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Objective The Norwood neoaortic arch biomechanical properties are abnormal due to reduced vessel wall compliance and abnormal geometry. Others have previously described neoaortic geometric distortion by the degree of diameter reduction (tapering) and associated this with mismatched ventricular-neoaortic coupling, abnormal flow hemodynamic parameters, and worse patient outcome. Our purposes were to investigate the influence of neoaortic tapering (ie, diameter reduction) on flow-mediated viscous energy loss (EL') in post-Norwood palliated hypoplastic left heart syndrome patients, and correlate flow-geometry with single ventricle power generation. Methods Twenty-six palliated hypoplastic left heart syndrome patients underwent comprehensive cardiac evaluation with 4-dimensional-flow magnetic resonance imaging. Patients were grouped into high- (group H, n = 13) and low- (group L, n = 13) degree neoaortic tapering using the median cutoff value of neoaortic diameter variance. EL' was calculated along standardized segments using 4-dimensional-flow magnetic resonance imaging. Flow-mediated power loss as a percentage of total power generated by the single ventricle was determined. Results Group H had a higher prevalence of abnormal recirculating flow in the neoaorta and elevated neoaortic EL' in the ascending aorta (1.0 vs 0.6 mW; P = .004). Group H EL' was increased across the entire thoracic aorta (2.6 vs 1.3 mW; P = .002) and accounted for 0.7% of generated ventricular power versus 0.3% in group L (P = .024). EL' directly correlated with the degree of ascending aortic dilation (R = 0.49; P = .012). Conclusions Patients with high degree neoaortic tapering have more perturbed flow through the neoaorta and increased EL'. Flow-mediated energy loss due to abnormal flow represents irreversibly wasted power generated by the single right ventricle. In patients with high-degree neoaortic tapering, EL' was more than 2-fold greater than low-degree tapering patients. These data suggest that oversizing the Norwood neoaortic reconstruction should be avoided and that patients with distorted neoaortic geometry may warrant increased surveillance for single-ventricle deterioration.

We investigated the incidence and predictors of failure to undergo the Fontan in children with hypoplastic left heart syndrome who survived superior cavopulmonary connection.The cohort consists of all patients with hypoplastic left heart syndrome who survived to hospital discharge after superior cavopulmonary connection between 1988 and 2017. The primary outcome was attrition, which was defined as death, nonsuitability for the Fontan, or cardiac transplantation before the Fontan. Subjects were excluded if they were awaiting the Fontan, were lost to follow-up, or underwent biventricular repair. The study period was divided into 4 eras based on changes in operative or medical management. Attrition was estimated with 95% confidence intervals, and predictors were identified using adjusted, logistic regression models.Of the 856 hospital survivors after superior cavopulmonary connection, 52 died, 7 were deemed unsuitable for Fontan, and 12 underwent or were awaiting heart transplant. Overall attrition was 8.3% (71/856). Attrition rate did not change significantly across eras. A best-fitting multiple logistic regression model was used, adjusting for superior cavopulmonary connection year and other influential covariates: right ventricle to pulmonary artery shunt at Norwood (P .01), total support time at superior cavopulmonary connection (P .01), atrioventricular valve reconstruction at superior cavopulmonary connection (P = .02), performance of other procedures at superior cavopulmonary connection (P = .01), and length of stay after superior cavopulmonary connection (P .01).In this study spanning more than 3 decades, 8.3% of children with hypoplastic left heart syndrome failed to undergo the Fontan after superior cavopulmonary connection. This attrition rate has not decreased over 30 years. Use of a right ventricle to pulmonary artery shunt at the Norwood procedure was associated with increased attrition.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, spread worldwide turning the coronavirus disease 2019 (COVID-19) into a pandemic. It is not known, yet, if children with congenital heart disease (CHD) would be at increased risk due to their cardiovascular condition or if they would benefit from their young age. This report describes one of the first documented cases of SARS-CoV-2 infection in a patient with congenital heart disease. We report a child stricken by COVID-19 in the early postoperative course of Fontan palliation of hypoplastic left heart syndrome (HLHS). Of highest relevance, we showed that COVID-19 could be a confounding factor for the diagnosis and management of patients with CHD. Particularly for those with cyanotic congenital heart disease, in which SARSCoV-2 infection can progress with significant hypoxemia and mimics surgical complications.

We present the evolution of Norwood operation outcomes and practice pattern changes over 15 years from a single institution in Saudi Arabia. We intended to identify time trends in patient selection, procedural details, and outcome predictors over time.Patients who underwent a Norwood operation (n = 145) between 2003 and 2018 with the use of a Blalock-Taussig shunt (BT group; n = 72), right ventricle to pulmonary artery shunt (Sano group; n = 66), or a primary cavopulmonary shunt (CPS group; n = 7) were included. The study outcomes were operative mortality, long-term survival, and multistate transition to CPS, Fontan, and death.Median age was 29 days. Predictors of operative mortality were lower weight (P = .026), and longer bypass time (P = .014), whereas age, and type of shunt were not. Predictors of improved long-term survival were greater weight at operation (P = .0016), later era (P = .006), and shorter bypass time (P = .001). The multistate model revealed that patients with lower weight were more likely to undergo Sano versus BT (P .001), and if BT was chosen in such patients, they were more likely to die (P = .027). The likelihood of receiving Sano shunt was 3-fold greater in the recent era (P = .003).Improved outcomes of the Norwood operation are evident in the recent era and with Sano shunt, especially in patients of smaller weight. Late presentation or older age is not a contraindication to Norwood operation. The incorporation of a primary CPS at stage one operation is feasible in selected patients.

