Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.1d. Increase our understanding of the initiation and progression of valvular heart disease (VHD) toward improving its diagnosis and therapy

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Overview

At present, the only generally accepted therapy for VHD is surgical repair or replacement of the affected valve.  Techniques are needed to identify individuals at risk and to predict the course of disease in each individual.  Less invasive therapies are needed to encourage intervention before symptoms develop.  A base of clinical evidence is needed as a foundation for disease management.

Each year, VHD in the U.S. accounts for over 20,000 deaths and over 90,000 hospitalizations at a cost of nearly $9 billion.  The overall prevalence of VHD in the U.S. is 2.5 percent, but the prevalence increases to over 13 percent for those aged 75 years and older. 

Bicuspid aortic valve (BAV), also known as bicommissural aortic valve, is the most common congenital cardiac malformation with a prevalence of 1-2 percent.  Individuals with BAV are at greater risk of developing VHD.

Strategies to Accomplish this Goal May Entail:

Basic Research:

  • Develop a detailed understanding of the molecular, cellular, and physiological mechanisms of initiation and progression of VHD, including the role of pathological processes such as inflammation, fibrosis, and calcification,.
  • Characterize the mechanics of native valves using imaging, computational modeling, and in vitro measurement.
  • Develop models of chronic and degenerative VHD.
  • Establish a foundation for personalized intervention in VHD:
  • Identify the genetic pathways involved in heart valve development and the mutations responsible for congenital malformations such as BAV.
  • Identify physical factors that contribute to the initiation and progression of VHD, such as shear stress.
  • Identify genetic factors that contribute to the initiation and progression of VHD and improve our understanding of their interaction with physical factors.

Translational Research:

  • Identify biomarkers for the initiation and progression of VHD.
  • Develop improved imaging methods, such as high-resolution echo and molecular imaging, to assess valvular structure and function and to detect and quantify subclinical VHD.
  • Develop image-based computational methods for planning interventions, such as models of flow dynamics and structure-fluid interaction.
  • Apply advances in regenerative biology to the development of bioprosthetic heart valves.
  • Continue the development of less invasive surgical techniques for early valve repair or replacement.

Clinical Research:

  • Identify lifestyle factors that contribute to the initiation and progression of VHD.
  • Determine appropriate timing of interventions for VHD.
  • Explore pharmacologic approaches to prevent or delay the development and progression of VHD and their associated clinical outcomes.
  • Develop and evaluate interventional cardiology techniques, such as percutaneous valve repair or replacement in adults and valvuloplasty in utero.
  • Develop and evaluate less invasive surgical and interventional techniques for early valve repair or replacement.

Contributing Sources:

September 2008

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