Goal 2: Reduce Human Disease

Promotion of human health and reduction of human disease

Congenital heart disease (CHD) is the most common birth defect and leading cause of defect-related infant mortality. With nearly 1 in 100 babies born annually with CHD, the needs of children and adults born with CHD are ongoing and costly. More focused research into CHD promotes human health and will result in a better quality of life, reduced premature death and lower healthcare costs.

Submitted by (@dstephens)

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

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Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease

Does screening for pulmonary hypertension (PH) of sickle cell disease (SCD) alter disease outcomes?

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 :

What is known about this topic:

1) An elevated tricuspid regurgitant jet velocity (TRV) by echocardiography occurs in 1/3 of HbSS adults, 10-25% of HbSC adults and 10-20% of HbSS adolescents.

 

2) An elevated TRV is associated with mortality risk in adults, but not children/adolescents

 

3) Epidemiologically, associations of an elevated TRV with markers of hemolysis and other disease complications (leg ulcers, priapism, proteinuria, etc.) exist.

 

4) Some patients with an elevated TRV have pulmonary hypertension but there is a high false positive rate.

Feasibility and challenges of addressing this CQ or CC :

Areas of controversy:

1) Does screening change outcomes? Currently, there is no established treatment for an elevated TRV. Are there either SCD related therapies (such as hydroxyurea) or treatments for disease associations (such as treatment for proteinuria) that change outcomes?

 

2) Does an elevated TRV predict an increased risk of venous thromboembolic disease, obstructive sleep apnea, asthma or other pulmonary diseases with established treatment?

 

3) What are the implications of an elevated TRV in the pediatric/adolescent population?

 

4) If screening is beneficial, what is the optimal frequency?

 

5) What is the best method of screening and what role does newer technologies such as genomics and proteomics play in identifying a higher risk group for whom screening would be more advantageous?

Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Risk factors and treatment options for pulmonary hypertension in Sickle Cell Disease

What are the risk factors and treatment options for pulmonary hypertension related to diastolic dysfunction in Sickle Cell Disease (SCD)?

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 :

What is known about this topic:

 

1) Pulmonary venous hypertension (PVH) related primarily to left ventricular diastolic dysfunction accounts for at least 50% of cases of PH in SCD patients.

 

2) PVH is an independent risk factor for mortality

 

3) Etiology of diastolic dysfunction in this population is unknown as well as the contribution of relative systemic hypertension

 

4) No specific therapies exist for this condition although traditional diastolic dysfunction CHF are at times eomployed. No standard of care exists.

Feasibility and challenges of addressing this CQ or CC :

Areas of Controversy:

 

1) What role, if any, does iron chelation play in disease prevention?

 

2) What role does treatment of systemic hypertension play in prevention and treatment?

 

3) Is obstructive sleep apnea a risk factor for diastolic dysfunction in this population?

 

4) Is there increased risk of VTE in this population?

 

5) Are SCD specific therapies (hydroxyurea, transfusions) beneficial in improving outcomes?

 

6) What is the best means of diagnosing PVH of SCD? Are there ways non-invasively to predict PAH vs PVH in this population?

 

7) Is cardiac MRI superior to echocardiography in evaluating diastolic function in this patient population?

Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Impact of Hydroxyurea on Organ Function

Does hydroxyurea preserve organ function in patients with sickle cell disease?

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 :

Hydroxyurea is the only disease-modifying medication for sickle cell disease, and has been shown to be effective in reducing complications such as pain crisis and acute chest syndrome in some patients. Evidence suggests that hydroxyurea is underused, and, understandably, efforts are underway to encourage more people to take advantage of this treatment. Determining that it preserves organ function or reduces organ damage could encourage greater use or, if not, encourage the development of other medications that can.

Feasibility and challenges of addressing this CQ or CC :

Given the greater understanding of sickle cell disease and improvements in life expectancy, it should be feasible to design a study that will supply sufficient data to answer this question.

