Organ and Tissue Transplant Therapies

• Cardiac Transplantation
  • History
    • Dr. Norman Shumway perfected the surgical technique and completed the first cardiac transplant between two canines in 1958.
      
    • The first successful adult heart transplants were performed in 1967 in Cape Town, South Africa by Dr. Christiaan Barnard (a trainee of Dr. Shumway, both of whom interned at the University of Minnesota) and in 1968, by Dr. Norman Shumway himself, in the United States (Stanford University).
    • The first successful pediatric heart transplant took place in 1984, in the United States and was performed by Dr. Eric A. Rose (Columbia University). The infant received a second transplant in 1989, and went on to live a long, productive life.
    • Since this time, significant advances have been made in surgical procedures and post-transplant management, as a result, transplantation is now safer and more widely performed.
  • Indications
    • Transplantation is generally considered when life expectancy from the underlying heart problem is less than 1 to 2 years if it were to follow the natural course, or when heart failure is so severe that there is very poor quality of life.
    • Often, transplantation is undertaken after previous surgical procedures and therapies fail to repair or palliate identified defects well enough to allow the patient to survive.
    • Nearly all pediatric patients, even those with significant congenital heart defects are amenable to the cardiac transplant procedure; albeit with different potential complications and surgical requirements. For example, anomalies of venous return, malposition of the heart or great arteries may require additional tissue from the donor and/or may require additional reconstruction at the time of transplant.
  • Contraindications and risks
    • The most important absolute contraindication to cardiac transplantation is severe elevation of pulmonary vascular resistance. Patients with fixed pulmonary hypertension are at risk of right ventricular failure of the donor heart. After transplantation, elevated pulmonary vascular resistance can overwhelm the right ventricle which has only been exposed to the normal, low pressure, pulmonary vascular resistance. In other words, patients with chronically elevated right arterial pressures, elevated pulmonary vascular resistance, and restrictive cardiomyopathy are all at risk for donor right ventricular failure.
    • Patients with a history of chronic malignancies are at risks for such recurrences; i.e., with the immunosuppressive therapies used post-transplantation. Note, that these immunosuppressive agents also have the potential to be toxic in patients with preexisting renal or hepatic dysfunction.
    • It is important to note, that identified preexisting psychiatric, psychosocial, and neurodevelopmental conditions of the patient and/or family are also taken into consideration for patient selection; as the required post-transplantation regimens for monitoring and immunosuppression therapies require diligence on the part of caretakers.
  • Allocation of donor organs
    • In the United States, the United Network for Organ Sharing is responsible for matching donors with recipients. This is done according to a well established criteria, including: compatibility and blood typing, the relative degree of decompensation of cardiovascular function in the recipient, the length of time on the waiting list, and/or the relative distances between donor and recipient (time to recover and deliver the donor organ).
    • The allocation process has the potential to be extremely difficult and requires careful judgments on the part of practitioners, so to best determine the likelihoods of successful transplants, and which patients have the greatest risks of death: i.e., whom could afford to remain on the waiting list.
  • Operations
    • The goal of cardiac transplantation is to retrieve and transplant a functional donor heart in the shortest amount of time. Once the donor/recipient match has been made, the heart is excised and induced into a hypothermic state with a cardioplegia solution. The heart is then transported to the recipient’s surgical site, where the recipient has been already prepared for transplant and placed on cardiopulmonary bypass. Ideally, the ischemic time of the heart, after procurement to implantation in the recipient, is less than four hours.
    • The operation in the recipient includes construction of anastomoses between the donor and recipient vessels in a sequential fashion. As in procurement, the goal is to limit the amount of time the patient is maintained on cardiopulmonary bypass.
  • Survival
    • Importantly, overall mortality for pediatric patients post-transplant has decreased significantly; since the first procedure in 1968. Survival has improved in pediatric recipients with each era analyzed, with overall survival at 1 year post-transplant now up to 90%, and 3 year survival of 85% (Amplatz Children’s Hospital, U of MN).
    • The survival rate for pediatric heart transplantation has improved in recent years with the introduction of better anti-rejection and immunosuppression therapies.
    • Half-life data (when 50% of patients are still alive) from the International Society for Heart and Lung Transplantation (ISHLT) illustrates this improvement.
      • Infants (less than 1 year): 19.2 years
      • Children (1-10 years): 15.6 years
      • Adolescents (11-17 years): 11.9 years
    • Note, infants who undergo transplantation elicit higher early mortality rates, but then significantly better long-term outcomes relative to patients in older age groups. The most common cause of death 30 days after transplant is acute failure of the transplanted heart, 1 to 5 years after is acute cellular rejection and infection, and beyond five years is chronic rejection.
• Tissue engineering
  • Transplantation to replace arteries or valves have considerable limitations. None of the current biological or synthetic devices fulfill the characteristics of an ideal replacement structure including the ability for blood to flow freely, potential for growth, durability, resistance to infection, and compatibility to prevent thrombus formation.
  • Recently, researchers have begun to focus efforts on engineering tissues that fulfill these criteria by making replacements for cardiac structures starting from the individual cells they are comprised of.
  • These structures have the potential to serve as alternatives to transplantation of either biological or synthetic replacements; however, significant challenges must be overcome before these methods become a reality.

References

1. International Registry for Heart & Lung Transplantation (2012). Pediatric Heart Transplantation [PowerPoint slides]. Retrieved from: http://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry
2. Keane, J.F., Lock, J.E., & Flyer, D.C. (2006). Nadas’ Pediatric Cardiology (2nd ed.). Philadelphia, PA: Saunders Elsevier.