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

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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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4 up votes
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Goal 2: Reduce Human Disease

Treatment of Major Depression in Patients with Heart Failure

Major depression (MD) is common in patients with heart failure, and it is an independent risk marker for functional decline, hospitalization, and mortality. Two large trials have shown that it can be difficult to treat. SADHART-CHF, a double-blind, placebo-controlled RCT (n=469), found that sertraline was not efficacious for MD in HF. MOOD-HF (n=372) showed that escitalopram was not efficacious. Smaller trials of cognitive-behavioral ...more »

Submitted by (@freedlak)

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

Details on the impact of addressing this CQ or CC :

Major depression causes considerable emotional distress and functional impairment. It follows a chronic or recurrent course in many cases, and untreated episodes can last for months or even years. When superimposed on chronic heart failure, major depression can accelerate functional decline, diminish quality of life, and increase the risks of hospitalization and mortality. Effective treatment of depression can, at minimum, improve quality of life. Treatment may also decrease the risk of adverse medical outcomes, but RCTs will be needed to evaluate the potential medical benefits of treating depression in HF.

Feasibility and challenges of addressing this CQ or CC :

Cognitive behavior therapy is the most promising approach tested so far, but there have been few trials of this intervention, any other psychotherapeutic treatment for depression, or antidepressant medications other than sertraline or escitalopram for major depression in HF. Additional phase II trials may be needed in order to identify the most promising approaches for testing in larger, multicenter RCTs.

Name of idea submitter and other team members who worked on this idea : Kenneth E. Freedland, PhD

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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

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Goal 2: Reduce Human Disease

Pediatric and Adult Heart Failure

How does the mechanism of pediatric heart failure differ from adult heart failure mechanisms?

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 : NHLBI Staff

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13 up votes
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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 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

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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 3: Advance Translational Research

Durable gene activity map at the individual level

A durable gene activity map of the individual to understand when certain gene sets are on vs off or dysfunctional over an individual’s lifetime as one way of guiding the precision of medicine for that patient. It would need to be person portable and universally exportable and interpretable across all of the EHRs.

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

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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

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33 up votes
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Goal 2: Reduce Human Disease

Regeneration of Failing Heart while Resting on Left Ventricular Assist Device

Heart transplant is the ultimate treatment for AHA stage-D heart failure. Due to availability, heart transplants will be limited to about 2,500 per year. Patients with AHA stage-D heart failure has estimated prevalence of 0.2% for age >45. Thus, patients in need far exceed organs available. A failed heart has very challenging environment for cellular therapy. Left ventricular assist device (LVAD) can offload the heart ...more »

Submitted by (@ctong0)

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 : Carl Tong

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Goal 2: Reduce Human Disease

Address bias of doctors treating obese patients

Twice I was allowed to develop severe heart failure symptoms that required hospitalization to treat because my primary care physician assumed that my ONLY problem was that I am fat. Every doctor knows that obesity can lead to the development of diabetes, heart diseases, joint damage and yet too many doctors on the frontlines just say: You're fat go diet. My first experience with this was when I was first diagnosed ...more »

Submitted by (@chriscage)

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

Details on the impact of addressing this CQ or CC :

I'd like to know how many patients die because their primary care doctors don't take their health complains seriously. If you can somehow get primary care doctors to open their eyes and do their jobs, patients like me might not be on the verge of death because their doctors refuse to listen. I had a history of heart failure, I told my primary care doctor that my first doctor completely missed the symptoms in 1996, including swollen ankles and feet, the inability to walk two blocks without stopping and having coughing fits that forced me out of bed into a wing-back chair. I started having those symptoms again in 2011 and ended up spending two and half weeks in a hospital in November 2012 to treat my problems and to drain 96 pounds of fluid from my body. I couldn't bend my legs to get into a car or a truck.

Feasibility and challenges of addressing this CQ or CC :

Of course it is possible to deal with this issue. The question is whether doctors and medical researchers are ready to be honest about the role neglect by primary care physicians plays in the overall health of their patients.

 

Both of the doctors who risked my life had good reputations. I liked them until they stopped listening to me. I had an echocardiogram in October 2011 my ejection fraction was between 20 and 15. I thought I was going to die. My doctor said: numbers don't mean anything??? One year later, I spent two and a half weeks in the hospital.

 

Why do you think I'm hopping mad. How many other patients are dealing with the same types of problems. I literally had to take Xanax because when my symptoms returned I was afraid that my stupid doctors would kill me by ignoring me again. I reported my fears in detail to United Healthcare, I switched to a more competent medical system. I'm losing weight and spent hours walking around Yosemite National Park last month. That's the difference between doctors who listen and doctors who don't. A patient should not be afraid that their doctor is so stupid that she or he will kill them .... accidentally.

Name of idea submitter and other team members who worked on this idea : Mary Crystal Cage

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