Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

Genetic risk factors for sudden cardiac death

What are the genetic risk factors for sudden cardiac death and failure to respond to CPR and defibrillation?

Submitted by (@rebecca.lehotzky)

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 : AHA Staff & Volunteers

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Goal 2: Reduce Human Disease

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

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

Submitted by (@dpinsky)

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

Feasibility and challenges of addressing this CQ or CC :

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

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Goal 2: Reduce Human Disease

Fundamental stress-response mechanisms in the heart.

What are the primary molecules and cellular signals associated with prolonged hypertensive stress that cause adverse myocardial tissue remodeling, and what strategies that prevent or reverse adverse remodeling can be developed and tested?

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 :

Could potentially contribute to the development of new therapies for heart disease and cardiomyopathies.

Feasibility and challenges of addressing this CQ or CC :

Yes, addressing this CQ may be feasible. Since it is likely that a multitude of signaling mechanisms are involved, an unbiased, global approach may be necessary to identify the key molecular pathways. However, experimental challenges remain and even developing appropriate animal models has been challenging.

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

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14 net votes
21 up votes
7 down votes
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Goal 2: Reduce Human Disease

Research priorities: Sleep disorders in women

Women are more likely to have insomnia and they develop the condition at an earlier age than men. Hormone changes and menopause are two key factors but little is known about the mechanisms, which will inform the treatment. This is an understudied area of scientific focus with vast potential public health impact.

Submitted by (@hjoffe)

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

Details on the impact of addressing this CQ or CC :

Women are more likely to have insomnia and they develop the condition at an earlier age than men. Hormone changes and menopause are two key factors but little is known about the mechanisms, which will inform the treatment. This is an understudied area of scientific focus with vast potential public health impact.

Feasibility and challenges of addressing this CQ or CC :

Systematic investigation of the hormonal basis and menopause symptom contribution to insomnia in midlife women requires skilled investigation and controlled study design given variability of symtpoms.

Name of idea submitter and other team members who worked on this idea : Hadine Joffe, MD MSc

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45 net votes
57 up votes
12 down votes
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Goal 2: Reduce Human Disease

Devices to Enhance AVF Eligibility and Maturation

There are about 400,000 patients with end-stage renal disease in the U.S. who depend on hemodialysis (HD) for their survival. Creating effective and reliable vascular access sites that can connect patients to HD machines remains a major unmet clinical need. HD patients who use an arteriovenous fistula (AVF) for vascular access live longer, healthier lives and cost less to care for. However, only about 55% of HD patients ...more »

Submitted by (@hloree)

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

Details on the impact of addressing this CQ or CC :

When a vein is connected to an artery to make an AVF, increased blood flow and wall shear stress (WSS) in the vein causes dilation, a critical element in AVF maturation and usability. However, with traditional AVF, the level of WSS cannot be controlled and small vein segments experience excessive WSS levels. Furthermore, the flow of blood from an artery is pulsatile, resulting in cyclic stretching of the vein wall, which has been shown in vitro to cause smooth muscle cell proliferation, which is linked to vein stenosis and AVF failure. A continuous flow source such as a rotary blood pump system may promote rapid vein dilation by delivering nonpulsatile blood and controlled WSS doses, potentially enabling more patients to receive AVF surgery and resulting in a large increase in the success rate from AVF surgery.

Feasibility and challenges of addressing this CQ or CC :

This research would be best addressed through the NHLBI's SBIR program. Phase I would fund design and prototyping of devices, which would be tested in large animal models of peripheral vein dilation alongside a conventional AVF. Phase II would fund development of the most promising devices in a range of sizes, design for manufacturing, design verification & validation, and preparation for first-in-human studies.

