2.1: PediaValve

PediaValve & the Tissue Engineered Heart Valve

Modified from Merryman (2008) in Science and Engineering Ethics 14

In the United States in 2002, nearly 20,000 people died from various forms of valvular heart disease. Heart valves serve two important functions: (1) assuring that circulating blood flows in only one direction through the heart; and (2) allowing the chambers of the heart to alternatively fill for ejection. When a valve (or valves) are impaired, death is likely.

However, there are currently solutions for a large portion of the population. For healthy adults, mechanical heart valves are suitable as they have excellent durability and longevity. However, other patient populations are not so lucky. Elderly patients and unhealthy young persons cannot typically accept mechanical heart valves and so instead typically receive bioprosthetic valves from a non-human animal or human cadaver. Bioprosthetic valves typically require future surgeries and have greater risk of failure than mechanical valves.

Additionally, bioprosthetic valves are extremely limited for the pediatric population due to size restrictions. Such valves are typically just too large to fit in a child’s chest. This is especially problematic for children born with valvular heart disease who need a solution as an infant or toddler. Any child in need of a heart valve replacement who does not receive one will, within a matter of months to just a few years, will die from their valvular heart disease.

Enter the Tissue Engineered Heart Valve

Recent academic research has shown the promise of Tissue Engineered Heart Valves (TEHVs) for pediatric application. TEHVs are live tissue, like bioprosthetic valves, but the entire valve is engineered and so the initial size of it can be controlled. The TEHV, once implanted, can then grow with the patient, unlike mechanical heart valves.

The key to TEHV production is the bioreactor used to create and exercise the valve prior to implantation. The bioreactor provides a sterile environment to ensure the TEHV will hold up both mechanically and biologically once implanted. It is imperative that the TEHV is fully functional upon implantation, for otherwise the heart would be stopped for an extended period of time likely resulting in brain damage or death.

PediaValve is a small company that has been working on two parallel designs for TEHV bioreactors. They are now at the point where they must decide which of the two bioreactor types to focus on for production, as they simply cannot produce both. They have sought your expert assistance in making the decision in an ethically responsible way. PediaValve informs you that both options are equally profitable for the company so that cannot help decide between the options.

The Bioreactors

PediaValve has been working on two different types of bioreactors: The Total Heart System (THS) and the Modular Valve Unit (MVU).

The Total Heart System is, as precisely as can be obtained, a replica of the human heart. It offers near flawless hemodynamic performance and laboratory studies have been excellent. Animal trials have also been very promising with the THS. To date, 20 sheep have been explanted at 20 weeks with a TEHV developed in the THS, and these TEHVs resemble the animal’s native valve. A single THS can be used to prepare up to 5 TEHVs.

The Modular Valve Unit aims to dramatically simplify the THS, removing costly components not deemed ‘absolutely essential’ in order to decrease the size and improve the usability of the unit. The MVU serves the same function as the THS, but differs vastly in its efficacy and performance. The MVU does not replicate heart function, but it is not know if this is necessary or if it is possible for a TEHV to properly develop in sub-optimal conditions. Laboratory studies have shown that 25% of the TEHVs fabricated in the MVU present with slight defects (as compared to 0% in the THS). These defects are important because the implanted valve will be exposed to high pressure, and defects can lead to tearing, causing the valve to fail. Animal studies have shown that the MVU develops valves to a comparable level of the THS; however, the animal explants were not as promising as with the THS 20 weeks after implantation. The MVU is a single use device, preparing one TEHV before needing replacement. However, each MVU is much cheaper than a single THS.

Technical Requirements and Distribution

Because each bioreactor does its job in a different way, they each have different requirements that affect distribution and usability.

Given the complexity of the THS, fewer will be distributed and they will all be housed in 4 regional centers around the United States. The THS requires highly trained and specialized personnel to operate. The lower cost and ease of use of the MVU means that it can be distributed worldwide and used by just about anyone after a single day of training.

Given these differences it has been estimated that about 100 children per year can be serviced by the THS while 1,000 children per year can be serviced by the MVU. Notably, the 100 children for the THS will need to find a way to one of the regional centers in the United States for treatment, while MVU-based treatment could be available just about anywhere.

Effect Predictions

The medical consultants for PediaValve have compiled a table outlining the predicted outcomes of both options over a 20-year period:

Eventuality Total Heart System (THS) Modular Valve Unit (MVU)
Implantations over 20 years 2,000 children in US 20,000 children worldwide
Surgical mortality (i.e., death during implantation surgery) 5% (100 children) 5% (1,000 children)
Deaths due to Acute Valve Failure within 1 year 1% (20 children) 10% (2,000 children)
Deaths due to chronic valve failure over the next 19 years 0.5% (10 children) 20% (4,000 children)
Survival to 20-year mark 93.5% (1,870 children) 65% (13,000 children)
Predicted survival to average life expectancy 70% of total implantations (1,400 children) 20% of total implantations (4,000 children)

License

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The Primacy of the Public by Marcus Schultz-Bergin is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.