Showing 34 ideas for tag "cardiac"

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.

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 Representation of the Elderly in Clinical Research

There is a need to optimize long-term cognitive and functional outcomes in the aging population during and after cardiothorasic surgery, including the development of simple, objective tools to enable risk stratification for vulnerability to neurocognitive deficit. First, cardiothoracic surgical trials and clinical studies should be more "age-representative" and reflect the increasing proportion of the aging population.... more »

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

Details on the impact of addressing this CQ or CC

Many answers would result from including the elderly in ongoing and planned clinical research and trials.

Feasibility and challenges of addressing this CQ or CC

This population is growing rapidly and available to be studied.
Elderly patients as a group face higher acute risks for complications and death following cardiothoracic surgery or coronary interventions, yet may also gain more long-term benefits from surgery due to their more severe disease. The balance between risks and benefits of surgery may be different in the older patient than in their younger counterparts. Major randomized trials that defined the “standard” for the field (e.g., CASS, VA cooperative, RITA, BARI, STICH) often failed to enroll many, if any, patients aged 75 years or older. The Joint NHLBI-AATS Working Group (http://aats.org/CME/2011-AATS-NHLBI-Symposium.cgi) identified several areas of high priority for cardiothoracic surgery research in the elderly.

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

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24 net votes
37 up votes
13 down votes
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Goal 2: Reduce Human Disease

Neurocardiology – A Challenge for Prevention of CV Disease

There is a need to recognize and study the interdependencies between the brain/peripheral nervous system and the heart/vascular systems in health and disease to develop interventions to detect, treat, and prevent cardiovascular disease.

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

Details on the impact of addressing this CQ or CC

Effective new therapies for treatment and prevention of cardiovascular disease

Feasibility and challenges of addressing this CQ or CC

long recognition of interactions between neural and CV system provide a wealth of background knowledge, while new imaging and electronic designs provide means for administering novel interventions.
Presently it is recognized that the autonomic nervous system plays a major role in the pathophysiology of arrhythmias leading to sudden cardiac death (SCD), and NHLBI supports ongoing studies to determine if modulation of nerves may provide an effective means to reduce the occurrence of ventricular arrhythmias associated with SCD. Already, investigators have suggested that therapies such as right, left, or bilateral cerviocothoracic sympathectomy may provide a novel and cost effective intervention for the prevention of SCD. It is also well known that the sympathetic nervous system is activated during the onset and progression of heart failure. Currently investigators have proposed studies of specific central brain sites and the nerve supply to the heart during chronic heart failure progression to gain a better understanding of this pathway as a therapeutic target for the treatment of HF. This and the translation of results from similar studies is a challenge that should be encouraged.

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

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23 net votes
35 up votes
12 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 »

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 2: Reduce Human Disease

Fundamental stress-response mechanisms in the heart.

What are the primary molecules and cellular signals associated with prolonged hypertensive stress that cause adverse myocardial tissue remodeling, and what strategies that prevent or reverse adverse remodeling can be developed and tested?

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

Details on the impact of addressing this CQ or CC

Could potentially contribute to the development of new therapies for heart disease and cardiomyopathies.

Feasibility and challenges of addressing this CQ or CC

Yes, addressing this CQ may be feasible. Since it is likely that a multitude of signaling mechanisms are involved, an unbiased, global approach may be necessary to identify the key molecular pathways. However, experimental challenges remain and even developing appropriate animal models has been challenging.

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

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14 net votes
21 up votes
7 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 »

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 2: Reduce Human Disease

Cardiac Arrhythmia Factors

What are the genetic and neurohormonal factors associated with cardiac arrthymias, and how might these factors be controlled to reduce arrhythmia incidence? How do we identify patients who are at imminent risk of arrhythmic death?

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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9 net votes
23 up votes
14 down votes
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Goal 2: Reduce Human Disease

Durable Tissue-Engineered Cardiac Valves

For replacement valves to achieve durable success, what are the best cell type(s), scaffold design, imaging approaches, and scalable manufacturing approaches?

