The ultimate goal of Fontan surgical planning is to provide additional insights into the clinical decision-making process. In its current state, surgical planning offers an accurate hemodynamic assessment of the pre-operative condition, provides anatomical constraints for potential surgical options, and produces decent post-operative predictions if boundary conditions are similar enough between the pre-operative and post-operative states. Moving forward, validation with post-operative data is a necessary step in order to assess the accuracy of surgical planning and determine which methodological improvements are needed. Future efforts to automate the surgical planning process will reduce the individual expertise needed and encourage use in the clinic by clinicians. As post-operative physiologic predictions improve, Fontan surgical planning will become an more effective tool to accurately model patient-specific hemodynamics.

Objective: Fontan surgical planning is an image-based, collaborative effort, which is hypothesized to result in improved patient outcomes. A common motivation for Fontan surgical planning is the progression (or concern for progression) of pulmonary arteriovenous malformations. The purpose of this study was to evaluate the accuracy of surgical planning predictions, specifically hepatic flow distribution (HFD), a known factor in pulmonary arteriovenous malformation progression, and identify methodological improvements needed to increase prediction accuracy. Methods: Twelve single-ventricle patients who were enrolled in a surgical planning protocol for Fontan surgery with pre- and postoperative cardiac imaging were included in this study. Computational fluid dynamics were used to compare HFD in the surgical planning prediction and actual postoperative conditions. Results: Overall, HFD prediction error was 17 ± 13%. This error was similar between surgery types (15 ± 18% and 18 ± 10% for revisions vs Fontan completions respectively; P =.73), but was significantly lower (6 ± 7%; P =.05) for hepatic to azygous shunts. Y-grafts and extracardiac conduits showed a strong correlation between prediction error and discrepancies in graft insertion points (r = 0.99; P <.001). Improving postoperative anatomy prediction significantly reduced overall HFD prediction error to 9 ± 6% (P =.03). Conclusions: Although Fontan surgical planning can offer accurate HFD predictions for specific graft types, methodological improvements are needed to increase overall accuracy. Specifically, improving postoperative anatomy prediction was shown to be an important target for future work. Future efforts and refinements to the surgical planning process will benefit from an improved understanding of the current state and will rely heavily on increased follow-up data.

Understanding developmental changes in contractility is critical to improving therapies for young cardiac patients. Isometric developed force was measured in human ventricular muscle strips from two age groups: newborns (<2 weeks) and infants (3–14 months) undergoing repair for congenital heart defects. Muscle strips were paced at several cycle lengths (CLs) to determine the force frequency response (FFR). Changes in Na/Ca exchanger (NCX), sarcoplasmic reticulum Ca-ATPase (SERCA) and phospholamban (PLB) were characterized. At CL 2000 ms, developed force was similar in the two groups. Decreasing CL increased developed force in the infant group to 131±8% (CL 1000 ms) and 157±18% (CL 500 ms) demonstrating a positive FFR. The FFR in the newborn group was flat. NCX mRNA and protein levels were significantly larger in the newborn than infant group whereas SERCA levels were unchanged. PLB mRNA levels and PLB/SERCA ratio increased with age. Immunostaining for NCX in isolated newborn cells showed peripheral staining. In infant cells, NCX was also found in T-tubules. SERCA staining was regular and striated in both groups. This study shows for the first time that the newborn human ventricle has a flat FFR, which increases with age and may be caused by developmental changes in calcium handling.

Objective: The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt. Methods: We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors. Results: Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status (P = .01), obstructed pulmonary venous return (P < .001), smaller ascending aorta (P = .02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome (P < .001) and lower gestational age (P < .001). The right ventricle-to-pulmonary artery shunt demonstrated better survival in the 51% of subjects who were full term with aortic atresia (P < .001). The modified Blalock-Taussig shunt was better among the 4% of subjects who were preterm with a patent aortic valve (P = .003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P < .03), but shunt type was not (P = .43). Conclusions: Independent risk factors for intermediate-term mortality include lower socioeconomic status, anatomy, genetic syndrome, and lower gestational age. Term infants with aortic atresia benefited from a right ventricle-to-pulmonary artery shunt, and preterm infants with a patent aortic valve benefited from a modified Blalock-Taussig shunt. Right ventricular function and anatomy, but not shunt type, were associated with transplantation.

