Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience.

OBJECTIVES: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.

Prognostic Value of RV Function Analysis During the Interstage Period in Patients with Hypoplastic Left Heart Syndrome.

Cardiac dysfunction is associated with mortality in children with hypoplastic left heart syndrome (HLHS). We evaluated the ability of qualitative and quantitative RV functional parameters to predict outcomes in HLHS patients. In this retrospective, single-center study, echocardiograms from 3 timepoints (pre-stage 1 palliation, 4-8 weeks post-stage 1 palliation, and pre-Glenn) were analyzed in infants with HLHS. Patients were stratified into two groups based on outcome of transplant-free survival post-Glenn (survivors) versus mortality or transplantation prior to Fontan (non-survivors). Images were retrospectively reviewed to obtain RV global longitudinal strain (RVGLS), RV-free wall strain (RVFWS), fractional area change (FAC), tricuspid annular systolic plane excursion (TAPSE), tissue motion annular displacement of the tricuspid valve (TMAD-TV) and qualitative systolic function assessment during the predetermined timepoints. An equal variance t-test and chi-square were used to determine significant differences and ROC curve analysis was performed to derive optimal cutoff values to predict mortality/transplant. A total of 47 patients met inclusion criteria, of which, 21 patients met composite endpoint. There were no significant differences in any RV functional parameter during the pre- or post-stage 1 palliation timepoints. The absolute values of RVFWS, RVGLS, and TMAD-TV were significantly greater in survivors than non-survivors during the pre-Glenn timepoint. A pre-Glenn RVGLS > -15.6 (AUC 0.79), RVFWS > -18.6 (AUC 0.75), and TMAD-TV < 12.6% (AUC 0.82) were sensitive and specific for predicting death or need for transplantation prior to Fontan completion. RVGLS, RVFWS, and TMAD-TV may help identify higher-risk HLHS patients during the interstage period.

Labyrinthine cor triatriatum sinister in fetal hypoplastic left heart syndrome is associated with poor outcomes.

OBJECTIVES: A subset of hypoplastic-left-heart-syndrome (HLHS) fetuses have a complex cor-triatriatum sinister that we named "labyrinthine-cor (L-cor)". We sought to determine the prevalence of L-cor in HLHS fetuses and hypothesized that it is associated with increased mortality. METHODS: This single-center retrospective cohort study included all HLHS fetuses from January 2010-December 2020. Fetuses with other hypoplastic-left-heart variants, inadequate images, lack of follow-up and fetal atrial-septal interventions were excluded. RAS was defined as the ratio of pulmonary-vein forward-to-reverse velocity-time-integral (VTI) ≤ 5 and severe-RAS defined as VTI-ratio <3. Kaplan-Meier survival-analysis was performed for the primary outcome of transplant-free survival for 62 weeks after gestational-age of 30 weeks (∼1 year). RESULTS: Of the 156 consecutive fetuses with HLHS, 11 (7.7%) had L-cor and 8/11 (72.7%) of these had RAS. When compared to HLHS-RAS without L-cor, fetuses with HLHS-RAS and L-cor were less likely to survive to 28 days (87% vs. 62.5%, p = 0.017) and to 1 year (69.6% vs. 25%, p = 0.029). When comparing by survival analysis, fetuses with severe-RAS with L-cor had lower survival compared severe-RAS without L-cor (p = 0.020). CONCLUSION: L-cor in fetal HLHS is associated with increased mortality. Recognition of this finding is important for prognostication and atrial-septal-intervention planning.

Association of Digoxin With Preserved Echocardiographic Indices in the Interstage Period: A Possible Mechanism to Explain Improved Survival?

