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Background Congestive heart failure is a leading cause of morbidity and mortality worldwide. One of the signs of congestive heart failure is fluid overload including pulmonary edema, peripheral edema, and ascites. The cause of fluid overload remains incompletely understood, and management of these patients continues to be a challenge. The role of lymphatic circulation abnormalities in the cause and pathophysiology of fluid overload also remains unclear. Here we report on a study in a large animal model of right heart failure caused by severe tricuspid regurgitation comparing cardiovascular and lymphatic findings in a group of animals that did not develop ascites with a group of animals that developed ascites. Methods and Results Thirteen Yorkshire pigs were included in this study divided into 2 groups. Group 1 included 6 animals that did not develop ascites, and Group 2 included 7 animals that had developed ascites. The groups were compared on hemodynamic parameters as well as comparison of the animal's lymphatic anatomy and function. There was no difference between the groups in degree of tricuspid regurgitation and central venous pressure, with inferior vena cava pressure measuring 11.6±1.6 versus 13.2±3.7 ( P =0.534) and superior vena cava pressure measuring 12.0±2.3 versus 13.7±3.2 ( P =0.366). There was also no difference between the groups in all measured hemodynamic parameters, including right ventricular pressure, pulmonary artery pressure, and left ventricular function. The weighted liver size in the ascites group was significantly larger than in the nonascites group (30.3±12.4 versus 63.3±14.0 mL/kg, respectively; P =0.001). The 2 groups also differed in the number of animals with regurgitant thoracic duct flow (Group 1: 1/6,17% versus Group 2: 6/7, 86%; P =0.029) and the minimal thoracic duct diameter (Group 1: 2.3±0.3 versus Group 2: 4.2±2.2; P =0.035). Conclusions In animals with right heart failure caused by severe tricuspid regurgitation, fluid overload did not correlate with hemodynamic parameters but rather with changes in the lymphatic system, including regurgitant lymphatic flow, minimal thoracic duct diameter, and liver size. This study is consistent with lymphatic dysfunction and not cardiovascular function playing a significant role in the cause of fluid overload. Further studies are needed to confirm these findings.

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.

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.

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.

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.

Background: No previous studies have studied the variation in costs between hospitals for catheterization procedures performed in children. Variation in cost not explained by differences in case-mix can indicate opportunities to improve efficiency and quality of care. Methods: A multicenter observational study was performed, studying total hospital costs of 9 common transcatheter procedures (diagnostic procedures in 2 populations and 7 interventional procedures) performed between 2007-2015 at hospitals contributing data to the Pediatric Health Information Systems database. Mixed effects models were used to adjust costs for case mix and to assess inter-hospital variation. Bayesian methods were used to calculate risk-standardized costs for each hospital. Results: The study included 35,637 procedures from 43 hospitals. Median costs (US 2015 dollars) increased roughly with technical complexity, from $8,249 (heart transplant diagnostic catheterization) to $38,909 (transcatheter pulmonary valve replacement). There was significant inter-hospital variation in cost for each procedure ( p Conclusion: There is significant inter-hospital variation in costs of transcatheter procedures after case-mix adjustment. Exploring the etiology of these differences is an opportunity to improve care of children with heart disease.

Background— Systemic-pulmonary collateral (SPC) flow occurs commonly in single ventricle patients after superior cavo-pulmonary connection, with unclear clinical significance. We sought to evaluate the association between SPC flow and acute post-Fontan clinical outcomes using a novel method of quantifying SPC flow by cardiac magnetic resonance (CMR) imaging. Methods and Results— All patients who had SPC flow quantified by CMR imaging before Fontan were retrospectively reviewed to assess for acute clinical outcomes after Fontan completion. Forty-four subjects were included who had Fontan completion between May 2008 and September 2010. SPC flow prior to Fontan measured 1.5±0.9 L/min/m 2 , accounting for 31±11% of total aortic flow and 44±15% of total pulmonary venous flow. There was a significant linear association between natural log-transformed duration of hospitalization and SPC flow as a proportion of total aortic (rho=0.31, P =0.04) and total pulmonary venous flow (rho=0.29, P =0.05). After adjustment for Fontan type and presence of a fenestration, absolute SPC flow was significantly associated with hospital duration ≥7 days (odds ratio [OR]=9.2, P =0.02) and chest tube duration ≥10 days (OR=22.7, P =0.009). Similar associations exist for SPC flow as a percentage of total aortic (OR=1.09, P =0.048 for hospitalization ≥7 days; OR=1.24, P =0.007 for chest tube duration ≥10 days) and total pulmonary venous flow (OR=1.07, P =0.048 for hospitalization ≥7 days; OR=1.18, P =0.006 for chest tube duration ≥10 days). Conclusions— Increasing SPC flow before Fontan, as measured by CMR imaging, is associated with increased duration of hospitalization and chest tube following Fontan completion.

