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Congenital heart disease can lead to notable lymphatic complications such as chylothorax, plastic bronchitis, protein-losing enteropathy, and ascites. Recent improvements in lymphatic imaging and the development of new lymphatic procedures can help alleviate symptoms and improve outcomes.

Patients with dextro-transposition of the great arteries (d-TGA) require surgical repair as neonates. These patients are at risk for post-operative chylothorax. We sought to describe the presentation, imaging, and outcomes after intervention for patients with d-TGA with post-operative chylothorax. A retrospective chart review was performed in patients with repaired d-TGA who were referred from 1/1/2013 to 4/1/2020 for evaluation of chylothorax. Patient history, lymphatic imaging, and interventional data were collected. Impact of intervention on lymphatic drainage was evaluated with a student’s t-test. Eight patients met inclusion criteria for this study. Five patients had a history of central venous thrombus leading to thoracic duct outlet occlusion. Five patients underwent intervention, two were managed conservatively, and one was not a candidate for intervention. Chylothorax resolved in six patients. There was a significant difference in output from 7 days prior to first intervention (114 mL/kg/day) compared to 28 days following final intervention (27 mL/kg/day, p = 0.034). There were no procedural complications. Chylothorax in patients with repaired transposition of the great arteries is often amenable to intervention. Early surveillance and management of central venous thrombosis may reduce the burden of lymphatic disease in these patients.

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.

Lymphatic flow disorders include a broad spectrum of abnormalities that can originate in the lymphatic or the venous system. The development of these disorders is multifactorial and is most commonly associated with congenital heart diseases and palliative surgeries that these patients undergo. Central lymphatic disorders might be secondary to traumatic leaks, lymphatic overproduction, conduction abnormalities or lymphedema, and they can progress to perfusion anomalies. Several imaging modalities have been used to visualize the lymphatic system. However, the imaging of central lymphatic flow has always been challenging. Dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) allows for visualization of central lymphatic flow disorders and has been recently applied for the assessment of plastic bronchitis, protein-losing enteropathy, chylothorax and chylopericardium, among other lymphatic disorders. The hepatic and mesenteric accesses are innovative and promising techniques for better identification and understanding of these abnormalities. The main objectives of this review are to discuss the physiology and anatomy of the lymphatic system and review the current uses of DCMRL in the diagnosis and management of lymphatic flow disorders.

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

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.

The aim of this study was to determine the feasibility of using contrast-enhanced ultrasound (CEUS) evaluation to determine thoracic duct (TD) outlet patency. Nine patients referred for lymphatic imaging and intervention underwent percutaneous intranodal ultrasound contrast injection and conventional lymphangiography (CL). Eight of 9 patients had a patent TD by CEUS and CL. One patient did not have a patent TD. There was 100% agreement between CEUS and CL. These results suggest that CEUS is an imaging modality that might be as accurate as CL in determining TD patency.

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

To report on our initial experience with intramesenteric (IM) dynamic contrast magnetic resonance lymphangiography (DCMRL) for evaluation of the lymphatics in patients with concern for mesenteric lymphatic flow disorders and to compare IM-DCMRL with intrahepatic (IH) and intranodal (IN) DCMRL. This is a retrospective review of imaging findings in 15 consecutive patients who presented with protein losing enteropathy (PLE) and/or ascites undergoing IM-DCMRL, IH-DCMRL, and IN-DCMRL. The IM-DCMRL technique involves the injection of a gadolinium contrast agent into the mesenteric lymphatic ducts or lymph nodes followed by imaging of the abdomen and chest with dynamic time-resolved MR lymphangiography. IM-DCMRL was successfully performed in 14/15 (93%) of the patients. When comparing IN-DCMRL with IM-DCMRL, there was a significant difference in the visualization of dermal backflow (p = 0.014), duodenal perfusion (p = 0.003), duodenal leak (p = 0.014), and peritoneal leak (p = 0.003). IM-DCMRL demonstrated peritoneal leak in 7 patients in contrast to IH-DCMRL which demonstrated leak in 4 patients and IN-DCMRL which did not demonstrate any peritoneal leaks. Duodenal leaks were seen by IH-DCMRL in 9 patients versus 5 with IM-DCMRL and none with IN-DCMRL. In one patient with congenital PLE, the three modalities showed different disconnected flow patterns with duodenal leak only seen by IM-DCMRL. There were no short-term complications from the procedures. IM-DCMRL is a feasible imaging technique for evaluation of the mesenteric lymphatics. In certain mesenteric lymphatic flow abnormalities, such as PLE and ascites, this imaging may be helpful for diagnosis and the planning of interventions and warrants further studies. • Intramesenteric dynamic contrast magnetic resonance lymphangiography (IM-DCMRL) is a new imaging technique to evaluate mesenteric lymphatic flow disorders such as ascites. • IM-DCMRL is able to image lymphatic leaks in patients with ascites and protein losing enteropathy not seen with intranodal (IN-DCMRL) imaging.

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.

Background Thoracic duct (TD) outflow obstruction causes high morbidity and mortality in newborns. It can be congenital/idiopathic or acquired (secondary to central venous thrombosis or injury during cardiothoracic surgery). Re-routing the TD to the venous system by microsurgical techniques to restore lymphatic flow is a potential surgical solution. We present a series of newborns and infants who underwent thoracic duct-to-vein anastomosis (TDVA) to restore TD outflow. Materials and methods A retrospective review of all TDVA September 2015–March 2019 was performed. All patients underwent extensive pre-operative imaging evaluation by dynamic MRI and fluoroscopic lymphangiography. The TDVAs were done under high-power microscopy. Results Eight patients underwent TDVA. Age at surgery was 1 to 9 months. Four patients had a history of cardiac surgery (one with complete thrombosis of the central venous system), one patient had a history of ECMO and thrombosis of the SVC, and three patients had a history of fetal hydrothorax and non-immune hydrops. Six patients had a successful TDVA with restoration of the lymphatic flow through the TD and clinical improvement. Two patients had a technically adequate TDVA but without improvement of the flow due to persistently high central venous pressure. Five patients remain alive, two patients died from complications of the lymphatic disorder, and one patient died from an unrelated cause. Conclusions Patients with congenital or acquired TD outlet obstruction for whom no improvement is achieved by non-surgical interventions may benefit from TDVA. A thorough understanding of the anatomy and physiology of each patient is critical for the success of the operation. Level of Evidence Level IV.

