Pulmonary Artery Banding and Arch Repair vs Norwood for Unbalanced Atrioventricular Canal Defect.

BACKGROUND: The outcomes of single-ventricle palliation in unbalanced atrioventricular canal defect with coarctation of aorta (uAVC+CoA) have not been well studied. Systemic ventricle outflow tract obstruction has a propensity to develop in these patients after aortic arch repair with pulmonary artery banding (arch-PAB), which may adversely affect survival and Fontan candidacy. METHODS: A retrospective review was performed of patients who underwent single-ventricle palliation for uAVC+CoA from 2000 to 2022. Patients were divided into 2 groups based on initial palliation: (1) arch-PAB and (2) Norwood procedure. Demographic and clinical characteristics were analyzed and compared along with survival data. RESULTS: Stage 1 palliation for uAVC+CoA was performed in 41 patients. Arch-PAB was performed in 14 infants and Norwood in 27 infants. Arch-PAB patients had more chromosomal abnormalities (28.6 vs 7.4%, P < .009) and less severe systemic ventricle outflow tract obstruction on baseline echocardiogram (0.0 vs 70.4%, P < .001). Survival to stage 3 palliation was lower for the arch-PAB group (28.6% vs 66.6%, P = .02). Arch-PAB remained a significant risk factor for mortality (hazard ratio, 2.93; 95% CI, 1.05-8.53; P = .04) after adjusting for chromosomal abnormalities and atrioventricular valve regurgitation. After arch-PAB, systemic ventricle outflow tract obstruction was diagnosed in 13 of 14 patients. Echocardiography underestimated the degree of outflow tract obstruction in 10 of 13 arch-PAB patients. CONCLUSIONS: Arch-PAB has worse outcomes than Norwood for uAVC+CoA. Systemic ventricle outflow tract obstruction develops in almost all patients after arch-PAB. Outflow tract obstruction is underestimated by the echocardiogram and requires a high index of suspicion, along with advanced imaging, to ensure timely diagnosis and management.

Neonatal heart transplantation in the United States: Trends and outcomes.

BACKGROUND: Heart transplantation in the neonatal period is associated with excellent survival. However, outcomes data are scant and have been obtained primarily from two single-center reports within the United States. We sought to analyze the outcomes of all neonatal heart transplants performed in the United States using the United Network for Organ Sharing (UNOS) dataset. METHODS: The UNOS dataset was queried for patients who underwent infant heart transplantation from 1987 to 2021. Patients were divided into two groups based on age - neonates (<=31 days), and older infants (32 days-365 days). Demographic and clinical characteristics were analyzed and compared, along with follow up survival data. RESULTS: Overall, 474 newborns have undergone heart transplantation in the United States since 1987. Freedom from death or re-transplantation for neonates was 63.5%, 58.8% and 51.6% at 5, 10, and 20 years, respectively. Patients in the newborn group had lower unadjusted survival compared to older infants (p < .001), but conditional 1-year survival was higher in neonates (p = .03). On multivariable analysis, there was no significant difference in survival between the two age groups (p = .43). Black race, congenital heart disease diagnosis, earlier surgical era, and preoperative mechanical circulatory support use were associated with lower survival among infant transplants (p < .05). CONCLUSIONS: Neonatal heart transplantation is associated with favorable long-term clinical outcomes. Neonates do not have a significant survival advantage over older infants. Widespread applicability is limited by the small number of available donors. Efforts to expand the donor pool to include non-standard donor populations ought to be considered.

Outcomes of Neonates Born with Symptomatic Tetralogy of Fallot and Absent Ductus Arteriosus.

