Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

Relevance of cardiovascular disease associated with autoimmunity research

NIH estimates up to 23.5 million Americans suffer from autoimmune disease (AD) and up to 24 million from heart diseases. As a result, NIH and AHA estimates the annual direct health care costs for AD to be in the range of $100 billion and $200 billion for heart and stroke diseases. Yet this area of research has been neglected and underfunded. The proposition is for NHLBI to partner with other NIH institutes dealing with ...more »

Submitted by (@mboutjdir)

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

Details on the impact of addressing this CQ or CC :

Reduce the impact of autoimmune diseases on the heart and vascular system.

Feasibility and challenges of addressing this CQ or CC :

Generate RFAs dedicated to the field of autoimmune associated cardiovascular diseases.

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

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Goal 2: Reduce Human Disease

Life-Course Approach to Science

We encourage the NHLBI to include research focused on children as a priority in their strategic vision. We encourage them to consider the implications of a life-course approach, where childhood presents a unique opportunity to set the trajectory for health risk as an adult. This also implies that interventions targeting children may have the greatest impact on the population as a whole in the long term.

Submitted by (@nhlbiforumadministrator)

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 : American Society of Pediatric Nephrology (ASPN)

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Goal 2: Reduce Human Disease

Clinical Trials in Pediatric Sleep Disorders

Effectiveness of medications for cataplexy in children.

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 :

Pediatric sleep experts agree that there appears to be a mini-epidemic of narcolepsy in children currently, characterized by acute onset of disease with severe symptoms and difficult to control cataplexy, in very young children. No drugs are approved for treatment of cataplexy in children, and drugs typically used in adults are not FDA-approved for use in children. A multicenter trial would be needed in order to accumulate sufficient cases for a randomized controlled trial.

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

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Goal 2: Reduce Human Disease

Iron Metabolism in thalassemia syndromes, and other rare and common anemias

Thanks to elegant work since the 1990s, many details of the role of iron regulation and metabolism have been elucidated. Recent efforts in academic and pharmaceutical laboratories aim to translate these discoveries into therapies that may alleviate anemia in iron-refractory states (including anemia of inflammation and congenital disorders), and may have important therapeutic effects in non-transfusion-dependent thalassemia, ...more »

Submitted by (@gcioffi)

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

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55 up votes
15 down votes
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Goal 2: Reduce Human Disease

Funding for Hemostasis & Thrombosis Research

Thrombotic disorders, a result of the inappropriate activation of the hemostatic system, remain major causes of morbidity and mortality in the United States. Cancer, cardiovascular disease, trauma, and many of the other causes of death in the U.S. frequently culminate in a fatal thrombotic event. Notably, thromboembolic disease affects 500,000 people annually and leads to 100,000 deaths in the United States alone. Current ...more »

Submitted by (@abrams)

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

Details on the impact of addressing this CQ or CC :

Following vascular injury, regulated hemostasis is both rapid and appropriate, thereby quenching hemorrhage. Nonetheless, it is clear that both hemostasis and thrombosis are dynamic processes, characterized by the sequential accumulation and removal of newly activated platelets and fibrin at sites of vascular damage. Over the past 10 years, research in hemostasis and thrombosis has been transformed, broadened and infused with new energy driven by novel technologies and ideas. NHLBI-funded science has revealed new pathways for platelet activation, for platelets in physiologic events outside of the hemostatic response, for coagulation proteases in modulating inflammation and tissue repair after injury, and new mechanistic insights into coagulation. Many tacitly accepted ideas in the field are yielding to these new mechanistic insights that suggest new ways to modulate coagulation leading to therapeutic gain. The NHLBI should continue its strong support of research to understand these mechanisms and should continue to bolster the training that will equip the next generation of scientists and physician-scientists to translate discovery from the lab to the bedside.

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Goal 2: Reduce Human Disease

Cardiac Defibrillator Therapy Management in the Elderly

Older patients have been largely under represented in the landmark clinical trials that have established the beneficial effects of ICD therapy on survival. With older age, comorbidities increase leading to a higher incidence of non-cardiac mortality. This is supported by very well documented decrease in the incidence of appropriate defibrillator shocks. Based on the above, it is important to know whether defibrillator ...more »

Submitted by (@sabas0)

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

Details on the impact of addressing this CQ or CC :

Given the increase in the proportion of older patients in the US, addressing these important questions regarding the value of defibrillator therapy in this stratum of the population is critical to:

1) Avoid unnecessary surgeries with its complications (short term and long term)

2) Reduce the cost of health care, primarily in a Medicare population

Feasibility and challenges of addressing this CQ or CC :

A large multi-center non-inferiority trial of CRT-P vs. CRT-D ( and at alater stage of ICD vs. No ICD) in the elderly is needed to answer these questions. These trials are feasible but require comittment and resources.

Name of idea submitter and other team members who worked on this idea : Samir Saba

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4 net votes
16 up votes
12 down votes
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Goal 2: Reduce Human Disease

Interstitial Lung Disease

Does the treatment of gastroesophageal reflux disease improve outcomes in patients with IPF?

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 are preliminary data to support the treatment of gastroesophageal

reflux (GER), in particular surgical treatment with laparoscopic fundoplication, as a disease modifying therapy for IPF. Many providers are prescribing medication or recommending surgery for GER in patients with IPF. Full disclosure, this compelling question submitter has submitted a UM1 grant application to study this question in a phase II clinical trial that is currently pending review.