OBJECTIVES: Protein-losing enteropathy (PLE) is a disorder of intestinal lymphatic flow resulting in leakage of protein-rich lymph into the gut lumen. Our primary aim was to report the imaging findings of dynamic contrast magnetic resonance lymphangiography (DCMRL) in patients with PLE. Our secondary objective was to use these imaging findings to characterize lymphatic phenotypes. METHODS: Single-center retrospective cohort study of patients with PLE unrelated to single-ventricle circulation who underwent DCMRL. We report imaging findings of intranodal (IN), intrahepatic (IH), and intramesenteric (IM) access points for DCMRL. RESULTS: Nineteen patients 0.3–58 years of age (median 1.2 years) underwent 29 DCMRL studies. Primary intestinal lymphangiectasia (PIL) was the most common referring diagnosis (42%). Other etiologies included constrictive pericarditis, thoracic insufficiency syndrome, and genetic disorders. IN-DCMRL demonstrated a normal central lymphatic system in all patients with an intact thoracic duct and localized duodenal leak in one patient (1/19, 5%). IH-DCMRL detected a duodenal leak in 12/17 (71%), and IM-DCMRL detected duodenal leak in 5/6 (83%). Independent of etiology, lymphatic leak was only visualized in the duodenum. CONCLUSIONS: In patients with PLE, imaging via DCMRL reveals that leak is localized to the duodenum regardless of etiology. Comprehensive imaging evaluation with three access points can provide detailed information about the site of duodenal leak.

Introduction: Balloon and stent angioplasty of the pulmonary arteries (PAs) are frequently performed following superior cavopulmonary connection (SCPC), not only to normalize the caliber of the affected PA but also in hopes of maximizing downstream growth over time. There are limited data on the impact on subsequent PA growth prior to total cavopulmonary connection (TCPC). Methods: A single-center, retrospective cohort study was performed on children who underwent transcatheter (TC) PA intervention following SCPC between January 1, 2010, and December 31, 2018. Growth of treated and contralateral PAs was measured at the lobar bifurcation (distal branch PA [DBPA]) and in the proximal lower lobe (lower lobe branch [LLB]) on serial angiograms. Growth rate was evaluated using a mixed-effect model clustered by individual patient with an interaction term for treated PA and time to evaluate for differential growth rates between treated and contralateral PAs. Results: Thirty-five patients underwent TC PA intervention following SCPC, at a median of 70 days (interquartile range: 19-297 days) postoperatively. Significant growth was seen at both DBPA and LLB for raw (0.8 mm/year, 95% CI: 0.6-1.0, P < .001 for both) and body surface area (BSA) adjusted measures (8.4mm/m2/year, 95% CI: 5.6-11.2, P < .001; 7.9 mm/m2/year, 95% CI: 5.5-10.2, P < .001). The growth rate of the treated vessel was not significantly different from that of the contralateral vessel at the DBPA or LLB positions for raw ( P = .71, .70) or BSA-adjusted measurements ( P = .86, .64). Conclusion: Transcatheter PA intervention was associated with normal distal PA growth rate relative to the untreated side.

Background Protein‐losing enteropathy (PLE) is a significant cause of morbidity and mortality in congenital heart disease patients with single ventricle physiology. Intrahepatic dynamic contrast‐enhanced magnetic resonance lymphangiography (IH‐DCMRL) is a novel diagnostic technique that may be useful in characterizing pathologic abdominal lymphatic flow in the congenital heart disease population and in diagnosing PLE. The objective of this study was to characterize differences in IH‐DCMRL findings in patients with single ventricle congenital heart disease with and without PLE. Methods and Results This was a single‐center retrospective study of IH‐DCMRL findings and clinical data in 41 consecutive patients, 20 with PLE and 21 without PLE, with single ventricle physiology referred for lymphatic evaluation. There were 3 distinct duodenal imaging patterns by IH‐DCMRL: (1) enhancement of the duodenal wall with leakage into the lumen, (2) enhancement of the duodenal wall without leakage into the lumen, and (3) no duodenal involvement. Patients with PLE were more likely to have duodenal involvement on IH‐DCMRL than patients without PLE ( P Conclusions IH‐DCMRL findings of lymphatic enhancement of the duodenal wall and leakage of lymph into the duodenal lumen are associated with PLE. IH‐DCMRL is a useful new modality for characterizing pathologic abdominal lymphatic flow in PLE and might be useful as a risk‐assessment tool for PLE in at‐risk patients.

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.

With improving survival of children with complex congenital heart disease (CCHD), postoperative complications, like protein-losing enteropathy (PLE) are increasingly encountered. A 3-year-old girl with surgically corrected CCHD (ventricular inversion/L-transposition of the great arteries, ventricular septal defect, pulmonary atresia, post-double switch procedure [Rastelli and Glenn]) developed chylothoraces. She was treated with pleurodesis, thoracic duct ligation and subsequently developed chylous ascites and PLE (serum albumin ≤0.9 g/dL) and was malnourished, despite nutritional rehabilitation. Lymphangioscintigraphy/single-photon emission computed tomography showed lymphatic obstruction at the cisterna chyli level. A segmental chyle leak and chylous lymphangiectasia were confirmed by gastrointestinal endoscopy, magnetic resonance (MR) enterography, and MR lymphangiography. Selective glue embolization of leaking intestinal lymphatic trunks led to prompt reversal of PLE. Serum albumin level and weight gain markedly improved and have been maintained for over 3 years. Selective interventional embolization reversed this devastating lymphatic complication of surgically corrected CCHD.

The treatment of lymphatic anomaly, a rare devastating disease spectrum of mostly unknown etiologies, depends on the patient manifestations1. Identifying the causal genes will allow for developing affordable therapies in keeping with precision medicine implementation2. Here we identified a recurrent gain-of-function ARAF mutation (c.640T>C:p.S214P) in a 12-year-old boy with advanced anomalous lymphatic disease unresponsive to conventional sirolimus therapy and in another, unrelated, adult patient. The mutation led to loss of a conserved phosphorylation site. Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions, which were rescued using the MEK inhibitor trametinib. The functional relevance of the mutation was also validated by recreating a lymphatic phenotype in a zebrafish model, with rescue of the anomalous phenotype using a MEK inhibitor. Subsequent therapy of the lead proband with a MEK inhibitor led to dramatic clinical improvement, with remodeling of the patient's lymphatic system with resolution of the lymphatic edema, marked improvement in his pulmonary function tests, cessation of supplemental oxygen requirements and near normalization of daily activities. Our results provide a representative demonstration of how knowledge of genetic classification and mechanistic understanding guides biologically based medical treatments, which in our instance was life-saving.

