The Future of Pediatric Cardiovascular Research

August 3 - 6, 2021


The National Heart, Lung, and Blood Institute (NHLBI) convened a virtual workshop of 26 investigators in pediatric heart disease with expertise ranging from fetal cardiology to the care of those with adult congenital heart disease and from basic science to clinical research. “The Future of Pediatric Cardiovascular Research” workshop was held on August 3 and 6, 2021, with the following objectives:

  • To identify current gaps and future research opportunities to reduce morbidity and mortality related to congenital heart disease (CHD) across the lifespan
  • To bring together experts in epidemiology, data science, translational research, ethics, biobanking, and other areas, along with experts in CHD across the lifespan, to brainstorm about the optimal research approaches to decrease morbidity and mortality
  • To inform the potential renewal or transformation of the Pediatric Heart Network (PHN)

The workshop is responsive to NHLBI Strategic Vision Objectives 2, 3, and 5-8.


Congenital heart defects occur in approximately 40,000 individuals in the United States each year [1]. Although improved diagnostic capacities, surgical techniques, peri-operative care, and catheter-based treatment have had a significant effect in reducing the overall infant mortality rate over the past 40 years, CHD is still responsible for the largest proportion, 30 to 50 percent, of mortality caused by birth defects among infants and young children [2]. With the improvement in infant mortality, as well as survival among older children, the prevalence of adult CHD more than doubled in the United States over the same period [2],[3]. Today, there are between 2 and 3 million adults and children living with CHD in the United States. Adults with CHD face a high risk of early death and disability [4], and because this is a relatively new population, there has not yet been a great deal of robust clinical research to inform patient care and outcomes.

Despite improved outcomes among individuals with CHD, racial, ethnic and other socioeconomic factors continue to affect outcomes. For example, the overall mortality of non-Hispanic Black individuals with CHD is 20 percent higher than that of White individuals [5]. Children whose mothers live in a very low-income neighborhood or one with a very low level of education faced a 29-34 percent higher risk of CHD than children in the wealthiest and most educated neighborhoods [6]. Little attention has been paid to date to the influence of social determinants of health and access to care on CHD outcomes.

We are entering an era of unprecedented data sharing, through the principles of sophisticated data science. Therefore, the answers to clinical problems are no longer solely dependent on clinical trials. Part of the goal for this workshop was to bring together experts in data science along with experts in CHD across the lifespan to brainstorm about the optimal research strategies for CHD across the lifespan.


The meeting agenda included an “open mic” session; there was an open invitation to external groups and individuals to contribute brief presentations of their perspectives on the current state of pediatric cardiovascular research and a vision for advancing the field. Workshop participants evaluated the research concepts and questions; this session was followed by focused presentations by participants on health equity, data sharing, creative clinical trial design, and innovation; and three breakout small-group sessions about lessons learned from prior achievements and shortcomings, the most critical knowledge and therapeutic gaps and related opportunities, and innovations.

Gaps and Opportunities

Based on input from the “open mic” session, and participating expert perspectives, workshop participants identified the following major gaps and related opportunities to advance the field of pediatric cardiovascular (CV) research:

Gap: Lack of Diversity—Pediatric CV clinical research lacks adequate representation among diverse segments of society, both in terms of investigators and research participants at academic medical centers. There is a demographic disconnect between patients and their families and researchers. This disconnect includes underrepresentation of persons coming from racial and ethnic minorities, rural geographic areas or other locations distant from major academic centers, the uninsured, and those speaking a primary language other than English, as well as other particular groups. This disconnect is not simply a matter of equity, but also results in biased results with potentially misleading results from a scientific perspective.

Related Opportunities:

  • Engage family-based advocacy organizations and other community groups to advise researchers on optimal study design, identification of meaningful outcome measures, and recruitment/retention strategies to ensure appropriate diversity.
  • Given that family-based advocacy organizations can suffer from the same systemic biases as described above, partner with those organizations to actively engage with underserved or otherwise disadvantaged communities to enhance appropriate representation.
  • Engage family-based advocacy organizations, policymakers, and public health organizations to disseminate research findings to the broad spectrum of patients/families, both to develop a more informed patient/family community and to earn the trust required to make headway in increasing participation.
  • Incorporate community engagement and family advisory strategies as integral to the PHN and other appropriate clinical research projects.
  • Implement targeted recruitment efforts to increase the diversity of participants in clinical trials.
  • Encourage diversity among clinical research investigators to facilitate recruiting more diverse study participants and to incorporate the perspectives of diverse communities more deeply into study design and performance.
  • Consider collaboration with the IdEA States Pediatric Clinical Trials Network and other relevant networks to broaden geographic diversity.

Gap: Inefficient Collaboration Across Data Platforms—There is no universal identification of individuals with CHD, or ability to track patients longitudinally to identify evolving outcomes and risk factors for these outcomes. This gap limits our ability to identify emerging patterns of disease development and course and the capacity to explore risk factors predisposing to adverse outcomes. Because of the small number of CHD patients seen at individual centers, there is a need for collaboration and data-sharing across centers and platforms to advance pediatric CHD research across the lifespan.

