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Evaluative research in interventional cardiology has focused on clinical and technical outcomes. Inclusion of economic data can enhance evaluative research by quantifying the relative economic burden incurred by different therapies. When combined with clinical outcomes, cost data can provide a measure of value (e.g., marginal cost-effectiveness). In some select situations, cost data can also be used as surrogates for complexity of care and morbidity. In this narrative review, we aim to provide a framework for the application of cost data in clinical trials and observational research, detailing how to incorporate this kind of data into interventional cardiology research.

We sought to characterize short- and long-term outcomes after superior cavopulmonary connection (SCPC) in children eligible for inclusion of antegrade pulmonary blood flow (APBF) in the SCPC circuit, exploring whether maintaining APBF was associated with outcomes.This was a retrospective cohort study of patients with single-ventricle heart disease and APBF who underwent SCPC at our center between January 1, 2000, and September 30, 2017. Patients were divided into 2 groups: APBF eliminated (APBF-), and APBF maintained (APBF+) at the time of SCPC.Of 149 patients, 108 (72.5%) were in APBF- and 41 (27.5%) were in APBF+. Of those in APBF+, 5 (12.2%) subsequently had APBF eliminated after SCPC. Patients in APBF+ had a higher prevalence of chest tube duration10 days and underwent more interventions during the post-SCPC hospitalization (1.9% vs 12%; P = .008 for both) but had shorter surgical support times at SCPC (P.0001). There were no differences in post-SCPC intensive care unit or hospital length of stay. During the study period, 82 patients (76%) in APBF- and 22 patients (54%) in APBF+ underwent Fontan completion. Patients in APBF+ had a greater weight gain from SCPC to Fontan (6.7 [1.8-22] kg vs 8.15 [4.4-20.6] kg; P = .012) and a shorter hospital length of stay after Fontan (9 [4-107] days vs 7.5 [4-14] days; P = .044).Short-term morbidity associated with maintaining APBF at the time of SCPC is modest, but longer term outcomes suggest potential benefits in those in whom APBF can be successfully maintained.

Background The Fontan circulation challenges the lymphatic system. Increasing production of lymphatic fluid and impeding lymphatic return, increased venous pressure may cause lymphatic dilatation and decrease lymphatic contractility. In-vitro studies have reported a lymphatic diameter-tension curve, with increasing passive stretch affecting the intrinsic contractile properties of each thoracic duct segment. We aimed to describe thoracic duct occlusion pressure and asses if thoracic duct dilation impairs contractility in individuals with a Fontan circulation and lymphatic failure. Methods Central venous pressure and thoracic duct measurements were retrospectively collected from 31 individuals with a Fontan circulation. Thoracic duct occlusion pressure was assessed during a period of external manual compression and used as an indicator of lymphatic vessel contractility. Measurements of pressure were correlated with measurements of the thoracic duct diameter in images obtained by dynamic contrast-enhanced MR lymphangiography. Results The average central venous pressure and average pressure of the thoracic duct were 17 mm Hg. During manual occlusion, the thoracic duct pressure significantly increased to 32 mm Hg. The average thoracic duct diameter was 3.3 mm. Thoracic duct diameter correlated closely with the central venous pressure. The rise in pressure following manual occlusion showed an inverse correlation with the diameter of the thoracic duct. Conclusion Higher central venous pressures are associated with increasing diameters of the thoracic duct. When challenged by manual occlusion, dilated thoracic ducts display a decreased ability to increase pressure. Dilatation and a resulting decreased contractility may partly explain the challenged lymphatic system in individuals with a Fontan circulation.

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.This study sought to compare the economic costs associated with PR and SR in neonates with sTOF.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.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.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.

BACKGROUND: Repair of complete atrioventricular canal (CAVC) is often complicated by atrioventricular valve regurgitation, particularly of the left-sided valve. Understanding the three-dimensional (3D) structure of the atrioventricular canal annulus prior to repair may help to inform optimized repair. However, the 3D shape and movement of the CAVC annulus has yet to be quantified nor has it been rigorously compared to a normal mitral valve annulus. METHODS: The complete annuli of 43 patients with CAVC were modeled in 4 cardiac phases using transthoracic 3D echocardiograms and custom code. The annular structure was compared to the annuli of 20 normal pediatric mitral valves using 3D metrics and statistical shape analysis (Procrustes analysis). RESULTS: The unrepaired CAVC annulus varied in shape significantly throughout the cardiac cycle. Procrustes analysis visually demonstrated that the average normalized CAVC annular shape is more planar than the normal mitral annulus. Quantitatively, the annular height to valve width ratio of the native left CAVC atrioventricular valve was significantly lower than that of a normal mitral valve in all systolic phases(p

