Goal 3: Advance Translational Research

Arrhythmia Therapies Based on Understanding Mechanisms

There is a need to translate these new insights of genetic, molecular, cellular, and tissue arrhythmia mechanisms into the development of novel, safe, and new therapeutic interventions for the treatment and prevention of cardiac arrhythmias.

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 :

Reduced socioeconomic burden of cardiac arrhythmias. Development of new technologies and recognition of new arrhythmia mechanisms.

Feasibility and challenges of addressing this CQ or CC :

Several studies have already recognized the unexpected antiarrhythmic effects of some therapies intended for other cardiovascular disease. For example statins, aldosterone blockers, and possibly some essential fatty acids may reduce arrhythmia burden in patients receiving these interventions. Clinical trials should be developed to demonstrate the efficacy of these interventions, and arrhythmia endpoints, including those for atrial fibrillation and sudden cardiac death, should be incorporated into other large clinical trials. Research into novel antiarrhythmic might focus on (a) drug development; (b) cell/gene-based therapy and tissue engineering; and (c) improvements in development and use of devices and ablation to prevent or inhibit arrhythmic electrical activity. Continued research might also focus on targeting of upstream regulatory cascades of ion channel expression and function. Continued antiarrhythmic strategies might include the exploration of novel delivery systems (e.g., utilizing advances in nanotechnology and microelectronics), biological pacemakers, AV node repair/bypass, and treatment and/or reversal of disease-induced myocardial remodeling and tachyarrhythmias. Evaluation of new therapies should include a cost analysis. Studies in both children and adults with congenital heart are needed. New interventions might include new pharmacologic approaches as well as advances in electrophysiologic imaging and improved approaches to ablation.

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

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51 net votes
86 up votes
35 down votes
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Goal 2: Reduce Human Disease

Fibrosis Across Organs: Bringing Together Investigators of Fibrosis of the Heart, Lungs and Bone Marrow

Fibrosis can affect essentially any tissue or organ, including the heart, lungs and bone marrow. Effective anti-fibrotic therapy has long been elusive, and transplantation has been the only therapy capable of restoring patient function as fibrotic diseases progress to organ failure. Although these diseases present clinically with organ-specific manifestations, they are now thought to share many common pathogenetic mechanisms. ...more »

Submitted by (@amtager)

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

Details on the impact of addressing this CQ or CC :

In the aggregate, diseases characterized by fibrosis have been estimated to account for up to 45% of developed world deaths. Fibrotic diseases addressed by the NHLBI include heart failure with preserved ejection fraction (HFpEF), idiopathic pulmonary fibrosis (IPF), and myelofibrosis (MF), among many others. Each fibrotic disease represents an area of great unmet clinical need, as patients suffer and die with no or limited effective disease-modifying therapies. The impact of developing effective therapies for each of these diseases individually would be great; the impact of developing therapies effective for the entire class of fibrotic diseases across organs would truly be enormous. The clinical burden of HFpEF is staggering – more than 650,000 new patients are diagnosed with heart failure in the US each year, half with diastolic dysfunction. Although not as prevalent, IPF and MF are particularly lethal. IPF has a median survival of approximately three years. MF is arguably the most aggressive of the myeloproliferative disorders and is associated with significantly shortened survival. Although agents such as spironolactone have been unable to treat fibrosis in HFpEF as yet, two anti-fibrotic drugs, pirfenidone and nintedanib, have now been shown to slow progression of IPF, and the oral JAK1/2 inhibitor ruxolitinib has been shown to improve MF survival. These early successes underscore the great impact that developing effective anti-fibrotic therapies will have.