To describe the technique and report on our initial experience with the use of intrahepatic dynamic contrast magnetic resonance lymphangiography (IH-DCMRL) for evaluation of the lymphatics in patients with hepatic lymphatic flow disorders. This is a retrospective review of the imaging and clinical findings in six consecutive patients undergoing IH-DCMRL. The technique involves injection of a gadolinium contrast agent into the intrahepatic lymphatic ducts followed by imaging of the abdomen and chest with both heavily T2-weighted imaging and dynamic time-resolved imaging. In six consecutive patients, IH-DCMRL was technically successful. There were four patients with protein-losing enteropathy (PLE) and two with ascites in this study. In the four patients with PLE, IH-DCMRL demonstrated hepatoduodenal connections with leak of contrast into the duodenal lumen not seen by conventional lymphangiography. In one patient with ascites, IH-DCMRL demonstrated lymphatic leakage into the peritoneal cavity not seen by intranodal lymphangiography. In the second patient with ascites, retrograde lymphatic perfusion of mesenteric lymphatic networks and nodes was seen. Venous contamination was seen in two patients. No biliary contamination was identified. There were no short-term complications. IH-DCMRL is a cross-sectional technique which successfully evaluated hepatic lymphatic flow disorders and warrants further investigation. • Intrahepatic dynamic contrast magnetic resonance lymphangiography (IH-DCMRL) is a new imaging technique to evaluate hepatic lymphatic flow disorders such as protein-losing enteropathy. • In comparison to conventional liver lymphangiography, IH-DCMRL offers a 3D imaging technique and better distal lymphatic contrast distribution and does not use ionizing radiation.

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Noonan syndrome is a multiorgan system disorder mediated by genetic defects along the RASknown as RASopathies. It is the second most common syndromic cause of congenital heart disease and, in ∼20% of the cases, is associated with severe lymphatic disorders, including chylothorax and protein-losing enteropathy. Recently, we reported on the use of mitogen-activated protein kinase inhibition in a patient with an ARAF mutation and severe lymphatic disorder leading to an abrupt improvement in symptoms and complete remodeling of the central lymphatic system. Here, we present a patient with Noonan syndrome and severe lymphatic abnormality, leading to transfusion-dependent upper gastrointestinal bleeding and protein-losing enteropathy. The patient stopped responding to medical therapy and underwent several lymphatic interventional procedures, which led only to a temporary improvement in symptoms. Because of a lack of other treatment options, an expanded access approval was obtained, and the patient initiated treatment by mitogen-activated protein kinase inhibition using trametinib. This led to resolution of her symptoms, with complete normalization of her electrolyte levels, hemoglobin, and albumin within 3 months of starting the drug. Similar to the previously reported case, she also had complete and generalized remodeling of her lymphatic system. In patients with RAS pathway defects complicated by a severe lymphatic disorder, inhibition of the RAS-MAPK pathway should be considered as a possible treatment option in patients who failed conventional treatment and might be a first-line treatment in the future.

Introduction: Symptomatic Heart failure (HF) is a leading cause of morbidity and mortality in the world. HF with right sided symptoms may result in fluid overload including edema and ascites. The pathophysiology of fluid overload is poorly understood with no clear association between symptoms and hemodynamic parameters. Hypothesis: In animals with RHF and elevated CVP, the presence of ascites correlates with changes in lymphatic function and is independent of myocardial function and hemodynamic parameters. Methods: RHF was induced in fifteen swine animals by creating severe tricuspid regurgitation. Hemodynamics and anatomic changes were characterized using fluoroscopy, echocardiogram, and MRI. Measurements of the thoracic duct (TD) were made in the abdomen and thorax and the cross-sectional area was calculated. TD regurgitant flow was identified with ethiodized oil injection into the TD and was noted to be present or absent. Data is reported as median (IQR). Results: All 15 animals developed RHF with a dilated right atrium (RA) and right ventricle (RV). Nine animals developed ascites. Comparing animals with and without ascites, there were no differences in IVC pressure(mmHg) 11.5 (7.7-13.4) vs. 11.9 (10.2-17.4) (p= 0.364), SVC pressure 12.8 (11.3-16.8) vs. 12 (8.3-14.9) (p=0.343). Other hemodynamics parameters including pulmonary artery (PA), RV, and RA pressure were also not significantly different. In addition, left ventricular (LV) ejection fraction was normal in both groups (68.7% (57.9-74.8) vs. 55% (53.1-69.4) (p=0.135)). However, animals in the ascites group had larger relative liver volume (mL/Kg) 59.1 (65.1-51.9) vs. 34.85 (42.3-24.1) (p = 0.003), larger dimension of the minimal TD size (mm) 3.2 (5.8-2.7) vs. 2.2 (2.6-2.0) (p=0.04), and more animals had TD regurgitant flow 89% vs. 16% (p=0.01). Conclusion: In animal model with RV failure, there is no association between hemodynamic parameters and occurrence of ascites, consistent with observations in humans. In contrast, parameters of lymphatic congestion differ significantly between the two groups supporting the notion that lymphatic dysfunction is a contributing cause of tissue congestion in patients with HF and elevated CVP.

Kaposiform lymphangiomatosis (KLA) is a rare lymphatic anomaly primarily affecting the mediastinum with high mortality rate. We present a patient with KLA and significant disease burden harboring a somatic point mutation in the Casitas B lineage lymphoma (CBL) gene. She was treated with MEK inhibition with complete resolution of symptoms, near‐complete resolution of lymphatic fluid burden, and remodeling of her lymphatic system. While patients with KLA have been reported to harbor mutations in NRAS, here we report for the first time a causative mutation in the CBL gene in a patient with KLA, successfully treated with Ras pathway inhibition., Report of a patient with the rare lymphatic anomaly, Kaposiform lymphangiomatosis (KLA). CBL proto‐oncogene mutation was identified and she was successfully treated by targeting the MAP kinase pathway.

