Pediatric heart transplantation after declaration of cardiocirculatory death.

In three infants awaiting orthotopic cardiac transplantation, transplantation was successfully performed with the use of organs from donors who had died from cardiocirculatory causes. The three recipients had blood group O and were in the highest-risk waiting-list category. The mean age of donors was 3.7 days, and the mean time to death after withdrawal from life support was 18.3 minutes. The 6-month survival rate was 100% for the 3 transplant recipients and 84% for 17 control infants who received transplants procured through standard organ donation. The mean number of rejection episodes among the three infants during the first 6 months after surgery was 0.3 per patient, as compared with 0.4 per patient among the controls. Echocardiographic measures of ventricular size and function at 6 months were similar among the three infants and the controls (left ventricular shortening fraction, 43.6% and 44.9%, respectively; P=0.73). No late deaths (within 3.5 years) have occurred in the three infants, and they have had functional and immunologic outcomes similar to those of controls. Mortality while awaiting a transplant is an order of magnitude higher in infants than in adults, and donors who died from cardiocirculatory causes offer an opportunity to decrease this waiting-list mortality.

Long-term outcome of palliation with internal pulmonary artery bands after primary heart transplantation for hypoplastic left heart syndrome.

The purpose of this study was to describe the long-term outcome of infants with hypoplastic left heart syndrome (HLHS) who underwent placement of internal pulmonary artery bands as part of a transcatheter palliation procedure followed by primary heart transplantation. Transcatheter palliation included stenting of the ductus arteriosus, decompression of the left atrium by atrial septostomy, and internal pulmonary artery band placement. Cardiac hemodynamics, pulmonary artery architecture, and pulmonary artery growth since transplantation are described. Nine infants with HLHS had internal pulmonary artery bands placed and underwent successful heart transplant. No infant required reconstruction of the pulmonary arteries at the time of transplant. At 1 year after transplant, all of the recipients had normal mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient. Pulmonary angiography performed at 1 year after transplant demonstrated no distortion of pulmonary artery anatomy with significant interval growth of the branch pulmonary arteries. There was 100% survival to hospital discharge after transplant in this cohort of infants. Transcatheter placement of internal pulmonary artery bands for HLHS offers protection of the pulmonary vascular bed while preserving pulmonary artery architecture and growth with good long-term outcome.

Prevalence of desmin mutations in dilated cardiomyopathy.

BACKGROUND: Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known. METHODS AND RESULTS: Denaturing high-performance liquid chromatography was used to screen DES for mutations in 116 DCM families from the Familial Dilated Cardiomyopathy Registry and in 309 subjects with DCM from the Beta-Blocker Evaluation of Survival Trial (BEST). DES mutations were transfected into SW13 and human smooth muscle cells and neonatal rat cardiac myocytes, and the effects on cytoskeletal desmin network architecture were analyzed with confocal microscopy. Five novel missense DES mutations, including the first localized to the highly conserved 1A domain, were detected in 6 subjects (1.4%). Transfection of DES mutations in the 2B domain severely disrupted the fine intracytoplasmic staining of desmin, causing clumping of the desmin protein. A tail domain mutation (Val459Ile) showed milder effects on desmin cytoplasmic network formation and appears to be a low-penetrant mutation restricted to black subjects. CONCLUSIONS: The prevalence of DES mutations in DCM is between 1% and 2%, and mutations in the 1A helical domain, as well as the 2B rod domain, are capable of causing a DCM phenotype. The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM.

Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group.

BACKGROUND: Since the initial utilization of heart transplantation as therapy for end-stage pediatric heart disease, improvements have occurred in outcomes with heart transplantation and surgical therapies for congenital heart disease along with the application of medical therapies to pediatric heart failure that have improved outcomes in adults. These events justify a reevaluation of the indications for heart transplantation in congenital heart disease and other causes of pediatric heart failure. METHODS AND RESULTS: A working group was commissioned to review accumulated experience with pediatric heart transplantation and its use in patients with unrepaired and/or previously repaired or palliated congenital heart disease (children and adults), in patients with pediatric cardiomyopathies, and in pediatric patients with prior heart transplantation. Evidence-based guidelines for the indications for heart transplantation or retransplantation for these conditions were developed. CONCLUSIONS: This evaluation has led to the development and refinement of indications for heart transplantation for patients with congenital heart disease and pediatric cardiomyopathies in addition to indications for pediatric heart retransplantation.