Single ventricle patients typically undergo some form of advanced diagnostic imaging prior to superior cavopulmonary connection (SCPC). We sought to evaluate variability of diagnostic practice and associated comprehensive risk. A retrospective evaluation across 4 institutions was performed (1/1/2010–9/30/2016) comparing the primary modalities of cardiac catheterization (CC), cardiac magnetic resonance (CMR), and cardiac computed tomography (CT). Associated risks included anesthesia/sedation, vascular access, total room time, contrast agent usage, radiation exposure, and adverse events (AEs). Of 617 patients undergoing SCPC, 409 (66%) underwent at least one advanced diagnostic imaging study in the 60 days prior to surgery. Seventy-eight of these patients (13%) were analyzed separately because of a concomitant cardiac intervention during CC. Of 331 (54%) with advanced imaging and without catheterization intervention, diagnostic CC was most common (59%), followed by CT (27%) and CMR (14%). Primary modality varied significantly by institution (p

Patent ductus arteriosus (PDA) stenting is an accepted method for securing pulmonary blood flow in cyanotic neonates. In neonates with pulmonary atresia and single source ductal-dependent pulmonary blood flow (SSPBF), PDA stenting remains controversial. We sought to evaluate outcomes in neonates with SSPBF, comparing PDA stenting and surgical Blalock–Taussig shunt (BTS). Neonates with SSPBF who underwent PDA stenting or BTS at the four centers of the Congenital Catheterization Research Collaborative from January 2008 to December 2015 were retrospectively reviewed. Reintervention on the BTS or PDA stent prior to planned surgical repair served as the primary endpoint. Additional analyses of peri-procedural complications, interventions, and pulmonary artery growth were performed. A propensity score was utilized to adjust for differences in factors. Thirty-five patients with PDA stents and 156 patients with BTS were included. The cohorts had similar baseline characteristics, procedural complications, and mortality. Interstage reintervention rates were higher in the PDA stent cohort (48.6% vs. 15.4%, p

Measuring the effect of a treatment on outcomes is an important goal for research in pediatric/congenital interventional cardiology. The breadth of anatomic and physiologic variations, patient ages, and genetic syndromes and noncardiac comorbid conditions all represent sources of potential confounding and effect modification that are major obstacles to this goal. If not accounted for, these factors can obscure the "true" treatment effect and lead to spurious conclusions about the relative efficacy and/or safety of therapies. In this review, we discuss the importance of confounding and effect modification in pediatric/congenital interventional cardiology research. We define these terms and discuss strategies (both in study design and data analysis) to mitigate error introduced by confounding and effect modification. The importance of confounding by indication in pediatric/congenital cardiology is discussed along with specific methods to address it.

The COVID-19 pandemic has posed tremendous stress on the health care system. Its effects on pediatric/congenital catheterization program practice and performance have not been described.The purpose of this study was to evaluate how case volumes, risk-profile, and outcomes of pediatric/congenital catheterization procedures changed in response to the first wave of COVID-19 and after that wave.A multicenter retrospective observational study was performed using Congenital Cardiac Catheterization Project on Outcomes Registry (C3PO) data to study changes in volume, case mix, and outcomes (high-severity adverse events [HSAEs]) during the first wave of COVID (March 1, 2020, to May 31, 2020) in comparison to the period prior to (January 1, 2019, to February 28, 2020) and after (June 1, 2020, to December 31, 2020) the first wave. Multivariable analyses adjusting for case type, hemodynamic vulnerability, and age group were performed. Hospital responses to the first wave were captured with an electronic study instrument.During the study period, 12,557 cases were performed at 14 C3PO hospitals (with 8% performed during the first wave of COVID and 32% in the postperiod). Center case volumes decreased from a median 32.1 cases/month (IQR: 20.7-49.0 cases/month) before COVID to 22 cases/month (IQR: 13-31 cases/month) during the first wave (Despite increased case-mix complexity, C3PO programs maintained, if not improved, their performance in terms of HSAE. Exploratory analyses of practice changes may inform future harm-reduction efforts.

