Association of patient-level characteristics with long-term outcomes after Fontan palliation: Rationale, design, and baseline characteristics of the Pediatric Cardiac Care Consortium Fontan cohort study.

BACKGROUND: The Fontan operation is used to palliate single ventricle congenital heart defects (CHD) but poses significant morbidity and mortality risks. We present the design, planned analyses, and rationale for a long-term Fontan cohort study aiming to examine the association of patient characteristics at the time of Fontan with post-Fontan morbidity and mortality. METHODS AND RESULTS: We used the Pediatric Cardiac Care Consortium (PCCC), a US-based, multicenter registry of pediatric cardiac surgeries to identify patients who underwent the Fontan procedure for single ventricle CHD between 1 and 21 years of age. The primary outcomes are in-hospital Fontan failure (death or takedown) and post-discharge mortality through 2022. A total of 1461 (males 62.1%) patients met eligibility criteria and were included in the analytical cohort. The median age at Fontan evaluation was 3.1 years (IQR: 2.4-4.3). While 95 patients experienced in-hospital Fontan failure (78 deaths and 17 Fontan takedown), 1366 (93.5%) survived to discharge with Fontan physiology and formed the long-term analysis cohort. Over a median follow-up of 21.2 years (IQR: 18.4-24.5) 184 post-discharge deaths occurred. Thirty-year post Fontan survival was 75.0% (95% CI: 72.3%-77.8%) for all Fontan types with higher rates for current techniques such as lateral tunnel and extracardiac conduit 77.1% (95% CI: 73.5-80.8). CONCLUSION: The PCCC Fontan study aims to identify predictors for post-Fontan morbidity and mortality, enabling risk- stratification and informing surveillance practices. Additionally, the study may guide therapeutic interventions aiming to optimize hemodynamics and enhance Fontan longevity for individual patients.

Long-Term Risk of Heart Failure-Related Death and Heart Transplant After Congenital Heart Surgery in Childhood (from the Pediatric Cardiac Care Consortium).

We aimed to describe the longitudinal risk of advanced heart failure (HF) leading to death, heart transplantation, or ventricular assist device (VAD) placement after congenital heart surgery (CHS) and how it varies across the spectrum of congenital heart disease. We linked the records of patients who underwent first CHS in the Pediatric Cardiac Care Consortium between 1982 and 2003 with the United States National Death Index and Organ Procurement and Transplantation Network databases. Primary outcome was time from CHS discharge to HF-related death, heart transplant, or VAD placement, analyzed with proportional hazards models accounting for competing mortality. In 35,610 patients who survived a first CHS, there were 799 HF deaths, transplants, or VADs over a median of 23 years (interquartile range, 19 to 27). Cumulative incidence at 25 years was 2.3% (95% confidence interval [CI] 2.1% to 2.4%). Compared to mild 2-ventricle defects, the adjusted subhazard ratio for moderate and severe 2-ventricle defects was 3.21 (95% CI 2.28 to 4.52) and 9.46 (95% CI 6.71 to 13.3), respectively, and for single-ventricle defects 31.8 (95% CI 22.2 to 45.6). Systemic right ventricle carried the highest risk 2 years after CHS (subhazard ratio 2.76 [95% CI 2.08 to 3.68]). All groups had higher rates of HF-related death compared with the general population (cause-specific standardized mortality ratio 56.1 [95% CI 51.0 to 61.2]). In conclusion, the risk of advanced HF leading to death, transplantation, or VAD was high across the spectrum of congenital heart disease. While severe defects carry the highest risk, those with mild disease are still at greater risk than the general population.

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.

Using pulse oximetry waveforms to detect coarctation of the aorta.

