Strategic Goal: Goal 2: Reduce Human Disease

Diaphragmatic dysfunction in critical illness

Diaphragmatic dysfunction occurs more frequently than clinically recognized in the setting of acute critical illness or injury. This contributes to both incipient and prolonged respiratory failure, as well as the growth of long-term acute care/rehab hospitalizations. We need a better understanding of the mechanisms of dysfunction as well as strategies to mitigate loss of diaphragmatic muscle mass, ultimately leading ...more »

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

This problem can be addressed through a combination of Integrative physiology and real-time data analytics.

Feasibility and challenges of addressing this CQ or CC :

Patients receiving critical care services in the United States are among the most close monitored, including continuous monitoring of cardiorespiratory physiology. Integrating high dimensional data from ICU data streams and applying big data analytics, in combination with primetime genomic and metabolomic technologies, makes answering this question imminently feasible.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

Voting

-1 net votes
1 up votes
2 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Pediatric heart failure

What is the best way to use what we have learned about the pediatric myocardium and cardiac-pulmonary interactions in congenital heart disease to develop new pathways for treating pediatric heart failure?

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 :

Improved treatment for pediatric patients suffering from heart failure.

Feasibility and challenges of addressing this CQ or CC :

n/a

Pediatric heart failure is almost always different from adult heart failure, due to varying mechanisms and underlying malformations.

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

Voting

13 net votes
23 up votes
10 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Impact of lung remodeling on congestive heart failure progression

End stage congestive heart failure (CHF) causes intensive lung remodeling beyond the type-2 pulmonary hypertension. CHF induced lung remodeling includes profound lung fibrosis, lung vascular remodeling and lung inflammation. Understanding CHF-induced lung remodeling is also critical to understand the right ventricular failure. However, this area is largely unstudied. Regulating CHF-induced lung remodeling and the underlying ...more »

Submitted by (@chenx106)

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

Details on the impact of addressing this CQ or CC :

To deal end-stage CHF will need team efforts from heart, lung, blood and immunology.

Name of idea submitter and other team members who worked on this idea : Yingjie Chen, Associate Professor, University of Minnesota

Voting

13 net votes
15 up votes
2 down votes
Active

Strategic Goal: Goal 3: Advance Translational Research

Human Heart Systems Biology

In the human failing heart, it is the systems biology that ultimately fails: electrical, mechanical, and chemical perturbations in their function do not manifest in isolation, but critically impact on each other in health and disease. Investigation of human myocardium, unlike inbred rodent models, is challenging since no two humans are identical. There is a need for the collection and assessment of clinical patient data, ...more »

Submitted by (@janssen.10)

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

Details on the impact of addressing this CQ or CC :

Procured/stored tissue from these hearts could be made available NHLBI/NIH-wide, and studied by a large number of investigators on protein levels, RNA/DNA level, and/or histological assessments. This data could then be correlated to any other parameter assessed on these hearts, providing correlative guidance, through systems biology/neural network programming, for future mechanistic studies. For each additional parameter investigated, the number of correlation analysis (with any and all parameters, including clinical and biometric parameters) would mathematically double.

Feasibility and challenges of addressing this CQ or CC :

Supporting the basic collection of these in vivo and in vitro parameters and possibly the logistics for tissue distribution to collect correlative mechanical, proteomics, genomics, and histology data for correlation with the in vivo and in vitro data would allow for an NIH/NHLBI-wide translational approach to human heart failure that could encompass everyone’s “favorite” molecule, protein, pathway, and disease etiology. A logistical challenge is that such a project would likely exceed the funding of a single standard grant, but more importantly would surely exceed the standard 4-5 year duration, requiring long-term vision, planning, and buy in from NIH/NHBLI and investigators.

Name of idea submitter and other team members who worked on this idea : Paul Janssen

Voting

6 net votes
13 up votes
7 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Preventing or reversing myocardial fibrosis

Conduct proof-of-concept studies and explore whether strategies to reverse or prevent fibrosis are feasible.

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 :

This challenge will lead to early studies of potential therapeutics for arrhythmias and heart failure. If successful, this would have huge impact.

Feasibility and challenges of addressing this CQ or CC :

Recent studies have identified some compelling signaling pathways that activate fibrosis so it is feasible to test them through creative experimentation.