ObjectivesTo characterize hepatic to systemic lymphatic connections in patients with systemic lymphatic disease using intra-hepatic lymphangiography and to compare outcomes after lymphatic intervention.MethodsIn this retrospective study, patients with intra-hepatic lymphangiography from May 2014 – April 2019 at our institution were included. Imaging review was performed and hepatic lymphatic connections and flow patterns were characterized. Clinical data were reviewed and comparisons between patients undergoing lymphatic intervention with or without abnormal hepatic lymphatics were performed.ResultsDuring the study period, 105 patients underwent intra-hepatic lymphangiography. Primary clinical presentation included ascites (19/105), chylothorax (27/105), plastic bronchitis (PB) (17/105), and protein losing enteropathy (PLE) (42/105). Five categories of hepatic lymphatic connections and flow patterns were identified (%): normal (25%, 26/105), hepatoperitoneal (12%, 13/105), hepatopulmonary (10.5%, 11/105), hepatomesenteric (7.5%, 8/105), and hepatoduodenal (41%, 43/105) with four patients having more than one abnormal pattern. A comparison between clinical presentation and imaging category revealed an increased likelihood of having ascites with hepatoperitoneal (p< .0001), chylothorax/PB with hepatopulmonary (p= .01), and PLE with hepatoduodenal (p< .001) connections. Seventy-six patients had a lymphatic intervention, 24% with normal, and 76% with abnormal liver lymphatics. There was no difference in length of hospital stay or mortality between the two groups, but there was a prolonged time to symptom resolution (p= .006) and persistent symptoms after 6 months (5% vs 44%,p= .002) in the group with abnormal liver lymphatics.ConclusionWe identified five liver lymphatic imaging categories with a substantial correlation to presenting lymphatic disease. Abnormal imaging patterns correlated with increased morbidity. Evaluation of liver lymphatics should be considered in patients with a systemic lymphatic disease if central lymphatic imaging is normal.Key Points•We identified five liver lymphatic imaging patterns: normal, hepatoperitoneal, hepatomesenteric, hepatopulmonary, and hepatoduodenal.•Imaging patterns were correlated with disease presentation (normal – chylothorax/PB, hepatoperitoneal – ascites/chylothorax, hepatopulmonary – chylothorax/PB, hepatoduodenal – PLE).•Abnormal imaging patterns correlated with increased morbidity.

Background: Lymphatic embolization therapy has proven effective for Fontan failure from plastic bronchitis or protein-losing enteropathy but not when multiple lymphatic compartments are involved; furthermore, embolization does not alter the underlying pathophysiology of lymphatic dysfunction. A technique for transcatheter thoracic duct decompression (TDD), rerouting the thoracic duct to the pulmonary venous atrium to treat multicompartment lymphatic failure is described and early outcomes presented. Methods: Initially covered stents were used to channel the innominate vein flow inside of the cavopulmonary pathway into the pulmonary venous atrium. A modified approach was developed where covered stents redirected innominate vein directly to the left atrium via an extravascular course. Baseline and follow-up data on all patients undergoing TDD were reviewed. Results: Twelve patients underwent TDD between March 2018 and February 2021 at a median age of 12 (range: 2–22) years. Lymphatic failure occurred in median of 3 compartments per patient (protein-losing enteropathy, ascites, pleural effusions, plastic bronchitis); 10 patients had lymphatic embolizations before TDD. TDD method was intra-Fontan tunnel in 4, direct approach in 7, and other in 1. There were no major procedural complications; 6 patients underwent subsequent procedures, most commonly to treat endoleaks. Lymphatic failure resolved in 6 patients, improved in 2, and was unchanged in 4 at 6 (range: 1–20) months follow-up. One patient died after TDD from Fontan failure. Conclusions: TDD is a promising new treatment for the failing Fontan physiology from multicompartment lymphatic failure. Additional work is needed to refine the technique and define optimal candidates.

Background:Multicentre research databases can provide insights into healthcare processes to improve outcomes and make practice recommendations for novel approaches. Effective audits can establish a framework for reporting research efforts, ensuring accurate reporting, and spearheading quality improvement. Although a variety of data auditing models and standards exist, barriers to effective auditing including costs, regulatory requirements, travel, and design complexity must be considered.Materials and methods:The Congenital Cardiac Research Collaborative conducted a virtual data training initiative and remote source data verification audit on a retrospective multicentre dataset. CCRC investigators across nine institutions were trained to extract and enter data into a robust dataset on patients with tetralogy of Fallot who required neonatal intervention. Centres provided de-identified source files for a randomised 10% patient sample audit. Key auditing variables, discrepancy types, and severity levels were analysed across two study groups, primary repair and staged repair.Results:Of the total 572 study patients, data from 58 patients (31 staged repairs and 27 primary repairs) were source data verified. Amongst the 1790 variables audited, 45 discrepancies were discovered, resulting in an overall accuracy rate of 97.5%. High accuracy rates were consistent across all CCRC institutions ranging from 94.6% to 99.4% and were reported for both minor (1.5%) and major discrepancies type classifications (1.1%).Conclusion:Findings indicate that implementing a virtual multicentre training initiative and remote source data verification audit can identify data quality concerns and produce a reliable, high-quality dataset. Remote auditing capacity is especially important during the current COVID-19 pandemic.