Objectives Staged surgical palliation for hypoplastic left heart syndrome results in an increased workload on the right ventricle serving as the systemic ventricle. Concerns for cardiac dysfunction and long-term heart failure have generated interest in first-in-infant, cell-based therapies as an additional surgical treatment modality. Methods A phase 1 clinical trial was conducted to evaluate the safety and feasibility of direct intramyocardial injection of autologous umbilical cord blood-derived mononuclear cells in 10 infants with hypoplastic left heart syndrome at the time of stage II palliation. Results All 10 patients underwent successful stage II palliation and intramyocardial injection of umbilical cord blood-derived mononuclear cells. Operative mortality was 0%. There was a single adverse event related to cell delivery: An injection site epicardial bleed that required simple oversew. The cohort did not demonstrate any significant safety concerns over 6 months. Additionally, the treatment group did not demonstrate any reduction in cardiac function in the context of the study related intramyocardial injections of autologous cells. Conclusions This phase 1 clinical trial showed that delivering autologous umbilical cord blood-derived mononuclear cells directly into the right ventricular myocardium during planned stage II surgical palliation for hypoplastic left heart syndrome was safe and feasible. Secondary findings of preservation of baseline right ventricular function throughout follow-up and normalized growth rates support the design of a phase 2b follow-up trial.

The study objective was to analyze outcomes of the hybrid strategy for ductal-dependent systemic circulation consisting of bilateral pulmonary artery banding with or without ductal stenting followed by delayed Norwood-type palliation or comprehensive stage II operation in high-risk neonates.A retrospective analysis was performed between December 2017 and March 2021. Thirty high-risk neonates underwent palliation with bilateral pulmonary artery banding: 11 with prostaglandin therapy and 19 with ductal stenting. Median (range) age and body weight of patients at hybrid stage I were 3 days (0-43) and 2.9 kg (1.1-4.2), respectively. Operative and interstage mortality, morbidity, and reintervention rates were assessed.Overall survival was 70% (21/30) at a median follow-up time of 9 months (range, 0-37) from hybrid stage I. Operative survival for hybrid stage I was 90% (27/30), of which 2 patients received palliative care, and there was 1 interstage death (4%, 1/27). After hybrid stage I, 37% of patients had a reintervention, and 3% (n = 1) used extracorporeal membrane oxygenation before the next stage of repair. Five patients are awaiting second-stage operation, and 9 patients are awaiting Fontan completion.High-risk neonates with hypoplastic left heart syndrome or its variants can be successfully palliated using the hybrid strategy and bridged to a delayed Norwood or comprehensive stage II operation with satisfactory survival. This operative approach is a promising alternative pathway for neonates deemed to be high risk due to multiple preoperative risk factors.

Elastic properties of the thoracic aorta are responsible for buffering systemic afterload, and may be particularly important in patients with Fontan circulation, in whom heart failure is a major source of attrition. The purpose of this study was to characterize regional stiffness in the ascending and descending aorta in patients with hypoplastic left heart syndrome and single left ventricle morphology after Fontan operation by cardiac magnetic resonance imaging, and to assess whether changes in aortic stiffness are associated with the ventricular function.Phase-contrast-derived pulse-wave velocity (PWV) and relative-area change (RAC) were measured in the ascending and descending aorta of patients with hypoplastic left heart syndrome (n = 9), patients with single left ventricle circulation (n = 18), and normal controls (n = 8) by magnetic resonance imaging. Stiffness metrics were then correlated with the ventricular volumetric and functional indices.Patients with hypoplastic left heart syndrome had elevated ascending aortic PWV along with reduced RAC when compared with controls (both P values .001). Patients with a single left ventricle presented no change in PWV but had reduced RAC in comparison to controls (P .01). There were no differences in PWV and RAC between all considered groups in the descending aorta. PWV and RAC measured in the ascending aorta correlated with end-systolic and end-diastolic volume indices, ventricular ejection fraction, and ventricular-vascular coupling ratio.Aortic stiffness is most elevated in patients with hypoplastic left heart syndrome, yet patients with single left ventricle morphology show signs of abnormal stiffness as well in the form of reduced aortic strain. Stiffness indices measured in the ascending aorta were associated with overall ventricular function and measures of aortoventricular coupling in both patient populations.

Objective A primary cavopulmonary shunt (CPS) as a component of the initial Norwood palliation could be an option in patients with hypoplastic left heart syndrome and single ventricle lesions. We present our initial experience with this approach in carefully selected patients with unrestricted pulmonary blood flow and low pulmonary vascular resistance (PVR). Methods The study included 16 patients; the mean age was 137.9± 84.2 days. All patients underwent a Norwood palliation consisting of atrial septectomy, Damus–Kaye–Stansel connection, and arch augmentation in addition to the CPS as the initial palliation. Results The mean preoperative pulmonary to systemic blood flow (Qp/Qs) ratio on room air (n= 9) and with 100% oxygen (n= 8) was 5.3± 3.2 and 8.6± 4.3, respectively. The mean PVR on room air (n= 10) and 100% oxygen (n= 9) was 4.8± 3.1 and 1.7± 0.97 Wood units.m2, respectively. Delayed chest closure was needed in 12 patients, and six patients required postoperative inhaled nitric oxide. One patient underwent takedown of the CPS and construction of the RV-PA conduit after one month. The mean ICU stay was 18.9 ± 15.4 days. There were two in-hospital deaths (48 hours and 8 days after surgery) and two post-discharge deaths (6 months and 2 years after hospital discharge). Seven patients have undergone the Fontan completion successfully, and five patients await further surgery. Conclusion First stage Norwood palliation with CPS for patients with hypoplastic left heart syndrome or single ventricle lesions is feasible in late presenters with low PVR.

Objective This study used cardiac magnetic resonance imaging to evaluate flow characteristics and ventricular hemodynamics for children with single right (hypoplastic left heart syndrome) and single left (hypoplastic right heart syndrome) systemic ventricle anatomy after Fontan palliation compared with normal biventricular controls. Methods Twenty children with single ventricle anatomy (hypoplastic left heart syndrome, n = 10; hypoplastic right heart syndrome, n = 10) underwent standardized 4-dimensional flow cardiac magnetic resonance and were compared with age-matched controls (n = 10). End-diastolic volume was partitioned into 4 defined components of variable kinetic energy (direct flow, retained inflow, delayed ejection, and residual volume) and compared between groups. Further, volumetric and functional parameters as defined by cardiac magnetic resonance were evaluated. Results Children with hypoplastic left heart syndrome had significantly increased indexed end-diastolic and end-systolic volumes compared with both hypoplastic right heart syndrome and control groups. Flow component analysis demonstrated diastolic inefficiency in both hypoplastic left heart syndrome and hypoplastic right heart syndrome groups compared with controls as defined by decreased direct flow and increased residual volumes. Decreased direct flow correlated with decreased ejection fraction and increased end-diastolic and end-systolic volume indices. Increased residual volume correlated with decreased ejection fraction and increased end-systolic volume index. Conclusions Fontan-palliated patients with single ventricle physiology (hypoplastic left heart syndrome and hypoplastic right heart syndrome) demonstrate altered and inefficient flow patterns in the systemic ventricle as defined by 4-dimensional flow cardiac magnetic resonance compared with normal biventricular controls. Decreased direct flow and increased residual volume indicate that diastolic ventricular dysfunction is prevalent after Fontan palliation. This study provides a foundation for future predictive modeling and cardiac magnetic resonance flow diagnostic studies in this high-risk patient population.

