Goal 2: Reduce Human Disease

Cardiometabolic Disease Risks Associated with Sleep Deficiency

How does insufficient sleep duration, irregular timed sleep schedules, and poor sleep quality contribute to the pathophysiology of lung, heart and blood 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 :

Sleep deficiency and untreated sleep disorders threaten the health of 20-30 percent of US adults through an increased risk of stroke, hypertension, diabetes, inflammatory disease, and all-cause mortality. Developing the scientific evidence-base of validated interventions will enhance the management of cardiometabolic and pulmonary risks to health, present new opportunities for secondary prevention, and reduce associated burden on health care systems.

Feasibility and challenges of addressing this CQ or CC :

Improving sleep health through informed public recognition of decision-relevant science, and relatively low cost therapies for management of sleep disorders are available for immediate assessment of impact in appropriate clinical trials to demonstrate efficacy and effectiveness.

Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease.

 

Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. The pathophysiological findings juxtaposed with epidemiological evidence of disease risk indicate that sleep deficiency contributes to an erosion of health across the lifespan over and above the effects of aging.

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

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Goal 3: Advance Translational Research

NHLBI Cardiovascular Engineering Strategy

Most impressive and impactful advances in CV diagnostics and therapies came in the last 50 years from CV engineering, including implantable devices and imaging technology. CV engineers are developing next breakthrough technology including tissue engineering and flexible electronics. However, organizational structure of NIH does not have an entity responsible for strategic development of CV engineering. NIBIB does not ...more »

Submitted by (@efimov)

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

Details on the impact of addressing this CQ or CC :

Cardiovascular Science produced numerous fundamental ideas, which frame our approaches to diagnostics and therapy of heart disease. However, translating these ideas to clinic very often requires engineering approaches. Examples of such breakthrough therapies are implantable pacemakers and defibrillators, stents, MRI, CT and many other imaging modalities. NIBIB supports many fields of biomedical engineering, except cardiovascular! NHLBI lacks a branch responsible for strategic development of cardiovascular engineering as a critical pathway to translation of basic science ideas. There is no study section or review group focusing on cardiovascular engineering. As a result, most of CV Engineering grants are reviewed by CV biologists, who lack engineering background and have quite different priorities and vision of the field. Next breakthrough developments will happen in tissue engineering, flexible/stretchable/biodegradable electronics, novel imaging modalities, computational physiology, and other classical biomedical engineering sub-fields. Unfortunately, they are less likely to happen in cardiovascular field, because NHLBI lacks corresponding organizational structure. A working group should be formed to frame NHLBI's vision for the future of cardiovascular engineering as an indispensable component for translation from CV biology to CV therapy.

Feasibility and challenges of addressing this CQ or CC :

Biomedical engineering has trained several generations of professionals in academia and industry, which pursue basic and translational research and development with great degree of success. CV Engineering is a standard component in numerous BME Departments. Large number of senior and junior CV engineers have been recognized for their significant contribution to CV health. There is enormous CV engineering expertise and experience, which should be leveraged by NHLBI, in order to broadly define institutional strategy not only for CV biology but also for CV engineering, which are equally important in development of future breakthrough therapies for CV disease. Currently, support for CV engineering is scattered across numerous mostly biology focused groups, lacking strategic vision and coherent policy. A number of talented CV engineers are forced to leave the field to pursue other areas of biomedical engineering, which enjoy better-organized professional group support.

Name of idea submitter and other team members who worked on this idea : Igor Efimov

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Goal 3: Advance Translational Research

Scientific priorities for HIV-related cardiovascular research

Millions of virally suppressed patients with HIV/AIDS survive to older ages and will become increasingly vulnerable to inflammation-associated cardiovascular disease. The critical challenge is to determine whether age-driven cardiovascular declines that occur HIV-infected people are exacerbated by the persistent systemic inflammatory drive that occurs in virally suppressed patients. Studies that document cardiovascular ...more »

Submitted by (@bgelman)