Background For patients with hypoplastic left heart syndrome, digoxin has been associated with reduced interstage mortality after the Norwood operation, but the mechanism of this benefit remains unclear. Preservation of right ventricular (RV) echocardiographic indices has been associated with better outcomes in hypoplastic left heart syndrome. Therefore, we sought to determine whether digoxin use is associated with preservation of the RV indices in the interstage period. Methods and Results We conducted a retrospective cohort study of prospectively collected data using the public use data set from the Pediatric Heart Network Single Ventricle Reconstruction trial, conducted in 15 North American centers between 2005 and 2008. We included all patients who survived the interstage period and had echocardiographic data post-Norwood and pre-Glenn operations. We used multivariable linear regression to compare changes in RV parameters, adjusting for relevant covariates. Of 289 patients, 94 received digoxin at discharge post-Norwood. There were no significant differences in baseline clinical characteristics or post-Norwood echocardiographic RV indices (RV end-diastolic volume indexed, RV end-systolic volume indexed, ejection fraction) in the digoxin versus no-digoxin groups. At the end of the interstage period and after adjustment for relevant covariates, patients on digoxin had better preserved RV indices compared with those not on digoxin for the ΔRV end-diastolic volume (11 versus 15 mL, P=0.026) and the ΔRV end-systolic volume (6 versus 9 mL, P=0.009) with the indexed ΔRV end-systolic volume (11 versus 20 mL/BSA1.3, P=0.034). The change in the RV ejection fraction during the interstage period between the 2 groups did not meet statistical significance (-2 versus -5, P=0.056); however, the trend continued to be favorable for the digoxin group. Conclusions Digoxin use during the interstage period is associated with better preservation of the RV volume and tricuspid valve measurements leading to less adverse remodeling of the single ventricle. These findings suggest a possible mechanism of action explaining digoxin's survival benefit during the interstage period.

[Prenatal diagnosis and early neonatal management of patients with hypoplastic left heart syndrome: Experience of a perinatal center]. / Diagnóstico prenatal y manejo neonatal precoz de pacientes con Síndrome de corazón izquierdo hipoplásico: Experiencia de un centro perinatal.

INTRODUCTION: Hypoplastic Left Heart Syndrome (HLHS) is the most common form of functional single-ventricle heart disease. Despite improvements in medical and surgical care, morbidity and mortality remain high, especially around the first surgical stage. OBJECTIVE: To describe the clinical characteristics of newborns with HLHS, seen at a perinatal referral center. PATIENTS AND METHOD: Retrospective des criptive study of all newborns with pre and/or postnatal diagnosis of HLHS between 2014 and 2019 in the Complejo Asistencial Dr. Sótero del Rio. Medical records were reviewed collecting demographic and perinatal variables, clinical evolution, mortality associated with the first surgery, and survival at one year. RESULTS: Nineteen patients were included. Most were term newborns and 13/19 were fema le. All had a prenatal diagnosis. Five patients had associated extracardiac anomalies. 16/19 required vasoactive drugs and 17/19 used invasive mechanical ventilation. Seven patients received enteral fe eding, without episodes of enterocolitis. The median age at transfer for surgery was 8 days. Thirteen patients underwent the Norwood procedure, with 31% of mortality, and 47% of survival at one year. CONCLUSIONS: Neonatal management of patients with HLHS is complex and the multidisciplinary approach is fundamental. Mortality around the first surgical stage of our cohort is greater than the international reports which could be influenced by the absence of fetal therapy and the higher inci dence of extracardiac malformations.

Changes in Provider Prescribing Behavior for Infants with Single Ventricle Physiology After Evidence-Based Publications.

