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 predictors of CAVD compared to the predictive power of these correlates with vascular disease (Ortlepp et al. Heart 2003). It is imperative to understand these differences such that CAVD can be treated at the earliest possible stages before calcification progresses to an irreversible endpoint.

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.

Tags (Keywords associated with the idea)



28 net votes
33 up votes
5 down votes
Idea No. 750