Cardiac Transplantation                                                                      

The first human transplant was undertaken in 1968 by Christian Barnard. Paediatric transplantation was developed in Europe by Magdi Yacoub in the early 1980’s. Currently 200 centres undertake 3,000 heart transplants (adults and children) worldwide.

The main indication is end stage cardiac failure - this is usually due to dilated cardiomyopathy but also occurs in some complex diseases.

The main limitation is the donor pool and the limited 4 hour time frame from explantation from donor to implantation into recipient. Complications include rejection and the complications of immunosuppression - opportunistic infections, lymphoproliferative disorders, renal dysfunction and hypertension.

Immunosuppression

This is required for life. Ciclosporin A (Neoral) and azathiaprine are the most commonly prescribed drugs. Ciclosporin is given orally and is monitored by whole blood levels and surveillance of renal function. Ideal levels are 150-300 microgram/l. Side effects include nephrotoxicity (the dose should be reduced in renal impairment), hepatic impairment, hypertension, headache, tremor, hypertrichosis and gum hypertrophy. Beware interactions with drugs that alter hepatic cytochrome p450 as they will affect blood ciclosporin levels. Erythromycin, fluconazole and amiodarone increase ciclosporin levels. Rifampicin and most anti-epileptic medication reduce ciclosporin levels.  
Azathioprine’s therapeutic effect is mediated by bone marrow suppression. Dosage (approximately 2 mg/kg/day) is governed by white cell count which should be maintained at 5 x 109/l or a neutrophil count >2 x 109/l. If counts are lower the dose should be reduced or withheld until recovery.

Rejection

The organ match is only uses the ABO grouping - there is insufficient time and donors to HLA match.
The symptoms of acute rejection include fever, malaise, anorexia, vomiting, breathlessness. Hepato-splenomegaly, and a gallop rhythm are frequently present. The WCC and CRP are usually increased. The ECG shows a 25% or more reduction in ECG summated voltages.

CXR shows cardiomegaly. Echocardiogram changes include reduced fractional shortening, ejection fraction, increased LVDD and wall thicknesses. There may be a pericardial effusion.

Endomyocardial biopsy may show histological changes and can be graded according to severity

Treatment of mild rejection is oral prednisolone. Acute severe rejection is treated with intravenous Methylprednisolone.

Chronic rejection causes accelerated coronary atherosclerosis. This is "silent" as the heart is denervated and ischaemic pain is not felt. Currently the only treatment is re-transplantation.

Opportunist Infections

Candida, Aspergillus, Pneumocystis, herpes simplex and cytomegalovirus are the commonest. Nystatin, cotrimoxazole and acyclovir are often given prophylactically.

Lymphoproliferative Disorders

EBV-related lymphoproliferative disease is a serious and not uncommon (20%) complication of paediatric cardiac transplantation. It presents with non-specific lymphadenopathy. Tonsillar enlargement is not uncommon. There is a UKCCSG protocol for the investigation and management of this disorder.

Renal Disease & Hypertension

Ciclosporin is a nephrotoxic drug and most have some degree of renal impairment - Tacrolimus is less nephrotoxic and is increasingly used as the first choice in immunosupression. Drugs that affect renal function will increase the chance of nephrotoxicity eg. ACE inhibitors and Cotrimoxazole may synergistically increase nephrotoxicity. If hypertension needs to be treated avoid ß‑blockers and use nifedipine with or without diuretics.

This page was last edited 14/2/2004

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