Survival and right ventricular performance for matched children after stage-1 Norwood: Modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery conduit.

OBJECTIVE: Early survival advantages after Norwood with right-ventricle-(RV)-to-pulmonary-artery conduit (NW-RVPA) over Norwood-operation with a Blalock-Taussig shunt (NW-BT) are offset by concerns regarding delayed RV dysfunction. We compared trends in survival, RV dysfunction, and tricuspid valve regurgitation (TR) between NW-RVPA and NW-BT for propensity-matched neonates with critical left ventricular outflow tract obstruction (LVOTO). METHODS: In an inception cohort (2005-2014; 21 institutions), 454 neonates with critical LVOTO underwent Norwood stage 1. Propensity-score matching paired 169 NW-RVPA patients with 169 NW-BT patients. End-states were compared between NW-RVPA and NW-BT using competing-risks, multiphase, parametric, hazard analysis. Post-Norwood echocardiogram reports (n = 2993) were used to grade RV dysfunction and TR. Time-related prevalence of ≥moderate RV dysfunction and TR were characterized using nonlinear mixed-model regression, and compared between groups via multiphase, parametric models. RESULTS: Overall 6-year survival was better after NW-RVPA (70%) versus NW-BT (55%; P < .001). Additionally, transplant-free survival during this time was better after NW-RVPA (64%) versus NW-BT (53%; P = .004). Overall prevalence of ≥moderate RV dysfunction reached 11% within 3 months post-Norwood. During this time, RV dysfunction after NW-BT was 16% versus 6% after NW-RVPA (P = .02), and coincided temporally with an increased early hazard for death. For survivors, late RV dysfunction was <5% and was not different between groups (P = .36). Overall prevalence of ≥moderate TR reached 13% at 2 years post-Norwood and was increased after NW-BT (16%) versus NW-RVPA (11%; P = .003). Late TR was similar between groups. CONCLUSIONS: Among propensity-score-matched neonates with critical LVOTO, NW-RVPA offers superior 6-year survival with no greater prevalence of RV dysfunction or TR than conventional NW-BT operations.

Calcium and phosphorus concentrations in native and decellularized semilunar valve tissues.

BACKGROUND AND AIM OF THE STUDY: Native, allograft, xenograft and bioprosthetic semilunar valves are all susceptible to calcific degeneration. However, intrinsic differences in baseline calcium and phosphorus tissue concentrations within mammalian normal valve structural components (e.g., cusps, sinus, vessel wall) additionally subdivided by tripartite regions (e.g., right-, left- and non-coronary leaflets) have never been systematically measured and reported. It was originally hypothesized that variations in normative tissue concentrations of calcium and phosphorus may correspond to subsequent clinical patterns of acquired dystrophic calcification; decellularization was also expected to reduce the tissue concentrations of these elements. METHODS: Native semilunar valves were freshly harvested from 12 juvenile sheep. Half of the valves were decellularized (six aortic and six pulmonary), while the other valves were flash-frozen at -80 degrees C within minutes of euthanasia as native valves. Elemental calcium and phosphorus concentrations were measured in the great vessels, sinus walls and cusps using inductively coupled plasma optical emission spectrometry (ICP-OES), and analyzed with non-parametric statistical tests. RESULTS: Calcium concentrations (microg/mg tissue; median (range) were similar in aortic native cusps (0.37 (0.21)), sinus walls (0.37 (0.09)) and aorta (0.37 (0.08)) (p = 0.8298). Pulmonary calcium concentrations were similar in cusps, but 10-25% higher in the native sinus (p = 0.0018) and pulmonary artery (p < 0.0001) compared to analogous aortic structures. All cusps had higher phosphorus concentrations than their respective conduit tissues. No tripartite regional variations were observed. Decellularization did not reduce the calcium content of cusps, but removed 50-55% of vessel and sinus wall calcium. However, up to 85% of phosphorus was removed from all valve tissues (p < 0.001). CONCLUSION: There were no significant differences in normal tissue concentrations of calcium between aortic valve functional structures, and no semilunar tripartite regional differences in either semilunar valve complex. Thus, the distribution of baseline tissue calcium content of healthy young valves is not inherently predictive of selective or asymmetric anatomical patterns of valve degenerative calcification. Native semilunar cusps contain the highest phosphorus concentrations. Decellularization reduces all elemental concentrations except for cuspal calcium.