Visual Abstract, Highlights • Children with a bidirectional superior cavopulmonary connection (Glenn circulation) develop dysregulated angiogenesis and pulmonary angiodysplasia in the form of arteriovenous malformations (AVMs). No targeted therapy exists. • The von Willebrand factor (vWF)–angiopoietin axis plays a major role in normal angiogenesis, angiodysplasia, and AVM formation in multiple diseases. • vWF and angiopoietin-2 (which destabilizes vessel formation) were abnormal in children with a Glenn circulation versus control children. Within Glenn patients, angiopoietin-1 (which stabilizes vessel formation) and angiogenesis were different in the systemic versus pulmonary circulation. Plasma angiopoietin-1 was lower in the pulmonary circulation of Glenn patients with pulmonary AVMs than Glenn patients without AVMs. • In parallel, differences in multiple angiogenic and inflammatory signaling peptides were observed between Glenn patients and controls, which indicated derangements in multiple angiogenic pathways in Glenn patients. • These findings support the novel hypothesis that abnormal vWF metabolism and angiopoietin signaling dysregulate angiogenesis and contribute to pulmonary AVM formation in children with a Glenn circulation. • The vWF-angiopoietin axis may be a target to correct angiogenic imbalance and reduce pulmonary angiodysplasia in Glenn patients., Summary Children with a bidirectional superior cavopulmonary (Glenn) circulation develop angiodysplasia and pulmonary arteriovenous malformations (AVMs). The von Willebrand factor (vWF)–angiopoietin axis plays a major role in AVM formation in multiple diseases. We observed derangements in global angiogenic signaling, vWF metabolism, angiopoietins, and in vitro angiogenesis in children with a Glenn circulation versus controls and within Glenn pulmonary versus systemic circulations. These findings support the novel hypothesis that abnormalities in the vWF-angiopoietin axis may dysregulate angiogenesis and contribute to Glenn pulmonary AVMs. The vWF-angiopoietin axis may be a target to correct angiogenic imbalance in Glenn patients, for whom no targeted therapy exists.

Objectives The objective of this study was to assess contemporary use of operator directed sedation (ODS) and anesthesiologist care (AC) in the pediatric/congenital cardiac catheterization laboratory (PCCL), specifically evaluating whether the use of operator-directed sedation was associated with increased risk of major adverse events. Background The safety of ODS relative to AC during PCCL procedures has been questioned. Methods A multicenter, retrospective cohort study was performed studying procedures habitually performed with ODS or AC at IMPACT (Improving Adult and Congenital Treatment) registry hospitals using ODS for ≥5% of cases. The risks for major adverse events (MAE) for ODS and AC cases were compared, adjusted for case mix. Current recommendations were evaluated by comparing the ratio of observed to expected MAE for cases in which ODS was inappropriate (inconsistent with those guidelines) with those for similar risk AC cases, as well as those in which ODS or AC was appropriate. Results Of the hospitals submitting data to IMPACT, 28 of 101 met inclusion criteria. Of the 7,042 cases performed using ODS at these centers, 88% would be inappropriate. Use of ODS was associated with lower likelihood of MAE both in observed results (p Conclusions Across a range of hospitals, ODS was used safely and with improved efficiency. Clinical judgment better identified cases in which ODS could be used than pre-procedural risk score. This should inform future guidelines for the use of ODS and AC in the catheterization laboratory

