Showing 33 ideas for tag "failure"

Goal 2: Reduce Human Disease

Neurocardiology – A Challenge for Prevention of CV Disease

There is a need to recognize and study the interdependencies between the brain/peripheral nervous system and the heart/vascular systems in health and disease to develop interventions to detect, treat, and prevent cardiovascular disease.

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

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Effective new therapies for treatment and prevention of cardiovascular disease

Feasibility and challenges of addressing this CQ or CC

long recognition of interactions between neural and CV system provide a wealth of background knowledge, while new imaging and electronic designs provide means for administering novel interventions.
Presently it is recognized that the autonomic nervous system plays a major role in the pathophysiology of arrhythmias leading to sudden cardiac death (SCD), and NHLBI supports ongoing studies to determine if modulation of nerves may provide an effective means to reduce the occurrence of ventricular arrhythmias associated with SCD. Already, investigators have suggested that therapies such as right, left, or bilateral cerviocothoracic sympathectomy may provide a novel and cost effective intervention for the prevention of SCD. It is also well known that the sympathetic nervous system is activated during the onset and progression of heart failure. Currently investigators have proposed studies of specific central brain sites and the nerve supply to the heart during chronic heart failure progression to gain a better understanding of this pathway as a therapeutic target for the treatment of HF. This and the translation of results from similar studies is a challenge that should be encouraged.

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

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Goal 2: Reduce Human Disease

Understanding Right Ventricular Function and Failure

There is a need for understanding of right heart failure (RHF) and its consequences following left ventricular assist device (LVAD) support, as well as to develop devices to optimally support the right ventricle.

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

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Understanding the pathophysiology and risk factors of right heart failure in the context of LVAD use might lead to preventative and therapeutic options for these patients.

Feasibility and challenges of addressing this CQ or CC

Current resources in terms of a National Registry for VADS (INTERMACS) exists and can be leveraged.
While we have a substantial understanding of the risk factors associated with poor outcomes of patients with heart failure and left ventricular dysfunction, much less is known about the syndrome of heart failure and right ventricular (RV) dysfunction. Right-sided heart failure occurs in approximately 20% of patients receiving LVAD support. Investigation into the pathophysiology of right ventricular failure and its consequences following LVAD support, including identification of risk factors and treatment strategies, remains a high priority according to the Joint NHLBI-American Association for Thoracic Surgery (AATS) Working Group convened in 2011 (http://aats.org/CME/2011-AATS-NHLBI-Symposium.cgi). Development of new devices designed to optimally support the RV are warranted.

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

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31 up votes
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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 address chronic heart failure (HF) through improved identification of patients at risk for HF and of patients with pathological ventricular remodeling who have minimal evidence of clinical HF, and more focused and individualized pharmacologic and lifestyle treatments and monitoring of patients with HF risk. Approaches would include big data collection, omics, statistical modeling, and focused clinical... more »

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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28 up votes
11 down votes
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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.

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

Stem Cell Immunology

We now can create critical cell types like cardiomyocytes etc. from stem cells. Additionally, we are learning the rules of using these cells to rebuild tissues. A major gap in our knowledge relates to the immunobiology of these cells. Lessons from transplantation medicine are only partially applicable, because solid organs are more complex and likely more immunogenic than defined cell populations.

How does the immune... more »

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

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We now can generate large quantities of critical cell types whose deficiencies underlie many chronic diseases like heart failure. This breakthrough brings us to the next-level impediment: the immune system. While induced pluripotent stem cells have the potential to obviate rejection, in practical terms this is cost-prohibitive: It will cost huge amounts of money to produce and qualify a single patient's cell dose. Moreover, human cardiomyocytes are potent when given to infarcted hearts in the acute or sub-acute phase of infarction, but they have no benefit with chronic heart failure. The 6 months required to produce iPSC-cardiomyocytes precludes their autologous use for myocardial infarction.

We need an off the shelf cell therapy product for myocardial infarction that can be mass produced and qualified for large numbers of patients. This means an allogeneic product is necessary. Identifying the immune response to cardiomyocytes or other cell products will teach us how to precisely immunosuppress the patient, thereby minimizing complications, or alternatively, how to engineer the cells so as to avoid immunogenicity in the first place.

Lessons from the study of cardiomyocyte transplantation could extend to dopamine neurons, pancreatic beta-cells, retinal cells, myelinating cells and many other areas that cause common chronic disease.

Feasibility and challenges of addressing this CQ or CC

We know a great deal of transplant immunology from hematopoietic stem cell transplantation (graft versus host) and from solid organ transplantation (host versus graft). There are good mouse and large animal (including non-human primate) models of stem cell differentiation and organ transplantation. This offers low hanging fruit where, in perhaps 5 years, we could discern the critical similarities and differences between transplanting stem cell derivatives and organ or marrow transplantation. These studies will inform clinical trials of allogeneic human stem cell derivatives that will be underway by then.

Success in this area will require bringing together researchers interested in stem cell biology and transplant immunology. A properly resourced RFA from NIH could be just the thing needed to promote this interaction.

Name of idea submitter and other team members who worked on this idea Charles Murry, MD, PhD

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23 net votes
45 up votes
22 down votes
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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 »

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

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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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5 net votes
21 up votes
16 down votes
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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 »

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

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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

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15 up votes
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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.

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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14 net votes
28 up votes
14 down votes
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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?

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

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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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13 net votes
23 up votes
10 down votes
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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.

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

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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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6 net votes
34 up votes
28 down 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 »

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

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

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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 »

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

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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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27 up votes
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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 »

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

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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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14 up votes
6 down votes
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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 »

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

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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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