Goal 1: Promote Human Health

Improving longterm outcomes after surgery for congenital heart disease

Survival has improved but neurobehavioral disabilty remains a common complication with adverse impacts on quality of life, educational and occupational attainments, and resource utilization. There is increasing evidence that brain development is abnormal, and leads to a rrisk of peri-operative brain injury. Studies are needed to; 1. Further define the prevalence and spectrum of neurobehavioral disability. 2, Understand ...more »

Submitted by (@gaynor)

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

Details on the impact of addressing this CQ or CC :

Survival has improved following surgery for complex congenital heart disease. There is an ever increasing population of adolescents and adults with repaired congenital heart defects. Neurobehvaioral disability can be identified in over 50% of survivors, including ADHD, autism spectrum disorders, learning disabilities and impaired motor skills. These deficits adversly affect their schools and job performance, as well as interactions with their peers and families. The need for special education and other rehabilitative services leads to significant resurce utilization and costs to society. Development of novel neuroprotective therapies will significantly improve the long-term outcomes for these fragile children.

Feasibility and challenges of addressing this CQ or CC :

Because of the small numbers of patients treated at single instituions, this project will require multi-institutional collaboration with long-term follow-up assessments. There is need for collabortaive databases, standardized neurodevelopment evaluations, and acquistion of genomic data. In particular, there is a need to development methodolgy to track outcomes from fetal life to adulthood.

Name of idea submitter and other team members who worked on this idea : J William Gaynor

Voting

18 net votes
23 up votes
5 down votes
Active

Goal 2: Reduce Human Disease

Cardiac rehabilitation in congenital heart disease

Does cardiac rehabilitation in children with Fontan physiology increase exercise capacity over the long term?

What are the benefits? What is the appropriate dose? What other CHD populations may benefit from cardiac rehabilitation?

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 :

Improve functional capacity and quality of life of patients with congenital heart disease.

Feasibility and challenges of addressing this CQ or CC :

Preliminary data has been promising but larger clinical trials are needed.

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

Voting

-3 net votes
10 up votes
13 down votes
Active

Goal 2: Reduce Human Disease

10. What biological variables are most influential in the development and clinical outcomes of heart disease and what can be don

Given that approximately 64 percent of women who died suddenly of CHD had no previous symptoms4 and that traditional risk factors and scores underestimate CHD risk in women, there is a need to identify unique markers for women at risk for CHD60.

 

( from 10 Report)

Submitted by (@scampbell)

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

Details on the impact of addressing this CQ or CC :

Early detection and correction of such variables as elevated cholesterol, hypertension, diabetes and cigarette smoking, can reduce atherosclerosis (the main cause of CHD) and improve outcomes. These are modifiable to some extent with changes in lifestyle, improved diet, exercise and smoking cessation. Psychosocial risk factors, such as low socioeconomic status, anxiety, and depression have also been linked to CHD and should be evaluated.

There are also biomarkers, biomediators, neurohormones, and surrogate markers which can signal CHD. Some of these can be modified, including

 

• neurohormones which are part of the renin-angiotensin-aldosterone system that directly impact angiotensin II and arginine vasopressin1, 61, 62

• markers of the inflammatory processes such as C-reactive protein which may be a useful predictor of CVD and correlates significantly with future risk of developing hypertension63, 64

• markers of heart failure such as B-type natriuretic peptide

Surrogate markers of atherosclerosis and CHD risk include left ventricular hypertrophy, intima-media arterial wall thickness, proteinuria and microalbuminuria, endothelial dysfunction, coronary calcification and anemia1, 62.

Feasibility and challenges of addressing this CQ or CC :

Research shows that a variety of treatments – from lifestyle/behavioral changes, medications, and interventional treatments – can interrupt the progression of CHD. Further research is needed to demonstrate whether lifestyle and behavioral changes in women with known or suspected CHD can improve prognosis. Innovative approaches to care management that encourage changes in lifestyle should be considered. These include customized care management and the use of multidisciplinary teams of health practitioners who coordinate care for women at risk. Further research is needed to determine whether reducing or minimizing the novel biomarkers associated with CHD will result in lower mortality rates.

Name of idea submitter and other team members who worked on this idea : Susan M. Campbell, WomenHeart Scientific Advisory Council

Voting

-3 net votes
5 up votes
8 down votes
Active

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

Voting

-4 net votes
3 up votes
7 down votes
Active

Goal 3: Advance Translational Research

Current State of Regenerative Medicine: Moving Stem Cell Research from Animals into Humans for Clinical Trials

Realizing the developmental and therapeutic potential of pluripotent human embryonic stem cell (hESC) derivatives has been hindered by the inefficiency and instability of generating clinically-relevant functional cells from pluripotent cells through conventional uncontrollable and incomplete multi-lineage differentiation.

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 :

Realizing the developmental and therapeutic potential of pluripotent human embryonic stem cell (hESC) derivatives has been hindered by the inefficiency and instability of generating clinically-relevant functional cells from pluripotent cells through conventional uncontrollable and incomplete multi-lineage differentiation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, resulting in inefficient, incomplete, and uncontrollable lineage-commitment that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity. In addition, undefined foreign or animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic.

