Multicentre comparative analysis of long-term outcomes after aortic valve replacement in children.

OBJECTIVE: The ideal valve substitute for surgical intervention of congenital aortic valve disease in children remains unclear. Data on outcomes beyond 10-15 years after valve replacement are limited but important for evaluating substitute longevity. We aimed to describe up to 25-year death/cardiac transplant by type of valve substitute and assess the potential impact of treatment centre. Our hypothesis was that patients with pulmonic valve autograft would have better survival than mechanical prosthetic. METHODS: This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a multi-institutional US-based registry of paediatric cardiac interventions, linked with the National Death Index and United Network for Organ Sharing through 2019. Children (0-20 years old) receiving aortic valve replacement (AVR) from 1982 to 2003 were identified. Kaplan-Meier transplant-free survival was calculated, and Cox proportional hazard models estimated hazard ratios for mechanical AVR (M-AVR) versus pulmonic valve autograft. RESULTS: Among 911 children, the median age at AVR was 13.4 years (IQR=8.4-16.5) and 73% were male. There were 10 cardiac transplants and 153 deaths, 5 after transplant. The 25-year transplant-free survival post AVR was 87.1% for autograft vs 76.2% for M-AVR and 72.0% for tissue (bioprosthetic or homograft). After adjustment, M-AVR remained related to increased mortality/transplant versus autograft (HR=1.9, 95% CI=1.1 to 3.4). Surprisingly, survival for patients with M-AVR, but not autograft, was lower for those treated in centres with higher in-hospital mortality. CONCLUSION: Pulmonic valve autograft provides the best long-term outcomes for children with aortic valve disease, but AVR results may depend on a centre's experience or patient selection.

Ab initio molecular dynamics modeling of single polyethylene chains: Scission kinetics and influence of radical under mechanical strain.

Ab initio molecular dynamics was used to estimate the response to constant imposed strain on a short polyethylene (PE) chain and a radical chain with a removed hydrogen atom. Two independent types of simulations were run. In the first case, the chains were strained by expanding a periodic cell, restraining the length but allowing the internal degrees of freedom to reach equilibrium. From these simulations, the average force on the chain was computed, and the resulting force was integrated to determine the Helmholtz free energy for chain stretching. In the second set of simulations, chains were constrained to various lengths, while a bond was restrained at various bond lengths using umbrella sampling. This provided free energy of bond scission for various chain strains. The sum of the two free energy functions results in an approximation of the free energy of chain scission under various strains and gives a realistic and new picture of the effect of chain strain on bond breaking. Unimolecular scission rates for each chain type were examined as a function of chain strain. The scission rate for the radical chain is several orders of magnitude larger than that of the pristine chain at smaller strains and at equilibrium. This highlights the importance of radical formation in PE rupture and is consistent with experiments. Constant strain results were used to derive a constant-force model for the radical chain that demonstrates a roll over in rate similar to the "catch-bond" behavior observed in protein membrane detachment experiments.

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.

On the Nature of Epoxy Resin Post-Curing.

Post-curing is intended to improve strength, elevate glass transition, and reduce residual stress and outgassing in thermosets. Also, experiments indicate post-curing temperatures lead to ether crosslinks and backbone dehydration. These results informed molecular dynamics methods to represent them and compare the resulting thermomechanical effects. Diglycidyl ether of bisphenol A (DGEBA)-diamino diphenyl sulfone (DDS) systems were examined. Independent variables were resin length, stoichiometry, and reaction type (i.e., amine addition, etherification, and dehydration). Etherification affected excess epoxide systems most. These were strengthened and became strain hardening. Systems which were both etherified and dehydrated were most consistent with results of post-curing experiments. Dehydration stiffened and strengthened systems with the longer resin molecules due to their intermediate hydroxyl groups for crosslinking. Changes in the concavity of functions fit to the specific volume versus temperature were used to detect thermal transitions. Etherification generally increased transition temperatures. Dehydration resulted in more transitions.

First Successful Open-Heart Surgery Utilizing Cross-Circulation in 1954.

