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 Outcomes After Interrupted Aortic Arch Repair.

BACKGROUND: Interrupted aortic arch (IAA) is associated with left ventricular outflow tract obstruction (LVOTO) and DiGeorge syndrome. High-risk infantile surgery is required to address IAA, with limited data available on long-term outcomes. We used the Pediatric Cardiac Care Consortium, a multicenter US-based registry for pediatric cardiac interventions, to assess long-term outcomes after IAA repair by patient characteristics and surgical approach. METHODS: This is a retrospective cohort study of patients undergoing IAA repair between 1982 and 2003. Kaplan-Meier plots and Cox proportional hazards regression were used to examine associations with postdischarge deaths tracked by matching with the US National Death Index. RESULTS: Of 390 patients meeting inclusion criteria, 309 (79.2%) survived to discharge. During a median follow-up of 23.6 years, 30-year survival reached 80.7% for patients surviving hospital discharge after initial IAA repair. Adjusted analysis revealed higher risk of death for type B vs type A (adjusted hazard ratio [aHR], 3.32; 95% CI, 1.48-7.44), staged repair (aHR, 2.50; 95% CI, 1.14-5.50), and LVOTO interventions during initial hospitalization (aHR, 4.12; 95% CI, 1.83-9.27) but not for LVOTO without need for interventions or presence of DiGeorge syndrome. There was a trend toward improved in-hospital and long-term survival over time during the study period. CONCLUSIONS: Staged repair, type B IAA, and need for LVOTO intervention during initial hospitalization for repair are associated with high risk of death out to 30 years. Survival outcomes are improving, but further efforts need to minimize staged approach and risks associated with LVOTO relief procedures.

Long-term Outcomes After Surgical Intervention for Congenital Supravalvar Aortic Stenosis in Children.

BACKGROUND: Primary supravalvar aortic stenosis (SVAS) is a rare congenital cardiovascular condition that can coexist with Williams-Beuren syndrome, coronary artery involvement, aortic coarctation, and pulmonary artery stenosis. SVAS repair can be achieved with low perioperative mortality, but long-term survival remains less well understood. We used the Pediatric Cardiac Care Consortium, a multicenter United States-based registry for pediatric cardiac operations, to assess long-term outcomes after SVAS repair. METHODS: We used Kaplan-Meier plots and Cox proportional hazards regression to examine factors associated with postdischarge deaths. These included sex, age-group, weight z-score, coexisting conditions (Williams-Beuren syndrome, coronary artery involvement, coarctation, and pulmonary artery stenosis), surgical techniques, and era, defined as early (1982-1995) or late (1996-2003). Survival was assessed by matching with the National Death Index through 2021. RESULTS: Of 333 patients who met inclusion criteria, 313 (94.0%) survived to discharge and 188 (60.1%) had identifiers for National Death Index matching. Over a median follow-up of 25.2 years (interquartile range, 21.1-29.4 years), 17 deaths occurred. The 30-year survival after discharge from SVAS repair was 88.7% (95% CI, 82.9%-94.8%). Infantile surgery and non-Williams-Beuren syndrome were associated with decreased 30-year survival. From the various repairs, the 2-sinus technique had better outcomes compared with all other types, except the 3-sinus technique (nonsignificant difference). Adjusted analysis revealed infantile age and type of repair as associated with postdischarge probability of death. CONCLUSIONS: These data demonstrate favorable long-term outcomes after SVAS repair, except for the infantile group that was associated with more diffuse arteriopathy. As techniques continue to evolve, future studies are warranted to investigate their long-term outcomes.

Survival After Single-Stage Repair of Truncus Arteriosus and Associated Defects.