Feasibility and challenges of addressing this CQ or CC :

Opportunity: Recent technology breakthroughs in hESC research have overcome some major obstacles in bringing hESC therapy derivatives towards clinical applications, including establishing defined culture systems for derivation and maintenance of clinical-grade pluripotent hESC and lineage-specific differentiation of pluripotent hESC by small molecule induction. Such milestone advances and medical innovations in hESC research enable direct conversion of pluripotent hESC into a large supply of homogeneous populations of clinical-grade hESC neuronal and heart cell therapy products for developing safe and effective stem cell therapies. Currently, these hESC neuronal and cardiomyocyte therapy derivatives are the only available human cell sources with adequate capacity to regenerate neurons and contractile heart muscles, vital for CNS and heart repair in the clinical setting.

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

Voting

-21 net votes
13 up votes
34 down votes
Active

Goal 1: Promote Human Health

Nicotine abuse and fetal programming of heart ischemic disease

It is well-known that cigarette smoking is a major risk factor of heart ischemic disease. However, little information is known about the maternal smoking and fetal programming of heart ischemic disease in adulthood. Recently, e-cigarette (nicotine use) during pregnancy is a worldwide health concern. Epidemiologic studies have indicated that cigarette smoking during pregnancy is associated with an increased risk of cardiovascular ...more »

Submitted by (@dxiao0)

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 : D Xiao

Voting

-3 net votes
5 up votes
8 down votes
Active

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)

Voting

-23 net votes
4 up votes
27 down votes
Active

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.

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 :

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

Voting

19 net votes
31 up votes
12 down votes
Active

Goal 1: Promote Human Health

Adult Cardiomyocytes in Culture

So much basic cardiovascular discovery relies on cell culture models. While cardiac cell lines exist (e.g. HL-1, H9c2), these often poorly model aspects of cardiomyocyte function in-situ (e.g. contractile function, metabolism). In contrast, primary cardiomyocytes isolated from adult animals (especially mice!) are not readily amenable to culture conditions. Even if cells can be kept alive, they are often refractory to ...more »

Submitted by (@paulbrookes)

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

Details on the impact of addressing this CQ or CC :

Addressing this challenge would provide tools for basic researchers to answer many key questions about basic cardiomyocyte function. Removing the "voodoo" element from these methodologies would be an enabling technology. In the neuron field, companies such as "brain bits" will ship tissue with specific protocols, to enable unskilled technicians to culture highly pure neuron subtypes in a matter of hours. Such methods have led to standardized methods in the field, which is good for reproducibility.

Feasibility and challenges of addressing this CQ or CC :

There have been several attempts at keeping adult myocytes alive in culture, using technologies such as electrical pacing, and inclusion of inhibitors in culture media. Likewise some AAV variants are known to transfect hearts in-vivo. However, no uniform widely-accepted methods are used between many different labs. Every lab has their own "trick" to get cells to behave. Many investigators can make a few cells on a dish survive, which is sufficient for single cell work (e.g. microscopy), but getting an entire culture of adult myocytes to survive beyond 24-48 hrs (the minimal time frame needed for genetic manipulations such as siRNA) would open up more common detection and assay measurements. Myocytes from larger animals (e.g. rabbits) are more stable and longer-lived in culture, but such methods do not appear to work for mouse CMs, which therefore precludes application of knockouts and other useful mouse resources.

Name of idea submitter and other team members who worked on this idea : Paul Brookes

Voting

-25 net votes
12 up votes
37 down votes
Active

Goal 2: Reduce Human Disease

PUFA Toxicity

Our diets contain 20 times more omega-6 fatty acids than the diets of humans before agriculture, industrial solvent extraction of seed oils and hydrogenation. These acids including linoleic and arachidonic acids are precursors to eicosanoids that mediate inflammation and blood clotting and the amount in our diet has been shown to correlate with negative health outcomes. Should NHLBI fund more research into the effects ...more »

Submitted by (@shoemajd)

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

Details on the impact of addressing this CQ or CC :

Federal regulations could limit the amount of omega-6 fatty acids in foods and significantly reduce the incidence of atherosclerosis, strokes, heart attacks, asthma and autoimmune disease.

Feasibility and challenges of addressing this CQ or CC :

Evidence already exists but should be confirmed in large scale studies

Name of idea submitter and other team members who worked on this idea : James Shoemaker MD PhD

Voting

-4 net votes
9 up votes
13 down votes
Active

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

Voting

67 net votes
75 up votes
8 down votes
Active

Goal 2: Reduce Human Disease

Heart Failure with Preserved Ejection Fraction Needs better understanding

Effective treatment for Heart Failure with Preserved Ejection Fraction (HFpEF) currently does not exist. Lack of understanding of underlying mechanism(s) probably contributed to this lack of treatment. The well studied neural-hormonal blockade will not work for HFpEF because down stream kinase targets of adrenergic stimulation enhances myocardial relaxation. Consequently, sustain research outside current main stream thinking ...more »

Submitted by (@ctong0)

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

Details on the impact of addressing this CQ or CC :

Modulation of myosin-actin interaction, energetics, and post translational modification need to be studied in the context of HFpEF. Elucidating underlying mechanism(s) and translating the discoveries toward effective treatment can solve the HFpEF enigma. With aging population, finding effective treatment for HFpEF is sorely needed.

Name of idea submitter and other team members who worked on this idea : Carl Tong

Voting

2 net votes
13 up votes
11 down votes
Active