Goal 2: Reduce Human Disease

What do we know about Heart Failure with Preserved Ejection Fraction (HFpEF)

Mortality is similar between HFpEF and HFrEF but we have currently no viable therapeutic option for HFpEF. There have been many large trials, but they all failed. Our basic understanding of the disease is very limited which contributed to failures of many prior trials and wasting $$$. We know very little about the pathophysiology of the disease . It is time to get back to the basic science and use our new tools (e.g. ...more »

Submitted by (@rezanezafat)

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

Details on the impact of addressing this CQ or CC :

Better therapy for HFpEF is an unmet clinical needs which will impact millions of patients

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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

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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

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Goal 1: Promote Human Health

THE RELEVANCE OF PREVENTION TRIALS

Prevention trials, implemented to reduce or delay progression to overt disease in a population at risk to the disease, are an important approach to health promotion. Therapies shown to reduce disease severity in patients with a specific disease are obvious, but not the only, candidates for a prevention trial in populations at high risk for prevalent diseases (such as heart failure, diabetes, COPD, asthma in children). ...more »

Submitted by (@media0)

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 implementing such trials is considerable. They will clearly address an important component of NHLBI’s mission with respect to effectiveness of therapies and behavioral interventions, and it has minimal and clearly definable overlap with commercial trials of specific therapeutic products. It will also provide an important public health focus – preventing disease or reducing the impact of disease processes, thus potentially reducing chronic care costs and increasing years of useful life.

Feasibility and challenges of addressing this CQ or CC :

The biggest challenge in designing and implementing prevention trials is identifying the target, “at risk” population most likely to develop the clinical disease from known biomarkers or early signs/symptoms. Increasing availability of large, population-based registries or databases maintained for other purposes provides a very cost-efficient mechanism to electronically screen and identify “at risk” individuals. The same mechanism may also facilitate implementation of pragmatic, electronically managed, cost efficient trials.

Name of idea submitter and other team members who worked on this idea : Sonja McKinlay other Team Members: Susan Assmann and Paul Stark

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Goal 2: Reduce Human Disease

Is heart failure reversible by diet and lifestyle changes?

Once heart failure has developed, can diet and exercise measures work to reverse it?

 

Well-designed clinical trials are needed to answer this question.

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 :

There is no known therapy that can reverse heart failure. Drug and device treatments may slow progress but not a cure. If diet and lifestyle changes could reverse heart failure, even if just in segments of the heart failure population, it would be a tremendous impact in saving lives and would have a great fiscal impact as well.

Feasibility and challenges of addressing this CQ or CC :

Innovative dietary and lifestyle intervention studies could be done cheaply and efficiently.

There is low impact, mostly anecdotal evidence that heart failure (HF) is reversible through diet and exercise, but no higher level research has investigated this question. It is an accepted notion that healthy diet and exercise can prevent cardiovascular diseases. Obesity, diabetes and coronary artery disease are strong risk factors for HF. Accordingly, a high portion of HF patients has ischemic etiology, is obese and/or diabetic. Diet and lifestyle interventions could beneficially influence these comorbidities and might reverse HF.

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

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Goal 2: Reduce Human Disease

What is the optimal management of coronary artery disease in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) have an extremely high risk of death from cardiovascular cause. The prognosis of patients with chronic kidney disease who also have coronary artery disease is worse than certain cancer. While great strides have been made to create awareness about breast cancer, there is paucity of knowledge about the cardiovascular risk of CKD patients among both physicians and patients. Moreover, ...more »

Submitted by (@sripal.bangalore)

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

Details on the impact of addressing this CQ or CC :

Patients with chronic kidney disease tend to be undertreated (from CV perspective), underrepresented (in clinical trials) and underdiagnosed with less referral for stress testing, even though cardiovascular cause is the leading cause of death in these patients. Patients with chronic kidney disease is a growing cohort and with increase in obesity and diabetes, the prevalence is exploding exponentially. The decision as to what is the best treatment option for patients with coronary artery disease who also have kidney disease- revascularization or medical therapy-is important and can be a paradigm shift in the way we treat such patients

Feasibility and challenges of addressing this CQ or CC :

Randomized clinical trials are urgently needed to answer this question.

Name of idea submitter and other team members who worked on this idea : Sripal Bangalore

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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

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Goal 3: Advance Translational Research

Guideline effectiveness in treating COPD patients with comorbidities vs. those without

What is the effectiveness of guideline recommendations for chronic obstructive pulmonary disease (COPD) care in patients with multimorbidity, including angina, heart failure, atrial fibrillation, diabetes mellitus, hypertension, and osteoporosis, vs. patients without these conditions?

Submitted by (@spencer)

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

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Goal 2: Reduce Human Disease

Heart Failure Therapies

We need much more support for critical basic research to understand and develop transformative therapies for this enormous health care burden. This is not simply a question of epidemiology and large multicenter population data bases. We really need hard core science. It is impossible to know where the next breakthrough will come, and setting aside funds for hot button things - stem cells, or iPS, or gene editing per ...more »

Submitted by (@dkass0)

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

Feasibility and challenges of addressing this CQ or CC :

NIH needs to stop trying to guess what the next big thing is and putting funds aside to support something that is popular at the moment. This has been done frankly with GWAS, with Stem cells, and perhaps ongoing now with "personalized medicine". All hot areas, but so are a ton of other things. IN my 30 years as a physician scientist, I cannot count on one hand the number of discoveries that were really transformative that came out of this type of ear-marked planning. Need more resources to support innovative individual scientists, particularly those with a track record of discovery, translation, and iinnovation We do not do that well enough at all.

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Goal 2: Reduce Human Disease

A Program of Research in the Prevention of Chronic Heart Failure

There is a need to improve identification and surveillance of persons at risk for heart failure and pathological ventricular remodeling prior to development of clinically overt heart failure.

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 :

Substantially reduce the age-adjusted incidence and population burden of chronic heart failure.

Feasibility and challenges of addressing this CQ or CC :

The big data and omics revolutions have made it feasible to collect and analyze a variety of data in large numbers of persons within a relatively short time. A very large sample size provides excellent statistical power. Also, the public health and economic magnitude of the problem create the urgency needed to address the critical challenge expeditiously.

Chronic heart failure (HF) is easily the most common and growing cardiovascular cause of hospitalization and impaired functional status and quality of life in the U.S. and much of the world. This is the case despite improved pharmacologic and lifestyle treatment of HF, as well as improved control of blood pressure in the general population. While some HF in the very elderly may reflect the aging process, the epidemiology suggests that most incident cases could be prevented or postponed for years. Also, there are major ethnic and socioeconomic disparities in the incidence of HF.

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

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Goal 2: Reduce Human Disease

Molecular determinants of pulmonary failure in sepsis

Respiratory failure in sepsis is almost universal and leads to worse clinical outcomes, yet it is poorly understood. Recent epidemics of pulmonary failure from respiratory viruses (e.g. influenza, SARS, MERS, etc) makes understanding molecular determinants of respiratory failure and the associated inflammatory and physiologic responses, critical for improving the health of our nation and potentially mitigating future ...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 :

Exploring and understanding the molecular determinants of pulmonary failure will impact not only the predictable complications of acute respiratory illnesses such as influenza, but also inform our understanidng and treatment of myriad other common respiratory illnesses resulting in pulmonary failure, such as pneumonia, chronic obstructive pulmonary disease, asthma, obesity hypoventilation, etc.

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. This highly monitored population is a nature source for studying longitudinal changes in molecular patterns and respiratory physiology.

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

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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

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