Name of idea submitter and other team members who worked on this idea : The Sickle Cell Association of New Jersey

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Goal 2: Reduce Human Disease

Improving understanding of heart attack mechanisms in women and targeting of treatment

There remain many differences between women and men in the risk of myocardial infarction (MI or “heart attack”), manifestations of MI and outcomes after MI. The time in which the facts about differences between the sexes were unknown or ignored has passed. However, there are many basic answers women and their physicians need, such as: a) Why are younger women with MI at such high risk of death as compared to their male ...more »

Submitted by (@harmony.reynolds)

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 sex differences is the most fundamental aspect of personalized medicine. When considering MI, some sex differences, such as lower risk of MI and a lesser extent of coronary artery disease (CAD, plaque buildup), favor women. Others, such as the 2-fold higher risk of death in younger women with MI and sex differences in the association between diabetes and MI, favor men. Insights into these and other sex differences should provide the foundation for optimal treatment for the prevention of MI and its complications.

Feasibility and challenges of addressing this CQ or CC :

Mechanistic and descriptive studies may be needed before clinical trials can be undertaken.

Name of idea submitter and other team members who worked on this idea : Harmony Reynolds

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Goal 2: Reduce Human Disease

Delivery of microRNA mimics

microRNA have potential to be new drugs for the treatment of different diseases. There is a need to improve methods for the synthesis and delivery of microRNA miimics.

Submitted by (@mahmood.hussain)

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

Details on the impact of addressing this CQ or CC :

mciroRNAs are susceptible to degradation by ubiquitously present RNAses, There is a special need developing new methods for their protection in plasma and improving the amounts of microRNAs delivered to target tissue. Another issue is to find ways of targeted delivery to specific tissues.

Feasibility and challenges of addressing this CQ or CC :

It should be feasible to synthesize new miR mimics that are more stable.

Also, it should be possible to find ways to their targeted delivery to specific tissues.

Name of idea submitter and other team members who worked on this idea : M. Mahmood Hussain

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Goal 2: Reduce Human Disease

Close the gap: Why do men die of cardiovascular disease (CVD) at an earlier age than women?

Despite evidence that women face challenges in receiving optimal CVD care, data show that men die at an earlier age than women of CVD. This health disparity remains unexplained and there are no specific interventions to address it.

Submitted by (@collerb)

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

Details on the impact of addressing this CQ or CC :

A comprehensive T1-T4 initiative is required to explore this health disparity, ranging from epidemiology to basic mechanisms , and to translate that knowledge into specific interventions.

 

Closing the gap would add ~4 years of life to men, representing a monumental health improvement.

Feasibility and challenges of addressing this CQ or CC :

Conceptually this is straightforward since so many data are already available about sex differences in cardiovascular biology. The challenge is to review the information from this frame of reference and with the specific goal of identifying interventions.

Name of idea submitter and other team members who worked on this idea : Barry Coller

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Goal 2: Reduce Human Disease

Optimization of Existing Therapies for Sickle Cell Disease

How can the safety, dosing and benefits of existing therapies for sickle cell disease such as hydroxyurea, be optimized in order to increase its efficacy and improve patient adherence?

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

Details on the impact of addressing this CQ or CC :

Hydroxyurea is a widely available disease-modifying therapy for sickle cell disease (SCD), but its effectiveness is currently limited by inadequate utilization, and less than optimal response. Research is needed to improve adherence to this evidence-based therapy and emphasis needs to be placed on determining whether therapy with hydroxyurea can prevent or even reverse organ dysfunction. In addition, research identifying new adjunct therapies to blood transfusion and hydroxyurea, as well as disease-specific therapies for co-morbidities such as kidney disease, hypertension, obstructive lung disease, and pulmonary hypertension will be valuable in the management and treatment of SCD.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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Goal 3: Advance Translational Research

Financial and psycosocial impact of transition in sickle cell disease

What are the financial and social implications for individuals living with SCD from adolescence transitioning into adult care? What impact does this transition have on the caregiver and family as a whole?

Submitted by (@sicklecellwarrior)

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

Details on the impact of addressing this CQ or CC :

It is very difficult for many living with SCD to maintain employment (many people have to rely on disability benefits to survive) finish school, even maintain relationships. Greater understanding of the financial and social impact would enable advocacy and direct patient service organizations to better prepare the transitioning population, reducing the financial strain on the individual and the growing medical debt incurred by hospitals and government social service programs.

