Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial.

BACKGROUND: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates TNF α production that amplifies allograft inflammation and may negatively affect transplant outcomes. METHODS: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase 2 clinical trial. A total of 225 primary transplant recipients of deceased-donor kidneys (KTx; 38.2% Black/African American, 44% White) were randomized to receive intravenous infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated before kidney reperfusion. All patients received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary end point was the difference between groups in mean 24-month eGFR. RESULTS: There was no difference in the primary end point of 24-month eGFR between IFX (52.45 ml/min per 1.73 m 2 ; 95% CI, 48.38 to 56.52) versus PLBO (57.35 ml/min per 1.73 m 2 ; 95% CI, 53.18 to 61.52; P =0.1). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ, and day 7 post-KTx plasma analyses showed approximately ten-fold lower TNF ( P <0.001) in IFX versus PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) versus PLBO (13.4%; P =0.004), with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) versus PLBO (4.9%; P =0.06). CONCLUSIONS: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peritransplant inflammation as a strategy to improve KTx outcomes.Clinical Trial registry name and registration number:clinicaltrials.gov (NCT02495077).

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Early outcomes for low-risk pediatric heart transplant recipients and steroid avoidance: A multicenter cohort study (Clinical Trials in Organ Transplantation in Children - CTOTC-04).

BACKGROUND: Immunosuppression strategies have changed over time in pediatric heart transplantation. Thus, comorbidity profiles may have evolved. Clinical Trials in Organ Transplantation in Children-04 is a multicenter, prospective, cohort study assessing the impact of pre-transplant sensitization on outcomes after pediatric heart transplantation. This sub-study reports 1-year outcomes among recipients without pre-transplant donor-specific antibodies (DSAs). METHODS: We recruited consecutive candidates (<21 years) at 8 centers. Sensitization status was determined by a core laboratory. Immunosuppression was standardized as follows: Thymoglobulin induction with tacrolimus and/or mycophenolate mofetil maintenance. Steroids were not used beyond 1 week. Rejection surveillance was by serial biopsy. RESULTS: There were 240 transplants. Subjects for this sub-study (n = 186) were non-sensitized (n = 108) or had no DSAs (n = 78). Median age was 6 years, 48.4% were male, and 38.2% had congenital heart disease. Patient survival was 94.5% (95% confidence interval, 90.1-97.0%). Freedom from any type of rejection was 67.5%. Risk factors for rejection were older age at transplant and presence of non-DSAs pre-transplant. Freedom from infection requiring hospitalization/intravenous anti-microbials was 75.4%. Freedom from rehospitalization was 40.3%. New-onset diabetes mellitus and post-transplant lymphoproliferative disorder (PTLD) occurred in 1.6% and 1.1% of subjects, respectively. There was no decline in renal function over the first year. Corticosteroids were used in 14.5% at 1 year. CONCLUSIONS: Pediatric heart transplantation recipients without DSAs at transplant and managed with a steroid avoidance regimen have excellent short-term survival and a low risk of first-year diabetes mellitus and PTLD. Rehospitalization remains common. These contemporary observations allow for improved caregiver and/or patient counseling and provide the necessary outcomes data to help design future randomized controlled trials.

Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant.

Noninvasive biomarkers are needed to monitor stable patients after kidney transplant (KT), because subclinical acute rejection (subAR), currently detectable only with surveillance biopsies, can lead to chronic rejection and graft loss. We conducted a multicenter study to develop a blood-based molecular biomarker for subAR using peripheral blood paired with surveillance biopsies and strict clinical phenotyping algorithms for discovery and validation. At a predefined threshold, 72% to 75% of KT recipients achieved a negative biomarker test correlating with the absence of subAR (negative predictive value: 78%-88%), while a positive test was obtained in 25% to 28% correlating with the presence of subAR (positive predictive value: 47%-61%). The clinical phenotype and biomarker independently and statistically correlated with a composite clinical endpoint (renal function, biopsy-proved acute rejection, ≥grade 2 interstitial fibrosis, and tubular atrophy), as well as with de novo donor-specific antibodies. We also found that <50% showed histologic improvement of subAR on follow-up biopsies despite treatment and that the biomarker could predict this outcome. Our data suggest that a blood-based biomarker that reduces the need for the indiscriminate use of invasive surveillance biopsies and that correlates with transplant outcomes could be used to monitor KT recipients with stable renal function, including after treatment for subAR, potentially improving KT outcomes.