BACKGROUND: The impact of published evidence on clinical practice has been understudied in pediatric cardiology. OBJECTIVE: We sought to assess changes in prescribing behavior for angiotensin-converting enzyme inhibitor (ACEI) and digoxin at discharge after initial palliation of infants with single ventricle (SV) physiology following the publication of two large studies: The Pediatric Heart Network Infant Single Ventricle (PHN-ISV) trial showing no benefit with routine ACEI use and the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) analysis showing an association between digoxin and survival. METHODS: ICD-9-10 codes identified SV infants from the Pediatric Health Information System (1/2004 to 1/2018) and charge codes identified medications at discharge. Generalized estimating equations implementing segmented logistic regressions modeled medication use, before and after (with a 3-month washout period) the relevant publication (ACEI 7/1/2010; digoxin 4/1/2016). A subgroup analysis was performed for hypoplastic left heart syndrome (HLHS). RESULTS: ACEI use (37 centers, n = 4700) at discharge did not change over time during the pre-publication period. After publication of the PHN-ISV trial, ACEI use decreased (OR: 0.61, CI 0.44-0.84, p = 0.003). Digoxin use (43 centers, n = 4778) decreased by 1% monthly before publication. After the NPC-QIC publication, digoxin use increased (OR: 2.07, CI 1.05-4.08, p = 0.04) with an ongoing increase of 9% per month. Results were similar for the HLHS subgroup. CONCLUSIONS: Prescribing behavior changed congruently after the publication of evidence-based studies, with decreased ACEI use and increased digoxin use at discharge following initial palliation of SV infants. Our findings suggest scientific findings were rapidly implemented into clinical practice.

Timing of Transfer and Mortality in Neonates with Hypoplastic Left Heart Syndrome in California.

Maternal race/ethnicity is associated with mortality in neonates with hypoplastic left heart syndrome (HLHS). We investigated whether maternal race/ethnicity and other sociodemographic factors affect timing of transfer after birth and whether timing of transfer impacts mortality in infants with HLHS. We linked two statewide databases, the California Perinatal Quality Care Collaborative and records from the Office of Statewide Health Planning and Development, to identify cases of HLHS born between 1/1/06 and 12/31/11. Cases were divided into three groups: birth at destination hospital, transfer on day of life 0-1 ("early transfer"), or transfer on day of life ≥ 2 ("late transfer"). We used log-binomial regression models to estimate relative risks (RR) for timing of transfer and Cox proportional hazard models to estimate hazard ratios (HR) for mortality. We excluded infants who died within 60 days of life without intervention from the main analyses of timing of transfer, since intervention may not have been planned in these infants. Of 556 cases, 107 died without intervention (19%) and another 52 (9%) died within 28 days. Of the 449 included in analyses of timing of transfer, 28% were born at the destination hospital, 49% were transferred early, and 23% were transferred late. Late transfer was more likely for infants of low birthweight (RR 1.74) and infants born to US-born Hispanic (RR 1.69) and black (RR 2.45) mothers. Low birthweight (HR 1.50), low 5-min Apgar score (HR 4.69), and the presence of other major congenital anomalies (HR 3.41), but not timing of transfer, predicted neonatal mortality. Late transfer was more likely in neonates born to US-born Hispanic and black mothers but was not associated with higher mortality.

Attrition between the superior cavopulmonary connection and the Fontan procedure in hypoplastic left heart syndrome.

OBJECTIVE: We investigated the incidence and predictors of failure to undergo the Fontan in children with hypoplastic left heart syndrome who survived superior cavopulmonary connection. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Comparison of Quantitative Versus Qualitative Assessment of Single Right Ventricular Function for the Prediction of Midterm Outcomes.