BACKGROUND: Coarctation of the aorta is a common form of critical congenital heart disease that remains challenging to diagnose prior to clinical deterioration. Despite current screening methods, infants with coarctation may present with life-threatening cardiogenic shock requiring urgent hospitalization and intervention. We sought to improve critical congenital heart disease screening by using a novel pulse oximetry waveform analysis, specifically focused on detection of coarctation of the aorta. METHODS AND RESULTS: Over a 2-year period, we obtained pulse oximetry waveform data on 18 neonates with coarctation of the aorta and 18 age-matched controls hospitalized in the cardiac intensive care unit at Children's Healthcare of Atlanta. Patients with coarctation were receiving prostaglandin E1 and had a patent ductus arteriosus. By analyzing discrete features in the waveforms, we identified statistically significant differences in the maximum rate of fall between patients with and without coarctation. This was accentuated when comparing the difference between the upper and lower extremities, with the lower extremities having a shallow slope angle when a coarctation was present (p-value 0.001). Postoperatively, there were still differences in the maximum rate of fall between the repaired coarctation patients and controls; however, these differences normalized when compared with the same individual's upper vs. lower extremities. Coarctation patients compared to themselves (preoperatively and postoperatively), demonstrated waveform differences between upper and lower extremities that were significantly reduced after successful surgery (p-value 0.028). This screening algorithm had an accuracy of detection of 72% with 0.61 sensitivity and 0.94 specificity. CONCLUSIONS: We were able to identify specific features in pulse oximetry waveforms that were able to accurately identify patients with coarctation and further demonstrated that these changes normalized after surgical repair. Pulse oximetry screening for congenital heart disease in neonates may thus be improved by including waveform analysis, aiming to identify coarctation of the aorta prior to critical illness. Further large-scale testing is required to validate this screening model among patients in a newborn nursery setting who are low risk for having coarctation.

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.

Myocarditis in the pediatric population: A review.

Myocarditis has a variable clinical presentation and there is still debate regarding accurate diagnostic criteria. Adding to the controversy surrounding this diagnosis, there is no clear consensus for the treatment or ongoing follow-up of patients with myocarditis. All of this makes the diagnosis and management of myocarditis a particular challenge in the pediatric population. Furthermore, the literature with respect to this topic is dynamic and ever-changing. In this review article, we aim to review and summarize the common clinical presentations of myocarditis, along with the latest recommendations for diagnostic criteria, treatment, and follow-up of patients with myocarditis.

Lessons learned in the use of clinical registry data in a multi-centre prospective study: the Pediatric Heart Network Residual Lesion Score Study.

BACKGROUND: Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology. OBJECTIVES: We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders' perspectives, and provide recommendations to guide future studies using this methodology. METHODS: The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff. RESULTS: Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes. CONCLUSIONS: Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.

Potential risk factors for Ebstein anomaly, National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Ebstein anomaly is a rare congenital heart defect (CHD) that, when severe, requires corrective surgery or other catheter-based intervention in the first year of life. Due to its rarity, risk factors for Ebstein anomaly remain largely unknown. Using national data, we examined 18 potential risk factors for Ebstein anomaly. METHODS: Using 1997-2011 data from the National Birth Defects Prevention Study, a population-based case-control study, we calculated crude and adjusted odds ratios and 95% confidence intervals for paternal age, maternal socio-demographics, reproductive history, and modifiable risk factors, and infant characteristics reported by mothers of 135 Ebstein anomaly cases and 11,829 controls. RESULTS: Mothers of Ebstein anomaly cases had 4.1 (95% confidence interval: 1.8, 9.5) times the odds of reporting a family history of CHD compared with mothers of controls. Ebstein anomaly was associated with maternal second-hand cigarette smoke exposure at home (odds ratio = 2.2 [95% confidence interval: 1.1, 4.4]), but not maternal cigarette smoking (odds ratio = 1.3 [95% confidence interval: 0.8, 2.1]). Odds were elevated, but the 95% confidence interval included 1.0, for maternal marijuana use (odds ratio = 1.8 [95% confidence interval: 0.9, 3.8]) and paternal age ≥40 years at delivery (odds ratio = 1.9 [95% confidence interval: 1.0, 3.5]). CONCLUSIONS: Maternal exposure to second-hand cigarette smoke at home and a family history of CHD were associated with elevated odds of Ebstein anomaly. Genetic analyses could clarify the potential heritability of Ebstein anomaly.

Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births.

IMPORTANCE: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. EXPOSURES: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. MAIN OUTCOMES AND MEASURES: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. RESULTS: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. CONCLUSIONS AND RELEVANCE: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.

Readmission After Pediatric Cardiothoracic Surgery: An Analysis of The Society of Thoracic Surgeons Database.

