Thank you for participating!

Thank you to all who contributed to the National Heart, Lung, and Blood Institute (NHLBI) Strategic Visioning Forum. Ultimately, over 1,000 ideas were submitted, with more than 42,000 votes. This remarkable response exceeded expectations and provided a wealth of ideas to draw upon as NHLBI moves forward. Please visit the NHLBI Strategic Visioning page to find out more about the NHLBI Strategic Visioning process.


Welcome to the National Heart, Lung, and Blood Institute (NHLBI) Strategic Visioning Forum. The Institute is gathering ideas for the most compelling scientific priorities in the four NHLBI Strategic Goals to address over the next decade.

Goal 2: Reduce Human Disease

Treatment of Major Depression in Patients with Heart Failure

Major depression (MD) is common in patients with heart failure, and it is an independent risk marker for functional decline, hospitalization, and mortality. Two large trials have shown that it can be difficult to treat. SADHART-CHF, a double-blind, placebo-controlled RCT (n=469), found that sertraline was not efficacious for MD in HF. MOOD-HF (n=372) showed that escitalopram was not efficacious. Smaller trials of cognitive-behavioral ...more »

Submitted by (@freedlak)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Major depression causes considerable emotional distress and functional impairment. It follows a chronic or recurrent course in many cases, and untreated episodes can last for months or even years. When superimposed on chronic heart failure, major depression can accelerate functional decline, diminish quality of life, and increase the risks of hospitalization and mortality. Effective treatment of depression can, at minimum, improve quality of life. Treatment may also decrease the risk of adverse medical outcomes, but RCTs will be needed to evaluate the potential medical benefits of treating depression in HF.

Feasibility and challenges of addressing this CQ or CC :

Cognitive behavior therapy is the most promising approach tested so far, but there have been few trials of this intervention, any other psychotherapeutic treatment for depression, or antidepressant medications other than sertraline or escitalopram for major depression in HF. Additional phase II trials may be needed in order to identify the most promising approaches for testing in larger, multicenter RCTs.

Name of idea submitter and other team members who worked on this idea : Kenneth E. Freedland, PhD

Voting

8 net votes
27 up votes
19 down votes
Active

Goal 2: Reduce Human Disease

Defining the developmental abnormalities leading to birth defects

Can we define the developmental abnormalities leading to birth defects and extrapolate that knowledge to define strategies for regeneration?

 

How can we recognize initiation of disease earlier?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

Voting

-1 net votes
8 up votes
9 down votes
Active

Goal 2: Reduce Human Disease

Environmental induction of congenital heart defects and finding means of prevention

Congenital heart defects (CHDs) continue to be the leading cause of death among all infants with birth defects. It is reported that approximately 10% of cardiac congenital anomalies have a genetic basis. An equal percentage, or ~10%, is due to environmental factors. For ~60% the etiology is unknown and considered to have a multifactorial basis, eg, environmental agents having a role against a specific genetic background, ...more »

Submitted by (@kerstilinask)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

College drinking is up especially among young women. Women of both high and low income levels drink, may be smoking marijuana, or are exposed to other environmental toxicants. Are there gender effects, as it has been reported that in the US, more male babies undergo severe cardiac surgeries than female. Few grants are presently funded that take a teratological approach to understanding mechanisms underlying induction of congenital heart defects that can occur before a women realizes being pregnant. The embryo may already have been harmed by then and the effects last a lifetime for the child. High dose folate may be preventative of CHDs and this needs to be better defined and the effects of high folate doses on the adult and fetus need to be analyzed. A possible role for gender should be defined.

Feasibility and challenges of addressing this CQ or CC :

A recommended goal is to emphasize the submission of grants specifically addressing the etiology of congenital heart defects due to environmental factors and their prevention, using cell and molecular teratological approaches. Reinstate a study section on Teratology and Toxicology of Birth Defects made up of PIs working in those fields. There used to be four such study sections and were all removed years back. One such section should be reinstated. Current study sections lack such individuals on the panels due to this area receiving little funding. The neural field is way ahead in funding this topic and as a result the heart tends not to be mentioned in available literature that is provided to women of child-bearing age. Yet the risk for heart anomalies is equally as high and important as are effects on neural development. Similarly, both have lifelong consequences for the individual physically and psychologically and in cost to society with repeating hospitalizations and surgeries. Effects on the heart may be so severe that death occurs already in utero and may not always be counted among the epidemiological studies.