Length of stay (LOS) has been proposed as a quality metric in congenital heart surgery, but LOS may be influenced by parental socioeconomic position (SEP). We aimed to examine the relationship between post-Norwood LOS and SEP.Patients undergoing a Norwood procedure from 2008 to 2018 for hypoplastic left heart syndrome from a single institution, who were discharged alive before second-stage palliation, were included. SEP was defined by Area Deprivation Index, distance from hospital, insurance status, and immigration status. A directed acyclic graph identified confounders for the effect of SEP on LOS, which included gestational age, hypoplastic left heart syndrome subtype, postoperative cardiac arrest, reoperations, and ventilator days. A negative binomial model was used to assess effect of SEP on LOS.In total, 98 patients were discharged alive at a median 37 days (15th-85th percentile 26-72). The majority of patients were children of US citizens and permanent residents (n = 89; 91%). Private insurance covered 54 (55%), with 44 (45%) covered by Medicaid or Tricare. Median Area Deprivation Index was 54 (15th-85th percentile, 25-87). Median distance traveled was 72 miles (15th-85th percentile, 17-469 miles). For every 10 percentile increase in Area Deprivation Index, LOS increased 4% (incidence rate ratio, 1.04; 95% CI, 1.007-1.077; P = .022). Insurance type, immigration status, and distance traveled did not affect postoperative length of stay.There is a significant relationship between SEP and LOS. Consideration of LOS as a quality indicator may penalize hospitals providing care for patients with lower parental SEP.

To assess the feasibility and outcomes of biventricular conversion following takedown of Fontan circulation.Retrospective analysis of patients who had takedown of Fontan circulation and conversion to biventricular circulation at a single center from September 2007 to April 2020. Failing Fontan physiology was defined as Fontan circulation pressure15 mm Hg and/or the presence of associated complications.Biventricular conversion was performed in 23 patients at a median age of 10.0 (7.5-13.0) years. Indications included failing Fontan physiology in 15 (65%) and elective takedown in 8 (35%) patients. A subset of patients (n = 6) underwent procedures for staged recruitment of the nondominant ventricle before conversion. Median z score of end-diastolic volume of borderline ventricle before takedown was -2.3 (-3.3, -1.3). Hypoplastic left heart syndrome (P .01) and sub-/aortic stenosis (P .01) were more common in these patients. Biventricular conversion with or without staged ventricular recruitment led to a significant increase in indexed end-diastolic volume (P .01), indexed end-systolic volume (P .01), and ventricular mass (P .01) of the nondominant ventricle (14 right, 9 left ventricle). There were 5 (22%) deaths (1 [4%] early death). All who underwent elective biventricular conversion survived, whereas 2-year survival rate for patients with a failing Fontan circulation was 72.7% (95% confidence interval, 37%-90%). The overall, 3-year reoperation-free survival was 86.7% (95% confidence interval, 56%-96%). Left dominant atrioventricular canal defect (P .01) and early era of biventricular conversion (P = .02) were significant predictors for mortality.A primary as well as a staged biventricular conversion is feasible in patients who have had previous Fontan procedure. Although this provides an alternative to transplantation in patients with failing Fontan, outcomes are worse in those with failing Fontan compared with elective takedown of Fontan circulation. Optimal timing needs further evaluation.

Objective Neonatal orthotopic heart transplantation was introduced in the 1980s as a treatment for complex congenital heart disease. Progress in single-ventricle palliation and biventricular correction has resulted in a decline in neonatal heart transplant volume. However, limited reports on neonatal heart transplants have demonstrated favorable outcomes. We report the long-term outcomes of patients with neonatal heart transplants at our institution spanning nearly 30 years. Methods A retrospective analysis of neonatal heart transplants and neonates listed for transplant was performed at Children's Hospital Colorado. Primary outcomes were early and late survival. Secondary outcomes were rejection episodes, retransplantation, and development of cardiac allograft vasculopathy or post-transplant lymphoproliferative disease. Results A total of 21 neonates underwent orthotopic heart transplantation at our institution. Among these, 10 neonates were transplanted from 1991 to 2000, 8 neonates were transplanted from 2001 to 2010, and 3 neonates were transplanted from 2011 to 2020. The average age of these patients was 17 days, and the average weight was 3.43 kg. Early survival was 95.2%. Survival at 1 and 5 years was 85.7% (confidence interval [CI], 61.9%-95.2%) and 75% (CI, 45.6%-85.5%), respectively. Of eligible patients, the 10-year and 20-year survival was 72.2% (CI, 45.1%-85.3%) and 50% (CI, 25.9%-70.1%), respectively. Conclusions Our institution reports favorable outcomes of neonatal heart transplantation. These results should be considered within the context of outcomes for patients awaiting transplant and the limited donor availability. However, the successful nature of these procedures suggest it may be necessary to reevaluate the indications for neonatal heart transplantation, particularly where risk of mortality and morbidity with palliative or corrective surgery is high.

