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Purpose Heart failure is a significant cause of morbidity and mortality in congenital heart disease patients especially for the subset whose right ventricle functions as the systemic ventricle. The physiological and molecular differences in the right ventricle (RV) and left ventricle (LV) lead to different abilities to adapt to adverse conditions and respond to pharmacological therapeutics. Currently data describing the molecular changes that occur in the systemic RV are lacking. Available animal models create an RV with volume and/or pressure overload however the LV remains at high pressure. Ventricular-ventricular interactions have a critical impact on cardiac function and are likely to alter gene expression independent of RV function. Methods To explore the distinct genetic regulatory networks of the RV and LV, we sequenced RNA from the RV and LV of late fetal, 1-week old, and 1-month old piglets. We identified gene expression differences in both chambers over this time course. Further, we have established a novel large animal model which creates a high pressure systemic RV with a low pressure subpulmonic LV by performing a reverse arterial switch followed by an atrial septectomy to allow sufficient oxygenation via atrial mixing. Using samples isolated from the RV following the reverse arterial switch procedure, we will determine the transcriptomic changes associated with the systemic RV. Gene expression profiles will be compared to age matched normal RV to identify molecular pathways that are perturbed in the systemic RV and compared to our LV and RV postnatal remodeling data to identify beneficial and pathogenic pathways for the RV under increased loading conditions. Results Analysis of postnatal cardiac chambers shows differentially expressed RV genes cluster into distinct patterns. In preliminary studies to generate a systemic RV, our team has successfully executed acute surgery in four week old piglets. Biventricular function was maintained with adequate systemic oxygenation saturation and angiography established that both the right and left reimplanted coronary arteries were patent. Conclusion As predicted by the lack of RV response to LV based therapies, our data confirmed that the genetic signature of the RV and LV during postnatal cardiac remodeling is distinct. Creation of a novel systemic RV model provides a platform to develop new therapeutics for congenial heart disease patients. [ABSTRACT FROM AUTHOR]

Background: Four similar transfusion reactions involving infants were reported in less than 1 year. After transfusion of red blood cells (RBCs) via syringe in the operating room, each patient experienced discolored urine, laboratory evidence of hemolysis, and acute kidney injury. Clerical and serologic investigations were unremarkable. Mechanical hemolysis was considered.Study Design and Methods: Simulated syringe transfusions were performed. Measurements included hematocrit (Hct), free hemoglobin, and visual hemolysis index. Washed and unwashed RBCs were tested with or without a recently introduced one-way valve, using a 24- or 16-gauge intravenous catheter. Constant manual pressure (1.43 ± 0.49 mL/sec) or syringe pump (2 mL/min) was used and a subset was timed.Results: The valve increased hemolysis during manual transfusion using both catheters with washed and unwashed RBCs. With the 24-gauge catheter, the change in Hct was -3.53 ± 0.69% with the valve and 0.22 ± 0.13% without (p < 0.00001). Comparing the individual valves tested, differences in hemolysis were observed (change in Hct, p < 0.0001). During manual transfusion with 24-gauge catheter and unwashed RBCs, the degree of hemolysis was greater when it took longer to transfuse with a valve (change in Hct versus time, r = -0.75, p < 0.0001) compared to a slight increase in hemolysis for samples that took less time to transfuse without a valve (change in Hct versus time, r = 0.58, p = 0.23).Conclusions: Mechanical hemolysis should be considered when investigating possible hemolytic transfusion reactions, especially with high rates of transfusion and use of a valve. During rapid manual transfusion with the valve, greater resistance was associated with increased hemolysis. [ABSTRACT FROM AUTHOR]

Background: Insertion of conduits from the right ventricle (RV) to the pulmonary artery (PA) is a commonly used technique for repair of congenital heart defects. The vast majority of infants and children will require reoperation and/or re-intervention to replace the conduit. Some children may require multiple reoperations, with the risk of death and morbidity increasing significantly with each subsequent operation. We evaluated the feasibility and performance of a relatively novel anisotropic conduit for cardiovascular repair in the growing lamb model., Materials and Methods: Lambs were allocated into a control ( n  = 3) or test ( n  = 4, anisotropic) conduit group. Control conventional polytetrafluoroethylene (PTFE) conduits or test anisotropic expanded PTFE (ePTFE) based test conduits measuring 10-11 mm in diameter were sewn as interpositional grafts in the main pulmonary artery (MPA) and followed up to 6 months. Clinical and echocardiographic evaluations were performed monthly with hemodynamic and angiographic assessment at 3 and 6 months., Results: Control conduits did not expand, all 3 animals developed one or more adverse events including tachypnea, ascites, inappetence, lethargy, and mortality due to severe right heart failure and significantly higher peak trans-conduit gradients (48.5 ± 5.1 p = 0.02). The test conduits spontaneously expanded up to 14.8 ± 0.8 mm in diameter, no adverse events were observed in any animals and trans-conduit gradients were significantly lower (27.0 ± 8.3, p = 0.02)., Conclusions: Anisotropic ePTFE conduits can be safely implanted in growing lambs with stable hemodynamics. This spontaneously expanding anisotropic conduit may represent a novel approach to congenital heart repairs that would avoid the need for reoperation or multiple operations.