Background: The single-ventricle reconstruction trial randomized patients with single right ventricle lesions to a modified Blalock-Taussig or right ventricle-to-pulmonary artery shunt at the Norwood. This analysis describes outcomes at the stage 2 procedure and factors associated with a longer hospital length of stay (LOS). Methods: We examined the association of shunt type with stage 2 hospital outcomes. Cox regression and bootstrapping were used to evaluate risk factors for longer LOS. We also examined characteristics associated with in-hospital death. Results: There were 393 subjects in the analytic cohort. Median stage 2 procedure hospital LOS (8 days; interquartile range [IQR], 6-14 days), hospital mortality (4.3%), transplantation (0.8%), median ventilator time (2 days; IQR, 1-3 days), median intensive care unit LOS (4 days; IQR, 3-7 days), number of additional cardiac procedures or complications, and serious adverse events did not differ by shunt type. Longer LOS was associated (R2 = 0.26) with center, longer post-Norwood LOS (hazard ratio [HR], 1.93 per log day; P <.001), nonelective timing of the stage 2 procedure (HR, 1.78; P <.001), and pulmonary artery (PA) stenosis (HR, 1.56; P <.001). By univariate analysis, nonelective stage 2 (65% vs 32%; P =.009), moderate or greater atrioventricular valve (AVV) regurgitation (75% vs 24%; P <.001), and AVV repair (53% vs 9%; P <.001) were among the risk factors associated with in-hospital death. Conclusions: Norwood LOS, PA stenoses, and nonelective stage 2 procedure, but not shunt type, are independently associated with longer LOS. Nonelective stage 2 procedure, moderate or greater AVV regurgitation, and need for AVV repair are among the risk factors for death.

Objective: Surgery for heart defects in children with trisomy 13 or 18 is controversial. We analyzed our 20-year experience. Methods: Since 2002, we performed 21 operations in 19 children with trisomy 13 (n = 8) or trisomy 18 (n = 11). Age at operation was 4 days to 12 years (median, 154 days). Principal diagnosis was ventricular septal defect in 10 patients, tetralogy of Fallot in 7 patients, arch hypoplasia in 1 patient, and patent ductus arteriosus in 1 patient. Results: The initial operation was ventricular septal defect closure in 9 patients, tetralogy of Fallot repair in 7 patients, pulmonary artery banding in 1 patient, patent ductus arteriosus ligation in 1 patient, and aortic arch/coarctation repair in 1 patient. There were no operative or hospital deaths. Median postoperative intensive care and hospital stays were 189 hours (interquartile range, 70-548) and 14 days (interquartile range, 8.0-37.0), respectively, compared with median hospital stays in our center for ventricular septal defect repair of 4.0 days and tetralogy of Fallot repair of 5.0 days. On median follow-up of 17.4 months (interquartile range, 6.0-68), 1 patient was lost to follow-up after 5 months. Two patients had reoperation without mortality. There have been 5 late deaths (4 with trisomy 18, 1 with trisomy 13) predominately due to respiratory failure from 4 months to 9.4 years postoperatively. Five-year survival was 66.6% compared with 24% in a group of unoperated patients with trisomy 13 or 18. Conclusions: Cardiac operation with an emphasis on complete repair can be performed safely in carefully selected children with trisomy 13 or trisomy 18. Hospital resource use measured by postoperative intensive care and hospital stays is considerably greater compared with nontrisomy 13 and 18.

Children with congenital heart diseases have increased morbidity and mortality, despite various surgical treatments, therefore warranting better treatment strategies. Here we investigate the role of age of human pediatric cardiac progenitor cells (hCPCs) on ventricular remodeling in a model of juvenile heart failure. hCPCs isolated from children undergoing reconstructive surgeries were divided into 3 groups based on age: neonate (1 day to 1month), infant (1month to 1 year), and child (1 to 5 years). Adolescent athymic rats were subjected to sham or pulmonary artery banding surgery to generate a model of right ventricular (RV) heart failure. Two weeks after surgery, hCPCs were injected in RV musculature noninvasively. Analysis of cardiac function4weekspost-transplantationdemonstratedsignificantly increased tricuspid annular plane systolic excursion and RV ejection fraction and significantly decreased wall thickness and fibrosis in rats transplanted with neonatal hCPCs compared with saline-injected rats. Computational modeling and systems biology analysis were performed on arrays and gave insights into potential mechanisms at the microRNA and gene level. Mechanisms including migration and proliferation assays, as suggested by computational modeling, showed improved chemotactic and proliferative capacity of neonatal hCPCs compared with infant/child hCPCs. In vivo immune staining further suggested increased recruitment of stem cell antigen 1-positive cells in the right ventricle. This is the first study to assess the role of hCPC age in juvenile RV heart failure. Interestingly, the reparative potential of hCPCs is age-dependent, with neonatal hCPCs exerting the maximum beneficial effect compared with infant and child hCPCs.

