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)

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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

Close the gap: Why do men die of cardiovascular disease (CVD) at an earlier age than women?

Despite evidence that women face challenges in receiving optimal CVD care, data show that men die at an earlier age than women of CVD. This health disparity remains unexplained and there are no specific interventions to address it.

Submitted by (@collerb)

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

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A comprehensive T1-T4 initiative is required to explore this health disparity, ranging from epidemiology to basic mechanisms , and to translate that knowledge into specific interventions.

 

Closing the gap would add ~4 years of life to men, representing a monumental health improvement.

Feasibility and challenges of addressing this CQ or CC :

Conceptually this is straightforward since so many data are already available about sex differences in cardiovascular biology. The challenge is to review the information from this frame of reference and with the specific goal of identifying interventions.

Name of idea submitter and other team members who worked on this idea : Barry Coller

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Goal 3: Advance Translational Research

Early prediction of cardiovascular disease by primary-care assessment

Tools for early assessment of cardiovascular disease have become available but not adopted in primary-care settings. Increased arterial stiffness is a well-known marker for advanced cardiovascular disease (CVD) and has been shown to be an independent predictor of cardiovascular mortality. In addition, arterial pulse wave velocity (PWV) has been readily accepted as a measure of arterial stiffness. Despite significant ...more »

Submitted by (@roy.wallen)

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

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In the US, 84 million adults will see their primary care physician for treatment of cardiovascular disease (CVD). CVD is responsible for an average of one death every 40 seconds. The direct and indirect costs of cardiovascular disease and stroke are approximately $315 billion, including the cost of health care services, medications to treat high blood pressure, and missed days of work. The World Health Organization states that 80% of premature heart disease and stroke is preventable. Focusing on assessing risk factors for cardiovascular disease, screening for individuals at risk, and then providing effective and affordable treatment to those who require it can prevent disability and death and improve quality of life.

 

In Europe, the European Society of Cardiology (ESC) has issued guidelines based on the weight of evidence in favor of the usefulness of screening for CVD by assessing arterial stiffness. These guidelines are supported by nonrandomized trials and suggest the development of randomized trials or meta-analyses. However, no guidelines exist in the US for screening for arterial stiffness from such organizations as the American Heart Association (AHA) and the American College of Cardiology (ACC). Existing guidelines to include assessment of cholesterol, lifestyle, obesity, and factors for risk are important. However, a simple, low-cost, objective measurement could be implemented at the point of primary care to improve early detection and treatment of CVD.

Feasibility and challenges of addressing this CQ or CC :

Screening capabilities and some level of clinical evidence exist for early detection of CVD. Therefore, implementation of a practice guideline in the US is very feasible. Studies and assessment from existing data such as have been completed by ESC can be replicated in the US and promulgated by AHA and ACC. This effort will require support from public and private entities, including universities, in order to see practice standards implemented.

 

Challenges to date include funding and the application of clinical protocols to support randomized studies or meta-analyses that will provide evidence for benefits of early screening. Further, public policy and current funding are focused on treatment rather than prevention. Existing reimbursement established by the Centers for Medicare & Medicaid Services (CMS) is focused on treatment rather than prevention and private insurance carriers have followed this same policy. Broader clinical study will support both the adoption of screening tools in primary care and broader reimbursement policy.

Name of idea submitter and other team members who worked on this idea : Roy Wallen

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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)

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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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Goal 2: Reduce Human Disease

Short comprehensive cardiac MR imaging in post-chemotherapy cancer patients

Critical Challenge

Submitted by (@str0001)

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

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Cardiovascular disease and cancer are frequently identified in the same patient. Both diseases are highly prevalent in the United States population, and cancer or its therapies can result in cardiovascular disease. Early diagnosis and prediction of cardiovascular disease in patients to undergo therapy will identify patients at higher risk for cardiac dysfunction and enable earlier diagnosis of subclinical cardiac dysfunction.

Feasibility and challenges of addressing this CQ or CC :

Cardiovascular magnetic resonance imaging (MR) is a powerful imaging modality for evaluating the heart function. Specifically, MR techniques allow for quantifying regional heart function, e.g. strain and strain rate, and may provide earlier markers of cardiovascular disease development than global measures of heart function, e.g. left ventricular ejection fraction, as estimated by echocardiography. Early identification of subclinical heart failure of post-chemotherapy cancer patients will allow for early and on-time chemotherapy change and personalized treatment.

