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?

Submitted by (@nhlbiforumadministrator1)

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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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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Goal 2: Reduce Human Disease

Ehlers-Danlos Syndrome: Effects on Cardiac Function

How does Ehlers-Danlos Syndrome affect the functioning of the heart and circulatory system?

Submitted by (@jeanneearleymcardle)

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

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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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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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Goal 3: Advance Translational Research

Paradigm shift in cardiac arrest rhythm and resuscitation

What resuscitation strategies targeted toward pulseless electrical activity (PEA)/asystole would be successful in preventing cardiac arrest (CA)? Furthermore, what are animal models of PEA/asystole, what is responsible of this major shift in the underlying rhythm of CA, and what is the phenotype?

Submitted by (@nhlbiforumadministrator1)

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 a critical need to address continuous shift in the primary rhythm of CA from VT/VF to PEA/asystole with new strategies to improve survival.

Feasibility and challenges of addressing this CQ or CC :

Data from major registries, such as ROC, CARES and other provide the needed population base and platform to analyze existing strategies, explore and develop and test new resuscitation strategies.

With the continuous decline in VT/VF proportion as the primary rhythm leading to cardiac arrest (CA), pulseless electrical activity (PEA) and asystole have become the dominant rhythms in CA. In early 70's VT/VF constituted more than half of the CA, which currently is ~ 28%. Major effort and defibrilation and resuscitation strategies have been successfully targeted toward VT/VF. The survival of PEA/asystole is dismal.

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

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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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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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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.

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 :

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.

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

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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 »

Submitted by (@sripal.bangalore)

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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Goal 3: Advance Translational Research

Disparities in cardiac arrest care

How do we eliminate disparities in cardiac arrest care?

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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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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