Background: Using a bifurcated Y-graft as the Fontan baffle is hypothesized to streamline and improve flow dynamics through the total cavopulmonary connection (TCPC). This study conducted numerical simulations to evaluate this hypothesis using postoperative data from 5 patients. Methods: Patients were imaged with cardiac magnetic resonance or computed tomography after receiving a bifurcated aorto-iliac Y-graft as their Fontan conduit. Numerical simulations were performed using in vivo flow rates, as well as 2 levels of simulated exercise. Two TCPC models were virtually created for each patient to serve as the basis for hemodynamic comparison. Comparative metrics included connection flow resistance and inferior vena caval flow distribution. Results: Results demonstrate good hemodynamic outcomes for the Y-graft options. The consistency of inferior vena caval flow distribution was improved over TCPC controls, whereas the connection resistances were generally no different from the TCPC values, except for 1 case in which there was a marked improvement under both resting and exercise conditions. Examination of the connection hemodynamics as they relate to surgical Y-graft implementation identified critical strategies and modifications that are needed to potentially realize the theoretical efficiency of such bifurcated connection designs. Conclusions: Five consecutive patients received a Y-graft connection to complete their Fontan procedure with positive hemodynamic results. Refining the surgical technique for implementation should result in further energetic improvements that may help improve long-term outcomes.

Background: Aortic arch reconstruction in neonates is commonly performed using deep hypothermic circulatory arrest. However, concerns have arisen regarding potential adverse neurologic outcomes from this complex procedure, raising questions about the best arterial cannulation approach for cerebral perfusion and effective systemic hypothermia. In this study, we use computational fluid dynamics to investigate the effect of different cannulation strategies in neonates. Methods: We used a realistic template of a hypoplastic neonatal aorta as the base geometry to investigate four cannulation options: (1) right innominate artery, (2) innominate root, (3) patent ductus arteriosus (PDA), or (4) innominate root and PDA. Performance was evaluated according to the numerically predicted cerebral and systemic flow distributions compared with physiologic perfusion under neonatal conditions. Results: The four cannulation strategies were associated with different local hemodynamics; however, this did not translate into any significant effect on the measured flow distributions. The largest difference only represented 0.8% of the cardiac output and was measured in the innominate artery, which received 23.2% of the cardiac output in option 3 vs 24% in option 4. Pulmonary artery snaring benefited all systemic vessels uniformly. Conclusions: Because of the very high vascular resistances in neonates, downstream vascular resistances dictated flow distribution to the different vascular beds rather than the cannulation strategy, allowing the surgical team to choose their method of preference. However, patients with aortic coarctation warrant further investigation and will most likely benefit from a 2-cannulae approach (option 4).

Background: Many factors affect outcomes after congenital cardiac surgery. Objectives: The RLS (Residual Lesion Score) study explored the impact of severity of residual lesions on post-operative outcomes across operations of varying complexity. Methods: In a prospective, multicenter, observational study, 17 sites enrolled 1,149 infants undergoing 5 common operations: tetralogy of Fallot repair (n = 250), complete atrioventricular septal defect repair (n = 249), arterial switch operation (n = 251), coarctation or interrupted arch with ventricular septal defect (VSD) repair (n = 150), and Norwood operation (n = 249). The RLS was assigned based on post-operative echocardiography and clinical events: RLS 1 (trivial or no residual lesions), RLS 2 (minor residual lesions), or RLS 3 (reintervention for or major residual lesions before discharge). The primary outcome was days alive and out of hospital within 30 post-operative days (60 for Norwood). Secondary outcomes assessed post-operative course, including major medical events and days in hospital. Results: RLS 3 (vs. RLS 1) was an independent risk factor for fewer days alive and out of hospital (p ≤ 0.008) and longer post-operative hospital stay (p ≤ 0.02) for all 5 operations, and for all secondary outcomes after coarctation or interrupted arch with VSD repair and Norwood (p ≤ 0.03). Outcomes for RLS 1 versus 2 did not differ consistently. RLS alone explained 5% (tetralogy of Fallot repair) to 20% (Norwood) of variation in the primary outcome. Conclusions: Adjusting for pre-operative factors, residual lesions after congenital cardiac surgery impacted in-hospital outcomes across operative complexity with greatest impact following complex operations. Minor residual lesions had minimal impact. These findings may provide guidance for surgeons when considering short-term risks and benefits of returning to bypass to repair residual lesions.