MATERIAL MATTERS COLUMN
The rise and fall of heart transplantation
Professor David Williams DSc, FREng retired from the University of Liverpool, after 40 years, at the end of 2007. He retains the position of Emeritus Professor there and now has a series of professorial appointments in North Carolina, USA; Sydney, Australia; Cape Town, South Africa; and in China. He offers consulting services from his company Morgan & Masterson, based in Brussels, Belgium. He is Editor-in-Chief of Biomaterials, the leading journal in the biomaterials field. He is Scientific Director of STEPS, the European Commission Framework VI Programme on a Systems Approach to Tissue Engineering Products and Processes.
The origins of transplantation
The Cape Town Museum is remarkable. The main wing of the old Groote Schuur Hospital has been replaced by a modern building and part of it converted into this museum. The operating theatres, which had been modernised, have been restored to their original form with original high ceilings and tiled floors and walls, and re-fitted as far as possible with the equipment that Barnard and his team used in 1967. It is a fascinating sight, with the original heart–lung machine, the bulky heat exchanger and oxygenator and excellently reproduced mannequins replicating the clinical staff. Many of the letters Barnard received at that time, both in praise and in damnation of him (for example, one is addressed “To the Butcher of Groote Schuur”) are displayed, together with the preserved hearts of Darvall and Washkansky. The history of medicine is an interesting and worthwhile subject, but let us move forward to today. Where has the technology moved to and what are the problems?
Factors that control success
Cost is one factor, although it is not decisive in terms ofthe progress of heart transplantation. Average actual hospital costs for the procedure are in the region of US$150 000, although this depends on the general health of the patient and the variable requirements for intensive care and length of hospital stay. Health economics have to be considered in the context of alternative therapies. It is interesting to note that the equivalent hospital costs for treatment by left ventricular assist devices (LVADs) are nearer to US$ 20 000.1 The availability of these competing technologies is also a factor in determining the need for transplantation. Although treatment with LVADs is now more readily available, so far this is not diminishing the need for heart transplants. LVADs are successful in many patients, offering as much as a 50% reduction in mortality compared with the best pharmaceutical therapies. However, they are usually considered to be a bridge to heart transplantation and this potentially creates an even larger demand for transplants. In addition, LVADs can of course only benefit those patients where it is the left ventricle alone that is seriously diseased; they are relatively ineffective in those patients where both ventricles are affected. The emergence of the total artificial heart provides for a potentially different outcome, but long term success and a reduction in the clinical need for transplants, have not been realised as yet.
One of the most significant issues is of course the availability of quality donor hearts. In the USA, nearly 100 000 people are on the waiting list and less than one third will receive a transplant. Of these, 10% die each year before a heart becomes available and a further 10% become too ill to undergo the procedure. In spite of many campaigns in many countries to increase the number of organ donors, and to introduce legally based opt-out rather than opt-in schemes, the actual number is still small and not significantly increasing. Equally important is the fact that the average age of donors appears to be increasing and, as a consequence, the quality of the donor hearts that are available is decreasing. The ideal donor would be an otherwise healthy individual in their early twenties who dies of a traumatic event. It is now more likely that the person is in middle age, probably with some existing disease, even their own heart disease, with high blood pressure and high cholesterol. In some places there is a serious shortage of young donors so that heart transplantation for children with congenital heart conditions is problematic.
The news is not all bad, however, and there are considerable prospects for much better outcomes from heart transplantation. The traditional procedure for transplantation has been to wait for confirmation of brain death before removal of the heart and then storing it in a cold ischemic state until transplantation. The maximum time for storage is four to six hours and the one year survival figures for transplant patients is significantly related to the length of time the heart is without blood between donor and recipient procedures.
In February 2007, in the General Hospital in Vienna, Austria, a new procedure was used for the first time involving the Organ Care System of TransMedics Inc. (Andover, Massachusetts, USA), which allows for beating hearts to be transplanted without the need for cold ischemic storage.2 Six other European centres are involved in the study. A little later in 2007, the US Food and Drugs Administration gave approval for a pilot phase of a trial of this technique in the US. The first procedure was performed in Pittsburgh, Pennsylvania, in April 2007. With this technique, immediately after removal from the donor, the heart is transferred to the System, where it is revived to a beating state and perfused with oxygen and nutrient rich blood. In the European study, all the first 20 patients survived beyond the first 30 days.
Heart transplantation has come far, but as yet it is not delivering the widespread benefits of which it is capable. At the moment there is no better treatment for end stage heart failure, but logistics, costs and other issues limit its effectiveness. It is supplemented by other heart assist technologies and may well be challenged by stem cell therapy and tissue engineering in the near future. It is to be hoped that the Concorde analogy does not come to pass.
1. P.L. Digiori et al., “Heart Transplant and Left Ventricular Assist Device Costs, “ J. Heart Lung Transplant, 24, 200–204 (2005).