The proband, now a 4-year-old female of mixed Caucasian and Japanese ancestry, was born at 29 weeks gestation via spontaneous vaginal delivery following a pregnancy complicated by fetal ascites, echogenic bowel, polyhydramnios, and incompetent cervix. The mother had no other pregnancy complications and had no recognized teratogen exposures throughout the pregnancy. Her length was 37 cm (37(th) centile), weight was 1.478 kg (80(th) centile), and occipitofrontal circumference (OFC) was 27 cm (20(th) centile). The family history was significant for maternal family members with pregnancy losses of unknown etiology: one each for the mother and maternal grandmother. The great maternal grandmother reported at least 4 or 5 pregnancy losses. Consanguinity was denied. The proband remained in the neonatal intensive care unit for the next 8 months for management of severe respiratory issues, ascites and feeding difficulties. During that time, she underwent placement of a tracheostomy, a Denver (peritoneovenous) shunt for ascitic-fluid drainage, an intravenous port and a gastrostomy tube for feeds (Fig. 1). Additional pertinent findings then include retinopathy of prematurity, subglottal stenosis grade IV, hypothyroidism, 11 sets of ribs, mild bilateral hydronephrosis, accessory spleen and persistent ascites (Fig. 2). At 20 months dysmorphologic evaluation was significant for macrocephaly, open anterior and posterior fontanelles, bicoronal craniosynostosis on CT scan, right posterior plagiocephaly, brachycephaly, cupped and prominent ears with hypoplastic antihelices, broad forehead, a short and upturned nose, telecanthus, ocular hypertelorism, depressed nasal bridge (Figure 3A–B), moderate ascites, bilateral overriding of the second and fourth toes over the third toe, short stature and hypotonia. At this latter time, she exhibited significant developmental delays; she was unable to sit unassisted or feed herself. However, she was able to crawl, pull to a stand and sit independently. The proband could feed herself but still required a G-tube for much of her nutrition. She was nonverbal but able to use 12 signs. She continued to require a tracheostomy but only for night-time mechanical ventilation. At 33 months when last evaluated, her height was 79.2 cm (97(th) centile). The patient’s severe ascites persisted throughout the first 2 years of her life. At age 22 months, she underwent lymphatic imaging at the Children’s Hospital of Philadelphia that revealed multiple dilated perihepatic lymphatic vessels and leakage of contrast material into the peritoneum (Fig. 4A–D). Subsequently, she underwent successful embolization of these lymphatic vessels with resolution of her ascites.

Background Recent studies suggest that lymphatic congestion plays a role in development of late Fontan complications, such as protein‐losing enteropathy. However, the role of the lymphatic circulation in early post‐Fontan outcomes is not well defined. Methods and Results This was a retrospective, single‐center study of patients undergoing first‐time Fontan completion from 2012 to 2017. The primary outcome was early Fontan complication ≤6 months after surgery, a composite of death, Fontan takedown, extracorporeal membrane oxygenation, chest tube drainage >14 days, cardiac catheterization, readmission, or transplant. Complication causes were assigned to 1 of 4 groups: (1) Fontan circuit obstruction, (2) ventricular dysfunction or atrioventricular valve regurgitation, (3) persistent pleural effusions in the absence of Fontan obstruction or ventricular dysfunction, and (4) chylothorax or plastic bronchitis. T2‐weighted magnetic resonance imaging sequences were used to assess for lymphatic perfusion abnormality. The cohort consisted of 238 patients. Fifty‐eight (24%) developed early complications: 20 of 58 (34.5%) in group 1, 8 of 58 (14%) in group 2, 18 of 58 (31%) in group 3, and 12 of 58 (20%) in group 4. Preoperative T2 imaging was available for 126 (53%) patients. Patients with high‐grade lymphatic abnormalities had 6 times greater odds of developing early complications ( P =0.001). Conclusions There is substantial morbidity in the early post‐Fontan period. Half of those who developed early complications had lymphatic failure or persistent effusions unrelated to structural or functional abnormalities. Preoperative T2 imaging demonstrated that patients with higher‐grade lymphatic perfusion abnormalities were significantly more likely to develop early complications. This has implications for risk stratification and optimization of patients before Fontan palliation.

Background: The arterial switch operation (ASO) is the gold standard operative correction of neonates with transposition of the great arteries and intact ventricular septum, with excellent operative survival. The associations between patient and surgeon characteristics and outcomes are well understood, but the associations between variation in preoperative care and outcomes are less well studied. Methods: A multicenter retrospective cohort study of infants undergoing neonatal ASO between January 2010 and September 2015 at hospitals contributing data to the Pediatric Health Information Systems database was performed. The association between preoperative care (timing of ASO, preoperative use of balloon atrial septostomy, prostaglandin infusion, mechanical ventilation, and vasoactive agents) and operative outcomes (mortality, length of stay, and cost) was studied with multivariable mixed-effects models. Results: Over the study period, 2159 neonates at 40 hospitals were evaluated. Perioperative mortality was 2.8%. Between hospitals, the use of adjuvant therapies and timing of ASO varied broadly. At the subject level, older age at ASO was associated with higher mortality risk (age >6 days: odds ratio, 1.90; 95% CI, 1.11–3.26; P =0.02), cost, and length of stay. Receipt of a balloon atrial septostomy was associated with lower mortality risk (odds ratio, 0.32; 95% CI, 0.17–0.59; P P =0.03), longer length of stay ( P P Conclusions: There was significant variation in preoperative care between hospitals. Some potentially modifiable aspects of perioperative care (timing of ASO and septostomy) were significantly associated with mortality, length of stay, and cost. Further research on the perioperative care of neonates is necessary to determine whether modifying practice on the basis of the observed associations translates into improved outcomes.

