Showing 10 ideas for tag "arrhythmias"

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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51 net votes
86 up votes
35 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.

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23 net votes
35 up votes
12 down votes
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Goal 1: Promote Human Health

Paracrine Signaling in the Heart

We need to improve the understanding of the molecular and physiological bases of paracrine signaling of heart, and use the knowledge gained to develop improved, effective approaches to diagnose, treat, and prevent cardiac disorders.

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

Details on the impact of addressing this CQ or CC

Although myocytes comprise approximately three-fourths of the entire volume of mammalian ventricles, they account for only about one-third of all myocardial cells. Ninety percent of the remaining myocardial cells are cardiac fibroblasts which are located primarily in the interstitium. Understanding how complex paracrine signals interact at the molecular, cellular, and organ levels continues to be a challenge to investigators. Clearly, the cardiac fibroblast plays an important role in signaling by its ability to respond to a wide variety of chemical signals that are involved in the paracrine regulation of cardiac function. These and other cardiac paracrine signaling pathways need to be better elucidated before specific clinical interventions targeting them are developed.

Feasibility and challenges of addressing this CQ or CC

This is presently an understudied area of research. Studies however suggest that paracrine factors released from fibroblasts are likely to play an important role in modulation of heart growth and function. This may be especially so in regulation of STEM cell differentiation and following insults to the adult heart.

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13 net votes
27 up votes
14 down votes
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Goal 2: Reduce Human Disease

Preventing or reversing myocardial fibrosis

Conduct proof-of-concept studies and explore whether strategies to reverse or prevent fibrosis are feasible.

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 challenge will lead to early studies of potential therapeutics for arrhythmias and heart failure. If successful, this would have huge impact.

Feasibility and challenges of addressing this CQ or CC

Recent studies have identified some compelling signaling pathways that activate fibrosis so it is feasible to test them through creative experimentation.
Fibrosis and fibrogenesis in the myocardium are clear indications that heart function is either declining or progressing towards decline. Although much of the current research continues to focus on unraveling mechanisms that lead to fibrosis and activation of fibrogenesis, there is as yet less focus on potential mechanisms to prevent or reverse fibrosis. This was in part due to insufficient understanding of major causes of fibrosis and mechanisms that activate fibrogenesis. However, findings from recent studies show that there are several compelling therapeutic targets that are ready to be tested to see whether fibrosis can be reversed or prevented.
May need strategies on how to best to succeed in implementing the research - e.g., what research mechanisms, what kind of teams, what kind of expertise, etc. To fine tune this, a focused workshop for advice may be helpful.

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19 net votes
33 up votes
14 down votes
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Goal 1: Promote Human Health

Understanding NANCs and Neuropeptide Function in the Heart

Understanding the complexity of NANC transmitter release and neuropeptide function could be helpful in establishing new, effective therapeutic strategies for treating heart 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

Could lead to the development of fundamental knowledge required to develop effective new therapeutic interventions to treat heart disease.

Feasibility and challenges of addressing this CQ or CC

Several studies have already demonstrated associations been NANC transmitter release and neuropeptide co-localization with pathogenic changes in cardiac function.
Identification within cardiac nerves of neural peptides that are co-released with traditional transmitters is an interesting and still emerging story. Studies with nonadrenergic, noncholinergic (NANC) transmitters in both the atria and ventricle have shown that a variety of neuropeptides also are localized within the heart, and several, including vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P, and calcitonin gene-related peptide, have been shown to markedly affect heart rate and modulate cardiac function. NPY is also elevated in heart failure patients, and other neuropeptides, including VIP, calcitonin gene related peptide (CGRP), substance P (SP) and their receptors are associated with various types of cardiomyopathies.

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3 net votes
14 up votes
11 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.

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

Implanted defibrillators

What are the effects of implanted defibrillators (ICDs) in patients with diseased, remodeled hearts?

Do ICDs influence future arrhythmia risk? Can devices be better designed to mitigate their possible deleterious effects?

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

Details on the impact of addressing this CQ or CC

Decrease cardiovascular disease and death. Improve quality of life for those utilizing ICDs.

Feasibility and challenges of addressing this CQ or CC

Recent advances in research and ICD technology

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

A toxic relationship? AF and subclinical and clinical thyroid dis

There is a need to create opportunities to explore clinically relevant basic and clinical research related to myocardial effects of thyroid hormone excess and deficiency, especially as it is related to atrial fibrillation.

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

Details on the impact of addressing this CQ or CC

Decrease development AF

Feasibility and challenges of addressing this CQ or CC

AF - top causes in HF, stroke.

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-11 net votes
3 up votes
14 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.

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-18 net votes
13 up votes
31 down votes
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