Strategic Goal: 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?

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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Strategic Goal: Goal 2: Reduce Human Disease

Risk scores for valvular heart disease

What is an appropriate risk score for intervention in valvular heart disease?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

More accurate risk estimates would provide clinicians with clearer guidance in selecting how and when to intervene in valvular heart disease.

Feasibility and challenges of addressing this CQ or CC :

The advent and rapid advance of transcatheter therapy for valvular heart disease makes this an opportune time to develop metrics to determine whether transcatheter or surgical intervention is most appropriate and when.

The decision to intervene, as well as the type of intervention, is based on individual risk scores such as the STS risk estimate or the Euroscore. However, these scores are derived only from surgical patients and do not take into account procedure-specific impediments, major organ system compromise, comorbidities, or the frailty of the patient.

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

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Strategic Goal: Goal 3: Advance Translational Research

COPD risk categories and resource utilization

Can a tool be developed to group patients into risk categories for resource utilization?

Submitted by (@jimandmarynelson)

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

Details on the impact of addressing this CQ or CC :

COPD is usually blamed on smoking - first-hand smoke, second-hand smoke, and third-hand smoke. In reality, smoking is a major contributing factor. However, many other factors may lead to destruction of the breathing mechanisms in human lungs. Premature birth, exposure to industrial or agricultural chemicals, breathing dirty air, and a genetic factor known as Alpha-1 Antitrypsin Deficiency, as well as other factors may lead to COPD. In addition, COPD encompasses emphysema, chronic bronchitis, and certain types of incurable asthma, normally a combination of two or more of these disorders.

Each category of COPD requires its individual research approach.

Name of idea submitter and other team members who worked on this idea : Mary E. Nelson, caregiver, Arizona State Advocacy Captain, Copd Foundation

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Strategic Goal: Goal 2: Reduce Human Disease

Understand the Impact of Thrombosis in Children with Cancer

CC: Despite the potential impact that venous thrombotic events (VTE) have on children with cancer, several unresolved issues remain. To date, we are yet to understand: - incidence/prevalence of VTE according to cancer type/staging - ideal imaging modalities to diagnose/follow VTE - thromboprophylaxis according to thrombosis risk stratification (development of VTE predictors) - efficacy/safety to anticoagulate children ...more »

Submitted by (@leonardo.brandao)

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

Details on the impact of addressing this CQ or CC :

Venous thrombotic events (VTE) are now occurring in 1/200 children admitted to a tertiary pediatric facility. In around 70-90% of cases, VTE occurs in children with an underlying condition, amongst which cancer represents up to 1/3 of patients. Within this group of patients, the thrombotic complications are associated with a higher morbidity (e.g. higher recurrence rates, high rate of CNS events in acute leukemia) and mortality. Nevertheless, the clinical challenges highlighted in the itemized Critical Challenge Section illustrate the lack of basic science, translational and clinical research available, as well as the paucity of evidence-based medicine recommendations necessary to acoount for the increasing number of patients with this complication.

On the other hand, pediatric oncology is one of the areas of pediatric care where the medical progresses of the last decades have drastically changed the natural history of cancer in children. In light of much higher survival rates for almost all types of pediatric cancer, the focus has now shifted towards decreasing treatment-related, as well as disease-related morbidities, increasing the quality of life of the many survivors. Because VTE is now recognized as one of the significant remaining complications within this patient population, addressing the list summarized herein would contribute to further improve the care of children with cancer.

Feasibility and challenges of addressing this CQ or CC :

The infrastructure that is already in place under the Children's Oncology Group (COG), where almost any new clinical and/or translational idea related to the care of children with cancer becomes part of a clinical trial, could be rolled over to explore many of the items listed under the CC Section.