Related Opportunities:

  • Coordinate efforts across institutions to develop a singular platform to link networks, registries, and other databases to support longitudinal research across the lifespan and the sharing of standardized electronic health record (EHR) data across institutions.
  • Investigate novel ways in which EHR and other real-world data can inform CHD research across the lifespan and how pragmatic trials can contribute to evidence generation.
  • Establish creative collaborations with data scientists, statisticians, industry, and others outside of pediatric cardiology.
  • Employ globally unique identifiers or other privacy-preserving record linkages as a means of linking data in a HIPAA-compliant fashion, including connection to fetal/neonatal records.

Gap: Lack of Comprehensive Clinical Research Strategies—There has been inadequate research consideration of topics outside the scope of clinical pediatric cardiology expertise, including mechanistic and discovery science/study design; impact of genetics, race/ethnicity/ancestry; and psychosocial factors that are important to patients and families. This gap also includes inefficient research designs.

Related Opportunities:

  • Collaborate with investigators outside CHD/pediatric cardiology. Identify groups that have been successful with cross-disciplinary collaboration in the study of rare diseases.
  • Incorporate genomics and other -omics into clinical care and diagnostics, including enhanced training of researchers and clinicians in this area.
  • Integrate study of mental health, neurodevelopment, end of life, and quality of life into the PHN and other pediatric CV research across the lifespan.
  • Integrate social determinants of health (SDoH) measures into the PHN and other pediatric CV clinical research across the lifespan.
  • Integrate nontraditional data: patient-reported outcomes (PROs), biomarkers, genomics and other -omics, wearables.
  • Adopt creative observational and intervention study designs, including adaptive/pragmatic trials and innovative, relevant endpoints (e.g., PROs, biomarkers, wearables).
  • Consider strategies for incorporating device trials into the PHN and other platforms through collaboration with the Food and Drug Administration’s System of Hospitals for Innovation in Pediatrics-Medical Devices (SHIP-MD), small business initiatives, and others, and facilitating subsequent commercialization.
  • Culturally normalize universal participation and align workflow to integrate clinical research as part of medical care through EHR tools, novel consent and enrollment structures, remote data capture, harnessing of ambulatory and inpatient physiological monitoring, etc.

Gap: Inadequate Translation and Implementation of Research Results—There is a disconnect between research results and implementation in the clinic.

Related Opportunities:

  • Expand application of learning health network models that include plans for evaluating effectiveness of model implementation on clinical outcomes.
  • Conduct implementation research; plan for implementation as part of clinical trial protocols.
    • Integrate real-time analytics to make data available to the clinician to improve clinical decision-making.

Gap: Inadequate Training—Early career investigators in the field need enhanced research training opportunities, particularly in newer disciplines such as data science, -omics, and adaptive trial design.

Related Opportunities:

  • Recruit and train a diverse next generation of CHD physician-scientists, including those in areas such as precision medicine, data science, and other rapidly evolving fields.
  • Explore new models for research support for early career investigators.
  • Embed Early Stage Investigators and skills-building activities into applicable networks and other platforms.

Gap: Limited Innovation/Lack of Transformational Research—Progress has been slow and incremental. What would we need to do today to transform practice 10-20 years from now?

Related Opportunities:

  • We have learned a great deal about the genetic variants, as well some of the toxic exposures or other environmental factors, associated with development of CHD. However, we still know little about the pathways by which these genetic and environmental factors cause disease. How might we develop and test hypotheses to shed light on the pathways and possible prevention strategies, analogous to the experience with folic acid and neural tube defects? Even less is known about genetic or epigenetic modifiers of disease course; how do we develop this sort of understanding into precision therapeutic strategies? Answering these questions should result in greater precision in applying therapies to the right patient at the right time.
  • Many comorbidities associated with CHD, such as neurocognitive concerns, have both environmental and genetic underpinnings. How can we better understand the underlying mechanisms and then use this knowledge to mitigate such complications?
  • What is the role of regenerative technologies in CHD across the lifespan? And how can we best attract experts from other fields, such as engineering, to tackle these complex problems?
  • Could the PHN, in concert with registries and other platforms, capture the approximately 15,000 newborns with complex CHD born each year, genotype them, bank other biologic tissue/blood, and follow them longitudinally to enrich our understanding of the life-course of CHD and risk factors for development of adverse sequelae? Such an effort could also create natural experiments assessing outcomes of different treatment strategies.


A white paper summary of the gaps and opportunities identified in the workshop will be forthcoming.


Gail D. Pearson, M.D., Sc.D.,
Kristin M. Burns, M.D.,
Kathleen Fenton, M.D., M.S.,
Victoria Pemberton, R.N.C., M.S.,