Goal 3: Advance Translational Research

Clinical Tools for Pediatric CVD Risk Reduction and Asthma Treat

What are effective strategies and clinical decision support tools that can maximize pediatric care providers’ adoption of evidence-based recommendations for assessment and treatment of cardiovascular risk factors and/or asthma? • Clinical recommendations and associated implementation tools are often incorporated into electronic medical records (EMRs). Currently there is no standard EMR format and therefore it is difficult ...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 :

• Cardiovascular disease (CVD) remains the leading cause of death and disability in North America. There is extensive evidence documenting the initiation of the atherosclerotic process, the pathologic basis for clinical heart disease, in childhood. Additionally, asthma a chronic condition that affects more than 7 million children in the U.S. and leading to numerous emergency visits.

• Among the major factors that are associated with increased clinical recommendation use are ease of access and feasibility. A common obstacle that providers face is the availability of proper information at the point of care.

• The Community Preventive Services Task Force recommends clinical decision-support systems for prevention of cardiovascular disease based on sufficient evidence of effectiveness in improving screening for CVD risk factors and practices for CVD-related preventive care services, clinical tests, and treatments. Mobile solutions may help to further facilitate this process.

• Successful implementation of clinical recommendations for prevention and treatment of CVD pediatric risk factors and asthma could greatly reduce the number of youth moving into adulthood at increased risk for CVD and could improve health outcomes for children with asthma.

Feasibility and challenges of addressing this CQ or CC :

• Most care providers have mobile devices or computers for use in the clinical setting. There is good evidence that clinical decision support tools (and other implementation tools) can help facilitate adoption of clinical recommendation.

• It is important to test strategies in a large scale intervention that will measure clinical CVD outcomes.

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

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Goal 2: Reduce Human Disease

Defining critical elements for irreversible myocardial injury

What are the critical mechanisms that account for progression from reversible to irreversible ischemia and reperfusion injury?

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 :

Understanding the mechanism of how myocardium becomes irreversibly injured will provide clarity for therapeutic intervention.

Feasibility and challenges of addressing this CQ or CC :

Advances in proteomics and databases of post-translational modifications may support the feasibility of discoveries in this area.

This information is key for designing novel therapeutic strategies for acute myocardial ischemic injury. This understanding will define the critical timing, location, and distribution of modulators, and amplitude required for activation of components involved in protective pathways.

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Goal 2: Reduce Human Disease

Can one integrate cardiac imaging studies with genetic,clinical, "omics", and historical data to predict disease and personalize

There are many novel imaging modalities, including radiographic, scintigraphic, sonographic, MR-based, and molecular for the heart and vessels. Patients have unique medical "signatures"- genetic risk factor profiles, epigenetic markings, "omics" profiles, and personal clinical and family history as well as symptom constellation and physical exam findings. Can these all be integrated into a single personalized profile ...more »

Submitted by (@dpinsky)

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

Feasibility and challenges of addressing this CQ or CC :

This will require a combination of informatics, state of the art imaging, and state of the art genetics and omics profiling with integration with the electronic health record.

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Goal 2: Reduce Human Disease

What is the role of diet and nutrition in treatment, management and prevention of Heart Failure?

Heart Failure (HF) remains a major public health burden. A working group was convened by NHLBI and ODS in June, 2013 to address the role of diet and nutrition in management of HF. A review of existing evidence produced no clear rationale for appropriate dietary interventions. On the contrary, the group developed recommendations for conducting additional research specifically on the role of sodium, fluid, nutrients, and ...more »

Submitted by (@lvanhorn)

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

Details on the impact of addressing this CQ or CC :

