Outcomes of heart transplants in children with heterotaxy syndrome.

OBJECTIVES: End-stage congenital heart disease (CHD) in children with heterotaxy syndrome might necessitate a heart transplant (HTx). An HTx in heterotaxy patients can be associated with several technical (e.g. redo, systemic/pulmonary-venous/situs anomalies, pulmonary artery reconstruction) and extra-cardiac (e.g. ciliary dyskinesia, infections, gastrointestinal) challenges. Our goal was to determine if heterotaxy syndrome is associated with increased early or late transplant risks. METHODS: The United Network for Organ Sharing transplant database was merged with the Paediatric Health Information System administrative database to identify children with heterotaxy who received an HTx. Characteristics and outcomes were compared between children with heterotaxy and contemporaneous non-heterotaxy congenital and non-congenital cardiomyopathy control groups. RESULTS: After we merged the databases, we divided our cohort of 1122 patients into 3 groups: the heterotaxy (n = 143), group the non-heterotaxy congenital (n = 428) group and the cardiomyopathy (n = 551) group. There were differences in the characteristics between the 3 groups, with the heterotaxy group being comparable to the non-heterotaxy congenital group. The waiting list duration was longer for the heterotaxy than for the non-heterotaxy congenital and cardiomyopathy groups (91 vs 63 vs 56 days, P < 0.001). Early post-transplant complications were similar for all groups except for operative mortality, which was 1% for the cardiomyopathy and 4% for the heterotaxy and non-heterotaxy congenital groups (P < 0.001). The post-transplant hospital stay was shorter for the cardiomyopathy (57 days) compared to the non-heterotaxy congenital (99 days) and heterotaxy (89 days) groups (P < 0.001). Whereas rejection prior to discharge was comparable between the heterotaxy and the CHD groups, it was higher at 1 year for the heterotaxy (22%) than for the non-heterotaxy congenital (19%) and cardiomyopathy (13%) groups (P < 0.001). Survival at 5 years was superior for the cardiomyopathy (87%) compared to the heterotaxy (69%) and non-heterotaxy congenital groups (78%) (P < 0.001). For the heterotaxy group, no risk factors affecting survival were identified on multivariable analysis. CONCLUSIONS: Regardless of the complexity, an HTx in selected children with heterotaxy is associated with good mid-term outcomes. Despite early results that are comparable to those of other patients with CHD, the increasing rejection rate at 1 year and the relatively accelerated attrition at mid-term warrant further follow-up. Due to database limitations in defining morphologic and surgical details, further work is warranted to delineate anatomical and surgical variables that could affect survival.

A novel approach to retrograde autologous priming for infant, pediatric and adult populations undergoing congenital heart surgery.

INTRODUCTION: Retrograde Autologous Priming (RAP) of cardiopulmonary bypass (CPB) circuits is an effective way to reduce prime volume, commonly through the transfer of prime into separate reservoirs or circuit manipulation. We describe a simple and safe technique for RAP without the need for any circuit modifications or manipulations. METHODS: For this technique, a separate roller pump for ultrafiltration (UF) is used. After adequate heparinization and arterial cannulation, the UF pump is initiated slowly, removing prime through the effluent of the UF, replacing with the patient's blood from the aortic cannula. Once the arterial line and UF circuit are autologous primed, the arterial head displaces reservoir crystalloid toward the UF circuit at a flow rate equal to the UF pump, displacing the crystalloid prime with blood from the UF circuit, autologous priming the boot and oxygenator with blood, crystalloid again being removed by the effluent. After venous cannulation, the venous line prime is replaced with autologous blood, the crystalloid removed by the effluent of the UF circuit via the arterial head. During RAP, if the patient becomes hypovolemic, either autologous volume is transfused back to the patient, or CPB is initiated, without the need for circuitry modifications. RESULTS: The patient population in this sample consisted of 63 patients ranging between 6.1 kg and 115.6 kg. The smaller the patient, the less blood volume available for RAP and therefore the less prime volume able to be removed. Overall percent removal increases as our patients size increases compared to total circuit volume. CONCLUSION: This RAP technique is a safe and effective way to achieve a standardized asanguinous prime for many regardless of patient or circuit size in the absence of contraindications such as low starting hematocrit, emergency surgery or physiologic instability. Most importantly, this potentially reduces the amount of hemodilution patients see from CPB initiation and therefore the lowest nadir hematocrit and consequently the amount of required homologous blood products needed during surgery.