Interventional cardiac catheterization procedures in pediatric cardiac transplant patients: transplant surgery is not the end of the road.

OBJECTIVES: The objectives of this study are to report the spectrum of cardiac lesions in pediatric patients post-orthotopic heart transplantation (OHT), the characteristics of patients who develop these lesions, and the feasibility of transcatheter intervention in treating these lesions. BACKGROUND: Indications for OHT in the pediatric population range from cardiomyopathy to complex congenital heart defects with and without prior palliation. These patients may have residual vascular access and great vessel abnormalities. METHODS: Data was collected through retrospective review of all OHT patients at our institution from 1988 to 2005. RESULTS: During the study period, 276 heart transplants were performed. Forty-seven patients, age 1.6 [0.1-26] years with a weight of 9.5 [3.5-96.0] kilograms, underwent 69 procedures. Patients with original diagnoses of hypoplastic left heart syndrome and failed palliations required intervention most frequently. Sixteen patients, all with a history of left sided disease, developed aortic arch obstruction. Fifteen were successfully treated with balloon angioplasty while one has recurrent supravalve aortic obstruction. Fourteen patients had superior vena cava obstruction treated with balloon angioplasty and/or stent placement. Twelve patients required no further intervention and two required further stent placement. Ilio-femoral vein occlusion was treated with balloon angioplasty alone in 4 patients and stent placement in 10 patients to achieve vessel patency. Other procedures included treatment of branch pulmonary artery and pulmonary vein stenosis. CONCLUSION: Anastomotic aortic arch and venous obstructive lesions should be sought following pediatric OHT as they occur in almost 20% of patients and can be successfully addressed using interventional techniques.

Carvedilol for children and adolescents with heart failure: a randomized controlled trial.

CONTEXT: Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. OBJECTIVE: To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. MAIN OUTCOME MEASURES: The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. RESULTS: There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). CONCLUSIONS: These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00052026.

Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.

BACKGROUND: Mutations in the beta-myosin heavy-chain (betaMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of alphaMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in alphaMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM. METHODS AND RESULTS: A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for alphaMyHC gene (MYH6) mutations. Three heterozygous MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring. All MYH6 mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of alphaMyHC, and were absent in at least 300 control chromosomes from an ethnically similar population. The DCM carrier phenotype was characterized by late onset, whereas the HCM phenotype was characterized by progression toward dilation, left ventricular dysfunction, and refractory heart failure. CONCLUSIONS: This study suggests that mutations in MYH6 may cause a spectrum of phenotypes ranging from DCM to HCM.

Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy.

Thymopoietin or TMPO (indicated by its alternative gene symbol, LAP2, in this work) has been proposed as a candidate disease gene for dilated cardiomyopathy (DCM), since a LAP2 product associates with nucleoplasmic lamins A/C, which are encoded by the DCM gene LMNA. We developed a study to screen for genetic mutations in LAP2 in a large collection of DCM patients and families. A total of 113 subjects from 88 families (56 with familial DCM (FDC) and 32 with sporadic DCM) were screened for LAP2 mutations using denaturing high-performance liquid chromatography and sequence analysis. We found a single putative mutation affecting the LAP2alpha isoform in one FDC pedigree. The mutation predicts an Arg690Cys substitution (c.2068C>T; p.R690C) located in the C-terminal domain of the LAP2alpha protein, a region that is known to interact with lamin A/C. RT-PCR, Western blot analyses, and immunolocalization revealed low-level LAP2alpha expression in adult cardiac muscle, and localization to a subset of nuclei. Mutated Arg690Cys LAP2alpha expressed in HeLa cells localized to the nucleoplasm like wild-type LAP2alpha, with no effect on peripheral and nucleoplasmic lamin A distribution. However, the in vitro interaction of mutated LAP2alpha with the pre-lamin A C-terminus was significantly compromised compared to the wild-type protein. LAP2 mutations may represent a rare cause of DCM. The Arg690Cys mutation altered the observed LAP2alpha interaction with A-type lamins. Our finding implicates a novel nuclear lamina-associated protein in the pathogenesis of genetic forms of dilated cardiomyopathy.

Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.

OBJECTIVES: We examined the prevalence, genotype-phenotype correlation, and natural history of lamin A/C gene (LMNA) mutations in subjects with dilated cardiomyopathy (DCM). BACKGROUND: Mutations in LMNA have been found in patients with DCM with familial conduction defects and muscular dystrophy, but the clinical spectrum, prognosis, and clinical relevance of laminopathies in DCM are unknown. BACKGROUND: A cohort of 49 nuclear families, 40 with familial DCM and 9 with sporadic DCM (269 subjects, 105 affected), was screened for mutations in LMNA using denaturing high-performance liquid chromatography and sequence analysis. Bivariate analysis of clinical predictors of LMNA mutation carrier status and Kaplan-Meier survival analysis were performed. RESULTS: Mutations in LMNA were detected in four families (8%), three with familial (R89L, 959delT, R377H) and one with sporadic DCM (S573L). There was significant phenotypic variability, but the presence of skeletal muscle involvement (p < 0.001), supraventricular arrhythmia (p = 0.003), conduction defects (p = 0.01), and "mildly" DCM (p = 0.006) were predictors of LMNA mutations. The LMNA mutation carriers had a significantly poorer cumulative survival compared with non-carrier DCM patients: event-free survival at the age of 45 years was 31% versus 75% in non-carriers. CONCLUSIONS: Mutations in LMNA cause a severe and progressive DCM in a relevant proportion of patients. Mutation screening should be considered in patients with DCM, in particular when clinical predictors of LMNA mutation are present, regardless of family history.

Regional myocardial velocities and isovolumic contraction acceleration before and after device closure of atrial septal defects: a color tissue Doppler study.

BACKGROUND: The study analyzed the effect of atrial septal defect (ASD) device closure on regional wall motion in the right (RV) and left ventricles (LV) using color tissue Doppler imaging (TDI). Atrial septal defect closure results in acute volume unloading of the RV. For unknown reasons, some patients develop acute left-sided heart failure postintervention. METHODS: Color TDI was performed in 39 pediatric ASD and 75 age-matched controls. Regional wall motion in 5 LV and 1 RV segment were analyzed before, immediately after, and 24 hours after interventional ASD closure. Off-line postprocessing of echocardiographic data was used to determine myocardial velocities and acceleration during isovolumic contraction (IVA). Isovolumic contraction acceleration is the slope of the upstroke of the isovolumic contraction wave (IVA = peak velocity/acceleration time). RESULTS: At baseline, patients with ASD had significantly higher RV systolic velocities than controls. Isovolumic contraction acceleration was similar in patients with ASD and controls. In the catheterization laboratory postintervention, conventional function parameters remained stable but systolic myocardial velocities decreased significantly in all segments. Diastolic velocities fell in LV segments but not in the RV. In contrast to velocities, IVA was stable during ASD device closure. On follow-up at 24 hours, myocardial velocities had normalized. CONCLUSIONS: Device closure of ASD results to an acute transient decrease of regional myocardial velocities in the LV and RV, whereas the load-insensitive marker isovolumic acceleration remained stable. Therefore, the velocity changes may represent a response to altered left and right ventricular loading conditions. Color TDI is a sensitive tool to analyze ventricular mechanics.

Non-invasive detection of acute allograft rejection in children by tissue Doppler imaging: myocardial velocities and myocardial acceleration during isovolumic contraction.