Fibrosis and fibrogenesis in the myocardium are clear indications that heart function is either declining or progressing towards decline. Although much of the current research continues to focus on unraveling mechanisms that lead to fibrosis and activation of fibrogenesis, there is as yet less focus on potential mechanisms to prevent or reverse fibrosis. This was in part due to insufficient understanding of major causes of fibrosis and mechanisms that activate fibrogenesis. However, findings from recent studies show that there are several compelling therapeutic targets that are ready to be tested to see whether fibrosis can be reversed or prevented.

May need strategies on how to best to succeed in implementing the research - e.g., what research mechanisms, what kind of teams, what kind of expertise, etc. To fine tune this, a focused workshop for advice may be helpful.

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

Voting

19 net votes
33 up votes
14 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

National network to study the pathobiology of sepsis

Sepsis is the leading cause of death in hospitalized patients, the 3rd leading cause of death in all people in the US, the most common condition leading to widespread vascular collapse, among the most common causes of respiratory failure, and a frequent cause of acute cardiac dysfunction.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Developing a national network to address important aspects of sepsis (causes and consequences of cardiac dysfunction, molecular determinants of respiratory failure) and serve as a trials group for testing novel interventions for new discoveries.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

Voting

2 net votes
4 up votes
2 down votes
Active

Strategic Goal: Goal 1: Promote Human Health

Understanding NANCs and Neuropeptide Function in the Heart

Understanding the complexity of NANC transmitter release and neuropeptide function could be helpful in establishing new, effective therapeutic strategies for treating heart disease.

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 :

Could lead to the development of fundamental knowledge required to develop effective new therapeutic interventions to treat heart disease.

Feasibility and challenges of addressing this CQ or CC :

Several studies have already demonstrated associations been NANC transmitter release and neuropeptide co-localization with pathogenic changes in cardiac function.

Identification within cardiac nerves of neural peptides that are co-released with traditional transmitters is an interesting and still emerging story. Studies with nonadrenergic, noncholinergic (NANC) transmitters in both the atria and ventricle have shown that a variety of neuropeptides also are localized within the heart, and several, including vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P, and calcitonin gene-related peptide, have been shown to markedly affect heart rate and modulate cardiac function. NPY is also elevated in heart failure patients, and other neuropeptides, including VIP, calcitonin gene related peptide (CGRP), substance P (SP) and their receptors are associated with various types of cardiomyopathies.

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

Voting

3 net votes
14 up votes
11 down votes
Active

Strategic Goal: Goal 1: Promote Human Health

A Systems Approach - Human Cardiac Electromechanical Activity

The challenge is to identify limitations in using data from non-human animal species for elucidation of human electromechanical function/activity and to identify what specific information and computational approaches need to be incorporated. To aid in achieving such a goal, it might be useful to convene a series of workshops to build consensus and improve communication among investigators working at the same horizontal ...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 :

This will provide an in silico computational platform to study human cardiac pathology. Note: by different horizontal levels, we mean for example measuring and modeling individual ion channels, transporters or myofilament properties in myocytes. By different vertical levels, we mean for example gogenomic/proteomic to cellular, and cellular to more integrative levels.

Feasibility and challenges of addressing this CQ or CC :

Advances in high-speed computation techniques and high-throughput measurement make the achievement of this challenge doable.

An integrated understanding of the eletromechanical activity of the human heart is needed to develop more effective approaches to cardiac disease diagnosis, treatment, and prevention. Robust computational models of human electromechanical activity that incorporate ion channel kinetics, calcium handling and dynamic changes in the intra-/extracellular milieu from human cardiac tissues are needed develop such an understanding and to provide an experimental platform to test interventions designed to maintain cardiac function. Computational models should be scalable and incorporate subcellular molecular mechanisms to whole system levels of integration to be most effective.

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

Voting

7 net votes
20 up votes
13 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Optimal hemoglobin threshold for transfusion in children with ARDS?

Do different hemoglobin transfusion thresholds alter outcomes in children with ARDS? What is the optimal *minimum* transfusion threshold for children with ARDS? What patient-centered outcomes can be affected by transfusion strategies: ventilator free days, time to organ function recovery, duration of intensive care stay, survival?

Submitted by (@greg.martin)

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 of Critical Care Medicine Executive Committee/Council

Voting

8 net votes
9 up votes
1 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

What is the role of diet and nutrition in treatment, management and prevention of Heart Failure?

