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Background: Postoperative atrioventricular block requiring pacemaker (AVB/PM) complicates 14% to 25% of biventricular repair operations for complex congenital heart disease (CHD) and in those with heterotaxy syndrome., Objectives: This study aimed to evaluate if intraoperative His bundle (HB) mapping during complex biventricular CHD repair can be performed safely and reduce postoperative AVB/PM., Methods: HB mapping was performed using a commercially available multielectrode grid catheter in patients with complex CHD undergoing biventricular repair between 2019 and 2022 compared with an unmapped cohort. The primary outcome was postoperative AVB/PM., Results: One hundred forty-nine patients underwent HB mapping compared to 201 unmapped controls. The median age of mapped patients was 1.9 years (Q1-Q3: 0.9-3.9 years). Heterotaxy syndrome was present in 31% (n = 46 of 149), ventricular septal defect in 95% (n = 142 of 149), and prior single ventricle palliation in 68% (n = 89 of 149). The HB was identified in 97% (n = 144 of 149) of cases. The median mapping time was 6 minutes. No episodes of intraoperative systemic air embolism occurred. Postoperative AVB/PM frequency was significantly reduced in mapped patients with heterotaxy (2% [n = 1 of 46] vs 16% [n = 11 of 67]; P = 0.026) and in patients without L-malposed great arteries (3% [n = 3 of 88] vs 11% [n = 15 of 134]; P = 0.045)., Conclusions: Intraoperative HB mapping can be performed safely and is associated with significantly reduced postoperative AVB/PM in select populations undergoing complex biventricular repair, including heterotaxy syndrome and non-L-malposed great arteries. Nonetheless, certain subgroups remain at risk for AVB/PM, showing the need for further improvements to current intraoperative HB mapping technology and techniques., Competing Interests: Funding Support and Author Disclosures The clinical work presented here was supported by a Strategic Investment Grant from the Heart Center at Boston Children’s Hospital. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Reintervention rates after patch-augmented reconstruction for hypoplastic aortic arch remain moderately high. We analyzed mid-term outcomes of aortic arch reconstruction to define modifiable reintervention risk factors., Methods: Excluding Damus-Kaye-Stansel anastomoses and previous arch repair, 338 patients underwent arch reconstruction from 2000-2021 at median age 6d (IQR 4-13d) and weight 3.2kg (IQR 2.8-3.7kg). Surgical technique was patch augmentation with coarctectomy ± interdigitation in 269 (80%), isolated patch aortoplasty in 41 (12%), and other reconstruction in 28 (8%). Risk factors for reintervention were assessed using competing risk models., Results: At median follow-up of 3.9y (IQR 1.1-8.0y), 35 (10.4%) patients required reintervention (30 endovascular, 12 surgical, 7 both). Ten-year cumulative incidence of death/transplant and reintervention were 10% (95%CI 4-20%) and 13% (95%CI 8-20%). On univariate analysis, isolated patch aortoplasty (p=0.002), aortic homograft patch material (p=0.006), and postoperative aortic size z-score ≤-2 for each segment were associated with greater risk of reintervention: ascending aorta (p=0.006), proximal (p=0.001) and distal (p=0.005) transverse arch, and aortic isthmus (p<0.001). On multivariable analysis, aortic homograft (HR 6.29, 95%CI 1.94-20.5, p=0.002) and postoperative isthmus z-score ≤-2 (HR 10.5, 95%CI 5.15-21.5, p<0.001) remained significant. Patients with repaired isthmus z-score ≤-2 had 72.8% (95%CI 44.6-94.4%) cumulative incidence of reintervention at 10 years, versus 6.8% (95%CI 4.1-11.4%) in those with z-score >-2., Conclusions: Aortic undersizing during patch-augmented reconstruction of hypoplastic aortic arch results in over 10% rate of reintervention at mid-term follow-up. Achieving adequate postoperative arch size is critical for preventing reintervention, with aortic isthmus size being of utmost importance., (Copyright © 2024. Published by Elsevier Inc.)