Impact of new allocation policy on waitlist and transplant outcomes of adult congenital heart patients supported with ECMO.

BACKGROUND: The use of ECMO as a bridge to heart transplantation has been growing rapidly in all heart transplant recipients since the implementation of the new UNOS allocation policy; however, the impact on adult congenital heart disease (ACHD) patients is not known. METHODS: We analyzed the UNOS data (2015-2021) for ACHD patients supported with extracorporeal membrane oxygenation (ECMO) during the waitlist, before and after October 2018, to assess the impact on the waitlist and posttransplant outcomes. We compared the characteristics and outcomes of ACHD patients with or without ECMO use during the waitlist and pre- and postpolicy changes. RESULTS: A total of 23 821 patients underwent heart transplantation, and only 918 (4%) had ACHD. Out of all ACHD patients undergoing heart transplants, 6% of patients in the prepolicy era and 7.6% in the postpolicy era were on ECMO at the time of listing. Those on ECMO were younger and sicker compared to the rest of the ACHD cohort. Those on ECMO had similar profiles pre- and postpolicy change; however, there was a very significant decrease in the waitlist time [136 days (IQR 29-384) vs. 38 days (IQR 11-108), p = 0.01]. There was no difference in waitlist mortality; however, competing risk analyses showed a higher likelihood of transplantation (51% vs. 29%) and a lower likelihood of death or deterioration (31% vs. 42%) postpolicy change. Long-term outcomes posttransplant for those supported with ECMO compared to the non-ECMO cohort are similar for ACHD patients, although there was higher attrition in the first year for the ECMO cohort. CONCLUSION: The new allocation policy has resulted in shorter waitlist times and a higher likelihood of transplantation for ACHD patients supported by ECMO. However, the appropriate use of ECMO and the underuse of durable circulatory support devices in this population need further exploration.

Normalizing Anti-Thrombin III for heparin management during routine cardiopulmonary bypass for congenital cardiothoracic surgery: A single institution practice review.

INTRODUCTION: Over the past decade, there has been an increase in the use of recombinant Anti-Thrombin III (AT-III) administration during neonatal and pediatric short- and long-term mechanical support for the replacement of acquired deficiencies. Recombinant AT-III (Thrombate) administration is an FDA licensed drug indicated primarily for patients with hereditary deficiency to treat and prevent thromboembolism and secondarily to prevent peri-operative and peri-partum thromboembolism. Herein we propose further use of Thrombate for primary AT-III deficiency of the newborn as well as for acquired dilution and consumption secondary to cardiopulmonary bypass (CPB). METHODOLOGY: All patients undergoing CPB obtain a preoperative AT-III level. Patients with identified deficiencies are normalized in the OR using recombinant AT-III as a patient load, in the CPB prime, or both. Patient baseline Heparin Dose Response (HDR) is assessed using the Heparin Management System (HMS) before being exposed to AT-III. If a patient load of AT-III is given, a second HDR is obtained and this AT-III Corrected HDR is used as the primary goal during CPB. Once CPB is initiated, an AT-III level is obtained with the first patient blood analysis. A subtherapeutic level results in an additional dose of AT-III. During the rewarm period, a final AT-III level is obtained and AT-III treated once again if subtherapeutic. A retrospective, matched analysis review of practice analyzing two groups, a Study Group (Repeat HDR, May 2022 onward) and Matched Group (Without Repeat HDR, July 2019 to April 2022), for age (D), weight (Kg) and operation was conducted. The focus of the study was to determine any change in heparin sensitivity identified post AT-III patient bolus load in the HDR (U/mL), Slope (U/mL/s), ACT (s), and total amount of heparin on CPB (U) and protamine (mg) used in each group. RESULTS: No significance was seen in Baseline AT-III (%), post heparin load HDR (U/mL), first CPB ACT (s), first CPB HDR (U/mL), or total CPB heparin (u/Kg) between the two groups. Statistical significance was seen in Baseline ACT (s), Baseline HDR (U/mL), Baseline Slope (U/mL/s), Post Heparin Load ACT (s), first CPB AT-III (%), and Protamine (mg/Kg) (p < .05). No statistical significance was seen in the Study Intragroup between pre versus post AT-III patient load baseline sample in ACT (s), however significance was seen in HDR (U/mL) and Slope (U/mL/s) (p < .05). CONCLUSION: Implementation of AT-III monitoring and therapy before and during CPB in conjunction with the HMS allows patients to maintain a steady state of anticoagulation with overall less need for excessive heparin replacement and potentially thrombin activation. The result is obtaining a steady state of anticoagulation, a reduced fluctuation in the heparin and ACT levels and a potential for lower co-morbidities associated with prolonged CPB times.