Objectives Protein losing enteropathy and plastic bronchitis are severe complications in Fontan circulation, with 5-year survival ranging from 46% to 88%. We report risk factors and outcomes of protein losing enteropathy and plastic bronchitis in patients undergoing the Fontan. Methods We performed a retrospective analysis of 1561 patients from the Australia New Zealand Fontan Registry. Two end points were death and cardiac transplantation examined with Cox regression (if no competing risks) or cumulative incidence curves and cause-specific Cs regression. Results A total of 55 patients with protein losing enteropathy/plastic bronchitis were included. Their median age at the Fontan was 5.7 years, and time to onset after the Fontan for protein losing enteropathy was 5.0 years and plastic bronchitis was 1.7 years. Independent predictors for developing protein losing enteropathy/plastic bronchitis were right-ventricular morphology with hypoplastic left-heart syndrome (hazard ratio, 2.30; confidence interval, 1.12-4.74), older age at Fontan (hazard ratio, 1.13; confidence interval, 1.03-1.23), and pleural effusions after Fontan (hazard ratio, 2.43; confidence interval, 1.09-5.41); left-ventricular morphology was protective (hazard ratio, 0.36; confidence interval, 0.18-0.70). In the protein losing enteropathy/plastic bronchitis population, freedom from death or transplantation after protein losing enteropathy/plastic bronchitis diagnosis at 5, 10, and 15 years was 70% (confidence interval, 58-85), 65% (confidence interval, 51-83), and 43% (confidence interval, 26-73), respectively; only older age (hazard ratio, 1.23; confidence interval, 1.01-1.52) was an independent predictor. Twenty-six surgical interventions were performed in 20 patients, comprising Fontan revisions (n = 5), fenestrations (n = 11), Fontan conversions (n = 5), atrioventricular valve repairs (n = 3), and hepatic vein diversion (n = 2). Conclusions Protein losing enteropathy and plastic bronchitis remain severe complications, preferably affecting patients with dominant right single ventricle, with older age at Fontan being a predictor of developing protein losing enteropathy/plastic bronchitis and poorer prognosis. Heart transplantation remains the ultimate treatment, with 30% dying or requiring transplantation within 5 years, and the remaining being stable for long periods.

Background Hypoxic-ischemic white matter brain injury commonly occurs in neonates with critical congenital heart disease. Recent work has shown that longer time to surgery is associated with increased risk for this injury. In this study we investigated changes in perinatal cerebral hemodynamics during the transition from fetal to neonatal circulation to ascertain mechanisms that might underlie this risk. Methods Neonates with either transposition of the great arteries (TGA) or hypoplastic left heart syndrome (HLHS) were recruited for preoperative noninvasive optical monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using diffuse optical spectroscopy and diffuse correlation spectroscopy, 2 noninvasive optical techniques. Measurements were acquired daily from day of consent until the morning of surgery. Temporal trends in these measured parameters during the preoperative period were assessed with a mixed effects model. Results Forty-eight neonates with TGA or HLHS were studied. Cerebral oxygen saturation was significantly and negatively correlated with time, and oxygen extraction fraction was significantly and positively correlated with time. Cerebral blood flow did not significantly change with time during the preoperative period. Conclusions In neonates with TGA or HLHS, increasing cerebral oxygen extraction combined with an abnormal cerebral blood flow response during the time between birth and heart surgery leads to a progressive decrease in cerebral tissue oxygenation The results support and help explain the physiological basis for recent studies that show longer time to surgery increases the risk of acquiring white matter injury.

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Background The use of ventricular assist devices (VADs) as a bridge-to-transplant in patients with single-ventricle physiology post–stage one palliation has been associated with poor outcomes. We describe our center's successful experience in the use of paracorporeal pulsatile VADs in the palliation of high-risk single ventricle physiology before or after the first stage of palliation with an impetus on pre-palliation implant. Methods This is a single-center retrospective review of univentricular patients implanted with the Berlin Heart EXCOR VAD. Our center's approach includes early implantation of the Berlin Heart EXCOR with common atrial cannulation, a cardiac index between 3.5 and 5 L/min/m2, and a bivalirudin-based anticoagulation regimen. Patient-related data were collected postimplant at week 1 and months 1, 2, and 3. Post-transplant data, including neurological outcomes, were collected. Results Nine patients were supported. Survival to discharge post-transplant was 83% (5/6) in patients bridged-to-transplant and 33% (1/3) in patients bridged-to-decision. Six patients had no previous palliation. Median hospital stay before implantation was 111 days for nonsurvivors versus 20 days for survivors. The need for extracorporeal membrane oxygenation and cardiopulmonary resuscitation in nonsurvivors versus survivors was 1 in 3 versus 1 in 6 and 2 in 3 versus 1 in 6, respectively. There were no major central nervous system complications except for 1 significant hemorrhagic event. The pediatric overall performance category score on follow-up was normal to mild disability in 83% of survivors. Limitations include hemolysis and intermittent periods of infection and/or inflammation. Conclusions The use of pulsatile paracorporeal VADs is a feasible option as a bridge-to-transplant in the peri–stage one high-risk single ventricle.

Background Measurement of cerebral venous oxyhemoglobin saturation (ScvO 2 ) is considered a gold standard in assessing the adequacy of tissue oxygen delivery (DO 2 ) after the stage 1 palliation (S1P), with SvO 2 2 . Regional oxygenation index (rSO 2 ) based on near-infrared resonance spectroscopy (NIRS) frequently is used to screen for compromised DO 2 , although its sensitivity to detect severe abnormalities in SvO 2 is uncertain. Methods ScvO 2 was measured by co-oximetry from the internal jugular vein as clinically indicated in 73 neonates after S1P. These values were compared with cerebral rSO 2 (FORE-SIGHT; CASMED) via mixed effects model linear regression, Bland-Altman analysis, and sensitivity analysis. Because NIRS devices measure a composite of arterial and venous blood, we calculated an rSO 2 -based ScvO 2 designed to remove arterial contamination from the rSO 2 signal: rSO 2 -based ScvO 2 = (rSO 2 − arterial oxygen saturation × 0.3)/0.7. Results Among 520 time-matched pairs of ScvO 2 and cerebral rSO 2 , the slope of the relationship between rSO 2 and ScvO 2 (after we adjusted for effects of hemoglobin) was 0.37 ± 0.04 with only modest correlation (r 2 = 0.39), and mean bias of +8.26. When ScvO 2 was 2 was 2 in the same range is >99%. Correction of rSO 2 for arterial contamination significantly decreased mean bias (+3.03) and improved the sensitivity of rSO 2 to detect ScvO 2 2 2 2 Conclusions Cerebral rSO 2 in isolation should not be used to detect low ScvO 2 , because its sensitivity is low, although correction of rSO 2 for arterial contamination may improve sensitivity. Cerebral rSO 2 of 50 or greater should not be considered reassuring, though values below 30 are specific for low ScvO 2 .