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc. community members

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Goal 2: Reduce Human Disease

Imaging indicators of metabolic syndrome and cardiopulmonary disease

Critical Challenge

Submitted by (@str0001)

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

Details on the impact of addressing this CQ or CC :

Obesity and metabolic syndrome affect a large portion of the population and affects multiple organ systems. Identifying obesity phenotypes by imaging will impact the significant healthcare issue presented by MetS and could provide a reliable, non-invasive index of disease severity, guide prevention and intervention response.

Feasibility and challenges of addressing this CQ or CC :

Metabolic syndrome, abnormal metabolism, may be potentially linked to obesity and cardiopulmonary disease. Theories exist but are in need of clarification. The relationship between metabolic syndrome and multiple other diseases including chronic obstructive lung disease, coronary atherosclerosis, and obesity warrants further investigation and can be elucidated through imaging. Advances in computed tomography (CT) and magnetic resonance imaging (MR) enable assessment of the cardiopulmonary manifestations, with promising MR techniques to complement high-resolution imaging data achievable with chest CT and coronary CT angiography. Assessment of CT and MR techniques in combination with three-dimensional quantitative analysis of manifestations of metabolic syndrome such as fat deposits derived from different adipocytes (white fat versus brown fat) such as in the subcutaneous, visceral, epicardial, and perivascular regions is feasible with current technology and may enable differentiation of those with varying risks of cardiovascular and pulmonary disease. The association of imaging parameters, metabolic syndrome, and associated diseases are in need of investigation, and knowledge gained may prove crucial for identifying those at risk for metabolic syndrome and at higher risk for complications in the large population of our country affected by obesity.

Name of idea submitter and other team members who worked on this idea : Society of Thoracic Radiology

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Goal 2: Reduce Human Disease

Noninvasive biomarkers for characterizing cardiovascular disease

Critical Challenge

Submitted by (@str0001)

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

Details on the impact of addressing this CQ or CC :

Phenotypical characterization of cardiovascular disease with computed tomography (CT) and magnetic resonance imaging (MR) to individualize targeted therapies for coronary artery and myocardial disease. Coronary artery disease is a major cause of patient death in the United States. Nonischemic myocardial disease includes entities with clinically heterogeneous presentations and is thus challenging to manage.

Feasibility and challenges of addressing this CQ or CC :

Currently CT and MR technology allows dynamic evaluation of the perfusion and contractility of the heart. Quantitative measures of disease burden, such as atherosclerotic plaque composition and myocardial texture imaging biomarkers (such as T1 mapping, activation mapping, flow pattern analysis, delayed myocardial enhancement), are possible. Positron emission tomography (PET)/MR, which combines metabolic with functional evaluation, is currently available and facilitates the development of targeted molecular-imaging techniques. Metrics derived from these techniques may serve to stratify patients noninvasively and direct appropriate therapies. Such imaging methods address noninvasive evaluation of cardiovascular disease, including ischemic heart disease but also myocardial diseases that include secondary and infiltrative cardiomyopathies, hypertrophic cardiomyopathy, and organ rejection in the scenario of transplantation.

Name of idea submitter and other team members who worked on this idea : Society of Thoracic Radiology

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Goal 2: Reduce Human Disease

Pulmonary Vascular Diseases

Does treatment with spironolactone improve outcomes in patients with pulmonary arterial hypertension (and/or pulmonary hypertension associated with diffuse parenchymal lung disease or COPD)? Spironolactone has been shown beneficial in CHF and many of the same mechanisms are at plan in RV failure from pulmonary hypertension. Again, no clear evidence whether this is a useful treatment or not, and no evidence to guide ...more »

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges of addressing this CQ or CC :

This is a view of problems in the field.

Pulmonary Hypertension Clinical Research: Current Problems and Possibilities

Current studies limited to the short term, with soft outcomes.

No mechanistic studies embedded in trials.

Control of phenotype is weak.

Small n: lumping of cohorts.

No factorial of advanced design.

No biological samples obtained for study.

Failure to study basic management issues.

Name of idea submitter and other team members who worked on this idea : ATS Member

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