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

Details on the impact of addressing this CQ or CC

Successfully meeting this challenge would lead to replacement heart valves that would not require lifelong anticoagulant medication. For younger patients, it would also eliminate revision surgeries as the implanted valves would grow with the patient over time.

Feasibility and challenges of addressing this CQ or CC

Tissue engineered valves have already been developed, but their durability must be increased. Cues can be drawn from the successes of other engineered tissues where long-term mechanical strength has been achieved.
Currently, valve replacement utilizes prosthetic and bio prosthetic materials. However, tissue engineered valves offer the prospect of living cardiovascular tissue substitutes in order to overcome the shortcomings of current prosthetic and bioprosthetic materials. Early prototypes have demonstrated satisfactory initial function, but competence deteriorates over time. Initial clinical demonstrations could target the right side of the circulation, such as the pulmonary valve in patients with congenital defects and the repair of the tricuspid valve, since these applications lack catastrophic hemodynamic consequences for valve failure.

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

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8 net votes
20 up votes
12 down votes
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Goal 2: Reduce Human Disease

Engineered ECM for heart repair

Utilizing advances in nano, bio, tissue and related engineering technologies to construct cardiac ECM for heart repair.

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

Details on the impact of addressing this CQ or CC

Will advance cell and gene based therapeutics for cardiac repair. Despite promise, efficacy of cell based therapies remains largely unproven and this may in part be due to poor understanding of cell-ECM interactions. Research efforts in engineering cardiac ECM have the potential to greatly advance such therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC

This research field is ripe for experimentation and testing.
A major thrust of recent efforts in repairing cardiac injury has focused on cell therapies. However, since the ECM provides the necessary scaffold for the cells it is important to consider the cell-ECM interactions when utilizing these approaches.

Will require multi-disciplinary expertise.

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

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3 net votes
19 up votes
16 down votes
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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?

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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1 net vote
16 up votes
15 down votes
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Goal 2: Reduce Human Disease

What is the optimal management of coronary artery disease in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) have an extremely high risk of death from cardiovascular cause. The prognosis of patients with chronic kidney disease who also have coronary artery disease is worse than certain cancer. While great strides have been made to create awareness about breast cancer, there is paucity of knowledge about the cardiovascular risk of CKD patients among both physicians and patients. Moreover,... more »

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 with chronic kidney disease tend to be undertreated (from CV perspective), underrepresented (in clinical trials) and underdiagnosed with less referral for stress testing, even though cardiovascular cause is the leading cause of death in these patients. Patients with chronic kidney disease is a growing cohort and with increase in obesity and diabetes, the prevalence is exploding exponentially. The decision as to what is the best treatment option for patients with coronary artery disease who also have kidney disease- revascularization or medical therapy-is important and can be a paradigm shift in the way we treat such patients

Feasibility and challenges of addressing this CQ or CC

Randomized clinical trials are urgently needed to answer this question.

Name of idea submitter and other team members who worked on this idea Sripal Bangalore

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

Does epinephrine improve outcomes in OHCA

Epinephrine is the primary drug that is used in resuscitation but observational studies and a few small RCT suggest that it improves short term but not long term outcomes. Factors such as timing, dose, quality fo CPR and post-resuscitation care all confound the issue. Large RCTs conducted at multiple centers are desperately needed to address this question.

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

Details on the impact of addressing this CQ or CC

If short terms outcomes are improved but not long term outcomes, we are only adding costs and not improving population health

Feasibility and challenges of addressing this CQ or CC

Will require a large prehospital clinical trials network and ideally also a current national registry of OHCA to address secular changes in other confounding variables

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

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

Why does loss of endoglin in adult blood cells lead to cardiac hypertrophy in HHT patients

Liver arteriovenous venous malformations creates a high flow shunt that over time creates high output cardiac failure with no effective treatments.

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 Marianne Clancy MPA, Chris Hughes PhD

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1 net vote
1 up votes
0 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 »

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

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4 up votes
4 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 »

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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2 up votes
2 down votes
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