OBJECTIVE: To test the hypothesis that neonates with symptomatic tetralogy of Fallot (TOF) and absent ductus arteriosus (ADA) have worse clinical outcomes compared with those with a ductus arteriosus (DA), and that this difference is driven by those born with ADA and with critically deficient pulmonary blood flow (CDPBF). STUDY DESIGN: We performed a retrospective, multicenter cohort study of neonates who underwent intervention for symptomatic TOF comparing death and reintervention between subjects with and without a DA identified on fetal echocardiogram or on echocardiogram performed in the first postnatal day. Exclusion criteria were as follows: inability to define DA status, collaterals supplying pulmonary blood flow, atrioventricular septal defect, and absent pulmonary valve. We defined CDPBF as undergoing a procedure to augment pulmonary blood flow on the date of birth or extracorporeal membrane oxygenation prior to such a procedure. RESULTS: The study cohort included 519 patients, among whom 11% had ADA. Patients with ADA were more likely to have a genetic syndrome and had smaller branch pulmonary artery size. In analyses adjusting for center, interventional treatment strategy, genetic syndrome, and minimum branch pulmonary artery size, ADA was associated with higher mortality risk (adjusted hazard ratio of 2.37 (95% CI: 1.07,5.27; P = .034). Seven patients had CDPBF (1.3% of the entire cohort and 12% of patients with ADA). CONCLUSIONS: A minority of symptomatic TOF neonates have ADA, which is associated with higher adjusted mortality risk compared with those with a DA. CDPBF appears to be a rare but important entity in this population.

Pulmonary Artery Hypoplasia in Neonates With Tetralogy of Fallot.

BACKGROUND: Neonates with symptomatic tetralogy of Fallot (sTOF) with hypoplastic pulmonary arteries (hPA) are considered high risk. Data are needed to inform the impact of hPA on outcomes, and the ideal management strategy. OBJECTIVES: The objectives of this study were to quantify the impact of hPA on outcomes in neonates with sTOF and measure the impact of strategy on pulmonary artery (PA) growth in this population. METHODS: Neonates with sTOF from 2005 to 2017 were reviewed from the Congenital Cardiac Research Collaborative. Criteria for hPA included a unilateral PA z score <-2.0 and contralateral PA z score <0. Primary outcome was mortality. Secondary outcomes included reintervention and PA growth. RESULTS: We included 542 neonates with sTOF, including 188 (35%) with hPA and 354 (65%) with normal PA, with median follow-up of 4.1 years. Median right and left hPA z scores were -2.19 (25th-75th percentile: -2.55 to -1.94) and -2.23 (25th-75th percentile: -2.64 to -1.91), respectively. Staged repair (vs primary TOF repair) was less common in the hPA cohort (36 vs 44%; P = 0.07). Survival was similar between groups (unadjusted P = 0.16; adjusted P = 0.25). Reintervention was more common in the hPA group (HR: 1.28; 95% CI: 1.01-1.63; P = 0.044); there was no difference after definitive repair (HR: 1.21; 95% CI: 0.93-1.58; P = 0.16). PA growth at 1 year was greater in the hPA cohort, particularly for the right PA (P < 0.001). CONCLUSIONS: Despite perception, the presence of hPA in neonates with sTOF conferred no increase in overall hazard of mortality or reintervention after definitive repair. PA growth was superior in the hPA cohort. These findings suggest that the presence of hPA does not adversely impact outcomes in sTOF.

Comparison of treatment strategies for neonates with tetralogy of Fallot and pulmonary atresia.

OBJECTIVE: Neonates with tetralogy of Fallot and pulmonary atresia (TOF/PA) but no major aorta-pulmonary collaterals are dependent on the arterial duct for pulmonary blood flow and require early intervention, either by primary (PR) or staged repair (SR) with initial palliation (IP) followed by complete repair (CR). The optimal approach has not been established. METHODS: Neonates with TOF/PA who underwent PR or SR were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Outcomes were compared between PR and SR (IP + CR) strategies. Propensity scoring was used to adjust for baseline differences. The primary outcome was mortality. Secondary outcomes included complications, length of stay, cardiopulmonary bypass and anesthesia times, reintervention (RI), and pulmonary artery (PA) growth. RESULTS: Of 282 neonates, 106 underwent PR and 176 underwent SR (IP: 144 surgical, 32 transcatheter). Patients who underwent SR were more likely to have DiGeorge syndrome and greater rates of mechanical ventilation before the initial intervention. Mortality was not significantly different. Duration of mechanical ventilation, inotrope use, and complication rates were similar. Cumulative length of stay, cardiopulmonary bypass, and anesthesia times favored PR (P ≤ .001). Early RI was more common in patients who underwent SR (rate ratio, 1.42; P = .003) but was similar after CR (P = .837). Conduit size at the time of CR was larger with SR. Right PA growth was greater with PR. CONCLUSIONS: In neonates with TOF/PA, SR is more common in greater-risk patients. Accounting for this, SR and PR strategies have similar mortality. Perioperative morbidities, RI, and right PA growth generally favor PR, whereas SR allows for larger initial conduit implantation.