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

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)

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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)

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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 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)

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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)

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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

Chronic stress and cardiovascular/metabolic disease

Chronic stress is a risk factor for obesity, cardiovascular disease, atherosclerosis, and stroke. Glucocorticoid hormones are elevated chronically in stressed conditions and are thought to contribute to the pathogenesis of metabolic and cardiovascular disease. Despite strong evidence for this, non-pharmacologic therapies to reduce stress are not currently part of standard care for the prevention or treatment of metabolic ...more »

Submitted by (@jlaakso)

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

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Understanding how stress contributes to cardiovascular and metabolic disease could lead to additional therapies targeting stress reduction for their prevention. The long-term impact of studies to establish and reduce the negative impact of stress on health could include better outcomes for stress reduction programs at work and strategies to reduce stress at home.

Feasibility and challenges of addressing this CQ or CC :

Clinical trials to evaluate the efficacy of non-pharmacologic therapies targeting stress reduction are already feasible including such interventions as exercise, improved sleep, mindfulness, and social interaction. Some of these have been evaluated on a small scale, but future clinical trials should include long-term follow up and be sufficiently populated for their outcomes to influence patient care. Pharmacologic therapies targeting the stress system have not yet emerged as options for prevention and treatment, and pose a greater challenge. They will require investigation into the mechanisms of stress effects on chronic disease as well as intelligent drug design to minimize systemic side effects.

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

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Goal 2: Reduce Human Disease

Hormonal influences on atherosclerotic cardiovascular disease (ASCVD)

Cardiovascular diseases are the leading cause of morbidity and mortality for both men and women worldwide. It has been established that post-menopausal women have decreased protection from ASCVD relative to premenopausal women and men. However, the hormonal basis of protection (or lack thereof) is not clear.

Submitted by (@jlaakso)

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

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By addressing this question, we will gain a greater understanding of hormone-based risk factors for ASCVD in women and men. Beyond expanding our fundamental knowledge of how hormones interact with cardiovascular systems, we could develop or improve therapeutic strategies for addressing risk factors for cardiovascular disease.

Feasibility and challenges of addressing this CQ or CC :

Addressing this question is feasible and could be most effectively addressed through strategic initiatives sponsored by the institute. It will require a systematic approach to investigating differences in hormonal status between pre and post-menopausal women, as well as comparing them to male hormonal status. At the level of basic research, progress in this area may be slowed because researchers are not currently required to balance the studies of males and females in preclinical research involving animal models.

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

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Goal 3: Advance Translational Research

Regenerative Medicine 2.0 in Heart and Lung Research - Back to the Drawing Board

Stem cell therapies have been quite successful in hematologic disease but the outcomes of clinical studies using stem cells for cardiopulmonary disease have been rather modest. Explanations for this discrepancy such as the fact that our blood has a high rate of physiologic, endogenous turnover and regeneration whereas these processes occur at far lower rates in the heart and lung. Furthermore, hematopoietic stem cells ...more »

Submitted by (@jalees)

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

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Some barriers to successfully implementing cardiopulmonary regeneration include the complex heterogeneous nature of the heart and lung.

 

Hematopoietic stem cells can give rise to all hematopoietic cells but the heart and lung appear to contain numerous pools of distinct regenerative stem and progenitor cells, many of which only regenerate a limited cell type in the respective organ. The approach of injecting one stem cell type that worked so well for hematopoietic stem cells is unlikely to work in the heart and lung.

 

We therefore need new approaches which combine multiple regenerative cell types and pathways in order to successfully repair and regenerate heart and lung tissues. These cell types will likely also require specific matrix cues since there are numerous, heterogeneous microenvironments in the heart and lung.

 

If we rethink our current approaches to regenerating the heart and lung and we use combined approaches in which multiple cell types and microevironments are concomitantly regenerated (ideally by large scale collaborations between laboratories), we are much more likely to achieve success.

 

This will represent a departure from the often practiced "Hey, let us inject our favorite cell" approach that worked so well in hematologic disease but these novel, combined approaches targeting multiple endogenous and/or exogenous regenerative cells could fundamentally change our ability to treat heart and lung disease.

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

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