Pulmonary arterioplasty with decellularized allogeneic patches.

BACKGROUND: Decellularized allogeneic nonvalved pulmonary artery patches for arterioplasty are a relatively new option compared with cryopreserved allogeneic, crosslinked xenogeneic bioprosthetic or synthetic materials. This study examines the midterm experience with a new decellularized allogeneic patch for congenital cardiac reconstructions. METHODS: For this prospective postmarket approval, nonrandomized, inclusive observational study, we collected data on a consecutive cohort of 108 patients with cardiovascular reconstructions using 120 decellularized allogeneic pulmonary artery patches (MatrACELL; LifeNet Health, Inc, Virginia Beach, VA) between September 2009 and December 2012. One hundred of the patches were used for pulmonary arterioplasties. Two patients were lost early to follow-up and excluded from subsequent survival and durability analyses. Data included demographics, surgical outcomes, subsequent reoperations, and catheter reinterventions. These variables were also collected for an immediately preceding retrospective consecutive cohort of 100 patients with 101 pulmonary arterioplasty patches who received classical cryopreserved pulmonary artery allografts (n=59 patches and patients) or synthetic materials (n=41 patients with 42 patches) for pulmonary arterioplasties between 2006 and 2009. RESULTS: In 106 patients with 118 decellularized patches, there were no device-related serious adverse events, no device failures, and no evidence of calcifications on chest roentgenograms. In contrast, the prior comparative pulmonary arterioplasty cohort of 100 patients experienced an overall 14.0% patch failure rate requiring device-related reoperations (p<0.0001) at mean duration of 194±104 days (range, 25 to 477 days). CONCLUSIONS: The intermediate-term data obtained in this study suggest favorable performance by decellularized pulmonary artery patches, with no material failures or reoperations provoked by device failure.

Neonatal acute myocardial infarction of unknown etiology treated with surgical thrombectomy.

Coronary artery thrombosis and resultant myocardial infarction in neonates are exceedingly rare. Seldom does a neonate survive this myocardial insult. Often there is an underlying predisposition to coronary artery thrombosis, such as thrombophilia, central line placement, or myocarditis. Treatment attempts have consisted of thrombolysis and supportive care. We present a case of acute left main coronary artery (LMCA) thrombosis of unknown etiology in a neonate, without ventricular dilatation. Flow into the LMCA was suggested echocardiographically, but a high clinical suspicion led to urgent cardiac catheterization. Once complete occlusion of the LMCA was demonstrated angiographically, emergent surgical thrombectomy was performed, which has never previously been reported.

Transesophageal Echocardiography in Healthy Young Adult Male Baboons (Papio hamadryas anubis): Normal Cardiac Anatomy and Function in Subhuman Primates Compared to Humans.

Implantable, viable tissue engineered cardiovascular constructs are rapidly approaching clinical translation. Species typically utilized as preclinical large animal models are food stock ungulates for which cross species biological and genomic differences with humans are great. Multiple authorities have recommended developing subhuman primate models for testing regenerative surgical strategies to mitigate xenotransplant inflammation. However, there is a lack of specific quantitative cardiac imaging comparisons between humans and the genomically similar baboons (Papio hamadryas anubis). This study was undertaken to translate to baboons transesophageal echocardiographic functional and dimensional criteria defined as necessary for defining cardiac anatomy and function in the perioperative setting. Seventeen young, healthy baboons (approximately 30 kg, similar to 5 year old children) were studied to determine whether the requisite 11 views and 52 measurement parameters could be reliably acquired by transesophageal echocardiography (TEE). The obtained measurements were compared to human adult normative literature values and to a large relational database of pediatric "normal heart" echo measurements. Comparisons to humans, when normalized to BSA, revealed a trend in baboons toward larger mitral and aortic valve effective orifice areas and much larger left ventricular muscle mass and wall thickness, but similar pulmonary and tricuspid valves. By modifying probe positioning relative to human techniques, all recommended TEE views except transgastric could be replicated. To supplement, two transthoracic apical views were discovered that in baboons could reliably replace the transgastric TEE view. Thus, all requisite echo views could be obtained for a complete cardiac evaluation in Papio hamadryas anubis to noninvasively quantify cardiac structural anatomy, physiology, and dimensions. Despite similarities between the species, there are subtle and important physiologic and anatomic differences when compared to human.