Name of idea submitter and other team members who worked on this idea : Howard Loree

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2 up votes
15 down votes
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Goal 2: Reduce Human Disease

5-minute MRI exam

MRI is a lengthy and expensive exam, but this is mainly because it has no ionizing radiation and is uniquely safe and uniquely versatile, leading to imaging sessions that last for 1/2 to 1 and 1/2 hours, with multiple scans, views and contrasts. MRI could provide better quality screening scans, compared to x-ray, ct or echo, in 5 minutes, without ecg-gating and lengthy preparation of the patient. However, the optimal ...more »

Submitted by (@danacpeters)

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

Details on the impact of addressing this CQ or CC :

5 minute MRI would be inexpensive and provide more diagnostic confidence, compared to the alternatives.

Feasibility and challenges of addressing this CQ or CC :

Identifying the best applications for 5 minute MRI.

Name of idea submitter and other team members who worked on this idea : Dana Peters, Assistant Professor of Diagnostic Radiology at Yale School of Medicine

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Goal 2: Reduce Human Disease

Effect of self-management plan for COPD

Does a collaborative self management plan for COPD reduce or increase mortality risk? (based on two conflicting VA studies)

Submitted by (@nhlbiforumadministrator)

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 : American Thoracic Society member

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2 net votes
2 up votes
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Goal 2: Reduce Human Disease

Moonshot: Turning the BMT EMR into a Research Record

The critical challenge is to develop a standards-based BMT electronic medical record (EMR) and integrate research capacity into the architecture of EMR systems. The ultimate goal would be to build de-identified complete data-sets which can be used to support observational studies and clinical trials, improve transplant outcomes and inform public policy.

Submitted by (@rakeshgoyal)

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

Details on the impact of addressing this CQ or CC :

Clinical research is constrained by a clumsy method of acquiring biomedical data, generally relying on manual capture of information from EMR back-to-paper which is then transcribed into registry or specific clinical trial databases. This method is labor intensive, fraught with opportunities for error, and increasingly difficult to defend in light of the high costs associated with clinical trials. Adoption of standards-based clinical documentation and creating access to source clinical data would reduce or do-away with resource-intensive, very expensive and time-consuming data abstraction, enhance data quality and depth, and accelerate translational research.

Feasibility and challenges of addressing this CQ or CC :

As BMT centers increasingly adopt EMR systems in the United States, a vast and potentially very useful data resource is being created. However, most EMR systems offer very generic formats for clinical documentation and the medical information is inconsistently expressed in vocabulary, structure, and format. One challenge is the development of common standards-based clinical documentation format and its adoption by EMR system vendors and BMT institutions to support structured data sharing.

 

Large transplant centers can build their own integration engines to link EMR with stem cell lab, HLA, donor care, workflow etc. However, a broad implementation of integration IT solutions would be needed amongst centers conducting BMT clinical trials.

 

While CIBMTR's FormsNet application and Clinical Trials Network allow electronic data submission, data professionals still need to manually enter the data. Another challenge in creating a centralized data resource would be to build interoperability between transplant centers and research entities. An alternative to a large centralized database could be a distributed research network which allows data holders to maintain logical and physical control over their data and mitigate security, proprietary, legal, and privacy concerns.

Name of idea submitter and other team members who worked on this idea : Rakesh Goyal

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57 net votes
71 up votes
14 down votes
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Goal 2: Reduce Human Disease

Predicting and monitoring atherosclerosis progression and vulnerable plaque

How to develop novel methods for predicting and monitoring atherosclerosis progression and vulnerable plaque including biomarkers and imaging?

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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3 net votes
4 up votes
1 down votes
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Goal 2: Reduce Human Disease

Low-dose and non-ionizing imaging for chronic lung 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 :

Imaging plays a crucial role in the initial evaluation of patients with suspected or surveillance of those with confirmed diffuse chronic lung disease. Attention towards developing alternative non-ionizing imaging technologies and evaluating the efficacy of radiation dose saving techniques will impact a large patient population.

