Heart transplantation
Much of the pioneering work into human heart transplantation was done by Shumway and Lower in the early 1960s but the first successful human heart transplantation was performed by Barnard in 1967. The early results were very poor and, in spite of the initial optimism for the technique, the number of centres declined to only a few Better patient and donor selection, together with the introduction of cyclosponin A, has led to a revival of the technique and it is now established as a treatment for end- stage cardiac failure in certain groups.
The main indication for heart transplantation is advanced terminal cardiac disease classified as New York Heart Association (NYHA) 4, with no alternative conventional medical or surgical treatment, and with a mortality rate higher than 90 per cent per year if transplantation is not carried out. Indeed, death commonly occurs while on the waiting list. Most cases referred for transplantation have either an ischaemic or a dilated cardiomyopathy. Rarer causes include postviral and hypertrophic obstructive cardiomyopathy. The patient needs careful preoperative assessment to determine the suitability for transplantation and counselling to prepare for the demands of life after transplantation. Younger patients tend to benefit most but the indications for transplantation have broadened since it was first introduced. Unfortunately, the limiting factor on the number of transplantations performed per year is the availability of donor hearts.
Absolute contraindications to transplantation include:
· active infection [or human immunodeficiency virus (HIV) positive];
· irreversible pulmonary hypertension;
· malignancy;
· another life-threatening illness.
Relative contraindications include:
· age >60 years;
· active duodenal ulceration;
· significant pulmonary vascular disease;
· creatinine clearance <30 mmol/litre;
· drug or alcohol abuse;
· psychiatric illness.
Donor selection is critically important if early postoperative problems are to be avoided. Potential donors will be certified as brain dead if two separate brain-stem function tests show no activity. Most donors have had head injuries or an intracerebral haemorrhage. Injuries to other organs may be present, but if the heart shows no evidence of injury then it may be used. Haemodynamic instability can occur at any time in these patients, and skilled intervention with judicious use of inotropes, ventilation and diuretics may be required to keep the patient stable until the organs are harvested. Ideal criteria for the donor include the following:
· age (<45 years for males, <50 years for females) - the incidence of coronary artery disease rises after these ages;
· weight (within 25 per cent of the recipient);
· ABO compatibility;
· no evidence of cardiac injury (normal EGG, normal chest radiograph);
· no increased requirements for inotropes;
· no evidence of active infection (HIV, hepatitis B or bacterial);
· no palpable coronary artery disease.
The donor operation is usually performed in conjunction with other transplant teams. If the liver and kidneys are to be used, they require some preliminary dissection before removal of the heart. The heart is exposed by a median sternotomy and the cavae are dissected from the pericardial reflections to expose more of their length. Heparin is given and the aorta cannulated with a perfusion catheter. The aorta is clamped and the inferior vena cava divided to allow venous blood to escape into the chest. Cold cardioplegic solution is infused under pressure into the aortic root and the heart arrests in diastole. A pulmonary vein is then divided to allow blood in the left atrium to escape. Once the cardioplegic solution is infused, the pulmonary veins are divided followed by the pulmonary artery. The aorta is then divided just below the cross-clamp, leaving only the superior vena cava to be divided. This is divided as high as possible to avoid damage to the sinoatrial node. Care should be taken that all central venous cannulae are withdrawn to avoid possible embolism in the donor heart. The heart is then stored in cardioplegic solution and transported in ice to the recipient hospital.
The recipient operation
Once it is clear that the donor heart is satisfactory then the recipient operation is started. The heart is approached through a median sternotomy and heparin is given intravenously. The cavae are cannulated separately and the aorta is cannulated just proximal to the innominate artery. Cardiopulmonary bypass is not started until the donor heart is in the operating room. The recipient heart is excised leaving a generous cuff of atria and interatrial septum. The donor heart is trimmed appropriately and suturing begins with the left atria, the right atria, the pulmonary artery and finally the aorta. The heart is then de-aired and the cross- clamp released. Ventricular activity usually starts spontaneously but occasionally temporary pacing is required. The heart is allowed to beat on bypass until rewarming is complete and haemostasis is achieved. Ventilation is commenced and cardiopulmonary bypass is slowly weaned until the donor heart is supporting the circulation.
Postoperative care
In common with all forms of allogeneic transplantation, the normal host response is to mount an immune response to the donor organ. To combat this problem, regimens of immunosuppressive therapy have been developed. Intravenous methylprednisolone and azathioprine are given at the time of operation and these are converted to the oral forms once the patient is able to tolerate oral or nasogastric fluids. Cyclosporin A is added if the renal function is satisfactory. Cyclosporin A is nephrotoxic and regular trough levels are required to avoid excessive toxicity. Treatment with azathioprine can result in liver dyscrasias and neutropenia. The incidence of rejection is greatest in the first year post-transplantation. The only reliable way of monitoring the presence or absence of rejection is by endomyocardial biopsy. This is an invasive procedure requiring cannulation of a major vein and taking small biopsies of the ventricular septum from the right ventricle. The presence of a lymphocytic infiltrate suggests rejection and myocyte necrosis implies severe rejection. A pulse of intravenous steroids is usually given as first-line treatment but other therapies include antilymphocyte globulin and the monoclonal antibody preparation OKT3. Most rejection episodes resolve with treatment but occasionally the rejection is refractory to treatment and the allograft fails.
Another important cause of morbidity and mortality in these patients is infection. Immunosuppression lowers the host's resistance to infection and opportunist infections in addition to common infections may occur. The most common site for infection is the chest. Antibiotics should not be commenced until a full infection screen (throat swabs, midstream urine, sputum and venous blood cultures) has been taken. Viral, protozoal and fungal infections may also occur. Late complications include accelerated graft vascular disease and systemic malignancy.
Alternatives to transplantation are being explored. Novel operations such as skeletal myoplasty, left ventricular reduction surgery and implantable ventricular assist devices have had some notable success but these procedures have yet to gain widespread acceptance.
Results
The perioperative mortality rate is about 10 per cent but patients surviving to leave hospital may have a 90 per cent 1- year survival. This falls to 70 per cent at 5 years and 60 per cent at 10 years. Patients surviving more than 1 year usually have a good exercise capacity and are able to return to work (Fig. 48.59).
Future prospects
Heart transplantation is limited by donor availability. Increasing the donor pool by widening donor criteria and increasing public awareness have helped, but demand exceeds supply. The use of xenografts is one possibility but ethical, logistic and rejection problems mean that this prospect is a long way off. Artificial hearts have a role to play in supporting the circulation until a heart becomes available for transplantation but they do not seem practical for long- term use.