Goal 2: Reduce Human Disease

How can we non-invasively, but still accurately, measure blood pressure in the pulmonary arteries?

Pulmonary hypertension (PH) is a complex, progressive condition characterized by high blood pressure in the lungs. The gold standard for measuring pressures in the pulmonary arteries is a right heart catheterization, where a special catheter is guided through the right side of the heart and into the pulmonary artery, the main vessel carrying blood to the lungs. This measurement is essential, as it allows physicians and ...more »

Submitted by (@katherinek)

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. In patients with pulmonary hypertension, the use of multiple tests to characterize the type and severity has long been recommended by global experts; one commonly used diagnostic algorithm recommends more than ten different tests to accurately define this complex, heterogeneous disease. Despite the algorithm used, to confirm a diagnosis of one specific type of PH, pulmonary arterial hypertension (PAH), one must always directly measure the pressures in the heart and pulmonary artery through a right heart catheterization (RHC). Complications for this procedure are rare, but not non-existent with potentially 1 in every 100 patients having a right heart catheterization experiencing a serious adverse event (Hoeper MM 2006). Patients would significantly benefit from a non-invasive method of quantifying their pulmonary artery pressures and/or disease progression, but to date this has not been possible with echocardiography due to measurement errors (Laver 2014), CT scan due in part to measurement inconsistencies (Alhamad 2011), and cardiac MRI due to lack of standardization and multicenter trials (Peacock 2013). Not only would wider utilization of a non-invasive method of measuring pulmonary artery pressures and disease progression potentially reduce the risk from RHC, depending on the modality it could lead to earlier diagnosis of this progressive disease and/or application in countries where RHC is less common.

Feasibility and challenges of addressing this CQ or CC :

Addressing a non-invasive method of measuring pulmonary artery pressures requires investment in both technology and multicenter clinical trials to validate these measures.

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

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Goal 2: Reduce Human Disease

Systems approaches to understand the pathogenesis of cardiovascular diseases, combined with in vivo validation

Critical Challenge

Submitted by (@yong.zhao)

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

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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 »

Submitted by (@murry0)

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

Details on the impact of addressing this CQ or CC :

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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45 up votes
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Goal 2: Reduce Human Disease

Prodromal symptoms and signs of a heart attack/acute coronary syndrome

Can early warning symptoms and signs of a heart attack (acute coronary syndrome) be quantified through standardized symptom surveys, biochemical measures, electrocardiographic, or other diagnostic means to enable earlier evaluation and treatment?

Submitted by (@mmhand)

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

Details on the impact of addressing this CQ or CC :

If patients could detect symptoms that have been demonstrated prospectively to herald an impending heart attack and/or if there were sensitive biochemical, electrocardiographic, or other tests that could be performed by patients/bystanders (e.g., in the home setting), by emergency medical services personnel, primary care providers or others in community settings to assist with decision support about seeking intervention for early symptoms/signs of an acute coronary syndrome, this would potentially save thousands of lives from heart attacks and sudden cardiac death.

Feasibility and challenges of addressing this CQ or CC :

Prodromal heart attack symptoms (waxing and waning of symptoms in advance of complete vessel occlusion) have not been prospectively described or quantified. The standard symptom constellations from epidemiologic surveys have been described for heart attack symptoms (ACS) though there is variability in symptom data collection among heart attack surveys as well. Also while there are biochemical tests for muscle damage (troponin), there is not a biochemical test for ischemia such as could be applied in the home or work setting. Similarly it would be helpful if a self-applied electrocardiogram by patients/bystanders could give a diagnosis of early ischemia (prior to occlusion) so patients could seek observational care.

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

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Goal 3: Advance Translational Research

Neglect of Valuable Heart Health Data

Routine bypass surgery generates left ventricle pressure and volumetric flow data which can be modeled by estimated parameters capable of determining a heart health index. This capability is also available online for the surgeon's

guidance and is applicable to any heart chamber.

Submitted by (@woneill)

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

Details on the impact of addressing this CQ or CC :

A comprehensive heart health state would be established

Feasibility and challenges of addressing this CQ or CC :

The theory has been proven multiple times, intellectual and political inertia are the roadblocks.

Name of idea submitter and other team members who worked on this idea : William ONeill, Jeffery Shuhiaber

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10 down votes
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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

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7 up votes
13 down votes
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Goal 3: Advance Translational Research

Risk Mitigation of Implantable Cardiovascular Devices

There is a serious need to improve implantable cardiovascular devices to eliminate, or at least substantially reduce, the risk of serious adverse events from occurring to more effectively treat patients.

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 :

Cardiovascular devices would be more widely used to treat such cardiovascular diseases as heart failure, coronary artery disease, valvular disease and, therefore, have a greater public health benefit. Furthermore, costs associated with treating the serious adverse events (e.g. hospitalizations, therapeutics, etc.) would decrease.

Feasibility and challenges of addressing this CQ or CC :

Technologies such as surface coatings and topographies as well as evolved design tools are under development already or are being used to mitigate the risks of devices currently being used or under development. A more concerted effort to do this would almost certainly help to substantially reduce the risks further, especially over the next 5-10 years.

Despite the widespread and growing use of implantable cardiovascular devices such as ventricular assist devices, stents, and prosthetic heart valves, substantial serious adverse events such as infections, neurological events, and bleeding limits the efficacy and use of the devices. Scientific and technological breakthroughs in such areas as biomaterials, design tools, coatings, and concomitant pharmacologic therapy are needed to address this challenge.