As summarized following the Working Group meeting,compared with the situation for cardiovascular risk factor management, there is little well-founded evidence regarding the efficacy, safety, and clinical impact of dietary modifications for patients with various HF phenotypes. The importance of diet and nutrition to promote health and prevent or control disease is well established. Research on obesity, hypertension and cardiovascular disease have contributed to the development of nutritional guidelines to prevent these disease in the general population but efforts to determine nutritional needs for the patient with HF lack high caliber evidence regarding safety, efficacy, and clinical impact of dietary modifications. The stronger evidence and focus on disease prevention and health promotion with diet modifications like DASH cannot be easily applied or extrapolated for disease management, especially HF, because of critical knowledge gaps and potential harm. Research on HF has more recently identified and differentiated medical treatment and interventions appropriate for HF with or without preserved ejection fractions. This only adds to the questions surrounding diet and nutritional approaches to help reduce and prevent HF readmissions.

Feasibility and challenges of addressing this CQ or CC :

Chronic HF often presents as a multisystem disease with important co-morbidities such as anemia, insulin resistance or diabetes, autonomic dysregulation, and impaired renal function. Intestinal dysfunction with impaired motility and circulation and disturbed intestinal barrier and flora may lead to a chronic inflammatory state and nutrient malabsorption. In advanced cases, catabolic/anabolic imbalance is associated with cardiac cachexia, a difficult to treat condition which itself carries a poor prognosis. Furthermore, psychosocial symptoms associated with HF, including depression and impaired cognition, can contribute to poor self-care and lack of adherence to recommended dietary, physical activity, and medication regimens. Nutritional status concerns for patients with HF increase with disease severity. Salt restriction is now controversial and clinicians give little attention to diet as a potential intervention to improve outcomes. Proposed recommendations:

1.Determine the correct sodium threshold; ranges of sodium and fluid intake, and the safety for sub-groups including HFPEF, HFREF, and cardiorenal syndrome. 2.Generate new knowledge which identifies therapeutic targets and understand the role of the gut microbiome on gastrointestinal malabsorption, inflammation, and protein balance in HF.

3.Apply innovative study designs to reduce evidence gaps 4.Develop technologies to facilitate nutrition research and address weight and multiple risk factors should be addressed.

Name of idea submitter and other team members who worked on this idea : Linda Van Horn, PhD, RD

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Goal 3: Advance Translational Research

Genetics and Genomics of Heart Disease

Identification of new genetic/genomic variants and risk genes often opens a new window to explore the fundamental molecular mechanisms underlying a disease and to develop new methods and strategies for diagnosis and treatment. Existing genomic variants and/or mutations explain only 10% to 20% heritability of common heart diseases. Much remains to be done in this important area. However, most genetic projects are discovery-driven ...more »

Submitted by (@wangq2)

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

Details on the impact of addressing this CQ or CC :

Identification of new genetic/genomic variants and risk genes often opens a new window to explore the fundamental molecular mechanisms underlying a disease and to develop new methods and strategies for diagnosis and treatment. Existing genomic variants and/or mutations explain only 10% to 20% heritability of common heart diseases. Much remains to be done in this important area. However, most genetic projects are discovery-driven and not hypothesis-driven, so that finding in this area has been extremely low. We recommend that genetics and genomics should be placed as a strong priority for NIH funding for the coming years.

Feasibility and challenges of addressing this CQ or CC :

Feasible

Name of idea submitter and other team members who worked on this idea : Qing Kenneth Wang

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Goal 4: Develop Workforce and Resources

Suipport new research using the R21 mechanism

The decision by NHLBI to not support the R21 mechanism may be stifling new and innovative research, partcularly by young investigators who do not have a track record of R01 funding. The critical challenge is to keep funding new ideas from younger investigators to keep their careers viable while they obtain the data and publications necessary for further R01-level funding.

Submitted by (@georgeporter)

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

Details on the impact of addressing this CQ or CC :

The state of NHLBI funding rates for R01s are so low that we are undoubtedly loosing many young researchers as the fail to obtain adequate support for their research. Funding R21 grants will allow new, innovative, and perhps risky projects to proceed, while keeping less established researchers in the field. Re-establishing R21 funding may prevent the impression that NHLBI is more interested in supporting established labs and not advocating for and supporting new investigators.