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 of this critical challenge would be to heighten the translational impact of HIV-related cardiovascular research. Key facets of this challenge are: 1) To give high priority to studies that use human tissue specimens that have been carefully annotated and biobanked, 2) To be certain that proposed studies employ tissue from age-appropriate comparison patients who were not HIV infected, and 3) To avoid giving undue credence to acute infection or in vitro infection models (as with tat and gp120 toxicology) that do not reflect immunologic and virologic mechanisms in virally suppressed patients. Millions of virally suppressed patients with HIV/AIDS survive to older ages, and become increasingly vulnerable to cardiovascular disease. Ischemia-related disease causes dysfunction especially in organs that depend on abundant blood flow such heart, brain and kidneys. All these organs are affected to some extent by persistent inflammation in virally suppressed HIV-infected patents. The compelling question/critical challenge is to determine whether age-associated cardiovascular changes are exacerbated by persistent mild systemic inflammatory drive that are found in blood vessels of virally suppressed patients. Studies that document the presence of cardiovascular changes in older infected people without controls, or in vitro models of acute infection, both do not address issues of high translational relevancy. Using human tissue specimens from age-appropriate controls does.

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

1) Obtaining well-annotated organ specimens from HIV infected and noninfected people is feasible. The National NeuroAIDS Tissue Consortium (NNTC) collection goes well beyond the CNS and includes heart, lung, kidney, gut, liver, spleen and other organs. Many of the organs specimens in the collection have been annotated with virological and immunological markers already.

2) Over 900 autopsies on HIV infected patients are banked by the NNTC and over 100 of these decedents were over the age of 50. Over 200 controls are effectively banked. These specimens and related clinical data are in the public domain at this time.

3) Age appropriate autopsies were done by the NNTC, and a large number of NIA sponsored tissue repositories have accumulated tissue from elderly patients.

Challenges:

1) The limitations of using autopsy material and the limits of a cross sectional view need to be better understood and appreciated. These studies should not be written off scientifically as "observational" or "not hypothesis driven."

2) The lessons of not using age-appropriate controls have NOT yet been learned in the HIV/AIDS research community. A prime example is an overabundance of brain aging surveys in HIV infected populations that did not contain age-appropriate controls. A controversial and inconclusive brain aging pathology literature was produced because of that.

Name of idea submitter and other team members who worked on this idea : Benjamin Gelman

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Goal 2: Reduce Human Disease

Development of non-contrast alternatives in cardiac magnetic resonance imaging

Critical Challenge

Submitted by (@str0001)

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

Details on the impact of addressing this CQ or CC :

Late gadolinium-enhancement cardiac magnetic resonance imaging (MR) plays a crucial role in the evaluation of patients with suspected myocardial scar tissue. Alternative methods to contrast-enhanced MR however are in need, given the number of patients who have concomitant compromised renal function and concern for nephrogenic systemic fibrosis. Noncontrast MR techniques such as diffusion-weighted imaging would complement and eventually replace gadolinium administration thus impacting the evaluation of those with suspected and confirmed infiltrative cardiac processes and systemic diseases.

Feasibility and challenges of addressing this CQ or CC :

Late gadolinium enhancement technique characterizes enhancement patterns of heart disease, identifies areas amenable to ablation, and aids in decisions pertaining to workup and therapy. The underlying mechanism of Brownian motion/diffusion in the expanded extracellular space makes diffusion weighted imaging a potential gadolinium-saving modality. Diffusion MR, applied primarily in the brain and abdominal imaging, is underutilized in the heart given respiratory and cardiac motion. A need exists to further develop and apply noncontrast MR techniques towards cardiovascular applications. Such methods are promising noncontrast alternatives to characterize patients with myocardial disease, determine those with differing prognoses, and direct appropriate therapies to subgroups.

Name of idea submitter and other team members who worked on this idea : Society of Thoracic Radiology

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6 up votes
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Goal 3: Advance Translational Research

Develop biomarker panel to predict CVD risk in -omics era

There is a need to utilize the vast data generated in -omics research to develop biomarker panels for better prediction of cardiovascular disease (CVD) risks. •Cardiovascular diseases develop over decades and different panels of markers may be required for different stages •Lead molecules as potential biomarkers need to be selected by a panel of experts •Standard procedures about sample preparation, data acquisition, ...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 :

•Develop specific and sensitive markers for early prevention with more predictive power. Biomarkers that can detect specific perturbations in the system, such as metabolic status and vascular integrity prior to the occurrence of the diseases can be used for early preventive treatment of cardiovascular diseases.

 

•Identify vulnerable population who cannot be identified by the current LDL-HDL profiling

 

•Allow for more personalized treatment

Feasibility and challenges of addressing this CQ or CC :

•An increase in system biology studies using –omic approaches have provided huge data to mine through and find potential biomarkers, such as microRNA, DNA, lipids, proteins, and other metabolites, which can be used to assess changes proceeding cardiovascular diseases occurrence.