BACKGROUND: The goal of this study was to describe in-hospital and long-term mortality after single-stage repair of truncus arteriosus communis (TAC) and explore factors associated with these outcomes. METHODS: This was a cohort study of consecutive patients undergoing single-stage TAC repair between 1982 and 2011 reported to the Pediatric Cardiac Care Consortium registry. In-hospital mortality was obtained for the entire cohort from registry records. Long-term mortality was obtained for patients with available identifiers by matching with the National Death Index through 2020. Kaplan-Meier survival estimates were created for up to 30 years after discharge. Cox regression models estimated hazard ratios for the associations with potential risk factors. RESULTS: A total of 647 patients (51% male) underwent single-stage TAC repair at a median age of 18 days; 53% had type I TAC, 13% had interrupted aortic arch, and 10% underwent concomitant truncal valve surgery. Of these, 486 (75%) patients survived to hospital discharge. After discharge, 215 patients had identifiers for tracking long-term outcomes; 30-year survival was 78%. Concomitant truncal valve surgery at the index procedure was associated with increased in-hospital and 30-year mortality. Concomitant interrupted aortic arch repair was not associated with increased in-hospital or 30-year mortality. CONCLUSIONS: Concomitant truncal valve surgery but not interrupted aortic arch was associated with higher in-hospital and long-term mortality. Careful consideration of the need and timing for truncal valve intervention may improve TAC outcomes.

Procedure-Specific Center Volume and Mortality After Infantile Congenital Heart Surgery.

BACKGROUND: Regionalization of congenital heart surgery (CHS) has been proposed to improve postsurgical outcomes by increasing experience in the care of high-risk patients. We sought to determine whether procedure-specific center volume was associated with mortality after infantile CHS up to 3 years post-procedure. METHODS: We analyzed data from 12,263 infants in the Pediatric Cardiac Care Consortium undergoing CHS between 1982 and 2003 at 46 centers within the United States. We used logistic regression to assess the association between procedure-specific center volume and mortality from discharge to 3 years post-procedure, accounting for clustering at the center level and adjusting for patient age and weight at surgery, chromosomal abnormality, and surgical era. RESULTS: We found decreased odds for in-hospital mortality for Norwood procedures (odds ratio [OR] 0.955, 95% CI 0.935-0.976), arterial switch operations (OR 0.924, 95% CI 0.889-0.961), tetralogy of Fallot repairs (OR 0.975, 95% CI 0.956-0.995), Glenn shunts (OR 0.971, 95% CI 0.943-1.000), and ventricular septal defect closures (OR 0.974, 95% CI 0.964-0.985). The association persisted up to 3 years post-surgery for Norwood procedures (OR 0.971, 95% CI 0.955-0.988), arterial switches (OR 0.929, 95% CI 0.890-0.970), and ventricular septal defect closures (OR 0.986, 95% CI 0.977-0.995); however, after excluding deaths that occurred within the first 90 days of following surgery, we observed no association between center volume and mortality for any of the procedures studied. CONCLUSIONS: These findings suggest that procedure-specific center volume is inversely associated with early postoperative mortality for infantile CHS across the complexity spectrum but has no measurable effect on later mortality.

Thirty-Year Survival After Cardiac Surgery in Children With Williams-Beuren Syndrome (from the Pediatric Cardiac Care Consortium Study).

Williams-Beuren syndrome (WBS) is a genetic condition frequently requiring interventions for associated congenital heart disease (CHD). Long-term survival data after cardiac interventions for children with WBS are sparse. This is a retrospective cohort study aiming to describe the 30-year survival outcomes of children with WBS after interventions for CHD using the Pediatric Cardiac Care Consortium (PCCC), a large North American-based registry of interventions for pediatric heart diseases, between 1982 and 2009. Outcomes were obtained from the PCCC and by linkage with the National Death Index through 2020. Survival of patients with WBS and their major subgroups was assessed by Kaplan-Meier survival curves and Cox regression. A total of 200 patients met the inclusion criteria of having their first intervention for CHD at a US PCCC center and age <21 years at time of intervention. The most common lesions were left heart obstructive lesions (LHOL), either in isolation (37%) or in combination with right heart obstructive lesions (RHOL) (49.0%), whereas isolated RHOL accounted for 11% of the total. The first procedure was surgery for 85.5% of the group, and the remainder underwent a transcatheter procedure. There were 5 in-hospital deaths (2.5%), and among survivors to hospital discharge, 164 had sufficient identifiers for National Death Index linkage. Over a median period of postdischarge follow-up of 23.7 years (interquartile range 18.7 to 27.3), 16 deaths occurred, with an overall 30-year survival rate of 90%. Survival rates ranged from 96.1% for isolated LHOL or RHOL to 83.4% for patients with combined disease (adjusted hazard ratio 4.7, 95% confidence intervals 1.35 to 16.59).