Feasibility and challenges of addressing this CQ or CC :

This challenge could be addressed by funding research efforts to identify and therapeutically target fundamental pathogenetic mechanisms shared by fibrotic diseases across organs. Although fibrotic diseases present clinically with organ-specific manifestations, there has been a growing appreciation of that these diseases share many aspects of their pathogenesis. Fibrosis In many of these diseases results from recurrent or non-resolving epithelial or endothelial injury, followed by over-exuberant or aberrant mesenchymal cell responses. Across all organs, these processes result in the pathologic accumulation of fibroblasts and extracellular matrix, with distortion of organ architecture and loss of organ function. Core pathways leading to epithelial and endothelial cell injury and senescence, to fibroblast accumulation and persistence, and to altered matrix biochemical and biomechanical properties, are now being identified. Therapeutics developed to target these core pathways could have broad clinical applicability. Funding initiatives aimed at better the characterization of core fibrotic pathways already identified, the identification of new core fibrotic pathways, and the development of therapies to target core fibrotic pathways, could allow the NHLBI to simultaneously and cost-effectively address the great unmet needs of the large patients with any of the many devastating fibrotic diseases that affect the heart, lungs and bone marrow.

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

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16 net votes
20 up votes
4 down votes
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Goal 3: Advance Translational Research

Surveillance systems to prevent in-hospital cardiac arrest

Can surveillance systems be developed to prevent in-hospital cardiac arrest outside the ICU?

Submitted by (@rebecca.lehotzky)

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 : AHA Staff & Volunteers

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-1 net votes
2 up votes
3 down votes
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Goal 2: Reduce Human Disease

Reducing Variability in Outcomes from Out of Hospital Cardiac Arrest

Out of hospital cardiac arrest remains a major cause of mortality in the United States and there is a large variability in survival within communities. We need to better understand the reasons for this variability which include patient, event, EMS system and care processes and work as a nation to reduce the variability but adopting best practices and actively addressing the barriers to change which can be social, cultural, ...more »

Submitted by (@dayam0)

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

Details on the impact of addressing this CQ or CC :

If we could reduce variability, we would save more lives and also enhance the chain of survival in our communities

Feasibility and challenges of addressing this CQ or CC :

will require that we connect multiple parts of the community including the population at risk, public health services and the health care system which is not always easy in silo systems or fragmented health care systems

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

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0 net votes
2 up votes
2 down votes
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Goal 2: Reduce Human Disease

Understanding Cardiothoracic Surgery in Elderly Populations

There is a vital need for evidence-based clinical evaluation tools to assess operative risk and post-operative recovery in the elderly, including biomarkers of physiologic age and a simple/reliable clinical evaluation scheme to determine frailty as a risk factor for poor surgical outcomes.

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 :

Development of tools to assess operative risk and post-operative recover in the elderly would improve surgical outcomes in this growing patient population.

Feasibility and challenges of addressing this CQ or CC :

This at risk population is growing rapidly.

Older patients represent an important, different, and under-studied subgroup of those undergoing cardiothoracic surgery according to the Joint NHLBI-AATS Working Group (http://aats.org/CME/2011-AATS-NHLBI-Symposium.cgi). Due to the aging of the US population and the increased severity of coronary and valve disease in older individuals, the use of cardiothoracic surgery in older patients in relative terms is growing rapidly. Between 1990 and 2008, the percentage of those aged 80 years or older has gone from 8% to 16% of total for bypass surgery and 14% to 30% of total for valve surgery.

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

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39 net votes
56 up votes
17 down votes
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Goal 2: Reduce Human Disease

Improving the Detection and Treatment of Cardiac Sarcoidosis

Sarcoidosis afflicts young adults, particularly African Americans and females, and often causes chronic disability or death. Cardiac sarcoidosis (CS) was once considered to be a rare disease manifestation; however, with the development of improved diagnostic testing procedures, such as MRI and PET scans, CS is now known to afflict up to 40% of sarcoidosis patients and is recognized as a major cause of death. The current ...more »

Submitted by (@elliott.crouser)

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

Details on the impact of addressing this CQ or CC :

Improved detection of cardiac sarcoidosis (CS) is necessary to screen for CS in the sarcoidosis population and to identify those patients requiring further testing and personalized treatments. The optimal CS detection tool would be able to quantify the burden of cardiac disease, and would provide insight into disease activity (e.g., acutely active/reversible versus inactive/irreversible cardiac disease). Once validated, the CS detection tool would be used to risk stratify patients for the purpose of initial and subsequent treatments.