Bioprosthetic Pulmonary Valve Dysfunction in Congenital Heart Disease.

BACKGROUND: We aim to identify the incidence and timing of dysfunction and failure of stented bioprosthetic valves in the pulmonary position in congenital heart disease patients. METHODS: A total of 482 congenital heart disease patients underwent 484 stented bioprosthetic pulmonary valve implantations between 2008 and 2018. There were 164 porcine valves (Porcine) and 320 bovine pericardial valves (Pericardial) implanted. Primary endpoints were survival, valve dysfunction, and valve failure. RESULTS: Pericardial valves were implanted in older patients (22.0, interquartile range [IQR] 14-33 vs 16.0, IQR 11-23 years, P < 0.001). Five-year survival (96.7% vs 97.9%) for the Pericardial and Porcine groups, respectively, were similar, P > 0.05. Forty-six (34%) Porcine and 75 (27%) Pericardial group patients met criteria for valve dysfunction at a median echocardiographic follow-up time of 7.43 years (IQR 4.1-9.5 years) and 3.26 years (IQR 1.7-4.7 years), respectively. More Pericardial group patients suffered from at least mild late PR while late median peak gradient was higher in the Porcine group, P < .001 for both. Risk factors for valve dysfunction included decreasing patient age for the entire cohort (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.00-1.04, P = .015) and lack of anticoagulation at discharge for the Porcine group (HR 3.06, 95% CI 1.03-9.10, P = .044) but not the Pericardial group. Five-year cumulative incidence of dysfunction was 39% for the Pericardial group and 17% for the Porcine group. CONCLUSIONS: Porcine stented and bovine pericardial stented valves can be implanted in the pulmonary position in all age groups safely. However, despite similar rates of valve failure, bovine pericardial stented valves have a higher incidence of valve dysfunction at mid-term follow-up.

Impact of Management Strategy on Feeding and Somatic Growth in Neonates with Symptomatic Tetralogy of Fallot: Results from the Congenital Cardiac Research Collaborative.

OBJECTIVE: To evaluate early growth following primary or staged repair of neonatal symptomatic tetralogy of Fallot (sTOF). STUDY DESIGN: We performed a retrospective, multicenter cohort study of consecutive infants with sTOF who underwent initial intervention at age ≤30 days, from 2005 to 2017. Management strategies were either primary repair or staged repair (ie, initial palliation followed by complete repair). The primary outcome was change in weight-for-age z-score (ΔWAZ) from the initial intervention to age 6 ± 2 months. Secondary outcomes included method and mode of feeding, feeding-related medications, and feeding-related readmissions. Propensity score adjustment was used to account for baseline differences between groups. A secondary analysis was performed comparing patients stratified by the presence of adequate growth (6-month ΔWAZ > -0.5) or inadequate growth (6-month ΔWAZ ≤ -0.5), independent of treatment strategy. RESULTS: The study cohort included 143 primary repair subjects and 240 staged repair subjects. Prematurity was more common in the staged repair group. After adjustment, median ΔWAZ did not differ between treatment groups over the first 6 months of life (primary: -0.43 [IQR, -1.17 to 0.50]; staged: -0.31 [IQR, -1.31 to 0.71]; P = .55). For the entire cohort, ΔWAZ was negative (-0.36; IQR, -1.21 to 0.63). There were no between-group differences in the secondary outcomes. Secondary analysis revealed that the subjects with adequate growth were more likely to be orally fed at initial hospital discharge (P = .04). CONCLUSIONS: In neonates with sTOF, growth trajectory over the first 6 months of life was substandard, irrespective of treatment strategy. Those patients with adequate growth were more likely to be discharged from the index procedure on oral feeds.

Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study).

