Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study.

Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.

Interferon Gamma ELISPOT Testing as a Risk-Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT-01 Multicenter Study.

Previous studies suggest that quantifying donor-reactive memory T cells prior to kidney transplantation by interferon gamma enzyme-linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation-01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6- or 12-month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell-depleting, rabbit anti-thymocyte globulin (ATG). Within the no-ATG subset, IFNγELISPOT(neg) subjects had higher 6- and 12-month eGFRs than IFNγELISPOT(pos) subjects, independent of biopsy-proven AR, peak PRA, human leukocyte antigen mismatches, African-American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor-reactive memory T cells.

Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury.

Noninvasive biomarkers are needed to assess immune risk and ultimately guide therapeutic decision-making following kidney transplantation. A requisite step toward these goals is validation of markers that diagnose and/or predict relevant transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol is a multicenter observational study of biomarkers in 280 adult and pediatric first kidney transplant recipients. We compared and validated urinary mRNAs and proteins as biomarkers to diagnose biopsy-proven acute rejection (AR) and stratify patients into groups based on risk for developing AR or progressive renal dysfunction. Among markers tested for diagnosing AR, urinary CXCL9 mRNA (odds ratio [OR] 2.77, positive predictive value [PPV] 61.5%, negative predictive value [NPV] 83%) and CXCL9 protein (OR 3.40, PPV 67.6%, NPV 92%) were the most robust. Low urinary CXCL9 protein in 6-month posttransplant urines obtained from stable allograft recipients classified individuals least likely to develop future AR or a decrement in estimated glomerular filtration rate between 6 and 24 months (92.5-99.3% NPV). Our results support using urinary CXCL9 for clinical decision-making following kidney transplantation. In the context of acute dysfunction, low values can rule out infectious/immunological causes of injury. Absent urinary CXCL9 at 6 months posttransplant defines a subgroup at low risk for incipient immune injury.

Solid-organ transplantation in older adults: current status and future research.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

Prevalence and risk factors for aortopulmonary collateral vessels after Fontan and bidirectional Glenn procedures.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of and risk factors for aortopulmonary collateral vessels in patients who have undergone a bidirectional Glenn or Fontan procedure, or both. BACKGROUND: Aortopulmonary collateral vessels are frequently observed angiographically in patients after a bidirectional Glenn or Fontan procedure. These vessels may provide a source of pulmonary blood flow competitive with anterograde cavopulmonary flow. METHODS: We performed a retrospective study of all patients (n = 196) who underwent catheterization between January 1, 1988 and February 29, 1992 (n = 268) after bidirectional Glenn or Fontan procedures and reviewed clinical, hemodynamic and angiographic phone data. RESULTS: Collateral vessels were diagnosed in 36% of patients. Patients who underwent the bidirectional Glenn procedure were more likely to have collateral vessels than patients who underwent the Fontan procedure (65% vs. 30%, respectively; p < 0.0001). Patients with a history of a Blalock-Taussig shunt were more likely to have collateral vessels than those without (50% vs. 24%, respectively; p = 0.0006). Discretely identifiable collateral vessels were measurable in 54 (20%) of 268 catheterizations. The total estimated cross-sectional area of these vessels averaged 10.7 +/- 7.2 mm2. In patients who underwent the bidirectional Glenn procedure, a step-up in oxygen saturation from the superior vena cava to the distal pulmonary arteries or an upper lobe filling defect, or both, on pulmonary angiogram predicted total estimated cross-sectional area of collateral vessels. Most collateral vessels originated from the internal mammary arteries (34%) and the thyrocervical trunks (22%). Only 9% of collateral vessels arising from the brachiocephalic vessels were visualized by aortogram; the remainder required selective angiography in the subclavian or more distal arteries. CONCLUSIONS: Aortopulmonary collateral vessels are common after bidirectional Glenn and Fontan procedures. Aortograms often fail to diagnose their presence. The left to right shunt carried by these vessels is associated with a step-up in oxygen saturation in the distal pulmonary arteries. The clinical significance and indications for closure of these vessels are not known.