Trends and outcomes of heart transplantation in adults with congenital heart disease.

OBJECTIVES: Heart transplantation for adult congenital heart disease is complicated and associated with challenging pretransplant support, long waiting and high early post-transplant mortality. We explored if surgical and medical advances and allocation system changes have affected outcomes. METHODS: From United Network for Organ Sharing database, adults with congenital heart disease listed for heart transplantation were queried. To explore practice and outcome trends, patients were divided into 4 eras (eras 1-3: nearly 3 equal periods from 1992 to 2018, era 4: after 2018, corresponding with new allocation system). Univariate and multivariable analysis was performed to evaluate outcomes. RESULTS: A total of 2737 patients were listed. There was gradual increase in listed and transplanted patients, along with significant increase in use of mechanical support, simultaneous kidney and liver transplantation. While proportion of transplanted remained constant, there was decrease in proportion delisted/died after listing (P = 0.01) and waiting list duration (P = 0.01), especially in era 4. Thirty-day post-transplant mortality remains high; however, it has significantly improved starting era 3 (P = 0.01). Current survival at 1-year and 5-years is 85% and 65%, with improvement mainly related to decreased early death. On multivariable analysis, factors associated with survival were lower glomerular filtration rate (hazard ratio = 0.99, P = 0.042), bilirubin (hazard ratio = 1.17, P<0.001) and mechanical ventilation (hazard ratio = 2.3, P=0.004). CONCLUSIONS: Heart transplantation in adults with congenital heart disease is increasing, along with added complexity, higher usage of pretransplant mechanical support and simultaneous organ transplantation. Despite that, more complex patients do not experience worse outcomes. Early mortality improved but remains high. New donor allocation system allowed shorter waiting time and higher proportion transplanted without altering early mortality.

The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: Recommendation for the care of children with trisomy 13 or trisomy 18 and a congenital heart defect.

OBJECTIVES: Recommendations for surgical repair of a congenital heart defect in children with trisomy 13 or trisomy 18 remain controversial, are subject to biases, and are largely unsupported with limited empirical data. This has created significant distrust and uncertainty among parents and could potentially lead to suboptimal care for patients. A working group, representing several clinical specialties involved with the care of these children, developed recommendations to assist in the decision-making process for congenital heart defect care in this population. The goal of these recommendations is to provide families and their health care teams with a framework for clinical decision making based on the literature and expert opinions. METHODS: This project was performed under the auspices of the AATS Congenital Heart Surgery Evidence-Based Medicine Taskforce. A Patient/Population, Intervention, Comparison/Control, Outcome process was used to generate preliminary statements and recommendations to address various aspects related to cardiac surgery in children with trisomy 13 or trisomy 18. Delphi methodology was then used iteratively to generate consensus among the group using a structured communication process. RESULTS: Nine recommendations were developed from a set of initial statements that arose from the Patient/Population, Intervention, Comparison/Control, Outcome process methodology following the groups' review of more than 500 articles. These recommendations were adjudicated by this group of experts using a modified Delphi process in a reproducible fashion and make up the current publication. The Class (strength) of recommendations was usually Class IIa (moderate benefit), and the overall level (quality) of evidence was level C-limited data. CONCLUSIONS: This is the first set of recommendations collated by an expert multidisciplinary group to address specific issues around indications for surgical intervention in children with trisomy 13 or trisomy 18 with congenital heart defect. Based on our analysis of recent data, we recommend that decisions should not be based solely on the presence of trisomy but, instead, should be made on a case-by-case basis, considering both the severity of the baby's heart disease as well as the presence of other anomalies. These recommendations offer a framework to assist parents and clinicians in surgical decision making for children who have trisomy 13 or trisomy 18 with congenital heart defect.