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

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Goal 1: Promote Human Health

Investigating Co-Morbidities in Women's Cardiovascular Health

There are important questions related to the cardiovascular health of women, and particularly to diagnostic and therapeutic challenges arising from the common existence of co-morbid conditions. The latter consideration, as well as the limitations of the budgets of individual institutes and centers at the NIH, suggest that it may be reasonable for the NHLBI to consider cross-NIH collaborations with I/Cs that have related ...more »

Submitted by (@rosemarie.robertson)

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

Details on the impact of addressing this CQ or CC :

Collaboration across I/Cs could encourage investigators or teams to explore new concepts underlying the etiology of common or rare cardiovascular diseases (CVD), including stroke, particularly those with gender-related differences. In addition, clinical research on these disorders would benefit from active consideration of the common co-morbidities seen in patients with CVD, especially as patients with these co-morbidities are often specifically excluded from clinical trials. Since the patients who will ultimately benefit from treatments developed will often suffer from multiple other disorders, the societal benefit would be substantial. While any single I/C could support such studies, collaborative funding would be likely to bring together new teams of investigators with novel ideas.

Feasibility and challenges of addressing this CQ or CC :

We believe that there is likely to be a good response from investigators, both basic and clinical, to collaborative, multi-I/C RFAs. It might be of additional benefit to provide some funds specifically for teams that are newly collaborative in response to the RFAs, to encourage increased cross-field collaboration.

Name of idea submitter and other team members who worked on this idea : Rose Marie Robertson for American Heart Association

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Goal 3: Advance Translational Research

Heart rate regulation as a therapeutic goal

Heart rate regulation is emerging as an effective treatment for heart failure and angina. However a critical challenge in the development of new therapeutics is the paucity of information about molecular and cellular determinants of heart rate.

Submitted by (@catherine.proenza)

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

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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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Goal 3: Advance Translational Research

Research Opportunities in HLB to Facilitate Aging in Place

There is a need for greater evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung, blood, sleep conditions to remain in their private homes if feasible, if technology is utilized that fosters clinical and epidemiologic research.

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 :

No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

Feasibility and challenges of addressing this CQ or CC :

Evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung and blood conditions remain in their private homes is feasible if technology is utilized that fosters clinical and epidemiologic research.

Many cardiovascular risk factors increase as the population ages including uncontrolled systolic hypertension and atherosclerosis both contributing to the well-being of our society and increasingly high health care costs (Izzo, Levy, & Black, 2012). No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

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

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Goal 3: Advance Translational Research

Exploring Future Cardiovascular Medicine: Heart Precursors Directed from Human Embryonic Stem Cells for Myocardium Regeneration

Cardiovascular disease (CVD) is a major health problem and the leading cause of death in the Western world. Currently, there is no treatment option or compound drug of molecular entity that can change the prognosis of CVD.

Submitted by (@xuejunparsons)

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 human stem cell is emerging as a new type of pharmacologic agent of cellular entity that is much more complex in structure, function, and activity than the conventional drug of molecular entity, which is usually comprised of simple chemicals or compounds. Since the etiologies of most diseases that involve both molecular and cellular processes are much more complex than simple chemicals or molecules, conventional chemical drugs are often severely limited by the molecular entity of the compound that usually targets or blocks certain pathological molecular pathways, which would otherwise be harmful to common molecular pathways shared in normal cellular processes of vital tissues and organs, thus, cause severe toxic side effects that may outweigh the benefits. For instance, a drug for weight loss may cause severe damage to the heart. In addition, the therapeutic effects of conventional drugs of molecular entity provide only temporary or short-term symptomatic relief but cannot change the prognosis of disease. As a result, millions of molecular leads generated in mainstream of biomedical research from animal studies and studies of other lower organisms have vanished before even reach clinical trials, or for a few lucky ones, in clinical trials. In the last few decades, despite of many animal leads, no drug of molecular entity has ever been approved by FDA as a new treatment for heart disease and failure for humans.

Feasibility and challenges of addressing this CQ or CC :

Opportunity: In contrast, the human stem cell has the potential for human tissue and function restoration that the conventional drug of molecular entity lacks. The ability of a human stem cell, by definition, to both self-renew and differentiation makes it a practically inexhaustible source of replacement cells for many devastating or fatal diseases that have been considered as incurable, such as neurodegenerative diseases and heart diseases. The pharmacologic activity of human stem cells is measured by their extraordinary cellular ability to regenerate the tissue or organ that has been damaged or lost, such as the heart in the case of human cardiac stem cells. Therefore, the pharmacologic utility of human stem cells cannot be satisfied only by their chaperone activity, if any, to produce trophic or protective molecules to rescue existing endogenous host cells that can simply be accomplished by a drug of molecular entity. The embryo-originated human embryonic stem cells (hESC) are not only pluripotent, but also incredibly stable and positive, proffering unique revenue to generate a large supply of cardiac lineage-committed stem/precursor/progenitor cells as well as functional cardiomyocytes as adequate human myocardial grafts for cell-based therapy. Currently, the hESC cardiomyocyte therapy derivatives provide the only available human cell sources with adequate capacity to regenerate the contractile heart muscles, vital for heart repair in the clinical setting.

Name of idea submitter and other team members who worked on this idea : Xuejun Parsons

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