Rational approach to use of heparin during cardiac catheterization in children.

OBJECTIVES: We sought to determine an anticoagulation protocol for use during cardiac catheterization in children. BACKGROUND: There are few data to indicate which dose of heparin represents adequate anticoagulation or how best to monitor its efficacy. In this study, adequate anticoagulation was defined as the amount of heparin needed to prevent a significant increase in serum fibrinopeptide A, a sensitive marker for thrombin activity. The degree of heparinization was estimated by the activated clotting time. METHODS: Thirty-six children (1 month to 19.5 years old) with congenital heart disease underwent diagnostic cardiac catheterization; 13 of these 36 patients had an additional interventional procedure. Sheaths and catheters were flushed with heparinized saline (1 IU/ml); during the procedure, 33 of the 36 patients received either a 50- or a 100-IU/kg heparin bolus. Paired fibrinopeptide A and activated clotting time samples were obtained throughout each procedure. RESULTS: Increasing the activated clotting time with heparin resulted in a dose-related decrease in fibrinopeptide A levels. A single heparin bolus of either 50 or 100 IU/kg elevated the activated clotting time above baseline level (209 +/- 52 s after 50 IU/kg, 270 +/- 57 s after 100 IU/kg vs. 133 +/- 20 s at baseline [p < 0.0001]) and reduced fibrinopeptide A levels below baseline (7.9 +/- 14 ng/ml after 50 IU/kg, 4.8 +/- 3.7 ng/ml after 100 IU/kg vs. 38 +/- 59 ng/ml at baseline [p < 0.0001]). Heparin flush alone did not increase the activated clotting time above baseline and failed to suppress an increase in fibrinopeptide A levels. There were no differences in activated clotting time and fibrinopeptide A values between patients undergoing diagnostic or interventional procedures. CONCLUSIONS: Administration of a heparin bolus to maintain an activated clotting time > 200 s prevented a significant increase in thrombin activity. Heparin flush alone did not provide adequate anticoagulation. Patients undergoing an interventional procedure did not require more heparin than that needed for a diagnostic procedure.

Hemodynamic data and survival in children with pulmonary hypertension.

OBJECTIVES: Using data from a multi-institutional data base, we sought to determine whether hemodynamic data predict duration of survival in children with primary or secondary pulmonary hypertension. BACKGROUND: Lung transplantation is a therapeutic option for children with pulmonary hypertension. Appropriate timing of lung transplantation requires reliable methods of predicting duration of survival in potential candidates. METHODS: A regional data base was used to obtain cardiac catheterization data on 50 children with mean pulmonary artery pressure (mPAP) > 25 mm Hg and indexed pulmonary resistance (Rp) > 4.5 Wood units. Data on survival were obtained from the participating centers. RESULTS: There were 15 patients without congenital heart disease (group 1) and 35 patients with congenital heart disease (group 2) for analysis. Actuarial survival at 1, 2 and 5 years was 86%, 69% and 69% in group 1 and 88% and 77% in group 2, respectively (p = NS). Hemodynamic variables that predicted survival on univariate analysis were mean right atrial pressure (mRAP) (p < 0.0001), mPAP (p = 0.034), Rp (p < 0.0001) and pulmonary flow (p = 0.003), as well as a variable that we generated-mRAP x Rp (p < 0.0001). On multivariate stepwise logistic regression analysis, mRAP x Rp was independently related to survival. A model using mRAP x Rp allows for the estimation of probability of death at 1 and 2 years after catheterization. CONCLUSIONS: Hemodynamic variables can predict survival in children with pulmonary hypertension in the presence or absence of congenital heart defects. This information can be used to determine the optimal timing of listing for lung transplantation.

Cardiac catheterization and test occlusion of the interatrial communication after the fenestrated Fontan operation.