Background— Transannular patch (TAP) repair of tetralogy of Fallot often results in significant right ventricular outflow tract (RVOT) dilation and distortion. We hypothesized that insertion of Melody valves into the proximal right and left branch pulmonary arteries (PAs) would reduce pulmonary regurgitation fraction (PRF) in an ovine model of pulmonary insufficiency and dilated RVOT. Methods and Results— Ten sheep underwent baseline cardiac catheterization, surgical pulmonary valvectomy, and TAP placement. A subset (n=5) had Melody valves (2 devices per animal) inserted into the proximal right and left PAs during the surgical procedure. Melody valves were placed distal to the right-upper-lobe (RUL) artery branch, leaving the RUL “unprotected.” Preoperative MRIs (n=5) were used to determine baseline RV ejection fraction (RVEF) and left ventricular (LV) EF. All surviving animals (n=9) underwent MRI and catheterization 6 weeks postsurgery. Mean PRF was lower in the Melody valve group (15±6% versus 37±3%; P =0.014). The unprotected RUL was responsible for 64% of the PRF measured in the Melody valve group. In the non-Melody group, the RVEF was lower than baseline ( P =0.003) and than in the Melody group ( P =0.05). The LVEF was also lower in the non-Melody group versus baseline ( P =0.004) and versus Melody ( P =0.01). Conclusions— Bilateral branch PA Melody valve implantation significantly reduced PRF and altered RV and LV function favorably in a model of TAP for tetralogy of Fallot. This novel intervention may offer potential benefit in treating patients with anatomically heterogeneous disease of the RVOT.

Introduction: Chronic postoperative pulmonary insufficiency (PPI) is the major cause of long-term morbidity and mortality in patients (pts) with tetralogy of Fallot (TOF). Pulmonary valve replacement (PVR) can mitigate the risk, but optimal timing for PVR remains controversial. Time-resolved 3D phase-contrast MRI (4DF) provides insight into complex intracardiac flow patterns. 4DF may help inform management decisions regarding timing of PVR. We describe the first quantitative serial 4DF analysis in an ovine model of PPI. Methods: A baseline cardiac MRI (CMRI) was performed on four Dorsett sheep (36-39kg) on a 3-Tesla Siemens scanner. Following baseline MRI, animals underwent pulmonary valvectomy and transannular patch (TAP) placement yielding PPI. Follow-up CMRI were obtained at 5mo and 7mo post-valvectomy (PoVa). Pathlines were emitted from a circular region of interest (ROI) representing the pulmonary valve annulus. Velocities, flow rate, and stresses were obtained throughout a complete cardiac cycle and compared across time. Results: Systolic max velocity, average velocity, and flow rate normal to the ROI plane decreased over time. Diastolic velocities increased at 5mo before decreasing at 7mo PoVa. Regurgitant flow was observed in diastole PoVa , and regurgitant flow rate increased with time. The max and average component of shear stress (viscosity = 3 cP) along the pulmonary artery wall decreased over time in systole. In diastole, shear stress increased at 5mo and decreased at 7mo. Parameters plotted in Figure 1. Conclusion: 4DF provides a new method for visualization and quantification of alterations in blood flow patterns in the right side of the heart in an ovine model of PPI. Alterations in above parameters may indicate myocardial and pulmonary vascular deterioration precedent to morphological changes. Characterization of altered flow patterns in human pts with TOF may help to ultimately inform decisions regarding timing of PVR.

