Cancer mortality in children surviving congenital heart interventions: A study from the Pediatric Cardiac Care Consortium.

INTRODUCTION: Children with congenital heart defects (CHD) have shorter life expectancy than the general population. Previous studies also suggest that patients with CHD have higher risk of cancer. This study aims to describe cancer-related mortality among patients with a history of CHD interventions using the Pediatric Cardiac Care Consortium (PCCC), a large US cohort of such patients. METHODS: We performed a retrospective cohort study of individuals (<21 years) who underwent interventions for CHD in the PCCC from 1982 to 2003. Patients surviving their first intervention were linked to the National Death Index through 2020. Multivariable models assessed risk of cancer-related death, adjusting for age, sex, race, and ethnicity. Patients with/without genetic abnormalities (mostly Down syndrome [DS]) were considered separately, due to expected differential risk in cancer. RESULTS: Among the 57,601 eligible patients in this study, cancer was the underlying or contributing cause of death for 208; with 20% among those with DS. Significantly increased risk of cancer-related death was apparent among patients with DS compared to the non-genetic group (aHR: 3.63, 95% confidence interval [CI]: 2.52-5.24, p < .001). For the group with non-genetic abnormalities, the highest association with cancer-related death compared to those with mild CHD was found among those with more severe CHD (severe two-ventricle aHR: 1.82, 95% CI: 1.04-3.20, p = .036, single-ventricle aHR: 4.68, 95% CI: 2.77-7.91, p < .001). CONCLUSIONS: Patients with more severe forms of CHD are at increased risk for cancer-related death. Despite our findings, we are unable to distinguish whether having CHD raises the risk of cancer or reduces survival.

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.

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.

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.

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.

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 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.

Long Term Outcomes of Tetralogy of Fallot With Absent Pulmonary Valve (from the Pediatric Cardiac Care Consortium).

Tetralogy of Fallot with absent pulmonary valve (TOF-APV) is a rare form of tetralogy with unique challenges due to the combination of pulmonary annular stenosis, severe pulmonary regurgitation, and airway compression secondary to aneurysmal dilatation of the pulmonary arteries. Data on the long-term outcomes of repaired TOF-APV are scarce. We used the Pediatric Cardiac Care Consortium (PCCC), a large US-based registry, to describe the postrepair transplant-free survival of patients with TOF-APV. We queried the PCCC for patients operated for TOF-APV between 1982 and 2003. Death or transplant events were ascertained from the PCCC and by linkage with the US National Death Index and the Organ Procurement Transplantation Network through December 2019. A total of 126 patients were identified with TOF-APV repair (primary n = 119, staged n = 7). The majority of them were repaired with a right ventricular to pulmonary artery conduit (n = 80, 64%) and 43 (34%) with transannular patch. In-hospital mortality occurred in 31 patients (25%); post discharge and over a median period of 19 years (IQR 0.37 to 23.7 years), 5 patients died and 2 underwent heart transplant, one of whom subsequently died. The 25-year transplant-free survival post discharge after TOF-APV repair was 92%, which was similar with the outcome of patients with simple TOF undergoing non-valve sparing procedures (94% log-rank test p = 0.455; aHR 1.37; 95% CI: 0.63 to 2.97, p = 0.432). In conclusion, early in-hospital mortality is high for TOF-APV; however, once repaired and survived to discharge, long term survival is similar to simple TOF with non-valve sparing procedures.

Impact of executive functioning on health-related quality of life of pediatric brain tumor survivors.

BACKGROUND: Brain tumor survivors are at risk for significant late effects following treatment completion that may adversely impact health-related quality of life (HRQOL). The current study examines the relationship between executive functioning (EF) and HRQOL in pediatric brain tumor survivors within a longitudinal framework. We hypothesized that early deficits in EF would be related to less optimal HRQOL in this population. PROCEDURE: The current study utilized retrospective medical chart review to identify neurocognitive correlates of HRQOL in 137 youth previously treated for a pediatric brain tumor. Participants completed the Pediatric Quality of Life Inventory (PedsQL) and neuropsychological assessment, including a well-validated measure of executive functioning (Behavior Rating Inventory of Executive Function; BRIEF). General linear regression and multivariate models were utilized to examine the relationship between child executive functioning and HRQOL. RESULTS: Multiple domains of child executive functioning, as reported by parents on the BRIEF, significantly predicted parent-proxy reported HRQOL after controlling for demographic and medical covariates, including child intellectual functioning (IF). Similarly, after controlling for covariates, the BRIEF Cognitive Regulation Index was a significant predictor of self-reported physical and school functioning domains of HRQOL. CONCLUSION: Current data demonstrate EF is a significant predictor of HRQOL during survivorship for youth previously diagnosed with a pediatric brain tumor. Results suggest that opportunities may exist to intervene and improve HRQOL of pediatric brain tumor survivors by targeting EF.

Quantifying the difference in risk of adverse events by induction treatment regimen in pediatric acute lymphoblastic leukemia.