Long-Term Outcomes of Cardiovascular Operations in Children With Connective Tissue Disorders.

Connective tissue disorders can be associated with significant cardiovascular morbidity needing cardiac surgery during childhood. In this retrospective study, we used the Pediatric Cardiac Care Consortium, a multicenter United States-based registry of pediatric cardiac interventions, to describe the long-term outcomes of patients who underwent their first surgery for connective tissue-related cardiovascular conditions aged <21 years. Between 1982 and 2003, a total of 103 patients were enrolled who underwent cardiac surgery for a connective tissue-related cardiovascular disorder, including 3 severe infantile cases operated on within the first year of life. Most patients underwent aortic site surgery (n = 85) as a composite graft (n = 50), valve-sparing (n = 33), or other aortic surgery (n = 2). The remaining patients underwent atrioventricular valve surgery (mitral 17, tricuspid 1). Of the 99 patients surviving to discharge, 80 (including the 3 infantile) had adequate identifiers for tracking long-term outcomes through 2019 through linkage with the National Death Index and the Organ Procurement. Over a median period of 19.5 years (interquartile range 16.0 to 23.1), 29 deaths and 1 transplant occurred in the noninfantile group, whereas all 3 infantile patients died before the age of 4 years. The postdischarge survival for the noninfantile group was 92.2%, 68.2%, and 56.7% at 10, 20, and 25 years, respectively. Cardiovascular-related pathology contributed to all deaths in the infantile and 89% (n = 27) of deaths for the noninfantile cases after hospital discharge. The significant late attrition from cardiovascular causes emphasizes the need for close monitoring and ongoing management in this population.

Outcomes Following Aortic Valve Replacement in Children With Conotruncal Anomalies.

OBJECTIVE: Conotruncal anomalies can develop aortopathy and/or aortic valve (AV) disease and AV replacement (AVR) is occasionally needed. We report long-term results and examine factors affecting survival following AVR in this group. METHODS: We queried the Pediatric Cardiac Care Consortium (PCCC, US database for interventions for congenital heart diseases) to identify patients with repaired conotruncal anomalies and AVR. Long-term outcomes were provided by the PCCC, the US National Death Index, and Organ Procurement and Transplantation Network. Competing risks analysis examined outcomes following AVR (death/transplantation, reoperation) and multivariable regression analysis assessed significant factors. RESULTS: One hundred six children with repaired conotruncal anomalies underwent AVR (1982-2003). Underlying anomaly was truncus (n = 40), d-transposition (n = 22), type-B interrupted arch (n = 16), double-outlet right ventricle (n = 12), pulmonary atresia with ventricular septal defect (n = 9), tetralogy of Fallot (n = 6), corrected transposition (n = 1). 18 (17%) had prior aortic valvuloplasty (surgical = 12, percutaneous = 6). Median age at AVR was 6.9 years (interquartile range = 2.5-12.4). AV pathophysiology was regurgitation (n = 83, 78%), stenosis (n = 9, 9%), and mixed (n = 14, 15%). AVR type was mechanical (n = 72, 68%), homograft (n = 21, 20%), and Ross (n = 13, 12%). Operative mortality was 13(12%). Infant age at AVR was risk factor (odds ratio = 55, 95% confidence interval [CI] = 6-539, P = .0006). On competing risks analysis, five years after AVR, 6% died or received transplantation, 20% had reoperation. Twenty-five years transplant-free survival was 53%. Factors associated with death after hospital discharge included mitral surgery (hazards ratio [HR] = 11, 95% CI = 3-39, P = .0002), underlying defect (HR = 2, 95% CI = 1-5, P = .446). Twenty years transplant-free survival in conotruncal anomalies group was inferior to matched children undergoing AVR for congenital non-conotruncal disease (61% vs 82%, P = .0012). CONCLUSIONS: Long-term survival following AVR in children with conotruncal anomalies is inferior to that of isolated congenital AV disease and is linked to an underlying cardiac defect. Although valve type was not associated with survival, infant age was a risk factor for operative mortality. Continuous attrition and high reoperation warrant vigilant monitoring.