A pioneering surgeon at the University of Minnesota, Dr C. Walton Lillehei, is still considered the "father of open-heart surgery". Dr Lillehei and his surgical team performed the first open-heart operations utilizing cross-circulation, including the first successful ventricular septal defect closure on a 3-year-old boy. Before his death at age 67, this patient arranged to donate his body to the University of Minnesota's Anatomy Bequest program. We describe this patient's medical history, and present unique images of internal/external cardiac anatomies and implanted devices obtained via direct visualizations, computed tomography, and fluoroscopy post-mortem. Additionally, we present computational models and 3-dimensional printed models.

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.

Outcomes of Mechanical Mitral Valve Replacement in Children.

BACKGROUND: Mitral valve anomalies in children are rare but frequently severe, recalcitrant, and not often amenable to primary repair, necessitating mechanical mitral valve replacement (M-MVR). This study examined outcomes of a cohort undergoing a first M-MVR at age younger than 21 years. METHODS: We queried the Pediatric Cardiac Care Consortium, a multi-institutional United States-based cardiac intervention registry, for patients undergoing first M-MVR for 2-ventricle congenital heart disease. Survival and transplant status through 2014 were obtained from Pediatric Cardiac Care Consortium and linkage with the National Death Index and the Organ Procurement and Transplantation Network. RESULTS: We identified 441 patients (median age, 4.3 years; interquartile range, 1.3 to 10.1 years) meeting study criteria. The commonest disease necessitating M-MVR was atrioventricular canal (44.3%). Early mortality (death <90 days after M-MVR) was 11.1%; there was increased risk of early death if age at M-MVR was younger than 2 years (odds ratio, 7.8; 95% confidence interval [CI], 1.1 to 56.6) and with concurrent other mechanical valve placement (odds ratio, 8.5; 95% CI, 2.0 to 35.6). In those surviving more than 90 days after M-MVR, transplant-free survival was 76% at 20 years of follow-up (median follow-up, 16.6 years; interquartile range, 11.9 to 21.3 years). Adjusted analysis in those who survived more than 90 days showed elevated risk of death/transplant for boys (hazard ratio, 1.5; 95% CI, 1.0 to 2.3), age at M-MVR younger than 2 years (10-year survival: hazard ratio, 4.3; 95% CI, 1.2 to 15.1), and nonbileaflet prosthesis placement (hazard ratio, 2.4; 95% CI, 1.3 to 4.3). CONCLUSIONS: M-MVR is a viable strategy in children with unrepairable mitral valve disease. Age younger than 2 years at the first M-MVR is associated with significant early risk of death and poorer long-term survival.

Sixty Years After Tetralogy of Fallot Correction.

This report describes one of the early cases of open surgical correction of tetralogy of Fallot performed by C. Walton Lillehei and colleagues at the University of Minnesota and discusses findings from the patient's follow-up 60 years later.

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.

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.

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.

Long-Term Outcomes of Children With Trisomy 13 and 18 After Congenital Heart Disease Interventions.

BACKGROUND: The purpose of this study is to report short- and long-term outcomes after congenital heart defect (CHD) interventions in patients with trisomy 13 or 18. METHODS: A retrospective review of the Pediatric Cardiac Care Consortium (PCCC) identified children with trisomy 13 or 18 with interventions for CHD between 1982 and 2008. Long-term survival and cause of death were obtained through linkage with the National Death Index. RESULTS: A total of 50 patients with trisomy 13 and 121 patients with trisomy 18 were enrolled in PCCC between 1982 and 2008; among them 29 patients with trisomy 13 and 69 patients with trisomy 18 underwent intervention for CHD. In-hospital mortality rates for patients with trisomy 13 or trisomy 18 were 27.6% and 13%, respectively. Causes of in-hospital death were primarily cardiac (64.7%) or multiple organ system failure (17.6%). National Death Index linkage confirmed 23 deaths after discharge. Median survival (conditioned to hospital discharge) was 14.8 years (95% confidence interval [CI]: 12.3 to 25.6 years) for patients with trisomy 13 and 16.2 years (95% CI: 12 to 20.4 years) for patients with trisomy 18. Causes of late death included cardiac (43.5%), respiratory (26.1%), and pulmonary hypertension (13%). CONCLUSIONS: In-hospital mortality rate for all surgical risk categories was higher in patients with trisomy 13 or 18 than that reported for the general population. However, patients with trisomy 13 or 18, who were selected as acceptable candidates for cardiac intervention and who survived CHD intervention, demonstrated longer survival than previously reported. These findings can be used to counsel families and make program-level decisions on offering intervention to carefully selected patients.