As a principle, VTE in children with cancer develop due to: a) host-related factors; b) chemotherapy/treatment-related factors; and c) disease-related issues. Therefore, protocol- and disease-specific studies could address, under the auspices of COG, the prevalence of VTE according to cancer type in a prospective manner. Similarly, high risk groups for VTE could be submitted to standardized imaging and/or biomarker investigation prospectivelly, in addition to collection of outcome data related to VTE and to anticoagulation protocols. Furthermore, tumor specimens/genetic markers could be evaluated and correlated to the study outcomes. The challenges of reaching consensus during protocol development would allow identification of equipoise for certain clinical scenarios, obviating the need of trials, or the use of consensus techniques, before diagnostic/therapeutic protocols could be adopted.

In conclusion, the develoment of a multidisciplinary task force (i.e. pediatric radiologists, oncologists, hematologists, molecular biology experts), which, for the most part, is already in place (i.e. COG), would be instrumental to foster research on this extremely clinically relevant area.

Name of idea submitter and other team members who worked on this idea : Leonardo R. Brandao, MD, MSc;

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Strategic Goal: Goal 2: Reduce Human Disease

Develop and validate a metric to address the full spectrum of patient-level comorbidities affecting critical illness

An individual metric to inform about the additive and not individual impact of comorbidities on critical illness and peri-operative mortality. For instance, we know the impact of COPD or MI or CKD on mortality after hemicolectomy, but not necessarily the additive impact of all three.

Submitted by (@greg.martin)

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 : Society of Critical Care Medicine Executive Committee/Council

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Strategic Goal: Goal 3: Advance Translational Research

Early prediction of cardiovascular disease by primary-care assessment

Tools for early assessment of cardiovascular disease have become available but not adopted in primary-care settings. Increased arterial stiffness is a well-known marker for advanced cardiovascular disease (CVD) and has been shown to be an independent predictor of cardiovascular mortality. In addition, arterial pulse wave velocity (PWV) has been readily accepted as a measure of arterial stiffness. Despite significant ...more »

Submitted by (@roy.wallen)

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 US, 84 million adults will see their primary care physician for treatment of cardiovascular disease (CVD). CVD is responsible for an average of one death every 40 seconds. The direct and indirect costs of cardiovascular disease and stroke are approximately $315 billion, including the cost of health care services, medications to treat high blood pressure, and missed days of work. The World Health Organization states that 80% of premature heart disease and stroke is preventable. Focusing on assessing risk factors for cardiovascular disease, screening for individuals at risk, and then providing effective and affordable treatment to those who require it can prevent disability and death and improve quality of life.

 

In Europe, the European Society of Cardiology (ESC) has issued guidelines based on the weight of evidence in favor of the usefulness of screening for CVD by assessing arterial stiffness. These guidelines are supported by nonrandomized trials and suggest the development of randomized trials or meta-analyses. However, no guidelines exist in the US for screening for arterial stiffness from such organizations as the American Heart Association (AHA) and the American College of Cardiology (ACC). Existing guidelines to include assessment of cholesterol, lifestyle, obesity, and factors for risk are important. However, a simple, low-cost, objective measurement could be implemented at the point of primary care to improve early detection and treatment of CVD.

Feasibility and challenges of addressing this CQ or CC :

Screening capabilities and some level of clinical evidence exist for early detection of CVD. Therefore, implementation of a practice guideline in the US is very feasible. Studies and assessment from existing data such as have been completed by ESC can be replicated in the US and promulgated by AHA and ACC. This effort will require support from public and private entities, including universities, in order to see practice standards implemented.

 

Challenges to date include funding and the application of clinical protocols to support randomized studies or meta-analyses that will provide evidence for benefits of early screening. Further, public policy and current funding are focused on treatment rather than prevention. Existing reimbursement established by the Centers for Medicare & Medicaid Services (CMS) is focused on treatment rather than prevention and private insurance carriers have followed this same policy. Broader clinical study will support both the adoption of screening tools in primary care and broader reimbursement policy.