OBJECTIVES: Our objective was to determine whether catheterization data obtained after a fenestrated Fontan operation influenced patient management or predicted functional status. BACKGROUND: Cardiac catheterization after a fenestrated Fontan operation is undertaken to identify residual lesions and to observe the patient's response to test occlusion of the baffle fenestration. METHODS: Sixty patients undergoing both a fenestrated Fontan operation before July 1991 and a postoperative catheterization before March 1992 were included in the study. Catheterization data were collected according to a test occlusion protocol; these data were reviewed, and the patient's clinical status at follow-up was ascertained. RESULTS: Test occlusion resulted in a significant increase in systemic venous pressure, arterial oxygen saturation and arteriovenous difference in oxygen content (p < 0.0001). After test occlusion, systemic venous pressure was 40% higher and systemic venous saturation 23% lower among patients with an unfavorable versus a favorable response to test occlusion, although differences between the two groups were subtle or inapparent in the baseline state. Branch pulmonary artery stenosis (identified and balloon dilated in 6 patients) and grade 2 or 3 aortopulmonary collateral vessels (identified and coil embolized in 20) were associated with elevation in systemic venous pressure (p < 0.01). After an average of 2 years of follow-up, there were no deaths, and 50 (83%) of 60 patients were in New York Heart Association functional class I. The only postoperative characteristic significantly associated with being in functional class I at follow-up was a systemic venous pressure < 17 mm Hg. CONCLUSIONS: Cardiac catheterization with test occlusion of the interatrial communication provides useful information after a fenestrated Fontan operation. Conditions associated with elevated systemic venous pressure should be sought and treated, and the response of systemic venous pressure to test occlusion should be considered when deciding whether to close an interatrial communication.

Transcatheter closure of a large patent ductus arteriosus with the clamshell septal umbrella.

In 14 patients undergoing transcatheter closure of a large (greater than 4 mm diameter) patent ductus arteriosus, occlusion was attempted with use of the Bard Clamshell septal umbrella. Patient age ranged from 0.7 to 30.4 years. Isolated patent ductus arteriosus was present in 11 patients; 3 had additional congenital heart lesions. Moderate or severe pulmonary hypertension was present in four patients. The diameter of the patent ductus arteriosus ranged from 4.5 to 14 mm, as determined by contrast injection through an 11F sheath or by balloon sizing; it appeared larger by this method than by the standard angiographic method. All 14 patent ductus arteriosi were successfully closed. Prior embolization of a Rashkind umbrella was the reason for using a Clamshell device in three patients; one additional embolization of a Clamshell device occurred. All errant devices were retrieved at cardiac catheterization, without associated hemodynamic instability. No other complications occurred. Among the 14 patients, 11 had complete ductal closure by Doppler color flow mapping at last follow-up and 3 had trivial residual flow. All four patients having associated complex lesions or pulmonary hypertension, or both, had symptomatic improvement after the procedure, although one child (with Shone's anomaly) died 3 months later. The Clamshell device provides stable and effective closure of a large patent ductus arteriosus, and allows transcatheter closure to be offered to some patients who were previously considered unsuitable for this procedure.

Enlarged bronchial arteries after early repair of transposition of the great arteries.

OBJECTIVES: This study was undertaken to define the incidence of enlarged bronchial arteries after early surgical repair of transposition of the great arteries by the arterial switch operation, and to report the results of catheter-directed therapy in five patients. BACKGROUND: Pathologic and angiographic studies have demonstrated enlarged bronchial arteries in patients with transposition of the great arteries. METHODS: A subjective 4-point scale was used to grade postoperative angiograms performed in 119 patients at our institution between January 1983 and December 1991. Grades 0 and 1 were designated if there was no opacification of the pulmonary arteries or veins, whereas grades 2 and 3 were assigned if there was such opacification. The median age at repair was 8 days (range 1 day to 13 months) and the median age at catheterization was 11.2 months (range 3.6 to 58.5). An intact ventricular septum was present in 84 (71%) of 119 patients. RESULTS: Significantly increased bronchial flow (grade 2 or 3) was present in 55 (46%) of 119 patients. Age at repair, age at catheterization and interval between repair and catheterization were not associated with significantly increased bronchial flow; however, an intact ventricular septum was weakly associated with increased flow (p = 0.04). Coil embolization was performed in five patients with complete occlusion of the vessels and no significant complications. CONCLUSIONS: Abnormally enlarged bronchial arteries are frequently identified at postoperative catheterization despite early repair and may explain continuous murmurs or persistent cardiomegaly in patients with otherwise normal noninvasive findings. When clinically indicated, catheter-directed therapy can be performed with good results.

