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.

Berry syndrome: a possible genetic link.

Berry syndrome comprises a rare combination of heart defects that includes aortopulmonary window, interrupted aortic arch, intact ventricular septum, and aortic origin of the right pulmonary artery. We report the case of a neonate confirmed to have Berry syndrome by transthoracic echocardiogram and computed tomography (CT). This neonate had the additional finding of an aberrant right subclavian artery arising from the descending aorta. A single-stage repair was successfully performed when the infant was 7 days of age. Genetic testing showed a 102-kb deletion within chromosome band 9p24.2; this deletion has not been previously linked to congenital heart defects. Berry syndrome can be diagnosed accurately by transthoracic echocardiogram and CT. There may be an underlying genetic etiology, and this possibility warrants further investigation.

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.

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.

The correlation of fluid balance changes during cardiopulmonary bypass to mortality in pediatric and congenital heart surgery patients.

Edema acquired during the perioperative period has long been associated with increased mortality. Edema acquired during cardiopulmonary bypass (CPB) may contribute to this mortality. The intent of this retrospective study was to test the premise that edema in the form of a positive fluid balance change (FBC) acquired during CPB correlated to mortality. If so, FBC from the beginning of CPB (baseline; FBC = 0) to the end of CPB may need to be monitored, measured, and controlled on CPB with the same ardor as blood pressure and pH. This retrospective analysis reviewed the FBC of 1540 pediatric and congenital heart surgery patients at the end of CPB. Additions and subtractions of fluid to the combined patient/CPB circuit were routinely quantified during CPB procedures and during periods of modified ultrafiltration (MUF). The primary outcome assessed was mortality during hospitalization. The overall mortality of the 1540 patients was 5.65% from all causes. Eighty percent (n = 1226, mortality = 4.65%) of the patients had a zero or negative FBC immediately after CPB/MUF. Twenty percent (n = 314, mortality = 9.55%) had a positive FBC. Positive FBC patients tended to be in higher risk categories, weighed more, and had longer pump times (p < .05) with an adjusted odds ratio for mortality of 1.73 (1.01-2.96, 95% confidence interval). There is a correlation between edema acquired during CPB and increased mortality in pediatric and congenital heart surgery patients. The potential exists for the perfusionist to optimize the fluid balance changes while on CPB to reduce mortality rates.

Identifying neonatal and pediatric cardiac and congenital diaphragmatic hernia extracorporeal membrane oxygenation patients at increased mortality risk.

UNLABELLED: A previous review from our institution established clinically measured cut-points that defined the late implementation of extracorporeal membrane oxygenation (ECMO) correlating to increased mortality in neonatal and pediatric respiratory patients. Using the same methods, this review evaluates pediatric and neonatal cardiac and congenital diaphragmatic hernia (CDH) patients to determine if the same cut-points exist in this higher risk patient population. Neonatal and pediatric cardiac and CDH patients placed on ECMO between November 1989 and December 2008 were retrospectively reviewed to determine the first adjusted anion gap (AGc), the first venoarterial carbon dioxide (CO2) gradient (p[v-a]CO2), and the first Viability Index (AGc + p[v-a]CO2 = INDEX) on ECMO. These markers were then analyzed to identify the presence of specific cut-points that marked an increased risk of mortality. The timing of surgery was also reviewed to assess the surgical morbidity on survival. The review of neonatal and pediatric cardiac and CDH patients (n = 205) with an overall survival of 46% showed that all three markers were elevated to varying degrees in the expired patients (n = 110). Histograms identified the following specific cut-points for increased mortality: the AGc > or = 23 mEq/L, the p[v-a]CO2 _ 16 mmHg, and the INDEX > or = 28. An elevated AGc and INDEX correlated with a significantly higher risk for mortality (p < .05), survival to discharge being 20% or less. Patients under the cut-points had survival rates of 51% or higher. The timing of surgery (before or after ECMO initiation) did not significantly impact survival in the combined cardiac and CDH group. An INDEX > or = 28 correlates with non-survival. We speculate that the late implementation of ECMO may lead to reperfusion injury, which causes reduced survival, and that ECMO intervention prior to reaching the cut-points may improve survival in neonatal and pediatric cardiac and CDH patients. KEYWORDS: cardiac, congenital, diaphragmatic, extracorporeal membrane oxygenation, neonate, pediatric.