Isolated pulmonary artery (PA) of ductal origin (IPADO) is a rare cardiac defect which requires surgical repair, with or without preceding palliation. We sought to determine the impact of treatment strategy on outcomes. Retrospective study of consecutive patients with IPADO that underwent staged or primary repair from 1/05 to 9/16 at 6 Congenital Cardiac Research Collaborative centers. Patients with single ventricle physiology, major aortopulmonary collaterals, or bilateral IPADO were excluded. Primary outcome was isolated PA z-score at late follow-up. Secondary outcomes included PA symmetry index (isolated:confluent PA diameter) and reintervention burden. Propensity score adjustment was used to account for baseline differences. Of 60 patients in the study cohort, 26 (43%) underwent staged and 34 (57%) primary repair. The staged and primary repair groups differed in weight at diagnosis and presence of other heart disease but not in baseline PA dimensions. Staged patients underwent ductal stent (n = 16) or surgical shunt (n = 10) placement followed by repair at 210 vs. 21 days in the primary repair group (p < 0.001). At median follow-up of 4.5 years post-repair, after adjustment, isolated PA z-score (− 0.74 [− 1.75, − 0.26] vs. − 1.95 [− 2.91, − 1.59], p = 0.012) and PA symmetry index (0.81 [0.49, 1.0] vs. 0.55 [0.48, 0.69], p = 0.042) significantly favored the staged repair group. Freedom from PA reintervention was not different between groups (adjusted HR 0.78 [0.41, 1.48]; p = 0.445). A staged approach to repair of IPADO is associated with superior isolated PA size and symmetry at late follow-up. Consideration should be given to initial palliation in IPADO patients, when feasible.

Objectives The aim of this study was to enumerate and categorize quality metrics relevant to the pediatric/congenital cardiac catheterization laboratory (PCCL). Background Diagnostic and interventional catheterization procedures are an increasingly important part of the care of young patients with cardiac disease. Measurement of the performance of PCCL programs in a stringent and consistent fashion is a crucial step toward improving outcomes. To the best of our knowledge, a systematic evaluation of current quality metrics in PCCL has not been performed previously. Methods Potential metrics were evaluated by: 1) a systematic review of peer-reviewed research; 2) a review of metrics from organizations interested in quality improvement, patient safety, and/or PCCL programs; and 3) a survey of U.S. PCCL cardiologists. Collected metrics were grouped on 2 dimensions: 1) Institute of Medicine domains; and 2) the Donabedian structure/process/outcome framework. Survey responses were dichotomized between favorable and unfavorable responses and then compared within and between categories. Results In the systematic review, 6 metrics were identified (from 9 publications), all focused on safety either as an outcome (adverse events [AEs], mortality, and failure to rescue along with radiation exposure) or as a structure (procedure volume or operator experience). Four organizations measure quality metrics of PCCL programs, of which only 1 publicly reports data. For the survey, 229 cardiologists from 118 hospital programs responded (66% of individuals and 72% of hospital programs). The highest favorable ratings were for safety metrics (p Conclusions There is a limited number of PCCL quality metrics, primarily focused on safety. Confidence in current risk adjustment methodology is low. The knowledge gaps identified should guide future research in the development of new quality metrics.

Introduction While frequently performed in the adult population, percutaneous coronary artery stent angioplasty (CSA) in infants is rare. CSA in infants is challenging because of limited options in terms of appropriately sized (length and diameter) stents, concern about stenting vessels with significant growth potential and limited data regarding durability of benefit. We report a multicenter case series of infants who underwent CSA. Methods A multicenter, retrospective case series of infants who underwent percutaneous CSA to treat post-operative coronary artery stenoses was performed. Results Six infants from 3 institutions who underwent post-operative CSA were identified. The anatomic diagnoses were d-transposition of the great arteries in 3 cases, anomalous left coronary artery from the pulmonary artery in 2 and supravalvar aortic stenosis in 1. All infants were critically ill at the time of CSA. Diameters of coronary artery stents used ranged from 2.25 to 2.75 mm. There were no procedural complications. All stents were patent immediately after placement and the clinical condition improved or stabilized in all patients. Follow-up angiography was available for 3 patients at 4 to 16 months post-CSA, at which time 67% (2/3) remained patent. Conclusion CSA is a feasible and effective therapy for critically ill infants with post-surgical coronary obstruction. Treatment appears to allow at least short-term reperfusion to facilitate recovery of ventricular function and potential development of collateral circulation when longer-term stent patency is not achieved. Longer-term stent patency and coronary artery health remain unanswered questions.

Neonatal chylothorax (NCTx) and central lymphatic flow disorder (CLFD) are historically challenging neonatal disorders with high morbidity and mortality. METHODS We conducted a retrospective study of 35 neonates with pulmonary lymphatic abnormalities at our institution who underwent lymphatic evaluation between December 2015 and September 2018. Patients with only pulmonary lymphatic perfusion syndrome were classified as NCTx and those with multiple flow abnormalities were classified as CLFD. Demographics, clinical characteristics, and outcomes were compared using t-tests/Wilcoxon rank sum tests and Fisher's exact tests. RESULTS All 35 patients had intranodal MR lymphangiography and 14 (40%) also had conventional fluoroscopic lymphangiography. Fifteen (42.8%) patients were diagnosed with NCTx and 20 (57.1%) were diagnosed with CLFD. Thirty-four (97.1%) patients had pleural effusions. None of the NCTx group had ascites, anasarca, or dermal backflow compared to 17 (85%) (p