Long-term outcomes after repair for anomalous right coronary artery from the pulmonary artery.

Anomalous right coronary artery from pulmonary artery (ARCAPA) is a rare congenital heart disease that can lead to abnormal coronary perfusion and a need for surgical repair. Here, we report the outcomes of patients who underwent ARCAPA surgery within the Pediatric Cardiac Care Consortium (PCCC), a North American registry of interventions for paediatric heart diseases. We queried the PCCC for patients undergoing surgical repair for ARCAPA at <18 years of age between 1982 and 2003. Outcomes were obtained from the PCCC and after linkage with the National Death Index (NDI) and the Organ Procurement and Transplantation Network (OPTN) through 2019. Twenty-four patients (males: 15) were identified having surgery for ARCAPA at a median age of 5.8 (IQR 2.7-10.3) years. Of them, 23 cases were considered "simple" (without major intracardiac disease) and one "complex" (co-existing with tetralogy of Fallot). Five patients presented with symptoms [chest pain (1), dyspnoea on exertion (2) or history of syncope (2)]; while the remaining 19 patients were referred for evaluation of either murmur or co-existing CHD. There was no in-hospital mortality after the surgical repair. Fourteen patients had sufficient identifiers for NDI/OPTN linkage; among them, only one death occurred from unrelated non-cardiac causes within a median period of 19.4 years of follow-up (IQR: 18-24.6). Outcomes were excellent after reimplantation up to 25 years later and further longitudinal monitoring is important to understand the interaction of pre-existing coronary pathology with the effects of ageing.

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.

Are Mechanical Prostheses Valid Alternatives to the Ross Procedure in Young Children Under 6 Years Old?

BACKGROUND: Aortic valve replacement in young children is associated with technical difficulties and potential morbidity. In contrast to the versatile Ross operation, mechanical prostheses (MP) are uncommonly used. METHODS: We examined transplant-free survival and cardiac reoperation among 124 young children (aged 1-6 years) who underwent the Ross operation (n = 84) or MP (n = 40) for congenital disease (1982-2003) using the Pediatric Cardiac Care Consortium database. We explored variables influencing outcomes. RESULTS: Children who received MP were operated in an earlier era and were more likely to have aortic regurgitation, conotruncal abnormalities, prior aortic valve surgery, and to need Konno annular enlargement. Although no significant differences were found in hospital mortality (1.2% vs 5.0%, P = .24) or 15-year transplant-free survival (94.1% vs 87.5%, P = .16) between Ross and MP recipients, survival diverged with later follow-up (91.3% vs 68.9%, respectively, at 25 years; P = .01). On multivariable regression analysis the association of MP use and transplant-free survival changed over time (hazard ratios, 0.8 [95% confidence interval, 0.1-4.4; P = .78] vs 6.0 [95% confidence interval, 0.6-63.1; P = .13], respectively) before and after 17 years. Cumulative incidence of cardiac reoperation at 10 years was 37.7% and 53.6% after the Ross procedure and MP, respectively (P = .05). The most common reoperation after the Ross procedure was conduit replacement and pacemaker ± automated internal cardiac defibrillator and after MP was pacemaker ± automated internal cardiac defibrillator and redo aortic valve replacement. CONCLUSIONS: Over the study period there was a trend for increased Ross utilization. Interestingly MP use was associated with comparable operative mortality and survival up to 17 years, albeit with higher need for redo aortic valve replacement. On longer follow-up survival diverged with increased attrition in the MP group, likely because of late valve- and reoperation-related complications.

Long-term Outcomes of Children Operated on for Anomalous Left Coronary Artery From the Pulmonary Artery.