Mortality in infants with hypoplastic left heart syndrome (HLHS) is strongly correlated with right ventricle (RV) dysfunction. Cell therapy has demonstrated potential improvements of RV dysfunction in animal models related to HLHS, and neonatal human derived c-kit+ cardiac-derived progenitor cells (CPCs) show superior efficacy when compared to adult human cardiac-derived CPCs (aCPCs). Neonatal CPCs (nCPCs) have yet to be investigated in humans. The CHILD trial (Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome) is a Phase I/II trial aimed at investigating intramyocardial administration of autologous nCPCs in HLHS infants by assessing the feasibility, safety, and potential efficacy of CPC therapy. Using an open-label, multicenter design, CHILD investigates nCPC safety and feasibility in the first enrollment group (Group A/Phase I). In the second enrollment group, CHILD uses a randomized, double-blinded, multicenter design (Group B/Phase II), to assess nCPC efficacy based on RV functional and structural characteristics. The study plans to enroll 32 patients across 4 institutions: Group A will enroll 10 patients, and Group B will enroll 22 patients. CHILD will provide important insights into the therapeutic potential of nCPCs in patients with HLHS.Clinical Trial Registration https://clinicaltrials.gov/ct2/home NCT03406884, First posted January 23, 2018.

Palliation Strategy to Achieve Complete Repair in Symptomatic Neonates with Tetralogy of Fallot.

Neonates with symptomatic tetralogy of Fallot (sTOF) may undergo palliations with varying physiology, namely systemic to pulmonary artery connections (SPC) or right ventricular outflow tract interventions (RVOTI). A comparison of palliative strategies based on the physiology created is lacking. Consecutive sTOF neonates undergoing SPC or RVOTI from 2005-2017 were reviewed from the Congenital Cardiac Research Collaborative. The primary outcome was survival with successful complete repair (CR) by 18 months. A variety of secondary outcomes were assessed including overall survival, hospitalization-related comorbidities, and interstage reinterventions. Propensity score adjustment was utilized to compare treatment strategies. The cohort included 252 SPC (surgical shunt = 226, ductus arteriosus stent = 26) and 68 RVOTI (balloon pulmonary valvuloplasty = 48, RVOT stent = 11, RVOT patch = 9) patients. Genetic syndrome (29 [42.6%] v 75 [29.8%], p = 0.04), weight < 2.5 kg (28 [41.2%] v 68 [27.0%], p = 0.023), bilateral pulmonary artery Z-score < - 2 (19 [28.0%] v 36 [14.3%], p = 0.008), and pre-intervention antegrade flow (48 [70.6%] v 104 [41.3%], p < 0.001) were more common in RVOTI. Significant center differences were noted (p < 0.001). Adjusted survival to CR by 18 months (HR = 0.87, 95% CI = 0.63-1.21, p = 0.41) and overall survival (HR = 2.08, 95% CI = 0.93-4.65, p = 0.074) were similar. RVOTI had increased interstage reintervention (HR = 2.15, 95% CI = 1.36-3.99, p = 0.001). Total anesthesia (243 [213, 277] v 328 [308, 351] minutes, p < 0.001) and cardiopulmonary bypass times (117 [103, 132] v 151 [143, 160] minutes, p < 0.001) favored RVOTI. In this multicenter comparison of physiologic palliation strategies for sTOF, survival to successful CR and overall survival were similar; however, reintervention burden was significantly higher in RVOTI.

Comparative Costs of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot.