Associated Factors and Impact of Persistent Renal Dysfunction in Pediatric Heart Transplantation.

BACKGROUND: We evaluated the impact of significant renal dysfunction (SRD) on listing and pediatric heart transplantation (PHT) outcomes. METHODS: The United Network of Organ Sharing registry was queried. Our cohort included 11,625 children listed for PHT (2000-2020). At listing, 1494 (13%) had SRD, defined as an estimated glomerular filtration rate of <45 mL/min/1.73 m2 and/or dialysis requirement. Characteristics of children with and without SRD were compared. SRD impact on outcomes was examined. Factors associated with waiting list mortality, persistent SRD at PHT, and post-PHT survival with and without simultaneous heart-kidney transplantation were assessed. RESULTS: Compared with children with an estimated glomerular filtration rate >45 mL/min/1.73 m2, those with SRD had higher waiting list death (37% vs 14%, P < .01) and lower transplantation rate (51% vs 71%, P < .01). On multivariable analysis, SRD was associated with waiting list death (hazard ratio, 3.016; P < .0001). Among 767 children with SRD who received PHT, 361 (47%) had persistent SRD at the time of PHT. On multivariable analysis, factors associated with persistent SRD were older age (odds ratio [OR], 1.147 per year; 95% CI, 1.046-1.258 per year; P = .0035), bilirubin (OR, 1.127 per 1-mg/dL; 95% CI, 1.061-1.197 per 1-mg/dL; P < .0001), dialysis (OR, 1.839; 95% CI, 1.017-3.326; P = .0115), mechanical ventilation (OR, 1.972; 95% CI, 1.336-2.911; P = .0006), extracorporeal membrane oxygenation (OR, 1.747; 95% CI, 1.074-2.842; P = .0247), and not using a ventricular assist device (VAD) (OR, 0.498 [VAD use]; 95% CI, 0.277-0.895 VAD use; P = .0198). Post-PHT survival was 72%, 70%, and 56% (P < .01) at 8 years for PHT alone with improved renal function, simultaneous heart-kidney transplantation (n = 69), and PHT alone with persistent SRD, respectively. CONCLUSIONS: SRD is associated with high waiting list death and decreased transplantation rate. Timely proper pre-PHT support with VAD could enhance kidney recovery. Simultaneous heart-kidney transplantation neutralized persistent SRD effect on survival and might be considered in high-risk patients such as those on dialysis, mechanical ventilation, or extracorporeal membrane oxygenation support.

Perioperative Morbidity and Outcomes in Pediatric Patients Transitioned From Extracorporeal Membrane Oxygenation to Ventricular Assist Device Support: A Study of the Society of Thoracic Surgeons Congenital Heart Surgery Database.

As a bridge to transplant strategy, children transitioned from extracorporeal membrane oxygenation (ECMO) to ventricular assist device (VAD) have higher waitlist mortality compared with those who receive de novo VAD. However, the contribution of the immediate perioperative period and differences in the two groups are not well studied. We performed a nested case-control study between children receiving de novo VAD (group 1) and those transitioned from ECMO to VAD (group 2) between 2014 and 2019 using The Society of Thoracic Surgeons (STS) database. A total of 735 children underwent VAD placement with 498 in group 1 and 237 in group 2. Patients in group 2 were significantly younger, smaller, and significantly sicker, were twice as likely to transition to biventricular VAD and need unplanned reoperations. Overall mortality was 16% for group 1 and 34% for group 2 ( p < 0.01). Regression analysis showed that ECMO use (odds ratio [OR], 2.17 [1.3-3.4]), ventilator need (OR, 2.2 [1.3-3.9]), and cardiogenic shock (OR, 1.8 [1.2-2.8]) were all independent preoperative predictors of VAD mortality while dialysis need (OR, 25.5 [8.6-75.3]), stroke (OR, 6.2 [3.1-12.6]), and bleeding (OR, 1.9 [1.1-3.4]) were independent postoperative predictors of VAD mortality within 30 days (all p < 0.05). The study demonstrated significant baseline differences between the two cohorts, warranting avoidance of comparison. Early elective VAD placement in this cohort of patients should be sought to avoid interim ECMO and high post-VAD mortality.