 

•The NIH-wide Big Data to Knowledge (BD2K) initiative launched in 2012 may have laid out some framework.

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

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Goal 4: Develop Workforce and Resources

Training Biomedical Research Experts for Life Beyond the Ivory Tower

Only 10-20% of graduates from PhD programs in the biomedical sciences will pursue a scientific career in the traditional tenure track academic model. This is in part due to a mismatch between a large number of highly qualified scientists and the relatively small number of tenure track positions available. Instead of viewing the careers of the 80-90% as "alternative careers", we have to accept that in fact the traditional ...more »

Submitted by (@jalees)

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 majority of trainees in NHLBI graduate and postdoctoral training programs will likely pursue a diverse spectrum of careers such as scientists in the biotech and pharmaceutical industry, educators, health and science journalists, editors, patent lawyers or health/science consultants in the world of finance and politics.

 

Most NHLBI T32 training grants are awarded to academic institutions and the mentors tend to be tenure-track or tenured academics with NIH R01 funding. The question we have to address is whether these traditional training programs and mentors are well-suited to advise and prepare trainees for careers outside of academia.

 

The NHLBI should fund novel training programs that require or encourage involving mentors outside of academia and funding training projects that allow trainees to work in industry, publishing, writing, politics, non-profits and other non-traditional areas related to heart, lung and blood research. This will prepare trainees for future careers and increase their likelihood of obtaining satisfying jobs.

Feasibility and challenges of addressing this CQ or CC :

Such newer T32 training programs will require a rethinking of the goals of training. There will be challenges for how to assess the quality and identify benchmarks of success for the training programs. Instead of merely looking at the number of publications by a trainee, one should also consider the impact they will make on society by using their expertise in biomedical research to improve education, health and science reporting, political and financial decisions, etc.

 

One should also consider awarding such training programs jointly to multiple institutions and encourage sharing of trainees. For example, a T32 program that wants to train future science writers and journalists with expertise in cardiovascular medicine would encourage their trainees to visit multiple partner institutions with expertise in cardiovascular medicine and in journalism/writing during their training period.

 

Instead of spending two years in one lab under a single mentor working on one or two projects, non-traditional T32 programs would encourage exposure to multiple projects, mentors, etc.

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

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Goal 2: Reduce Human Disease

Randomized trial of low carbohydrate high fat dietary pattern

There is a need for a large, simple, hard outcome trial of dietary advice to measure the effects of lowering simple carbohydrates versus lowering unhealthy fats. The main challenge will be to overcome bias favoring the more conventional dietary approach.

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 :

Substantial numbers are moving towards low carbohydrate/high fat diets to the extent that since 2000 the macronutrient composition of the US diet has changed towards lower carbohydrate and higher fat intakes; however, CV mortality rates continue to decline. The outcome of the trial will help frame future guidelines for healthy diets.

Feasibility and challenges of addressing this CQ or CC :

Yes, since computer or smartphone based intervention materials and passive outcome collections (CMS, NDI, health care organizations) are increasingly being utilized.

Low carbohydrate high fat (LCHF) diets first popularized for weight reduction are increasingly being promoted to prevent diabetes and cardiovascular disease. All trials to date have been small and short term. Compared to more traditional high carbohydrate low fat diets, LCHF diets may be somewhat more beneficial for weight control, glucose homeostasis, and dyslipidemia, but less beneficial for LDL reduction.

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

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Goal 3: Advance Translational Research

Risk Mitigation of Implantable Cardiovascular Devices

There is a serious need to improve implantable cardiovascular devices to eliminate, or at least substantially reduce, the risk of serious adverse events from occurring to more effectively treat patients.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Cardiovascular devices would be more widely used to treat such cardiovascular diseases as heart failure, coronary artery disease, valvular disease and, therefore, have a greater public health benefit. Furthermore, costs associated with treating the serious adverse events (e.g. hospitalizations, therapeutics, etc.) would decrease.

Feasibility and challenges of addressing this CQ or CC :

Technologies such as surface coatings and topographies as well as evolved design tools are under development already or are being used to mitigate the risks of devices currently being used or under development. A more concerted effort to do this would almost certainly help to substantially reduce the risks further, especially over the next 5-10 years.

