Pauline Whitmore

Lung transplantation and life extension in children with cystic fibrosis.

BACKGROUND Lung transplantation has been available as therapy for end-stage lung disease since the early 1980s, but survival after transplantation remains poor, with continued controversy as to the survival benefit from the procedure. We examined the effect of lung or heart-lung transplantation on the survival of a cohort of children with cystic fibrosis and severe lung disease. METHODS Between May, 1988, and May, 1998, 124 children with cystic fibrosis were accepted for lung transplantation. 47 received transplants, 68 died while they awaited organs, and nine remained on the active waiting list. We constructed a proportional-hazards model that used variables of prognostic significance in this population. By including transplant status as a time-dependent covariate, we were able to calculate a hazard ratio for transplantation. Date of entry into the study was the date when children were added to the list for transplantation, and measurements were taken at this time. Children were accepted for transplantation if they had a life expectancy of 2 years or less, a poor quality of life, and no contraindications to transplantation. FINDINGS After 1 year, 35 (74%) children were still alive; after 5 years 12 (33%) children were alive. The univariate hazard ratio for transplantation was 0.41 (95% CI 0.23-0.74; p=0.003). Transplantation remained significantly associated with survival after correction for differences in age, sex, height-corrected forced expiratory volume in 1 s, minimum oxygen saturation during a 12 min walk, haemoglobin concentration, albumin concentration, and age-corrected resting heart rate (hazard ratio 0.31 [0.13-0.72]; p=0.007). INTERPRETATION If centres follow our criteria for accepting patients for transplantation, and achieve similar survival after transplantation, they could expect a survival benefit for their patients in line with our results.

The waiting game: bridging to paediatric heart transplantation

BACKGROUND Although mechanical circulatory support might not increase the number of adults surviving to transplantation, because of the shortage of donor organs, the situation might be different for children. Our aim was to assess the effect of mechanical assist devices to bridge children with end-stage cardiomyopathy to heart transplantation. METHODS A 5-year retrospective review was undertaken with data from the UK paediatric transplant programme and from bridging to transplant done at two paediatric transplant centres in the UK. FINDINGS Between Jan 1, 1998 and Dec 31, 2002, 22 children with end-stage cardiomyopathy, median age 5.7 years (range 1.2-17), were supported by a mechanical assist device as a bridge to first heart transplantation, with a 77% survival rate to hospital discharge. Nine were supported by a paracorporeal ventricular assist device, six received transplantation, five survived to discharge (55%), with one late death. 13 were supported by extra-corporeal membrane oxygenation, and 12 were transplanted and survived to discharge (92%) with one late death. With urgent listing, the median waiting time for a heart was 7.5 days (range 1.5-22 days). The correlation between the proportion of patients bridged to transplantation and the proportion of patients dying while on the transplant waiting list was r=-0.93, p=0.02. INTERPRETATION Our findings lend support to the hypothesis that a national mechanical assist programme to bridge children to transplantation can minimise the number dying while on the heart transplant waiting list. In the context of urgent listing and a short waiting time, extra-corporeal membrane oxygenation seems to provide the safest form of support.

Positive Pretransplantation Cytomegalovirus Serology Is a Risk Factor for Cardiac Allograft Vasculopathy in Children

Background— Cytomegalovirus (CMV) infection has been implicated as a cause of posttransplantation coronary artery disease in adults. The purpose of this retrospective observational study was to evaluate the effect of CMV on outcome after heart transplantation in children. Methods and Results— Risk factors tested were recipient age, sex, and pretransplantation CMV serology; use of anti-CMV prophylaxis; posttransplantation evidence of CMV infection; and donor CMV serology. Transplantations were stratified traditionally according to CMV risk as low risk (recipient negative/donor negative), intermediate risk (recipient positive), and high risk (recipient negative/donor positive). Primary outcome measures were (1) development of coronary artery vasculopathy, (2) mortality (or graft loss) that occurred outside the early postoperative period, and (3) death (or graft loss) due to vasculopathy. Analysis was by proportional hazards modeling. A total of 165 children underwent heart transplantation, with a mean age at transplantation of 7.8 (SD 5.6) years. Thirty-two children had laboratory evidence of CMV infection after transplantation, but only 6 developed CMV disease or syndrome. Traditional CMV risk stratification correlated well with CMV infection but did not predict mortality, coronary artery disease, or coronary death. In contrast, positive recipient CMV was the only independent predictor of all 3 outcome measures: coronary artery disease (hazard ratio=3.6), all-cause mortality (partial hazard ratio=4.1), and coronary death (hazard ratio=4.6). Conclusions— In children, pretransplantation recipient CMV status is a more powerful predictor for the development of clinically significant vasculopathy and subsequent death than traditional risk stratification. This phenomenon warrants further investigation.