Impact of early ventricular unloading on exercise performance in preadolescents with single ventricle Fontan physiology.

OBJECTIVES: We sought to determine if early ventricular volume unloading improves aerobic capacity in patients with single ventricle Fontan physiology. BACKGROUND: Surgical strategies for patients with single ventricle include intermediate staging or early Fontan completion to reduce the adverse affects of prolonged ventricular volume load. The impact of this strategy on exercise performance has not been evaluated. METHODS: Retrospectively, we reviewed the exercise stress test results of all preadolescents with single ventricle Fontan physiology. "Volume unloading" was considered to have occurred at the time of bidirectional cavopulmonary anastomosis or at the time of Fontan surgery in those patients who did not undergo intermediate staging. Potential predictors of aerobic capacity were analyzed using multivariate regression. RESULTS: The patients (n = 46) achieved a mean percentage predicted of maximal oxygen consumption (VO2max) of 76.1% +/- 21.1%. The mean age at the time of volume unloading was 2.7 +/- 2.4 years, and the mean age at testing was 8.7 +/- 2 years. Intermediate staging was performed in 16 of 46 patients (35%). In multivariate analysis, younger age at volume unloading was associated with increased aerobic capacity (p = 0.003). Other variables were not predictive. The subgroup of patients who underwent volume unloading before two years of age achieved a mean percentage predicted VO2max of 88.6% +/- 24.1%. CONCLUSIONS: Preadolescents with single ventricle who undergo volume unloading surgery at an early age demonstrate superior aerobic capacity compared with those whose surgery is delayed until a later age.

Successful use of alternate waste nitrogen agents and hemodialysis in a patient with hyperammonemic coma after heart-lung transplantation.

BACKGROUND: Lethal hyperammonemic coma has been reported in 2 adults after lung transplantation. It was associated with a massive elevation of brain glutamine levels, while plasma glutamine levels were normal or only slightly elevated. In liver tissue, glutamine synthetase activity was markedly reduced, and the histologic findings resembled those of Reye syndrome. The adequacy of therapy commonly used for inherited disorders of the urea cycle has not been adequately evaluated in patients with this form of secondary hyperammonemia. OBJECTIVE: To determine whether hemodialysis, in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy, would be efficacious in a patient with hyperammonemic coma after solid-organ transplantation. DESIGN: Case report. SETTING: A children's hospital. PATIENT: A 41-year-old woman with congenital heart disease developed a hyperammonemic coma with brain edema 19 days after undergoing a combined heart and lung transplantation. METHODS: Ammonium was measured in plasma. Amino acids were quantitated in plasma and cerebrospinal fluid by column chromatography. The effectiveness of therapy was assessed by measuring plasma ammonium levels and intracranial pressure and performing sequential neurological examinations. RESULTS: The patient had the anomalous combination of increased cerebrospinal fluid and decreased plasma glutamine levels. To our knowledge, she is the first patient with this complication after solid-organ transplantation to survive after combined therapy with sodium phenylacetate, sodium benzoate, arginine hydrochloride, and hemodialysis. Complications of the acute coma included focal motor seizures, which were controlled with carbamazepine, and difficulty with short-term memory. CONCLUSIONS: The aggressive use of hemodialysis in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy may allow survival in patients after solid-organ transplantation. An acute acquired derangement in extra-central nervous system glutamine metabolism may play a role in the production of hyperammonemia in this illness that resembles Reye syndrome, and, as in other hyperammonemic disorders, the duration and degree of elevation of brain glutamine levels may be the important determining factors in responsiveness to therapy.

Outcome of children with pulmonary hypertension referred for lung or heart and lung transplantation.