Feasibility and challenges of addressing this CQ or CC :

Given the limited budget of R21s, they will not have as large an impact on the overall budget of NHLBI as the equivalent number of funded R01 grants. Therefore, this change is feasible from a financial standpoint. Obviously, funding R21s will decrease funding for other mechanisms. Finally, it is possible that many of these grants will not lead to advances in the field, but it is my understanding that studies show the same thing about R01s.

Name of idea submitter and other team members who worked on this idea : George Porter

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Goal 1: Promote Human Health

Promoting health through simultaneous prevention of obesity and eating disorders

How to best promote healthy weight while also not stigmatizing obesity and creating risk for eating disorders (i.e., weight concern and body dissatisfaction) in youth. How to tackle both without contributing in unwitting way to development of either.

Submitted by (@tantillo)

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

Details on the impact of addressing this CQ or CC :

Studies show that diets do not lead to sustained health benefits for the majority of people and several studies indicate that dieting is actually a consistent predictor of future weight gain. Repeated cycles of losing and gaining weight are linked to heart disease, stroke, diabetes and altered immune function. Children and adolescents are especially vulnerable to the impact of dieting. Several long-term research studies show that girls and boys who use unhealthy weight control practices (including dieting) in early teen years are more likely to become overweight five years later, even if they started out at normal weight. These studies also show that early teen boys and girls who use unhealthy weight control practices are at greater risk for binge eating, use of severe weight control practices ( vomiting, diet pills, laxatives and water pills), and eating disorders compared with adolescents not using weight-control behaviors.

 

Since our culture tends to create weight bias and obesity stigmatization, it is not surprising to see our children become increasingly fearful of becoming “fat.” Weight concern can be experienced by underweight, average weight and overweight children and teens. Studies have shown that body dissatisfaction, especially weight concern (for early teen boys and girls), can lead to overweight, binge eating, severe weight control practices, and eating disorders. Weight teasing by family members and peers can also increase the risk for eating disorders.

Feasibility and challenges of addressing this CQ or CC :

Challenges include creating teams of researchers who will collaborate across the two fields. I believe if we could create such teams we could

move both fields ahead with regard to prevention and a focus on health (behaviors that are health promoting), not BMI (a number) or an emphasis on intake.

 

The key to both health problems involves the ecology in which youth are located b/c this ecology influences body image, intake, activity, self regulation and self care.

Name of idea submitter and other team members who worked on this idea : Mary Tantillo PhD PMHCNS-BC FAED

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Goal 4: Develop Workforce and Resources

Establishment of an independent study section on Pulmonary Vascular Biology and Translational Research

The research on pulmonary vascular biology including smooth muscle cell biology and endothelial cell biology and related pulmonary vascular diseases such as pulmonary hypertension and related right heart failure, and endothelial dysfunction in lung vascular inflammation and acute lung injury, as well as pulmonary embolism and lung transplantation has been rapidly expanding. The field is attracting an ever increasing ...more »

Submitted by (@yyzhao)

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

Details on the impact of addressing this CQ or CC :

Establishment of a study section on Pulmonary Vascular Biology and Translational Research will provide adequate funding to stimulate innovative research on this rapidly expanding field and promote translational research and thereby promote human health by providing potential novel therapeutic strategies for the devastating diseases such as pulmonary hypertension and acute lung injury.