Name of idea submitter and other team members who worked on this idea : Kersti K. Linask, PhD

Voting

-7 net votes
16 up votes
23 down votes
Active

Goal 2: Reduce Human Disease

The role of Extracorporeal Photopheresis (ECP) in the prophylaxis and treatment of acute & chronic Graft Versus Host Disease

In Acute Graft Versus Host Disease (aGVHD), we would like to examine whether early and intensified delivery of ECP as part of standard prophylaxis will decrease overall corticosteroid exposure while preserving expected relapse rates in patients undergoing unrelated donor hematopoietic stem cell transplantation (HSCT). Chronic GVHD (cGVHD) is common after HSCT (30-50% recipients) and is a major contributor to late transplant-related ...more »

Submitted by (@js2745)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Patients who develop aGVHD undergo toxic therapy with high-dose corticosteroids, often for long durations, resulting in high morbidity and treatment related mortality. Alternatively, T cell depletion of the donor graft to reduce GVHD is associated with high rates of infection and relapse of the disease that led to the HSCT. Targeting other pathways of GVHD pathogenesis may preserve the beneficial immune reconstitution and graft-versus-tumor (GVT) effects, while ameliorating the severity of GVHD. One such pathway involves regulatory T cells (T regs), which inhibit T cell alloreactivity, and are correlated with the incidence and severity of GVHD without loss of GVT. To date, there is no consensus on a standard second-line therapy for aGVHD, and current approaches focus mainly on intensification of immunosuppression. Addressing this compelling question will help to decrease overall corticosteroid exposure while preserving the expected relapse rates in patients undergoing unrelated donor HSCT.

 

Appropriate initial therapy for cGVHD involves high doses & prolonged use (yrs) of corticosteroids, while patients still develop irreversible sclerotic manifestations of disease. Early intervention prior to disease onset may help prevent cGVHD development or lessen its severity, requiring less corticosteroid exposure. Addressing the compelling question for cGVHD will help decrease exposure to drugs with associated morbidity, while preserving expected relapse rates in these patients.

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

 

* GVHD has relatively high incidence after HSCT and at the same time there is a lack of consensus on standard second line therapy for the disease. Thus, there will be increased interest in developing and participation in those studies.

 

** ECP is generally well tolerated and complications are infrequent.

 

*** There is a great potential for multi-discipline collaboration approach in this patients’ population.

 

*** There is an opportunity to engage industry partners in the design and support for these studies.

 

**** There are numerous scientific opportunities for meritorious science as there have been limited systematic studies of ECP mechanisms of as well as standardization of apheresis protocols based on GVHD disease state.

 

 

 

Challenges:

 

* Limited number of institutions providing ECP treatment.

 

** Cost of the procedures (although Centers for Medicare and Medicaid Services now covers ECP for cGVHD).

 

*** There is a very limited number of animal models available for apheresis research in general, and studies of the mechanism(s) of action of photopheresis have been very limited as well as difficult and expensive to perform. However understanding pathological mechanisms and its relationship to response to apheresis is critical for optimization and advancement of patient care.