The First Cardiac Operation Using Cardiopulmonary Bypass.

The first open heart operation ever performed was by Clarence Dennis on April 5, 1951, at the University of Minnesota. For several years he had worked developing a heart-lung machine. The operation was on a young girl considered to have an ostium secundum atrial septal defect, but at the procedure a large ostium primum was identified instead. It could not be repaired, and the child died. The anatomic details of this heart have not been previously presented. For historical purposes, the clinical history, intraoperative course, and pathologic details will be discussed and shown.

The First Repair of Cor Triatriatum.

This article describes the first patient treated surgically for cor triatriatum, and also describes preoperative testing, operative findings, and procedures, as well as follow-up.

In-Hospital Vital Status and Heart Transplants After Intervention for Congenital Heart Disease in the Pediatric Cardiac Care Consortium: Completeness of Ascertainment Using the National Death Index and United Network for Organ Sharing Datasets.

BACKGROUND: The long-term outcomes of patients undergoing interventions for congenital heart disease (CHD) remain largely unknown. We linked the Pediatric Cardiac Care Consortium (PCCC) with the National Death Index (NDI) and the United Network for Organ Sharing Dataset (UNOS) registries to study mortality and transplant occurring up to 32 years postintervention. The objective of the current analysis was to determine the sensitivity of this linkage in identifying patients who are known to have died or undergone heart transplant. METHODS AND RESULTS: We used direct identifiers from 59 324 subjects registered in the PCCC between 1982 and 2003 to test for completeness of case ascertainment of subjects with known vital and heart transplant status by linkage with the NDI and UNOS registries. Of the 4612 in-hospital deaths, 3873 were identified by the NDI as "true" matches for a sensitivity of 84.0% (95% CI, 82.9-85.0). There was no difference in sensitivity across 25 congenital cardiovascular conditions after adjustment for age, sex, race, presence of first name, death year, and residence at death. Of 455 known heart transplants in the PCCC, there were 408 matches in the UNOS registry, for a sensitivity of 89.7% (95% CI, 86.9-92.3). An additional 4851 deaths and 363 transplants that occurred outside the PCCC were identified through 2014. CONCLUSIONS: The linkage of the PCCC with the NDI and UNOS national registries is feasible with a satisfactory sensitivity. This linkage provides a conservative estimate of the long-term death and heart transplant events in this cohort.

Bond breaking in epoxy systems: A combined QM/MM approach.

A novel method to combine quantum mechanics (QM) and molecular mechanics has been developed to accurately and efficiently account for covalent bond breaking in polymer systems under high strain without the use of predetermined break locations. Use of this method will provide a better fundamental understanding of the mechano-chemical origins of fracture in thermosets. Since classical force fields cannot accurately account for bond breaking, and QM is too demanding to simulate large systems, a hybrid approach is required. In the method presented here, strain is applied to the system using a classical force field, and all bond lengths are monitored. When a bond is stretched past a threshold value, a zone surrounding the bond is used in a QM energy minimization to determine which, if any, bonds break. The QM results are then used to reconstitute the system to continue the classical simulation at progressively larger strain until another QM calculation is triggered. In this way, a QM calculation is only computed when and where needed, allowing for efficient simulations. A robust QM method for energy minimization has been determined, as well as appropriate values for the QM zone size and the threshold bond length. Compute times do not differ dramatically from classical molecular mechanical simulations.