Rationale and Objectives This study aimed to describe prenatal and postnatal imaging features and outcomes of neonates with neonatal lymphatic disorders (NLDs). Materials and Methods An institutional review board-approved search of the radiology database for patients with NLD identified five patients. Inclusion criteria include prenatal imaging (fetal magnetic resonance [MR] imaging and ultrasound) and postnatal three-dimensional T2 Sampling Perfection with Application optimized Contrasts using different flip angle Evolution (SPACE) and dynamic contrast-enhanced MR lymphangiography within 6 months of life. Chart review was undertaken to evaluate morbidity and mortality. Results Prenatal finding of “nutmeg lung” or fetal pulmonary lymphatic disorder was identified in all five patients on fetal MR imaging, and in four of five patients on fetal ultrasound. Postnatal dynamic contrast-enhanced MR lymphangiography demonstrated abnormal lymphatic flow to the lungs in four of five patients, but absent in the single patient with coexisting hypoplastic left heart syndrome (HLHS). Dermal backflow was seen in one patient, also the only patient with prenatal body wall edema. Three patients with lymphatic flow to the lungs only were classified as neonatal chylothorax. The patient with dermal backflow and perfusion to the lungs was diagnosed with central lymphatic flow disorder (CLFD). The HLHS patient with normal lymphatic perfusion maintained the HLHS diagnosis. Of the five patients, the patient with CLFD and the one with HLHS expired because of respiratory distress. Conclusions NLDs can be recognized on prenatal and postnatal imaging and may be primary, as in neonatal chylothorax or CLFD, or secondary. In this small series, “nutmeg lung” was present in all patients. Prenatal imaging demonstrates that body wall edema may correlate with postnatal dermal backflow, which, in our small cohort, carried a poor prognosis.

The initial "Frontiers in Fontan Failure" conference in 2015 in Atlanta, GA, provided an opportunity for experts in the field of pediatric cardiology and adult congenital heart disease to focus on the etiology, physiology, and potential interventions for patients with "Failing Fontan" physiology. Four types of "Fontan Failure" were described and then published by Dr Book et al. The acknowledgment that even Dr Fontan himself realized that the Fontan procedure "imposed a gradually declining functional capacity and premature late death after an initial period of often excellent palliation." The purpose of the second "Frontiers in Fontan Failure" was to further the discussion regarding new data and technologies as well as novel interventions. The 2017 "Frontiers in Fontan Failure: Innovation and Improving Outcomes" was sponsored by Children's Healthcare of Atlanta, Sibley Heart Center Cardiology, and Emory University School of Medicine. Future directions in the management of Fontan failure include further investigations into the risk of sudden cardiac death and how to properly prevent it, achievable interventions in modifying the Fontan physiology to treat or prevent late complications, and improved and refined algorithms in Fontan surveillance. Finally, further research into the interventional treatment of lymphatic-related complications hold the promise of marked improvement in the quality of life of advanced Fontan failure patients and as such should be encouraged and contributed to.

The recent adoption of an improved lymphatic access technique coupled with Dynamic Contrast-enhanced Magnetic Resonance Lymphangiography has introduced the ability to diagnose and treat severe lymphatic disorders unresponsive to other therapies. All pediatric patients presenting for lymphatic procedures require general anesthesia presenting challenges in managing highly morbid and comorbid conditions both from logistical as well as medical aspects. General anesthesia is used because of the procedural requirement for immobility to accurately place needles and catheters, treat pain secondary to contrast and glue injections, and to accommodate additional procedures. We reviewed a one-year cohort of all pediatric patients in a newly created Center for Lymphatic Imaging and Intervention at a tertiary care children's hospital presenting for lymphatic procedures. The patients ranged in age from 4 days to 17 years and weighed from 2.5 to 92 kg. There were 106 anesthetics for 68 patients. Patients were functionally impaired (98% ASA 3 or 4) and included significant comorbidities (79.4%). Concurrent with lymphatic imaging and intervention additional procedures were frequently performed (76%). They included cardiac catheterization, bronchoscopy, endoscopy, and drain placement (thoracic or abdominal). Paralysis and controlled ventilation was used for all interventions. Reversal of paralysis and tracheal extubation occurred in all patients not previously managed by invasive respiratory support. All patients having an intervention were admitted to intensive care for observation where escalation of care or complications (fever, hypotension, bleeding, or stroke) occurred in 25% in the first 24 hours.

Background Protein-losing enteropathy (PLE), characterized by loss of proteins in the intestine, is a devastating complication in patients with congenital heart disease. The cause of PLE is unknown, but lymphatic involvement has been suspected. Objectives The authors evaluated the use of lymphangiographic imaging and liver lymphatic embolization as a treatment for PLE. Methods This was a single-center, retrospective review of imaging and interventions used in 8 consecutive patients with liver lymphatic embolization and congenital heart disease with elevated central venous pressure complicated by PLE. Results Liver lymphangiography was performed in 8 patients (5 males, 3 females; median age, 21 years), 7 of whom demonstrated leakage of liver lymph into the duodenum through abnormal hepatoduodenal lymphatic communications. This was confirmed by duodenoscopy with simultaneous injection of isosulfan blue dye into the liver lymphatics in 6 of 7 patients. Liver lymphatic embolization with ethiodized oil in 2 patients resulted in a temporary increase in albumin blood level and symptom improvement in 1 patient, but was complicated by duodenal bleeding in both patients. Of the remaining 6 patients, liver lymphatic embolization with n-butyl cyanoacrylate glue resulted in sustained improvement of the serum albumin level and symptoms in 3 patients, temporary improvement in 2 patients, and no change in 1 patient with median follow-up of 135 days (range, 84 to 1,005 days). Conclusions The authors demonstrated liver lymph leakage as a cause of PLE in patients with congenital heart disease and elevated central venous pressure. Lymphatic embolization led to improved albumin levels and relief of symptoms. Further experience with the technique is needed to determine long-term outcome of this procedure.

Background aims: Manufacturing of potent chimeric antigen receptor (CAR) T cells requires phenotypically naive and early memory T cells. We hypothesized lymphatic fluid collected from the thoracic duct of children would serve as a unique reservoir for early T cells, which could then be used for CAR T-cell therapy. Methods: We evaluated lymphatic fluid collected from 25 pediatric patients undergoing thoracic duct cannulation for other clinical indications. Results: Lymphatic fluid in the thoracic duct was rich in T cells, with higher percentage of naive and stem central memory T-cell subsets compared with paired blood samples. T cells from lymphatic fluid showed decreased negative checkpoint regulators on the surface and increased rapid expansion with bead activation. Creation of CD19-directed CAR T cells from blood and lymphatic T cells showed similar lentiviral transduction properties, but CAR T cells generated from lymphatic fluid produced superior cytotoxicity in a murine leukemia model because they were able to achieve equivalent tumor eradication at lower doses. Conclusions: These results are the first characterization of T cells from the thoracic duct of pediatric patients and suggest an alternative approach for manufacturing of cellular therapy that will improve both expansion and cytotoxic effect.