Equivalent performance of epicardial versus endocardial permanent pacing in children: a single institution and manufacturer experience.

BACKGROUND: Children requiring permanent pacing have a lifelong need for follow-up. Epicardial leads have traditionally fared worse than endocardial counterparts. We tested the hypothesis that steroid-eluting epicardial and endocardial leads had equivalent outcomes. METHODS: We reviewed medical records of 148 children, mean age 8.2 +/- 4.8 years, in whom a dual-chamber pacemaker system with steroid-eluting leads from a single manufacturer was implanted. Primary outcome was mortality. Secondary outcomes included freedom from lead failure and pacemaker system reintervention. Loss of capture-sensing, lead displacement-fracture, exit block, and high thresholds constituted lead failure. Reintervention included need for lead revision or generator change. RESULTS: There was no early mortality. Late mortality occurred once (0.5 +/- 0.5 deaths/1,000 patient-months) and eight times (3.4 +/- 1.2 deaths/1,000 patient-months) in the endocardial and epicardial groups, respectively. The relative hazard of endocardial versus epicardial site for lead failure was 0.408 (p = 0.038) and for reintervention was 0.629 (p = 0.002). Endocardial and epicardial groups differed in important ways: concomitant cardiac surgery 5% (3 of 61) versus 27% (27 of 99); congenital heart disease 33% (20 of 61) versus 90% (89 of 99); single ventricle physiology 13% (8 of 61) versus 52% (51/99); and age (10.5 +/- 4.5 years vs 5.5 +/- 5.2 years). Adjusting for these covariants, the relative hazard for freedom from lead failure for endocardial versus epicardial leads was 0.546 (p = 0.360). The adjusted relative hazard for freedom from reintervention was 0.157 (p = 0.045). CONCLUSIONS: Technologic advances attenuate important differences in lead failure rates between endocardial and epicardial steroid-eluting pacing leads and thus bridge the performance gap between these fixation modes.

Aortic valve-sparing repair with autologous pericardial leaflet extension has low long-term mortality and reoperation rates in children and adults.

OBJECTIVES: We sought to establish whether there was a difference in outcome after aortic valve repair with autologous pericardial leaflet extension in pediatric and adult populations. METHODS: In our study, 128 patients (pediatric and adult) underwent valvular pericardial extension repair at our institution from 1997 through 2006. The patients were divided into either the pediatric group (< or =18 years of age; n = 54/128, 42%), with a mean age of 8.4 +/- 5.4 (range, 0-17 years), or the adult group (n = 74/128, 58%), with a mean age of 48.9 +/- 19.7 (range, 19-85 years). The endpoints of the study were mortality and reoperation rates. RESULTS: Thirty-day mortality for the adult group was 0, and for the pediatric group it was 1/54 (1.8%), with no statistical difference (P = .1) between the groups. Late mortality for the pediatric group was 2/54 (3.7%) and in the adult group was 2/74 (2.7%). There was no statistical difference (P = .12) between the groups. In the pediatric group, there were 6 total reoperations (6/54) in 5 patients, with one patient undergoing reoperation twice. From these 6 cases, 3 were re-repair and 3 had aortic valve replacement; the mean interval between original repair and reoperation was 4.3 +/- 2.5 years (range, 0.1-7.7 years). In the adult group, there were 5 total reoperations (5/74). From these 5 cases, 3 had aortic valve replacement and 2 re-repair; the mean interval between original repair and reoperation was 3.5 +/- 3 years (range, 0.1-7 years). There was no statistical difference in the reoperation rate between the 2 groups (P= .38). At late follow-up, 82% of all patients in the adult group had no aortic regurgitation or only a trace (grades 0 and 1) and 78% of all patients in the pediatric group had no aortic regurgitation or only a trace (grades 0 and 1). There was no statistical difference in either aortic regurgitation (P = .06) or aortic stenosis (P = .28) between the 2 groups. CONCLUSIONS: Aortic valve repair with autologous pericardial leaflet extension has low mortality and morbidity rates, as well as good mid-term durability in both the pediatric and the adult groups.

Aortic valve-sparing repair with autologous pericardial leaflet extension has a greater early re-operation rate in congenital versus acquired valve disease.