Feasibility and challenges of addressing this CQ or CC :

Current and evolving imaging techniques have rapidly improved the detection of sarcoidosis, so these technologies are feasible. However, it is unclear how to interpret the results of these novel imaging techniques in the context of treating humans with sarcoidosis. A number of challenges remain (e.g., how to distinguish active from inactive cardiac sarcoidosis, and how to objectively assess disease severity as relates to the risk of serious adverse cardiac events). A strength of this project being that this field is poised for clinical investigations designed to improve cardiac sarcoidosis detection and treatment using existing technologies.

Name of idea submitter and other team members who worked on this idea : Elliott Crouser, Subha Raman, Nabeel Hamzeh, Lisa Maier

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-4 net votes
2 up votes
6 down votes
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Goal 2: Reduce Human Disease

Developing Standards of Care for adult muscular dystrophy (FSHD, DM) patients affected by hypercarbic respiratory insufficiency

There is an unmet need for the NHLBI to foster basic, preclinical and clinical research on the pulmonary consequences of respiratory insufficiency, and specifically with hypercarbic (high CO2) respiratory insufficiency, in facioscapulohumeral muscular dystrophy (FSHD) and other adult muscular dystrophies. The adult muscular dystrophies have received insufficient attention, both from research and clinical practice perspectives. ...more »

Submitted by (@daniel.perez)

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

Feasibility and challenges of addressing this CQ or CC :

As with cardiomyopathy and arrhythmia, currently little data is available as to how to best measure/monitor, and when and how to intervene in, the respiratory complications of the adult muscular dystrophies (FSHD, DM, LGMD) using respiratory therapy, non-invasive ventilation (bi-Pap, Trilogy) or ventilation. The absence of home-based sleep studies and technologies to easily assess hypercapnia are identified as a significant gap in knowledge. Additionally, since the cardiac and pulmonary hypercarbic respiratory insufficiency complications are inextricably linked, studies of the interrelationship between cardiac and pulmonary consequences of the muscular dystrophies (congestive heart failure, pulmonary hypertension) are needed, and interdisciplinary teams of researchers may be best equipped to conduct them.

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

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-11 net votes
4 up votes
15 down votes
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Goal 2: Reduce Human Disease

What causes variation in severity of skeletal muscle, lung, pulmonary and heart system symptoms in FSHD muscular dystrophy

Loss of diaphragm function and impaired respiration is a leading driver of morbidity and mortality in the adult muscular dystrophies such as facioscapulohumeral muscular dystrophy, and therefore requires additional study

Submitted by (@daniel.perez)

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

Details on the impact of addressing this CQ or CC :

Muscular dystrophies comprise a heterogeneous group of genetic diseases often characterized by multi-systemic effects and distinct patterns of muscle involvement. While a characteristic pattern of muscle weakness has traditionally been used to define the different subtypes of muscular dystrophy, the cause for the regional distribution of muscle weakness, often with sparing of specific muscle groups, has largely remained unresolved. Moreover, many muscular dystrophies such as the most common form facioscapulohumeral muscular dystrophy, show noticeable variation in disease onset and progression, both between as well as within families. Involvement of the diaphragm and muscles of respiration often proceeds at a rate different from other striated muscles. Loss of diaphragm function and impaired respiration is a leading driver of morbidity and mortality in the muscle diseases, and therefore requires additional study in adult muscular dystrophy.

Feasibility and challenges of addressing this CQ or CC :

Studies in mice and humans have provided some evidence for genetic modifiers of disease onset, presentation and progression, but a comprehensive explanation for the observed differences in skeletal muscle, lung, pulmonary and heart system involvement and disease progression is currently lacking. Disease penetrance may be affected by genetic background or gene-environment interactions. Future studies on the identification and validation of such factors, both genetic and non-genetic (off target effects of drugs, diet, exercise), may provide insight into strategies that delay disease onset, prevent off-target effects of drugs and improve quality of life.