BACKGROUND: Hospital readmission after pediatric cardiac surgery is incompletely understood. This study analyzed data from The Society of Thoracic Surgeons Congenital Heart Surgery Database to determine prevalence, to describe patient characteristics, and to evaluate risk factors for readmission. METHODS: Readmission was defined by the "readmission within 30 days after discharge" field. Routine variables were summarized. Regression analysis was used to identify factors associated with readmission. RESULTS: The study cohort included 56,429 patient records from 100 centers. Overall, 6,208 (11%) patients were readmitted. The most common reasons for readmission were respiratory or airway complications (14.2%), septic or infectious complications (11.4%), and reasons not related to the preceding surgical procedure (20.2%). Primary reason for readmission varied across benchmark operation groups. In multivariable analysis, factors associated with increased odds of readmission included the presence of noncardiac abnormalities (odds ratio [OR], 1.24), chromosomal abnormalities or genetic syndromes (OR, 1.24), preoperative mechanical circulatory support (OR, 1.36), other preoperative factors (OR, 1.21), prior cardiac surgery (OR, 1.31), Hispanic ethnicity (OR, 1.13), higher STAT procedural complexity (Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery) (STAT level 3 vs 1, OR, 1.22; STAT 4 vs 1, OR, 1.48; STAT 5 vs 1, OR, 2.62), prolonged postoperative length of stay (OR, 1.07 per day from 0 to 14 days; OR, 1.01 per week >14 days), any major complication (OR, 1.27), any other postoperative complications (OR, 2.00), and discharge on a weekday (OR, 1.07). CONCLUSIONS: Readmission is common after congenital heart surgery, mostly for noncardiovascular reasons. Process improvement initiatives targeted at high-risk patients could minimize its impact.

Long-term outcomes after intervention for pulmonary atresia with intact ventricular septum.

OBJECTIVE: Pulmonary atresia with intact ventricular septum (PA/IVS) can be treated by various operative and catheter-based interventions. We aim to understand the long-term transplant-free survival of patients with PA/IVS by treatment strategy. METHODS: Cohort study from the Pediatric Cardiac Care Consortium, a multi-institutional registry with prospectively acquired outcome data after linkage with the National Death Index and the Organ Procurement and Transplantation Network. RESULTS: Eligible patients underwent neonatal surgery or catheter-based intervention for PA/IVS between 1982 and 2003 (median follow-up of 16.7 years, IQR: 12.6-22.7). Over the study period, 616 patients with PA/IVS underwent one of three initial interventions: aortopulmonary shunt, right ventricular decompression or both. Risk factors for death at initial intervention included earlier birth era (1982-1992), chromosomal abnormality and atresia of one or both coronary ostia. Among survivors of neonatal hospitalisation (n=491), there were 99 deaths (4 post-transplant) and 10 transplants (median age of death or transplant 0.7 years, IQR: 0.3-1.8 years). Definite repair or last-stage palliation was achieved in the form of completed two-ventricle repair (n=201), one-and-a-half ventricle (n=39) or Fontan (n=96). Overall 20-year survival was 66%, but for patients discharged alive after definitive repair, it reached 97.6% for single-ventricle patients, 90.9% for those with one-and-a-half ventricle and 98.0% for those with complete two-ventricle repair (log-rank p=0.052). CONCLUSIONS: Transplant-free survival in PA/IVS is poor due to significant infantile and interstage mortality. Survival into early adulthood is excellent for patients reaching completion of their intended path independent of type of repair.

Long-term Outcomes of Tetralogy of Fallot: A Study From the Pediatric Cardiac Care Consortium.

Importance: Tetralogy of Fallot (TOF) is a surgically repairable form of cyanotic congenital heart disease. Multicenter data for long-term survival following repair are sparse. Objective: To evaluate the long-term transplant-free survival of TOF by surgical strategy adjusted for era and patient characteristics. Design, Setting, and Participants: Retrospective cohort study enriched with data from the National Death Index and the Organ Procurement and Transplantation Network through 2014. Multicenter cohort from the Pediatric Cardiac Care Consortium (PCCC), a large, US-based clinical registry for interventions for congenital heart disease. The cohort included patients with adequate identifiers for linkage with the National Death Index and the Organ Procurement and Transplantation Network who were enrolled in the PCCC registry between 1982 and 2003 and survived surgical repair of simple TOF. Data were analyzed between September 2015 and April 2018. Exposures: We examined patient-associated and surgery-associated risk factors affecting survival. Main Outcomes and Measures: We analyzed the transplant-free survival during early (<6 years) and late (≥6 years) phase after TOF surgical repair. Results: Of the 3283 patients who survived repair for simple TOF and met the study's inclusion criteria, 56.4% were male and 43.6% were female. Twenty-five-year survival following TOF repair was 94.5%. Multivariable analysis demonstrated increased risk of early mortality with staged repair (HR, 2.68; 95% CI, 1.59-4.49) and non-valve-sparing operation (HR, 3.76; 95% CI, 1.53-9.19). Presence of a genetic abnormality was associated with increased risk of death both in the early (HR, 3.64; 95% CI, 2.05-6.47) and late postoperative phase (HR, 4.41; 95% CI, 2.62-7.44). Conclusions and Relevance: Long-term survival after simple TOF repair is excellent. Staged repair and non-valve-sparing operations were negatively associated with survival in the early postrepair phase but not the late postrepair phase. These data are important for patients with repaired TOF and their caretakers and may guide surgical strategies for optimizing the long-term outcomes of this population.