OBJECTIVE: We sought to establish whether there was a difference in outcome after aortic valve repair with autologous pericardial leaflet extension in acquired versus congenital valvular disease. METHODS: One hundred and twenty-eight patients underwent reparative aortic valve surgery at our institution from 1997 through 2005 for acquired or congenital aortic valve disease. The acquired group (43/128) (34%) had a mean age of 56.4+/-20.3 years (range, 7.8-84.6 years) and the congenital group (85/128) (66%) had a mean age of 16.9+/-19.2 years (range, 0.3-82 years). The endpoints of the study were mortality and reoperation rates. RESULTS: Thirty-day mortality was 0/43 (0%) in the congenital group and 1/85 (1.1%) in the acquired group. Late mortality in the acquired group was 3/43 (7%) and 3/84 (3.5%) in the congenital group (neither early nor late proportion of mortality is significantly different between the two groups, according to the nonparametric Binomial test for proportions). There were 13 total reoperations among 11 patients: 1/43 (2.3%) in the acquired group and 10/85 (11.7%) in the congenital group (p=0.07). Two patients from the congenital group were reoperated on twice. The mean interval between original repair and reoperation was 3.6+/-5 years (range, 0-7 years) for acquired and 3.5+/-2.5 years (range, 0-7 years) for the congenital group (Wilcoxon 2-sample test, p=0.7). Total early reoperation rate (<30 days after first surgery) was 11/128 (8.5%); for the congenital group 9/85 (10.5%) and for the acquired group 2/43 (4.6%). Early reoperation rate was significantly higher among the congenital group (p=0.013). The remaining patients are well at mean follow-up of 2.8+/-2.4 years (range 0-7.9). In the acquired group, the mean postoperative aortic regurgitation and stenosis grade by echocardiography was 0.5+/-0.3 (scale, 0-4) and 0.3+/-0.1, respectively. In the congenital group, the follow-up, mean aortic regurgitation and stenosis were 0.9+/-0.8 and 0.5+/-0.3, respectively. CONCLUSIONS: There was no significant difference in early or late mortality and late reoperation rate between the two groups. Early reoperation rate was higher in the congenital versus the acquired aortic valvular disease group. This study supports the fact that the valve-sparing technique is safe and reproducible and repeatable in patients with acquired valve disease.

Long-term experience of girdling the ascending aorta with Dacron mesh as definitive treatment for aneurysmal dilation.

BACKGROUND: The management of the mildly to moderately dilated ascending aorta (3.5 to 4.9 cm) in cardiac surgery remains controversial. Therapeutic options have included radical aortic resection with synthetic graft substitution, external aortic reinforcement or wrap, with or without partial aortic wall excision, and a watch-and-wait approach. We reviewed our institutional experience with Dacron (DuPont, Wilmington, DE) mesh wrap support of dilated ascending aortas. METHODS: During the last 20 years, 102 patients with aneurysmal dilatation of the ascending aorta underwent wrapping of the ascending aorta with a fine Dacron mesh from the ventricular-aortic junction to the origin of the innominate artery. For the last 10 years, the wrap was anchored to the aortic annulus with pledgeted sutures. Aortic diameters up to 6 cm, without focal areas of thinning, were wrapped. Aortic diameters exceeding 6 cm, or with focal thinning, underwent tailored aortic wall resection and wrapping. Primary end points of the study included mortality, aortic diameter growth, dissection or rupture, or both. RESULTS: The mean age of the group was 54.7 +/- 19 years (range, 12 to 90 years). A single patient underwent aortic wrapping without cardiopulmonary bypass. Sixty-six patients (65%) required additional aortic valve surgery. Five patients (5%) had reinforcement of dilated sinuses with glutaraldehyde-treated pericardial patches combined with wrapping. Twenty-seven patients (26%) had combined coronary and valve surgery, and 2 patients had coronary revascularization alone. There was neither early nor hospital mortality. Among the 81 patients (79%) we were able to contact, 7 (7%) late deaths had occurred at 0.5, 1, 3, and 9 years after operation that were unrelated to aortic pathology. Various levels of follow-up were obtained in the 88 patients (86.2%). In 78 patients, echocardiograms, computed tomography angiograms, or magnetic resonance angiograms were obtained. In 2 of these patients, aneurysmal dilatation of the sinuses developed below the wrap and reoperation was required. No patient in whom the mesh wrap was anchored to the aortic annulus required reoperation. All 81 patients that were contacted by us and monitored by referring physicians were asymptomatic and free of problems related to the aorta. The mean (+/- SD) preoperative diameter of the ascending aorta was 49.2 +/- 7.8 mm (range, 35 to 87 mm), the postwrap intraoperative diameter was 32.9 +/- 3.4 mm (range, 20 to 40 mm), and the follow-up postoperative aortic diameter was 35.6 +/- 12.7 mm (range, 27 to 52 mm). The mean average change in the aortic diameter during the follow-up period was 2.6 +/- 14.8 mm (range, -7 to 22 mm), a mean of 8%. The mean follow-up period was 5.7 years (median, 4.77 years; range, 9 days to 21 years). There were no infections or other early complications related to the wrap. CONCLUSIONS: Dacron mesh support of the moderately dilated aneurysmal ascending aorta, alone or in conjunction with coronary revascularization, aortic root surgery, or valvular operations, or both, is safe and durable. Dacron mesh is transparent and stretchable, permitting tight girdling of the aorta. These properties prevent hematoma formation, facilitate proximal vein graft anastomoses, and provide visualization and access to aortic suture lines. Finally, this technique retards further aortic dilation, altering the natural history of aortic aneurysms.