Name of idea submitter and other team members who worked on this idea : Roy Wallen

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Strategic Goal: Goal 2: Reduce Human Disease

Adult cardiovascular risk in patients with congenital heart disease

Do patients with congenital heart disease have the same, higher, or lower risk for coronary artery disease as they age into adulthood?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

By improving our understanding of cardiovascular risk in patients with congenital heart disease we may be able to improve our surveillance for disease and intervene earlier to address this risk factors. The adult population with congenital heart disease is undergoing rapid growth.

Feasibility and challenges of addressing this CQ or CC :

The adult population with congenital heart disease is undergoing rapid growth. Novel uses of electronic health records (EHRs) and registries may enable us to answer these questions in a cost-efficient manner.

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

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Strategic Goal: Goal 2: Reduce Human Disease

Venous Thromboembolism

There is a great need for the development and evaluation of biomarkers for the study of venous thromboembolism (VTE) pathophysiology and risk assessment.

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

Details on the impact of addressing this CQ or CC :

Recent efforts to evaluate biomarkers for VTE occurrence and recurrence have led to the identification of multiple potential candidates, including P-selectin, E-selectin, D-dimer, various microparticles, and various inflammatory cytokines. However, no specific biomarker has yet emerged for routine clinical use for individual VTE risk stratification and personal targeted therapeutics. The development of improved animal models will advance the study of VTE pathophysiology, allowing for more accurate evaluation of emerging biomarkers and initial assessments of potential advanced therapeutic interventions. Also, the identification and prioritization of novel VTE biomarkers will be needed to help improve our understanding of the molecular mechanisms underlying VTE, so as to shepherd the development of novel mechanisms of therapy beyond anticoagulation.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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Strategic Goal: Goal 2: Reduce Human Disease

Can Psychological Science Improve Weight Loss?

Will sensitivity to the psychological aspects of obesity, including lifestyle priorities and motivations, improve the efficacy of long-term effectiveness of weight loss and obesity prevention interventions?

Submitted by (@nhlbiforumadministrator)

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 primary focus on principles of psychology may result in significantly improved control of the obesity epidemic. Effective interventions could reduce the risk of diabetes, sleep apnea, and hypertension. This research could also affect clinical practice guidelines for weight loss and obesity treatment.

Feasibility and challenges of addressing this CQ or CC :

Psychological science has been successful in developing effective treatments for a number of conditions, including sleep disorders, depressive symptoms, anxiety and phobias. Many of the behavioral principles employed in such interventions (e.g., cognitive restructuring, motivational methods) could be translated for the prevention and treatment of obesity within a reasonable time frame. Additional attention should be directed to the needs of population subgroups in which obesity is most prevalent.

In their Viewpoint article on weight loss intervention research, Pagoto and Appelhans (JAMA, 2013, see attachment) question whether a continued focus on dietary factors in research on weight loss and obesity is warranted. Their commentary raises the importance of attention to the individual psychological characteristics that influence adherence to weight loss interventions rather than dietary composition.

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

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Strategic Goal: Goal 2: Reduce Human Disease

Identifying the High Venous Thromboembolism-Risk Individual

Over 500,000 incident or recurrent venous thromboembolism (VTE) events occur annually in the US. Almost one-quarter of acute pulmonary embolism patients suffer sudden death. To improve survival, the occurrence of VTE must be reduced. However, the incidence of VTE has increased over the last 30 years. Moreover, near universal prophylaxis of patients hospitalized for surgery or for medical illness has not reduced hospitalization-associated ...more »

Submitted by (@heit.john)

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 and safe VTE prophylaxis regimens are widely available but near universal prophylaxis of hospitalized patients has failed to reduce the occurrence of VTE. Moreover, about half of all VTE events in the community are unrelated to hospitalization. Known major VTE risk factors account for about 85% of all VTE disease in the community but have a poor predictive value for the individual. Identifying the high VTE-risk individual by incorporating genetic variation and biomarkers into clinical risk prediction scores will reduce VTE occurrence by allowing providers to stratify VTE risk and target risk factor modification and/or intensive VTE prophylaxis to the high VTE-risk individual.