Mortality Following Pediatric Congenital Heart Surgery: An Analysis of the Causes of Death Derived From the National Death Index.

Background Prior research has focused on early outcomes after congenital heart surgery, but less is known about later risks. We aimed to determine the late causes of death among children (<21 years of age) surviving their initial congenital heart surgery. Methods and Results This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a US-based registry of interventions for congenital heart defects (CHD). Excluding patients with chromosomal anomalies or inadequate identifiers, we matched those surviving their first congenital heart surgery (1982-2003) against the National Death Index through 2014. Causes of death were obtained from the National Death Index to calculate cause-specific standardized mortality ratios (SMRs). Among 31 132 patients, 2527 deaths (8.1%) occurred over a median follow-up period of 18 years. Causes of death varied by time after surgery and severity of CHD but, overall, 69.9% of deaths were attributed to the CHD or another cardiovascular disorder, with a SMR for CHD/cardiovascular disorder of 67.7 (95% confidence interval: 64.5-70.8). Adjusted odds ratios revealed increased risk of death from CHD/cardiovascular disorder in females [odds ratio=1.28; 95% confidence interval (1.04-1.58); P=0.018] with leading cardiovascular disorder contributing to death being cardiac arrest (16.8%), heart failure (14.8%), and arrhythmias (9.1%). Other major causes of death included coexisting congenital malformations (4.7%, SMR: 7.0), respiratory diseases (3.6%, SMR: 8.2), infections (3.4%, SMR: 8.2), and neoplasms (2.1%, SMR: 1.9). Conclusions Survivors of congenital heart surgery face long-term risks of premature mortality mostly related to residual CHD pathology, heart failure, and arrhythmias, but also to other noncardiac conditions. Ongoing monitoring is warranted to identify target factors to address residual morbidities and improve long-term outcomes.

Long-Term Survival After Arterial Versus Atrial Switch in d-Transposition of the Great Arteries.

BACKGROUND: The arterial switch operation (ASO) became the procedure of choice for dextro-transposition of the great arteries (d-TGA) nearly 30 years ago, but the long-term results of this operation are unknown. We aimed to compare the long-term transplant-free survival of patients with d-TGA who underwent ASO versus atrial switch in the Pediatric Cardiac Care Consortium. METHODS: We performed a retrospective cohort study of d-TGA patients undergoing ASO or atrial switch in the United States between 1982 and 1991. Long-term transplant-free survival was obtained by linking Pediatric Cardiac Care Consortium data with the National Death Index and the Organ Procurement and Transplant Network. Kaplan-Meier survival plots were constructed, and multivariable regression was used to compare long-term transplant-free survival. RESULTS: Of 554 d-TGA patients who underwent ASO (n = 259) or atrial switch (n = 295), the 20-year overall transplant-free survival was 82.1% for those undergoing ASO and 76.3% for those who had atrial switch procedure. Adjusted overall transplant-free survival beyond 10 years after operation was superior for ASO compared with atrial switch (hazard ratio 0.07, 95% confidence interval: 0.01 to 0.52, p = 0.009). During this period, the ASO had higher in-hospital mortality than the atrial switch (21.6% versus 12.9%, p = 0.007). After excluding patients with in-hospital mortality, the transplant-free survival 20 years after repair was 97.7% for the ASO patients versus 86.3% for the atrial switch patients. CONCLUSIONS: Despite initial higher in-hospital mortality for ASO during the study period, there is a significant long-term transplant-free survival advantage for ASO as compared with atrial switch for d-TGA surgery. Ongoing monitoring is required to assess late risk of cardiovascular disease.

Trends in Long-Term Mortality After Congenital Heart Surgery.