Pulmonary lymphatic flow disorders involve the abnormal lymphatic flow via lymphatic channels to the lungs and pleural space. Plastic bronchitis and chylothorax are the main complications of this abnormal lymphatic perfusion, which has been termed pulmonary lymphatic perfusion syndrome (PLPS). Following lymphatic access, dynamic contrast MR lymphangiography is the imaging modality of choice to diagnose these disorders. Management includes medical therapy, percutaneous interventions under fluoroscopy, and surgical interventions.

Background Risk‐adjusted adverse event ( AE ) rates have been used to measure the quality of pediatric and congenital cardiac catheterization laboratories. In other settings, failure to rescue ( FTR ) has demonstrated utility as a quality metric. Methods and Results A multicenter retrospective cohort study was performed using data from the IMPACT (Improving Adult and Congenital Treatment) Registry between January 2010 and December 2016. A modified FTR metric was developed for pediatric and congenital cardiac catheterization laboratories and then compared with pooled AEs . The associations between patient‐ and hospital‐level factors and outcomes were evaluated using hierarchical logistic regression models. Hospital risk standardized ratios were then calculated. Rankings of risk standardized ratios for each outcome were compared to determine whether AEs and FTR identified the same high‐ and low‐performing centers. During the study period, 77 580 catheterizations were performed at 91 hospitals. Higher annual hospital catheterization volume was associated with lower odds of FTR (odds ratio: 0.68 per 300 cases; P =0.0003). No association was seen between catheterization volume and odds of AEs . Odds of AEs were instead associated with patient‐ and procedure‐level factors. There was no correlation between risk standardized ratio ranks for FTR and pooled AEs ( P =0.46). Hospital ranks by catheterization volume and FTR were associated ( r =−0.28, P =0.01) with the largest volume hospitals having the lowest risk of FTR . Conclusions In contrast to AEs , FTR was not strongly associated with patient‐ and procedure‐level factors and was significantly associated with pediatric and congenital cardiac catheterization laboratory volume. Hospital rankings based on FTR and AEs were not significantly correlated. We conclude that FTR is a complementary measure of catheterization laboratory quality and should be included in future research and quality‐improvement projects.

In patients with total cavopulmonary connections, elevated central venous pressures (CVP) have detrimental effects on the lymphatic system causing an imbalance in fluid production and drainage of the interstitium. This combination may result in life-threatening lymphatic complications including plastic bronchitis (PB), protein losing enteropathy (PLE), chylothorax, and ascites. While embolization of the abnormal lymphatics has greatly improved outcomes from these complications, alternative treatment strategies have been proposed that would result in improved lymphatic drainage while leaving the lymphatic system intact. We report two novel transcatheter approaches for thoracic duct (TD) decompression in two patients who developed PLE after completion of the Fontan procedure as part of staged palliation for congenital heart disease. In addition, one patient had severe concurrent PB. In both patients, a connection was created between a left superior vena cava (LSVC) to the left atrium allowing for a nonsurgical method to decompress the TD. This procedure resulted in significant clinical and laboratory improvement of both patients' PLE and other symptoms of lymphatic dysfunction.

The risks and benefits of pharmacologic treatment and operative closure of patent ductus arteriosus (O-PDA) in premature infants remain controversial. Recent series have demonstrated the feasibility of transcatheter PDA closure (TC-PDA) in increasingly small infants. The effect of this change on practice has not been evaluated.A multicenter observational study of infants treated in neonatal intensive care units in hospitals contributing data to the Pediatric Health Information Systems Database from January 2007 to December 2017 was performed to study trends in the propensities for (1) mechanical closure of PDA and (2) TC-PDA versus O-PDA, as well as interhospital variation in practice.A total of 6,214 subjects at 44 hospitals were studied (5% TC-PDA). Subject median gestational age was 25 weeks (interquartile range: 24-27 weeks). Median age at closure was 24 days (interquartile range: 14-36 days). The proportion of all neonatal intensive care unit patients undergoing either O-PDA or TC-PDA decreased (3.1% in 2007 and 0.7% in 2017, P .001), whereas the proportion in which TC-PDA was used increased significantly (0.1% in 2007 to 29.0% in 2017). Case-mix-adjusted multivariable models similarly demonstrated increasing propensity to pursue TC-PDA (odds ratio [OR] 1.66 per year, P .001) with acceleration of the trend after 2014 (OR 2.46 per year, P .001) as well as significant practice variation (P .001, median OR 4.6) across the study period.In the face of decreasing closure of PDA, the use of TC-PDA increased dramatically with significant practice variability. This demonstrates that there is equipoise for potential clinical trials.

Background Cardiac catheterization is an important but costly component of health care for young patients with cardiac disease. Measurement of variation in their cost between hospitals and identification of the reasons for this variation may help reduce cost without compromising quality. Methods and Results Using data from Pediatric Health Information Systems Database from January 2007 to December 2015, the costs of 9 procedures were measured. Mixed‐effects multivariable models were used to generate case‐mix–adjusted estimates of each hospital's cost for each procedure and measure interhospital variation. Procedures (n=35 637) from 43 hospitals were studied. Median costs varied from $8249 (diagnostic catheterization after orthotopic heart transplantation) to $38 909 (transcatheter pulmonary valve replacement). There was marked variation in the cost of procedures between hospitals with 3.5‐ to 8.9‐fold differences in the case‐mix–adjusted cost between the most and least expensive hospitals. No significant correlation was found between hospitals’ procedure‐specific mortality rates and costs. Higher procedure volume was not associated with lower cost except for diagnostic procedures in heart transplant patients and pulmonary artery angioplasty. At the hospital level, the proportion of cases that were outliers (>95th percentile) was significantly associated with rank in terms of cost (Spearman's ρ ranging from 0.37 to 0.89, P Conclusions Large‐magnitude hospital variation in cost was not explained by case‐mix or volume. Further research is necessary to determine the degree to which variation in cost is the result of differences in the efficiency of the delivery of healthcare services and the rate of catastrophic adverse outcomes and resultant protracted and expensive hospitalizations.