Use of an apical suctioning device for placement of a posterior epicardial defibrillator patch: a case report.

We report a case of a 43-year-old man with dilated cardiomyopathy and intractable ventricular tachycardias who did not respond to percutaneous implantable cardioverter defibrillator therapy and required implantation of epicardial patches. An apical suctioning device was used to retract the apex of the heart outside the mediastinal domain. The device provided excellent exposure and hemodynamic stability to safely implant the posterior epicardial patch.

Risk factors for early death and reoperation following biventricular repair of pulmonary atresia with intact ventricular septum.

OBJECTIVE: Since a functional right ventricle is desirable when repairing pulmonary atresia with intact ventricular septum, we sought to determine the factors that portend a successful biventricular repair in these children. METHODS: A review of operative records at UCLA between 1982 and 2001 revealed 56 patients diagnosed with pulmonary atresia with intact ventricular septum that underwent either a partial (n=26) or complete biventricular repair. Kaplan-Meier survival curves with log rank statistics were used to evaluate the influence of demographic, technical, and anatomic factors on survival and need for reoperation. RESULTS: Five-year actuarial survival following biventricular repair was 91.5%. Non-Caucasian race (p=0.011) and omission of palliative right ventricular outflow tract obstruction (RVOTO) relief (p=0.042) were risk factors for early death. All patients with adequate follow-up required reoperation with median duration of 6.9 years. The most common cause of early reoperation (<1 year) was wound infection (35.3%) while pulmonary valve replacement (58.8%) constituted the majority of late reoperations. Risk factors for wound infection included female sex (p=0.011) and use of a synthetic transannular patch (p=0.085). The most significant risk factor for early pulmonary valve replacement was the use of a monocusp pericardial valve in the pulmonary annular position (p=0.003). CONCLUSIONS: Excellent survival follows biventricular repair of pulmonary atresia with intact ventricular septum if RVOTO relief is performed in conjunction with initial palliation. Although most patients eventually require reoperation, avoidance of synthetic transannular patches and monocusp pericardial pulmonary valves may reduce the incidence of wound infection and delay need for pulmonary valve replacement.

Peri-operative renal function and outcome after orthotopic heart transplantation.

