Goal 3: Advance Translational Research

Guideline effectiveness in treating COPD patients with comorbidities vs. those without

What is the effectiveness of guideline recommendations for chronic obstructive pulmonary disease (COPD) care in patients with multimorbidity, including angina, heart failure, atrial fibrillation, diabetes mellitus, hypertension, and osteoporosis, vs. patients without these conditions?

Submitted by (@spencer)

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

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Goal 2: Reduce Human Disease

Blood Pressure Recommendation

What should be the systolic blood pressure goal for pharmacological treatment, and should it vary by age or by cardiovascular disease (CVD) risk category?

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 :

Despite fifty years of clinical trial research and forty years of national guideline activity, important clinical questions remain under intense scientific debate. The importance of these questions are underline by the scientific consensus that hypertension is most important cardiovascular risk factor globally, in fact, more important than even tobacco use.

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

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Goal 2: Reduce Human Disease

Development of right ventricular-targeted therapies in pulmonary arterial hypertension (PAH)

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. A great increase in the treatment armamentarium has been noted for this rare disease in the past 20 years, with 12 new PAH-targeted therapies. Though these therapies do improve cardiac performance, this is most likely due to their primary ...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 :

Since 2006, 12 medical therapies for PAH have been approved by the FDA, which have increased survival of this rare disease from around 2.8 years to approximately 9 years; these therapies primarily act by dilating the pulmonary arteries in order to reduce pulmonary vascular resistance to blood flow. However, patients continue to die from right ventricular failure, highlighting the important relationship of the pulmonary arterial system and right ventricle (RV). Despite patients ultimately dying from RV failure, little is known about the effect of the currently available PAH-targeted therapies on RV functional support. Prostacyclins, PDE5i, and sGC agonists are thought to enhance RV contractility—though the long-term effects remain unknown—while ERAs are thought to reduce it. The direct RV effect of some potential therapies targeting the pseudo-malignancy theory of PAH is a concern, as these therapies seek to reduce the hypertrophy and angiogenesis that may actually be supporting the adapting RV. Further, therapies targeting the ventricle directly have historically been centered on the LV—for example β-adrenergic receptor blockers and RAS inhibition—and either remain controversial or without data in the RV. There remains no identified RV-specific therapy to either provide support through increase contractility or molecularly prevent the progression from RV hypertrophy to ultimate failure.

Feasibility and challenges of addressing this CQ or CC :

The primary challenge of addressing this CC on the lack of RV-targeted therapies for the treatment of PAH 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, and subsequently responds differently to autocrine, paracrine, neuroendocrine, pressure, and pharmaceutical changes to name only a few. However, when identified, these RV biologic distinctions can be translated and tested clinically to more comprehensively and appropriately treat the RV-arterial uncoupling ultimately leading to right heart failure: through both reduction in afterload and an increase in contractility.

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

Developing approaches to the dissemination of behavioral weight loss programs

The Challenge is to make behavioral weight loss programs readily available to he many overweight and obese patients who need them. Behaivoral weight loss programs are effective in producing weight losses of 7-10% of initial body weight, which has been shown to have major beneficial effects on a number of diseases relevant to NHLBI--including hypertension and sleep apnea. However, at present, these programs are not widely ...more »

Submitted by (@rwing0)

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

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Goal 2: Reduce Human Disease

Would patients with pulmonary arterial hypertension (PAH) benefit from background anticoagulation in addition to their PAH-targe

Pulmonary hypertension (PH) is a complex, progressive condition characterized by high blood pressure in the lungs. For several decades, oral anticoagulation has been recommended by some societies for patients with a specific form of PH called pulmonary arterial hypertension. However, the evidence currently supporting this recommendation is very limited. To date, no prospective randomized clinical trial has been completed ...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 :

The evolution of the anticoagulation recommendation in pulmonary arterial hypertension (PAH) is a relatively logical one at face value. Early in the modern era of PAH management, a “thrombosis” in the small pulmonary arteries was identified and described; studies since then have demonstrated hypercoagulability in patients with severe disease. Together, these observations led to a theory that in-situ thrombosis contributed to the PAH disease progression and a belief that anticoagulation should be beneficial. The empirical evidence currently supporting this recommendation comes mostly from a retrospective cohort study of the European COMPERA PH registry and a systematic review of 7 retrospective cohort studies that are at least 10 years old—2 of which did not suggest a survival benefit—and in a time where only 4 of the widely used PAH-targeted therapies were approved by the FDA. Purely based on observational evidence with a number of potential biases, warfarin (Coumadin) is widely used in PAH management to this day. Warfarin in this patient population is not without its risks, as some subgroups of PAH patients are at increased risk of bleeding complications based on their disease process alone. Assessing the true benefit of this widely used background therapy could allow clinicians and patients to more accurately weigh the risks and burden of anticoagulation with a true understanding of the survival benefit.

Feasibility and challenges of addressing this CQ or CC :

Addressing this compelling question is indeed feasible through an NIH-sponsored randomized, double-blind, placebo-controlled trial of anticoagulation in patients with certain types of pulmonary arterial hypertension.

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

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

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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3 net votes
3 up votes
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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

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 »

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 :

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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Goal 3: Advance Translational Research

Calcium channels in cardiovascular functions and diseases

Fifty years ago Prof. Harald Reuter of the University of Bern, Switzerland obtained the first experimentally supported evidence that the calcium channel is a physiologically distinct entity. Further stimulated by the synthesis of the dihydropyridine calcium channel blocker nifedipine, the field of calcium channel research rapidly encompassed cardiovascular and other powerful biomedical directions.

Submitted by (@soldatovn.humgenex)

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 coming Theme Issue of Current Molecular Pharmacology "50th Anniversary of Calcium Channel Research: Biomedical Perspectives" brings together leading experts in calcium channel research with the aim of discussing new ideas and recent developments in research of voltage gated calcium channels and calcium signaling with specific focus on biomedical perspectives. This CMP Theme issue may be particularly interesting for those who are involved in molecular cardiovascular research. Please see further: http://benthamscience.com/journal/upcoming-articles.php?journalID=cmp

Feasibility and challenges of addressing this CQ or CC :

In 2010, heart diseases cost the United States $316.4 billion in health care services, medications, and lost productivity (Circulation 2010, 121, e1). Search for new therapeutical targets associated with the family of calcium channels becomes an increasingly powerful future direction.

Name of idea submitter and other team members who worked on this idea : Nikolai M. Soldatov, Ph.D., Guest Editor, and authors of 23 papers of the CMP Theme Issue

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1 up votes
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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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54 net votes
74 up votes
20 down votes
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Goal 2: Reduce Human Disease

Critical Challenge

• One of the most important public health issues the Nation faces is the rising incidence of heart failure. HF incidence rates have risen faster than predicted. The prevalence will increase as better and more therapy becomes available. While heart failure is the biggest ticket item in the Medicare budget, the cost to society will increase more than it has already. But much HF can be prevented or onset prolonged. Investing ...more »

Submitted by (@tsansone)

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

Details on the impact of addressing this CQ or CC :

See attached file

Feasibility and challenges of addressing this CQ or CC :

Critical Challenge

Name of idea submitter and other team members who worked on this idea : ASH Officers, Committee Members

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