The purpose of this study was to evaluate the association between the method of procedural sedation and outcomes for congenital cardiac catheterization procedures.The safety of operator-directed sedation (ODS) in the pediatric/congenital cardiac catheterization laboratory has been questioned. To our knowledge, the relative safety of ODS versus general anesthesia (GA) in these cases has not to date been critically evaluated.A single-center retrospective cohort study was performed to compare the relative safety, cost, and times of catheterization procedures performed with ODS and those performed with GA from a cardiac anesthesiologist. The risk of adverse outcomes was compared using propensity-score-adjusted models. Using the same propensity score, procedure times and relative charges were also compared.Over the study period, 4,424 procedures in 2,547 patients were studied. Of these, 27% of cases were performed with ODS. ODS procedures were 70% diagnostic procedures, 17% device closure of patent ductus arteriosus, 5% balloon pulmonary valvuloplasty, and 3% pulmonary artery angioplasty. The risk of adverse event in adjusted models for ODS cases was significantly lower than in GA cases (odds ratio: 0.66; 95% confidence interval: 0.45 to 0.95; p = 0.03). Total room time and case time were also significantly shorter (p 0.001). Professional (charge ratio: 0.88; p 0.001) and hospital (charge ratio: 0.84; p 0.001) charges for ODS cases were also lower than those for GA cases.This study demonstrates that clinical judgment can identify subjects in whom ODS is not associated with increased risk of adverse events. The use of ODS was associated with reduced case times and charges. In combination, these findings suggest that the selective use of ODS can allow for greater efficiency and higher value care without sacrificing safety.

BACKGROUND: The Fontan operation is performed for surgical palliation of single ventricle physiology. This operation is usually preceded by a superior cavopulmonary connection (SCPC); lymphatic abnormalities after SCPC may be demonstrated at MRI and prior to the Fontan operation. PURPOSE: To determine if the degree of neck and thoracic lymphatic abnormalities at T2-weighted MRI in patients after superior cavopulmonary connection (SCPC) correlated with surgical outcomes from the Fontan procedure. MATERIALS AND METHODS: Patients for whom SCPC was performed for palliation of single ventricle disease who underwent chest MRI between July 2012 and May 2015 at a single institution were retrospectively reviewed. T2-weighted images were scored as lymphatic type 1 (little or no T2 mediastinal and supraclavicular signal) to type 4 (T2 signal into both the mediastinum and the lung parenchyma). Fontan takedown, duration of post-Fontan hospitalization and pleural effusion, postoperative plastic bronchitis, need for transplant, and mortality were tabulated. The relationship between lymphatic type and clinical outcomes was evaluated by using analysis of variance (ANOVA), the Kruskal-Wallis H test, and the Fisher exact test. RESULTS: A total of 83 patients (mean age, 7.9 years ± 2.6) were evaluated. Among these 83 patients, 53 (64%) were classified with type 1 or 2 lymphatic abnormalities, 17 (20%) with type 3, and 12 (16%) with type 4. The rate of failure of Fontan completion was higher in patients with type 4 than in type 1 or 2 (54% vs 2%, respectively; P = .004). Need for cardiac transplant (one of 13 [8%]) and death (three of 13 [23%]) occurred only in type 4. Median postoperative length of stay was longer for patients with type 4 than for those with types 1 or 2 (29 days vs 9 days, respectively; P < .01). CONCLUSION: Greater MRI-based severity of lymphatic abnormalities in patients prior to planned Fontan procedure was associated with failure of Fontan completion and longer postoperative stay. © RSNA, 2019 Online supplemental material is available for this article.

The management of lymphatic malformations (LMs) is challenging, particularly for large and complex lesions involving anatomical structures in the adjacent tissue. While lymphovenous anastomosis (LVA) has been reported as an effective treatment for lymphedema, it has hardly been described as a treatment for LM. Virtual reality has the ability to visualize human structures in three dimensions and can be used for the preoperative planning of complex cases. Here, we describe the first case of the management of an LM by LVA preoperatively planned with virtual reality. A young woman presented with an LM previously treated by gross excision. Following persistent complaints of swelling, a minimally invasive microsurgical intervention was planned. The results of the single photon emission tomography with computed tomography (SPECT-CT) and lymphoscintigraphy were analyzed using a virtual reality program, and a 3D patient-specific model was constructed. Based on the combined findings of this 3D model and lymphography with a fluorescent marker, a precise skin incision could be determined and one lymph vessel was anastomosed to a nearby vein. The swelling of the thigh reduced and the discomfort disappeared. Although more reports are needed to confirm its efficacy, LVA planned with virtual reality constructed images appears to be a valuable treatment option for complex lesions, including LMs.

The lymphatic system was discovered in the early days of medicine, however, the ability to image and treat lymphatic abnormalities has only developed over the last 10 to 15 years. In this time, the presence of lymphatic disorders with congenital heart disease has been described and better understood. Advances in imaging modalities have led to novel MRI techniques including dynamic contrast enhanced magnetic resonance lymphangiograms (DCMRL) as well as conventional lymphangiograms to better delineate lymphatic pathology. Using these modalities, it is now possible to diagnose and treat a wide array of lymphatic abnormalities including chylous effusions, chylous ascites, plastic bronchitis, and protein losing enteropathy. Therapies have advanced to involve percutaneous, transabdominal thoracic duct access with treatment of lymphatic problems using liquid embolic material, covered stents, and coils. In cases of thoracic duct occlusion, re-establishing flow is the first line of treatment which can be performed using a novel microsurgical lympho-venous anastomosis technique. In patients with single ventricle physiology, it is essential to image the lymphatics using intra-nodal, intra-hepatic, and intra-mesenteric DCMRL prior to intervening. In these patients, care must be taken to prevent complete occlusion of the thoracic duct to avoid creating another source of lymphatic problems. Current and future lymphatic management involves a combination of catheter-based and surgical interventions as well as the use of novel medical therapies, such as MEK inhibitors, to remodel abnormal lymphatic architecture. Synopsis This article strives to review the current status of the field of lymphatic imaging and interventions in congenital heart diseases and briefly outlines future directions as the field evolves.