Despite the widespread and growing use of implantable cardiovascular devices such as ventricular assist devices, stents, and prosthetic heart valves, substantial serious adverse events such as infections, neurological events, and bleeding limits the efficacy and use of the devices. Scientific and technological breakthroughs in such areas as biomaterials, design tools, coatings, and concomitant pharmacologic therapy are needed to address this challenge.

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

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9 up votes
23 down votes
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Goal 3: Advance Translational Research

Treating cardiovascular disease in persons with mental health disorders

How can we most effectively prevent and treat cardiovascular disease among persons with serious mental disorders?

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 :

Clinical anxiety disorders affects 40 million people in the US and the lifetime prevalence of PTSD is 6-8%,. The incidence of PTSD in particular is rapidly expanding in the US; this condition doubles the risk of a cardiac event.

 

The prevalence rates are higher in some populations; 3 out of 10 US military veterans have a diagnosis of PTSD, and many more are undiagnosed. Among patients at a VA, a diagnosis of PTSD increased the probability of circulatory problems (odds ratio 3.7). In another study, every additional PTSD symptom increased the risk of developing cardiovascular disease by 17%. Thus, the impact of developing more effective treatments adapted to the needs of this vulnerable population could be significant.

Feasibility and challenges of addressing this CQ or CC :

As the incidence of many mental health disorders such as PTSD and depression increases, the need for developing and adapting treatments for this population becomes critical.

 

Effective treatments may not be optimal for persons with serious mental illnesses and strategies to tailor treatments to the challenges of this vulnerable population are needed.

Individuals with mental illnesses such as major depressive disorder, bipolar disorder, and anxiety disorders are at significantly higher risk for cardiovascular disease than are those without these illnesses. Those with serious mental illnesses die an average of 25 years earlier, frequently from cardiovascular disease. The incidence of PTSD is rapidly expanding in the US; this condition doubles the risk of cardiovascular events.

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

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30 up votes
11 down votes
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Goal 2: Reduce Human Disease

Understanding the Role of the Vasculature in Dementia

Dementia is traditionally grouped into vascular dementia, Alzheimer's dementia, Parkinson's dementia and other causes of dementia. Vascular dementia is generally thought to be a consequence of strokes but there are some recent studies indicating that even Alzheimer's dementia may have a vascular underpinning. Vascular permeability is increased in the early stages of Alzheimer's disease and it is possible that similar ...more »

Submitted by (@jalees)

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 NHLBI could fund programs which enable vascular biologists to collaborate with neuroscientists and neurologists in order to understand whether the vasculature has a causal role in the progression of dementia.

 

 

 

Can interventions that improve vascular function prevent the progression of dementia? Instead of using broad interventions such as statins which affect numerous signaling pathways, vascular biologists could target selected aspects of vascular health such as improving vascular barrier function and vascular regeneration.

 

If these interventions that have been shown to be efficacious in other vascular beds outside of the brain are also effective in the brain, then important new therapies could be developed for dementia which is likely to become one of the leading cause of death in the next decades.

Feasibility and challenges of addressing this CQ or CC :

A key challenge for targeting the brain vasculature will be the blood-brain barrier. Understanding the role of the blood-brain barrier in dementia will be a prerequisite to developing novel vasculature-directed therapies.

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

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4 down votes
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Goal 3: Advance Translational Research

Greating grant mechanism for fostering collaboration with industrial partners

There is a disconnect between the cardiovascular devices industry and the basic research that is conducted in the field by biomedical engineering researchers. Technological solutions that the industry is converging to are not well informed by the advances in basic translational research. A distinct funding mechanism should be created for fostering such collaborations. To motivate for profit cardiovascular device manufacturers ...more »

Submitted by (@danny.bluestein)

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 : Danny Bluestein, Ph.D.

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Goal 1: Promote Human Health

Transformative Impact of Proteomics

The proteomics field has dramatically progressed over the past 20 years, with advancements and improvements in experimental designs and sample preparation protocols, as well as mass spectrometry equipment, approaches, and analysis. This has resulted in substantial forward progress towards a proteomic pipeline to establish cause and effect mechanisms of cardiovascular disease. There is a need for CV proteomics that resolve ...more »

Submitted by (@mllindsey)

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 necessary tools have been assembled, and managing implementation will reduce the time required for completion of larger scale projects.

Feasibility and challenges of addressing this CQ or CC :

high feasibility; the challenge will be managing communication across groups to maximize impact

Name of idea submitter and other team members who worked on this idea : Merry Lindsey

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