We reviewed our institutional experience with 24 children with pulmonary hypertension, who were referred for lung or heart and lung transplantation. Diagnosis, age, and previously published predictive survival scores calculated at the time of referral were analyzed as predictors of pretransplant death. Among the 24 children, 7 did not meet criteria for listing and 17 were listed for transplantation. Of those listed, eight died waiting, two await transplantation, and seven were transplanted and are alive and well 7-20 months after transplantation. Poor functional status (New York Heart Association class 3 or 4) at the time of referral was significantly associated with death before transplant (P=0.05) in univariate analysis. Analysis of the predictive scores was possible in 21 of 24 patients; lower predictive scores were significantly associated with death before transplantation and shorter duration of survival without transplantation in univariate analysis. Multivariate analysis (Cox regression) confirmed that lower scores were significantly associated with poor survival. We conclude that children with pulmonary hypertension are often referred for transplantation too late in the course of their disease. Early complete hemodynamic evaluation before the onset of severe symptoms, followed by serial evaluations of disease progression and consultation with a transplant center, should result in earlier, more appropriate time of listing and improved survival. A systematic study of pretransplant mortality among all children listed for lung transplantation would provide a basis for clinical decision making and policies affecting organ allocation.

Pediatric lung transplantation--are there surgical contraindications?

Lung transplantation has evolved as a successful treatment for end-stage cardiopulmonary disease in children; however, clear guidelines regarding surgical exclusion criteria for pediatric lung transplant candidates have not been well-established. Since December 1994, we have performed 10 bilateral lung transplants and 1 heart-lung transplant in 10 recipients (mean age, 7 years; range, 3 months to 19 years). Indications for transplantation included pulmonary vascular disease (n=6), bronchiolitis obliterans (n=2), bronchopulmonary dysplasia (n=1), graft failure due to viral pneumonitis (n=1), and cystic fibrosis (n=1). Among the 10 patients, 4 were evaluated elsewhere for lung transplantation; of these, 3 were rejected by 1 or more programs because of "high-risk" characteristics. We considered 8 of the 10 patients to have 1 or more "high-risk" characteristics, as follows: previous chest operations other than open lung biopsy (n=6 patients having 1-4 previous operations), ventilator-dependence with tracheostomy and high-dose corticosteroids (n=4), redo lung transplant (n=2), concomitant intracardiac repair (n=6), portal hypertension (n=1), and the use of extracorporeal membrane oxygenation (ECMO) at the time of transplant (n=1). Our standard operative approach was a bilateral thoracosternotomy. Cardiopulmonary bypass was used for explant of the recipient lungs and implant of the donor lungs, and during repair of coexisting congenital heart defects. Aprotinin and fresh whole blood were administered during the procedure to aid in hemostasis. Concomitant procedures were frequently performed and included repair of an intra-atrial baffle leak (prior Mustard procedure), closure of an atrial septal defect, repair of partial anomalous pulmonary venous return, reconstruction of the pulmonary venous confluence, ECMO decannulation, and splenectomy. There were no operative deaths, and no patient required re-exploration for bleeding. One patient had primary graft failure due to adenovirus infection of the donor lungs, and required prolonged mechanical ventilation and eventually ECMO support until retransplantation was performed. The mean hospital stay after transplant was 25+/-13 days (range, 10-56 days). All patients were discharged with a natural airway. Airway complications consisted of one bronchial anastomotic stricture which required dilation, for a complication rate of 5% per anastomoses at risk. One patient required reoperation for stenosis of the superior vena cava. There have been no late deaths, with a mean follow-up of 7+/-4 months (range, 1-13 months). We attribute this 100% operative and short-term survival in these "high-risk" pediatric lung transplant recipients to our operative methods, a multidisciplinary approach to postoperative management, and the enormous physiologic reserve of pediatric patients. Therefore, the standard exclusion criteria used for adult lung transplantation may not be applicable to the pediatric age group. We hope to use these data to expand the use of lung transplantation in pediatric patients.

Effectiveness of pharmacomechanical thrombolysis in infants and children.