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.

Defining the late implementation of extracorporeal membrane oxygenation (ECMO) by identifying increased mortality risk using specific physiologic cut-points in neonatal and pediatric respiratory patients.

There is no reliable clinical indicator showing how long extracorporeal membrane oxygenation (ECMO) implementation can be delayed before the risk of death becomes unacceptably high in neonatal and pediatric respiratory patients. However, the late use of ECMO may be defined by the elevation of specific physiologic markers separate from pulmonary function and hemodynamic assessments that indicate when the optimal time for implementation of ECMO has past, resulting in a higher than normal mortality, possibly due to reperfusion injury. Neonatal patients were reviewed retrospectively to determine if later implementation of ECMO correlated to increased mortality. Neonatal and pediatric respiratory patients placed on ECMO were reviewed retrospectively to determine if the first adjusted anion gap (AGc), the first venoarterial CO2 gradient (p[v-a] CO2), or the first Viability Index (AGc + p[v-a]CO2 = INDEX) on ECMO could be used to identify a cut-point for increased mortality. Expired neonates (n = 31) were placed on ECMO an average of 2 days later than neonatal survivors (n = 163). The review of 210 respiratory neonatal and pediatric ECMO patients with an overall survival of 82% showed that all three markers were elevated in the expired patients (n = 38, p < .05). Cut-points were an AGc > or = 23 mEq/L, the p[v-a]CO2 > or = 16 mmHg, and the INDEX > or = 28. These values correlated with a significantly higher risk of mortality (p < .05); survival to discharge being 43% or less. Patients under the cut-points had survival rates of 84% or higher. Starting ECMO too late may cause reperfusion injury that reduces survival. This study describes specific physiologic markers taken soon after ECMO initiation that correlate with mortality. These markers, if assessed earlier, may allow for a more timely ECMO implementation and higher survival.

Gene expression in pediatric heart disease with emphasis on conotruncal defects.

Developmental abnormalities of the heart are the underlying cause of many congenital heart malformations. The embryological development of the integrated cardiovascular tissue is the result of multiple tissue and cell-to-cell interactions involving temporal and spatial events under genetic control. Recent technological advances, like microarray analysis of gene expression, are providing new tools to aid in deciphering the complex networks of gene expression that regulate cardiac development. Here, we review our current understanding of the genetics of congenital heart disorders with emphasis on gene expression studies and report preliminary data from infants with conotruncal defects. We report our microarray analysis showing over- and underexpression of individual genes and gene network interactions from dysplastic pulmonic tissue from two infants with tetralogy of Fallot compared with normal pulmonic tissue from an unaffected control infant.

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.

Determinants of mortality and type of repair in neonates with pulmonary atresia and intact ventricular septum.

OBJECTIVE: We sought to define the prevalence of definitive end states and their determinants in children given a diagnosis of pulmonary atresia and intact ventricular septum during the neonatal period. METHODS: Between 1987 and 1997, 408 neonates with pulmonary atresia and intact ventricular septum were entered into a prospective study by 33 institutions. Competing risks analysis was used to demonstrate the prevalence of 6 end states. Factors predictive of attaining each end state were identified by means of multivariable analysis with bootstrap validation. RESULTS: Overall survival was 77% at 1 month, 70% at 6 months, 60% at 5 years, and 58% at 15 years. Prevalence of end states 15 years after entry were as follows: 2-ventricle repair, 33%; Fontan repair, 20%; 1.5-ventricle repair, 5%; heart transplant, 2%; death before reaching definitive repair, 38%; and alive without definitive repair, 2%. Patient-related factors discriminating among end states primarily included adequacy of right-sided heart structures, degree of aberration of coronary circulation, low birth weight, and tricuspid valve regurgitation. After adjusting for these factors, 2 institutions were predictive of 2-ventricle repair, 1 of Fontan repair, and 6 of death before definitive repair. Two institutions were predictive of both 2-ventricle and Fontan repair. These 2 institutions achieved a higher risk-adjusted prevalence of definitive repair and a lower prevalence of prerepair mortality. CONCLUSIONS: Characteristics of neonates with pulmonary atresia and intact ventricular septum predict type of definitive repair. A morphologically driven institutional protocol emphasizing both 2-ventricle and Fontan pathways might mitigate the negative effect of unfavorable morphology. In the current era, 85% of neonates are likely to reach a definitive surgical end point, with 2-ventricle repair achieved in an estimated 50%.

