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.

Monitoring of Epstein-Barr viral load in pediatric heart and lung transplant recipients by real-time polymerase chain reaction.

BACKGROUND: Elevation in Epstein-Barr virus (EBV) load measured in peripheral blood has been proposed as a marker for development of post-transplant lymphoproliferative disease (PTLD), but there are few published data examining this relationship. We report the longitudinal surveillance of EBV for all recipients of heart (HTx), heart-lung (HLTx) and lung (LTx) transplants at our institution. METHODS: The study population included all patients transplanted between January 2003 and July 2004. EBV load was serially measured in peripheral blood by real-time polymerase chain reaction (PCR). Results were correlated with recipient pre-transplant EBV status and development of PTLD. RESULTS: Forty-four transplant operations were performed, including 33 HTx, 6 HLTx and 5 LTx. Thirty-two (73%) of the patients were EBV seropositive pre-transplant. Nineteen (44%) pediatric recipients developed EB viremia, including 17 HTx, 1 HLTx and 1 LTx. Eleven (58%) of these patients were EBV seropositive pre-transplant. EBV was first detected at a median of 30.5 days (range 2 to 81) post-transplant. The median peak EBV load in that group was 10,099 copies/ml (range 5,935 to 255,466) whole blood. One patient with cystic fibrosis post-LTx developed PTLD localized in the colon. This patient was EBV seronegative pre-transplant; peak EBV load was 14,513 copies/ml. Acute infectious mononucleosis was seen in 1 case. Positive pre-transplant EBV status did not predict post-transplant EB viremia (positive predictive value 0.03). CONCLUSIONS: Contrary to earlier reports, our data demonstrate that a high EBV load does not lead to PTLD early post-transplant. These results do not support the practice of pre-emptively reducing immunosuppression in patients with raised EBV load.

High prevalence of gastroesophageal reflux in children after lung transplantation.

Bronchiolitis obliterans and its clinical correlate bronchiolitis obliterans syndrome (BOS) are a major cause of morbidity and mortality following lung transplantation. Gastroesophageal reflux disease (GERD) may be a contributing factor for the development of BOS. Since 2002, all recipients of lung and heart-lung transplantation at our institution have been routinely investigated for GERD. In this observational study, we report on the prevalence of GERD in this population, including all pediatric patients undergoing single (SLTx) or double (DLTx) lung transplantation or heart-lung (HLTx) transplantation from January 2003-May 2004. GERD was assessed 3-6 months after transplantation by 24-hr pH testing. The fraction time (Ft) with a pH < 4 within a 24-hr period was recorded. Spirometry data, episodes of confirmed acute rejection, and demographic data were also collected. Ten transplant operations were performed: 4 DLTx, 1 SLTx, and 5 HLTx. Nine patients had cystic fibrosis. One patient had end-stage pulmonary disease secondary to chronic aspiration pneumonia and postadenovirus lung damage. Of 10 patients tested, 2 had severe GERD (Ft > 20%), 5 had moderate GERD (Ft 10-20%), 2 had mild GERD (Ft 5-10%), and 1 had no GERD. The only patient in this group with no GERD had a Nissen fundoplication pretransplant. All study patients were asymptomatic for GERD. All patients with episodes of rejection had moderate to severe GERD posttransplant. There was no association between severity of GERD and peak spirometry results posttransplant. Moderate to severe GERD is common following lung transplantation in children.

Pediatric cardiothoracic domino transplantation: the psychological costs and benefits.

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.

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.

Improved early outcome for end-stage dilated cardiomyopathy in children.

OBJECTIVE: To review the impact of management changes on the early outcomes of end-stage dilated cardiomyopathy in children. METHODS: We conducted a retrospective study of all consecutive children with end-stage dilated cardiomyopathy who received hospital treatment since 1992. Over the past 3 years the following management changes were made: (1) more aggressive use of mechanical cardiac assistance; (2) high priority listing for transplantation; and (3) ABO incompatible transplants for infants. Outcomes for 46 patients admitted between 1992 and 1999 (group I) were compared with 53 patients between 2000 and March 2003 (group II). RESULTS: In group I, 12 (26%) patients received mechanical support with recovery in 3 and transplantation in 5 (1 died). In group II, 19 (36%) patients received extracorporeal membrane oxygenation, with recovery in 5 and transplantation in 12 (all survived). The use of mechanical assistance was associated with high morbidity related to bleeding, end-organ failure, and long-term mechanical ventilation. Five patients in group II received ABO incompatible transplants and all survived. There have been no episodes of rejection or need for increased immunosuppressive therapy. Hospital mortality has been significantly reduced (group I, 37% vs group II, 11%; P <.05). CONCLUSIONS: Recent refinements in the management of end-stage dilated cardiomyopathy in children have significantly reduced early mortality. Identification of markers of early myocardial recovery and development of mechanical devices for longer term and more physiologic support are essential to achieve further improvements in outcome.