BACKGROUND: Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. We sought to evaluate the relationship between renal function and outcomes after orthotopic heart transplantation (OHT). METHODS: We conducted a retrospective review of 622 adults who underwent 628 consecutive OHTs between 1994 and 2001 at our institution. The recipients were divided into either normal (Group 1) or impaired (Group 2) pre-operative renal function. Impaired renal function was defined as creatinine clearance (CrCl) < 40 ml/min (Cockroft-Gault formula). Meanwhile, patients in Group 1 (normal) were defined by CrCl > or = 40 ml/min. The primary end points of the study were early and late mortality. The secondary end point included post-operative renal failure defined by the requirement of dialysis or renal allograft in the early post-operative period. The Kaplan-Meier method was used to determine actuarial survival. RESULTS: Early mortality was 7% (38/531) in Group 1 and 17% (16/96) in Group 2 (p = 0.002). Similarly, the death rate per 100 patient-years was 4.8 and 8.1 for the groups, respectively (p = 0.03). Nine percent of patients in Group 1 required post-operative dialysis (49/531), whereas 32% of recipients in Group 2 required this intervention (31/96) (p < 0.001). Early mortality was 41% for patients requiring post-operative dialysis and 3% for those not requiring such intervention (p < 0.001). Early mortality after post-operative dialysis was 41% (20/49) in Group 1 and 42% (13/31) in Group 2 (p = 0.2). CONCLUSIONS: CrCl < 40 ml/min is a useful marker for increased post-operative renal failure and mortality. Recipients who require post-operative dialysis have greatly increased mortality regardless of pre-operative CrCl. Dialysis in patients after heart transplantation carries a prohibitive risk. Dialysis as a bridge to renal transplantation may reduce this high mortality rate.

Post-transplant lymphoproliferative disorder following pediatric heart transplantation.

Immunosuppression after heart transplantation is implicated in development of post-transplant lymphoproliferative disorder (PTLD). Despite a higher prevalence of PTLD in children, there is scarce knowledge about incidence, pathophysiologic mechanisms and risk factors for PTLD in pediatric recipients of cardiac allografts. We examined retrospectively the medical records of all 143 pediatric patients (mean age 9.2 +/- 6.1 yr) who received donor allografts between 1984 and 2002 and survived over 30 days. Five children (3.5%) developed PTLD over a mean follow-up period of 41.1 +/- 46.0 months. Time from transplant to diagnosis of PTLD ranged from 3.9 to 112 months (mean 48.0 +/- 41.9 months). Excluding PTLD, no other malignancies were found in this population. Actuarial freedom from PTLD was 99.2%, 99.2% and 96.2% at 1, 2, and 5 yr, respectively. Children who developed PTLD were more likely (by univariate analysis) to have been Rh negative (p = 0.01), Rh mismatched (p = 0.003), Epstein-Barr virus (EBV) seronegative (p = 0.001) and transplanted for congenital heart disease (p < 0.02). PTLD was associated with significant morbidity and mortality with a mean survival following diagnosis of 21.2 months. PTLD is a serious complicating outcome of cardiac transplantation that occurs in approximately 3.5% of children. Aside of immunosuppression, risk factors in this series for developing PTLD include EBV seronegativity and Rh negative status and mismatch. Non-hematogenous malignancies are rare in light of short allograft half-life.

Successful management of patients with pulmonary atresia with intact ventricular septum using a three tier grading system for right ventricular hypoplasia.

BACKGROUND: We sought to validate a simple grading scheme for right ventricular hypoplasia in determining suitability for a biventricular repair. METHODS: We reviewed the medical records for 106 patients with pulmonary atresia-intact ventricular septum (PA-IVS) treated between 1982 and 2001. Over this period, children were assigned to mild (> 2/3 normal size, 23.7% of patients), moderate (1/3 to 2/3, 41.2%), or severe (1/3, 35.1%) right ventricular hypoplasia, and this grouping, along with severity of coronary anomalies (45% right ventricle to coronary fistulae, 16% with right ventricle dependent coronary circulation [RVDCC]), triaged children to eventual single ventricle (severe) or two-ventricle (mild or moderate) repair. RESULTS: Actuarial 10-year survival was 86.3% with mortality predicted by severe hypoplasia (odds ratio [OR] 12.9, p < 0.001), RVDCC (OR 15.0, p < 0.001), and non-Caucasian race (OR 10.7, p < 0.001). Multivariate analysis with a Cox proportional hazards model confirmed only RVDCC (risk ratio [RR] 10.9, p = 0.0009} and non-Caucasian race (RR 6.9, p = 0.007) as significant. Although not an independent risk factor for survival, the degree of hypoplasia was the most important determinant for definitive repair. Severe hypoplasia virtually precluded two-ventricle repair (OR 33.1, p < 0.001 by chi2 analysis) and was the strongest risk factor for a one-ventricle system (OR 78.7, p < 0.001). Actuarial survival after either repair was 91%, and no biventricular repair later converted to a Fontan system. CONCLUSIONS: Surgical management of patients based on this three tier grade for right ventricular hypoplasia results in excellent survival and correctly predicts patients destined for eventual Fontan and biventricular repair.