Name of idea submitter and other team members who worked on this idea : Youyang Zhao, Kurt Denmark, Asrar B. Malik, Mark Gladwin, Jahar Bhattacharya, Michael Matthay, Sharon Rounds, Jason Yuan

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50 up votes
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Goal 4: Develop Workforce and Resources

Translational training programs

The strategic vision to enhance translation and to enhance the workforce both require training that spans the scope of basic science, pre-clinical development, clinical trials. We lack coherent mechanisms for training the next generation of translational researchers, some of whom may be MDs, and some PhDs. A program should provide cross-training of Clinical Fellows and Postdocs to reflect the needed interactions between ...more »

Submitted by (@wjones7)

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

Details on the impact of addressing this CQ or CC :

The impact will trainees with more comprehensive exposure and involvement in translation of science from the bench to bedside. MDs will spend more time in labs or involved in pre-clinical work, PhDs will become CITI certified and assist with enrollment of clinical trials and trial design. Journal clubs will span the sciences, the clinical practice and the translational realm including regulatory and industry considerations. Trainees can use this background whether they go on in medicine, science, translation, or industry to fit and contribute to an increasingly translational medical bioscience field.

Feasibility and challenges of addressing this CQ or CC :

Feasibility must include a academic medicine environment active in translational biomedical science such that the mentors can include scientists, physicians and physician/scientists, some of whom are translators. Some of the scientists should be from industry and perhaps projects and funding can involve industry/Pharm as well these will benefit from an educated workforce. Challenges involve individuals at the sites putting the right teams together, but many Universities are doing this with incubators and translational units at present. This will further the clinical involvement to include Fellows in Fellowship programs in Cardiology, Medicine and Surgery.

Name of idea submitter and other team members who worked on this idea : Keith Jones

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38 up votes
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Goal 2: Reduce Human Disease

Why does loss of endoglin in adult blood cells lead to cardiac hypertrophy in HHT patients

Liver arteriovenous venous malformations creates a high flow shunt that over time creates high output cardiac failure with no effective treatments.

Submitted by (@mariannes.clancy)

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 : Marianne Clancy MPA, Chris Hughes PhD

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Goal 2: Reduce Human Disease

Seeking the secret behind “resilience” to a variety of HLBS diseases

What is the secret behind the “resilience” some people have to heart, lung, blood, and sleep (HLBS) diseases?

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 :

Results of such research should reveal physiological mechanisms of resilience that could be used to develop interventions that would prevent or cure a variety of heart, lung, blood, and sleep diseases.

Feasibility and challenges of addressing this CQ or CC :

Advances in omics, clinical testing

, accumulation of large sets of clinical data and samples

, big data tools

, and increased interest from public (normal volunteers) and patients to participate in large scientific experiments make it feasible.

For instance, these may be healthy people carrying genetic mutations strongly associated with HLBS diseases (or causing rare/familial genetic diseases – these might easier to focus on first), but also people who are not hypertensive, hypercholesterolemic, or diabetic in spite of consistently making bad dietary choices, people who did not develop lung conditions in spite of high pollutant exposure, or are otherwise “protected” from other heart, lung, blood and sleep diseases. This reasoning is not very different from that used to identify ApoA Milano, or even PCSK9 or the “longevity genes”. Such information should reveal physiological mechanisms that could be leveraged to develop interventions to prevent or cure HLBS diseases.

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

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26 up votes
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Goal 4: Develop Workforce and Resources

Medical student research training in LMIC settings

What are the strategies for heart, lung, blood, sleep workforce to gain first-hand international experience in clinical research/implementation research training in low- and middle-income country (LMIC) settings?

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

• Among the students who earn medical degrees in the United States, very few of them have been sufficiently trained to address the health needs of the most vulnerable populations.

• An international exposure in an LMIC setting would have enormous impact on clinical practice and research

• Any medical student interested in broadening their training may have opportunities for clinical and non-clinical hands-on experience and in turn this would increase number of physicians and researchers in global health.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: • The NHLBI has a wealth of experience in training and career development programs in general and has supported and worked with global centers of excellence in this area.

• This experience can be used to leverage international experience in clinical practice and research outcomes in LMIC settings.

 

Challenges: • NHLBI would have to develop additional training mechanism(s) to foster clinical practice and research in an LMIC area.

 

• Resources for this unique training may be a challenge.

 

• Helping patients from vulnerable populations would involve confronting cultural differences and language barriers.

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

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