Showing 10 ideas for tag "aortic"

Goal 2: Reduce Human Disease

Does lowering circulating lipoprotein(a) levels influence cardiovascular outcomes?

A comprehensive research strategy and plan is needed to determine the most efficient, safe, cost-effective and widely applicable strategy to decrease circulating levels of lipoprotein(a) and to determine whether lowering circulating lipoprotein(a) levels will reduce the risk of developing cardiovascular disease such as a heart attack or a stroke as well as the progression of atherosclerosis or aortic stenosis.

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

Details on the impact of addressing this CQ or CC

Approximately 20% of the population are characterized by elevated circulating levels of lipoprotein(a), regardless of age, gender or blood cholesterol levels. Estimates suggest that up to 90% of the variation in plasma lipoprotein(a) levels could be due to genetic factors, which makes lipoprotein(a) the most prevalent inherited risk factor for cardiovascular diseases (CVD). Large-scale genetic studies have shown that Lipoprotein(a) was the strongest genetic determinant of CVD such as atherosclerosis and aortic stenosis. Lipoprotein(a) is one of the strongest predictors of residual CVD risk and has been shown to improve CVD risk prediction in several population-based studies. Lipoprotein(a) is also one of the strongest known risk factors for spontaneous ischemic stroke in childhood.
A comprehensive research strategy aiming at identifying, evaluating interaction with other risk factors, treating and educating patients with elevated lipoprotein(a) levels would result in substantial reductions of health care costs in the US and around the globe by reducing the burden of CVD while simultaneously improving the quality of life of these patients.

Feasibility and challenges of addressing this CQ or CC

The list of pharmaceutical agents that reduce lipoprotein(a) levels is steadily increasing. There are approximately half a dozen strategies that have been shown to significantly and safely lower lipoprotein(a) levels. One of the challenges of this research strategy will be to determine which of these strategies represent the most efficient, safe, cost-effective and widely applicable approach to lower lipoprotein(a) levels and CVD outcomes.
Increasing awareness on lipoprotein(a) and CVD will also be of utmost importance for this effort as relatively few physicians perform lipoprotein(a) testing and even fewer patients are aware of their lipoprotein(a) level. The first sign of high lipoprotein(a) is often a heart attack or stroke. Our challenge will be to identify patients with high lipoprotein(a) that could be enrolled in trials of risk characterization and lipoprotein(a)-lowering.

Name of idea submitter and other team members who worked on this idea Sandra Revill Tremulis on behalf of the Lipoprotein(a) Foundation Scientific Advisory Board

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Goal 2: Reduce Human Disease

Discovering unique targets to treat and cure calcific aortic valve disease

Calcific aortic valve disease (CAVD) is a major contributor of cardiovascular morbidity and mortality. No therapeutic strategies currently exist to prevent or treat CAVD. The aortic valve represents a unique and highly dynamic tissue, and it is important to recognize that although CAVD shares many commonalities with atherosclerosis, traditional risk factors for atherosclerotic plaque development remain relatively poor... 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

CAVD progresses in three stages (New et al. Circ Res 2011): inflammation-mediated initiation, propagation of calcification, and end-stage stenosis. Reversibility at the end-stage remains unclear. To address this critical challenge, research is needed in:

- Early molecular imaging modalities
- Animal models that mimic human pathophysiology
- Factors differentiating valvular and vascular cell phenotypes
- Understanding the genesis of calcification
- CAVD biomarker identification

CAVD is directly responsible for more than 14,000 deaths annually in the USA alone. With valve replacement as the only available clinical option, patients often cope with a deteriorating quality of life until diminished valve function demands intervention. In fact, only 50% of patients with CAVD are referred for surgery, and only 40% are actually admitted for aortic valve replacement (Bach et al., JHVD 2011). In addition, the surgical valve replacement has limitations, including complications attributable to anticoagulation and the need for re-operation because of the limited lifespan of prosthetic valves (Yutzey et al, ATVB 2014). Therefore, the development of novel therapeutic strategies that target the early events in CAVD would represent a tremendous benefit for patients.

Feasibility and challenges of addressing this CQ or CC

The first step in addressing this challenge is to recognize that the aortic valve and CAVD are distinct from other cardiovascular diseases and allocate resources to address the unique properties. This is a feasible goal, but achieving tangible outcomes will require a multidisciplinary approach to study the areas of research outlined above. The NHLBI is well-suited to facilitate the requisite collaborative approach.