BACKGROUND: Congenital heart surgery has improved the survival of patients with even the most complex defects, but the long-term survival after these procedures has not been fully described. OBJECTIVES: The purpose of this study was to evaluate the long-term survival of patients (age <21 years) who were operated on for congenital heart defects (CHDs). METHODS: This study used the Pediatric Cardiac Care Consortium data, a U.S.-based, multicenter registry of pediatric cardiac surgery. Survival analysis included 35,998 patients who survived their first congenital heart surgery at <21 years of age and had adequate identifiers for linkage with the National Death Index through 2014. Survival was compared to that in the general population using standardized mortality ratios (SMRs). RESULTS: After a median follow-up of 18 years (645,806 person-years), 3,191 deaths occurred with an overall SMR of 8.3 (95% confidence interval [CI]: 8.0 to 8.7). The 15-year SMR decreased from 12.7 (95% CI: 11.9 to 13.6) in the early era (1982 to 1992) to 10.0 (95% CI: 9.3 to 10.8) in the late era (1998 to 2003). The SMR remained elevated even for mild forms of CHD such as patent ductus arteriosus (SMR 4.5) and atrial septal defects (SMR 4.9). The largest decreases in SMR occurred for patients with transposition of great arteries (early: 11.0 vs. late: 3.8; p < 0.05), complete atrioventricular canal (31.3 vs. 15.3; p < 0.05), and single ventricle (53.7 vs. 31.3; p < 0.05). CONCLUSIONS: In this large U.S. cohort, long-term mortality after congenital heart surgery was elevated across all forms of CHD. Survival has improved over time, particularly for severe defects with significant changes in their management strategy, but still lags behind the general population.

Genetic and Extracardiac Anomalies Are Associated With Inferior Single Ventricle Palliation Outcomes.

BACKGROUND: We examined the effect of genetic syndromes and extracardiac (GS/EC) anomalies on single-ventricle (SV) palliation with focus on hospital and interstage death and progression toward subsequent palliation stages. METHODS: First-stage palliation was performed in 530 neonates with SV: Norwood in 284 (53%), shunt in 173 (33%), and band in 73 (14%). Outcomes were compared between those with GS/EC anomalies (121 [23%]) and without GS/EC anomalies (409 [77%]). Regression analyses were adjusted for other risk factors (age, sex, prematurity, weight, SV anomaly, and first-stage palliation operation). RESULTS: GS/EC anomalies varied among SV defects (range, 3% for double-inlet left ventricle to 100% for atrial isomerism). Patients with GS/EC anomalies required significantly longer durations of mechanical ventilation and intensive care unit and hospital stay. Although patients had comparable rates of extracorporeal membrane oxygenation (13% vs 11%, p = 0.552) and unplanned reoperation (16% vs 11%, p = 0.189), hospital mortality was higher in patients with GS/EC anomalies (24% vs 12%, p = 0.0008). After discharge, patients with GS/EC anomalies had higher interstage death, with lower progression to Glenn (60% vs 77%, p = 0.002) and lower 10-year survival (56% vs 76%, p < 0.001). After adjustment for other risk factors, GS/EC anomalies significantly affected survival in almost all subgroups of patients. CONCLUSIONS: The presence of GS/EC anomalies varies among SV anomalies and is associated with additional risk factors such as prematurity and low weight. After adjusting for other risk factors, GS/EC anomalies are associated with prolonged recovery after first-stage palliation and increased hospital and interstage death, with subsequently fewer patients progressing toward Glenn shunt. The increased death risk in those patients is highest in the first 6 months and persists for 2 to 3 years after first-stage palliation, suggesting the need for more vigilant monitoring and outpatient care in these high-risk patients.

Association of Preoperative Cell Counts With Outcomes After Operation for Congenital Heart Disease.

BACKGROUND: We examined the association of preoperative cell count abnormalities, which have been shown to be associated with outcomes in adult cardiac patients, with morbidity and mortality after operation for congenital heart disease (CHD) in children. METHODS: We performed a retrospective cohort study on 4,865 children undergoing cardiac operation from 2004 to 2014. Our exposures of interest were presence of preoperative lymphopenia (lymphocyte count ≤ 3,000 cells/µL), thrombocytopenia (platelet count < 150 × 103/µL), and neutrophilia (neutrophil count ≥ 7,000 cells/µL). Our outcomes of interest were mortality status, postoperative length of stay (LOS), and occurrence of postoperative complications. We performed logistic and linear regressions to determine the associations of preoperative cell counts with mortality, LOS, and complications, adjusting for age, sex, race or ethnicity, presence of a genetic syndrome, and Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality category. RESULTS: Overall mortality was 2.8%, median LOS was 6 days, and 7.6% of patients had postoperative complications. Lymphopenia was associated with increased odds of postoperative mortality (odds ratio 1.67, 95% confidence interval: 1.15 to 2.43, p = 0.007). Lymphopenia, thrombocytopenia, and neutrophilia were all associated with longer postoperative LOS. Lymphopenia and thrombocytopenia were associated with increased occurrence of postoperative sepsis, and neutrophilia was associated with need for postoperative mechanical circulatory support. CONCLUSIONS: In children undergoing CHD operation, preoperative lymphopenia is associated with increased in-hospital mortality postoperatively. Preoperative lymphopenia, neutrophilia, and thrombocytopenia are associated with longer postoperative LOS and with development of postoperative complications. Preoperative cell counts may serve as important prognostic markers in preoperative planning for patients with CHD.