Objectives To evaluate short- and middle-term outcomes after transcatheter patent ductus arteriosus (TC-PDA) closure in small infants, specifically device-related left pulmonary artery (LPA) stenosis and aortic coarctation, risk factors, and changes over time. Background Recent studies have demonstrated successful transcatheter PDA (TC-PDA) closure in small infants. LPA stenosis and aortic coarctation have been seen after TC-PDA, but it is not clear whether device-related LPA/aortic obstruction persists. Methods A single-center retrospective study of infants ≤4 kg who underwent TC-PDA closure from February 1, 2007 to September 1, 2018 was performed, evaluating the incidence and risk factors for LPA stenosis and coarctation. Results Forty-four patients underwent successful TC-PDA with Amplatzer Vascular Plug II (AVPII; n = 30), Amplatzer Duct Occluder II-Additional Sizes (n = 10), Amplatzer Duct Occluder I (n = 3), and coil-filled AVPI (n = 1) devices, all via an antegrade approach. Median birthweight and procedural weight were 890 g (range: 490-3,250) and 2.8 kg (range: 1.2-4.0), respectively. Median follow-up was 0.7 years (range: 2 days-7 years). Thirty-eight patients had post-procedure echocardiograms assessing LPA/aortic obstruction. Of those, 17 had LPA flow acceleration/stenosis (≥1.5 m/s), which improved or resolved in all patients with available follow-up; 3 developed mild coarctation (>2 m/s), which improved in the two with more than short-term follow-up; 4 developed mild flow acceleration (1.5-2 m/s) in the descending aorta, which resolved in three and increased in one (2.4 m/s). Flow acceleration in the LPA was associated with younger procedural age, larger PDA minimal diameter, and placement of a device other than the AVPII. There was no device-related mortality or need for reintervention. Conclusion TC-PDA in small infants is effective, without significant complications. Device-related LPA/aortic obstruction can improve with time/growth.

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.

Repair of complete atrioventricular canal (CAVC) is often complicated by residual left atrioventricular valve regurgitation. The structure of the mitral and tricuspid valves in biventricular hearts has previously been shown to be associated with valve dysfunction. However, the three-dimensional (3D) structure of the entire unrepaired CAVC valve has not been quantified. Understanding the 3D structure of the CAVC may inform optimized repair.Novel open-source work flows were created in SlicerHeart for the modeling and quantification of CAVC valves on the basis of 3D echocardiographic images. These methods were applied to model the annulus, leaflets, and papillary muscle (PM) structure of 35 patients (29 with trisomy 21) with CAVC using transthoracic 3D echocardiography. The mean leaflet and annular shapes were calculated and visualized using shape analysis. Metrics of the complete native CAVC valve structure were compared with those of normal mitral valves using the Mann-Whitney U test. Associations between CAVC structure and atrioventricular valve regurgitation were analyzed.CAVC leaflet metrics varied throughout systole. Compared with normal mitral valves, the left CAVC PMs were more acutely angled in relation to the annular plane (P .001). In addition, the anterolateral PM was laterally and inferiorly rotated in CAVC, while the posteromedial PM was more superiorly and laterally rotated, relative to normal mitral valves (P .001). Lower native CAVC atrioventricular valve annular height and annular height-to-valve width ratio before repair were both associated with moderate or greater left atrioventricular valve regurgitation after repair (P .01).It is feasible to model and quantify 3D CAVC structure using 3D echocardiographic images. The results demonstrate significant variation in CAVC structure across the cohort and differences in annular, leaflet, and PM structure compared with the mitral valve. These tools may be used in future studies to catalyze future research intended to identify structural associations of valve dysfunction and to optimize repair in this vulnerable and complex population.

Fontan-associated protein losing enteropathy is a challenge to treat and is a major contributor to morbidity and mortality in patients with palliated single ventricle. Numerous strategies for management have been proposed, with confusion as to how best to stratify and implement care among the many treatments available. Medical management can be helpful in some, while novel lymphatic interventions hold potential for remission with good results. We review our institutional approach to protein losing enteropathy after Fontan operation and provide a suggested algorithm and pathway for effective care.