Name of idea submitter and other team members who worked on this idea Joshua D. Hutcheson, Ph.D. and Elena Aikawa, M.D., Ph.D.

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33 up votes
5 down votes
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Goal 2: Reduce Human Disease

Management strategies for severe, asymptomatic aortic stenosis

What is the optimal management approach to severe asymptomatic calcific aortic stenosis (surgical aortic valve replacement (AVR) or deferred surgical AVR until development of symptoms (watchful waiting))?

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

Details on the impact of addressing this CQ or CC

Several non-randomized, retrospective analyses suggest early surgery results in improved survival but significant controversy remains. Answering this compelling question will clear up this conundrum of clinical management in this prevalent disease.

Feasibility and challenges of addressing this CQ or CC

It is feasible to answer this question over the next 5-10 years because the disease is prevalent and growing with the aging population and there is equipoise within the medical community about current management options.

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

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

Recognition of bicuspid aortic valve's complexity, life threatening potential, and familial implications.

There is a persistent perception that bicuspid aortic valve (BAV), the most common congenital heart defect (estimated to occur in up to 6 million Americans), is a benign condition that may not require treatment until later in life, if at all. The implications for other blood relatives, although referenced in medical literature, may not be acknowledged. This notion, coupled with the inability to identify those most at... 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

On the contrary, the presence of BAV should serve as a warning for potentially very serious issues for the individual and their blood relatives, including those with apparently normal trileaflet aortic valves. Childhood heart murmurs, deemed innocent and forgotten, may in fact be the first hint of a malformed aortic valve. Some born with BAV will undergo not just one but multiple surgeries, and some will lose their lives. Others in the family, considered trileaflet, may develop aortic aneurysm and experience dissection.
Despite an estimated incidence of up to 2% of the population and prevalence in males, there is no well-defined screening for this condition, leaving undiagnosed individuals vulnerable to endocarditis, valvular disease, and aortic dissection or rupture. Aortic coarctation may also be present and remain undetected for varying periods of time. Brain aneurysms have been found in some BAV families.

Those diagnosed with BAV may not be offered, or fail to seek, follow up care. Enjoying generally good health, they may fail to secure health insurance, believing they are not at risk, and find themselves with very limited options when abruptly confronted with the need for surgery.

Feasibility and challenges of addressing this CQ or CC

This condition is not rare and will be commonly encountered in the community. Enough is currently known to alert medical professionals as well as the public of potential complications in individuals and blood relatives. The challenge is to overcome the perception, however well meant, that there is no need for concern, especially at younger ages.

Name of idea submitter and other team members who worked on this idea Arlys Velebir, Bicuspid Aortic Foundation

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Goal 2: Reduce Human Disease

Decline in autopsies is an obstacle to understanding bicuspid aortic valve and thoracic aortic disease.

Greater understanding of the incidence, associated mortality, and unique characteristics of bicuspid aortic valve (BAV) and thoracic aortic disease are needed. An increase in autopsies would be an important source in advancing understanding.

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

Details on the impact of addressing this CQ or CC

The implications of the decline in autopsies were recently described in the Wall Street Journal article “What Autopsies Can Teach”,(March 9, 2015). The incidence and implications of BAV, as well as other subtle malformations of the aortic valve not typically detected by imaging or noted in surgery reports, would benefit from better characterization. In addition, BAV is associated with sudden death due to aortic dissection and rupture, as well as complications due to aortic valve disease (stenosis or regurgitation). Prior to the advent of surgery and imaging technology, clinicians were informed through autopsies, and much of their findings regarding BAV and thoracic aortic disease remain relevant. However, to advance further, autopsies remain an invaluable information source. In the absence of autopsies, the opportunity to meticulously examine the aortic valve, other heart valves, and aortic anatomy are lost. Due to the prevalence of coronary artery disease, it is important to separate valvular and aortic deaths from those due to myocardial infarction.

Feasibility and challenges of addressing this CQ or CC

Active participation of families who would benefit from clarification of the condition of blood relatives at death, possibly including incorporation of new capabilities such as genetic analysis of tissue, would be possible immediately if this were given priority in the medical community. Given the estimated prevalence in the population, the understanding gained would benefit not just immediate family members, but the general public. Cost may be viewed as an obstacle, as well as medicolegal concerns. However, in light of incomplete data and understanding, answers found in death may be invaluable gifts to the living now and for generations to come.