Heart Failure (HF) remains a major public health burden. A working group was convened by NHLBI and ODS in June, 2013 to address the role of diet and nutrition in management of HF. A review of existing evidence produced no clear rationale for appropriate dietary interventions. On the contrary, the group developed recommendations for conducting additional research specifically on the role of sodium, fluid, nutrients, and ...more »

Submitted by (@lvanhorn)

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

Details on the impact of addressing this CQ or CC :

As summarized following the Working Group meeting,compared with the situation for cardiovascular risk factor management, there is little well-founded evidence regarding the efficacy, safety, and clinical impact of dietary modifications for patients with various HF phenotypes. The importance of diet and nutrition to promote health and prevent or control disease is well established. Research on obesity, hypertension and cardiovascular disease have contributed to the development of nutritional guidelines to prevent these disease in the general population but efforts to determine nutritional needs for the patient with HF lack high caliber evidence regarding safety, efficacy, and clinical impact of dietary modifications. The stronger evidence and focus on disease prevention and health promotion with diet modifications like DASH cannot be easily applied or extrapolated for disease management, especially HF, because of critical knowledge gaps and potential harm. Research on HF has more recently identified and differentiated medical treatment and interventions appropriate for HF with or without preserved ejection fractions. This only adds to the questions surrounding diet and nutritional approaches to help reduce and prevent HF readmissions.

Feasibility and challenges of addressing this CQ or CC :

Chronic HF often presents as a multisystem disease with important co-morbidities such as anemia, insulin resistance or diabetes, autonomic dysregulation, and impaired renal function. Intestinal dysfunction with impaired motility and circulation and disturbed intestinal barrier and flora may lead to a chronic inflammatory state and nutrient malabsorption. In advanced cases, catabolic/anabolic imbalance is associated with cardiac cachexia, a difficult to treat condition which itself carries a poor prognosis. Furthermore, psychosocial symptoms associated with HF, including depression and impaired cognition, can contribute to poor self-care and lack of adherence to recommended dietary, physical activity, and medication regimens. Nutritional status concerns for patients with HF increase with disease severity. Salt restriction is now controversial and clinicians give little attention to diet as a potential intervention to improve outcomes. Proposed recommendations:

1.Determine the correct sodium threshold; ranges of sodium and fluid intake, and the safety for sub-groups including HFPEF, HFREF, and cardiorenal syndrome. 2.Generate new knowledge which identifies therapeutic targets and understand the role of the gut microbiome on gastrointestinal malabsorption, inflammation, and protein balance in HF.

3.Apply innovative study designs to reduce evidence gaps 4.Develop technologies to facilitate nutrition research and address weight and multiple risk factors should be addressed.

Name of idea submitter and other team members who worked on this idea : Linda Van Horn, PhD, RD

Voting

2 net votes
3 up votes
1 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Therapy for Heart Failure with Preserved Ejection Fraction

Are existing neurohormonal antagonist drugs effective in HFPEF ?

Submitted by (@lars.lund)

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

Details on the impact of addressing this CQ or CC :

HFPEF is as serious as HFREF and as many forms of cancer. But there is no therapy. Generic neurohormonal antagonist drugs are effective in HFREF and have potential in HFPEF. They will not be studied by industry and trials need public funding.

Feasibility and challenges of addressing this CQ or CC :

The challenge is streamlined efficient trials. This can be addressed with the registry-randomized trial concept.

Name of idea submitter and other team members who worked on this idea : Lars H. Lund

Voting

-6 net votes
7 up votes
13 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Modulation of cardiac contraction and relaxation in heart failure: role of systemic inflammation

Is cardiac contraction and relaxation in heart failure modulated by the systemic inflammatory response? There is overwhelming evidence that inflammatory biomarkers predict worse outcome in acute and chronic heart failure. Despite the wealth of evidence, clinical trials in this area have either not been completed, failed, or provided inconclusive results. The questions that remain are: 1) Is inflammation a mechanism ...more »

Submitted by (@aabbate)

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

Details on the impact of addressing this CQ or CC :

Addressing this question may fill a decades-old gap in our understanding of the role of inflammation in heart failure, and potentially lead to novel prognostic biomarkers and/or improved therapeutics.

Feasibility and challenges of addressing this CQ or CC :

All the preclinical and clinical tools are available.

Name of idea submitter and other team members who worked on this idea : Antonio Abbate

Voting

8 net votes
14 up votes
6 down votes
Active