D. Aravot

Cardiac transplant waiting lists, donor shortage and retransplantation and implications for using donor hearts

Abstract Cardiac transplantation is established as the standard therapy for end-stage heart failure. 1 The shortage of donors is the limiting factor in heart transplantation. 2 Much emphasis has been placed on increasing donor referrals 3 and appropriate management of potential donors to widen the donor pool. 4 An alternative approach is to examine potential cardiac transplant recipients and identify patient subgroups with poor survival. We assessed the impact of donor shortage on the mortality of patients awaiting operation.

Cardiac and lung transplantation.

The lirst successful clinical cardiac transplant was performed by Christian Barnard in Cape Town, South Africa, in 1967. After a flurry of activity worldwide, poor Initial results limited the use of this technique. Several further developments were necessary before the procedure could be applied more widely. During the 197Os, further work, principally at Stanford Hospital in California, established improvements in patient management related to the detection and treatment of rejection. These included the use of repeated cardiac biopsy to detect cardiac allograft rejection and the use of anti-thymocyte globulin. In addition, the legal definition of brain death became accepted in several countries and methods for long-distance organ retrieval were successfully developed.

Alternative method for cardiac transplantation: Surgical considerations and technical aspects

A simplified technique for complete orthotopic cardiac transplantation is described. The potential technical difficulties and surgical considerations are discussed.

Cardiac Retransplantation: Is It an Ethical Use of Scarce Resource?

Cardiac transplantation is established as the standard therapy for end-stage heart failure.The acute shortage of donors is the limiting factor preventing its wider application at present (Wallwork 1989). Regular audit is necessary to ensure that the best potential is being realised from each organ. We assessed the impact of donor shortage on our cardiac transplant programme. We also noted that retransplanted patients had a particularly poor outcome and attempted to identify preventable risk factors.

Coronary flow reserve is impaired early after cardiac transplantation.

The highest mortality rate after cardiac transplantation, at present, occurs within the first year after cardiac transplantation. The state of the coronary microcirculation soon after cardiac transplantation has not been previously assessed. We investigated the hypothesis that coronary flow reserve (CFR) is impaired in the early postoperative period after cardiac transplantation. A 3F intracoronary Doppler flow probe was inserted into the left anterior descending coronary artery and maximal coronary flow was assessed using the non-endothelial-dependent vasodilator papaverine. We compared two groups of patients: group A--13 patients studied 3 months after operation; and group B--25 patients studied at a median of 4 years after operation (range 2-8 years) without coronary occlusive disease (COD). CFR was defined as the quotient of maximum hyperaemic to resting velocity (vel). CFR was markedly impaired in group A patients compared with group B (3.3 SEM 0.3 versus 4.2 SEM 0.2, P < 0.01). No significant differences between mean resting or peak velocities, original diagnosis, age, active rejection, blood pressure, lipid levels, ischaemic time, cyclosporin levels or cytomegalovirus (CMV) status were noted. Responses to papaverine in resistance coronary vessels are impaired in the early postoperative period after cardiac transplantation. This is caused by a combination of higher resting flow and lower peak flow in the early group. This impairment of function in the coronary microcirculation may contribute to early graft dysfunction and reflect changes in vascular smooth muscle function leading to the development of COD.