Bioengineered human and allogeneic pulmonary valve conduits chronically implanted orthotopically in baboons: hemodynamic performance and immunologic consequences.

OBJECTIVE: This study assesses in a baboon model the hemodynamics and human leukocyte antigen immunogenicity of chronically implanted bioengineered (decellularized with collagen conditioning treatments) human and baboon heart valve scaffolds. METHODS: Fourteen baboons underwent pulmonary valve replacement, 8 with decellularized and conditioned (bioengineered) pulmonary valves derived from allogeneic (N = 3) or xenogeneic (human) (N = 5) hearts; for comparison, 6 baboons received clinically relevant reference cryopreserved or porcine valved conduits. Panel-reactive serum antibodies (human leukocyte antigen class I and II), complement fixing antibodies (C1q binding), and C-reactive protein titers were measured serially until elective sacrifice at 10 or 26 weeks. Serial transesophageal echocardiograms measured valve function and geometry. Differences were analyzed with Kruskal-Wallis and Wilcoxon rank-sum tests. RESULTS: All animals survived and thrived, exhibiting excellent immediate implanted valve function by transesophageal echocardiograms. Over time, reference valves developed a smaller effective orifice area index (median, 0.84 cm(2)/m(2); range, 1.22 cm(2)/m(2)), whereas all bioengineered valves remained normal (effective orifice area index median, 2.45 cm(2)/m(2); range, 1.35 cm(2)/m(2); P = .005). None of the bioengineered valves developed elevated peak transvalvular gradients: 5.5 (6.0) mm Hg versus 12.5 (23.0) mm Hg (P = .003). Cryopreserved valves provoked the most intense antibody responses. Two of 5 human bioengineered and 2 of 3 baboon bioengineered valves did not provoke any class I antibodies. Bioengineered human (but not baboon) scaffolds provoked class II antibodies. C1q(+) antibodies developed in 4 recipients. CONCLUSIONS: Valve dysfunction correlated with markers for more intense inflammatory provocation. The tested bioengineering methods reduced antigenicity of both human and baboon valves. Bioengineered replacement valves from both species were hemodynamically equivalent to native valves.

Noncoding RNA expression in myocardium from infants with tetralogy of Fallot.

BACKGROUND: The importance of noncoding RNAs (ncRNA), especially microRNAs (miRNAs), for maintaining stability in the developing vertebrate heart has recently become apparent; however, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. METHODS AND RESULTS: We examined the expression of miRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, 3 fetal heart samples, and 8 normally developing infants. We found 61 miRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared with normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a surprising resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of miRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 miRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and 2 spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of genes that are critical for cardiac development. Taken together, these observations suggest a link between levels of snoRNA that target spliceosomal RNAs, spliceosomal function, and heart development. CONCLUSIONS: This is the first report characterizing ncRNA expression in a congenital heart defect. The striking shift in expression of ncRNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing, and translation of developmentally important genes and possibly contributing to the cardiac defect.

Effects of cryopreservation, decellularization and novel extracellular matrix conditioning on the quasi-static and time-dependent properties of the pulmonary valve leaflet.

Decellularized allografts offer potential as heart valve substitutes and scaffolds for cell seeding. The effects of decellularization on the quasi-static and time-dependent mechanical behavior of the pulmonary valve leaflet under biaxial loading conditions have not previously been reported in the literature. In the current study, the stress-strain, relaxation and creep behaviors of the ovine pulmonary valve leaflet were investigated under planar-biaxial loading conditions to determine the effects of decellularization and a novel post-decellularization extracellular matrix (ECM) conditioning process. As expected, decellularization resulted in increased stretch along the loading axes. A reduction in relaxation was observed following decellularization. This was accompanied by a reduction in glycosaminoglycan (GAG) content. Based on previous implant studies, these changes may be of little functional consequence in the short term; however, the long term effects of decreased relaxation and GAG content remain unknown. Some restoration of relaxation was observed following ECM conditioning, especially in the circumferential specimen direction, which may help mitigate any detrimental effects due to decellularization. Regardless of processing, creep under biaxial loading was negligible.

