Goal 3: Advance Translational Research

Developing Curative Approaches to Cardiovascular Disease rather than Chronic Magement

Most Pharmacological interventions in cardiovascular diseases tend to address to be used in palliative manner and chronically. There is urgent need for treatments that are curative. This goes to identifying molecular drivers of the diseases and targeting them to correct the underlying pathophysiology rather than symptom suppression.

Submitted by (@john.buolamwini)

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

Details on the impact of addressing this CQ or CC :

True conquer of cardiovascular diseases, and reversing the chronic nature of these diseases.

Feasibility and challenges of addressing this CQ or CC :

Possible but challenging requiring a highly multidisciplinary approach and collaboration.

Name of idea submitter and other team members who worked on this idea : John. K. Buolamwini

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Goal 2: Reduce Human Disease

Interstitial Lung Disease

Is FVC a valid surrogate for mortality in patients with idiopathic pulmonary 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 :

This question is central to all future clinical research in the field and MUST be answered in the context of an interventional clinical trial. Longitudinal cohort studies correlating FVC change with survival are insufficient. The intervention that would make the most sense to test currently is pirfenidone. It is approved for use in many countries and many experts (including the submitter of this compelling question) believe it is likely effective. A mortality-driven clinical trial of pirfenidone vs. placebo would address this question directly, as well as determine the true impact of pirfenidone on clinically meaningful endpoints.

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

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Goal 2: Reduce Human Disease

Bicuspid aortic valve is not a “one size fits all” condition. Variations exist within families and the population generally.

Clinical disease manifestations in individuals and families where bicuspid aortic valve is present may best be described as a spectrum, with considerable variability in presentation. Patients and families would benefit from an individualized approach, which does include familial medical history, but couples that information with current best understanding of BAV, considering both variations and risks.

Submitted by (@bavtad)

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

Details on the impact of addressing this CQ or CC :

This variability of aortic disease expression (aorta and valve), while amenable to trend analysis, does not lend itself well to a “one size fits all” approach to care. Some individuals and families display other characteristics in their body suggestive of additional complexity. Brain aneurysms are also mentioned in the literature in the presence of BAV.

 

Braverman’s article, “Guidelines for management of bicuspid aortic valve aneurysms: what’s the clinician to do?” highlights the variation in guidelines regarding elective aneurysm surgery in BAV patients, discusses why “one size fits all” is not appropriate, and supports the importance of an individualized approach.

 

Individuals and families face some degree of distress, most particularly those stricken by the serious injury or death of a loved one, and anguish over their future. Some, told surgery was many years away, or that they were fixed for life, have lived to discover those well intentioned words were far from accurate. Others, diagnosed with BAV, have lost their lives.

 

Individualized care, rather than general statements meant to reassure a large and varied population, is important in order to live confidently and proactively continue with follow up. An approach to care that does not use “always” and “never” thinking, and that avoids predictions interpreted as fact, will do a great deal to instill confidence and engagement in BAV individuals and families, who make life decisions based on what they are told.

Feasibility and challenges of addressing this CQ or CC :

This is an intelligent population that is well suited to grasp the issues and participate in decision making. Patients and families desire to be told accurately what is and is not known, to be assessed individually, and to have greater understanding of the implications for blood relatives. They desire to have an informed voice in their treatment decisions, including the timing of elective surgery based on surgical risk versus the risk of living with the disease

Name of idea submitter and other team members who worked on this idea : Arlys Velebir, Bicuspid Aortic Foundation

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Goal 2: Reduce Human Disease

Reversing pulmonary fibrosis/interstitial lung disease

Can a multipronged approach to reversing/repairing scar tissue in pulmonary fibrosis be deployed as soon as possible?

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 :

Despite high mortality rates and frustrating disease management marked by exacerbations and uncertainty including chronic oxygen supplementation, pulmonary fibrosis patients lack evidence-based treatments to reverse and repair the fibrotic process. These patients comprise a comparatively smaller proportion of lung disease patients such as chronic obstructive pulmonary disease and asthma and owing to their smaller number, have not been studied in large-scale randomized controlled trials. Treatments that need to be critically studied include regenerating lung tissue through stem cell treatment, artificial/ mechanical lung (augmentation) technology, and new drugs to directly reverse scar tissue, not simply to arrest the fibrotic process as with the two new available drugs for IPF patients.