Between March 1995 and February 2000, 10 children with major thromboses were treated with local pharmacomechanical thrombolysis. Clinical improvement was found in 8 patients: follow-up angiography showed complete thrombus resolution in 5 patients and subtotal resolution in 4.

Maturational and hemodynamic factors predictive of increased cyanosis after bidirectional cavopulmonary anastomosis.

Bidirectional cavopulmonary anastomosis (BCA) is thought to be beneficial in the palliation of patients with univentricular congenital heart disease considered at high risk for Fontan repair. Experience with patients undergoing BCA suggested that those who were older or larger at the time of surgery tended to be more cyanotic postoperatively than their younger and smaller counterparts. This study was designed to identify correlates of systemic arterial oxygen saturation after BCA. Specifically, it was postulated that maturational changes in blood flow distribution might be associated with decreasing arterial oxygen saturation. Database records of all 110 patients undergoing BCA at our institution from June 1988 until the end of 1991 were reviewed. Postoperative catheterization data were available for 66 patients. Twenty-one patients were excluded because they had potentially reversible causes of cyanosis yielding inestimable degrees of error in hemodynamic calculations. In the remaining 45 patients, univariate and multivariate regression analyses were used to identify correlates of systemic arterial oxygen saturation. Growth and maturation as represented by body surface area exhibited a highly significant inverse correlation with arterial oxygen saturation (p = 0.005), as did pulmonary vascular resistance (p = 0.003). Patients who underwent BCA when > 3.9 years of age or with body surface area > 0.65 m2 were at significantly increased risk for excessive postoperative cyanosis, defined as systemic arterial oxygen saturation < or = 75% (p < 0.005). The interval between surgery and catheterization correlated directly with arterial oxygen saturation (p = 0.002), indicating a tendency toward earlier study of more cyanotic patients. None of the other variables examined correlated significantly with arterial oxygen saturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenovirus infection in the lung results in graft failure after lung transplantation.

OBJECTIVES: Our goal was to examine the relationship between viral pneumonia and outcome in pediatric patients undergoing lung or heart-lung transplantation. METHODS: Prospective surveillance for common respiratory viruses of childhood was performed in all patients undergoing lung or heart-lung transplantation. Specimens were examined for the presence of replicating virus (by culture), viral genome (by polymerase chain reaction), and viral antigen (by immunofluorescence and immunohistochemical staining). The relationship between viral infection and outcome was examined. RESULTS: Sixteen patients underwent 19 transplants during the study period, with follow-up of 1 to 26 months. Virus was identified in the transplanted lung in 29 instances; adenovirus was identified most commonly (8/16 patients) and had the greatest impact on outcome. In 2 patients with early, fulminant infection, adenovirus was also identified in the donor. Adenovirus was significantly associated with respiratory failure leading to death or graft loss and with the histologic diagnosis of obliterative bronchiolitis (P < or = .002 in each case). CONCLUSIONS: Adenovirus infection in the transplanted lung is significantly associated with graft failure, histologic obliterative bronchiolitis, and death. Health care personnel and families must be vigilant in preventing exposure of transplant recipients to this virus. Availability of a rapid and reliable test for adenovirus in donors and recipients would have an impact on management and could improve outcome for pediatric lung recipients.

Modifications to the cavopulmonary anastomosis do not eliminate early sinus node dysfunction.

