Showing 6 ideas for tag "scd"

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)

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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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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8 net votes
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

Impact of each VOC Crisis in patients with sickle cell disease

While the long term cumulative effects of frequency, duration and severity of VOC on mortality is known in SCD, there is little known about the impact of each individual crisis or the amount of damage during crisis versus background smoldering ischemia from the disease. Any effort in quantifying this for SCD in the absence of interventional agents initially, and then as a potential measurement of the benefit of drug... 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

This may help science inform additional treatment options for sickle cell disease, and serve as a cornerstone for further research particularly in the realms of drug development that addresses individual components of a sickle cell crisis.

Feasibility and challenges of addressing this CQ or CC

This is feasible but has not been chosen as a research prerogative. A challenge is that there is no current way to measure what happens internally during a VOC.

Name of idea submitter and other team members who worked on this idea Tosin Ola, Greg Gorgas

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3 up votes
0 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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