Increasing donor-recipient weight mismatch in infant heart transplantation is associated with shorter waitlist duration and no increased morbidity or mortality.

OBJECTIVES: Infants awaiting paediatric heart transplantation (PHT) experience long waitlist duration and high mortality due to donor shortage. Using the United Network for Organ Sharing database, we explored if increasing donor-recipient weight ratio (DRWR) >2.0 (recommended cutoff) was associated with adverse outcomes. METHODS: Between 2007 and 2020, 1392 infants received PHT. We divided cohort into 3 groups: A (DRWR ≤1.0, n = 239, 17%), B (DRWR 1.0-2.0, n = 947, 68%), C (DRWR >2.0, n = 206, 15%). Group characteristics and PHT outcomes were analysed. RESULTS: DRWR ranged between 0.5 and 4.1. Underlying pathology (congenital versus cardiomyopathy), gender, race, renal function and mechanical circulatory support were comparable between groups. Group C patients were more likely to be ventilated, to receive ABO blood group (ABO)-incompatible heart and to have longer donor ischaemic time. Waitlist duration was significantly shorter for group C (33 vs 50 days, P < 0.1). Early outcomes for groups A, B and C were the following (respectively): operative death (6%, 4%, 3%, P = 0.29), primary graft dysfunction (5%, 3%, 3%, P = 0.30), renal failure (10%, 7%, 7%, P = 0.42) and stroke (3%, 4%, 1%, P = 0.36). The DRWR group was not associated with operative death in either congenital (odds ratio (OR) = 0.819, 95% confidence interval (CI) = 0.523-1.282) or cardiomyopathy (OR = 1.221, 95% CI = 0.780-1.912) patients and only significant factor was pre-PHT extracorporeal membrane oxygenation (OR = 4.400, 95% CI = 2.761-7.010). Additionally, survival at 1 year (87%, 87%, 85%, P = 0.80) and 5 years (76%, 78%, 77%, P = 0.80) was comparable between the DRWR groups. CONCLUSIONS: Infants who received PHT with DRWR >2.0, up to 4.1, experienced shorter waitlist duration with no demonstrable increase in peri-transplant complications, operative or late mortality. Historic practice to avoid DRWR > 2.0 due to complications (e.g. hypertension-related stroke, graft dysfunction, death) is not currently supported in infants and stretching DRWR acceptance criteria would decrease PHT waitlist duration and potentially improve waitlist complications and mortality.

Outcomes After Hybrid Palliation for Infants With Critical Left Heart Obstruction.

BACKGROUND: Hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) is an initial management strategy for infants with critical left heart obstruction and serves as palliation until subsequent operations are pursued. OBJECTIVES: This study sought to determine patient characteristics and factors associated with subsequent outcomes for infants who underwent hybrid palliation. METHODS: From 2005 to 2019, 214 of 1,236 prospectively enrolled infants within the Congenital Heart Surgeons' Society's critical left heart obstruction cohort underwent hybrid palliation across 24 institutions. Multivariable hazard modeling with competing risk methodology was performed to determine risk and factors associated with outcomes of biventricular repair, Fontan procedure, transplantation, or death. RESULTS: Preoperative comorbidities (eg, prematurity, low birth weight, genetic syndrome) were identified in 70% of infants (150 of 214). Median follow-up was 7 years, ranging up to 17 years. Overall 12-year survival was 55%. At 5 years after hybrid palliation, 9% had biventricular repair, 36% had Fontan procedure, 12% had transplantation, 35% died without surgical endpoints, and 8% were alive without an endpoint. Factors associated with transplantation were absence of ductal stent, older age, absent interatrial communication, smaller aortic root size, larger tricuspid valve area z-score, and larger left ventricular volume. Factors associated with death were low birth weight, concomitant genetic syndrome, cardiopulmonary bypass use during hybrid palliation, moderate to severe tricuspid valve regurgitation, and smaller ascending aortic size. CONCLUSIONS: Mortality remains high after hybrid palliation for infants with critical left heart obstruction. Nonetheless, hybrid palliation may facilitate biventricular repair for some infants and for others may serve as stabilization for intended functional univentricular palliation or primary transplantation.