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

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Goal 2: Reduce Human Disease

Benefits of intraosseous access on outcomes from OHCA

Vascular access is a challenge in the setting of out-of-hospital cardiac arrest (OHCA). The failure of medications to impact outcomes may be in part related to the delay in drug delivery from the IV route. EMS systems have adopted intraosseous (IO) access but it is not clear if these are affecting outcome and there has been no large RCT. The current IO access devices are expensive and use different routes (sternal, tibia, ...more »

Submitted by (@dayam0)

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

Details on the impact of addressing this CQ or CC :

At over a 100 dollars per device, the costs of using an IO line for estimated 300K arrests in the United States is 30 million dollars. We need to know if this route works and the optimal location for placement.

Feasibility and challenges of addressing this CQ or CC :

Funding, willingness to study this in a well designed clinical trial

Name of idea submitter and other team members who worked on this idea : Mohamud Daya

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Goal 2: Reduce Human Disease

The role of Extracorporeal Photopheresis (ECP) in the prevention and treatment of rejection of heart and lung transplants

According to the ISHLT, more than 4,000 patients undergo a heart transplant each year, and almost 4,000 receive single or double lung transplants. Their prognosis depends heavily on the avoidance of rejection, which claims the majority of their lives. For heart transplant recipients, the median survival is 11 years, while for lung transplant recipients, it is approximately 5 years. The current most common anti-rejection ...more »

Submitted by (@mmarques)

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

Details on the impact of addressing this CQ or CC :

Patients who are fortunate to receive a matched heart or one or two lungs transplants are at high risk of dying from rejection early and even years after the operation. Thus, they are given cocktails of highly toxic anti-rejection drugs for the rest of their lives. Unfortunately, despite compliance with their drug regimens, many patients still suffer repeated episodes of rejection that may be fatal. In addition, they develop serious side-effects such as diabetes, infections, malignancies, renal failure, etc. ECP has been shown efficacy in preventing and treating cardiac transplant rejection, but the data are limited. ECP appears to benefit such patients by causing an increase in the number of circulating T regulatory (“T regs”) cells. T regs are known to mediate immune tolerance, the ultimate goal of a long-term successful transplant. The role of ECP in lung transplantation is mostly unknown. Very preliminary data have been gathered from retrospective studies. We suspect that patients with early bronchiolitis obliterans syndrome (“BOS”) will benefit from ECP prior to developing irreversible pulmonary damage. In both types of transplants, however, it is unknown when should ECP be started, how often it should be employed (treatment schedule), and for how long. Finally, the most compelling argument to use ECP in heart and lung transplantation is its excellent side-effect profile. Furthermore, ECP may allow a decrease in the number of drugs needed to prevent rejection.

Feasibility and challenges of addressing this CQ or CC :

Many patients with heart and lung transplants develop severe and often fatal rejection despite the current drug options to prevent rejection. ECP could be added to their treatment regimens and decrease side-effects, improving long-term survival.

 

ECP is generally well tolerated and complications are extremely infrequent.

 

There is a great potential for multi-disciplinary collaboration between Apheresis Medicine, Cardiology, and Pulmonary specialists.

 

It is conceivable that manufacturers of ECP instruments will be interested in contributing to the design and support of these studies.

 

Such studies could shed light in the mechanism of action of ECP in heart and lung transplantation.

 

There is a need to develop standardized treatment regimens based on well designed clinical trials to further optimize the use of ECP. Development and standardization of measurable outcomes is critical for the success of clinical studies in apheresis in general, and ECP in particular.

 

Challenges:

1. Limited number of institutions providing ECP treatment.

2. Cost of ECP procedures.

3. Small number of animal models available for apheresis research. Thus, limited studies of ECP mechanism(s) of action. However, understanding pathological mechanisms and their relationship to response to apheresis is critical for optimization and advancement of patient care in heart and lung transplantation.

4. Lack of infra-structure for apheresis research.

Name of idea submitter and other team members who worked on this idea : Marisa Marques on behalf of ASFA

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102 up votes
22 down votes
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Goal 2: Reduce Human Disease

Randomized trial of low carbohydrate high fat dietary pattern

There is a need for a large, simple, hard outcome trial of dietary advice to measure the effects of lowering simple carbohydrates versus lowering unhealthy fats. The main challenge will be to overcome bias favoring the more conventional dietary approach.

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 :

Substantial numbers are moving towards low carbohydrate/high fat diets to the extent that since 2000 the macronutrient composition of the US diet has changed towards lower carbohydrate and higher fat intakes; however, CV mortality rates continue to decline. The outcome of the trial will help frame future guidelines for healthy diets.

Feasibility and challenges of addressing this CQ or CC :

Yes, since computer or smartphone based intervention materials and passive outcome collections (CMS, NDI, health care organizations) are increasingly being utilized.

Low carbohydrate high fat (LCHF) diets first popularized for weight reduction are increasingly being promoted to prevent diabetes and cardiovascular disease. All trials to date have been small and short term. Compared to more traditional high carbohydrate low fat diets, LCHF diets may be somewhat more beneficial for weight control, glucose homeostasis, and dyslipidemia, but less beneficial for LDL reduction.

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

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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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6 down votes
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