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

New anti-thrombotic approaches with minimal adverse effect of bleeding

All current anti-thrombotic drugs have the adverse effect of excessive bleeding, which is associated with mortality and poor prognosis. Thus, there is a need to develop new generations of anti-thrombotics that have minimal adverse effect of bleeding.

Submitted by (@xdu000)

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

Name of idea submitter and other team members who worked on this idea : Xiaoping Du

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7 net votes
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2 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 »

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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5 net votes
21 up votes
16 down votes
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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

Clinical Trials and Rare Diseases

Strategies and infrastructure to support clinical trials in rare diseases must go further in the development of critical partnerships with advocacy organizations. These partnerships must be formalized and based on models that help to accelerate the research.

Submitted by (@dappell)

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

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11 net votes
13 up votes
2 down 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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-4 net votes
3 up votes
7 down votes
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Goal 2: Reduce Human Disease

Prevent cytopenia in septic patients

Sepsis is the leading cause of death in critically ill patients in the USA, affecting particularly young children and the elderly. A hallmark of septic shock patients upon diagnosis is peripheral blood cytopenia. This persistent cytopenia commonly affects myeloid, lymphoid and erythroid lineages resulting in immunosuppression and is a well-established predictor of fatal outcome. Clinical trials targeting the production ...more »

Submitted by (@ben.croker)

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

Details on the impact of addressing this CQ or CC :

The current standard-of-care for sepsis patients involves supportive therapy and the early administration of antibiotics, which has been essentially unchanged in 40 years. Therapies that prevent the loss of immune cells are likely to be beneficial to avoid immune suppression and prevent the development of life-threatening systemic infection.

Feasibility and challenges of addressing this CQ or CC :

One of the challenges of addressing this question are the large number of biochemical pathways that influence hematopoiesis. Most have not been studied in the context of infection in animal models or in clinical samples. But many animal models and reagents exist that would enable researchers to study this problem. The study of hematopoiesis during infection is feasible and a number of broad questions could be addressed:

a. Do hematopoietic cells and their precursors undergo cell death in response to intracellular pathogens leading to immune suppression?

b. Are hematopoietic cells and their precursors affected by extracellular pathogen-derived products or host-derived molecules resulting from severe injury? Does this lead to cell death and/or prevent the proliferation and differentiation of hematopoietic stem and progenitor cells?

c. How do genetic factors, chronic infection and comorbidities increase the activity of cell death pathways and/or impair the proliferation and differentiation of hematopoietic stem and progenitor cells?

Name of idea submitter and other team members who worked on this idea : Ben Croker

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Goal 2: Reduce Human Disease

In pulmonary arterial hypertension (PAH), how can right ventricular function be improved in the setting of increased afterload

Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. Significant improvements have been made in medical management with through approved pulmonary vasodilator therapies. However, long-term right ventricular afterload reductions have still not yet been achieved. The process by which the ...more »

Submitted by (@katherinek)

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

Details on the impact of addressing this CQ or CC :

Understanding of many components of the PAH disease state have evolved significantly in the past thirty years. When initially described by an NIH registry, in a time where pulmonary transplantation was the only treatment for PAH, the average life expectancy of PAH patients was estimated to be 2.8 years. Since then, 12 PAH-targeted therapies have been approved by the FDA; these therapies primarily act by dilating the pulmonary arteries in order to allow blood to flow easier through the pulmonary vascular system. Despite these advances and complex therapies, long-term afterload reduction is not achievable in most PAH patients. Patients continue to die from right ventricular failure, highlighting the important relationship of the pulmonary arterial system and right ventricle. Little is known about how and why the RV progresses from hypertrophy to full RV failure, the diagnostic signs indicating early RV failure, and how best to intervene to support the failing ventricle. Knowledge in this area is critical, however, as the RV is able to recover in many patients with severe PAH after lung transplantation. The relationship between the lung vasculature and cardiac function, and specifically a characterization of RV failure, was included as a research opportunity in the Strategic Plan for Lung Vascular Research in an NHLBI-ORDR Workshop Report (Erzurum S, et al. 2010).