Name of idea submitter and other team members who worked on this idea Arlys Velebir, Bicuspid Aortic Foundation

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Goal 2: Reduce Human Disease

Mechanics of aortic dissection

The mechanical events in the wall leading to aortic dissection are not well described because merely stating that cellular or biopolymer connections have weakened does not predict the path of the rupture through the media or the risk of rupture. Elucidate the mechanical role of substructures such as collagen fibers, elastin sheets, smooth muscle cells and interstitial fluid in the progression of dissection. Study in animal... more »

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

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While in recent years the lives of patients with aortic dissection have increasingly been saved, an understanding of the mechanisms involved might suggest new techniques to increase the percentage who survive aortic dissection.

Feasibility and challenges of addressing this CQ or CC

Knowing the mechanisms involved in dissection is more important than attempting to determine and measure some critical rupture stress because of the large differences between specimen aortas within a given species.

Name of idea submitter and other team members who worked on this idea Henry W. Haslach, Jr.

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17 up votes
10 down votes
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Goal 2: Reduce Human Disease

Controversies exist regarding thoracic aortic disease imaging

Controversies exist regarding aortic disease imaging (the aorta as well as the aortic valve, including characterization in the presence of a bicuspid aortic valve (BAV)). Many imaging approaches are optimized for evaluation of coronary artery disease rather than aortic disease. Without accurate characterization, the degree of disease progression may be under estimated, patient symptoms may be discounted, and those who... 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

Imaging specifically tailored to BAV and the thoracic aortic aneurysm population is needed. This includes efforts to identify subtle forms of aortic valve malformation such as the “forme fruste” BAV as described by Sperling and Lubet.

  1. Echocardiogram is a useful noninvasive imaging tool, however, it is believed to miss detection of as many as 50% of BAVs.
  2. The exercise echocardiogram is useful for evaluation of wall motion abnormality, which may be present in those with coronary artery disease or other underlying sources of myocardial injury. However, this is not a common issue in those with BAV. Rather, accurate assessment of BAV function is necessary. Pressure testing for eccentric AI and the short axis view of the AV area, including clear visualization of both the open and closed valve, may not be employed, and consequently clarity of BAV functioning is not achieved.
  3. Although there are open questions about aortic size relative to timing of elective surgery, size of the aorta is a diagnostic parameter, and is frequently done via CT imaging. CT images are typically captured in diastole, which is appropriate for coronary artery disease. However, the aorta will be undersized if measured in diastole. Measurement of the aorta in systole captures the aorta when most distended.
  4. Other considerations, such as the presence of bovine arch anatomy, may not be noted, since their relevance may not be appreciated.
Feasibility and challenges of addressing this CQ or CC

Current imaging technology is widely available in most medical communities. It is very feasible, by focusing on valvular and aortic conditions separately from coronary artery disease, to optimize imaging for these conditions and make these imaging approaches broadly available to patients.

Name of idea submitter and other team members who worked on this idea Arlys Velebir, Bicuspid Aortic Foundation

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Goal 3: Advance Translational Research

How can we determine a patient’s risk of a life-threatening aortic dissection?

Even though science and technology has advanced, many of the advancements have not met the critical challenge of making significant changes in patient therapies for improved outcomes and thus have not been able to break through the translational barrier. In today’s world, risk of aortic dissection is still based purely on a crude size measurement. It is true that evidence indicates that aortic root aneurysm above 4.5... more »

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

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We need tools to assess vascular function and morphology to determine the weakness and/or strength of the aorta. We need biomarkers and predicators of outcomes for aneurysms and acute aortic dissection. We also need to understand the actual physical limitation of the aorta and where there may actual be physical barriers which cannot be overcome by drug therapies.

Utilizing singe gene disorders like Marfan syndrome can help to develop the tools needed to access not only risk but can provide candidate pathways that can contribute to more complex, common and polygenetic disorders and moving research to the preclinical and clinical stage to prioritize therapeutic targets in many related and common diseases..

