

Dr. Campbell also presented imaging data for patients with acute COVID-19 infection. Although resolution is lower than CT, the lack of radiation exposure allows longer follow-up. Results from oxygen mapping in COVID-19 reveal reduced oxygen regions in recovered patients, suggesting that continued monitoring is needed. Quantitative lung perfusion shows perfusion deficits in patients with COVID-19, and low perfusion persists even in recovery.

Low-field MRI can be used to guide cardiovascular procedures. In a video, Dr. Campbell showed an MRI-guided cardiac catheterization. Comparing an X-ray to MRI, the device is easier to see with an X-ray, but the tissue being biopsied is clearer with MRI. Regarding the potential for human MRI catheterization, MRI produces accurate measurement of pulmonary vascular resistance. Low-field MRI has overcome previous issues with device safety which hampered clinical translation, since radiofrequency-induced heating of metallic devices is greatly reduced. Dr. Campbell also noted that use of MRI in cardiac ablation allows the clinician to see the effect on tissue and heart function in real time.

VI. NHLBI CONCEPT CLEARANCE

The NHLBI staff presented 17 concepts for clearance. Members expressed support for these concepts during discussions. They also asked for clarification on certain details and offered recommendations.

Title: Strategies to Innovate EmeRgENcy Care Clinical Trials (SIREN) Trans-NIH Network Renewal (U24)

Description: The overarching goal of this concept is to improve the outcomes of patients with neurologic, cardiac, respiratory, hematologic, and trauma emergencies. It renews NHLBI’s investment in a trans-NIH multidisciplinary network for emergency-care clinical trials to identify effective treatments given in the earliest stages of care.

Title: Secondary Participation in Renewal of PAR-17-255 Limited Competition: National Swine Resource and Research Center (U42)

Description: This concept proposes an initiative to support the use of a large animal model, the pig, as a useful model of diseases relevant to NHLBI’s mission. It provides an additional 5 years of support for the trans-NIH National Swine Resource and Research Center, thereby increasing the understanding of human health and disease through the support of swine models for biomedical research.

Title: Renewal of NOT-HL-20-769: Bold New Bioengineering Research for Heart, Lung, Blood and Sleep Disorders and Diseases (R21)

Description: This concept fosters discovery-driven bioengineering ideas relevant across NHLBI’s mission. It provides a cost-effective way to support proof-of-concept efforts transitioning to R01 and other follow-up funding, targeting ideas that advance NHLBI’s mission.

Title: NHLBI Career Transition Award for Intramural Postdoctoral Fellows and Research Trainees (K22)

Description: This concept supports talented NHLBI intramural postdoctoral fellows to prepare them for extramural research. It supports awardees through a mentored intramural phase (1–2 years) and a second extramural phase, which requires that awardees secure a faculty appointment at an extramural institution.

Title: Secondary Participation Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (U54, U24)

Description: This concept proposes a competitive renewal initiative, in collaboration with the National Institute of Neurological Disorders and Stroke, to support multidisciplinary ME/CFS research across a network of academic institutions. It further builds on the successes of the current network, helps develop the capacity to collect biospecimens, and fosters career development.

Title: Opportunities for Collaborative Research at the NIH Clinical Center (U01)

Description: This concept would create research opportunities not available elsewhere through supporting extramural and intramural collaborative research at the NIH Clinical Center. It would provide access to state-of-the-art equipment and expertise, platforms for translational research, and rare disease cohorts.

Title: Notice of Special Interest: Resilience and Vulnerability following Acute Heart, Lung, Blood, and Sleep Insults in People with HIV (R01, Clinical Trial Not Allowed)

Description: This NOSI concept stimulates research on resilience and vulnerability following acute heart, lung, blood, and sleep (HLBS) diseases and disorders in people with HIV as compared with people who are not HIV-positive. It investigates factors—including HIV infection, antiviral treatment, age, sex, gender, and social determinants of health—related to the transition from acute insult to complete recovery, partial recovery, or persistent residual dysfunction. Proposals will be considered across the spectrum of basic science to population science.

Title: Notice of Special Interest (NOSI): Examining Effects of HIV Pre-Exposure Prophylaxis (PrEP) on Heart, Lung, Blood, and Sleep Function (NOSI linked to PA-20-185 and PA-20-183) (R01)

Description: This NOSI concept seeks to stimulate research focused on the impact of PrEP on HLBS function. PrEP is the cornerstone of efforts to prevent HIV transmission. Positive or negative effects of PrEP on HLBS diseases, however, remain relatively unstudied.

Title: Stimulating Access to Research in Residency (StARR) Program Renewal (R38)

Description: As part of a cross-NIH initiative concept, the StARR program provides clinicians with research experiences early in their careers to recruit, retain, and accelerate independence in research. The R38 program supports institutional applications with novel approaches to timing, duration, faculty engagement, and administrative oversight.

Title: Secondary Participation in RFA-OD-22-001: Research Resource for Human Organs and Tissues (Limited Competition U42)

Description: This concept would renew support for the trans-NIH initiative for the Research Resource for Human Organs and Tissues (HTORR). The research resource facilitates the procurement, preservation, and distribution of fresh, fixed, and frozen tissues and organs for basic and clinical research. Cofunding by NHLBI will support tissue and specimen collection, storage, and distribution for HLBS research. The resource provides specimens to study a multitude of HLBS disorders. HTORR also has a specific focus on LAM research, working closely with NHLBI and The LAM Foundation on tissue procurement. In addition, the resource will provide specimens for new research, focusing on sarcoidosis and heart failure.

Titles: Catalyze Product Definition: Devices, Diagnostics and Tools (R61/R33, R33); Small Molecules and Biologics (R61/R33, R33); Catalyze Enabling Technologies and Transformative Platforms (R33)

Description: The NHLBI Catalyze Program provides a comprehensive suite of support and services to help transition basic scientific discoveries into viable diagnostic and therapeutic candidates ready for human testing. It also develops translational researchers fluent in product development and entrepreneurship. The above five initiatives are a suite of renewal RFAs addressing product development, as well as enabling technologies and transformative platforms. Of the product development initiatives, the first two focus on devices and diagnostics, and the second two focus on therapeutics. The enabling technologies and transformative platforms initiative support development of a new generation of diagnostic and therapeutic products.

Title: NHLBI SBIR Phase IIB Competing Renewals for Heart, Lung, Blood, and Sleep Technologies with Small Commercial Markets (R44)

Title: NHLBI SBIR Phase IIB Bridge Awards to Accelerate the Commercialization of Technologies for Heart, Lung, Blood, and Sleep Disorders and Diseases (R44)

Description: The two concepts above facilitate the capital-intensive steps of involved in transitioning from completed Phase IIB projects to the commercialization stage. Both initiatives incentivize partnerships between successful Phase IIB awardees and third-party investors and/or strategic partners. The first initiative focuses on the validation of NHLBI mission-focused technologies that address rare diseases or pediatric indications. The second initiative focuses on validation of technologies for all HLBS indications.

CLOSING REMARKS

Dr. Moen adjourned the meeting at 3:35 p.m.