The differences in overall morbidity by induction treatment regimen for pediatric acute lymphoblastic leukemia (ALL) are unknown. We examined a cohort of children with ALL who received induction chemotherapy between January 2010 and May 2018. We evaluated 20 clinically relevant adverse events (AEs) and readmission and ICU admission rates. Outcomes were compared between standard 3- and 4-drug treatment regimens in multivariate analyses using Cox proportional hazard ratios. Among 486 eligible patients, the risks of sepsis (HR = 2.16, 95% CI = 1.11-4.19), hypoxia (HR = 2.08, 95% CI = 1.03-4.18), hyperbilirubinemia (HR = 2.48, 95% CI = 1.07-5.74), hyperglycemia (HR = 2.65, 95% CI = 1.29-5.42), thromboembolic event (HR = 4.50, 95% CI = 1.30-15.6), and hyponatremia (HR = 7.88, 95% CI = 1.26-49.4) were significantly higher during 4-drug induction. Despite no differences in readmission or ICU admission rates, 4-drug induction patients had greater total inpatient days (12 vs. 4 days; p<.0001). In conclusion, pediatric patients receiving 4-drug induction for ALL experience higher morbidity. These results inform care practices and patient guidance during induction therapy.

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.

Valve Replacement in Children with Single Ventricle Physiology.

Severe atrioventricular valve (AVV) or semilunar valve (SLV) regurgitation in the setting of a single ventricle physiology may proceed to valve replacement if repair strategies fail. Outcome data for these children are limited. We present transplant-free survival of a case series of children with single ventricle physiology undergoing either atrioventricular replacement (AVVR) or semilunar valve replacement (SLVR) from a multi-institutional, US-based registry (Pediatric Cardiac Care Consortium-PCCC). Outcomes were derived from PCCC and by linkage with the National Death Index (NDI) and Organ Procurement Transplant Network (OPTN). Fifty children with single ventricle physiology were identified to have received either AVVR (n = 38) or SLVR (n = 12). There were 17 in-hospital deaths including 8 intraoperative deaths (all intraoperative deaths were among children requiring AVVR). The in-hospital mortality was 42% and 8% for AVVR and SLVR, respectively. Among the 33 children surviving to hospital discharge, follow-up was available in 15 (46%). Death or cardiac transplant after hospital discharge occurred in 10-death in 4 (all among those requiring AVVR), cardiac transplant in 6 (2 following AVVR, 4 following SLVR). Valve replacement in children with single ventricle physiology, especially AVVR, is associated with poor outcomes. Alternative palliation strategies should be considered in children with single ventricle physiology with significant AVV or SLV regurgitations.

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.

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.

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.

Sistas Inspiring Sistas Through Activity and Support (SISTAS): Study Design and Demographics of Participants.

Introduction: Recruiting racial, ethnic, and other underserved minorities into conventional clinic-based and other trials is known to be challenging. The Sistas Inspiring Sistas Through Activity and Support (SISTAS) Program was a one-year randomized controlled trial (RCT) to promote physical activity and healthy eating among AA women in SC to reduce inflammatory biomarkers, which are linked to increased breast cancer (BrCa) risk and mortality. This study describes the development, recruitment, and implementation of the SISTAS clinical trial and provides baseline characteristics of the study participants. Methods: SISTAS was developed using community-based participatory research (CBPR) approaches. At baseline, study participants completed assessments and underwent clinical measurements and blood draws to measure C-reactive protein (CRP) and interleukin-6 (IL-6). Participants randomized to the intervention received 12 weekly classes followed by nine monthly booster sessions. Post-intervention measurements were assessed at 12-week and 12-month follow-ups. Results: We recruited a total of 337 women who tended to: be middle-aged (mean age 48.2 years); have some college education; be employed full-time; have Medicare as their primary insurance; be non-smokers; and perceive their personal health as good. On average, the women were pre-hypertensive at baseline (mean systolic blood pressure = 133.9 mm Hg; mean diastolic blood pressure = 84.0 mm Hg) and morbidly obese (mean BMI >40.0 kg/m2); the mean fat mass and fat-free mass among participants were 106.4 lb and 121.0 lb, respectively. Conclusion: The SISTAS RCT addresses some of the gaps in the literature with respect to CBPR interventions targeting AA women, such as implementing diet and physical activity in CBPR-based studies to decrease BrCa risk.

Outcomes after surgical coronary artery revascularisation in children with congenital heart disease.

OBJECTIVE: Surgical coronary revascularisation in children with congenital heart disease (CHD) is a rare event for which limited information is available. In this study, we review the indications and outcomes of surgical coronary revascularisation from the Pediatric Cardiac Care Consortium, a large US-based multicentre registry of interventions for CHD. METHODS: This is a retrospective cohort study of children (<18 years old) with CHD who underwent surgical coronary revascularisation between 1982 and 2011. In-hospital mortality and graft patency data were obtained from the registry. Long-term transplant-free survival through 2014 was achieved for patients with adequate identifiers via linkage with the US National Death Index and the Organ Procurement and Transplantation Network. RESULTS: Coronary revascularisation was accomplished by bypass grafting (n=72, median age 6.8 years, range 3 days-17.4 years) or other operations (n=65, median age 2.6 years, range 5 days-16.7 years) in 137 patients. Most revascularisations were related to the aortic root (61.3%) or coronary anomalies (27.7%), but 10.9% of them were unrelated to either of them. Twenty in-hospital deaths occurred, 70% of them after urgent 'rescue' revascularisation in association with another operation. Long-term outcomes were available by external linkage for 54 patients surviving to hospital discharge (median follow-up time 15.0 years, max follow-up 29.8 years) with a 15-year transplant-free survival of 91% (95% CI 83% to 99%). CONCLUSIONS: Surgical coronary revascularisation can be performed in children with CHD with acceptable immediate and long-term survival. Outcomes are dependent on indication, with the highest mortality in rescue procedures.