Showing 11 ideas for tag "death"

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.

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

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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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86 up 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 3: Advance Translational Research

Develop an Effective and Functional Biological Pacemaker

There is a need to develop a biological pacemaker for pediatric patients that would react to neurohumoral factors that normally modulate heart function, as well as adapt to the growing heart.

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

Details on the impact of addressing this CQ or CC

Reduce risks associated with the increasing use implantable pacemakers. Increase reliability of artificial electrical pacemakers.

Feasibility and challenges of addressing this CQ or CC

Animal studies have already demonstrated feasibility of cell- and gene-based as well as hybrid approaches.
The introduction of implantable medical devices using electrical impulses through electrodes placed in the heart to regulate its beating in patients whose native cardiac pacemakers fail— i.e., implantable electronic pacemakers— have permitted hundreds of thousands of individuals to live extended, relatively normal lives. Many advances since the introduction of implantable pacemakers into medical practice during the latter half of the 20th century have improved reliability, but their use still carries significant risks; e.g., lead fracture, infection, malfunction, and the need for replacement.
To date experimental cell therapy, gene therapy, and hybrid approaches have been used to create biological pacemakers in animal models. These incorporate the use of human embryonic stem cells or induced pluripotent stem cells or overexpression of the transcription factor, TBX18, to produce functional biological pacemakers in large animal models. Other gene therapy approaches have also been used to generate functional biological pacemakers in animals. These include overexpression of ion channels impacting diastolic membrane depolarization and excitability in non-pace making regions of large animal hearts. Beta-2 receptor or adenylyl cyclase overexpression represent other strategies that have been employed. Finally, a hybrid approach has used human mesenchymal stem cells loaded with the pacemaker gene HCN2is to induce pacemaker activity in large animals. Thus multiple approaches exist and collaboration is needed between investigative groups to overcome the challenge of creating and testing an effective and reliable biological pacemaker in humans.

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

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23 up votes
15 down votes
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Goal 3: Advance Translational Research

Translation of an intervention to reduce sudden cardiac death

There is a need to identify and to develop pharmaceutical interventions for patients at risk for sudden cardiac death (SCD).

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

Details on the impact of addressing this CQ or CC

Markedly reduce sudden cardiac death in high populations. Lead to a new pharmacologic paradigm for preventing lethal cardiac arrhythmias.

Feasibility and challenges of addressing this CQ or CC

Investigators have already demonstrated in animal models of SCD that inhibition of mitochondrial Na/Ca-exchange is associated with a reduction in ventricular arrhythmias and SCD without a change in corrected-QTC.
Using a novel guinea pig model of heart failure and sudden cardiac death (SCD), researchers (Circ Res. 2014 Jun 20;115(1):44-54) have demonstrated that inhibition of the mitochondrial sodium-calcium exchanger prevents SCD. In people, SCD accounts for 170,000 to 450,000 deaths per year in the US. Basic research focused on identifying cardiac ion channel inhibitors have failed to results in antiarrhythmic drugs that prevent SCD. And although clinical research has thus far failed to identify individuals at risk of suffering a SCD in the general population, subpopulations (for example, those with a low ejection fraction months after suffering a myocardial infarction) have been identified that are at high risk. If an effective pharmaceutical intervention was developed that reduces SCD, deaths in these populations would be markedly reduced. Strategies need to be developed to translate this promising basic science finding into saving lives.

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

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19 up votes
14 down votes
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Goal 2: Reduce Human Disease

RCT of stepped-care depression treatment on CV events & death

Does treating depression improve survival and reduce major adverse cardiac events in acute coronary syndrome patients?

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 substantial evidence base now exists showing that depression is associated with a two-fold increased risk of death and recurrent CV events in cardiac patients, leading to a recent AHA scientific statement recommending its elevation to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome (Lichtman et al., 2014). Yet there is currently no clinical trial evidence that reducing depression improves cardiac morbidity and mortality. A clinical trial, using new, more effective depression treatment methods, such as collaborative care approaches that combine psychological counseling with medication in stepped-care fashion, is needed to determine whether effective treatment of depression can improve survival and reduce clinical cardiovascular events in cardiac patients.

Feasibility and challenges of addressing this CQ or CC

Newer stepped-care treatments for depression, combining medication and psychotherapy, have recently been developed and found to more effectively reduce depression than earlier treatments. By using these newer treatment methods to substantially lower depression, we can better answer the question as to whether treating the newly acknowledged risk factor of depression in ACS patients can improve clinical outcomes in these patients.