Long-Term Transplant-Free Survival After Repair of Total Anomalous Pulmonary Venous Connection.

BACKGROUND: Long-term survival, risk of transplantation, and causes of death after repair of total anomalous pulmonary venous connection (TAPVC) remain unknown. By linking the Pediatric Cardiac Care Consortium with the National Death Index and the United Network for Organ Sharing, we evaluated long-term transplant-free survival in children undergoing repair of TAPVC. METHODS: We identified 777 infants within the Pediatric Cardiac Care Consortium who underwent TAPVC repair (median 21 days; interquartile range, 5 to 80) and had sufficient personal identifiers for linkage with the National Death Index and United Network for Organ Sharing. Sixty-six deaths, ten cardiac transplantations, and one bilateral lung transplantation had occurred by the end of 2014. Data collected included age and weight at time of procedure, TAPVC type, associated cardiac lesions, and postoperative length of stay. The study cohort was divided into simple and complex TAPVC based on the presence of an associated cardiac lesion. Parametric survival plots were constructed, and risk factor analyses were performed to identify demographic and clinical characteristics associated with long-term outcomes. RESULTS: Mortality or need for transplantation was 9.7% with a median follow-up of 18.4 years and a median age of death or transplant of 0.74 years. The risk of mortality and transplant after TAPVC repair was highest during the first 18 months after hospital discharge. Cardiac causes accounted for the majority of deaths. Multivariate regression models for transplant-free survival demonstrated that complex TAPVC, mixed TAPVC, and postoperative length of stay were associated with increased risk of death/transplant. CONCLUSIONS: Transplant-free survival after TAPVC repair is excellent, with most deaths or transplant events occurring early. Factors associated with the worst long-term outcomes included complex TAPVC, mixed TAPVC, and prolonged postoperative length of stay.

Development and impact of arrhythmias after the Norwood procedure: A report from the Pediatric Heart Network.

OBJECTIVES: The study objective was to determine the predictors of new-onset arrhythmia among infants with single-ventricle anomalies during the post-Norwood hospitalization and the association of those arrhythmias with postoperative outcomes (ventilator time and length of stay) and interstage mortality. METHODS: After excluding patients with preoperative arrhythmias, we used data from the Pediatric Heart Network Single Ventricle Reconstruction Trial to identify risk factors for tachyarrhythmias (atrial fibrillation, atrial flutter, supraventricular tachycardia, junctional ectopic tachycardia, and ventricular tachycardia) and atrioventricular block (second or third degree) among 544 eligible patients. We then determined the association of arrhythmia with outcomes during the post-Norwood hospitalization and interstage period, adjusting for identified risk factors and previously published factors. RESULTS: Tachyarrhythmias were noted in 20% of subjects, and atrioventricular block was noted in 4% of subjects. Potentially significant risk factors for tachyarrhythmia included the presence of modified Blalock-Taussig shunt (P = .08) and age at Norwood (P = .07, with risk decreasing each day at age 8-20 days); the only significant risk factor for atrioventricular block was undergoing a concomitant procedure at the time of the Norwood (P = .001), with the greatest risk being in those undergoing a tricuspid valve procedure. Both tachyarrhythmias and atrioventricular block were associated with longer ventilation time and length of stay (P < .001 for all analyses). Tachyarrhythmias were not associated with interstage mortality; atrioventricular block was associated with mortality among those without a pacemaker in the unadjusted analysis (hazard ratio, 2.3; P = .02), but not after adding covariates. CONCLUSIONS: Tachyarrhythmias are common after the Norwood procedure, but atrioventricular block may portend a greater risk for interstage mortality.