Novel tubing connectors reduce ECMO circuit thrombosis.

BACKGROUND: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions. METHODS: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots. RESULTS: In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine (p < 0.0001). In the long-term goat ECMO circuits, the traditional connectors exhibited more thrombi (p < 0.04), and these thrombi were more likely to protrude into the lumen of the tubing (p < 0.001). CONCLUSION: Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis.

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.

Critical Care Therapies Pre and Post Heart Transplant and Their Impact: Analysis from The Pediatric Cardiac Critical Care Consortium.

BACKGROUND: Few studies highlighting the critical care management of patients after heart HTx (HTx) have been published to date. This analysis provides a contemporary representation of critical care burden pre- and post-HTx, describes care differences based on pre-transplant diagnosis and outlines the impact of intensive care unit (ICU) therapies on outcomes. METHODS: Data from PC4 Collaborative Registry was analyzed for pediatric patients undergoing HTx between 08/2014-04/2022. RESULTS: 1877 HTx in 1857 patients were reported from 42 centers; 56.5% had congenital heart disease (CHD). Patients with CHD were younger, smaller, more likely male, White race, and publicly insured. Their pre-HTx ICU course was characterized by a higher need for catheterization, increased likelihood of inotropic support and mechanical ventilation with lower VAD rates. Their operative courses were significant for longer bypass and cross-clamp times. Postoperatively, CHD patients required more CPR and utilized more ICU therapies such as inotropes, ECMO and renal replacement. Those with CHD had a longer duration of ventilatory support (68.6 vs. 27.3 hours), total hospital stays (37.1 vs. 22.9 days) and higher hospital mortality (7.8% vs. 1.8%); all p<0.0001. Longer cardiopulmonary bypass and longer deep hypothermic circulatory arrest times and delayed sternal closure were independent risk factors for hospital mortality. Lastly, there was no association between total surgical volume for a center and outcomes but there was a significant relationship between center transplant volume and outcomes with higher volume centers demonstrating significantly lower mortality. CONCLUSION: A diagnosis of CHD prior to HTx is associated with a greater use of ICU specific therapies compared non-CHD cohort. Operative factors, particularly in CHD patients, are independently associated with higher hospital mortality as was low transplant volume at the center. The study provides basis for further investigating ICU and operative factors that can be modified to improve transplant outcomes.

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.

Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

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.

Bartonella henselae infection-mediated shunt nephritis.

Serum anti-neutrophil cytoplasmic antibody (ANCA) positivity with membranoproliferative pattern on renal biopsy can be due to ANCA-associated vasculitis as well as chronic indolent infections. We present the case of an adolescent boy with congenital heart disease and history of cardiac surgery who presented with severe acute kidney injury requiring hemodialysis. Renal biopsy showed membranoproliferative glomerulonephritis with full-house immunofluorescence pattern. Low serum complements, PR3 ANCA positivity and elevated Bartonella immunoglobulin titers suggested a diagnosis of infective endocarditis-associated glomerulonephritis. Cardiac shunt revision and antibiotic therapy lead to improvement in kidney function. Chronic infections lead to formation of immune complexes that may cause deposit within the renal parenchyma and induce production of ANCA. The distinction of ANCA-associated vasculitis and chronic infections causing acute kidney injury is important in determining therapeutic management. While rare in the pediatric population, we highlight the importance in considering indolent infections in patients with acute glomerulonephritis and ANCA positivity, especially with risk factors.

Paediatric heart transplantation: life-saving but not yet a cure.

In the 1980s, heart transplantation was the first successful treatment for infants born with hypoplastic left heart syndrome. Infants who have required heart transplantation benefit from immunologic "advantages," including long-term survival free from cardiac allograft vasculopathy. Currently ∼ 90% of children undergoing a heart transplant are reaching their first-year anniversary and the clinical practices of paediatric heart transplantation have dramatically improved. These successes are largely attributed to research sponsored by the Pediatric Heart Transplant Study Group, the International Society of Heart and Lung Transplantation and, more recently, the Non-profits Enduring Hearts and Additional Ventures. Despite these successes, the field is challenged to increase progress to achieve long-term survival into adulthood. The wait-list mortality, especially among infants, is unacceptably high often leading to palliative measures that can increase post-transplant mortality. Cardiac allograft vasculopathy remains a major cause for progressive graft loss of function and sudden death. The relative tolerance seen in immature recipients has not been translated to modifying older recipients' post-transplant outcomes. The modifiable cause(s) for the increased risks of transplantation in children of different ethnicities and races require definition. Addressing these challenges faces the reality that for-profit research favours funding adult recipients, with ∼ 10-fold greater numbers, and their more modest longevity goals. Advocacy for funding "incentives" such as the Orphan Drug rules in the United States and upholding principles of equity and inclusion are critical to addressing the challenges of paediatric heart transplant recipients worldwide.