Feasibility and challenges of addressing this CQ or CC :

Imaging, particularly computed tomography (CT) plays a major role in the evaluation of diffuse pulmonary disease. High resolution CT (HRCT) characterizes parenchymal patterns of lung disease, identifies areas amenable to biopsy, and aids in decisions pertaining to workup and therapy of lung disease. With multidetector CT technology, volumetric HRCT enables evaluation of the entire lung volume for diffuse lung disease. The utility of CT needs to be balanced with the exposure of patients to ionizing radiation, particularly younger-aged individuals who are more sensitive to ionizing radiation. In CT, dose-saving techniques enable imaging of the parenchyma at ultra-low dose levels. Additionally, an understanding of low radiation-dose CT techniques that preserve the diagnostic ability for diffuse lung disease, while maintaining the precision of quantitative measures, is needed. Magnetic resonance imaging (MR) is underutilized as an imaging tool given respiratory motion and limitations in spatial resolution. A need exists to develop and apply MR imaging techniques with spatial resolution approaching that of high resolution CT. Promising advances in the MR technology has occurred, and continued development and application will provide alternative and non-ionizing options for imaging patients with diffuse lung disease affecting both the parenchyma and airways.

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

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8 net votes
10 up votes
2 down votes
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Goal 2: Reduce Human Disease

What are the biological consequences of sleep loss or disruption and how can they best be avoided?

Arousals in obstructive sleep apena (OSA) are life saving, but the associated disruption of sleep is now thought to cause cognitive impairment, increased risk of high blood pressure and atherosclerosis, as well as glucose intolerance and metabolic syndrome. The mechanisms for these downstream effects, however, are not well understood. Can these specific pathophysiological mechanisms be identified, and can ways for mitigating ...more »

Submitted by (@csaper)

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 identifying the mechanisms by which sleep loss or disruption affects cognitive, cardiovascular, and metabolic function, we hope to find key regulatory points for which interventions may be developed. For example, if we can allow respiratory reflex responses to reopen the airway without EEG activation during OSA, we may be able to forestall some of the cognitive consequences of inadequate sleep. If we can prevent the autonomic responses associated with the EEG arousals and increases in respiratory drive, we may be able to block the repetiive elevations of blood pressure that lead to long term hypertension and accelerated atherosclerosis. If we can identify the reason for metabolic derangement associated with OSA, we may find, for example, that it is due to circadian misalignment and find ways to realign the sequence of metabolic events with the actual wake-sleep patterns of the patients. Finally, if we can potentiate the respiratory reflexes that re-establish the airway in OSA, without triggering the other components of arousals, we may be able to minimize or prevent the apneas. While current methods for treating OSA (e.g., CPAP and dental appliances) help many people, many others cannot tolerate these devices, and we require additional modes of therapy to mitigate the consequences of OSA.

Feasibility and challenges of addressing this CQ or CC :

The methods are currently available to address the questions that are raised above. The revolution in methods for evaluating the functions of neural circuits, using optogenetics and chemogenetics, for example, should allow us to identify brain circuits that are involved in the various components of the reflex responses to apnea. We can examine their neurotransmitters and receptors, and design new therapies based on manipulating CNS circuitry. Methods for assessing ongoing autonomic, respiratory, and metabolic responses in genetically mutated mouse modesl may require further miniaturization of various physiological methods, but this field is also rapidly advancing. Finally, methods for examining ongoing changes in neuronal activity in the living brain of awake mice are rapidly advancing.

Name of idea submitter and other team members who worked on this idea : Clifford B Saper, MD, PhD

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96 net votes
125 up votes
29 down votes
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Goal 2: Reduce Human Disease

Interstitial Lung Disease

Does prednisone therapy improve outcomes in acute exacerbation of IPF?

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 :

It is common practice to give high-dose prednisone to patients experiencing acute exacerbation of IPF, a relatively common (10-15% annual risk) and deadly event, but there are no good data to support its use. There is a significant risk of morbidity from this therapy. A well-designed multicenter trial could answer this question definitively.

Name of idea submitter and other team members who worked on this idea : ATS Member

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2 net votes
2 up votes
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