Pediatric mechanical circulatory support - a review.

The history of mechanical circulatory support began in 1953, as the first heart-lung machine enabled surgeons to perform complex open heart surgery. Heart failure is more prevalent in adults than pediatric patients which has led to the development of devices for adults with end-stage heart failure at a faster pace. Pediatric mechanical circulatory support has been derived from adult durable devices and subsequently applied in the adolescent population. The application of adult devices in children is inherently problematic due to size mismatch, especially in smaller patients. There has been an increasing interest in developing durable pumps that are appropriate for children for several reasons, with the primary factor being the number of children with end-stage heart failure far exceeding the number of potential donors. Mechanical circulatory support (MCS) for children can be divided into short-term temporary support and long-term durable support. The goal of this review is to discuss the devices available for the pediatric population and review the options for support in complex patients including single-ventricle anatomy, biventricular support, and total artificial heart options. We will also briefly discuss the Pumps for Kids, Infants, and Neonates (PumpKIN) Trial and MCS registries, including the Advanced Cardiac Therapies Improving Outcomes Network (ACTION).

Hybrid palliation versus nonhybrid management for a multi-institutional cohort of infants with critical left heart obstruction.

OBJECTIVE: To compare patient characteristics and overall survival for infants with critical left heart obstruction after hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) versus nonhybrid management (eg, Norwood, primary transplantation, biventricular repair, or transcatheter/surgical aortic valvotomy). METHODS: From 2005 to 2019, 1045 infants in the Congenital Heart Surgeons' Society critical left heart obstruction cohort underwent interventions across 28 institutions. Using a balancing score propensity analysis, 214 infants who underwent hybrid palliation and 831 infants who underwent nonhybrid management were proportionately matched regarding variables significantly associated with mortality and variables noted to significantly differ between groups. Overall survival between the 2 groups was adjusted by applying balancing scores to nonparametric estimates. RESULTS: Compared with the nonhybrid management group, infants who underwent hybrid palliation had lower birth weight, smaller gestational age, and higher prevalence of in-utero interventions, noncardiac comorbidities, preoperative mechanical ventilation, absent interatrial communication, and moderate or severe mitral valve stenosis (all P values < .03). Unadjusted 12-year survival after hybrid palliation and nonhybrid management, was 55% versus 69%, respectively. After matching, 12-year survival after hybrid palliation versus nonhybrid management was 58% versus 63%, respectively (P = .37). Among matched infants born weighing <2.5 kg, 2-year survival after hybrid palliation versus nonhybrid management was 37% versus 51%, respectively (P = .22). CONCLUSIONS: Infants born with critical left heart obstruction who undergo hybrid palliation have more high-risk characteristics and anatomy versus infants who undergo nonhybrid management. Nonetheless, after adjustment, there was no significant difference in 12-year survival after hybrid palliation versus nonhybrid management. Mortality remains high, and hybrid palliation confers no survival advantage, even for lower-birth-weight infants.

Left Main Coronary Artery Ostial Stenosis in a Pediatric Patient With Sudden Cardiac Arrest.

Pediatric resuscitated sudden cardiac arrest may result from diverse conditions and, therefore, warrants a comprehensive work-up. Although rare, coronary artery abnormalities must be ruled out in these patients. We describe a case with congenital left main coronary artery ostial stenosis diagnosed using advanced imaging techniques. (Level of Difficulty: Advanced.).