Initial pediatric cardiac experience with decellularized allograft patches.

PURPOSE: This study examines use patterns, early outcomes, and technical surgical adaptability of a newly approved decellularized allograft pulmonary artery patch for right ventricular outflow tract reconstructions in neonates and infants, including primary operations and reoperations. DESCRIPTION: The study includes the 44 consecutive initial patients in which 46 patches were used for cardiovascular reconstruction between September 2009 and September 2010. Recorded variables include sex, age at operation, adverse outcome end points (eg, death, stenosis, aneurysm), congenital diagnoses, postoperative complications, and number, type, and location of patches. EVALUATION: Patients were a mean age of 290±343 days at operation, and 54.5% were boys. Three types of patch were used: 58.7% thin, 21.7% thick, and 19.6% hemipulmonary. No device-related deaths or adverse events occurred. A biopsy specimen of one patch at elective reoperation demonstrated active recellularization, with no inflammation. CONCLUSIONS: These patches have a wide range of applicability. Handling and technical flexibility is excellent and superior to standard options. There appears to be potential for autologous revitalization of the tissue.

Streptococcus pneumoniae causing mycotic aneurysm in a pediatric patient with coarctation of the aorta.

Mycotic aneurysms are rare in patients with congenital heart disease, but may occur in those with aortic coarctation and abnormal aortic valve. Rapid diagnosis of mycotic aneurysm is of extreme importance given the significant reported incidence of morbidity and mortality across all age groups. Aortic aneurysm is uncommon before the second decade of life, and here we report a 10-year-old male patient with new diagnosis of aortic coarctation and bicuspid aortic valve, who developed a rapidly enlarging mycotic aneurysm from Streptococcus pneumoniae. Cardiac magnetic resonance imaging was crucial in making the diagnosis, as well as in follow-up.

Determining cell seeding dosages for tissue engineering human pulmonary valves.

BACKGROUND: This study examines in vitro seeding of decellularized human pulmonary valves (hPVs) with human valve interstitial cells (hVICs) isolated from unrelated donor aortic valve leaflets. An assay was developed to assess seeding using precut uniform sized biopsies from whole hPVs for sequential evaluation of seeding efficiency, proliferation, and migration. MATERIALS AND METHODS: Scaffolds for seeding were created from decellularized hPVs using a reciprocating osmolality, double detergent, enzyme, multiple solvent protocol. hVICs seeded decellularized leaflet and sinus wall scaffolds were incubated in either static or cyclic pressure bioreactors. Low, medium, and high initial cell seeding "dosing" densities were assayed at subsequent three time points, using eight replicates each (n = 576 biopsies including manufactured scaffold controls). Metabolically viable seeded cells were quantified by MTT assay. Histology defined cell locations and morphology. RESULTS: After 24 h of static seeding with 2.5 × 10(5) cells (medium dose), 100 ± 13 cells/mm(2) (2.5%) attached to leaflets, compared with 193 ± 21 cells/mm(2) (8%) for sinuses. Subsequent 4 d in static culture yielded 894 ± 84 and 838 ± 50 cells/mm(2)versus pulsatile culture yielding 80 ± 12 and 79 ± 12 cells/mm(2) for leaflet and sinus, respectively. However, 76.0% ± 12.2% of cells in leaflets in the pulsatile bioreactor were subsurface as compared to 21.4% ± 3.9% in statically cultured leaflets (P < 0.001). CONCLUSION: Different seeding modes suggest a tradeoff between surface proliferation resulting in higher absolute cell numbers for static seeding versus fewer cells in a cyclic pressure bioreactor but with a greater percentage having migrated into the matrix. The medium seeding dose determined to be optimal is actually feasible for tissue engineering heart valves, and can be achieved by fairly traditional cell amplification methods.

Performance and morphology of decellularized pulmonary valves implanted in juvenile sheep.