Background: Cardiovascular repair in children often requires implant of conduits which do not have growth potential and will require reoperation. In the current study we sought to determine the feasibility of catheter-based interventions of anisotropic conduits inserted as interposition grafts in the main pulmonary artery (MPA) of growing lambs., Methods: Lambs underwent interpositional implant of either an anisotropic expanded polytetrafluoroethylene (ePTFE) (Test) conduit or conventional PTFE (Control) conduit. In the postoperative period, lambs were anesthetized and underwent catheter-based interventions consisting of hemodynamic and angiographic data collection, balloon dilation and/or stenting of the conduit at 3, 6 or 9 month postoperative time point., Results: At 3 months, control lambs showed significant increases in right ventricular pressures and trans-conduit gradients in comparison to test lambs. Test conduit diameters were significantly larger compared to controls due to spontaneous radial expansion of the anisotropic conduit. Balloon dilation of test conduits at 3 and 6 months showed a reduction in RV pressure and statistically significant improvement in the RV outflow tract gradient as well as significant increase in graft diameter, compared to both control and pre-dilation conditions. Furthermore, the test conduit diameter increased significantly compared to the pre-balloon and control conditions at each time point. Necropsy of test conduits showed no evidence of tears, perforations, or clot and smooth interiors with well-healed anastomoses., Conclusions: Anisotropic conduits implanted as interposition grafts in the MPA show spontaneous expansion, and can safely and effectively undergo catheter-based interventions, with significant increases in graft diameter occurring after balloon dilation.

There are no reports on the performance of the arterial switch operation (ASO) in a normal heart with normally related great vessels. The objective of this study was to determine whether the ASO could be performed in a healthy animal model. Cardiopulmonary bypass (CPB) and coronary translocation techniques were used to perform ASO in neonatal piglets or a staged ASO with prior main pulmonary artery (PA) banding. Primary ASO was performed in four neonatal piglets. Coronary translocation was effective with angiograms confirming patency. Piglets could not be weaned from CPB due to right ventricle (RV) dysfunction. To improve RV function for the ASO, nine piglets had PA banding. All survived the procedure. Post-banding RV pressure increased from a mean of 20.3 ± 2.2 mmHg to 36.5 ± 7.3 mmHg (p = 0.007). At 58 ± 1 days post-banding, piglets underwent cardiac MRIs revealing RV hypertrophy, and RV pressure overload with mildly reduced RV function. Catheterization confirmed RV systolic pressures of 84.0 ± 6.7 mmHg with LV systolic pressure 83.3 ± 6.7 mmHg (p = 0.43). The remaining five PA banded piglets underwent ASO at 51 ± 0 days post-banding. Three of five were weaned from bypass with patent coronary arteries and adequate RV function. We were able to successfully perform an arterial switch with documented patent coronary arteries on standard anatomy great vessels in a healthy animal model. To our knowledge this is the first time this procedure has been successfully performed. The model may have implications for studying the failing systemic RV, and may support a novel approach for management of borderline, pulsatile left ventricles.

We describe the use of virtual reality technology for surgical planning in the successful separation of thoracopagus conjoined twins. Three-dimensional models were created from computed tomography angiograms to simulate the patient's anatomy on a virtual stereoscopic display. Members of the surgical teams reviewed the anatomical models to localize an interatrial communication that allowed blood to flow between the two hearts. The surgical plan to close the 1-mm interatrial communication was significantly modified based on the pre-procedural spatial awareness of the anatomy presented in the virtual visualization. The virtual stereoscopic display was critical for the surgical team to successfully separate the twins and provides a useful case study for the use of virtual reality technology in surgical planning. Both twins survived the operation and were subsequently discharged from the hospital.