BACKGROUND: In adults, an acute decrease of regional myocardial velocities is a sensitive marker of rejection. In children, velocities are more variable. A new marker, myocardial acceleration during isovolumic contraction (IVA), appears to be less age-dependent than myocardial velocities. This study therefore compared tissue Doppler (TDI)-derived velocities and IVA as potential rejection markers for children. METHODS: TDI was performed in 15 pediatric heart transplant recipients (age 8.0 +/- 3.6 years) during acute rejection and at baseline without rejection, 50 additional transplant children without rejection (7.8 +/- 5.9 years) and 30 age-matched healthy children (7.5 +/- 5.2 years). Color Doppler cine-loops of 3 cardiac cycles were stored as echocardiographic raw data. Using off-line post-processing, systolic (S) and diastolic (E) myocardial velocities and IVA were measured in 5 basal left ventricular segments. IVA is the peak isovolumic contraction wave velocity divided by acceleration time. RESULTS: Without rejection, transplant children had significantly lower diastolic velocities (basal lateral E 10.4 +/- 2.9 vs 11.9 +/- 2.6 cm/s; p < 0.001) and systolic velocities (S 5.6 +/- 1.4 vs 7.1 +/- 2.0 cm/s; p < 0.001) than normal age-matched controls, but IVA was similar (1.2 +/- 1.4 vs 1.3 +/- 0.5 m/s2). During rejection, all markers decreased significantly compared with age-matched normal control, the non-rejecting transplant group and individual baseline values. CONCLUSIONS: Regional myocardial velocities change significantly during acute allograft rejection in children. However, many children already have wall motion abnormalities at baseline, so results are often difficult to interpret. In contrast, isovolumic acceleration was normal without rejection and selectively decreased during the event. IVA is a promising non-invasive rejection marker for pediatric patients.

Catheter-based interventional palliation for hypoplastic left heart syndrome.

Catheter-based interventional palliation of infants with hypoplastic left heart syndrome (HLHS) has been successfully used to stabilize infants awaiting orthotopic heart transplantation. The three critical palliative requirements for HLHS are ductal patentcy, left heart decompression, and the regulation of pulmonary flow. We reviewed our experience in 40 infants with ductal stenting, and 17 of these 40 infants underwent placement of internal pulmonary artery bands. The infants ranged in age from 2 days to 7 months and from 2.1 to 6.6 kg in weight. There was one procedure-related death after balloon septostomy. The duration of palliation was from 3 days to 1 year. Late survival was 75% with long-term palliation or transplantation. Experience and anatomy of the RV outflow tract/ductus arteriosus was related to technical complications. Infants with mesoversion (12%) were more likely to have procedural and late complications (65%). Internal pulmonary artery bands provide predictable and effective protection of the distal pulmonary artery bed. Pulmonary artery reconstruction was not required, and there were no late pulmonary artery stenoses. We conclude that interventional catheter-based palliation of HLHS has been proven in principle, and further gains in experience and technology will likely make this desirable in the majority of infants with hypoplastic left heart syndrome.

The Pediatric Randomized Carvedilol Trial in Children with Heart Failure: rationale and design.

BACKGROUND: Carvedilol is a medication with both beta-receptor and alpha-receptor blocking properties that has been approved for the treatment of heart failure in adults. Little is known about its safety, efficacy, pharmacokinetics, and dosing profile in children. METHODS: The primary objective of this study is to evaluate the efficacy of carvedilol administered twice daily for 8 months in terms of its effect compared with placebo on a composite measure of clinical outcomes in children with symptomatic systemic ventricular systolic dysfunction and heart failure. The secondary objectives are to determine the effect of carvedilol on individual components of a composite of clinical outcomes (hospitalizations for worsening heart failure, all-cause mortality and cardiovascular hospitalizations, all cause mortality, heart failure symptoms, and patient and physician global assessment); determine the effect of carvedilol on echocardiographic indices of ventricular function and remodeling; characterize the pharmacokinetics of carvedilol in pediatric patients with heart failure; characterize the effects carvedilol on neurohormonal systems; and provide data for the selection of an optimal titration schedule and daily dose of carvedilol in children with heart failure. This study will enroll 150 children between birth and 17 years of age with chronic symptomatic heart failure caused by systemic ventricular systolic dysfunction. CONCLUSION: This study will determine whether carvedilol improves symptoms in children with heart failure as a result of systemic ventricular systolic dysfunction. The study also will provide information on echocardiographic changes of ventricular performance and neurohormonal levels in children with heart failure before and after treatment with carvedilol, in addition to pharmacokinetics of carvedilol in children.

Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure.

OBJECTIVES: Elevated pulmonary vascular resistance may contribute to late Fontan circulation failure but is difficult to assess in such patients. Our aims were to assess outcomes of patients with failed Fontan circulation after heart transplantation and to determine whether elevated pulmonary vascular resistance might have contributed to the failure. METHODS: Fifteen patients (14 Fontan circulations, 1 Kawashima circulation) underwent transplantation. The most common indication was ventricular dysfunction (mean ventricular end-diastolic pressure 12.5 mm Hg). Patients with early failures (n = 4) required transplantation less than 1 year after the Fontan operation. Those with late failures (n = 11) underwent transplantation at least 1 year after the Fontan operation. Mean age at transplantation was 11.6 years. Mean Fontan-transplantation interval was 7.4 years. Mean pulmonary arterial pressure, transpulmonary gradient, and pulmonary vascular resistance before and after transplantation were assessed. Paired t tests of variable differences were used to compare variables. Survival was estimated by the Kaplan-Meier method. RESULTS: In-hospital mortality was 7%. There were 2 late events (1 death, 1 retransplantation) related to compliance or rejection issues. Graft survivals were 93%, 82%, and 82% at 3, 5, and 7 years, respectively. Posttransplantation pulmonary vascular resistance was elevated (>2.0 Wood units . m 2 ) in 11 of 14 survivors past initial hospitalization (mean 3.3 +/- 1.7 Wood units . m 2 ). Only patients with early Fontan failures (3 of 4) had normal posttransplantation pulmonary vascular resistance. In paired comparisons, posttransplantation transpulmonary gradient was increased by a mean of 6.8 mm Hg ( P < .0001) relative to pretransplantation value. CONCLUSIONS: Outcomes after heart transplantation for failed Fontan circulation were good. Mild-to-moderate pulmonary vascular disease was evident after heart transplantation for late failure. Elevated pulmonary vascular resistance is a likely contributor to Fontan circulation failure.

Diastolic performance assessed by tissue Doppler after pediatric heart transplantation.

BACKGROUND: Diastolic performance, indexed by tissue Doppler imaging (TDI), has been reported to predict cellular rejection in adult heart recipients, but the predictive value of TDI after pediatric heart transplantation is unknown. METHODS: TDI-derived diastolic performance was studied in 37 pediatric (median age 2.54 years) heart recipients in the absence and presence of rejection. Maximum velocities in diastole of the left ventricular posterior wall thinning (diastvelLVPWmax) and medial mitral valve annulus (MVA) were determined in 160 echocardiograms from recipients who experienced either no rejection (Group 1, n = 22) or >or=1 rejection episode(s) (Group 2, n = 14) during the study interval (2 years). There was 1 death in the immediate post-transplant period not included in the analyses. RESULTS: The diastvelLVPWmax determined by TDI in Group 1 increased during the first 90 days post-transplant (r = 0.31; p = 0.05), was heart-rate-dependent (r = 0.591; p < 0.001), and was significantly lower than the veILVPWmax determined from digitized M-mode tracings (116 +/- 31 vs 135 +/- 44 mm/s; p < 0.05). In a sub-group of children transplanted during the study and followed for >or=1 year (n = 9), diastvelLPWmax, determined by TDI, was lower in infant recipients (n = 6; 106.5 +/- 22 mm/s) than in older recipients (n = 3; 135 +/- 36 mm/s; p = 0.015). With rejection, diastvelLVPWmax, determined by M mode (147 +/- 13 vs 104 +/- 11 mm/s; p < 0.05), was decreased compared with baseline recipient studies prior to rejection. In contrast, rejection did not significantly change diastvelLVPWmax, as determined by TDI. MVA E/A (peak early-to-late diastolic velocity ratio) was significantly decreased with rejection (1.37 +/- 0.23 vs 0.92 +/- 0.22; p < 0.05). As a single parameter, an MVA E/A <1.1 was predictive of rejection in 4 of 10 recipients with MVA E/A >or=1.1 pre-rejection. CONCLUSIONS: TDI-derived diastvelLVPWmax varied with age at transplant, heart rate and time post-transplant. A decrease in TDI-derived MVA E/A, but not diastvelLVPWmax, can be of additional predictive value in non-invasive surveillance for rejection in pediatric heart recipients.