 

****Lack of infra-structure for apheresis research.

Name of idea submitter and other team members who worked on this idea : Joseph Schwartz on behalf of ASFA

Voting

103 net votes
126 up votes
23 down votes
Active

Goal 3: Advance Translational Research

Advancing the science of translating evidence into practice

What are the best ways for the NHLBI to advance the evolving science of translating robust evidence into clinical practice domestically and globally? How to personalize broad research evidence for individual patients? How to predict and evaluate the impact of evidence-based interventions? How to identify implementation methods available in industry and elsewhere that work best and are most translatable in healthcare? ...more »

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

• Reduce mortality and morbidity

• Improved quality of life

• Higher proportion of people receiving evidence-based care and at goal for that care

• Reduced disparities in health and healthcare

Feasibility and challenges of addressing this CQ or CC :

Challenges:

• Lack of research methodology in this area – may need new scientific approaches

 

• Lack of current capacities and capabilities in this area

 

• Current silos that separate research enterprise from industry, as well as NHLBI from other ICs

 

• Divisions between performance of clinical trials and implementation research

 

• Lack of clarity which federal agencies and NIH Institutes are ‘in charge’ of implementation and/or prioritize this as part of their mission and budget

 

• Lack of wide sharing of best practices of other implementation models

 

• Improving the science in this area needs to include methods and metrics development

 

• The accumulated knowledge of clinical trialists and implementation researchers is often not shared

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

Voting

13 net votes
27 up votes
14 down votes
Active

Goal 3: Advance Translational Research

Integrating New Genomic Discoveries with Genome Editing Towards Personalized Medicine

The human genome is a veritable digital library of information that includes millions of regulatory elements and the expansive classes of long and short noncoding RNAs. These noncoding sequences represent a rich source of sequence variation (eg, SNPs), but the role such sequence variants play in the control of gene expression or noncoding RNA function is poorly understood. Many noncoding sequence variants will prove to ...more »

Submitted by (@j.m.miano)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

We have limited knowledge of the noncoding sequence aspect of the human genome. Defining the full monty of noncoding sequences and their function will provide a more advanced understanding of CV development, homeostasis, and disease. This will be facilitated best by a centralized repository of data modeled after the UCSC Genome Browser. Further, with all functional noncoding sequences in hand, it will be an easy exercise to place, in context, sequence variants that could impact noncoding sequence function. For example, it would be important to know whether a sequence variant in a specific TFBS confers protection or susceptibility to disease. CRISPR-Cas9 could easily model such noncoding sequence variants in cells (and animals) for further exploration of function and responsiveness to intervention. As the cost of WGS continues to fall, more and more genomes will be sequenced with the identification of rare alleles that could have large explanatory power for an individual's CVD and associated treatment responses. Integrating individual genomic data with electronic health data (obviously requiring careful planning and implentation) will, in turn, allow for hypothesis testing based on experimental data accumulating in the centralized database. Ultimately, personalized medicine will be achieved by intersecting patient genomic data with wet lab data that would, in turn, inform the best route of action using CRISPR-Cas9 in patient-derived pluripotent stem cells.

Feasibility and challenges of addressing this CQ or CC :

Developing an interactive and continually updated "Cardiovascular Browser" is certainly feasible. The approach should be much like that taken by the pioneers of the Human Genome Project; that is, all participating labs should make data freely available. The data would include, among other things, expression analysis of noncoding sequences and their relationship to protein-coding genes, regulatory aspects of all coding and noncoding genes in cells of the cardiovascular system and presence of regulatory SNPs, functional annotation of noncoding sequences and sequence variants therein using CRISPR-Cas9 genome editing, and systems biology data that would integrate the accumulating data. Challenges include organizational aspects of a centralized database, appropriate selection of cell types (primary or immortal) and experimental conditions (human cells or animal model?) to capture as much information relating to CVD progression as possible (eg, noncoding sequence expression and function in [a] ECs at disturbed flow regions, [b] SMCs following exposure to oxidized LDL and [c] cardiac myocytes treated with chemotherpy or pressure overload). A challenge with CRISPR-Cas9 continues to be that of inadvertant off target effects (especially in cells). Patient privacy and safeguards against discrimination (eg, insurability) will be key. A board of CV scientists (term limited) and lay persons would thus be needed to develop, implement, and continually revise data management and directions.

Name of idea submitter and other team members who worked on this idea : Joseph Miano

Voting

6 net votes
16 up votes
10 down votes
Active

Goal 2: Reduce Human Disease

How should platelet (PLT) transfusions be used to treat active bleeding?