Feasibility and challenges of addressing this CQ or CC :

Genetic variation and plasma biomarkers associated with VTE have been identified among individuals of European ancestry and are readily available for incorporation into clinical VTE risk prediction tools. Limited work has identified genetic variation associated with VTE among individuals of African ancestry but more work is needed in this area. Active cancer accounts for about 20% of all incident VTE and genetic variation associated with VTE compounds VTE risk in cancer patients. More work is needed to identify plasma biomarkers and cancer tissue expression characteristics that are associated with VTE in cancer patients. Acute trauma/fracture accounts for about 12% of all VTE in the community and these patients are at high risk for both VTE and anticoagulant-associated bleeding. More work is needed to incorporate genetic variation and plasma biomarkers into risk prediction scores for the individual acute trauma/fracture patient. Finally, large candidate gene and GWA studies have identified relatively common, low VTE-risk genetic variation that together account for about 5% of VTE. Clearly, additional as yet, unidentified high VTE-risk genes exist. Additional studies are needed to identify these high VTE-risk genes, both in populations of European and African origin.

Name of idea submitter and other team members who worked on this idea : John A. Heit, MD

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Strategic Goal: Goal 2: Reduce Human Disease

Restoring Balance to Stroke Prevention in Older AFib Patients

Improving Tools for Anticoagulation Decision-Making

Submitted by (@cbens0)

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

Details on the impact of addressing this CQ or CC :

AFib increases stroke risk by five-fold and doubles the risk that a stroke will result in permanent disability. While oral anticoagulation (OAC) is highly effective at reducing stroke risk, elderly patients are often under-anticoagulated. This is in part due to an under-appreciation of the stroke risk associated with AFib and the tendency of some health care professionals to prioritize perceived bleeding risk over stroke prophylaxis. Because current bleeding risk assessment tools are imperfect and largely unable to predict patients who are likely to have bleeding complications, they are often not utilized—or if used, do not truly predict which patients are at risk of a bleed. An improved bleeding risk tool is critical to improved risk assessment in the elderly. That bleeding risk tool should then be combined with the stroke risk tool for single risk stratification to streamline anticoagulation decision-making.

Feasibility and challenges of addressing this CQ or CC :

Developing effective integrated risk assessment tools is feasible only if there is consensus on the validity of the clinical information being provided. The approach to this critical challenge is two-fold. First, needed research that improves the reliability of bleeding risk assessment in the elderly should be pursued. Second, stroke and bleeding risk tools should be combined into a single risk stratification tool. This will require significant investment and focus, but the resulting bleeding risk assessment combined with the accepted CHA2DS2-VASc score, would significantly impact the 40 - 60% of patients who are currently not on an anticoagulant and are at increased risk of stroke and death.

Name of idea submitter and other team members who worked on this idea : AFib Optimal Treatment Task Force

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Strategic Goal: Goal 3: Advance Translational Research

Develop biomarker panel to predict CVD risk in -omics era

There is a need to utilize the vast data generated in -omics research to develop biomarker panels for better prediction of cardiovascular disease (CVD) risks. •Cardiovascular diseases develop over decades and different panels of markers may be required for different stages •Lead molecules as potential biomarkers need to be selected by a panel of experts •Standard procedures about sample preparation, data acquisition, ...more »

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 :

•Develop specific and sensitive markers for early prevention with more predictive power. Biomarkers that can detect specific perturbations in the system, such as metabolic status and vascular integrity prior to the occurrence of the diseases can be used for early preventive treatment of cardiovascular diseases.

 

•Identify vulnerable population who cannot be identified by the current LDL-HDL profiling

 

•Allow for more personalized treatment

Feasibility and challenges of addressing this CQ or CC :

•An increase in system biology studies using –omic approaches have provided huge data to mine through and find potential biomarkers, such as microRNA, DNA, lipids, proteins, and other metabolites, which can be used to assess changes proceeding cardiovascular diseases occurrence.

 

•The NIH-wide Big Data to Knowledge (BD2K) initiative launched in 2012 may have laid out some framework.

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

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