Objective Poor survival following surgical palliation for hypoplastic left heart syndrome (HLHS) raises the question of the need for a paradigm shift. This is the first human study to investigate the possibility of primary "in-series" palliation in neonates and infants with HLHS in an acute setting with the aid of 2 types of mechanical assist: superior vena cava (SVC)–to–pulmonary artery (PA) pump assist and SVC–to–right atrium (RA) oxygenation assist. Methods By rearranging the cannula sites and flow rates for modified ultrafiltration, 2 types of mechanically assisted bidirectional cavopulmonary shunt (BCPS) circulation were simulated for 20 minutes. Three neonates undergoing a stage I Norwood procedure were assigned to SVC-PA pump assist, and 3 infants undergoing stage II BCPS were assigned to SVC-RA oxygenation assist. Hemodynamic parameters, blood gas values, and arterial (SaO 2 ) and regional cerebral tissue (rCTO 2 ) saturations were analyzed. Results All 6 patients completed the study without hemodynamic compromise. In the SVC-PA pump assist group, a mean arterial pressure >40 mm Hg was maintained. SVC pressure was lower ( P = .01) and cerebral perfusion pressure (CPP) was higher ( P = .03) during the last 10 minutes of assist compared with Norwood physiology. SaO 2 >80%, rCTO 2 >60%, and mixed venous saturation ≥59% were maintained, comparable to values with Norwood physiology. In the SVC-RA oxygenation assist group, with full or 50% support, mean blood pressure >50 mm Hg, SVC pressure 50%, and CPP >40 mm Hg were maintained, which were comparable to BCPS physiology. Conclusions Two types of mechanical assist to support primary in-series palliation are feasible in the acute setting. Both modes of mechanical assist maintained oxygenation, as well as systemic and cerebral perfusion.

Single-ventricle palliation (SVP) for children with unbalanced atrioventricular septal defect (uAVSD) is thought to carry a poor prognosis, but limited data have been reported.We performed a retrospective review of children with uAVSD who underwent SVP at a single institution. Data were obtained from medical records and correspondence with general practitioners and cardiologists.Between 1976 and 2016, a total of 139 patients underwent SVP for uAVSD. A neonatal palliative procedure was performed in 83.5% of these patients (116 of 139), and early mortality occurred in 11.2% (13 of 116). Ninety-four patients underwent stage II palliation, with an early mortality of 6.4% (6 of 94). Eighty patients (57.6%) underwent Fontan completion, with an early mortality of 3.8% (3 of 80). Interstage mortality was 11.7% (12 of 103) between stages I and II and 17.0% (15 of 88) between stage II and Fontan. Long-term survival was 66.5% (95% confidence interval [CI], 57.9%-73.9%) at 5 years, 64.4% (95% CI, 55.5%-72.0%) at 15 years, and 57.8% (95% CI, 47.5%-66.8%) at 25 years. Survival post-Fontan was 94.9% (95% CI, 86.9%-98.0%) at 5 years, 92.0% (95% CI, 80.6%-96.8%) at 15 years, and 82.4% (95% CI, 61.5%-92.6%) at 25 years. Risk factors associated with death or transplantation were aortic atresia (hazard ratio [HR], 5.3; P = .03) and hypoplastic aortic arch (HR, 2.5; P = .02). Atrioventricular valve operations were required in 31.7% of the patients (44 of 139), with 31.8% of them (14 of 44) requiring a further operation.Children undergoing SVP for uAVSD have substantial mortality, with60% survival at 25 years. However, survival of children who achieve Fontan completion is better than has been reported previously.

Objectives Endothelial-to-mesenchymal transition (EndMT) has been identified as the underlying mechanism of endocardial fibroelastosis (EFE) formation. The purpose of this study was to determine whether hemodynamic alterations due to valvar defects promote EndMT and whether age-specific structural changes affect ventricular diastolic compliance despite extensive surgical resection of EFE tissue. Material and Methods We analyzed EFE tissue from 24 patients with hypoplastic left heart syndrome (HLHS) who underwent left ventricular (LV) rehabilitation surgery at Boston Children's Hospital between December 2011 and March 2018. Six patients with flow disturbances across the aortic valve and/or mitral valve but no HLHS diagnosis and macroscopic appearance of “EFE-like tissue” in the LV were included for comparison. All samples were examined for amount of collagen/elastin production and degradation, and presence of active EndMT by histologic analysis. Results EFE tissue from patients with and without HLHS consisted predominantly of elastin and collagen fibers. There was no alteration in degradation activity for collagen or elastin as shown by in situ zymography. Active EndMT was found in all patients with and without HLHS with flow disturbances (“EFE-like”). In patients with HLHS, EFE infiltrated into the underlying myocardium with increasing age. Conclusions Patients with and without HLHS with flow disturbances due to stenotic or incompetent valves develop EndMT-derived fibrotic tissue covering the LV. When EFE recurs, it is directly associated with flow disturbances and switches to an infiltrative growth pattern with increasing age, leading to increased diastolic stiffness of the LV.