BACKGROUND: Recent data have demonstrated that overall mortality and adverse events are not significantly different for primary repair (PR) and staged repair (SR) approaches to management of neonates with symptomatic tetralogy of Fallot (sTOF). Cost data can be used to compare the relative value (cost for similar outcomes) of these approaches and are a potentially more sensitive measure of morbidity. OBJECTIVES: This study sought to compare the economic costs associated with PR and SR in neonates with sTOF. METHODS: Data from a multicenter retrospective cohort study of neonates with sTOF were merged with administrative data to compare total costs and cost per day alive over the first 18 months of life in a propensity score-adjusted analysis. A secondary analysis evaluated differences in department-level costs. RESULTS: In total, 324 subjects from 6 centers from January 2011 to November 2017 were studied (40% PR). The 18-month cumulative mortality (P = 0.18), procedural complications (P = 0.10), hospital complications (P = 0.94), and reinterventions (P = 0.22) did not differ between PR and SR. Total 18-month costs for PR (median $179,494 [IQR: $121,760-$310,721]) were less than for SR (median: $222,799 [IQR: $167,581-$327,113]) (P < 0.001). Cost per day alive (P = 0.005) and department-level costs were also all lower for PR. In propensity score-adjusted analyses, PR was associated with lower total cost (cost ratio: 0.73; P < 0.001) and lower department-level costs. CONCLUSIONS: In this multicenter study of neonates with sTOF, PR was associated with lower costs. Given similar overall mortality between treatment strategies, this finding suggests that PR provides superior value.

Propranolol treatment for chylothorax after congenital cardiac surgery.

OBJECTIVE: Postoperative chylothorax causes significant morbidities in pediatric patients with cardiac disease. New treatment approaches based on evolving understanding of underlying lymphatic dysfunction are being developed. We hypothesized that propranolol reduces morbidities and duration of chest tube requirement in high-output chylous effusion. METHODS: The postoperative courses of 50 pediatric patients with cardiac disease and high-output chylous effusion (control, n = 25; propranolol-treated, n = 25) were reviewed, including morbidities, length of hospitalization, and duration of chest tube requirement. Statistical analysis was performed using Welch's t test, Kruskal-Wallis tests for continuous variables, and chi-square and Fisher exact tests for categorical variables. Univariable logistic regression was used to determine predictors of response. RESULTS: Propranolol response was defined as 80% or more drainage reduction in 9 days or less. Treated patients were grouped into responders (<9 days) and nonresponders (>10 days). Neither initial amount of drainage (P = .12) nor day of propranolol initiation (P = .17) correlated with response. When compared with controls and nonresponders, responders had significantly fewer days with chest tube requirement (P < .01), infection (P < .0002), and thrombus (P = .005), and shorter hospitalization (P < .05). All patients had low serum albumin, although nonresponders had significantly decreased serum albumin when compared with responders and control patients (P < .002), and were more likely to receive albumin replacement (P < .01). Malnutrition was prevalent in all patient groups. CONCLUSIONS: Responders to propranolol had significantly less morbidity and duration of chest tube requirement when compared with control patients and nonresponders. Nonresponders did not have worse outcomes than control patients. We conclude that propranolol may be an effective treatment of patients with refractory chylothorax.

Cardiac surgery in children with trisomy 13 or trisomy 18: How safe is it?

Objective: Surgery for heart defects in children with trisomy 13 or 18 is controversial. We analyzed our 20-year experience. Methods: Since 2002, we performed 21 operations in 19 children with trisomy 13 (n = 8) or trisomy 18 (n = 11). Age at operation was 4 days to 12 years (median, 154 days). Principal diagnosis was ventricular septal defect in 10 patients, tetralogy of Fallot in 7 patients, arch hypoplasia in 1 patient, and patent ductus arteriosus in 1 patient. Results: The initial operation was ventricular septal defect closure in 9 patients, tetralogy of Fallot repair in 7 patients, pulmonary artery banding in 1 patient, patent ductus arteriosus ligation in 1 patient, and aortic arch/coarctation repair in 1 patient. There were no operative or hospital deaths. Median postoperative intensive care and hospital stays were 189 hours (interquartile range, 70-548) and 14 days (interquartile range, 8.0-37.0), respectively, compared with median hospital stays in our center for ventricular septal defect repair of 4.0 days and tetralogy of Fallot repair of 5.0 days. On median follow-up of 17.4 months (interquartile range, 6.0-68), 1 patient was lost to follow-up after 5 months. Two patients had reoperation without mortality. There have been 5 late deaths (4 with trisomy 18, 1 with trisomy 13) predominately due to respiratory failure from 4 months to 9.4 years postoperatively. Five-year survival was 66.6% compared with 24% in a group of unoperated patients with trisomy 13 or 18. Conclusions: Cardiac operation with an emphasis on complete repair can be performed safely in carefully selected children with trisomy 13 or trisomy 18. Hospital resource use measured by postoperative intensive care and hospital stays is considerably greater compared with nontrisomy 13 and 18.