Feasibility and challenges of addressing this CQ or CC :

Challenges are smaller numbers of available patients available for clinical trials compared with other lung conditions such as COPD and asthma and lack of research funding. Also the etiology of the disease is multifactorial and the categories of fibrosis difficult to accurately diagnose and understand.

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

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Goal 2: Reduce Human Disease

Prevention of rheumatic heart disease

Global health system outcomes studies are needed to identify impediments to successful primary and secondary prevention of rheumatic heart disease.

Other approaches, such as development of a vaccine for group A streptococcus and delaying disease progression once valve damage is present, could also be explored.

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 :

On a global basis, rheumatic fever remains the primary cause of valvular heart disease. Although the prevalence is much less in developed countries, pockets remain among groups with less access to healthcare.

Feasibility and challenges of addressing this CQ or CC :

Global health outcome studies could be performed over the next 5-10 years. The use of recently-developed point-of-care diagnostic tests could support these studies.

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

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7 up votes
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Goal 2: Reduce Human Disease

Hypoxia, acute chest syndrome and sickle cell disease

What markers in sickle cell disease can predict hypoxia after acute chest syndrome or pneumonia?

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 :

Understanding that sickle cell disease has a character of depriving oxygen, is there any predicators that can tell if a child will have hypoxia after experiencing acute chest syndrome or pneumonia.

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

Rare Disease Registry

NHLBI should establish a rare disease registry.

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 :

While we agree that some registries of the past had limited utility, state of the art registries of today are different. Registries of rare diseases need support. If left to the foundations and CTSA awards, many of these registries can capture clinical and physiologic data, but struggle to fund radiological repositories and biorepositories that can capture genomic data. When I look at the landscape of those lung diseases that have nothing, the list is very long. “Idiopathic” Fibrotic NSIP, acute interstitial pneumonia, rheumatoid interstitial lung disease, acute and chronic eosinophilic pneumonia, cryptogenic organizing pneumonia, aspiration associated lung disease, radiation pneumonitis, eosinophilic bronchitis, mycobacterium avium complex, hepatopulmonary syndrome, and Churg-Strauss vasculitis while individually very rare make up 3-5% of all lung diseases. If we put 3-5% of the Lung Division budget into these diseases, the impact would be huge. Meaningful impact would include a mentorship program for patient foundations, CTSA directed collaborative biorepositories, a Rare Lung Disease Centers of Excellence program (possibly modeled after the NIH program in diseases of unknown cause), and a conference structure that is funded as a core component of the Lung Division budget. Most important is to assure that linkage to the patients who participate is assured after the collection of the biosamples is obtained.

Feasibility and challenges of addressing this CQ or CC :

To the extent that you might influence NIH politics, one important impediment to this science is the inability of the NIH to keep and sustain patient identifiers. If the IRS can do it, why can’t NIH? Although I realize that this last part is out of your personal control, an internal registry mechanism sponsored by the NHLBI would transform the landscape of the institute for rare disease science. It would solve the problems associated with internal registries being unable to join with other international endeavors (NIH LAM Registry for example).

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

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Goal 2: Reduce Human Disease

Should clinical primary prevention of ASCVD be guided by subclincal disease or estimated risk?

Current approaches to guiding use of clinical primary prevention interventions, e.g., statins and aspirin, are based on treating patients who exceed a specific risk threshold. The performance of risk estimation is good, but not outstanding, and results from clinical and population studies continue to support the value of new biomarkers. Given the widespread use of preventive therapies, the lack of untreated cohorts is ...more »

Submitted by (@david.goff)

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 size of the US and global population qualifying for treatment with a statin or aspirin for primary prevention of ASCVD is immense. Given the performance of risk estimation, even if risk estimation were universally implemented, patients would be misclassified with the consequence of being under or over treated. If treatment based on presence of subclinical disease is more cost-effective, the benefits of preventive therapies can be enjoyed by larger proportions of our population and more ASCVD can be averted. Given the ionizing radiation, albeit low intensity, associated with CT scanning, it is incumbent on the biomedical research community to document the advantages, if any, of a subclinical disease guided approach to provision of clinical primary prevention services for ASCVD.

