Faculty Bibliography

BACKGROUND: The left ventricle (LV) adapts to chronic hypoxia by expressing protective angiogenic, metabolic, and antioxidant genes to improve O2 delivery and energy production, and to minimize reoxygenation injury. The ability of the right ventricle (RV) to adapt to hypoxia in children with tetralogy of Fallot (TOF) is unknown. METHODS AND RESULTS: Gene expression using real-time polymerase chain reaction was measured in RV myocardium obtained during surgical repair of TOF from 23 patients: 13 cyanotic and 10 acyanotic. Results were compared between the 2 groups and correlated with age at surgery, severity of cyanosis, and early postoperative course. The cyanotic patients were younger at surgery compared with acyanotic (5+/-3 versus 9+/-4 months; P=0.01), had higher hematocrit (43+/-4 versus 38+/-3 grams/dL; P=0.004), and lower O2 saturations (84+/-4% versus 98+/-2%; (P<0.001). Cyanotic patients had a significantly lower expression of vascular endothelial growth factor (VEGF), glycolytic enzymes, and glutathione peroxidase (GPX) (P<0.05), and a higher expression of collagen (P<0.01) compared with acyanotic patients. Gene expression correlated inversely with severity of cyanosis ie, preoperative hematocrit (P<0.01) and positively with preoperative saturation (P<0.05). The relationship between gene expression and cyanosis was independent of age at surgery. Ca2+ handling genes did not correlate with the severity of hypoxia. Lower angiogenic, glycolytic, and antioxidant gene expression correlated with increasing postoperative lactate (P<0.05). CONCLUSIONS: The RV fails to up regulate adaptive pathways in response to increasing hypoxia in children with TOF. The implications of an early maladaptive response of the RV on long-term RV function require further investigation

BACKGROUND: Patients with both interrupted aortic arch (IAA) and truncus arteriosus (TA) have worse outcomes than those with either lesion in isolation. We determined outcomes and associated factors in this rare group. METHODS: From 1987 to 1997, 50 (11%) of 472 neonates with IAA were identified with TA. Site of aortic arch interruption was distal to the left subclavian artery in 16% and between the left common carotid and subclavian artery in 84%. From the common arterial trunk, the pulmonary arteries arose from a main pulmonary trunk in 46%, common orifice in 22%, and separate orifices in 32%. At presentation, truncal valve stenosis was present in 12% and regurgitation in 22%. RESULTS: There were 34 deaths, with a single early hazard phase. Overall survival from admission was 44%, 39%, and 31% at 6 months, 1 year, and 10 years, respectively. One patient had primary cardiac transplantation and 4 died without any intervention. The IAA repair alone was performed in 7 patients, with single stage repair of both IAA and TA in 38 patients. Associated factors for overall time-related death include female gender (p < 0.001), type III TA (p < 0.001) and one institution (low-risk; p < 0.001). Results improved somewhat over time (p < 0.001). At 5 years after IAA repair only 28% were alive without arch repair intervention, and at 5 years after TA repair only 18% were alive without conduit reoperation. CONCLUSIONS: The combination of IAA and TA carries high early mortality, with high risk of reinterventions in survivors. One stage repair of both TA and IAA is the optimal management

BACKGROUND: The Ross procedure is commonly used to treat aortic valve disease in pediatric and adult patients. For infants, data are limited regarding survival, reintervention, autograft growth, and function. METHODS AND RESULTS: The Ross procedure was performed in 27 infants <18 months of age (median age 5.7 months). All patients had congenital aortic stenosis (AS); associated lesions included subAS (n=9), supravalvular AS (n=2), coarctation (n=5), and interrupted aortic arch (n=2). Median follow-up was 6.1 years (range 0.2 to 12.9). There were 3 early deaths and no late deaths. Freedom from reintervention for homograft dysfunction was 87% at 8 years; freedom from autograft reintervention was 100%. Follow-up echocardiograms were available in 17 patients. Estimated peak autograft gradient was 55 mm Hg in one patient and <10 mm Hg in 16. Mild autograft insufficiency was seen in 4 patients; 13 had none. Autograft diameter was measured early postoperatively and at latest follow-up. The mean z score increased from 0.63 to 3.2 (P<0.01) at the annulus and from 0.26 to 2.2 (P<0.01) at the sinus. In a subgroup, the mean autograft z score increased significantly from the postoperative period to 1 year for both the annulus (0.72 to 3.2, P<0.01) and the sinus (0.26 to 2.2, P<0.01), but remained unchanged thereafter. CONCLUSIONS: The Ross procedure effectively relieves AS in infants. Homograft reintervention occurred in 13% within 8 years. No patient developed significant autograft insufficiency or required autograft reintervention during the follow-up period. Dilatation of the autograft occurred during the first year after surgery and stabilized thereafter

The risk for cerebrovascular events (CVEs) is increased in children with functional single ventricles (FSVs). However, there are limited data indicating the prevalence of CVEs or the role of preventative therapy. To measure the prevalence of clinically evident CVEs in patients with FSVs, identify risk factors, and analyze the effect of aspirin on the risk for CVEs, a retrospective chart review was performed on all patients who underwent Fontan palliation at the University of Michigan from January 1, 1975, to June 30, 1998 (n = 402). Data collected included original anatomy, Fontan type, date of CVE, medications at the time of CVE, intraoperative placement of fenestration, and date of last follow-up. The overall mortality rate was 12%. There were 38 CVEs (9%), of which only 11 (3%, or 0.0036/patient-year) could not be attributed to a defined event (catheterization, extracorporeal membrane oxygenation, or cardiac arrest). Anticoagulation with aspirin was associated with a statistically significantly decreased risk for CVEs. Fontan type was not associated with the risk for CVEs. Thus, patients with FSVs are at increased risk for CVEs, although the de novo risk was low. Aspirin use is associated with a decreased risk for CVEs