OBJECTIVE: To determine whether operations that theoretically jeopardize the sinus node (hemi-Fontan and/or lateral tunnel Fontan procedures) are associated with a greater risk of sinus node dysfunction than those that theoretically spare the sinus node (bidirectional Glenn and/or extracardiac conduit). METHODS: Between January 1, 1996, and December 31, 1999, a prospective cohort study was conducted evaluating the incidence of sinus node dysfunction in patients undergoing a bidirectional Glenn or hemi-Fontan procedure and those in whom the Fontan repair was completed with either an extracardiac conduit or a lateral tunnel. Sinus node dysfunction was defined (1) as a heart rate more than 2 SD below age-adjusted norms or (2) as a predominant junctional rhythm and/or a sinus pause of more than 3 seconds as determined by the resting electrocardiogram and/or ambulatory monitoring at hospital discharge. RESULTS: Fifty-one patients had a bidirectional Glenn shunt (mean age 7.8 +/- 5.1 months) and 79 a hemi-Fontan procedure (mean age 6.9 +/- 2.8 months). The incidence of sinus node dysfunction on postoperative day 1 was significantly higher after the hemi-Fontan (36%) than after the bidirectional Glenn shunt (9.8%); however, by hospital discharge this difference was no longer apparent (hemi-Fontan [8%]; bidirectional Glenn [6%]; P = not significant). No difference in early sinus node dysfunction was discernible after the extracardiac conduit (4/30 [13%]) compared with the lateral tunnel Fontan procedure (6/46 [13%]) (P = not significant). No diagnostic or perioperative variables were predictive of sinus node dysfunction. CONCLUSIONS: Avoidance of surgery near the sinus node has no discernible effect on the development of early sinus node dysfunction. Thus, concerns about early sinus node dysfunction should not override patient anatomy or surgeon preference as determinants of which cavopulmonary anastomosis to perform.

Factors associated with marked reduction in mortality for Fontan operations in patients with single ventricle.

The Fontan operation was originally employed for patients with tricuspid atresia, but its application has been extended to those with a variety of complex defects in which there is functionally only a single ventricular chamber. The outcome of 225 modified Fontan operations carried out between 1984 and 1990 at the Children's Hospital, Boston, for patients with defects other than tricuspid atresia was reviewed. Overall 30 patients (13.3%) had failure of this operation (death or takedown). Results improved significantly during the period of the study, with failure rates of 6.5% (2 of 31) and 3.4% (2 of 59) in the last 2 years of the review. Multivariate analysis showed that pulmonary artery distortion, pulmonary artery pressure, age less than 3 years, use of a nonoxygenated glucose K+ cardioplegic solution, and cardiopulmonary bypass time greater than 180 minutes were associated with worse outcome, while "favorable" atrioventricular valve anatomy (non-left atrioventricular valve stenosis/atresia or common atrioventricular valve) and age greater than 9 years were associated with improved outcome. Excluding cardiopulmonary bypass time from the multivariate analysis, the technique of atrial partitioning for patients with left atrioventricular valve atresia/stenosis became the most important variable, followed by the others noted in the initial multivariate analysis except for age greater than 9 years. In the last 2 years of the study 31.1% of patients were less than 3 years of age. During the period of the study there was no significant decline in preoperative risk factors. These results show that modified Fontan operations can be carried out with a high likelihood of success in properly selected patients with complex defects in whom there is functionally a single ventricle.

Outcome of infants listed for lung or heart/lung transplantation.

BACKGROUND: Little is known about outcome, characteristics, or organ availability for infants listed for lung or heart/lung transplantation. METHODS: Within a 45-month period at one institution, all pediatric patients who were listed for primary lung or heart/lung transplantation and who reached the end point of either transplant or death prior to transplant were identified. Outcomes for those patients listed as younger than and older than 1 year of age were compared. RESULTS: Among 48 pediatric patients, 19 were infants less than one year of age. The median age among infants at listing was 3.7 months (range 0.5 to 8.9 months). Death before transplant occurred in 10 of 19 infants (53%) compared with 14 of 29 (48%) children. When comparing those infants who died prior to transplant with those who received organs, there were no significant differences with respect to size, blood type, age at listing, presence of pulmonary hypertension, or type of transplant for which the patient was listed. There was a trend toward poorer pre-transplant survival for infants when compared with children. Waiting times were significantly shorter for infants vs children (p = 0.02). The incidence of acute cellular rejection and serious infection was similar in the 2 groups. Infants had significantly longer hospitalization post-transplant and a trend toward poorer hospital survival, although survival at 1 year was comparable between the 2 groups. CONCLUSION: The outcome for infants listed for lung or heart/lung transplantation is similar to that of children; thus, very young age should not be considered a contraindication to lung or heart/lung transplantation. Earlier diagnosis and listing may decrease pre-transplant mortality.