Multiple studies have shown that quantitative evaluation of right ventricular (RV) systolic function in children with hypoplastic left heart syndrome (HLHS) is associated with outcomes. However, the most widely used method is qualitative, or subjective echocardiographic evaluation. Tricuspid annular displacement (TMAD) is a quantitative method and has been shown to be associated with transplant/death in a cohort of pediatric patients with HLHS. In this study, the same echocardiograms used in the quantitative TMAD study were qualitatively evaluated to see if the assessment correlated with midterm outcomes. We hypothesized that TMAD measures would outperform qualitative measurements. A previously published retrospective study of patients with systemic right ventricle demonstrated that TMAD measurements of function prior to the Glenn procedure were associated with midterm mortality/transplant (mean TMAD 12.4% for survivors and 10.0% for non-survivors/transplant, p = 0.03). Echocardiographic images used in that study were re-evaluated using qualitative assessment of function. A score between severely depressed (0) and supra-normal (7) was assigned independently by three cardiologists. A chart review included short-term clinical outcome measures in addition to midterm mortality/transplant. Spearman correlations and logistic regression were used to estimate the associations between function scores and clinical outcomes. Function scores were measured with acceptable inter- and intra-rater reliabilities in 47 patients who had echocardiograms used in the prior analysis before their bidirectional Glenn. The mean functional score was 5.3 ± 1.32 in survivors and 5.0 ± 1.02 in non-survivors/transplant. Subjective echocardiographic scores of function were not predictive of mortality (p = 0.23). Scores were correlated with length of cardiac intensive care unit stay (Spearman's rho = - 0.31, p = 0.04), but not post-Glenn total length of hospital stay (p = 0.4). A sub-analysis was performed for each individual operator. Only one of three operators produced scores with a significant association with mortality/transplant (p = 0.01, p = 0.25, p = 0.22, respectively). Averaged subjective measurement of function by three pediatric cardiologists in children with single right ventricle prior to the Glenn procedure was not associated with midterm outcomes. Previous work based on the same echocardiograms showed that quantitative analysis was associated with midterm outcomes. This suggests quantitative analysis may be more useful in prognostication. Future studies could confirm these results and identify which quantitative methods are most helpful.

Incidence and impact of acute kidney injury in patients with hypoplastic left heart syndrome following the hybrid stage 1 palliation.

OBJECTIVE: Acute kidney injury leads to worse outcomes following paediatric cardiac surgery. There is a lack of literature focusing on acute kidney injury after the Hybrid stage 1 palliation for single ventricle physiology. Patients undergoing the Hybrid Stage 1, as a primary option, may have a lower incidence of kidney injury than previously reported. When present, kidney injury may increase the risk of post-operative morbidity and mortality. METHODS: A retrospective, single centre review was conducted in patients with hypoplastic left heart syndrome who underwent Hybrid Stage 1 from 2008 to 2018. Acute kidney injury was defined as a dichotomous yes (meeting any injury criteria) or no (no injury) utilising two different criteria utilised in paediatrics. The impact of kidney injury on perioperative characteristics and 30-day mortality was analysed. RESULTS: The incidence of acute kidney injury is 13.4-20.7%, with a severe injury rate of 2.4%. Patients without a prenatal diagnosis of hypoplastic left heart syndrome have a higher incidence of kidney injury than those prenatally diagnosed, (40% versus 14.5%, p = 0.024). Patients with acute kidney injury have a significantly higher incidence of 30-day mortality, 27.3%, compared to without, 5.6% (p = 0.047). DISCUSSION: The incidence of severe acute kidney injury after the Hybrid Stage 1 palliation is low. A prenatal diagnosis may be associated with a lower incidence of kidney injury following the Hybrid Stage 1. Though uncommon, severe acute kidney injury following Hybrid Stage 1 may be associated with higher 30-day mortality.

Predictors of Transplant-Free Survival After the Norwood Procedure.

BACKGROUND: Birth weight, preterm delivery, and size for gestational age are surrogate markers for development that are commonly used in congenital heart surgery. Understanding the associations of these variables with patient outcomes is of great importance. METHODS: This study included all patients with hypoplastic left heart syndrome who underwent a Norwood procedure at a single institution from 1995 to 2018. Low birth weight was defined as weight less than 2.5 kg, and preterm delivery occurred at less than 37 weeks' gestation. Overall and conditional analyses were performed to evaluate for association with outcomes after the Norwood procedure. Secondary analyses evaluated the association of development measures with postoperative length of stay and ventilator duration. RESULTS: In total, 303 neonates (60% male) underwent the Norwood procedure and were followed for a median of 3.9 years (interquartile range, 0.5 to 10.4 years). Median birth weight was 3.1 kg (interquartile range, 2.8 to 3.4 kg). Patients with low birth weight had decreased transplant-free survival compared with patients with a normal birth weight (hazard ratio, 1.7; 95% confidence interval, 1.03 to 2.82; P = .039). When conditioning on survival to second-stage palliation, patients born small for gestational age had decreased transplant-free survival compared with patients born at appropriate size for gestational age (hazard ratio, 2.8; 95% confidence interval, 1.31 to 6.09; P = .008). Patients delivered preterm had a longer hospital length of stay (median, 55 days vs 31 days; P = .02) and more ventilator days compared with patients delivered at term (median, 7 days vs 4 days; P = .004). CONCLUSIONS: Various developmental markers have differing prognostic importance for patients undergoing the Norwood procedure. Understanding these differences can help guide preoperative decision making and patient selection.