BACKGROUND: Because of cryopreserved heart valve-mediated immune responses, decellularized allograft valves are an attractive option in children and young adults. The objective of this study was to investigate the performance and morphologic features of decellularized pulmonary valves implanted in the right ventricular outflow tract of juvenile sheep. METHODS: Right ventricular outflow tract reconstructions in juvenile sheep (160±9 days) using cryopreserved pulmonary allografts (n=6), porcine aortic root bioprostheses (n=4), or detergent/enzyme-decellularized pulmonary allografts (n=8) were performed. Valve performance (echocardiography) and morphologic features (gross, radiographic, and histologic examination) were evaluated 20 weeks after implantation. RESULTS: Decellularization reduced DNA in valve cusps by 99.3%. Bioprosthetic valves had the largest peak and mean gradients versus decellularized valves (p=0.03; p<0.001) and cryopreserved valves (p=0.01; p=0.001), which were similar (p=0.45; p=0.40). Regurgitation was minimal and similar for all groups (p=0.16). No cusp calcification was observed in any valve type. Arterial wall calcification was present in cryopreserved and bioprosthetic grafts but not in decellularized valves. No autologous recellularization or inflammation occurred in bioprostheses, whereas cellularity progressively decreased in cryopreserved grafts. Autologous recellularization was present in decellularized arterial walls and variably extending into the cusps. CONCLUSIONS: Cryopreserved and decellularized graft hemodynamic performance was comparable. Autologous recellularization of the decellularized pulmonary arterial wall was consistently observed, with variable cusp recellularization. As demonstrated in this study, decellularized allograft valves have the potential for autologous recellularization.

Gene expression in cardiac tissues from infants with idiopathic conotruncal defects.

BACKGROUND: Tetralogy of Fallot (TOF) is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot. METHODS: We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions) and compared gene expression patterns to normally developing subjects. RESULTS: We detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV) of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation). However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, p = 0.017 and Notch, p = 0.003) appeared to be generally suppressed. CONCLUSIONS: The suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.

Pediatric cardiopulmonary bypass adaptations for long-term survival of baboons undergoing pulmonary artery replacement.

Cardiopulmonary bypass (CPB) protocols of the baboon (Papio cynocephalus anubis) are limited to obtaining experimental data without concern for long-term survival. In the evaluation of pulmonary artery tissue engineered heart valves (TEHVs), pediatric CPB methods are adapted to accommodate the animals' unique physiology enabling survival up to 6 months until elective sacrifice. Aortic access was by a 14F arterial cannula and atrial access by a single 24F venous cannula.The CPB circuit includes a 3.3 L/min flow rated oxygenator, 1/4" x %" arterial-venous loop, 3/8" raceway, and bubble trap. The prime contains 700 mL Plasma-Lyte, 700 units heparin, 5 mL of 50% dextrose, and 20 mg amiodarone. Heparinization (200 u/kg) targets an activated clotting time of 350 seconds. Normothermic CPB was initiated at a 2.5 L/m2/min cardiac index with a mean arterial pressure of 55-80 mmHg. Weaning was monitored with transesophageal echocardiogram. Post-CPB circuit blood was re-infused. Chest tubes were removed with cessation of bleeding. Extubation was performed upon spontaneous breathing. The animals were conscious and upright 3 hours post-CPB. Bioprosthetic valves or TEHVs were implanted as pulmonary replacements in 20 baboons: weight = 27.5 +/- 5.6 kg, height = 73 +/- 7 cm, body surface area = 0.77 m2 +/- 0.08, mean blood flow = 1.973 +/- .254 L/min, core temperature = 37.1 +/- .1 degree C, and CPB time = 60 +/- 40 minutes. No acidosis accompanied CPB. Sixteen animals survived, four expired. Three died of right ventricular failure and one of an anaphylactoid reaction. Surviving animals had normally functioning replacement valves and ventricles. Baboon CPB requires modifications to include high systemic blood pressure for adequate perfusion into small coronary arteries, careful CPB weaning to prevent ventricular distention, and drug and fluid interventions to abate variable venous return related to a muscularized spleno-splanchnic venous capacity.

Persistent risk of subsequent procedures and mortality in patients after interrupted aortic arch repair: a Congenital Heart Surgeons' Society study.

