Goal 2: Reduce Human Disease

Improve vascular healing and extend long term benefit of interventions

How can we develop new approaches to improve vascular healing and extend the long term benefits of vascular interventions for more patients?

Submitted by (@societyforvascularsurgery)

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

Details on the impact of addressing this CQ or CC :

­The response to vascular injury, whether it be catheter interventions, bypass surgery, or chronic implants, is a reactive process characterized by inflammation, cell proliferation, and fibrosis leading to failure. Better understanding of the mechanisms of vessel remodeling, and restoring homeostasis, is needed to improve prediction, develop and translate new treatments. This remains the leading scientific problem in vascular medicine and surgery. New approaches such as proteomics, lipidomics, molecular imaging offer new opportunities in this realm.

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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Goal 2: Reduce Human Disease

RFA on EC-cardiomyocyte interactions in the mechanisms and treatments of cardiovascular diseases

Often under recognized, the cardiac endothelial cells are highly abundant in the heart, and may have important roles in modulating cardiac function, besides simply serving as structural component of blood vessels. Evidences of ours and others have indicated an emerging role of cardiac endothelial cells signaling to cardiomyocytes to mediate important pathophysiological responses. Nonetheless, detailed mechanisms of ...more »

Submitted by (@hcai00)

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

Details on the impact of addressing this CQ or CC :

Successfully addressing this question would no double reveal novel mechanisms and ways of monitoring treatment responses of cardiovascular disease, ultimately leading to novel drug targets, valuable biomarkers and extended new directions of basic research as well.

Feasibility and challenges of addressing this CQ or CC :

Tools of studying these cells are mostly available. Both adult cardiomyocytes and endothelial cells from the heart can be isolated and cultured, although cardiomyotyes need to used within 24 hrs and cannot be passaged. However successful preparation of these cells from WT and transgenic animals would permit co-culture experiments and mechanistic studies. These cells can also be studied using in-situ techniques either detecting molecular changes/events or dynamic interactions. Potential challenges would side in selective targeting of these cells, for example, either ECs or cardiomyocytes, once a potential therapeutic is in the testing. Nonetheless, PECAM-ab conjugated techniques have been employed to specifically deliver proteins to endothelial cells, so I am confident most of the challenges can be worked out, particularly within a RFA awardees group with frequent exchanges of ideas.

Name of idea submitter and other team members who worked on this idea : Hua Linda Cai, University of California Los Angeles

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Goal 3: Advance Translational Research

Animal models of vascular diseases

How can we better model human vascular disease in all its complexity?

­This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.

Submitted by (@societyforvascularsurgery)

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 for Vascular Surgery

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Goal 3: Advance Translational Research

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors in trauma patients - physiologic effects and impact on outcomes

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors are new, undetectable and irreversible. We have no data on how well these drugs correlate with current measures of coagulopathy such as thromboelastography, or whether antifibrinolytics should be used in patients who are on these drugs. These drugs may increase incidence of traumatic brain injury after minor injury. They are also going to be used increasingly in ...more »

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Understanding pathophysiology of coagulopathy in trauma patients due to these drugs may lead to innovations in management of coagulopathy and help increase our ability to predict/prognostic poor clinical outcomes in patients on these new anticoagulants, detect these drugs in a timely manner and develop antidotes/reversal agents. 

Feasibility and challenges of addressing this CQ or CC :

These are eminently feasible with adequate support from the NHLBI. Challenges will be finding collaborations or institutions that have enough clinical volume and adequate basic science/translational research infrastructure to look at these questions seriously.

Name of idea submitter and other team members who worked on this idea : Sudha Jayaraman

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Goal 2: Reduce Human Disease

Determining the significance of variants of unknown significance

Variants of unknown significance (VUS) confound the value of genetic testing. We need to improve our understanding of the clinical significance of VUS so we can more definitively re-classify them as pathologic or benign variants.

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Next gen sequencing and clinical genetic testing are becoming a more frequent component of clinical care. Not infrequently a VUS result is returned providing little clinical value to the patient. Determining the significance of these variants will be extremely valuable to patients undergoing genetic testing.

Feasibility and challenges of addressing this CQ or CC :

Bioinformatics and big data infrastructure will mature over the next several years to allow us to record VUS results, follow patients longitudinally, aggregate data, and ultimately determine the significance of VUS.

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

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Goal 3: Advance Translational Research

Improving patient-clinician communication and decision-making for patients wiith serious heart, lung or blood diseases

How can we ensure that patients with serious heart, lung, or blood diseases fully understand their prognosis, treatment options, and the risks and benefits of those options and help them make decisions that fully incorporate their own personal values, goals, and treatment preferneces?

Submitted by (@jrc000)

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

Details on the impact of addressing this CQ or CC :

Patients with serious heart, lung and blood diseases are often faced with dificult treatment decisions that involve tradeoffs and long-term consequences without adequate understanding of their prognosis and the risks and benefits of treatment. There is emerging consensus that a shared decision-making approach provides the best support for patients and their families in this situcation, but there is evidence that this is not happening and there is inadequate data to guide the best approach to ensuring it does happen. Dramatic advances in treatment technologies make treatment choices ever more complex and often make the tradeoffs more difficult to fully understand. Advances in our ability to help patients and their families through this decision-making process have not kept up with these advances in treatment options.

Feasibility and challenges of addressing this CQ or CC :

Incorporation of palliative care approaches, decision aides, and improvements in clinician-patient communication provide the opportunity to make important advances in this area, but have not been fully developed or incorporated. There is an opportunity to advance the communication, decision-making, and implementation science to have a dramatic impact on enhancing healthcare and quality of life for patients and thier families.