BACKGROUND: We examined the outcomes of children (<18 years) operated on for anomalous left coronary artery from the pulmonary artery (ALCAPA). METHODS: We linked patients undergoing ALCAPA repair between 1982 and 2003 in the Pediatric Cardiac Care Consortium with the National Death Index and the Organ Procurement and Transplantation Network to examine their outcomes through 2019. RESULTS: We identified 228 children (median age, 6.0 months) operated on for ALCAPA. At the time of repair, 38.6% had severe mitral regurgitation (MR), and 71.4% had severe left ventricular (LV) dysfunction. Repair included primarily coronary reimplantation in 173 and the Takeuchi procedure in 34; concurrently, 18 underwent mitral valve (MV) operation. In-hospital death occurred in 31 (13.6%) and was not associated with MR severity (P = .846); however, among patients with moderate or severe MR, risk of death was 28% lower when undergoing MV operation (P = .033). After adjustment for other risk factors, only infant operation reached statistical significance for in-hospital death (adjusted odds ratio, 12.99; 95% CI, 1.61-104.59; P = .016). Among those discharged alive with long-term data available (n = 155), the 30-year transplant-free survival reached 95.5% (95% CI, 92.3%-98.8%) and was not associated with the degree of preoperative MR or LV dysfunction. Coronary reimplantation was associated with better long-term survival compared with other surgical techniques (adjusted odds ratio, 0.11; 95% CI, 0.02-0.74; P = .023). CONCLUSIONS: Favorable long-term outcomes can be expected after coronary artery reimplantation for ALCAPA, even in patients with severe LV dysfunction at presentation. MV operation predicted decreased risk for in-hospital mortality in patients with moderate/severe MR, but MR severity predicted neither in-hospital nor longer-term outcomes.

Common deletion variants causing protocadherin-α deficiency contribute to the complex genetics of BAV and left-sided congenital heart disease.

Bicuspid aortic valve (BAV) with ~1%-2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA). Mouse and human studies indicate LVOTO is genetically heterogeneous with a complex genetic etiology. Homozygous mutation in the Pcdha protocadherin gene cluster in mice can cause BAV, and also HLHS and other LVOTO phenotypes when accompanied by a second mutation. Here we show two common deletion copy number variants (delCNVs) within the PCDHA gene cluster are associated with LVOTO. Analysis of 1,218 white individuals with LVOTO versus 463 disease-free local control individuals yielded odds ratios (ORs) at 1.47 (95% confidence interval [CI], 1.13-1.92; p = 4.2 × 10-3) for LVOTO, 1.47 (95% CI, 1.10-1.97; p = 0.01) for BAV, 6.13 (95% CI, 2.75-13.7; p = 9.7 × 10-6) for CoA, and 1.49 (95% CI, 1.07-2.08; p = 0.019) for HLHS. Increased OR was observed for all LVOTO phenotypes in homozygous or compound heterozygous PCDHA delCNV genotype comparison versus wild type. Analysis of an independent white cohort (381 affected individuals, 1,352 control individuals) replicated the PCDHA delCNV association with LVOTO. Generalizability of these findings is suggested by similar observations in Black and Chinese individuals with LVOTO. Analysis of Pcdha mutant mice showed reduced PCDHA expression at regions of cell-cell contact in aortic smooth muscle and cushion mesenchyme, suggesting potential mechanisms for BAV pathogenesis and aortopathy. Together, these findings indicate common variants causing PCDHA deficiency play a significant role in the genetic etiology of common and rare LVOTO-CHD.

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.

Thirty-Year Survival after Cardiac Surgery for Patients with Turner Syndrome.

OBJECTIVE: To evaluate long-term survival in patients with Turner syndrome after congenital heart surgery with a focus on left heart obstructive lesions (LHOLs). STUDY DESIGN: We queried the Pediatric Cardiac Care Consortium, a US-based registry of congenital heart surgery, for patients with Turner syndrome undergoing congenital heart surgery at <21 years of age between 1982 and 2011. Outcomes were obtained from the Pediatric Cardiac Care Consortium and from national death and transplant registries through 2019. Survival of patients with Turner syndrome and nonsyndromic patients with similar LHOL was compared by Kaplan-Meier survival curves and Cox regression adjusted for age, congenital heart disease, and era. RESULTS: We identified 179 patients with Turner syndrome operated for LHOL: 161 with 2-ventricle lesions (coarctation n = 149, aortic stenosis n = 12) and 18 with hypoplastic left heart (HLH) variants. There were 157 with 2-ventricle LHOL and 6 with HLH survived to discharge. Among survivors to hospital discharge, the 30-year transplant-free survival was 90.4% for Turner syndrome with 2-ventricle lesions and 90.9% for nonsyndromic comparators (adjusted hazard ratio [aHR] 1.15, 95% CI 0.64-2.04). The postdischarge survival for HLH was 33% for Turner syndrome and 51% for nonsyndromic patients, with these numbers being too small for meaningful comparisons. There was a higher risk for cardiovascular disease events in patients with Turner syndrome vs male (aHR 3.72, 95% CI 1.64-8.39) and female comparators (aHR 4.55, 95% CI 1.87-11.06) excluding heart failure deaths. CONCLUSIONS: The 30-year transplant-free survival is similar for patients with Turner syndrome and nonsyndromic comparators with operated 2-ventricle LHOL without excess congenital heart disease risk. However, patients with Turner Syndrome still face increased cardiovascular disease morbidity, stressing the importance of lifelong comorbidity surveillance in this population.