Multiple randomized controlled trials have been performed to evaluate the use of prophylactic PLT transfusions in non-bleeding, thrombocytopenic hematology-oncology patients. However no high-quality data exist to guide PLT transfusions in actively bleeding patients inclduing pediatric and adult medical and surgical patients. After hematology-oncology patients, cardiac surgery patients are the next largest group of PLT ...more »

Submitted by (@bldbuddy)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

PLT count is almost always the only laboratory result considered in deciding to transfuse PLTs. But PLT counts provide no information about PLT hemostatic function and its contribution to bleeding. A variety of in vitro coagulation tests have been developed: viscoelastography, whole blood PLT aggregometry, etc. But while testing-based transfusion algorithms may reduce blood product utilization, it has not been established that any in vitro test can either predict or help reduce bleeding. There is a gold standard method to assess clinical efficacy of transfused PLTs: incidence of grade 2 or higher bleeding in clinical trials of thrombocytopenic hematology-oncology patients receiving prophylactic PLT transfusions. No analogous gold standard of PLT hemostatic efficacy exists for therapeutic PLT transfusions to treat active bleeding. There is a pressing need to develop such a standard. Establishing reliable methods for evaluating the effects of PLT transfusion in actively bleeding patients will improve our understanding of how different factors (storage conditions, pathogen reduction etc.) affect the functional performance of PLTs.

Feasibility and challenges of addressing this CQ or CC :

PLT transfusions are administered routinely to support bleeding pediatric and adult medical and surgical patients. Opportunities to conduct clinical trials in various settings (cardiac surgery, neurosurgery, orthopedic surgery, trauma, etc.) are widely available. PLT transfusion is commonly used to support bleeding patients receiving perioperative supportive therapies such as extracorporeal membrane oxygenation (ECMO). These clinical situations represent critical opportunities to improve the care of bleeding patients. This approach will simultaneously facilitate comprehensive evaluation and validation of both current and novel in vitro tests of hemostasis. If a given in vitro test were reproducibly shown to correlate strongly with bleeding reduction caused by PLT transfusion, then by definition that would be a clinically meaningful test. Finally, this line of inquiry will allow assessment of the adverse effects of PLT transfusion in bleeding patients.

Name of idea submitter and other team members who worked on this idea : Terry Gernsheimer, University of Washington, for the 2015 NHLBI for the State of the Science in Transfusion Medicine

Voting

30 net votes
44 up votes
14 down votes
Active

Goal 1: Promote Human Health

Mechanisms of cardiac aging

The electrical and mechanical function of cardiac myocytes is compromised with age, but little is known about the age-related changes that occur within individual myocytes.

Submitted by (@catherine.proenza)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Voting

19 net votes
32 up votes
13 down votes
Active

Goal 2: Reduce Human Disease

Transplant to Cure Older Adults with Hematologic Malignancy-Removing the Blindfold

While transplant for patients 60 and older for high-risk hematologic malignancies has increased and observational data are promising, the risks and benefits of translant versus non-transplant remain largely unknown. We now have the tools and mechanisms to remove the blindfold! The NHLBI should support the cooperative groups in conjunction with the BMT-CTN to establish a common framework for transplant trials in older ...more »

Submitted by (@aartz0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Hematologic malignancies are more common and less treatable in older patients. This trend will contine as the number and proportion of older people in society increases. Older patients are frequently treated but rarely on studies. The availability of haploidentical and cord donor sources, better supportive care, and more tolerable regimens permits transplant to be widely accessible and utilized.

 

A critical question for the entire field of hematologic malignancies is determing the risks and benefits of allogeneic transplant for older adults. This question is posed across the country, every day by every patient and physician struggling to treat older adults with hematologic malignancies. The confluence of molecular and cytogenetic disease markers and novel measures of patient health should permit identifying those most likely to be cured and those least likely to benefit. Such data will ultimately inform the next generation of transplant trials in this population.