Name of idea submitter and other team members who worked on this idea : J. Randall Curtis, MD, MPH

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Goal 2: Reduce Human Disease

Does epinephrine improve outcomes in OHCA

Epinephrine is the primary drug that is used in resuscitation but observational studies and a few small RCT suggest that it improves short term but not long term outcomes. Factors such as timing, dose, quality fo CPR and post-resuscitation care all confound the issue. Large RCTs conducted at multiple centers are desperately needed to address this question.

Submitted by (@dayam0)

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

Details on the impact of addressing this CQ or CC :

If short terms outcomes are improved but not long term outcomes, we are only adding costs and not improving population health

Feasibility and challenges of addressing this CQ or CC :

Will require a large prehospital clinical trials network and ideally also a current national registry of OHCA to address secular changes in other confounding variables

Name of idea submitter and other team members who worked on this idea : Mohamud Daya

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Goal 2: Reduce Human Disease

Interactions between anticoagulant therapy and antiretroviral drugs

Cardiovascular pathology has become a major problem in the management of the HIV-infected patient during the ART era. A large number of HIV patients will receive anticoagulants drugs for secondary prevention of cardiovascular disease. It is therefore critical to understand the interactions between antiretroviral therapy and anticoagulant therapy to safely treat HIV patients.

Submitted by (@pandrea)

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

Details on the impact of addressing this CQ or CC :

With over 50% of HIV-infected patients in the US anticipated to be > 50 years of age by 2015, the overall risk of CVD will be significantly higher and could become the main challenge for the management of chronic HIV infection. A large number of HIV-infected patients with CVD will therefore need treatment for primary and secondary prevention of atherothrombotic events. The secondary prevention of CVD almost invariably includes prescription of one or multiple anticoagulants drugs. It is therefore conceivable that anticoagulant therapies will be frequently associated with ART for the management of HIV patients, which already developed CVD. The interactions between these therapies are not well studied and are critical for the management of the HIV-infected patients.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: 1) retrospective studies on a large number of HIV patients that had cardiovascular events and were treated with antiretroviral drugs; 2) prospective studies comparing different antiretroviral regimens associated with the most current anticoagulant therapy recommended for secondary prevention of CV disease; 3) use of animal models of AIDS for testing new anticoagulants and the interaction with the antiretroviral drugs.

Name of idea submitter and other team members who worked on this idea : Ivona Pandrea

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Goal 1: Promote Human Health

Nicotine abuse and fetal programming of heart ischemic disease

It is well-known that cigarette smoking is a major risk factor of heart ischemic disease. However, little information is known about the maternal smoking and fetal programming of heart ischemic disease in adulthood. Recently, e-cigarette (nicotine use) during pregnancy is a worldwide health concern. Epidemiologic studies have indicated that cigarette smoking during pregnancy is associated with an increased risk of cardiovascular ...more »

Submitted by (@dxiao0)

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

Name of idea submitter and other team members who worked on this idea : D Xiao

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Goal 3: Advance Translational Research

Palliative and hospice care for COPD patients

Does palliative care and/or hospice care as practiced across communities improve end-of-life care for COPD – specifically, does it reduce the burden of symptoms, improve HRQoL and satisfaction, reduce utilization in last 6 months of life (i.e. hospital visits, cost, invasive ventilation use, etc), improve the end-of-life experience, and increase the concordance of place of death to expressed patient preferences?

Submitted by (@k.willard)

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

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Goal 2: Reduce Human Disease

What is the effect of variant genes on AVM development in HHT

Natural genetic variation between individuals can influence the outcome of carrying an HHT mutation. Some gene variants may be protective while others may increase the risk of AVM or telangiectasis. By identifying the variant genes that alter risk of AVM may give clues to the molecular mechanisms of AVM formation and provide new drug targets

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

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Goal 4: Develop Workforce and Resources

Reproducibility Initiatives in Heart, Lung and Blood Research

Scientists feel tremendous pressure to publish numerous scientific papers in order to receive NIH funding and tenure at academic institutions. Cognitive biases of scientists and publication biases of journals that publish this barrage of papers will likely result in the publication of findings that are probably not reproducible (see "Why Most Published Research Findings Are False" by John P. A. Ioannidis in PLOS Medicine ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

By distinguishing research findings which are reproducible from those which aren't, researchers will be able to build future research programs on solid scientific foundations.

 

There are many reasons for why research may not be reproducible, ranging from simple biological variations (cells from one supplier may behave differently than cells from a different supplier) to conscious/unconscious biases or misconduct. No matter what the underlying cause is, irreproducible research findings that are not recognized as such will result in a tremendous waste of time and resources. Graduate students or postdoctoral trainees may waste entire years of their precious training period conducting experiments that are based on published papers which may turn out to be irreproducible.

 

NHLBI could significantly improve the quality of research by building an infrastructure that supports the assessment of reproducibility and widely shares these findings.

Feasibility and challenges of addressing this CQ or CC :

One of the challenges for assessing reproducibility of published work is that it is considered not very innovative and there is no funding available. NIH grants are awarded to highly innovative proposals which venture into new territories and not proposals which want to confirm the validity of published work. However, the returns of investing into reproducibility testing might be enormous because irreproducible results would be identified and weeded out, thus preventing loss of resources and time.

 

The NHLBI could develop funding mechanisms specifically designed to support research proposals that will test the reproducibility of high impact findings that have not yet been independently verified. The study sections would review these proposals using novel criteria designed for such studies. The emphasis of the study section review would lie on questions such as "Is this an important enough question that it merits reproducibility testing?" instead of the traditional "Is this a cutting-edge technology that nobody has previously used?"

 

Challenges would include identifying journals that would published results of these studies and agreeing on what constitutes reproducibility (i.e. is it enough if the major conclusion or effect is reproduced even though the effect size may be very different?).

Name of idea submitter and other team members who worked on this idea : Jalees Rehman

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