Mechanical limitation of pulmonary blood flow facilitates heart transplantation in older infants with hypoplastic left heart syndrome.

OBJECTIVES: Progression of pulmonary vascular disease limits heart transplantation for hypoplastic left heart syndrome (HLHS) to early infancy. Our objective was to assess the impact of bilateral pulmonary artery banding (PAB) on the operative courses of HLHS infants transplanted at ages older than 4 months. METHODS: Courses of all HLHS patients in our center who remained listed to age >or=120 days before heart transplantation were assessed. Patients undergoing transplantation after standard management (control group) were compared to patients having a prior pulmonary blood flow limiting procedure (PAB group). RESULTS: Of 16 identified patients, one crossed over to stage I Norwood on day 185 and died post-operatively. Fifteen patients were transplanted at age >or=120 days (control group n=9, PAB group n=6). Four PAB patients had open PA band placement. Two PAB patients underwent experimental percutaneous bilateral internal pulmonary artery flow limiting device insertion. The PAB group mean age at banding was 141+/-54 days, and mean interval from PAB to transplant was 35+/-31 days (range 1.5-68 days). No differences in age at transplant, weight at transplant, warm graft ischemia time or total graft ischemia time were detected between groups. Mean times of mechanical ventilation (control 143+/-69h vs. PAB 44+/-13h), inhaled nitric oxide (control 126+/-70h vs. PAB 37+/-9h), inotropic support (control 171+/-64h vs. PAB 87+/-17h), intensive care unit (ICU) stay (control 8.3+/-2.7 days vs. PAB 4.5+/-1.4 days), and hospital stay (control 10.4+/-3.9 days vs. PAB 7.0+/-1.1 days) were all lower in the PAB group (P<0.05 all comparisons). Two control patients died, three required extracorporeal membrane oxygenation (ECMO), and six did not tolerate primary chest closure. No PAB patient died or required ECMO. All PAB patients tolerated primary chest closure. All PAB patients had widely patent branch pulmonary arteries with no re-interventions to date. All hospital survivors remain alive (mean follow-up, control 50.2 months, PAB 11.5 months). CONCLUSIONS: Pre-transplant mechanical limitation of pulmonary blood flow simplified management and reduced morbidity for HLHS patients undergoing heart transplantation at ages >or=4 months. This strategy extends the permissible transplant waiting time in older infants with HLHS.

Heart transplantation for the failing Fontan circulation.

The failing Fontan circulation presents difficult treatment challenges. When Fontan revision and or intervention for treatable arrhythmias are not feasible, heart transplantation is the only therapeutic option. Particular challenges presented by these patients include limited ability to assess hemodynamics, complex anatomy, multiple prior procedures, and unique underlying pathologic states. These issues complicate the decision-making process for further surgical intervention verses transplantation. The pretransplant evaluation, transplant operation, and postoperative management are more problematic for these patients compared with most patients undergoing transplantation. Consequently, failing Fontan patients constitute one of the highest risk heart transplant subsets.