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.

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.

The American Association for Thoracic Surgery (AATS) 2024 expert consensus document: Management of neonates and infants with Ebstein anomaly.

OBJECTIVES: Symptomatic neonates and infants with Ebstein anomaly (EA) require complex management. A group of experts was commissioned by the American Association for Thoracic Surgery to provide a framework on this topic focusing on risk stratification and management. METHODS: The EA Clinical Congenital Practice Standards Committee is a multinational and multidisciplinary group of surgeons and cardiologists with expertise in EA. A citation search in PubMed, Embase, Scopus, and Web of Science was performed using key words related to EA. The search was restricted to the English language and the year 2000 or later and yielded 455 results, of which 71 were related to neonates and infants. Expert consensus statements with class of recommendation and level of evidence were developed using a modified Delphi method, requiring 80% of members votes with at least 75% agreement on each statement. RESULTS: When evaluating fetuses with EA, those with severe cardiomegaly, retrograde or bidirectional shunt at the ductal level, pulmonary valve atresia, circular shunt, left ventricular dysfunction, or fetal hydrops should be considered high risk for intrauterine demise and postnatal morbidity and mortality. Neonates with EA and severe cardiomegaly, prematurity (<32 weeks), intrauterine growth restriction, pulmonary valve atresia, circular shunt, left ventricular dysfunction, or cardiogenic shock should be considered high risk for morbidity and mortality. Hemodynamically unstable neonates with a circular shunt should have emergent interruption of the circular shunt. Neonates in refractory cardiogenic shock may be palliated with the Starnes procedure. Children may be assessed for later biventricular repair after the Starnes procedure. Neonates without high-risk features of EA may be monitored for spontaneous closure of the patent ductus arteriosus (PDA). Hemodynamically stable neonates with significant pulmonary regurgitation at risk for circular shunt with normal right ventricular systolic pressure should have an attempt at medical closure of the PDA. A medical trial of PDA closure in neonates with functional pulmonary atresia and normal right ventricular systolic pressure (>20-25 mm Hg) should be performed. Neonates who are hemodynamically stable without pulmonary regurgitation but inadequate antegrade pulmonary blood flow may be considered for a PDA stent or systemic to pulmonary artery shunt. CONCLUSIONS: Risk stratification is essential in neonates and infants with EA. Palliative comfort care may be reasonable in neonates with associated risk factors that may include prematurity, genetic syndromes, other major medical comorbidities, ventricular dysfunction, or sepsis. Neonates who are unstable with a circular shunt should have emergent interruption of the circular shunt. Neonates who are unstable are most commonly palliated with the Starnes procedure. Neonates who are stable should undergo ductal closure. Neonates who are stable with inadequate pulmonary flow may have ductal stenting or a systemic-to-pulmonary artery shunt. Subsequent procedures after Starnes palliation include either single-ventricle palliation or biventricular repair strategies.

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.

Mitral Valve Replacement in Infants and Children: Experience Using a 15-mm Mechanical Valve.

BACKGROUND: Reports using a 15-mm mechanical valve for mitral valve replacement (MMVR) in children are limited. We review our center's operative and postoperative experience with this valve. METHODS: We performed a single-center retrospective chart review identifying patients having undergone MMVRs between 2009 and 2022. We analyzed short- and long-term outcomes using descriptive statistics. RESULTS: Fifteen patients underwent 16 MMVRs with no operative deaths. The median age and weight at the time of operation was 6.2 months (interquartile range [IQR] 4.4-13.7), and 5.16 kg (IQR 4.5-6.9), respectively. Ten implants (66%) were placed in the supraannular position. Median postoperative duration of intubation was 1.5 days (IQR 1.0-3.75), cardiac intensive care unit length of stay was 6 days (IQR 3-13.5), and overall hospital length of stay was 17.0 days (IQR 12-48.5). Three patients (20%) experienced major adverse events postoperatively. Four of 13 patients discharged home (31%) required readmission within 30 days for subtherapeutic/supratherapeutic international normalized ratio values. There were no surgical mortalities and 4 late mortalities (27%). Six patients underwent subsequent MMVR at a median time to second MMVR of 6.8 (IQR 3.6-8.9) years. There are 6 patients with the original 15-mm MVR at a median time of 4.7 years since placement. CONCLUSIONS: We present the largest single-center cohort of patients having undergone 15-mm MMVR. Our experience is distinguished by a lower rate of major adverse events than previously reported, durability of the device, and a rapid postoperative recovery time. Appropriate and consistent anticoagulation is a notable challenge in this age group.

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.

Incidence and recovery of post-surgical heart block in children following cardiac surgery.

BACKGROUND: A subset of patients who develop post-surgical heart block have recovery of atrioventricular node function. Factors predicting recovery are not understood. We investigated our centre's incidence of post-surgical heart block and examine factors associated with recovery of atrioventricular node function. METHODS: We conducted a single-centre retrospective study of patients 0 - 21 years who underwent cardiac surgery between January 2010 and December 2019 and experienced post-operative heart block. Data including patient and clinical characteristics and operative variables were collected and analysed. RESULTS: Of 6333 surgical hospitalisations, 128 (2%) patients developed post-operative heart block. Of the 128 patients, 90 (70%) had return of atrioventricular node function, and 38 (30%) had pacemaker placement. Of the 38 patients who underwent pacemaker placement, 6 (15.8%) had recovery of atrioventricular node function noted on long-term follow-up. Median time from onset of heart block to late atrioventricular node recovery was 13 days (Interquartile range: 5 - 117). Patients with single-ventricle physiology (p = 0.04), greater weight (p = 0.03), and shorter cardiopulmonary bypass time (p = 0.015) were more likely to have recovery. The use of post-operative steroids was similar between all groups (p = 0.445). Infectious or wound complications were similar between pacemaker groups (p = 1). CONCLUSIONS: Two per cent of patients who underwent congenital cardiac surgery developed post-operative heart block, and 0.6% underwent pacemaker placement. Early recovery of atrioventricular node was associated with greater weight at the time of surgery, single-ventricle physiology, and shorter cardiopulmonary bypass time. Late recovery of atrioventricular node conduction following pacemaker placement occurred in 15.8% of patients.

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.

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.

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.