Feasibility and challenges of addressing this CQ or CC :

The number of patients with any of these diseases (e.g., AML, MDS, NHL and perhaps ALL) who are 60 years and older is significant. The challenge is to develop a coordinated effort to prospectively capture disease and patient health data to answer which subgroups benefit or do not.

Methods to capture patient health status have already been developed through a standardized Geriatric Assessment used in the Alliance and other studies. Most of the survey can be done electronically by a patient or by telephone. Disease based molecular markers have emerged as standard measures within cooperative group studies to augment cytogenetic and morphologic classification.

 

Ensuring cooperative groups develop uniform design and data may be difficult. Yet investigators gain much and lose little by standardizing the data capture of what already occurs (patients moving to transplant on hematologic malignancy trials).

 

Another challenge is to develop standardized measures after transplant beyond survival such as function free survival and quality of life that are patient centered. Electronic tools to capture data, especially for non-transplant patients, will greatly reduce this burden.

Name of idea submitter and other team members who worked on this idea : Andrew Artz

Voting

20 net votes
36 up votes
16 down votes
Active

Goal 4: Develop Workforce and Resources

Leveraging support from local institutions

Create a "Center of Excellence" designation in Cardiovascular Research akin to NCI's Comprehensive Cancer Center designation. Specific qualifications for such a designation will need to be defined. However this will encourage institutions to invest heavily in CV research to support such designation. In this way, local institutions will partner with NHLBI to support discovery in heart and vascular research.

Submitted by (@dgutt0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

this will raise awareness of cardiovascular disease as a strategic area of investment for academic and private institutions. It would educate patients and encourage them to participate in compelling clinical trials in respected and trusted institutions. It would cause institutions to strive for excellence in research.

Name of idea submitter and other team members who worked on this idea : David Gutterman

Voting

-17 net votes
13 up votes
30 down votes
Active

Goal 2: Reduce Human Disease

Improving patient-centered outcome assessments in HLBS studies

What types of newer patient-centered quality of life assessment tools can be employed in heart, lung, blood and sleep studies so that they can be validated and refined to improve our measurement of quality of life outcomes in populations of interest to NHLBI?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Improving our ability to precisely measure heart, lung, blood, and sleep patients' quality of life can enable evaluation of a treatment's impact on patient-centered outcomes such as overall quality of life and its components -- pain, symptoms, and a patients' social, psychological, and physical functioning.

Feasibility and challenges of addressing this CQ or CC :

New tools have been developed, notably through the PROMIS common fund project, that allow potentially more precise, reliable, valid and sensitive measurement of Q of L outcomes, with less patient burden. These tools are available but require validation in HLBS populations to allow widespread adoption and routine use in NHLBI-supported clinical trials and population studies.

Advances in biomedical science mean we are living longer with chronic diseases, and the goal of treatment increasingly focuses on disease management, maximizing function, and improving quality of life, not just lengthening life. In addition, patient-centered approaches to health care encourage a view of patients as “whole persons” with emphasis on function and capturing the "patient's voice," not just mortality/morbidity outcomes. Functional and quality of life outcomes, e.g., assessment of pain, symptoms, emotional distress, physical & social functioning, are critically important outcomes to many HLBS patients, but their measurement requires self-reports of patient experiences and thus pose challenges to precise, valid and reliable assessment.

 

Assessment tools using computerized adaptive testing (CAT), such as those developed in the Patient-Reported Outcomes Measurement Information System (PROMIS) project, have been shown to be precise, valid, sensitive to change and easier to administer than traditional Q of L measures in a limited number of studies, but they require validation in HLBS patient populations before they can be used more widely in NHLBI-funded studies.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

Voting

11 net votes
20 up votes
9 down votes
Active

Goal 2: Reduce Human Disease

Develop and validate a metric to address the full spectrum of patient-level comorbidities affecting critical illness

An individual metric to inform about the additive and not individual impact of comorbidities on critical illness and peri-operative mortality. For instance, we know the impact of COPD or MI or CKD on mortality after hemicolectomy, but not necessarily the additive impact of all three.

Submitted by (@greg.martin)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

Voting

2 net votes
4 up votes
2 down votes
Active