Incidence and Timing of Thrombosis After the Norwood Procedure in the Single-Ventricle Reconstruction Trial.

Background Thrombosis is common in infants undergoing staged surgeries for single-ventricle congenital heart disease. The reported incidence and timing of thrombosis varies widely, making it difficult to understand the burden of thrombosis and develop approaches for prevention. We aimed to determine the timing and cumulative incidence of thrombosis following the stage I Norwood procedure and identify clinical characteristics associated with thrombosis. Methods and Results We analyzed data from the Pediatric Heart Network Single Ventricle Reconstruction trial from 2005 to 2009 and identified infants with first-time thrombotic events. In 549 infants, the cumulative incidence of thrombosis was 21.2% (n=57) from stage I through stage II. Most events occurred during stage I (n=35/57, 65%), with a median time to thrombosis of 15 days. We used a Cox proportional hazards model to estimate the association of clinical variables with thrombosis. After adjusting for baseline variables, boys had a higher hazard of thrombosis (adjusted hazard ratio [HR], 2.69; 95% CI, 1.44-5.05; P=0.002), non-hypoplastic left heart syndrome cardiac anatomy was associated with a higher early hazard of thrombosis (adjusted HR, 3.93; 95% CI, 1.89-8.17; P<0.001), and longer cardiopulmonary bypass time was also associated with thrombosis (per 10-minute increase, adjusted HR, 1.07; 95% CI, 1.01-1.12; P=0.02). Lower oxygen saturation after the Norwood procedure increased the hazard for thrombosis in the unadjusted model (HR, 1.08; 95% CI, 1.02-1.14; P=0.011). Conclusions Thrombosis affects 1 in 5 infants through Stage II discharge, with most events occurring during stage I. Male sex, non-hypoplastic left heart syndrome anatomy, longer cardiopulmonary bypass time, and lower stage I oxygen saturation were associated with thrombosis.

Socioeconomic Status and Long-term Outcomes in Single Ventricle Heart Disease.

BACKGROUND: Low socioeconomic status (SES) has emerged as an important risk factor for higher short-term mortality and neurodevelopmental outcomes in children with hypoplastic left heart syndrome and related anomalies; yet little is known about how SES affects these outcomes over the long-term. METHODS: We linked data from the Single Ventricle Reconstruction trial to US Census Bureau data to analyze the relationship of neighborhood SES tertiles with mortality and transplantation, neurodevelopment, quality of life, and functional status at 5 and 6 years post-Norwood procedure (N = 525). Cox proportional hazards regression and linear regression were used to assess the association of SES with mortality and neurodevelopmental outcomes, respectively. RESULTS: Patients in the lowest SES tertile were more likely to be racial minorities, older at stage 2 and Fontan procedures, and to have more complications and fewer cardiac catheterizations over follow-up (all P < .05) compared with patients in higher SES tertiles. Unadjusted mortality was highest for patients in the lowest SES tertile and lowest in the highest tertile (41% vs 29%, respectively; log-rank P = .027). Adjustment for patient birth and Norwood factors attenuated these differences slightly (P = .055). Patients in the lowest SES tertile reported lower functional status and lower fine motor, problem-solving, adaptive behavior, and communication skills at 6 years (all P < .05). These differences persisted after adjustment for baseline and post-Norwood factors. Quality of life did not differ by SES. CONCLUSIONS: Among patients with hypoplastic left heart syndrome, those with low SES have worse neurodevelopmental and functional status outcomes at 6 years. These differences were not explained by other patient or clinical characteristics.

