Current Projects in Vascular Biology

 Generation of Prosthetic Heart Valves

According to the American Heart Association (AHA), congenital cardiovascular defects are the most common cause of death amongst infants, noting that heart defects account for the death of over 24% of newborns that die from birth defects.  These heart defects are present at birth and arise from abnormal formation of the heart or major blood vessels while the infant is in the womb.  These defects can affect 1 or all 4 of the valves, each disrupting the flow of blood through the heart.  Currently, there are 25 described congenital heart defects including valvular defects, atrial or ventricular septal defects, aortic stenosis, hypoplastic left heart syndrome, and many others.     

View a list of all Congenital Heart Defects

AHA projects that in the coming year over 32,000 infants are expected to be affected with some form of heart defect that will require single or multiple invasive treatments throughout their first year of life.  One set of congenital defects of interest to UNMC surgeon and researcher, Dr. James Hammel, MD, are valvular defects.   Although the level of care has increased dramatically over the last 50 years, there are currently no sufficient prosthetic heart valves that exist for infants and children who suffer from abnormally developed or diseased heart valves.

Prosthetic heart valves have been in use since the 1960s and have progressively developed since.  However, no ideal valve exists, especially for infants and children.  Issues such as size, durability, strength, long-term coagulation, ability to grow with the child and adjust to the physical demands imposed during childhood and young adult life are all factors that must be considered when choosing an appropriate prosthetic valve.  To date, there is nothing available in the medical/biological market that can accommodate all these needs.  

Dr. Hammel, a renowned cardiothoracic surgeon who specializes in corrective neo-natal and pediatric cardiovascular surgery at Children’s Hospital in Omaha, is working to find a better option for heart valve replacements and patches that will not require life long anti-coagulation or immunosuppressive drugs nor additional surgical intervention later in life.  The current therapies available for those suffering from congenital valvular defects are:

      1.  Implantation of a bioprosthesis:

  • Tissue reconstruction of bovine (cow) pericardium to enhance weak valves or create new valves all together
  • Treated porcine (pig) or bovine (cow) valves for implantation

      2.  Implantation of mechanically engineered prosthesis

      3. Human cadaver homograph

      4. Allograft using patients own pulmonary valve to replace the damaged aortic valve 

 

Each of these options has their drawbacks and scientists have yet to come through with a model that is entirely effective. 

      1)   Porcine and Bovine tissues are heavily treated with chemicals to affix and stabilize the tissue, reduce antigenicity, protect the tissue from the recipients defense systems, and minimize their propensity to calcify.   Exposure to these chemicals, however, kills all associated fibroblasts, disabling the tissue to remodel or regenerate in the same fashion that a functional valve would.  This leads to tissue degeneration over time and eventually failure of the prosthesis. 

      2)   Although very durable, mechanically engineered valves are not able to “grow with” the child and would need replacements often, increasing mortality with each replacement.  In addition, synthetic materials induce an immune response, coagulation, and hemolysis making them unsuitable option for repair.        

      3)   Allografts from organ donors provide a limited amount of tissue and is dependent casualties and their lifespan is limited.  In addition, calcification and degeneration are observed later in life.

      4)   Autologous tissue reconstruction techniques can only be used to repair particular anomalies but is primarily performed in children.  Existing, healthy tissue must be available and accessible. 

      5)   Administration of long-term anti-coagulation drugs is required due to risk of thromboembolic complications with the valve

      6)   A minimal amount of surgeons have mastered the allograft technique and this repair is selectively offered.



Researchers at UNMC are working to find new ways of developing functional heart valves that may begin to diminish some of the hurdles and secondary complications associated with current methods in heart valve repair.

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