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

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-10 net votes
6 up votes
16 down votes
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Goal 2: Reduce Human Disease

Problem of sudden cardiac death

Among major causes of cardiac mortality cardiac arrest stands as a cause of death that rivals all other causes in terms of frequency. There has been at best only modest improvement in resuscitation over recent years. No wonder with so little NHLBI funding going into this cause compared to acute MI and heart failure. Hopefully the IOM report on cardiac resuscition will be a call to action that will highlight these NIHBI ...more »

Submitted by (@mlw500)

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

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0 net votes
4 up votes
4 down votes
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Goal 2: Reduce Human Disease

Molecular basis for cardiac and neurological damage after cardiac arrest

What is the sequence and time course of molecular events that cause irreversible cardiovascular and neurologic dysfunction during and after cardiac arrest?

Submitted by (@rebecca.lehotzky)

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 : AHA Staff & Volunteers

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-4 net votes
1 up votes
5 down votes
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Goal 2: Reduce Human Disease

How should platelet (PLT) transfusions be used to treat active bleeding?

Multiple randomized controlled trials have been performed to evaluate the use of prophylactic PLT transfusions in non-bleeding, thrombocytopenic hematology-oncology patients. However no high-quality data exist to guide PLT transfusions in actively bleeding patients inclduing pediatric and adult medical and surgical patients. After hematology-oncology patients, cardiac surgery patients are the next largest group of PLT ...more »

Submitted by (@bldbuddy)

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

Details on the impact of addressing this CQ or CC :

PLT count is almost always the only laboratory result considered in deciding to transfuse PLTs. But PLT counts provide no information about PLT hemostatic function and its contribution to bleeding. A variety of in vitro coagulation tests have been developed: viscoelastography, whole blood PLT aggregometry, etc. But while testing-based transfusion algorithms may reduce blood product utilization, it has not been established that any in vitro test can either predict or help reduce bleeding. There is a gold standard method to assess clinical efficacy of transfused PLTs: incidence of grade 2 or higher bleeding in clinical trials of thrombocytopenic hematology-oncology patients receiving prophylactic PLT transfusions. No analogous gold standard of PLT hemostatic efficacy exists for therapeutic PLT transfusions to treat active bleeding. There is a pressing need to develop such a standard. Establishing reliable methods for evaluating the effects of PLT transfusion in actively bleeding patients will improve our understanding of how different factors (storage conditions, pathogen reduction etc.) affect the functional performance of PLTs.

Feasibility and challenges of addressing this CQ or CC :

PLT transfusions are administered routinely to support bleeding pediatric and adult medical and surgical patients. Opportunities to conduct clinical trials in various settings (cardiac surgery, neurosurgery, orthopedic surgery, trauma, etc.) are widely available. PLT transfusion is commonly used to support bleeding patients receiving perioperative supportive therapies such as extracorporeal membrane oxygenation (ECMO). These clinical situations represent critical opportunities to improve the care of bleeding patients. This approach will simultaneously facilitate comprehensive evaluation and validation of both current and novel in vitro tests of hemostasis. If a given in vitro test were reproducibly shown to correlate strongly with bleeding reduction caused by PLT transfusion, then by definition that would be a clinically meaningful test. Finally, this line of inquiry will allow assessment of the adverse effects of PLT transfusion in bleeding patients.

Name of idea submitter and other team members who worked on this idea : Terry Gernsheimer, University of Washington, for the 2015 NHLBI for the State of the Science in Transfusion Medicine

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30 net votes
44 up votes
14 down votes
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Goal 1: Promote Human Health

Mechanisms of cardiac aging

The electrical and mechanical function of cardiac myocytes is compromised with age, but little is known about the age-related changes that occur within individual myocytes.

Submitted by (@catherine.proenza)

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

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19 net votes
32 up votes
13 down votes
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