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.

Impact of the Pediatric ABO Policy Change on Listings, Transplants, and Outcomes for Children Younger Than 2 Years Listed for Heart Transplantation in the United States.

BACKGROUND: We assessed the impact of the liberalized ABO pediatric policy change on candidate characteristics and outcomes for children undergoing heart transplant (HT). METHODS AND RESULTS: Children <2 years undergoing HT with ABO strategy reported at listing and HT from December 2011 to November 2020 to the Scientific Registry of Transplant Recipients database were included. Characteristics at listing, HT, and outcomes during the waitlist and post-transplant were compared before the policy change (December 16, 2011 to July 6, 2016), and after the policy change (July 7, 2016 to November 30, 2020). The percentage of ABO-incompatible (ABOi) listings did not increase immediately after the policy change (P = .93); however, ABOi transplants increased by 18% (P < .0001). At listing, both before and after the policy change, ABOi candidates had higher urgency status, renal dysfunction, lower albumin, and required more cardiac support (intravenous inotropes, mechanical ventilation) than those listed ABO compatible (ABOc). On multivariable analysis, there were no differences in waitlist mortality between children listed as ABOi and ABOc before the policy change (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.61-1.05, P = .10) or after the policy change (aHR 1.2, 95% CI 0.85-1.6, P = .33). Post-transplant graft survival was worse for ABOi transplanted children before the policy change (aHR 1.8, 95% CI 1.1-2.8, P = .014), but not significantly different after the policy change (aHR 0.94, 95% CI 0.61-1.4, P = .76). After the policy change, ABOi listed children had significantly shorter waitlist times (P < .05). CONCLUSIONS: The recent pediatric ABO policy change has significantly increased the percentage of ABOi transplantations and decreased waitlist times for children listed ABOi. This change in policy has resulted in broader applicability and actual performance of ABOi transplantation with equal access to ABOi or ABOc organs, and thus eliminated the potential disadvantage of only secondary allocation to ABOi recipients.

Research Gaps in Pediatric Heart Failure: Defining the Gaps and Then Closing Them Over the Next Decade.

Given the numerous opportunities and the wide knowledge gaps in pediatric heart failure, an international group of pediatric heart failure experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric heart failure domain that scientists and funding agencies need to focus on over the next decade.

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.

Are dynamic measurements of central venous pressure in Fontan circulation during exercise or volume loading superior to resting measurements?

BACKGROUND: The main objective measure to assess the health of the Fontan circulation is the pressure measurement of the superior vena cava or pulmonary arteries. We reviewed the literature for benefits of measuring resting pressure in the Fontan circuit and explored whether dynamic measurement by volume loading or exercise has the potential to refine this diagnostic tool. METHODS: PubMed was searched for articles showing a relationship between resting post-operative central venous pressure or pulmonary artery pressure and Fontan failure. Relationships between post-operative central venous pressure or pulmonary artery pressure and volume loading changes, such as during exercise or volume loading during cardiac catheterization, were also queried. RESULTS: A total of 44 articles mentioned relationships between resting central venous pressure or pulmonary artery pressure and Fontan failure. Only 26 included an analysis between the variables and only seven of those articles found pressure to be predictive of Fontan failure. Ten articles examined the relationship between exercise or volume loading and outcomes and demonstrated a large individual variation of pressures under these dynamic conditions. CONCLUSIONS: Based on current literature, there is not a lot of strong evidence to show that elevated resting central venous pressure or pulmonary artery pressure is predictive of Fontan failure. Some individuals experience dramatic increases in central venous pressure or pulmonary artery pressure under increased loading conditions with exercise or bolus fluid infusion, while others experience increases closer to that of a healthy control population. Further studies are needed to examine whether more dynamic and continuous monitoring of systemic venous pressures might better predict outcomes in patients with Fontan circulation.

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.

Risk Factors for Extubation Failure After Pediatric Cardiac Surgery and Impact on Outcomes: A Multicenter Analysis.

