The future of heart and lung transplantation
February 7, 2011 1 Comment
Blog Post by Clive Lewis, Andrew Klein, Nick Lees and Stephen Webb, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, CB23 3RE
The field of transplantation has spawned more new specialties and Nobel prize winners than any other in medicine. Christiaan Barnard’s performed the first heart transplant in 1969 in Cape Town, South Africa. The first lung transplant was performed even earlier, in 1963, by Hardy and colleagues at the University of Mississippi in the USA, although two decades passed before this procedure become a viable option for end stage lung disease. Heart transplant is now the treatment of choice for selected patients with advanced heart failure, with over 85,000 procedures having been performed worldwide during the last 40 years. On average, more than 5000 heart transplants are undertaken every year, in more than 225 centres.
Two important challenges transplantation are the increasing numbers of referrals, and the falling number of suitable donor organs available. This has lead to a major imbalance between supply and demand. Allocation of a scarce resource (the donor organ) can be viewed from two different perspectives: From the recipient’s point, it could be argued that the organ should be allocated to the most ill patient. From the point of view of the wider community of heart or lung failure patients, society in general, and the donor family, it might be argued that the organ is given to the recipient predicted to have the best long-term outcome after a transplant. In practice, a compromise between these two positions is required. In addition, understanding the short and long-term survival of recipients is important to place transplantation within the context of the success of other medical and surgical therapies because, despite the success of transplantation and improvements in recipient outcome, only a small fraction of advanced heart and lung failure patients can be treated by this modality.
The current state of heart transplantation
In the early years, survival after heart transplantation was limited to the medium-term, with frequent mortality due to rejection and severe infection (one year survival averaged 30% in 1967-1973, rising to 60% in 1974-1980). Subsequently, survival has increased with each decade, although the biggest improvement has been during the first year after transplant due to advances in donor management, cardioplegia, intensive care and, particularly, immunosuppression with the introduction of cyclosporine. The International Society for Heart and Lung Transplantation (ISHLT) Registry is the largest dataset for heart transplantation worldwide, and shows a half-life of 10 years following transplant conditional upon surviving the first year of 13 years. Paediatric transplant has even better results with half-life of 11.3 years (recipients aged 11-17 years), 15.5 years (1-10 years) and 18 years (<1 year). Importantly, there is also a significant improvement in functional status and quality of life with over 90% of recipients having no functional limitations during the first 7 years, over 50% working or retired at one, three and five years and re-hospitalization in less than 25% of patients one year after heart transplant.
Patients with New York Heart Association (NYHA) Class IV heart failure persisting despite best medical therapy will generally derive prognostic benefit from heart transplantation. Cardiomyopathy (predominantly dilated forms) and coronary artery disease account for almost 90% of all recipients, with the latter number decreasing in recent years.
Mechanical cardiac support (intra-aortic balloon pump, extra-corporeal membrane oxygenation and ventricular assist device) is used as a bridge to transplant in the UK, particularly for those who deteriorate on the HT waiting list. New generation ventricular assist devices (VADs) are smaller and more reliable, with smaller drivelines and controllers which allow long-term support over several years for advanced HF patients. Used widely in the rest of Europe and the US, VADs provide good quality of life with improved prognosis, but with complications including infection, embolic events and device malfunction. It is hoped that a programme of long-term VAD implantation will commence in the UK in 2011. Xenotransplantation was a great hope for the future a decade ago, but remains a long way from clinical application due failure to completely understand immunobiology, and concerns about transmissible zoonotic infection.
The current state of lung transplantation
This is a proven treatment option for carefully selected patients with end-stage lung disease, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (PAH).
Generally, sequential bilateral transplant is performed, but single lung transplant may be offered to patients with COPD and IPF. LT recipients generally have single organ failure, severe exercise limitation and symptoms, and a life-expectancy of less than 2 years.
Lung transplantation improves prognosis, symptoms and quality of life with most recipients living independent lives and many returning to education or employment. Outcomes for lung trasnplant lag behind other solid organ transplants with an overall mean five year survival of 50%, although survival rates vary according to transplant procedure, era, patient age and underlying diagnosis. Recent improvements in survival are due to better surgical techniques, perioperative anaesthetic and intensive care management and careful long-term surveillance and management.
Infections, especially pulmonary, are the most common cause of morbidity and mortality at any point. Predisposing factors include direct exposure to the external environment, impaired mucociliary clearance, reduced cough, and injury to the bronchial mucosa. Lung transplant is associated with higher rates of acute rejection than other solid organ transplants, necessitating higher levels of immunosuppression.
A number of developments may improve the outcome and address donor shortages: live lung lobar transplantation (including bilateral lobe transplantation); Novalung (non-pulsatile lung-assist membrane ventilation to support patients in lung failure waiting for transplantation); improved lung preservation (reduced incidence of primary graft dysfunction); lung donation after cardiac death (lungs remain viable for several hours after cardiac arrest and has led to a recent small increase in the UK) and, recently, clinical use of ex-vivo lung perfusion (donor lungs are perfused and ventilated in a closed system, allowing preservation, assessment and optimization of marginal organs prior to transplantation).
Recent press reports highlight an increasing number of donors in the UK, and a favourable state of transplantation in general with the total number of all organ transplants carried out in the UK rising for the fifth year in succession, reaching 3706 in 2009. However the number of potential cardiothoracic organ donors has been steadily decreasing, and around 10% of patients die whilst on the waiting list for for heart or lung transplant. Patients also have long waits with a median waiting time for adult non-urgent heart of 183 days and 511 days for adult lung transplant. Unfortunately, the number of heart transplants performed worldwide is declining every year. This trend is seen in Europe, and particularly in the UK, whilst the number of hearts transplanted in the US remains fairly static. In 2008 the UK Organ Donation Taskforce set out to increase organ donation rates by 50% by 2013. The taskforce’s recommendations have resulted in an increase in the overall rate of donation from 13 to 15.5 per million of the population.
To learn more about all aspects of transplantation, look out for Organ Transplantation: A Clinical Guide. edited by Andrew Klein, Lewis C, Masden J. published byCambridge University Press, available from July 2011
Andrew Klein is aslo co-editor of Core Topics in Cardiothoracic Critical Care, published by Cambridge University Press