Cardiac surgery in children with end-stage liver disease awaiting liver transplantation.

BACKGROUND: Cardiac repair for congenital heart disease in children awaiting liver transplantation presents unique therapeutic challenges and dilemmas. We tested the hypothesis that operations in these children requiring cardiopulmonary bypass (CPB) were not associated with prohibitive morbidity and mortality. METHODS: Over the last 10 years (1994-2004), five infants were identified in our database with end-stage liver disease and awaiting liver transplantation that required cardiac surgery. Primary end point for the study was mortality. Secondary end points included morbidity and time to liver transplantation. The new pediatric end-stage liver disease (PELD) model was used to score liver disease severity. RESULTS: Three boys and two girls with mean age of 8.6 months (range, 1.5-21 months) and mean PELD of 18.0 (range, 10-29) required CPB for repair. The only early mortality in the series occurred after cardiac arrest during creation of a central shunt. The child expired two days later despite extracorporeal membrane oxygenation support. The patient had important myocardial hypertrophy. All other patients survived and underwent successful liver transplantation. CONCLUSIONS: Children with significant congenital heart disease awaiting liver transplantation can undergo safe cardiac repair with judicious perioperative support thereby reducing the risks of subsequent liver transplantation.

Results of aortic valve-sparing and restoration with autologous pericardial leaflet extensions in congenital heart disease.

BACKGROUND: The purpose of this study is to evaluate the efficacy of aortic valve-sparing repair with glutaraldehyde-treated autologous pericardium in congenital valvular pathology. METHODS: Sixty-two patients underwent reparative aortic valve surgery from January 1997 through December 2003. The mean age was 25 +/- 20 years (+/- standard deviation) (range, 10 days to 81 years). Fifty percent (31 of 62) were less than 19 years old at operation. The diagnoses included bicuspid aortic valve (39 patients), ventricular septal defect (14 patients), severe aortic stenosis (6 patients), subaortic stenosis (7 patients), bacterial endocarditis (7 patients), neonatal truncus arteriosus (2 patients), Shone's complex (2 patients), transposition complex (1 patient), double-chambered right ventricle (1 patient), and Marfan's syndrome (1 patient). Twelve patients (19 %) had prior sternotomy and cardiac operations. Valve-sparing techniques included pericardial leaflet extensions in 62 patients, creation of one or more pericardial neoaortic sinuses in 8, subcommissuroplasty in 8, pericardial patch of perforated leaflets in 9, Dacron mesh wrap (Boston Scientific, Wayne, NJ) of dilated ascending aorta in 12, and concomitant tricuspid and mitral valve repairs in 3 and 4 patients, respectively. RESULTS: There was one early death (1.6%). There were no late deaths at a mean follow-up of 25 +/- 16 (range, 0.1 to 72.5 months). Six patients required reoperation and prosthetic or homograft replacement for aortic valve incompetence. One out of 6 reoperations required re-repair. The remaining patients are well with a mean aortic regurgitation grade by echocardiography of 1.3 +/- 0.9 (scale, 0 to 4). CONCLUSIONS: Aortic valve repair with pericardial leaflet extension is a promising technique for the growing child.

Does duration of donor brain injury affect outcome after orthotopic pediatric heart transplantation?

OBJECTIVE: We tested the hypothesis that duration of donor brain injury and death would have an adverse effect on recipient rejection and mortality in pediatric heart transplantation. METHODS: Ninety-three cardiac transplants were performed at our center from July 1, 1997, through June 30, 2003. The primary study end points were the number of rejection episodes and the time to first rejection. Secondary outcomes were early and late mortality. RESULTS: Among 88 recipients of 93 cardiac allografts, 5 (6%) and 1 (1%) received second and third allografts, respectively. Overall patient mortality (3 early and 2 late) was 6% (5/88), and overall graft loss was 6% (6/93). Median time from donor brain injury to declaration of brain death (brain injury interval), time from brain death to donor cardiectomy (brain death interval), and graft ischemia time were 38, 24, and 3.3 hours, respectively. Cox regression analysis (adjusting for United Network for Organ Sharing status, ventilator dependence, extracorporeal membrane oxygenation and ventricular-assist device status, diagnosis of congenital heart disease, sex and cytomegalovirus mismatches, and type of immunosuppression) demonstrated that recipients of donor hearts with relatively long periods from brain injury to death declaration or from death to organ removal had significantly improved rejection-free survival (hazard ratios 0.3, P = .01, and 0.5, P = .05, for brain injury and brain death times, respectively). Prolonged donor heart ischemia did not impact rejection rate. Increasing brain injury interval, brain death interval, and graft ischemia time had no significant effect on mortality. CONCLUSION: Longer brain injury and death intervals correlated with improved freedom from rejection but had no effect on mortality.