Objectives Cardiosphere-derived cell (CDC) transplantation has been shown to attenuate right ventricular (RV) dysfunction in patients with hypoplastic left heart syndrome. However, live cell transplantation requires complex handling protocols that may limit its use. Exosomes are protein and nucleic acid-containing nanovesicles secreted by many cell types, including stem cells, which have been shown to exert a cardioprotective effect comparable with whole cells following myocardial injury. We therefore sought to evaluate 3 human CDC-derived exosome preparations in a juvenile porcine model of acute pressure-induced RV dysfunction. Methods Twenty immunocompetent juvenile Yorkshire pigs (7-10 kg) underwent pulmonary arterial banding followed by intramyocardial test agent administration: control (n = 6), XO-1 (n = 4), XO-2 (n = 5), and XO-3 (n = 5). Animals were monitored for 28 days postoperatively with periodic phlebotomy and echocardiography, followed by extensive postmortem gross and histopathologic analysis. Results All animals survived the banding operation. One died suddenly on postoperative day 1; another was excluded due to nonstandard response to banding. Of the remaining animals, there were no clinical concerns. RV fractional area change was improved in the XO-1 and XO-2 groups relative to controls at postoperative day 28. On histologic analysis, exosome-treated groups exhibited decreased cardiomyocyte hypertrophy with respect to controls. Conclusions Human CDC-derived exosome administration was associated with significant preservation of RV systolic function in the setting of acute pressure overload. Such acellular preparations may prove superior to whole cells and may represent a novel therapeutic approach to clinical myocardial injury.

Objective To develop a risk score to predict mortality or transplant in the interstage period. Background The “interstage” period between the stage 1 and stage 2 palliation is a time of high morbidity and mortality for infants with single-ventricle congenital heart disease. Methods This was an analysis of patients with single-ventricle congenital heart disease requiring arch reconstruction who were enrolled in the National Pediatric Cardiology Quality Improvement Collaborative registry from 2008 to 2015. The primary composite endpoint was interstage mortality or transplant. Multivariable logistic regression and classification and regression tree analysis were performed on two-thirds of the patients (“learning cohort”) to build a risk score for the composite endpoint, that was validated in the remaining patients (“validation cohort”). Results In the 2128 patients analyzed in the registry, the overall event rate was 9% (153 [7%] deaths, 42 [2%] transplants). In the learning cohort, factors independently associated with the composite endpoint were (1) type of Norwood; (2) postoperative ECMO; (3) discharge with Opiates; (4) No Digoxin at discharge; (5) postoperative Arch obstruction, (6) moderate-to-severe Tricuspid regurgitation without an oxygen requirement, and (7) Extra Oxygen required at discharge in patients with moderate-to-severe tricuspid regurgitation. This model was used to create a weighted risk score (“NEONATE” score; 0-76 points), with >75% accuracy in the learning and validation cohorts. In the validation cohort, the event rate in patients with a score >17 was nearly three times those with a score ≤17. Conclusions We introduce a risk score that can be used post-stage 1 palliation to predict freedom from interstage mortality or transplant.

Objectives Acute coronary artery obstruction is a rare complication of congenital heart disease surgery but imposes a high burden of morbidity and mortality. Previous case series have described episodes in specific congenital heart lesions or surgical repairs but have not examined the complication in all-comers to congenital heart surgery. We hypothesize that shorter time from a clinically recognized postoperative sentinel event suggestive of coronary ischemia to diagnosis of coronary obstruction is associated with improved clinical outcomes. Methods This was a single-center, retrospective review of patients diagnosed with acute coronary artery obstruction by angiography following surgical repair of congenital heart disease between January 2000 and June 2016. Results In total, 34 patients were identified. The most common procedures associated with coronary artery obstruction were the Norwood procedure, arterial switch operation, and aortic valve repair/replacement. In total, 79% required mechanical circulatory support, 41% died, and 27% were listed for heart transplant. Patients who died or were listed for heart transplant had longer median sentinel-event-to-cardiac-catheterization time (28 [6-168] hours vs 10 [3-56] hours, P = .001), and longer median sentinel-event-to-intervention time (32 [11-350] hours vs 13 [5-59] hours, P = .003). Patients with hypoplastic left heart syndrome were at greater risk of death or transplant listing (odds ratio, 9.23, P = .03). Conclusions Time from clinically relevant postoperative sentinel event to diagnosis of coronary artery obstruction by angiography was associated with transplant-listing-free survival. Clinicians should maintain a high index of suspicion for coronary obstruction and consider early catheterization and coronary angiography for patients in whom post-operative coronary compromise is suspected.

Objectives Sudden death is common in patients with hypoplastic left heart syndrome and comparable lesions with parallel systemic and pulmonary circulation from a common ventricular chamber. It is hypothesized that unforeseen acute deterioration is preceded by subtle changes in physiologic dynamics before overt clinical extremis. Our objective was to develop a computer algorithm to automatically recognize precursors to deterioration in real-time, providing an early warning to care staff. Methods Continuous high-resolution physiologic recordings were obtained from 25 children with parallel systemic and pulmonary circulation who were admitted to the cardiovascular intensive care unit of Texas Children's Hospital between their early neonatal palliation and stage 2 surgical palliation. Instances of cardiorespiratory deterioration (defined as the need for cardiopulmonary resuscitation or endotracheal intubation) were found via a chart review. A classification algorithm was applied to both primary and derived parameters that were significantly associated with deterioration. The algorithm was optimized to discriminate predeterioration physiology from stable physiology. Results Twenty cardiorespiratory deterioration events were identified in 13 of the 25 infants. The resulting algorithm was both sensitive and specific for detecting impending events, 1 to 2 hours in advance of overt extremis (receiver operating characteristic area = 0.91, 95% confidence interval = 0.88-0.94). Conclusions Automated, intelligent analysis of standard physiologic data in real-time can detect signs of clinical deterioration too subtle for the clinician to observe without the aid of a computer. This metric may serve as an early warning indicator of critical deterioration in patients with parallel systemic and pulmonary circulation.