Heart transplantation for dilated cardiomyopathy.

Between 1988 and 1994, 23 patients underwent heart transplantation for dilated cardiomyopathy. The age of the 13 boys and 10 girls was from 8 months to 16 years (mean 7.1 years). Selection criteria included failure to thrive despite maximal antifailure treatment and/or intravenous inotrope dependence. The aetiology of cardiomyopathy was idiopathic (n = 13), congenital (n = 3), anthracycline induced (n = 4), Barths syndrome (n = 1), and maternal systemic lupus erythematosus (n = 2). The waiting period of heart transplantation ranged from one day to 147 days (mean 22 days). Maintenance immunosuppression included cyclosporin, azathioprine, and prednisolone. Follow up after transplantation was from one month to 62 months (median 27 months) with a mean actuarial survival of 95% at one year and 87% at three years. Four patients developed coronary artery disease, one of whom died as a consequence 15 months after heart transplantation. Heart transplantation has emerged as an acceptable therapeutic option, at least in the short term, for patients with dilated cardiomyopathy.

Pediatric cardiothoracic domino transplantation: the psychological costs and benefits.

Abstract:  The first domino transplants were carried out in the UK in 1987, since which time 52 such procedures have been carried out involving patients within the paediatric cardiothoracic transplant programmes of Harefield and Great Ormond Street Hospitals. Although there are medical advantages in using domino organs – such as the ability for preoperative cross‐matching, the heart not being subjected to the biochemical changes of brain death and less post‐transplant coronary artery disease in the recipients of domino hearts compared with the recipients of hearts from cadaveric donors – the psychological sequelae for both donor and recipient have not been previously studied. The objective of this study was to identify the main psychological themes for patients involved in the domino programmes at the two hospitals, focusing on those situations where both patients were cared for in the same tertiary centre. Patients and their families were interviewed during routine outpatient clinic visits. Negative themes identified by patients included anxiety, guilt, resentment and anger if either patient had a poor outcome or suffered significant complications, disappointment and low self‐esteem for potential donors whose heart was not used and recipient awareness of donor characteristics. Positive themes included gratefulness, comfort for the recipient that someone had not had to die for them directly and the benefit to the donor of giving their heart to another patient. In conclusion, domino transplantation has many medical advantages but there are significant negative psychological concomitants which need to be addressed within the multi‐disciplinary management of these patients.

Resourse implications of ECMO as a bridge to paediatric heart transplant

Bridging children to heart transplantation remains difficult because of unsuitability of many adult VADs. Since 2000, we have adopted a policy of using ECMO. To date, we have bridged 8 children to transplant, all of whom have survived, but have had complicated post-operative courses, which has resource implications for the multidisciplinary team looking after them. Tracheostomy was performed on 5 children post transplant. All patients had marked muscle weakness requiring a prolonged period of rehabilitation physiotherapy. The median time from surgery to walking unaided was 12 days (range 4-34 days). The psychological impact of ECMO and transplantation on these children was manifest in a variety of modes: depression, anxiety, delusions, nightmares and denial. All of these children required significantly more input from the multidisciplinary team than children who had undergone transplant without being bridged on ECMO. The rehabilitation course centred around physiotherapy, psychology, nutrition, medical and nursing expertise, as well as parental input, for these children to improve their quality of life. To date, all of these children have returned to school and are NYHA class 1. Although physically rehabilitated, psychological input and assessments continued. In conclusion, ECMO as a bridge to paediatric heart transplant has a low mortality. Morbidity is high and adequate resources need to be allocated for a multidisciplinary team to help these children return to a normal life.