Introduction: Interest in high fidelity aortic flow phantoms remains significant even with advancements in computational fluid dynamic methods. We present a process for creating a patient-specific, compliant aortic arch and valve (AoV) along with our corresponding validation efforts. Methods: A rendered aortic volume was created by threshold-based segmentation in Mimics (Materialise, Leuven, Belgium) and edited in 3-matic to create a 3D printed mold (Object Connex 5000, Stratasys, Edina, Minnesota) into which a polyurethane based resin (Smooth-on, Easton, Pennsylvania) was cast. The AoV was created in a similar manner and ultimately seated in the distal end of an inlet port designed to induce laminar flow. The arch, with fixed inlet, was then constrained to the correct anatomical conformation by a custom rapid prototyped chamber. An MRI-compatible pump programmed to match the patient’s flow profile managed flow of a 40% glycerin-aqueous solution. Both through-plane and 4D phase contrast velocity mapping MRI sequences were acquired and compared to the patient data with time-elapse flow streamlines calculated by GTFlow version 2.0.1 (GyroTools, Zurich Switzerland). Results: The phantom remained robust and compliant throughout the dynamic loading occurring under pulsatile flow. Registration revealed good alignment of the phantom lumen to the segmented patient aorta. 4D flow analysis showed an unusual left-handed helical flow pattern in both the in vivo patient data and derived phantom flows. Flow measurements in the ascending and descending aorta of the model agreed within 5% of the actual patient measured flow. Conclusions: We have demonstrated a viable method to create patient-specific flow phantoms, which closely mimic the physiological system for which they are modeled. Further studies are needed to optimize the valve anatomy and wall compliance.

Percutaneous pulmonary valve replacement is one of the most important advancements in the field of interventional cardiology in the past decade.1,2 However, currently available technologies are not applicable to patients with oversized right ventricular outflow tracts (RVOTs), especially when there is concomitant proximal branch pulmonary artery (PA) stenosis. This combination commonly is encountered in clinical practice. Our group has a longstanding interest in these complex patients, and we have recently published preclinical studies describing the feasibility and short-term effects of implanting 2 Melody valves—1 into each proximal branch PA—in an ovine model of postoperative pulmonary insufficiency and dilated RVOT.3 This report describes bilateral branch PA Melody valve implantation to treat complex RVOT dysfunction in a high-risk patient. At presentation, the patient was a 27-year-old woman with a complex medical history. Her cardiac condition was double-outlet RV with pulmonary stenosis and interrupted inferior vena cava with azygos continuation to a left-sided superior vena cava. She was status post-Waterston shunt as an infant, with subsequent closure of the ventricular septal defect and patch augmentation of the RVOT. Three months before catheterization, the patient presented to her cardiologist with symptoms of progressive activity intolerance over the past year. She was oxygen dependent and on long-term continuous positive airway pressure therapy. Comorbidities included VATER and Klippel-Feil syndromes, renal agenesis, Mullerian agenesis, gout, and obesity. The patient had undergone multiple spinal fusion and Harrington rod procedures as well as repair of tracheoesophageal …

Background: Coronary occlusive ischemic events are responsible for 50 –70% of cardiac arrests in adults. We investigated the effects of intra-CPR mild hypothermia (HTM) (target 32–33°C) with and without volume loading on return to spontaneous circulation (ROSC) and infarction size in a severe, mid-LAD occlusion model of cardiac arrest. Methods: 46 (27±2.3kg) pigs had their mid LAD balloon occluded and were divided in 5 groups. After 15 minutes, ventricular fibrillation (VF) was electrically induced and 5 minutes of untreated VF were followed by 5 minutes of pneumatic vest CPR with a set compression pressure (250mmHg). If ROSC was obtained, animals were followed for another 95 minutes for a total LAD occlusion time of 120 min. Subsequently the balloon was deflated and 90 min of reperfusion were followed by myocardial staining to define area at risk (AAR) and myocardial infarct size. Group A had no additional intervention. Group B received immediately post ROSC surface cooling with cooling blankets and ice. Group C received intra-CPR 680±23ml of 28°C 0.9% NS via a central femoral venous catheter. Group D received during CPR 673±26 of 4°C NS followed by post ROSC surface cooling as in group B. Group E received intra-CPR and post ROSC volume-sparing HTM with an Endovascular Therapeutic Hypothermia System (ETHS) placed into the right atrium and set at a target of 32°C. Results: During CPR, coronary perfusion pressure was significantly decreased in groups C and D compared to groups A, B and E but groups D and E had significantly reduced infarct size. Group E had significantly improved EF compared to all other groups. Table . Conclusions: Intra-CPR HTM significantly reduces myocardial infarction size. Volume loading during CPR is detrimental for ROSC due to reduction of coronary perfusion pressure. ETHS intra-CPR application improves ROSC and post-resuscitation LV function and minimizes infarction in this ischemia-reperfusion cardiac arrest model. Results