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

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22 up votes
17 down votes
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Goal 1: Promote Human Health

Hierarchical control of cardiac excitability

Imbalances in membrane excitability underlie a broad range of cardiac arrhythmias and conduction defects. Although we now know the genes encoding almost all ion channels, we have little understanding of how the macromolecular composition and relative numbers of different channel types is achieved to exert exquisite control over membrane potential changes in time. Even minor changes in this balance can lead to sudden... 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

The mechanisms involved reside at every conceivable level – genomic and epigenetic, transcriptional, translational and posttranslational. The tools required include structural biology, super resolution microscopy, single-molecule measurements, advanced molecular biology approaches, and bioinformatics and systems biology approaches. Fulfilling this unmet need will inform any system in which stoichiometry of macromolecular complexes critically determines normal function, and will therefore have a broad, transformative reach. The work will reveal novel mechanisms that will serve as targets for disease and therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC

Addressing this problem requires coordinated efforts by multidisciplinary investigators using diverse approaches as described above. Above all it requires a commitment of resources to basic science advances without which translation is impossible.

Name of idea submitter and other team members who worked on this idea Gail Robertson

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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

Fish Oil or Snake Oil: Is There Antiarrhythmic Benefit?

Does fish oil supplement intervention truly reduce arrhythmia burden in the general population?

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

Details on the impact of addressing this CQ or CC

Low-cost effect preventative antiarrhythmic therapy

Feasibility and challenges of addressing this CQ or CC

Low cost wearable, internet-connected devices make it possible to inexpensively collect heart rate and physiometric data from a large number of people to determine and predict arrhythmia risk.
Observational studies have suggested that either cardiac arrest or sudden death is associated with low dietary intake and blood levels of polyunsaturated fatty acids and that a fish diet or dietary supplementation with polyunsaturated fatty acids (the GISSI-Prevenzione study) decrease mortality and/or sudden death following myocardial infarction. However, NHLBI-supported and other randomized, double blind studies of the antiarrhythmic efficacy of fish oil supplements in patients with a high arrhythmic risk and implantable cardioverter defibrillators have failed to demonstrate benefit. Similarly, fish oil supplements in patients at risk for atrial fibrillation (AF) have shown no benefit. Yet evidence from studies in laboratory animals continue to suggest that omega-3 fatty acids present in fish oil provide benefits that should be antiarrhythmic. These and other fundamental research studies in isolated tissues and laboratory animals continue to lead to uncertainty as to whether patients with cardiac arrhythmias may benefit from fish oil supplements.

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

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13 up votes
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Goal 2: Reduce Human Disease

What are the Determinants of Short Term Prediction of Heart Attacks?

In spite of many years of research, we still cannot predict the short term risk of a heart attack or sudden CHD death. Most CHD deaths occur outside of the hospital. In spite of improvement of out-of-hospital emergency care, most “sudden death events” are still not successfully resuscitated.

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 strong evidence of interrelationship between inflammation, thrombogenesis, especially activation of tissue factor and platelets, and risk of a heart attack or sudden death. This is especially true in individuals who have pneumonia, influenza, etc. but also perhaps in relationship to environmental factors such as air pollution. Development of early identification and treatment approaches could substantially reduce CHD mortality.

Feasibility and challenges of addressing this CQ or CC

The NHLBI has certainly had a major commitment in studying the interrelationship between inflammation and CHD. However, there is a need to go into the field and evaluation the interrelationship between inflammation, especially infection, drug therapies and short term acute precipitation of heart attacks. For example, there is suggestive evidence that older individuals on aspirin who have pneumonia may have reduced risk of a heart attack and sudden CHD death. Further studies linking work at the National Institute of Allergy and Infectious Diseases and the Heart and Lung Institute should attempt to further understand the interrelationships between infection, inflammation, and activation of tissue factor and platelets, and risk of thrombosis and heart attack and whether specific drug therapies, especially in high risk older individuals or even among individuals who have had previous CVD or high atherosclerotic burden, whether newer drugs could substantially reduce the risk of a heart attack.

Name of idea submitter and other team members who worked on this idea Lewis H. Kuller, MD, DrPH

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Goal 3: Advance Translational Research

Screening the work force for genetic arrhythmias

Is anyone in your family at risk for a potentially lethal genetic arrhythmia? 4000 young people die each year because they bear a genetic mutation that makes them susceptible to a sudden fatal arrhythmia. The symptoms are easy to identify and awareness of these symptoms would help unsuspecting families.

 

It is estimated that one of these syndromes (LQTS) is 3 times more common in the US than childhood leukemia.

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

Details on the impact of addressing this CQ or CC

There are 3 simple warning signs for families bearing dominant mutations that could lead to arrhythmia and sudden death. These are unexplained fainting or seizure during exercise or startle, an unexplained sudden death of a young family member, chest pain and/or shortness of breath during exercise. A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias.

Feasibility and challenges of addressing this CQ or CC

A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias. Such potential patients could then be further screening by a EKG and a consult with a cardiologist.

Name of idea submitter and other team members who worked on this idea Andy Golden

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Goal 2: Reduce Human Disease

Genetic risk factors for sudden cardiac death

What are the genetic risk factors for sudden cardiac death and failure to respond to CPR and defibrillation?

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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