Goal 2: Reduce Human Disease

Hypertension in the Pediatric Population

We also wish to draw attention to the rise in the prevalence of hypertension in the pediatric population, mostly as a consequence of the childhood obesity epidemic.

Submitted by (@nhlbiforumadministrator)

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Additionally, hospitalizations related to pediatric hypertension have doubled over the past decade. These phenomena have clear and profound implications for the future cardiovascular health of the American population. The NHLBI has been instrumental in supporting studies in pediatric hypertension in the past, and we encourage a continued focus on pediatric populations for future hypertension research.

Name of idea submitter and other team members who worked on this idea : American Society of Pediatric Nephrology (ASPN)

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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)

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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)

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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

Pulmonary Complications of Sickle Cell Disease

Do SCD patients with hemodynamics consistent with pulmonary arterial hypertension (PAH) respond to medications designed to treat PAH?

Submitted by (@nhlbiforumadministrator)

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What is known about this topic:

1) Case series have demonstrated potential therapeutic benefits for endothelin receptor antagonists, phosphodiesterase 5 inhibitors and prostacyclins in PH of SCD patients

2) Three attempted randomized placebo controlled trials of these agents in SCD patients have not gone to completion and, as a result, were under-powered to demonstrate efficacy.

3) Sildenafil produced an increase in hospitalization for pain crises in this population.

4) Anecdotally, select SCD patients with PAH have hemodynamic and clinical benefits from PAH medications.

5) Approximately ½ of PH in SCD patients have some degree of pulmonary venous hypertension and these medications may not be helpful here.

Feasibility and challenges of addressing this CQ or CC :

Areas of controversy:

1) Only one of the three randomized controlled trials required a PAH diagnosis prior to randomization, so the actual question hasn’t been properly addressed.

2) SCD patients with PAH are different than idiopathic PAH patients in terms of their underlying disease, so possibly the treatment response is different.

3) What are the right clinical trial endpoints for this population?

4) What is the role of SCD specific therapy (hydroxyurea, transfusions) in treating PAH of SCD?

5) How can investigators design a clinical trial which allows for enough patient accrual to achieve its endpoints?

6) What novel therapies can be developed to treat this population?

7) What unrecognized medication toxicities are SCD patients at increased risk for?

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

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Goal 2: Reduce Human Disease

Can Psychological Science Improve Weight Loss?

Will sensitivity to the psychological aspects of obesity, including lifestyle priorities and motivations, improve the efficacy of long-term effectiveness of weight loss and obesity prevention interventions?

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 :

A primary focus on principles of psychology may result in significantly improved control of the obesity epidemic. Effective interventions could reduce the risk of diabetes, sleep apnea, and hypertension. This research could also affect clinical practice guidelines for weight loss and obesity treatment.

Feasibility and challenges of addressing this CQ or CC :

Psychological science has been successful in developing effective treatments for a number of conditions, including sleep disorders, depressive symptoms, anxiety and phobias. Many of the behavioral principles employed in such interventions (e.g., cognitive restructuring, motivational methods) could be translated for the prevention and treatment of obesity within a reasonable time frame. Additional attention should be directed to the needs of population subgroups in which obesity is most prevalent.

In their Viewpoint article on weight loss intervention research, Pagoto and Appelhans (JAMA, 2013, see attachment) question whether a continued focus on dietary factors in research on weight loss and obesity is warranted. Their commentary raises the importance of attention to the individual psychological characteristics that influence adherence to weight loss interventions rather than dietary composition.

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

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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 improve identification and surveillance of persons at risk for heart failure and pathological ventricular remodeling prior to development of clinically overt heart failure.

Submitted by (@nhlbiforumadministrator)

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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 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)

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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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Goal 2: Reduce Human Disease

Seeking the secret behind “resilience” to a variety of HLBS diseases

What is the secret behind the “resilience” some people have to heart, lung, blood, and sleep (HLBS) diseases?

Submitted by (@nhlbiforumadministrator)

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Details on the impact of addressing this CQ or CC :

Results of such research should reveal physiological mechanisms of resilience that could be used to develop interventions that would prevent or cure a variety of heart, lung, blood, and sleep diseases.

Feasibility and challenges of addressing this CQ or CC :

Advances in omics, clinical testing

, accumulation of large sets of clinical data and samples

, big data tools

, and increased interest from public (normal volunteers) and patients to participate in large scientific experiments make it feasible.

For instance, these may be healthy people carrying genetic mutations strongly associated with HLBS diseases (or causing rare/familial genetic diseases – these might easier to focus on first), but also people who are not hypertensive, hypercholesterolemic, or diabetic in spite of consistently making bad dietary choices, people who did not develop lung conditions in spite of high pollutant exposure, or are otherwise “protected” from other heart, lung, blood and sleep diseases. This reasoning is not very different from that used to identify ApoA Milano, or even PCSK9 or the “longevity genes”. Such information should reveal physiological mechanisms that could be leveraged to develop interventions to prevent or cure HLBS diseases.

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

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Goal 2: Reduce Human Disease

Biomarkers of Pulmonary Hypertension

What are informative and clinically relevant biomarkers of pulmonary hypertension (PH)?

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This research emphasis would help identify novel pulmonary hypertension biomarkers of disease risk and progression that can be used for early detection or as outcome measures in prevention trials or treatment of PH, which is a disease currently still not curable with high mortality rate.

Feasibility and challenges of addressing this CQ or CC :

NHLBI Division of Lung Diseases just launched the multi-center PVDOMICS research program last September that will enroll ~1,500 patients in the next 5 years for deep phenotyping PH. PVDOMICS will provide a perfect foundation and platform for this proposed featured study about informative and clinically relevant biomarkers of PH, and make answering this proposed question more feasible in the next 5-10 years.

Although significant advances in the treatment of pulmonary hypertension have been made in the past two decades, currently pulmonary hypertension remains a devastating disease without many clinically relevant and specific biomarkers available. Novel new informative and clinically relevant pulmonary hypertension biomarkers would greatly help advance the subtype-specific early diagnosis and precision treatment of this disease that could potentially decrease the mortality of PH.

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

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Goal 2: Reduce Human Disease

Identification and validation of surrogate endpoints for long-term morbidity in Sickle Cell Disease

Research in sickle cell disease (SCD) has mostly focused on preventing or treating acute medical events, such as vaso-occlusive pain, acute chest syndrome, and, in pediatric patients, acute strokes. Chronic SCD complications such as chronic kidney disease or pulmonary hypertension, develop over decades, thus are poor choices for clinical trial endpoints. There is a great need to develop surrogate endpoints that predict ...more »

Submitted by (@hulbertm)

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Longitudinal cohorts of SCD patients, spanning childhood and adulthood, with biobanking DNA, plasma, and serum, and standardized clinical and imaging assessments will allow identification predictors of negative clinical outcomes. An NHLBI-funded national SCD clinical registry with biobanking will be necessary to validate any surrogate endpoints.

Name of idea submitter and other team members who worked on this idea : Monica Hulbert

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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

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)

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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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