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

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6 up votes
2 down votes
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Goal 2: Reduce Human Disease

Controversies exist regarding the treatment of the thoracic aorta in those with bicuspid aortic valve

Controversies exist regarding the treatment of the thoracic aorta in those with bicuspid aortic valve (BAV), in particular: 1) conflicting views regarding criteria for elective surgery, particularly aneurysm size 2) extent of thoracic aortic aneurysm repair.

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

Details on the impact of addressing this CQ or CC

This is a population that may approach 6 million Americans, without inclusion of their trileaflet aortic valve blood relatives. The controversy generally revolves around when to intervene surgically to prevent an aortic catastrophe, and how much of the ascending aorta should be removed (will any residual ascending aorta enlarge over time, and if so, what risk does this represent versus another aortic surgery later?).

Compounding this is the recognition in the literature of significant percentages of aortic dissection at sizes occurring below the guidelines for elective surgery. Patients do not realize that sometimes they are told to wait for elective surgery based on a size difference roughly as small as the thickness of a nickel (approximately 2 mm) or a dime (just over 1 mm).

The implications of this uncertainty in their treatment are staggering, particularly in light of the potential consequences for the most vulnerable individual, which include sudden death. Even those who survive an aortic emergency, with a chronically damaged aorta, face a very different future from that of someone with a non-emergent aortic repair with no residual aortic injury. Surgical uncertainty regarding the aorta should also consider valve surgeries needed by some individuals, and the total number of surgeries an individual may ultimately face.

Many with BAV are vibrant and active, if they avoid premature injury or death. Their disability or loss robs society of their many gifts.

Feasibility and challenges of addressing this CQ or CC

The medical literature reflects varying information and findings, perhaps due in part to the spectrum of expression across this large population, and the characterization of relatively small numbers of individuals under varied scenarios. Some may be carefully followed and receive medical treatment for blood pressure. Others may not receive those benefits, some being diagnosed only in emergency settings. Greater consistency in knowledge and treatment would benefit individuals and families. Advancements are very feasible within a five to ten year period and could greatly benefit the future of those undergoing surgery.

In the interim, patients are empowered when they understand these controversies: the known data regarding aortic size and dissection, and the considerations around the extent of aortic removal, and are fully engaged in elective surgery decisions.

Name of idea submitter and other team members who worked on this idea Arlys Velebir, Bicuspid Aortic Foundation

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Goal 2: Reduce Human Disease

Bicuspid aortic valve is not a “one size fits all” condition. Variations exist within families and the population generally.

Clinical disease manifestations in individuals and families where bicuspid aortic valve is present may best be described as a spectrum, with considerable variability in presentation. Patients and families would benefit from an individualized approach, which does include familial medical history, but couples that information with current best understanding of BAV, considering both variations and risks.

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 variability of aortic disease expression (aorta and valve), while amenable to trend analysis, does not lend itself well to a “one size fits all” approach to care. Some individuals and families display other characteristics in their body suggestive of additional complexity. Brain aneurysms are also mentioned in the literature in the presence of BAV.

Braverman’s article, “Guidelines for management of bicuspid aortic valve aneurysms: what’s the clinician to do?” highlights the variation in guidelines regarding elective aneurysm surgery in BAV patients, discusses why “one size fits all” is not appropriate, and supports the importance of an individualized approach.

Individuals and families face some degree of distress, most particularly those stricken by the serious injury or death of a loved one, and anguish over their future. Some, told surgery was many years away, or that they were fixed for life, have lived to discover those well intentioned words were far from accurate. Others, diagnosed with BAV, have lost their lives.

Individualized care, rather than general statements meant to reassure a large and varied population, is important in order to live confidently and proactively continue with follow up. An approach to care that does not use “always” and “never” thinking, and that avoids predictions interpreted as fact, will do a great deal to instill confidence and engagement in BAV individuals and families, who make life decisions based on what they are told.

Feasibility and challenges of addressing this CQ or CC

This is an intelligent population that is well suited to grasp the issues and participate in decision making. Patients and families desire to be told accurately what is and is not known, to be assessed individually, and to have greater understanding of the implications for blood relatives. They desire to have an informed voice in their treatment decisions, including the timing of elective surgery based on surgical risk versus the risk of living with the disease

Name of idea submitter and other team members who worked on this idea Arlys Velebir, Bicuspid Aortic Foundation

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10 up votes
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