OBJECTIVE: The purpose of this study was to evaluate the outcome and risk factors for implant failure in pediatric patients who underwent pulmonary position homograft placement for right ventricular outflow tract obstruction compared with conduit placement as a component of the Ross operation. Actuarial 5-year survivals for cryopreserved right ventricle-to-pulmonary artery homografts range from 55% to 94% at all ages. It is not known whether there is a difference in homograft durability when utilized for right ventricular outflow tract obstruction or as part of the Ross operation. METHODS: The records of all pediatric patients receiving a right ventricle-to-pulmonary artery homograft from July 1989 through October 2003 were reviewed. Ninety-eight consecutive patients were studied (26 Ross, 72 non-Ross). In addition to Ross versus non-Ross comparisons, other potential risk factors for homograft failure analyzed included age at operation, follow-up time, type of surgery, and homograft type and size. RESULTS: Ross and non-Ross patients were comparable in age at the time of the operation and follow-up time. Homograft failure rates were 12% and 51% for Ross and non-Ross patients, respectively. Freedom from reintervention was 93% in the Ross and 66% in the non-Ross group at 5 years (P = .019). On multivariate analysis, non-Ross operation and age less than 2 years were significant predictors of homograft failure. CONCLUSIONS: 1. Pediatric patients undergoing the Ross operation have longer homograft survival than pediatric patients treated for right ventricular outflow tract obstruction, independent of age. 2. Homografts placed in patients less than 2 years of age have shorter homograft survival

Heart transplantation with ABO blood type-incompatible donors has historically been contraindicated because of the high risk of an immediate hyperacute humoral graft rejection. The immature neonatal immune system presents an immunologic window that allows for breaching the ABO barrier before the natural development of anti-ABO antibodies. Information from a small series of neonates has demonstrated similar survival rates and posttransplant outcomes compared to ABO-compatible transplantations. In the posttransplant period, particular attention is placed on the surveillance of graft-specific antibody production and monitoring for immunologic signs and symptoms of early graft vasculopathy. This article presents a case study of a neonate with congenital heart disease who underwent one of the first successful ABO-incompatible heart transplantations in the United States

OBJECTIVES: We reviewed our experience with repair of truncus arteriosus to assess the effect of type of right ventricular outflow tract reconstruction on perioperative morbidity, survival, and freedom from catheter-based interventions and reoperation. METHODS: Patients undergoing repair of truncus arteriosus from June 1990 through February 2004 were evaluated on the basis of operative procedure regarding preoperative and postoperative variables, the need for postoperative catheter-based intervention or reoperation, and survival on the basis of univariate, multivariable, and actuarial analyses. RESULTS: Of 54 study patients, 15 (28%) received a valved homograft, and 39 (72%) received a direct connection with a variety of hood materials. Five (9.1%) patients died. Valved homograft recipients were more likely to require reoperation than patients receiving direct connections (40% vs 15%, P = .046); however, valved homograft and direct connection recipients had a similar incidence of the combined end point of reoperation or catheter-based intervention (40.0% vs 37.5%, P = .865). Univariate and multivariable modeling demonstrated use of valved homografts or direct connections with an autologous pericardial hood to be predictive of the need for later catheter-based intervention or reoperation. Actuarial analysis demonstrated a trend toward improved outcomes in the direct connection group and within the direct connection cohort, a statistically significant difference on the basis of hood type. CONCLUSIONS: Although the direct connection technique might not prevent later catheter-based intervention, it does reduce the need for reoperation. Outcomes among direct connection recipients were associated with hood type: polytetrafluoroethylene hoods (W. L. Gore & Associates, Inc, Tempe, Ariz) had the lowest rate of reintervention, and untreated autologous pericardial hoods had the highest rate of reintervention. We report excellent outcomes with primary repair of truncus arteriosus. Where anatomically appropriate, we advocate the direct connection technique

BACKGROUND: Many cardiac transplant programs have liberalized donor eligibility criteria in an attempt to maximize donor supply and to accommodate increasing demand. Although many studies have evaluated the potential adverse effects of prolonged donor ischemic time (DIT) in adults undergoing cardiac transplantation, relatively few have focused specifically on pediatric recipients that include a substantial number of patients and long-term follow-up. The focus of this study was to examine the effect of extended DIT on mortality after pediatric heart transplantation. METHODS: We conducted a retrospective review of our pediatric cardiac transplant experience in the past 11 years, comparing patients who received allografts and had ischemic times >240 minutes with those who had ischemic times <240 minutes. RESULTS: A total of 129 pediatric patients (<19 years) underwent orthotopic heart transplantation, of whom 78 (60.5%) had DIT <240 minutes and 51 (39.5%) had DIT >240 minutes. We found no statistically significant difference in age, sex, race, height, weight, or donor age between the groups (p = not significant). Post-transplant survival at 1, 5, and 10 years was similar for both groups: 91.2%, 88.0%, and 85.2%, respectively, for patients with DIT <240 minutes vs 89.6%, 87.2%, and 79.8%, respectively, for patients with DIT >240 minutes (p = 0.433). Additionally, using Cox proportional hazard models, extended DIT >240 minutes was not a statistically significant independent predictor of post-transplant mortality (odds ratio, 0.655; 95% confidence interval, 0.518-0.972; p = 0.684; standard error = 0.468). CONCLUSION: Procurement of hearts from distant locations with associated extended DIT is justified in the setting of increased demand and a fixed donor population