Objective: To determine whether prenatal diagnosis lowers the risk of preoperative brain injury by assessing differences in the incidence of preoperative brain injury across centers., Study Design: From 2 prospective cohorts of newborns with complex congenital heart disease studied by preoperative cerebral magnetic resonance imaging, one cohort from the University Medical Center Utrecht (UMCU) and a combined cohort from the University of California San Francisco (UCSF) and University of British Columbia (UBC), patients with aortic arch obstruction were selected and their imaging and clinical course reviewed., Results: Birth characteristics were comparable between UMCU (n = 33) and UCSF/UBC (n = 54). Patients had a hypoplastic aortic arch with either coarctation/interruption or hypoplastic left heart syndrome. In subjects with prenatal diagnosis, there was a significant difference in the prevalence of white matter injury (WMI) between centers (11 of 22 [50%] at UMCU vs 4 of 30 [13%] at UCSF/UBC; P < .01). Prenatal diagnosis was protective for WMI at UCSF/UBC (13% prenatal diagnoses vs 50% postnatal diagnoses; P < .01), but not at UMCU (50% vs 46%, respectively; P > .99). Differences in clinical practice between prenatally diagnosed subjects at UMCU vs UCSF/UBC included older age at surgery, less time spent in the intensive care unit, greater use of diuretics, less use of total parenteral nutrition (P < .01), and a greater incidence of infections (P = .01). In patients diagnosed postnatally, the prevalence of WMI was similar in the 2 centers (46% at UMCU vs 50% at UCSF/UBC; P > .99). Stroke prevalence was similar in the 2 centers regardless of prenatal diagnosis (prenatal diagnosis: 4.5% at Utrecht vs 6.7% at UCSF/UBC, P = .75; postnatal diagnosis: 9.1% vs 13%, respectively, P > .99)., Conclusion: Prenatal diagnosis can be protective for WMI, but this protection may be dependent on specific clinical management practices that differ across centers., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The study objective was to determine the association between preoperative B-type natriuretic peptide levels and outcome after total cavopulmonary connection. Surgical palliation of univentricular cardiac defects requires a series of staged operations, ending in a total cavopulmonary connection. Although outcomes have improved, there remains an unpredictable risk of early total cavopulmonary connection takedown. The prediction of adverse postoperative outcomes is imprecise, despite an extensive preoperative evaluation., Methods: We prospectively enrolled 50 patients undergoing total cavopulmonary connection. We collected preoperative clinical data, preoperative plasma B-type natriuretic peptide levels, and postoperative outcomes, including the incidence of an adverse outcome within 1 year of surgery (defined as death, total cavopulmonary connection takedown, or the need for cardiac transplantation)., Results: The mean age of patients was 4.7 years (standard deviation, 2.1 years). The median (interquartile range) preoperative B-type natriuretic peptide levels were higher in patients who required total cavopulmonary connection takedown and early postoperative mechanical cardiac support (n = 3; median, 55; interquartile range, 42-121) compared with those with a good outcome (n = 47; median, 11; interquartile range, 5-17) (P < .05). A preoperative B-type natriuretic peptide level of 40 pg/mL or greater was highly associated with the need for total cavopulmonary connection takedown (sensitivity, 100%; specificity, 93%; P < .05), yielding a positive predictive value of 50% and a negative predictive value of 100%. Higher preoperative B-type natriuretic peptide levels also were associated with longer intensive care unit length of stay, longer hospital length of stay, and increased incidence of low cardiac output syndrome (P < .05)., Conclusions: Preoperative B-type natriuretic peptide blood levels are uniquely associated with the need for mechanical support early after total cavopulmonary connection and total cavopulmonary connection takedown, and thus may provide important information in addition to the standard preoperative assessment., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background and Purpose: Brain injury is common in newborns with congenital heart disease (CHD) requiring neonatal surgery. The purpose of this study is to define the risk factors for preoperative and postoperative brain injuries and their association with functional cardiac anatomic groups., Methods: Sixty-two neonates with CHD were studied with preoperative MRI, and 53 received postoperative scans. Clinical and therapeutic characteristics were compared in newborns with and without newly acquired brain injuries. A subset of 16 consecutive patients was monitored with intraoperative cerebral near-infrared spectroscopy., Results: Brain injury was observed in 56% of patients. Preoperative brain injury, seen in 39%, was most commonly stroke and was associated with balloon atrial septostomy (P=0.002). Postoperative brain injury, seen in 35%, was most commonly white matter injury and was particularly common in neonates with single-ventricle physiology and aortic arch obstruction (P=0.001). Risk factors associated with acquired postoperative brain injury included cardiopulmonary bypass (CPB) with regional cerebral perfusion (P=0.01) and lower intraoperative cerebral hemoglobin oxygen saturation during the myocardial ischemic period of CPB (P=0.008). In a multivariable model, new postoperative white matter injury was specifically associated with low mean blood pressure during the first postoperative day (P=0.04)., Conclusions: Specific modifiable risk factors can be identified for preoperative and postoperative white matter injury and stroke associated with neonatal surgery for CHD. The high incidence of postoperative injury observed despite new methodologies of CPB indicates the need for ongoing evaluation to optimize neurological outcome.