Decreasing Interstage Mortality After the Norwood Procedure: A 30-Year Experience.

Background The superior cavo-pulmonary connection was introduced at our institution in 1988 for infants undergoing surgery for hypoplastic left heart syndrome. Patients with hypoplastic left heart syndrome remain at high risk for mortality in the time period between the Norwood procedure and the superior cavo-pulmonary connection. The primary objectives of this study were to compare interstage mortality across 4 eras and analyze factors that may impact interstage mortality. Methods and Results Patients with hypoplastic left heart syndrome who underwent the Norwood procedure, were discharged from the hospital, and were eligible for superior cavo-pulmonary connection between January 1, 1988, and December 31, 2017, were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated with 95% CIs. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality. There were 1111 patients who met the inclusion criteria. Overall, interstage mortality was 120/1111 (10.8%). Interstage mortality was significantly lower in era 4 relative to era 1 (4.6% versus 13.4%; P=0.02) during the time that age at the superior cavo-pulmonary connection was the lowest (135 days; P<0.01) and the interstage monitoring program was introduced. In addition, use of the right ventricle to pulmonary artery shunt was associated with decreased interstage mortality (P=0.02) and was more routinely practiced in era 4. Conclusions During this 30-year experience, the risk of interstage mortality decreased significantly in the most recent era. Factors that coincide with this finding include younger age at superior cavo-pulmonary connection, introduction of an interstage monitoring program, and increased use of the right ventricle to pulmonary artery shunt.

Bidirectional Glenn Procedure in Patients Less Than 3 Months of Age: A 14-Year Experience.

BACKGROUND: Contradictory data exist regarding timing of stage 2 palliation (S2P). Prolonged interstage hospitalizations and home surveillance programs have contributed to a more rapid progression to S2P. Our goal is to describe the S2P population and explore the relationships of clinical outcomes and S2P timing at our institution over the last 14 years. METHODS: S2P procedures from 2004 to 2018 at a single institution were included in a retrospective analysis. The analysis was stratified by S2P timing and clinical variables. The primary outcome was Fontan completion, and secondary outcomes included mortality and orthotopic heart transplantation rate, as well as perioperative clinical variables. RESULTS: A total of 114 patients who underwent S2P were included. The median age and weight at S2P were 100 days (interquartile range [IQR], 87-119) and 5.1 (IQR, 4.6-5.5) kg, respectively. The median age in the early group was 79 (IQR, 73-87) days and in the nonearly group was 107 (IQR, 100-124) days. Ninety percent of cavopulmonary anastomoses were augmented with an ePTFE (expanded polytetrafluoroethylene) patch. The overall Fontan completion rate was 76%, without differences in Kaplan-Meier estimates. There were no operative mortalities and no differences in late mortality rate (P = .30). CONCLUSIONS: The interstage period continues to be high risk for those undergoing single-ventricle palliation. In our experience, S2P performed at less than 90 days seems to be a viable and safe procedure when indicated, resulting in comparable Fontan completion rates.

Angiotensin-Converting Enzyme Inhibitor Prescription for Patients With Single Ventricle Physiology Enrolled in the NPC-QIC Registry.