Publicly available data from the Pediatric Heart Network's Single Ventricle Reconstruction Trial was analyzed to determine the prevalence, timing, risk factors for, and impact of second- and third-degree heart block (HB) on outcomes in patients who underwent stage 1 palliation (S1P) for hypoplastic left heart syndrome (HLHS).The presence and date of onset of post-S1P HB occurring within the first year of life, potential risk factors for HB, and factors known to predict poor outcomes after S1P were extracted. Multivariable logistic and Cox regression analyses were performed to identify risk factors for HB and to determine the effect of HB on 3-year transplantation-free survival.Among the 549 patients in the cohort, 33 (6%) developed HB after S1P. The median interval between S1P and HB was 8 days (interquartile range, 0-133 days). Regression analysis showed that tricuspid valve repair during S1P and obstruction of pulmonary venous drainage requiring pre-S1P intervention were independently associated with HB (adjusted odds ratio [aOR], 11.6, 95% confidence interval [CI] 3.3-40; P .001 and aOR, 5.1; 95% CI, 1.3-20.6; P = .02, respectively). Transplantation-free survival at 3 years was lower for those with HB (39% vs 65%; P = .004). HB remained associated with transplantation-free survival after controlling for known risk factors (adjusted hazard ratio, 3.1; 95% CI, 1.9-5.0; P .001). Nine children (27%) had a pacemaker implanted, and 7 of these children (78%) died or underwent heart transplantation.HB after S1P is rare but heralds a poor outcome. Careful monitoring of these patients is recommended given their significantly increased risks of death and heart transplantation.

Objective We tested the hypotheses that volume overload and cyanosis observed in the pre-Fontan single ventricular circulation are associated with increased ventricular fibrogenesis, that the Fontan procedure helps to reduce fibrogenesis, and that persistently increased fibrogenesis in the Fontan ventricle is associated with ventricular diastolic dysfunction. Methods Levels of serum amino-terminal procollagen type III, a marker of tissue fibrogenesis, were measured in 172 patients with single ventricle circulation and 149 controls. Patients were divided into 3 groups according to surgical stage: 59 patients after Blalock–Taussig shunt or pulmonary banding, 60 patients after Glenn surgery (Glenn group), and 53 patients after Fontan surgery (Fontan group). Results Serum amino-terminal procollagen type III levels were significantly higher among the 3 single ventricle groups than among control patients, but decreased with each surgical stage (0.604, 0.176, 0.143, and 0.073 U/mL, for Blalock–Taussig shunt or pulmonary banding, Glenn, Fontan, and controls, respectively). Severity of volume load and cyanosis were independent determinants of increased amino-terminal procollagen type III levels in patients before Fontan surgery, and persistently increased amino-terminal procollagen type III after Fontan surgery was associated with ventricular diastolic stiffening ( r = 0.494, P = .009). Data also indicated close associations between amino-terminal procollagen type III levels and activation of the renin–angiotensin–aldosterone system, suggesting potential involvement of this hormonal system in the increased fibrogenesis after Fontan surgery. Conclusions These results suggest that serum amino-terminal procollagen type III may provide important diagnostic information on myocardial fibrosis in patients with single ventricle circulation and raise the possibility that ventricular fibrogenesis may be a potential therapeutic target in this population.

Objectives Patients with hypoplastic left heart syndrome are at risk for neurodevelopmental impairment. Hypoxic-ischemic brain injury during neonatal treatment might be a relevant cause. We evaluated the association between cerebral oxygenation in the perioperative course of the Norwood procedure and neurodevelopmental outcome. Methods Cerebral tissue oxygen saturation (ScO 2 ) was obtained by near-infrared spectroscopy for 24 hours before and 48 hours after surgery in 43 patients. Full-scale, verbal, and performance IQ scores were evaluated with the Wechsler Preschool and Primary Scale of Intelligence at a median of 4.5 years (range, 3.5-6.8 years). Cognitive functions were assessed with the German Kognitiver Entwicklungstest fur das Kindergartenalter (KET-KID). Results Mean IQ scores and KET-KID percentile ranks were in the lower-normal range (full-scale IQ, 94 ± 11; verbal IQ, 97 ± 13; performance IQ, 93 ± 9; KET-KID global, 42 ± 27; verbal, 48 ± 29; nonverbal, 37 ± 23). Scores were below average (full scale IQ 2 was lower in patients scoring below average (56.8% ± 7.1% vs 61.7% ± 5.8%; P = .028) and was correlated with full-scale IQ ( r = 0.495; P = .001), verbal IQ ( r = 0.524; P = .001), and performance IQ ( r = 0.386; P = .012) scores, and with global ( r = 0.360; P = .018) and verbal ( r = 0.395, P = .009) KET-KID scores. A relationship between IQ or KET-KID scores and postoperative ScO 2 was not found. Gestational age, head circumference z -score, age at surgery, and postoperative length of stay were associated with IQ and KET-KID scores. Conclusions Neurodevelopmental outcome was in the lower-normal range. Along with innate patient factors, preoperative cerebral tissue oxygenation is likely an important determinant of cognitive development.

Neonates with congenital heart disease are at risk for impaired neurodevelopment after cardiac surgery. We hypothesized that intraoperative EEG activity may provide insight into future neurodevelopmental outcomes.Neonates requiring surgery had continuous intraoperative EEG and hemodynamic monitoring. The level of EEG suppression was classified as either: slow and continuous; moderate burst suppression; severe burst suppression; or isoelectric (no brain activity for3 minutes). Follow-up neurodevelopmental outcomes were assessed using the Vineland Adaptive Behavior Scale II (Vineland-II).Twenty-one neonates requiring cardiac surgery developed a slow and continuous EEG pattern after general anesthesia. Ten neonates (48%) maintained continuous brain electrical activity with moderate burst suppression as the maximum level of EEG suppression. Eleven neonates (52%) developed severe burst suppression that progressed into an isoelectric state during the deep hypothermic period required for circulatory arrest. However, the duration of this state was significantly longer than circulatory arrest times (111.1 ± 50 vs 22.3 ± 17 minutes; P.001). At a mean follow-up at 5.6 ± 1.0 years, compared with neonates with continuous brain electrical activity, neonates who developed an isoelectric state had lower Vineland-II scores in communication. There was an inverse relationship between composite Vineland-II scores and duration of isoelectric activity (R = -0.75, P = .01). Of neonates who experienced an isoelectric state, durations of90 minutes were associated with the lowest Vineland-II scores (125.0 ± 2.6 vs 81.1 ± 12.7; P.01).The duration of cortical isoelectric states seems related to neurodevelopmental outcomes. Strategies using continuous EEG monitoring to minimize isoelectric states may be useful during complex congenital heart surgery.