Outcomes after the Norwood operation in neonates with critical aortic stenosis or aortic valve atresia.

OBJECTIVE: This study was undertaken to determine the demographic, anatomic, institutional, and surgical risk factors associated with outcomes after the Norwood operation. METHODS: A total of 710 of 985 neonates with critical aortic stenosis or atresia enrolled in a prospective 29-institution study between 1994 and 2000 underwent the Norwood operation. Admission echocardiograms were independently reviewed for 64% of neonates. Competing risks analyses were constructed for outcomes after Norwood operation and after cavopulmonary shunt. Incremental risk factors for outcome events were sought. RESULTS: Overall survivals after the Norwood operation were 72%, 60%, and 54% at 1 month, 1 year, and 5 years, respectively. According to competing risks analysis, 97% of neonates reached a subsequent transition state by 18 months after Norwood operation, consisting of death (37%), cavopulmonary shunt (58%), or other state (2%, cardiac transplantation, biventricular repair, or Fontan operation). Risk factors for death occurring before subsequent transition included patient-specific variables (lower birth weight, smaller ascending aorta, older age at Norwood operation), institutional variables (institutions enrolling < or =10 neonates, two institutions enrolling >/=40 neonates), and procedural variables (shunt originating from aorta, longer circulatory arrest time, and management of the ascending aorta). Of neonates undergoing cavopulmonary shunt, 91% had reached a subsequent transition state by 6 years after cavopulmonary shunt, consisting of Fontan operation (79%), death (9%), or cardiac transplantation (3%). Risk factors for death occurring before subsequent transition included younger age at cavopulmonary shunt and need for right atrioventricular valve repair. CONCLUSIONS: Competing risks analysis defines the prevalence of the various outcomes after Norwood operation and predicts improved outcomes with successful modification of controllable risk factors.

Endocarditis caused by Staphylococcus lugdunensis.

We describe a case of native valve endocarditis caused by Staphylococcus lugdunensis, a perineal skin commensal, and review 28 other cases from the medical literature. Correctly identifying this coagulase-negative organism is critical because endocarditis is usually associated with left sided valvular disruption and life-threatening embolic complications, reminiscent of disease caused by Staphylococcus aureus. Urgent surgical intervention is necessary in most cases.

Pulmonary atresia, ventricular septal defect, and multiple aorta pulmonary collateral arteries.

Pulmonary atresia with ventricular septal defect and major aorta pulmonary collaterals arteries is a rare and complex congenital cardiac defect. There is considerable variability in the anatomy, morphology, and geometry of the native pulmonary arteries and the collateral vessels. While the ultimate goal of therapy is a biventricular correction with complete unifocalization, establishment of right ventricular to pulmonary arterial continuity, and closure of all intracardiac defects, achieving this endpoint can be frustrating and difficult. A carefully considered approach for each individual patient is required. Patients with appropriate anatomy may undergo a definitive single-stage unifocalization and biventricular correction in early infancy. Patients with less favorable anatomy will require a more eclectic approach. While our knowledge of the genetics of this defect is rudimentary, further advances in genetic understanding and technology hold tremendous promise for the development of future therapies.

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.

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.

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.

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.

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.

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.