Feasibility and challenges of addressing this CQ or CC :

The primary challenge of addressing this CQ on how right ventricular function can be improved in the setting of increased afterload is the comprehensive analysis and support that will need to be provided, spanning from basic to clinical science. To begin, strong support of biologic characterization of the right ventricle needs to be provided. The RV is distinctly different from the more comprehensively studied left ventricle (LV), and subsequently responds differently to changes in pressure, neurotransmitters, hormones, and pharmaceutical therapies to name only a few. However, when identified, these RV biologic distinctions can be further explored to develop a better understanding of RV failure and potential points of intervention.

Name of idea submitter and other team members who worked on this idea : Katherine Kroner, Michael Patrick Gray, PHA

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72 up votes
7 down votes
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Goal 2: Reduce Human Disease

Improve HLA matching in lung transplant

Can we increase HLA matching in lung transplantation and improve outcomes?

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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-10 net votes
6 up votes
16 down votes
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Goal 2: Reduce Human Disease

Decreasing risk for cardiometabolic disorders in pregnancy with a focus on preeclampsia

The prevalence of cardiometabolic disorders of pregnancy are increasing rapidly in women in the United States, particularly in black women. These disorders have a significant impact on the development of CVD in women as they age and on their offspring. The science to answer these questions are both mechanistic(understanding underlying mecanism of disease, esp preeclampsia) and behavioral. New methods of gathering ...more »

Submitted by (@pajohnson)

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

Details on the impact of addressing this CQ or CC :

By addressing cardiometabolic disease in pregnancy, we have the ability to improve long-term maternal and child health. The global implications for focusing on this problem are also profound. The potential for research that spans basic, translational, outcomes and lifestyle interventions is potentially great. There is opportunity for NHLBI to partner with NICHD, and Fogarty to undertake a broad and wide initiative that has the ability to save lives in the US and globally.

Name of idea submitter and other team members who worked on this idea : Paula Johnson

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1 net vote
3 up 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.

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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6 net votes
34 up votes
28 down votes
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Goal 2: Reduce Human Disease

Implanted defibrillators

What are the effects of implanted defibrillators (ICDs) in patients with diseased, remodeled hearts?

Do ICDs influence future arrhythmia risk? Can devices be better designed to mitigate their possible deleterious effects?

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 :

Decrease cardiovascular disease and death. Improve quality of life for those utilizing ICDs.

Feasibility and challenges of addressing this CQ or CC :

Recent advances in research and ICD technology

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

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-5 net votes
4 up votes
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Goal 2: Reduce Human Disease

Controversies exist regarding thoracic aortic disease imaging

Controversies exist regarding aortic disease imaging (the aorta as well as the aortic valve, including characterization in the presence of a bicuspid aortic valve (BAV)). Many imaging approaches are optimized for evaluation of coronary artery disease rather than aortic disease. Without accurate characterization, the degree of disease progression may be under estimated, patient symptoms may be discounted, and those who ...more »

Submitted by (@bavtad)

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

Details on the impact of addressing this CQ or CC :

Imaging specifically tailored to BAV and the thoracic aortic aneurysm population is needed. This includes efforts to identify subtle forms of aortic valve malformation such as the “forme fruste” BAV as described by Sperling and Lubet.

1. Echocardiogram is a useful noninvasive imaging tool, however, it is believed to miss detection of as many as 50% of BAVs.

2. The exercise echocardiogram is useful for evaluation of wall motion abnormality, which may be present in those with coronary artery disease or other underlying sources of myocardial injury. However, this is not a common issue in those with BAV. Rather, accurate assessment of BAV function is necessary. Pressure testing for eccentric AI and the short axis view of the AV area, including clear visualization of both the open and closed valve, may not be employed, and consequently clarity of BAV functioning is not achieved.

3. Although there are open questions about aortic size relative to timing of elective surgery, size of the aorta is a diagnostic parameter, and is frequently done via CT imaging. CT images are typically captured in diastole, which is appropriate for coronary artery disease. However, the aorta will be undersized if measured in diastole. Measurement of the aorta in systole captures the aorta when most distended.

4. Other considerations, such as the presence of bovine arch anatomy, may not be noted, since their relevance may not be appreciated.

Feasibility and challenges of addressing this CQ or CC :

Current imaging technology is widely available in most medical communities. It is very feasible, by focusing on valvular and aortic conditions separately from coronary artery disease, to optimize imaging for these conditions and make these imaging approaches broadly available to patients.

Name of idea submitter and other team members who worked on this idea : Arlys Velebir, Bicuspid Aortic Foundation

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11 down votes
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