Outcome of hearts with cold ischemic time greater than 300 minutes. A case-matched study.

OBJECTIVE: Expansion of potential donor pool may be facilitated by using cardiac allografts with long ischemic time. Early graft failure and potential relation to transplant coronary artery disease remains a concern. We sought to evaluate outcomes of heart transplantation in recipients of donor allografts with prolonged ischemia time. METHODS: The study group consisted of 46 (mean age, 52 years) consecutive patients at UCLA from 1994 to 2002 that underwent heart transplantation with ischemia time > 300 min. This group was compared to a case-matched control group of 46 (mean age, 51 years) patients identified from our database during this time frame for the following factors: UNOS status, congenital heart disease diagnosis, preop inotropes, pretransplantation creatinine > 1.5 and recipient age. Primary endpoint was mortality and secondary were rejection rate and transplant coronary artery disease. Allografts were perfused and stored in cold University of Wisconsin solution. RESULTS: Mean donor ages of the study and case-matched control group were 34+/-15 and 34+/-14 years, respectively. Mean ischemia times were 388 (range, 301-600 min) and 173 (range, 96-236 min), respectively. The death incidence rate per 100 transplants per year was 9% for the study group and 7.4% for the matched group (P = 0.50). Thirty-day mortality for the study and case-matched groups were 4.3 and 2.1%, respectively (P = 0.9). Late mortality was 16.5 and 18.5%, respectively (P = 0.9). The risk of death after 30 days was 7.5 and 5.8%, respectively (P = 0.5, log-rank). One-year incidence of acute cellular rejection in the study and case-matched groups were 2 and 4.5% (P = 0.36), respectively. One-year incidence of transplant coronary artery disease in the study and case-matched groups were 4.3 and 5.4%, respectively (P = 0.68). CONCLUSIONS: Donor hearts with ischemia time greater than 300 min provide comparable early and intermediate outcomes given judicious and careful donor and recipient matching and our current techniques of myocardial preservation and modified reperfusion.

Redo submammary incision for median sternotomy and cardiac repair.

BACKGROUND: Minimally invasive and cosmetically attractive approaches are fashionable in conducting cardiac operations. METHODS: We reviewed retrospectively our experience in patients undergoing cardiac operations by means of redo submammary incisions. RESULTS: Fifteen consecutive female patients with a mean age of 13.2 years (range, 0.7 to 44 years) underwent reoperation through a former submammary incision. Seventy-three percent (11 of 15) had median sternotomy, cardiopulmonary bypass, and cardiac repairs. The mean aortic cross-clamp and cardiopulmonary bypass times were 78 +/- 49.7 minutes (range, 16 to 182 minutes) and 114.4 +/- 66.4 minutes (range, 27 to 261 minutes), respectively. Twenty-seven percent (4 of 15) had off-pump procedures; 3 for pacemaker-related issues (1 a third time reentry) and 1 for removal of sternal wires. Mean time interval between the primary submammary incision and reoperation was 5.4 +/- 5.6 years (range, 0.01 to 20 years). Mean first 24 hours Hemovac drainage was 3.2 +/- 2.4 mL/kg (range, 0.4 to 8.5 mL/kg). Mean intensive care unit and hospital stays were 2.1 +/- 1.7 days (range, 0.0 to 5 days) and 5.5 +/- 3.6 days (range, 0.80 to 13 days), respectively. One patient exhibited a chylothorax requiring ligation of her thoracic duct. Another patient had an infected seroma requiring incision and drainage 2 months postoperatively. Skin necrosis and infection were absent in this group. Breast development and lactation were normal. The cosmetic results were satisfactory. There was no mortality. CONCLUSIONS: Redo sternotomies performed through redo transverse submammary incisions are safe for cardiac repair and result in acceptable cosmetic and functional results.