Feasibility and challenges of addressing this CQ or CC :

Many people will be concordant for the two methods of guiding provision of therapy, about 65% of middle aged and older adults. That is, many people will be high risk and have subclinical disease and many people will below risk and not have subclinical disease. It is only the discordant people, i.e., high risk people without subclinical disease and low risk people with subclinical disease, who will be informative study participants. Hence, many people will need to be screened to identify the roughly 35% who are discordant, and would be treated differently by the two approaches.

 

People may be unwilling to accept randomization once they know the information about their estimated risk and presence or absence of subclinical disease. If a low participation rate among eligible persons is observed, an even larger population of screenees would be needed.

 

A vanguard phase could provide information about these potential challenges.

Name of idea submitter and other team members who worked on this idea : David Goff, Donald Lloyd-Jones, Phil Greeland.....

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6 up votes
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Goal 2: Reduce Human Disease

Defining the developmental abnormalities leading to birth defects

Can we define the developmental abnormalities leading to birth defects and extrapolate that knowledge to define strategies for regeneration?

 

How can we recognize initiation of disease earlier?

Submitted by (@nhlbiforumadministrator)

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 : NHLBI Staff

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8 up votes
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Goal 2: Reduce Human Disease

Interstitial Lung Disease

Do the non-pharmacological interventions of pulmonary rehabilitation and supplemental oxygen for exertional hypoxemia improve quality of life and functional status in patients with chronic fibrotic ILD?

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 :

There is good evidence from small controlled trials that pulmonary rehabilitation improves walk distance and shortness of breath in patients with chronic ILD. Both pulmonary rehabilitation and supplemental oxygen are commonly recommended to these patients at great cost. A randomized clinical trial using factorial design could address the impact of these two therapies individually as well as together on clinically meaningful outcomes.

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

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Goal 2: Reduce Human Disease

Enhanced Pain Research in Sickle Cell Disease

There is a need for more enhanced pain research in order to help improve sickle cell disease patient outcomes and quality of life.

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

Details on the impact of addressing this CQ or CC :

Pain is the most common clinical manifestation of sickle cell disease (SCD) and accounts for a large proportion of emergency department visits and hospitalizations. Due to its impact on the patients’ quality of life, there is a need for more basic and clinical research studies focused on understanding the mechanisms of different pain syndromes as well as the role of neurotransmitters and inflammation in acute and chronic SCD pain. Also, comparative effectiveness studies in the management of chronic pain will be crucial in helping to improve the patients’ overall quality of life.

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 2: Reduce Human Disease

Inflammation and outcomes following pediatric cardiac operations

What is the contribution of the inflammatory response to postoperative recovery following pediatric cardiac operations and what strategies can improve outcomes?

Submitted by (@grahamem)

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

Details on the impact of addressing this CQ or CC :

Congenital heart disease is the most common cause of birth defects, with about 40,000 new cases born per year in the US. Affected individuals experience morbidity and mortality that generate health and economic consequences significantly out of proportion to their numbers. An estimated 10,000 of these patients will undergo cardiac surgery involving cardiopulmonary bypass (CPB). Furthermore, it is estimated that over 300,000 children in the US under age 21 have congenital cardiovascular disease and that 38% of these children will have had one or more surgical procedures. The use of CPB in neonates in particular has increased steadily over the past two decades. Further, neonates are generally sicker and consume more resources, including postoperative mechanical ventilation, ICU stay and hospital stay. Consequently, reducing the deleterious effects of CPB will have the largest impact in this group of patients.

Feasibility and challenges of addressing this CQ or CC :

Research has begun to assess the inflammatory response to cardiopulmonary bypass in pediatrics. However, the magnitude and importance of its contribution to complicating postoperative recovery remains elusive. Clinical trials have begun to assess the efficacy of generalized anti-inflammatory therapies, typically steroids, with conflicting results. No therapy has been recognized as the standard of care. It’s critical that we improve our understanding of the molecular and cellular mechanisms of this inflammatory response and resulting derangements in vascular permeability and develop novel treatment strategies for infants and children undergoing cardiopulmonary bypass.

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