BACKGROUND Carotid artery (CA) and axillary artery (AA) access are increasingly used for transcatheter stenting of the patent ductus arteriosus (PDA), although reports are limited. METHODS The Congenital Catheterization Research Collaborative (CCRC) reviewed multicenter data from infants who underwent PDA stenting via the CA or AA approach from 2008 to 2017, and compared outcomes to those of infants undergoing PDA stenting via the femoral artery (FA) approach. Post-procedure ultrasound (US) imaging was reviewed. RESULTS Forty-nine infants underwent PDA stenting from the CA (n = 43) or AA (n = 6) approach, compared with 55 infants who underwent PDA stenting from the FA approach. The PDA was the sole pulmonary blood flow (PBF) source in 61% of infants in the CA/AA cohort, compared with 33% of the FA cohort (p

Anticoagulation in children is problematic for multiple reasons. Currently used anticoagulants have significant disadvantages and may negatively affect quality of life (QOL). This manuscript describes the design, rationale, and methods of a prospective, randomized, open label phase II multi-national clinical trial of a direct oral anticoagulant (DOAC), apixaban, in children and infants with congenital and acquired heart disease. This trial is designed to gather preliminary safety and pharmacokinetics (PK) data, as well as generate data on QOL of individuals taking apixaban compared to the standard of care (SOC) anticoagulants vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). A key issue this trial seeks to address is the practice of using therapeutics tested in adult trials in the pediatric population without robust pediatric safety or efficacy data. Pediatric heart diseases are not common, and specific diagnoses often meet the criteria of a rare disease; thus, statistical efficacy may be difficult to achieve. This trial will provide valuable PK and safety data intended to inform clinical practice for anticoagulation in pediatric heart diseases, a setting in which a fully powered phase III clinical trial is not feasible. A second consideration this trial addresses is that metrics besides efficacy, such as QOL, have not been traditionally used as endpoints in regulated anticoagulation studies yet may add substantial weight to the clinical decision for use of a DOAC in place of VKA or LMWH. This study examines QOL related to both heart disease and anticoagulation among children randomized to either SOC or apixaban. There are considerable strengths and benefits to conducting a clinical trial in pediatric rare disease populations via an industry-academic collaboration. The SAXOPHONE study represents a collaboration between Bristol-Myers Squibb (BMS)/Pfizer Alliance, and the National Heart, Lung, and Blood Institute's (NHLBI) Pediatric Heart Network (PHN) and may be an attractive model for future pediatric drug trials.

For infants with shunt-dependent or ductal-dependent single ventricle heart disease, poor growth is common and associated with morbidity and impaired neurodevelopmental outcomes. Although attention has focused on nutrition to promote weight gain, little is known about the relation between heart failure and growth factors. A prospective observational pilot study was performed to assess the relation between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors (insulin-like growth factor 1 [IGF-1] and insulin-like growth factor-binding protein 3) at 3 visits: (1) before discharge from neonatal intervention with the establishment of stable pulmonary blood flow, (2) immediately before superior cavopulmonary connection, and (3) before discharge after superior cavopulmonary connection operation. The relation between BNP and growth factors was analyzed using Spearman pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered worthy of further exploration using a p0.10, given the exploratory nature of the study. The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at visit 1 and decreased over time (287 pg/dl [interquartile range 147 to 794], 85 pg/dl [52 to 183], and 90 pg/dl [70 to 138]). Median IGF-1 Z score was0 at each visit but increased over time (-0.9 [interquartile range -1.1 to 0.1], -0.7 [-1.2 to 0.1], and -0.5 [-1.2 to 0]). Inverse correlations were found between BNP and IGF-1 at visit 1 (r = -0.40, p = 0.097), BNP and IGF-1 and insulin-like growth factor-binding protein 3 at visit 2 (r = -0.33, p = 0.080 and r = -0.33, p = 0.085, respectively) and BNP and IGF-1 Z score at visit 3 (r = -0.42, p = 0.049). Significant relations were likewise found between the change in BNP and the change in IGF-1 between visits 1 and 3 (p = 0.046) and between visits 2 and 3 (p = 0.048). In conclusion, this pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth.