To report our improving institutional experience with the hybrid alternative surgical strategy for the management of hypoplastic left heart syndrome, in which hybrid stage 1 is followed by a comprehensive stage 2 procedure (removal of patent ductus arteriosus stent and pulmonary artery [PA] bands, aorta and PA reconstruction, Damus-Kaye-Stansel, atrial septectomy, Glenn).In this Institutional Review Board-approved retrospective review of all patients undergoing a comprehensive stage 2 procedure between January 2002 and December 2014, data were compared between the pre-protocol group (n = 64; January 2002 to March 2010) and the post-protocol group (n = 55; March 2010 to December 2014). These 2 groups flank the implementation of a perioperative management protocol to prevent PA thrombosis.Pre-protocol mortality was 19% (12 of 64), with the most common mode of death involving PA thrombosis in at least 7 patients, with an urgent indication for surgery and age as contributing factors. Care modifications instituted in March 2010 included avoidance of procedures on an emergent basis or in patients aged3 months, use of a systemic PA shunt in cases of too-small superior vena cava and/or PA, completion angiogram with a low threshold for intraoperative stenting, and postoperative anticoagulation therapy for 6 weeks. There was a significant decrease in mortality (2 of 55; 4%; P = .01), PA thrombosis (0 of 55; 0%; P = .01), and use of extracorporeal membrane oxygenation (0/55 [0%] compared with 7 of 64 [11%]; P = .01) after protocol implementation.Despite the technical challenges of the comprehensive stage 2 procedure, excellent outcomes are attainable. Experience coupled with an internal quality review drove the implementation of a successful perioperative management protocol.

Objectives The purpose of this article is to provide thoracic and cardiovascular surgeons with a practical step-by-step strategy to use in collaboration with a biostatistician for implementation of competing risks analysis when analyzing time-to-event data. Patients may have an outside event that precludes the event of interest. Traditional time-to-event analysis incorrectly assumes noninformative censoring in this scenario, which will lead to invalid results and conclusions. Methods The steps are (1) to determine whether competing risks analysis is needed, (2) to perform a nonparametric analysis, (3) to perform a model-based analysis, (4) to interpret the results, and (5) to compare to traditional survival analysis methods. We apply our approach to a hypothetical cardiovascular surgery example in determining the hazard of mortality after the stage 3 Fontan operation associated with prematurity among patients with hypoplastic left heart syndrome who had successful completion of Norwood stage 1 while incorporating mortality during the stage 2 bidirectional Glenn procedure as a competing risk. We apply nonparametric, semiparametric, and parametric methods. Results Although Cox regression establishes prematurity as a significant risk factor of mortality after stage 3 (hazard ratio, 1.26; 95% confidence interval, 1.06-1.50; P = .009), the competing risks analysis with the Fine-Gray model accounting for mortality after stage 2 determines that prematurity is not a significant predictor (hazard ratio, 1.07; 95% confidence interval, 0.90-1.27; P = .467). Conclusions This article provides a practical step-by-step approach for making competing risks more accessible for cardiac surgeons collaborating with a biostatistician in analyzing and interpreting time-to-event data.

Objective Immediate extubation may have outcome benefits when judiciously instituted after neonatal congenital cardiac surgery. We sought to evaluate the outcomes of immediate extubation specifically in neonates undergoing stage 1 Norwood palliation of hypoplastic left heart syndrome. Methods Consecutive neonates undergoing stage 1 Norwood (January 2010 to December 2016) for hypoplastic left heart syndrome were retrospectively studied. Immediate extubation was defined as successful extubation before termination of anesthetic care. Preoperative and intraoperative variables were compared between immediate extubation and nonimmediate extubation groups, and bivariate analyses and descriptive methods were used to express the association of outcome variables with immediate extubation. Data were expressed as number and percent for categoric variables, and median and interquartile range for continuous variables. Results Of 23 patients who underwent stage 1 palliation, 5 had immediate extubation (22%). There were no differences in preoperative or intraoperative factors between patients who did and did not undergo immediate extubation. There were no deaths in the immediate extubation group. In the nonimmediate extubation group, 3 patients died before hospital discharge. One patient who had immediate extubation and 4 patients among those who did not have immediate extubation had to be reintubated in the 96 hours that followed extubation (P = 1). Intensive care unit length of stay was 8 (3-17) and 8 (5-18) (days) for the immediate extubation group and nonimmediate extubation groups, respectively (P = .71). Conclusions Immediate extubation strategy was safely accomplished in one-fifth of this cohort of hypoplastic left heart syndrome. A larger cohort may delineate the determinants of immediate extubation and its benefits in infants undergoing stage 1 single ventricle palliation.

Objective Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality. Methods From 2005 to 2017, 593 neonates in the Congenital Heart Surgeons' Society Critical Left Heart Obstruction cohort underwent a Norwood procedure. Median follow-up was 3.7 years. Multivariable parametric models, including a modulated renewal analysis, were performed. Results Of the 593 neonates, 146 (25%) underwent 218 reinterventions for arch obstruction after the Norwood procedure: catheter-based (n = 168) or surgical (n = 50) at a median age of 4.3 months (quartile 1-quartile 3, 2.6-5.7). Interdigitation of the distal aortic anastomosis was protective against arch reintervention. Development of ≥ moderate tricuspid valve regurgitation and right ventricular dysfunction at any point was associated with arch reintervention. Nonsignificant variables for arch reintervention included shunt type and preoperative aortic measurements. Surgical arch reintervention was protective against arch reintervention, but transcatheter reintervention was associated with increased reintervention. Arch reintervention was not associated with increased mortality. There was wide institutional variation in incidence of arch reintervention (range, 0-40 reinterventions per 100 years patient follow-up) and in preintervention gradient (range, 0-64 mm Hg). Conclusions Interdigitation of the distal aortic anastomosis during the Norwood procedure decreased the risk of arch reintervention. Surgical arch reintervention is more definitive than transcatheter. Arch reintervention after the Norwood procedure is not associated with increased mortality. Serial surveillance for arch obstruction, integrated with changes in right ventricular function and tricuspid valve regurgitation, is recommended after the Norwood procedure to improve outcomes.