OBJECTIVE: Multiple subsequent procedures directed at the arch and/or the left ventricular outflow tract are frequently required after interrupted aortic arch repair. We the investigated patterns and factors associated with these subsequent procedures and mortality. METHODS: We reviewed the data from 447 patients with interrupted aortic arch at 33 institutions enrolled from 1987 to 1997. We classified the subsequent procedures by type (catheter-based or surgical) and focus (arch, left ventricular outflow tract, and "other" cardiovascular lesions). We used competing risks and modulated renewal analysis to explore subsequent procedures. RESULTS: There were 158 subsequent arch and 100 left ventricular outflow tract procedures. Freedom from death at 21 years was 60% overall. The risk of additional subsequent arch procedures decreased after the first subsequent arch procedure in the acute phase, but did not significantly change in the chronic phase. The risk of additional subsequent left ventricular outflow tract procedures increased after the first subsequent left ventricular outflow tract procedure in the chronic phase. The risk factors for subsequent arch procedures and mortality, but not for subsequent outflow track procedures, were related in a complex way to previous procedures and their timing. CONCLUSIONS: Interrupted aortic arch is a chronic disease in which patients often undergo multiple subsequent procedures with persistent risk for additional intervention and mortality. The risk factors are related to the nature and timing of previous procedures and to the morphology and details of the index procedure. Interrupted aortic arch should be considered a chronic disorder.

The nonfenestrated extracardiac Fontan procedure: a cohort of 145 patients.

BACKGROUND: There are limited data available on the outcomes of single-ventricle patients who have undergone a nonfenestrated extracardiac Fontan procedure. This study examined the clinical experience of a large cohort of patients from a single institution who received this procedure. METHODS: A retrospective data set of 145 patients who underwent a nonfenestrated extracardiac Fontan procedure from July 1997 to September 2008 was reviewed. RESULTS: The hospital survival was 94.5%. Takedown of the Fontan conduit was necessary in 4 patients (2.8%), and 3 of these 4 patients were also operative deaths. Although female sex (p = 0.048), cardiopulmonary bypass time (p = 0.002), and aortic cross-clamp time (p = 0.007) were found to be significant in the univariate analysis, only sex (p = 0.035; odds ratio, 3.869; 95% confidence limits, 1.097 to 13.644) and cardiopulmonary bypass time in minutes (p = 0.001; odds ratio, 1.023; 95% confidence limits, 1.009 to 1.037) were found to be significant in the multivariate analysis for hospital survival. The late survival was 95.6% (131 of 137 patients) with a mean follow-up of 3.3 years (range, 0.0 to 10.8 years). The freedom from Fontan failure was 92% at 1 year, 89% at 5 years, and 82% at 10 years. Stepwise logistic regression found cardiopulmonary bypass time (p = 0.003; odds ratio, 1.023; 95% confidence limits, 1.008 to 1.039) to be a significant risk factor for late survival. CONCLUSIONS: The nonfenestrated extracardiac Fontan procedure can be successfully used in the palliation of single-ventricle patients.

Intraoperative hyperglycemia and postoperative bacteremia in the pediatric cardiac surgery patient.

BACKGROUND: Intraoperative hyperglycemia has been found to be associated with a higher incidence of postoperative infections in the adult cardiac surgery population. The goal of this study was to determine the association of intraoperative hyperglycemia and postoperative bacteremia in the pediatric population. METHODS: A retrospective chart review of all cardiac surgical cases for patients 18 years of age or younger requiring cardiopulmonary bypass support between June 2002 and July 2007 yielded 1,132 total cases representing 992 unique patients. Patient demographic and clinical data of interest were collected. Descriptive statistics and regression analyses were performed to investigate the hypothesized relationship between glucose levels and infection rates. RESULTS: From the 992 patient records examined, 15 patients exhibited a bacteremia within 14 days of surgery (1.5%). The association between the highest glucose during cardiopulmonary bypass and bacteremia reached statistical significance when the glucose level reached 175 mg/dL (chi(2) = 4.59, 1 degree of freedom; p = 0.032). A patient was more than three times as likely to have a postoperative bacteremia when the glucose level reached this amount or exceeded it (odds ratio, 3.3, 95% confidence interval, 1.04 to 10.39). Ten of the 15 (66.7%) postoperative infections occurred in patients with peak bypass glucose levels of at least 175 mg/dL. CONCLUSIONS: Intraoperative hyperglycemia was found to be associated with a higher risk of postoperative bacteremia in the pediatric cardiac surgery population.

Decellularization reduces calcification while improving both durability and 1-year functional results of pulmonary homograft valves in juvenile sheep.