Comparison of management strategies for neonates with symptomatic tetralogy of Fallot and weight <2.5 kg.

OBJECTIVE: To compare management strategies for neonates <2.5 kg with tetralogy of Fallot and symptomatic cyanosis who either undergo staged repair (SR) (initial palliation followed by later complete repair) or primary repair (PR). METHODS: Consecutive neonates with tetralogy of Fallot and symptomatic cyanosis weighing <2.5 kg at initial intervention and between 2005 and 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Primary outcome was mortality and secondary outcomes included component (eg, initial palliation, complete repair, or primary repair) and cumulative (SR: initial palliation followed by later complete repair) hospital and intensive care unit lengths of stay, durations of ventilation, inotrope use, cardiopulmonary bypass time, procedural complications, and reintervention. Outcomes were compared with propensity score adjustments with PR as the reference group. RESULTS: The cohort included 76 SR (initial palliation: 53 surgical and 23 transcatheter) and 44 PR patients. The observed risk of overall mortality was similar between SR and PR groups (15.8% vs 18.2%: P = .735). The adjusted hazard of mortality remained similar between groups overall (hazard ratio, 0.59; 95% confidence interval, 0.26-1.36; P = .214), as well as during short-term (<4 months: hazard ratio, 0.37; 95% confidence interval, 0.13-1.09; P = .071) and midterm (>4 months: hazard ratio, 1.32; 95% confidence interval, 0.30-5.79; P = .717) follow-up. Reintervention in the first 18 months was common in both groups (53.2% vs 48.4%; hazard ratio, 1.69; 95% confidence interval, 0.96-2.28; P = .072). Adjusted procedural complications and neonatal morbidity burden were overall lower in the SR group. Cumulative secondary outcome burdens largely favored the PR group. CONCLUSIONS: In this study comparing SR and PR treatment strategies for neonates with tetralogy of Fallot and symptomatic cyanosis and weight <2.5 kg, mortality and reintervention burden was high and independent of treatment strategy. Other potential advantages were observed with each approach.

Lymphatic Endothelial Cell Defects in Congenital Cardiac Patients With Postoperative Chylothorax.

OBJECTIVES: Chylothorax following cardiac surgery for congenital cardiac anomalies is a complication associated with severe morbidities and mortality. We hypothesize that there are intrinsic defects in the lymphatics of congenital cardiac patients. METHODS: Postsurgical chylothorax lymphatic endothelial cells (pcLECs) (n = 10) were isolated from the chylous fluid from congenital cardiac defect patients, and characterized by fluorescent-activated cell sorting, immunofluorescent staining, and quantitative RT-PCR. Results were compared to normal human dermal lymphatic endothelial cells (HdLECs). pcLECs (n = 3) and HdLECs were xenografted into immunocompromised mice. Implants and postoperative chylothorax patient's pulmonary tissues were characterized by immunostaining for lymphatic endothelial proteins. RESULTS: pcLECs expressed endothelial markers VECADHERIN, CD31, VEGFR2, lymphatic endothelial markers PROX1, podoplanin, VEGFR3, and progenitor endothelial markers CD90 and CD146. However, pcLECs had key differences relative to HdLECs, including altered expression and mislocalization of junctional proteins (VECADHERIN and CD31), and essential endothelial proteins, VEGFR2, VEGFR3, and PROX1. When xenografted in mice, pcLECs formed dilated lymphatic channels with poor cell-cell association. Similar to congenital lymphatic anomalies, the pulmonary lymphatics were dilated in a patient who developed postoperative chylothorax after cardiac surgery. CONCLUSIONS: Recent studies have shown that some postoperative chylothoraces in congenital cardiac anomalies are associated with anatomical lymphatic defects. We found that pcLECs have defects in expression and localization of proteins necessary to maintain lymphatic specification and function. This pcLEC phenotype is similar to that observed in lymphatic endothelial cells from congenital lymphatic anomalies. Co-existence of lymphatic anomalies should be considered as a feature of congenital cardiac anomalies.