Coronary flow reserve and coronary occlusive disease

The functional effects of coronary occlusive disease (COD) in cardiac transplant patients on small-resistance coronary vessels are unclear. We investigated the changes in coronary flow reserve (CFR) in response to the non-specific smooth muscle vasodilator papaverine. A 3F Doppler probe was inserted into the left anterior descending (LAD) coronary artery in 61 patients following orthotopic heart transplantation. Studies were performed in 57 males and 4 females with a mean age of 46 years (range 20-61 years). The median time from operation was 4 years (range 3 months to 10 years). Coronary blood velocity was measured at rest (RFV) and maximum hyperaemia (PFV) produced by intracoronary papaverine. Coronary flow reserve (CFR) was defined as the ratio of PFV to RFV. Minor lesions in epicardial vessels were found in 23 transplant patients. The mean percentage diameter of the most severe lesion in the coronary tree was 23% SD 3% including 12 lesions in the LAD coronary artery itself (mean 24% SD 4%). Patients with COD had an impaired CFR (2.6 SEM 0.2) compared with normals (3.9 SEM 0.2, P = 0.0003), adjusting for year after operation. Mean resting flow velocity was similar in both groups (minor COD, 6.8 cm/s SEM 1.2; normals, 7.1 cm/s SEM 0.6), but mean peak flow velocity response to papverine was reduced (16.5 cm/s SEM 2.5 versus 27.3 cm/s SEM 2.6; P = 0.007). In the presence of minor epicardial disease, coronary flow reserve in resistance vessels was reduced due to impairment of peak flow. This demonstrates that non-endothelial-dependent coronary resistance vessel vasodilatation is abnormal and may be caused by a defect in vascular smooth muscle function.

Dominoes - dogma or drama?

Sir: We read with interest the editorial “Dominoes-pragmatism or piracy?” by Dr. Cooper regarding his opinion of heart-lung transplantation and ‘domino’ transplantation. He also reports the excellent results of his centre with bilateral lung transplantation; his 10% mortality at 1 year compares very well to the 20% mortality worldwide [2]. However, there is considerable dogma in his article concerning heart-lung transplantation, i. e. the potential cardiac complications, the “piracy” of the limited donor pool, the efficacy of the operation for end-stage pulmonary disease and the ethics of ‘domino’ transplantation. We would like to address each of these points, including the effect of prolonged ischaemia on lung transplants. At our centre we have now performed a total of 112 heart-lung transplants, of which 30 patients have donated their heart for ‘domino’ transplantation. Actuarial l-year survival for heart-lung transplantation is75 % compared to 91 YO for ‘domino’ heart-lung donors [l]. Moreover, there has been no significant morbidity in these patients due to cardiac complications such as rejection, denervation or coronary occlusive disease, which Dr. Cooper alludes to as potential problems. Centres that perform ‘domino’ transplantation do not “distort organ distribution”; a strict rota by the British Transplantation Service offers the organs evenly to each centre. That centre may use the organs for their own unit and will offer unplaced organs to other centres. Historically, the ‘domino’ hospital has used the generated heart for its own recipients. We have used 21 of 30 ‘domino’ hearts. However, of the last 10 ‘dominoes’, we have exported 6 to other transplant centres in the United Kingdom, and “conflict” has not beengenerated between heart and heart-lung centres. Dr. Cooper also suggests that heart-lung recipients have to wait longer than bilateral lung recipients for a suitable donor. In our experience we have not encountered a donor in whom both lungs are transplantable but not the heart; however, if the situation arose, the heart-lung centres in the United Kingdom, all of which have lung transplant programs, would still be able to utilise the organs. Dr. Cooper concludes from the 3.5-year survival of six double lung transplants that bilateral lung replacement is the valid surgical option for end-stage lung disease despite a 25% mortality. Long-term outcome in bilateral lung transplants needs to be assessed. The function of the second lung with the prolonged ischaemic time will be most interesting as we have demonstrated a correlation between prolonged ischaemic time and recurrent rejection episodes, which predisposes to Obliterative bronchiolitis [4]. To say that his early results raise “serious ethical considerations” with regard to heart-lung transplantation is premature and is a damning statement about a successful operation that has established long-term results (55 YO survival at 3 years). At present, heart-lung transplantation is an acceptable operation in end-stage lung disease, and i t would be unethical not to use the heart for a ‘domino’ procedure [3]. The role of bilateral lung replacement in the treatment of end-stage lung disease is a dramatic development in patients with reasonable cardiac function. Long-term results must be assessed and compared to heart-lung transplantation before condemning this established and successful surgical approach. While heart-lung transplantation remains the ‘gold standard’, the use of the ‘domino’ heart remains an excellent method for utilising the limited organs available.