Background The routine use of angiotensin-converting enzyme inhibitors (ACEI) during palliation of hypoplastic left heart syndrome is controversial. We sought to describe ACEI prescription in the interstage between stage 1 palliation (stage I Norwood procedure) discharge and stage 2 palliation (stage II superior cavopulmonary anastomosis procedure) admission using the NPC-QIC (National Pediatric Cardiology Quality Improvement Collaborative) registry. Methods and Results Analysis of all patients (n=2180) enrolled in NPC-QIC from 2008 to 2016 included preoperative anatomy, risk factors, and echocardiographic data. ACEI were prescribed at stage I Norwood procedure discharge in 38% of patients. ACEI prescription declined from 2011 to 2016 compared with pre-2010 (36.8% versus 45%; P=0.005) with significant variation across centers (range 7-100%; P<0.001) and decreased prescribing rates associated with increased center volume (P=0.004). There was no difference in interstage mortality (P=0.662), change in atrioventricular valve regurgitation (P=0.101), or change in ventricular dysfunction (P=0.134) between groups. In multivariable analysis of all patients, atrioventricular septal defect (odds ratio [OR], 1.84; 95% CI, 1.28-2.65) or double outlet right ventricle (OR, 1.47; CI, 1.02-2.11), and preoperative mechanical ventilation (OR, 1.37; 95% CI, 1.12-1.68) were associated with increased ACEI prescription. In multivariable analysis of patients with complete echocardiographic data (n=812), ACEI prescription was more common with at least moderate atrioventricular valve regurgitation (OR, 1.88; 95% CI, 1.22-2.31). Conclusions ACEI prescription remains common in the interstage despite limited evidence of benefit. ACEI prescription is associated with preoperative mechanical ventilation, double outlet right ventricle, and atrioventricular valve regurgitation with marked inter-center variation. ACEI prescription is not associated with reduction in mortality, ventricular dysfunction, or atrioventricular valve regurgitation during the interstage.

Improved National Outcomes Achieved in a Cardiac Learning Health Collaborative Based on Early Performance Level.

OBJECTIVE: Within the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC), a learning health network developed to improve outcomes for patients with hypoplastic left heart syndrome and variants, we assessed which centers contributed to reductions in mortality and growth failure. STUDY DESIGN: Centers within the NPC-QIC were divided into tertiles based on early performance for mortality and separately for growth failure. These groups were evaluated for improvement from the early to late time period and compared with the other groups in the late time period. RESULTS: Mortality was 3.8% for the high-performing, 7.6% for the medium-performing, and 14.4% for the low-performing groups in the early time period. Only the low-performing group had a significant change (P < .001) from the early to late period. In the late period, there was no difference in mortality between the high- (5.7%), medium- (7%), and low- (4.6%) performing centers (P = .5). Growth failure occurred in 13.9% for the high-performing, 21.9% for the medium-performing, and 32.8% for the low-performing groups in the early time period. Only the low-performing group had a significant change (P < .001) over time. In the late period, there was no significant difference in growth failure between the high- (19.8%), medium- (21.5%), and low- (13.5%) performing groups (P = .054). CONCLUSIONS: Improvements in the NPC-QIC mortality and growth measures are primarily driven by improvement in those performing the worst in these areas initially without compromising the success of high-performing centers. Focus for improvement may vary by center based on performance.

Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome: A Decision Analysis.

BACKGROUND: Fetal aortic valvuloplasty (FAV) may prevent progression of midgestation aortic stenosis to hypoplastic left heart syndrome. However, FAV has well-established risks, and its survival benefit remains unknown. Our primary aim was to determine whether FAV for midgestation aortic stenosis increases survival from fetal diagnosis to age 6 years. METHODS AND RESULTS: We performed a retrospective analysis of 143 fetuses who underwent FAV from 2000 to 2017 and a secondary analysis of the Pediatric Heart Network Single Ventricle Reconstruction trial. Using these results, we developed a decision model to estimate probability of transplant-free survival from fetal diagnosis to age 6 years and postnatal restricted mean transplant-free survival time. FAV was technically successful in 84% of 143 fetuses with fetal demise in 8%. Biventricular circulation was achieved in 50% of 111 live-born infants with successful FAV but in only 16% of the 19 patients with unsuccessful FAV. The model projected overlapping probabilities of transplant-free survival to age 6 years at 75% (95% CI, 67%-82%) with FAV versus 72% (95% CI, 61%-82%) with expectant fetal management, resulting in a restricted mean transplant-free survival time benefit of 1.2 months. When limiting analyses to the improved FAV experience since 2009 to reflect current practice, (probability of technical success [94%], fetal demise [4%], and biventricular circulation [66%]), the model projected that FAV increased the probability of survival to age 6 years to 82% (95% CI, 73%-89%). Expectant management is favored if risk of fetal demise exceeded 12% or probability of biventricular circulation fell below 26%, but FAV remained favored over plausible recent range of technical success. CONCLUSIONS: Our model suggests that FAV provides a modest, medium-term survival benefit over expectant fetal management. Appropriate patient selection and low risk of fetal demise with FAV are critical factors for obtaining a survival benefit.