IMPORTANCE: Extubation failure (EF) after pediatric cardiac surgery is associated with increased morbidity and mortality. OBJECTIVES: We sought to describe the risk factors associated with early (< 48 hr) and late (48 hr ≤ 168 hr) EF after pediatric cardiac surgery and the clinical implications of these two types of EF. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study using prospectively collected clinical data for the Pediatric Cardiac Critical Care Consortium (PC4) Registry. Pediatric patients undergoing Society of Thoracic Surgeons benchmark operation or heart transplant between 2013 and 2018 available in the PC4 Registry were included. MAIN OUTCOMES AND MEASURES: We analyzed demographics and risk factors associated with EFs (primary outcome) including by type of surgery. We identified potentially modifiable risk factors. Clinical outcomes of mortality and length of stay (LOS) were reported. RESULTS: Overall 18,278 extubations were analyzed. Unplanned extubations were excluded from the analysis. The rate of early EF was 5.2% (948) and late EF was 2.5% (461). Cardiopulmonary bypass time, ventilator duration, airway anomaly, genetic abnormalities, pleural effusion, and diaphragm paralysis contributed to both early and late EF. Extubation during day remote from shift change and nasotracheal route of initial intubation was associated with decreased risk of early EF. Extubation in the operating room was associated with an increased risk of early EF but with decreased risk of late EF. Across all operations except arterial switch, EF portrayed an increased burden of LOS and mortality. CONCLUSION AND RELEVANCE: Both early and late EF are associated with significant increase in LOS and mortality. Study provides potential benchmarking data by type of surgery. Modifiable risk factors such as route of intubation, time of extubation as well as treatment of potential contributors such as diaphragm paralysis or pleural effusion can serve as focus areas for reducing EFs.

Impact of Antegrade Pulmonary Blood Flow as Patients Progress Through Single-Ventricle Palliations.

BACKGROUND: The impact of antegrade pulmonary blood flow (APBF) during single-ventricle (SV) palliation continues to be debated. We sought to assess its impact on the hemodynamic profile and the short- and long-term outcomes of patients progressing through stages of SV palliation. METHODS: A retrospective single-center study was conducted of SV patients who underwent surgery between January 2010 and December 2020. Patients with APBF were matched to those with no APBF by a propensity score based on body surface area, sex, and type of systemic ventricle. Analysis was performed using appropriate statistics with a significance level of P = .05. RESULTS: Sixty-three patients with APBF were matched with 95 patients with no APBF. At the pre-stage 2 catheterization, APBF patients had a larger left pulmonary artery diameter (z score, 0.1 vs -0.8; P < .042). Patients with APBF had shorter cardiopulmonary bypass time (57.0 vs 79.0 minutes), shorter duration of mechanical ventilation (14.1 vs 17.4 hours), and shorter hospital length of stay (5.0 vs 7.0 days) at stage 2 palliation (P < .05). In the multivariable Cox regression analysis, patients with hypoplastic pulmonary arteries (z scores < -2; adjusted hazard ratio, 9.17) and patients with chromosomal abnormalities/genetic syndrome (adjusted hazard ratio, 4.03) were at increased risk for poor outcomes (P < .05). During the follow-up period, there was no significant difference in risk of the composite poor outcome and long-term survival between groups. CONCLUSIONS: SV patients with APBF had shorter cardiopulmonary bypass time, duration of mechanical ventilation, and hospital length of stay after stage 2 palliation. Patients with hypoplastic pulmonary arteries or chromosomal abnormalities/genetic syndromes had increased risk for poor outcomes. Maintaining APBF has better short-term outcomes, but there are no long-term hemodynamic or survival benefits.

Elective and non-elective endomyocardial biopsy in heart transplant patients and procedural outcomes: An IMPACT registry analysis.

