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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Goal 2: Reduce Human Disease

Noninvasive biomarkers for characterizing cardiovascular disease

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 :

Phenotypical characterization of cardiovascular disease with computed tomography (CT) and magnetic resonance imaging (MR) to individualize targeted therapies for coronary artery and myocardial disease. Coronary artery disease is a major cause of patient death in the United States. Nonischemic myocardial disease includes entities with clinically heterogeneous presentations and is thus challenging to manage.

Feasibility and challenges of addressing this CQ or CC :

Currently CT and MR technology allows dynamic evaluation of the perfusion and contractility of the heart. Quantitative measures of disease burden, such as atherosclerotic plaque composition and myocardial texture imaging biomarkers (such as T1 mapping, activation mapping, flow pattern analysis, delayed myocardial enhancement), are possible. Positron emission tomography (PET)/MR, which combines metabolic with functional evaluation, is currently available and facilitates the development of targeted molecular-imaging techniques. Metrics derived from these techniques may serve to stratify patients noninvasively and direct appropriate therapies. Such imaging methods address noninvasive evaluation of cardiovascular disease, including ischemic heart disease but also myocardial diseases that include secondary and infiltrative cardiomyopathies, hypertrophic cardiomyopathy, and organ rejection in the scenario of transplantation.

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

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Goal 3: Advance Translational Research

Enhancing Cardiovascular Health in Childhood Through Adulthood

To enhance or maintain ideal cardiovascular health (CVH) in children and adolescents, what novel and long-term interventions can be implemented using multi-level (i.e., targeting individual, family, community, and built environment) and sustainable approaches?

Would implementation and translation of the AHA 2020 impact goals in children and adolescents enhance their CVH through adulthood?

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 :

Broad impact on the health of children and adolescents and ultimately, the health of the nation.

Feasibility and challenges of addressing this CQ or CC :

Because there are some proven modalities in small-scale studies for improving cardiovascular health in children. Most are short-term or tested mostly in adults. This CQ focuses on trials that could span 10 years from Childhood into adulthood.

NHLBI has supported numerous large-scale trials (e.g., Girls health Enrichment Multisite Studies-GEMS, PATHWAYS, Child and Adolescent Trials for Cardiovascular Health-CATCH, Trial of Activity in Adolescent Girls-TAAG, and other investigated interventions in children and adolescents along with NICHD and other ICs) that could be harnessed to support this initiative.). NHLBI is supporting multi-level trials such as the Childhood Obesity Prevention and Treatment Research (COPTR) Consortium) that could provide modalities to enhance CVH in youth. Currently, there are no long-term trials spanning childhood through young adulthood in the US on this topic. An example of such a study is The Special Turku Coronary Risk Factor Intervention Project for Children [STRIP] study in Finland. Pahkala et al., Circulation. 2013;127:2088-2096.

 

A major challenge is cost, retention in trial and long-term adherence to intervention modalities. These could be mitigated using public-private funds (cost), incentives and/or clinical trial methodologies to enhance participation and adherence. Ability to motivate children and adolescents throughout their growth could be a challenge.

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

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Goal 2: Reduce Human Disease

Imaging indicators of metabolic syndrome and cardiopulmonary disease

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 :

Obesity and metabolic syndrome affect a large portion of the population and affects multiple organ systems. Identifying obesity phenotypes by imaging will impact the significant healthcare issue presented by MetS and could provide a reliable, non-invasive index of disease severity, guide prevention and intervention response.

Feasibility and challenges of addressing this CQ or CC :

Metabolic syndrome, abnormal metabolism, may be potentially linked to obesity and cardiopulmonary disease. Theories exist but are in need of clarification. The relationship between metabolic syndrome and multiple other diseases including chronic obstructive lung disease, coronary atherosclerosis, and obesity warrants further investigation and can be elucidated through imaging. Advances in computed tomography (CT) and magnetic resonance imaging (MR) enable assessment of the cardiopulmonary manifestations, with promising MR techniques to complement high-resolution imaging data achievable with chest CT and coronary CT angiography. Assessment of CT and MR techniques in combination with three-dimensional quantitative analysis of manifestations of metabolic syndrome such as fat deposits derived from different adipocytes (white fat versus brown fat) such as in the subcutaneous, visceral, epicardial, and perivascular regions is feasible with current technology and may enable differentiation of those with varying risks of cardiovascular and pulmonary disease. The association of imaging parameters, metabolic syndrome, and associated diseases are in need of investigation, and knowledge gained may prove crucial for identifying those at risk for metabolic syndrome and at higher risk for complications in the large population of our country affected by obesity.

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

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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

Balancing Risks and Benefits: How Do Clinical Guidelines in Cardiovascular Medicine Promote the Health of an Individual?

Much of the hopes for precision medicine (as outlined Dr. Dr. Collins) are based on deriving large amounts of genomic, proteomic, epigenomic and metabolomic data on large cohorts of patients. It will take decades to build these cohorts and even more time to analyze them and derive specific conclusions on how these will help individualize treatments. However, there is a pressing need for how to individualize contemporary ...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 :

Decisions on whether or not to place a patient with atrial fibrillation on chronic anticoagulation or on statin therapy are often based on guidelines and cardiovascular risk calculators.

 

Patients with a higher risk of stroke are more likely to receive anticoagulation and patients with a higher risk of a myocardial infarction are more likely to receive statin therapy.

 

However, these cardiovascular risk calculators do not really take into account the potential side effects and impact on the lifestyle of the patients.

 

Physicians will stop anticoagulation in a patient with atrial fibrillation if the patient has suffered a life-threatening bleed but there are no specific evidence-based guidelines as to how one should proceed if the bleeding is minor.

 

it is easy to compute the cardiovascular risk and overall mortality benefit of placing a patient on statins but how does one factor in the impact that statins have on the quality of life of an individual?

 

Developing novel evidence-based approaches to individualize therapies that factor in cardiovascular benefits as well as potential side effects and diminished quality of life could have a major impact on appropriately using treatments and reduce the arbitrariness of some medical decisions.

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

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Goal 2: Reduce Human Disease

Diet and prevention of cardiovascular events

In the US, what kind of diet(s) is/are best for preventing hard cardiovascular events?

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 :

Provide an evidence base for public policy on diet.

Feasibility and challenges of addressing this CQ or CC :

The Spaniards have shown that this kind of trial is possible. We have tools and interest in place for pragmatic trials.

 

The PREDIMED trial (done in Spain) randomized ~7000 adults and found that a diet supplemented with olive oil or nuts reduced cardiovascular events compared to a "low-fat" diet. However, in Spain the Mediterranean diet is arguably the norm.

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

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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 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 2: Reduce Human Disease

Addressing low-level-evidence in cardiovascular guidelines

There is a need for the NHLBI to systematically assess CV guidelines that have public health importance and that can be addressed by pragmatic, government-funded trials.

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 :

A much greater proportion of CV guidelines which dictate practice standards would be based on high-quality scientific evidence.

Feasibility and challenges of addressing this CQ or CC :

Guidelines are already written and levels of evidence are already assessed (by others). Methods for conducting pragmatic trials exist (e.g. embedding in registries, leveraging digital resources, recognizing the importance of pragmatic trials within the clinical community).

More than 85% of active CV guideline are based on less than level 1A evidence.

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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