Impact of Confounding on Cost, Survival, and Length-of-Stay Outcomes for Neonates with Hypoplastic Left Heart Syndrome Undergoing Stage 1 Palliation Surgery.

The objective of this analysis was to update trends in LOS and costs by survivorship and ECMO use among neonates with hypoplastic left heart syndrome (HLHS) undergoing stage 1 palliation surgery using 2016 data from the Healthcare Cost and Utilization Project Kids' Inpatient Database. We identified neonates ≤ 28 days old with HLHS undergoing Stage 1 surgery, defined as a Norwood procedure with modified Blalock-Taussig (BT) shunt, Sano modification, or both. Multivariable regression with year random effects was used to compare LOS and costs by hospital region, case volume, survivorship, and ECMO vs. no ECMO. An E-value analysis, an approach for conducting sensitivity analysis for unmeasured confounding, was performed to determine if unmeasured confounding contributed to the observed effects. Significant differences in total costs, LOS, and mortality were noted by hospital region, ECMO use, and sub-analyses of case volume. However, other than ECMO use and mortality, the maximum E-value confidence interval bound was 1.71, suggesting that these differences would disappear with an unmeasured confounder 1.71 times more associated with both the outcome and exposure (e.g., socioeconomic factors, environment, etc.) Our findings confirm previous literature demonstrating significant resource utilization among Norwood patients, particularly those undergoing ECMO use. Based on our E-value analysis, differences by hospital region and case volume can be explained by moderate unobserved confounding, rather than a reflection of the quality of care provided. Future analyses on surgical quality must account for unobserved factors to provide meaningful information for quality improvement.

Procedural, pregnancy, and short-term outcomes after fetal aortic valvuloplasty.

OBJECTIVES: We aimed to evaluate the effect of technical aspects of fetal aortic valvuloplasty (FAV) on procedural risks and pregnancy outcomes. BACKGROUND: FAV is performed in cases of severe mid-gestation aortic stenosis with the goal of preventing hypoplastic left heart syndrome (HLHS). METHODS: The International Fetal Cardiac Intervention Registry was queried for fetuses who underwent FAV from 2002 to 2018, excluding one high-volume center. RESULTS: The 108 fetuses had an attempted cardiac puncture (mean gestational age [GA] 26.1 ± 3.3 weeks). 83.3% of attempted interventions were technically successful (increased forward flow/new aortic insufficiency). The interventional cannula was larger than 19 g in 70.4%. More than one cardiac puncture was performed in 25.0%. Intraprocedural complications occurred in 48.1%, including bradycardia (34.1%), pericardial (22.2%) or pleural effusion (2.7%) requiring drainage, and balloon rupture (5.6%). Death within 48 hr occurred in 16.7% of fetuses. Of the 81 patients born alive, 59 were discharged home, 34 of whom had biventricular circulation. More than one cardiac puncture was associated with higher complication rates (p < .001). Larger cannula size was associated with higher pericardial effusion rates (p = .044). On multivariate analysis, technical success (odds ratio [OR] = 10.9, 95% confidence interval [CI] = 2.2-53.5, p = .003) and later GA at intervention (OR = 1.5, 95% CI = 1.2-1.9, p = .002) were associated with increased odds of live birth. CONCLUSIONS: FAV is an often successful but high-risk procedure. Multiple cardiac punctures are associated with increased complication and fetal mortality rates. Later GA at intervention and technical success were independently associated with increased odds of live birth. However, performing the procedure later in gestation may miss the window to prevent progression to HLHS.