BACKGROUND: Endomyocardial biopsies are standard of care for transplant surveillance, however the procedural risks are not well established, especially in children. The purpose of the study was therefore to assess procedural risks and outcomes associated with elective (surveillance) biopsies and non-elective (clinically indicated) biopsies. METHODS: We used the NCDR IMPACT registry database for this retrospective analysis. Patients undergoing an endomyocardial biopsy were identified using the procedural code, with a diagnosis of heart transplantation required. Data regarding indication, hemodynamics, adverse events and outcomes was gathered and analyzed. RESULTS: A total of 32 547 endomyocardial biopsies were performed between 2012-2020; 31 298 (96.5%) elective and 1133 (3.5%) were non-elective biopsies. Non-elective biopsy was more commonly performed in infants and in those above 18 years of age, in female and in Black race patients and in those with non-private insurance (all p < .05) and showed hemodynamic derangements. Overall rate of complications was low. Combined major adverse events were more common in non-elective patients, with sicker patient profile, use of general anesthesia and femoral access with overall decline in these events over time. CONCLUSIONS: This large-scale analysis shows safety of surveillance biopsies and that non-elective biopsies carry a small but significant risk of major adverse event. Patient profile impacts the safety of the procedure. These data may serve as important comparison point for newer non-invasive tests and for bench marking, especially in children.

Incidence of cytomegalovirus DNAemia in pediatric kidney, liver, and heart transplant recipients: Efficacy and risk factors associated with failure of weight-based dosed valganciclovir prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) is associated with morbidity and mortality in solid organ transplant recipients (SOTR). Valganciclovir (VGC) is extensively used for prophylaxis. Optimal dosing in children, risk factors for failure, and the impact of dose adjustments on CMV DNAemia is not well established. METHODS: This retrospective cohort study of pediatric SOTR transplanted between 2010-2018 evaluated the epidemiology of CMV DNAemia and used Cox-regression to assess the risk factors for CMV DNAemia within one-year following SOTR. RESULTS: In 393 pediatric SOTR (heart [96, 24.4%], kidney [180, 45.6%], liver [117, 29.8%]; median age 9.5 ± 0.3 years), overall CMV DNAemia incidence was 6.6/10 000 days (95%CI 5.1/10 000-7.9/10 000) and varied by organ groups: heart 8.2/10 000 days (95%CI 4.9/10 000-11.4/10 000), kidney 5.8/10 000 days (95%CI 3.9/10 000-7.8/10 000), liver 6.2/10 000 days (95%CI 3.7/10 000-8.7/10 000). CMV DNAemia was detected in 75 of 275 (27.2%) patients who received prophylaxis (40 cases occurred during prophylaxis and 35 occurred after completion of prophylaxis). The median VGC dose given according to institutional weight-based algorithm was approximately 1.5-fold lower than the manufacturer-recommended dose. This discordance was more prominent at younger age groups (3.2-fold lower in <2-year-old [100 mg versus 325 mg], 2.5-fold lower in <6-year-old [200 mg versus 447 mg]). Dose reduction due to adverse events was an independent risk factor for breakthrough CMV DNAemia (hazard ratio 2.2, 95%CI 1.2-3.8) among patients with similar age, CMV risk stratification, starting VGC dose, immunosuppressive therapy, and organ group. CONCLUSION: CMV events occurred while on VGC prophylaxis. Weight-based VGC may prevent supratherapeutic VGC exposure especially in younger children. Dose reduction of VGC prophylaxis for adverse event management places patients at an increased risk for CMV DNAemia suggesting other agents with fewer adverse effects should be considered and need to be studied in children.

Influence of Body Mass Index in Donor-Recipient Size Mismatch in Pediatric Heart Transplantation.

BACKGROUND: Body weight is the traditional metric for matching donor and recipient size for pediatric heart transplantation (pHT). We hypothesized that mismatch in body mass index (BMI) or body surface area (BSA) rather than weight is better associated with outcomes of transplantation and therefore should be used for donor-recipient size matching. METHODS: Analysis of the United Network for Organ Sharing database limited to pHT recipients was performed. Donor and recipient mismatch groups were created for weight, BMI, and BSA ratios. Differences in recipient characteristics between each cohort and the impact of mismatch on outcomes were statistically analyzed. RESULTS: A total of 4,465 patients were included in the analysis of which 43% had congenital heart disease (CHD). There were significant differences in patient characteristics by matching, independent of the matching parameter. Multivariable regression analysis showed that a low donor-recipient BMI ratio (compared to normal) (CHD OR 1.70; non-CHD 2.78) was a predictor of one-year mortality (all P < .001) in both CHD and non-CHD cohorts. Low BMI ratio was also associated with worse long-term survival in non-CHD groups, but not in the CHD cohort. Weight and BSA ratio did not predict one year or long-term survival. CONCLUSION: The use of low BMI donors compared to recipient may predict poor early and long-term survival and therefore should be avoided in pHT. The use of BMI matching may improve donor-recipient matching in pHT.