Objective: We sought to define patient characteristics, outcomes, and associated factors after mitral valve replacement in children., Methods: We included 104 children undergoing at least one mitral valve replacement between 1980 and 2003 and reviewed clinical records. Competing-risks methodology was used to determine time-related prevalence and associated risk factors after initial mitral valve replacement for death and repeat replacement., Results: The underlying mitral valve disease was congenital in 83%, rheumatic in 13%, Marfan syndrome in 3%, and isolated endocarditis in 1%, with 64% having primarily regurgitation, 16% having stenosis, 20% having both, and 32% having undergone previous valvotomy, valvuloplasty, or repair. There were 137 valve replacements, with 26 patients having more than one. Valve prosthesis type was St Jude Medical in 37%, Bjork-Shiley in 25%, Carbomedics in 20%, Ionescu-Shiley in 10%, and other types in 8%. Both early and late complications were common. Median age at the initial replacement was 5.9 years (range, birth to 19 years). Competing-risks analysis predicted 19% to have died at 15 years after initial replacement, with risk factors including noncongenital valve morphology, lower weight, and longer duration of cardiopulmonary bypass. A repeat replacement was predicted for 71%, with risk factors including the presence of multiple left-heart obstructive lesions and Ionescu-Shiley valve prosthesis., Conclusions: Mitral valve replacement might be necessary in children with extremely dysplastic valves and severe hemodynamic impairment or after failed repair. However, with the appropriate selection of the prosthetic valve and reduction of cardiopulmonary bypass time, surgeons might decrease mortality and increase prosthesis longevity.

Background: Cardiopulmonary bypass induces marked and persistent depression of circulating thyroid hormones in infants and children, possibly contributing to postoperative morbidity. Clinical studies have evaluated parenteral triiodothyronine supplementation after cardiopulmonary bypass in children. However, these investigations had relatively small subject numbers as well as age and diagnosis heterogeneity, thereby limiting ability to determine clinical effect. A double-blind, randomized, placebo-controlled trial is needed to define clinical safety and efficacy of triiodothyronine supplementation in infants., Methods and Results: The Triiodothyronine for Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) study is a multicenter, randomized, clinical trial designed to determine safety and efficacy of triiodothyronine supplementation in children <2 years of age undergoing surgical procedures for congenital heart disease. Duration of mechanical ventilation after completion of cardiopulmonary bypass is the primary clinical outcome parameter with multiple secondary clinical and hemodynamic parameters. Nearly 200 patients will be randomly assigned to receive either triiodothyronine or placebo. Patient assignment will be performed using a stratified block randomization according to specific preoperative diagnosis., Conclusions: The TRICC study will provide important data regarding the efficacy and safety of triiodothyronine in this age-specific population undergoing surgery for congenital heart disease.

Background: For neonates with critical aortic valve stenosis who are selected for biventricular repair, valvotomy can be achieved surgically (SAV) or by transcatheter balloon dilation (BAV)., Methods and Results: Data regarding 110 neonates with critical aortic valve stenosis were evaluated in a study by the Congenital Heart Surgeons Society from 1994 to 1999. Reduced left ventricular function was present in 46% of neonates. The initial procedure was SAV in 28 patients and BAV in 82 patients. Mean percent reduction in systolic gradient was significantly greater with BAV (65+/-17%) than SAV (41+/-32%; P<0.001). Higher residual median gradients were present in the SAV versus BAV group (36 mm Hg [range, 10 to 85 mm Hg] versus 20 mm Hg [0 to 85 mm Hg], P<0.001). Important aortic regurgitation was more often present after BAV (18%) than SAV (3%; P=0.07). Time-related survival after valvotomy was 82% at 1 month and 72% at 5 years, with no significant difference for SAV versus BAV, even after adjustment for differences in patient and disease characteristics. Independent risk factors for mortality were mechanical ventilation before valvotomy, smaller aortic valve annulus (z score), smaller aortic diameter at the sinotubular junction (z score), and a smaller subaortic region. A second procedure was performed in 46 survivors. Estimates for freedom from reintervention were 91% at 1 month and 48% at 5 years after the initial valvotomy and did not differ significantly between groups., Conclusions: SAV and BAV for neonatal critical aortic stenosis have similar outcomes. There is a greater likelihood of important aortic regurgitation with BAV and of residual stenosis with SAV.