The lymphatic system plays an important role in immune regulation, transport of metabolites, and fluid balance. The key circulatory role of the lymphatic system is to transport fluid from tissue back into the venous system via lymphovenous connections. Despite the centuries-old recognition of this key role, there has been poor understanding of lymphatic flow pathophysiology because of a lack of a simple reliable noninvasive clinical lymphatic imaging method. This lack of clinical imaging has limited the treatment options for patients with lymphatic flow disorders. Recent development of noncontrast magnetic resonance (MR) lymphangiogram and dynamic contrast MR lymphangiography make it possible to visualize central lymphatic anatomy and flow dynamics with high spatial and temporal resolution. Dynamic contrast MR lymphangiography has provided insight into understanding the pathophysiology of several pulmonary lymphatic flow disorders and provides guidance for interventional procedures. Another important development has been intranodal lymphangiogram, which has now replaced pedal lymphangiogram as the main lymphatic interventional modality, and which provides quick and reliable access to the central lymphatic ducts for interventional procedures. These new techniques have led to a resurgence in interest in the lymphatic system and the development of new treatments for patients with lymphatic flow disorders.

Balloon and stent angioplasty of the pulmonary arteries (PA) is often performed following superior cavopulmonary connection (SCPC), not only to normalize the caliber of the affected PA but also in hopes of maximizing growth of the downstream pulmonary vascular tree. To our knowledge, this impact has

Protein-losing enteropathy (PLE) is a common cause of morbidity and mortality in patients with single-ventricle (SV) physiology. Pathologic, retrograde lymphatic flow from the liver to the duodenum and leakage of lymph into the bowel lumen is implicated in PLE. Intrahepatic dynamic contrast-enhanced

Children with Noonan syndrome are known to have increased risk for lymphatic disorders, the extent and nature of which are poorly understood. Our objective was to describe the imaging findings of the central lymphatic abnormalities in children with Noonan syndrome who underwent central lymphatic imaging. We conducted a single-center retrospective review of all children with a confirmed history of Noonan syndrome who presented for lymphatic imaging over a 5-year period. Imaging evaluation was performed on unenhanced T2-weighted (T2-W) imaging, dynamic-contrast MR lymphangiography or conventional lymphangiography. Two readers evaluated the imaging in consensus for the distribution of fluid on T2-W imaging and for lymphatic flow of intranodal contrast agent and thoracic duct abnormalities on dynamic-contrast MR lymphangiography and conventional lymphangiography. We performed a chart review for clinical history and outcomes. We identified a total of 10 children, all but one of whom had congenital heart disease. Presenting symptoms included chylothorax (n=9) and ascites (n=1). Nine had T2-W imaging, seven had dynamic-contrast MR lymphangiography, and seven had conventional lymphangiography. All with T2-W imaging had pleural effusions. On both dynamic-contrast MR lymphangiography and conventional lymphangiography, perfusion to the lung was seen (n=6), with intercostal flow also seen on dynamic-contrast MR lymphangiography (n=6). The thoracic duct was not present in three children and the central thoracic duct was not present in three. A double thoracic duct was seen in two children. Children with Noonan syndrome and clinical evidence of lymphatic dysfunction have central lymphatic abnormalities characterized by retrograde intercostal flow, pulmonary lymphatic perfusion, and thoracic duct abnormalities.

Background Percutaneous lymphatic intervention (PCL) is a promising new therapy for plastic bronchitis (PB). We characterized bronchoalveolar lavage (BAL) and cast morphology in surgically repaired congenital heart disease (CHD) patients with PB during PCL. We quantified respiratory and bronchoscopic characteristics and correlated them with post-intervention respiratory outcomes. Methods We retrospectively reviewed patients with PB and surgically repaired CHD undergoing PCL and bronchoscopy at our institution. Pre-intervention characteristics, bronchoscopy notes, BAL cell counts, virology, and cultures were collected. A pathologist blinded to clinical data reviewed cast specimens. Respiratory outcomes were evaluated through standardized telephone questionnaire. Results Sixty-two patients were included with a median follow-up of 20 months. No patients experienced airway bleeding, obstruction, or prolonged intubation related to bronchoscopy. Of BAL infectious studies, the positive results were 4 (8%) fungal, 6 (11%) bacterial, and 6 (14%) viral. Median BAL count per 100 cells for neutrophils, lymphocytes, and eosinophils were 13, 10, and 0, respectively. Of 23 bronchial casts analyzed, all contained lymphocytes, and 19 (83%) were proteinaceous, with 14 containing neutrophils and/or eosinophils. Median BAL neutrophil count was greater in patients with proteinaceous neutrophilic or eosinophilic casts compared to casts without neutrophils or lymphocytes (P = 0.030). Post-intervention, there was a significant reduction in respiratory medications and support and casting frequency. Conclusions The predominance of neutrophilic proteinaceous casts and high percentage of positive BAL infectious studies support short-term fibrinolytic and anti-infective therapies in PB in select patients. Flexible bronchoscopy enables safe assessment of cast burden. PCL effectively treats PB and reduces respiratory therapies.

With the expanding horizon of microsurgical techniques, novel treatment strategies for lymphatic abnormalities are increasingly reported. Described in this article is the first reported use of lymphovenous anastomosis surgery to manage recalcitrant chylothoraces in infants. Chylothorax is an increasingly common postoperative complication after pediatric cardiac surgery, with a reported incidence of up to 9.2 percent in infants. Although conservative nutritional therapy has a reported 70 percent success rate in this patient population, failed conservative management leading to persistent chylothorax is associated with a significant risk of multisystem complications and mortality. Once conservative medical strategies are deemed unsuccessful, surgical or radiologic interventions, such as percutaneous thoracic duct embolization or ligation, are often attempted. However, these procedures lack high-level evidence in the infant population and remain a challenge, given the small size of the lymphatic vessels. As such, we report our experience with performing lymphovenous anastomoses in two infants who had developed refractory chylothoraces secondary to thoracic duct injury following cardiac surgery for congenital cardiac anomalies. In addition, this article reviews the relevant pathophysiology of chylothoraces, current treatment algorithm following failed conservative management, and potential role of the microsurgeon in the multidisciplinary management of this life-threatening problem. As part of the evolving microsurgery frontier, physiologic operations, such as lymphovenous anastomosis, may have a considerable role in the management of refractory pediatric chylothoraces. In our experience, lymphovenous anastomosis can restore normal lymphatic circulation within 1 to 2 weeks, liberate patients from mechanical ventilation, and enable expeditious return to enteral feeding. Clinical question/level of evidence Therapeutic, V.