OBJECTIVE: The juvenile sheep functional valve chronic implant calcification model was used to compare long-term calcification rates, functional performance, and durability for 3 types of right ventricular outflow tract implants: classically cryopreserved homografts and 2 decellularized pulmonary valved conduits. METHODS: Fifteen juvenile sheep were randomly assigned to one of 3 study arms and underwent pulmonary valve replacement. The arms included the following: (1) cryopreserved ovine pulmonary valves; (2) cryopreserved, decellularized, saline (1 degrees C-10 degrees C)-stored ovine pulmonary valves; and (3) cryopreserved, decellularized, glycerolized (-80 degrees C) stored ovine pulmonary valves. Animal growth, serial echocardiographic results (with valve performance assessment), dimensions, and tissue-specific calcification measurements were compared with pre-explant angiographic analysis and right ventricular outflow tract pressure measurements, cardiac magnetic resonance imaging, specimen radiographic analysis, gross explant pathology, and histopathology. Parametric and nonparametric statistical analysis were performed. RESULTS: All but 2 study animals receiving implants thrived postoperatively, with similar growth rates, explant valve dimensions, ventricular functions, cardiac output, and indices during the study. As determined by means of echocardiographic analysis, 3 animals in arm 1 (and one in arm 2) had leaflet dysfunction. Valve regurgitation was recognized in 1 survivor each from both arms 1 and 2. Although 1 arm 1 animal died with calcified subacute bacterial endocarditis, and the other 4 had leaflet and conduit wall calcification by the time of death, no arm 2 or arm 3 animals demonstrated leaflet calcium, and no arm 3 and only 1 arm 2 animals had calcium in the conduit wall over the entire year, as determined with any measurement method. All cryopreserved conduit walls had calcium by 20 weeks, whereas only 1 of 10 decellularized conduits (arms 2 plus 3) had wall calcium. CONCLUSION: Cryopreserved-decellularized-glycerolized valves retained normal valve function, with absent leaflet and minimal wall calcifications 1 year postoperatively, as opposed to classically cryopreserved allografts. These results might be predictive of the prolonged durability and functionality of a cryopreserved-decellularized-glycerolized allograft valve.

Critical left ventricular outflow tract obstruction: The disproportionate impact of biventricular repair in borderline cases.

OBJECTIVE: In critical left ventricular outflow tract obstruction, the common perception that biventricular physiology is superior to univentricular physiology has led to a bias favoring biventricular repair. We hypothesized that pursuit of biventricular repair in borderline candidates increases mortality. METHODS: Between 1994 and 2001, 362 neonates with critical left ventricular outflow tract obstruction were prospectively enrolled by 26 institutions. Initial procedure indicated intended univentricular repair (n = 223; 84 deaths) or biventricular repair (n = 139; 39 deaths). Parametric risk-hazard analysis identified predictors of death for univentricular and for biventricular repair, which allowed prediction of the 5-year univentricular survival advantage for every infant. Survival was scrutinized for children managed discordantly to univentricular survival advantage predictions. RESULTS: Incremental factors for death after univentricular repair were as follows: tricuspid regurgitation, smaller mitral annulus z-score, smaller indexed dominant ventricular length, and presence of a large ventricular septal defect; risk factors after biventricular repair were as follows: minimum left ventricular outflow tract diameter, endocardial fibroelastosis, left ventricular dysfunction, and smaller mid-aortic arch. These variables formed the univentricular survival advantage tool (all P < .0001, R(2) = 0.92). Discordant management was more common with biventricular than with univentricular repair (56% vs 21%; P < .01). Discordant pursuit of biventricular repair was associated with significantly more observed versus expected deaths (biventricular repair 30 vs 14; P < .001; univentricular repair 20 vs 13; P = .02). Survival after biventricular repair is sensitive to changes in univentricular survival advantage values, especially in borderline candidates. In contrast, univentricular repair survival is insensitive to changes in univentricular survival advantage values. CONCLUSIONS: Inappropriate pursuit of biventricular repair in borderline candidates is more frequent and more consequential in survival terms than is inappropriate pursuit of univentricular repair. Use of the univentricular survival advantage tool will help identify infants for whom univentricular repair may be a better choice than attempting biventricular repair.

Truncus arteriosus associated with interrupted aortic arch in 50 neonates: a Congenital Heart Surgeons Society study.

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.