Long-Term Survival and Causes of Death in Children with Trisomy 21 After Congenital Heart Surgery.

OBJECTIVE: To evaluate long-term transplant-free survival and causes of death in the trisomy 21 (T21) population after surgery for congenital heart disease (CHD) in comparison with patients who are euploidic. STUDY DESIGN: This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, enriched with prospectively collected data from the National Death Index and the Organ Procurement and Transplantation Network for patients with sufficient direct identifiers. Kaplan-Meier survival plots were generated and multivariable Cox proportional hazards models were used to examine risk factors for mortality between patients with T21 and 1:1 matched patients with comparable CHD who are euploidic. RESULTS: A long-term survival analysis was completed for 3376 patients with T21 (75 155 person-years) who met inclusion criteria. The 30-year survival rate for patients with T21 ranged from 92.1% for ventricular septal defect to 65.3% for complex common atrioventricular canal. Of these, 2185 patients with T21 were successfully matched with a patient who was euploidic. After a median follow-up of 22.86 years (IQR, 19.45-27.14 years), 213 deaths occurred in the T21 group (9.7%) compared with 123 (5.6%) in the euploidic comparators. After adjustment for age, sex, era, CHD complexity, and initial palliation, the hazard ratio of CHD-related mortality was 1.34 times higher in patients with T21 (95% CI, 0.92-1.97; P = .127). CONCLUSIONS: CHD-related mortality for patients with T21 after cardiac surgical intervention is comparable with euploidic comparators. Children with T21 require lifelong surveillance for co-occurring conditions associated with their chromosomal abnormality.

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.

Postoperative and long-term outcomes in children with Trisomy 21 and single ventricle palliation.

OBJECTIVE: Patients with Trisomy 21 (T21) and single ventricle (SV) physiology present unique challenges compared to euploidic counterparts. This study reports postoperative and long-term outcomes in patients with T21 and SV palliation. DESIGN: This retrospective cohort study from the Pediatric Cardiac Care Consortium (PCCC) included patients with T21 (<21 years old) that underwent surgical palliation for SV between 1982 and 2008 and control patients without known genetic anomaly following Fontan palliation for similar diagnoses. Kaplan-Meier survival plots were created based on death events obtained from the PCCC and by linkage with the National Death Index (NDI) and the Organ Procurement and Transplantation Network (OPTN) through 2014 for patients with adequate identifiers. RESULTS: We identified 118 children with T21 who underwent initial surgical SV palliation. Among 90 (75.6%) patients surviving their first surgery, 66 (73.3%) underwent Glenn anastomosis and 25 (27.8%) completed Fontan palliation with in-hospital survival of 80.3% and 76.0%, respectively. Fifty-three patients had sufficient identifiers for PCCC-NDI-OPTN linkage. Ten-year survival, conditioned on discharge alive after the Fontan procedure, was 66.7% compared to 92.2% for 51 controls without genetic anomaly (P = .001). Median age at death for T21 patients following initial surgical SV palliation was 2.69 years (IQR 1.34-7.12) with most deaths (89.2%) attributed to the underlying congenital heart disease (CHD). CONCLUSIONS: Children with T21 and SV are at high risk for procedural and long-term mortality related to their genetic condition and underlying CHD. Nevertheless, a select group of patients can successfully complete Glenn or Fontan palliation, reaching satisfactory long-term survival.

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.