Background: Stenting of the patent ductus arteriosus (PDA) is an established palliative option for infants with ductal-dependent pulmonary blood flow. Following initial palliation, reintervention on the PDA stent is common, but risk factors have not been characterized. Methods: Infants with ductal-dependent pulmonary blood flow palliated with PDA stent between 2008 and 2015 were reviewed within the Congenital Cardiac Research Collaborative. Rates and risk factors for reintervention were analyzed. Results: Among 105 infants who underwent successful PDA stenting, 41 patients (39%) underwent a total of 53 reinterventions on the PDA stent, with all but one occurring within 6 months of the initial intervention. Stent redilation constituted the majority of reintervention (n=35; 66%) followed by additional stent placement (n=11; 21%) and surgical shunt placement (n=7; 13%). The majority of reintervention was nonurgent, and there were no deaths during the reintervention procedure. All but one reintervention occurred within 6 months of the initial procedure. On univariate analysis, risk factors for reintervention included anticipated single-ventricle physiology, lack of prior balloon pulmonary valvuloplasty, use of drug-eluting stent, and increased ductal tortuosity. Conclusions: In infants with ductal-dependent pulmonary blood flow palliated with PDA stent implantation, reintervention is common, can be performed safely, and is associated with both anatomic/procedural factors and anticipated final physiology.

Introduction: Absent ductus arteriosus (ADA) is a poorly described feature associated with tetralogy of Fallot (TOF). We compare characteristics and outcomes of neonates with symptomatic TOF (sTOF) with ADA to those with a ductus arteriosus (DA). Hypothesis: We hypothesized: neonates with sTOF and ADA would have similar outcomes to those born with a DA, and a small portion of the ADA cohort would have critically-deficient pulmonary blood flow (CDPBF). Methods: Consecutive neonates with sTOF who underwent intervention during the neonatal period from 2005—2017 were identified from the Congenital Cardiac Research Collaborative. Those with DA on echocardiogram performed on the first day of life or on fetal echocardiogram were identified and compared to those with ADA. ADA neonates who required ECMO or intervention to augment PBF on the first day of life were defined as having CDPBF. Patient characteristics and outcomes were compared between DA and ADA groups. Results: Among 519 neonates, 460 (89%) had a DA and 59 (11%) had ADA. ADA neonates were more likely to carry a genetic or syndromic diagnosis, had smaller branch PA sizes, and were more likely to receive a transannular patch compared to those with a DA. Despite this, reintervention rates were similar (data not shown), and there was only a small difference in mortality that did not reach statistical significance. Of ADA neonates, 7/59 (12%) had CDPBF. Compared to ADA neonates without CDPBF, those with CDPBF had lower baseline oxygen saturation (58 vs 87%, p=0.031) and smaller pulmonary valve (PV) annular z-score (-2.9 vs -2.5, p=0.015) with similar reintervention rates and mortality. Conclusion: ADA is relatively common in sTOF. Despite higher rates of comorbidities, mid-term reintervention rates and mortality are similar to those with DA. CDPBF is a rare, high-risk feature of infants with sTOF and ADA. Smaller PV size may be a marker of CDPBF. Future work should focus on prenatal factors to identify fetuses with TOF, ADA and CDPBF.

Introduction: Children with single ventricle (SV) congenital heart disease have high morbidity, mortality and resource utilization when admitted to the hospital but few data exist on emergency department (ED) visits. Understanding patterns in ED encounters among children with SV may target interventions to improve outcomes. We described a national sample of SV ED visits and evaluated patient characteristics, encounters, and trends in admissions, charge, and mortality. Methods: This retrospective cohort study evaluates ED encounter level data from the 2006-2018 Nationwide Emergency Department Sample. Patients < 18y with SV were identified using ICD-9/10 codes. Results: From 2006-2018, 52,512 SV ED visits were identified. Most SV ED encounters were male (61%) and < 4y (65%). Patients with > 1 complex chronic condition (CCC) comprised nearly 1/3 encounters (32%). Half of encounters (49%) resulted in admission or transfer, and the median inflation-adjusted charge per ED encounter was $1,939 (IQR $1,098-3,217). Nearly 1 in 50 SV ED visits resulted in death, in the ED or during the associated admission. Independent predictors of admission included age > 2 CCC’s [OR 6.89 (5.56, 8.53)]. Independent predictors of mortality included age > 2 CCC’s [OR 2.19 (1.43, 3.36)]. Annual SV visits increased from 3,082 to 5,483 ( p for trend=0.003) and the inflation-adjusted charge per ED encounter increased by 50%, from $1,760 to $2,612 ( p for trend=0.002). There was no identified change in mortality ( p for trend=0.08). Conclusions: Half of ED visits of children with SV result in admission/transfer and 2% result in death. While the incidence and charges of SV ED visits increased over the years studied, there was no identified change in mortality. The high admission/transfer rate for children with SV presenting to the ED reflect a high-risk population; further attention must be given to improving their outcomes.

To evaluate early growth following primary or staged repair of neonatal symptomatic tetralogy of Fallot (sTOF).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.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).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.