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: The Fontan operation, a palliative procedure for single ventricle patients, has evolved to improve outcomes and reduce complications. While extracardiac conduit (ECC) is favored for its simplicity and potential hemodynamic benefits, concerns arise about conduit size adequacy over time. Undersized ECC conduits may cause hemodynamic inefficiencies and long-term complications, while oversizing can lead to flow disturbances, stagnation, and thrombosis, necessitating surgical revision or upsizing to optimize hemodynamics., Objectives: The study aimed to predict the impact of upsizing by developing a patient-specific workflow using cardiac magnetic resonance-based imaging and computational fluid dynamics to assess Fontan hemodynamic changes and determine the most optimal conduit size., Methods: We simulated upsizing in patient-specific models, computing reduction in power loss (PL), and analyzed pressure gradients, wall shear stress (WSS), and other local flow dynamic parameters such as vorticity and viscous dissipation that influence PL in a Fontan. Additionally, we quantified the impact of upsizing on hepatic flow distribution (HFD)., Results: Across the patient cohort, upsizing resulted in a PL reduction of 16 %-63 %, with the greatest reduction observed in patients with the smallest pre-existing conduit sizes (14 mm). The optimal conduit size for minimizing PL was highly patient-specific. For instance, a 20 mm conduit reduced PL by 63 % in one patient, while another patient showed 16 % reduction with upsizing. Pressure gradients decreased by 15 %-35 %, correlating with the reduction in PL, while WSS decreased consistently with upsizing. Vorticity and viscous dissipation exhibited more variability but followed the overall trend of reduced PL. HFD changes were modest with a maximum variation of 30 %., Conclusions: Our findings underscore the importance of individualized approaches in Fontan conduit upsizing. CFD-based quantitative evaluations of PL, pressure gradients, HFD, and WSS can guide optimal conduit sizing, improving long-term outcomes for patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:VG reports research funding from the AHA (19TPA34860013), the NHLBI/NIH (R01HL161507) and in-kind research support from NSF (high-performance computing resources from TACC). AS, EE, DH, PEH, and RR report research funding from the NHLBI/NIH (R01HL161507)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Valve-sparing root replacement (VSRR) is attractive for aortic root dilation as it preserves the native aortic valve (AoV). Low effective height (eH) after reconstruction is a risk factor for repair failure and reoperation. We developed and validated a quantitative AoV repair strategy to reliably restore normal valve proportions to promote long-term function., Methods: Normal AoV proportions were used to derive geometric relationships for sinotubular junction diameter (D STJ ), free edge length (FEL), free edge angle, and commissure height. These relationships informed two models for predicting eH following VSRR: (1) assuming valve symmetry and (2) accounting for valve asymmetry. Porcine heart (n = 6) ex vivo validation was performed under 4 VSRR scenarios: "Ideal" (tube graft size targeting FEL/D STJ  = 1.28), "Oversized" (one graft size larger than Ideal), "Undersized" (two sizes smaller), and "Undersized + Plicated" (FEL/D STJ  = 1.28 restored with leaflet plication)., Results: Our analytical models predicted eH using preoperative measurements and estimated reconstructed dimensions. The Oversized graft exhibited similar eH to Ideal but higher regurgitation in the ex vivo model, whereas the Undersized graft demonstrated lower eH and regurgitation. Plication in the Undersized graft restored valve function (regurgitation & eH) similar to Ideal in the ex vivo model and above Ideal in the analytical models. Both analytical models predicted ex vivo eH well except in the Oversized and Undersized + Plicated conditions., Conclusion: Utilizing measurements from preoperative imaging and simple mathematical models, patient-specific operative plans for VSRR can be created by estimating valve dimensions necessary to achieve favorable valve features post-repair. Clinical application of this approach promises to improve consistency in achieving optimal long-term dimensions and durability., Competing Interests: Declarations Competing Interests The authors have no relevant financial or non-financial interests to disclose. IRB Approval In vitro studies were performed with exemption by Boston Children’s Hospital IRB. Informed Consent Not applicable., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Computational models of patients and medical devices can be combined to perform an in silico clinical trial (ISCT) to investigate questions related to device safety and/or effectiveness across the total product life cycle. ISCTs can potentially accelerate product development by more quickly informing device design and testing or they could be used to refine, reduce, or in some cases to completely replace human subjects in a clinical trial. There are numerous potential benefits of ISCTs. An important caveat, however, is that an ISCT is a virtual representation of the real world that has to be shown to be credible before being relied upon to make decisions that have the potential to cause patient harm. There are many challenges to establishing ISCT credibility. ISCTs can integrate many different submodels that potentially use different modeling types (e.g., physics-based, data-driven, rule-based) that necessitate different strategies and approaches for generating credibility evidence. ISCT submodels can include those for the medical device, the patient, the interaction of the device and patient, generating virtual patients, clinical decision making and simulating an intervention (e.g., device implantation), and translating acute physics-based simulation outputs to health-related clinical outcomes (e.g., device safety and/or effectiveness endpoints). Establishing the credibility of each ISCT submodel is challenging, but is nonetheless important because inaccurate output from a single submodel could potentially compromise the credibility of the entire ISCT. The objective of this study is to begin addressing some of these challenges and to identify general strategies for establishing ISCT credibility. Most notably, we propose a hierarchical approach for assessing the credibility of an ISCT that involves systematically gathering credibility evidence for each ISCT submodel in isolation before demonstrating credibility of the full ISCT. Also, following FDA Guidance for assessing computational model credibility, we provide suggestions for ways to clearly describe each of the ISCT submodels and the full ISCT, discuss considerations for performing an ISCT model risk assessment, identify common challenges to demonstrating ISCT credibility, and present strategies for addressing these challenges using our proposed hierarchical approach. Finally, in the Appendix we illustrate the many concepts described here using a hypothetical ISCT example., Competing Interests: TB, JY, and SL were employed by the company Dassault Systémes, makers of the software applications 3DEXPERIENCE, Abaqus, and Dymola that were used in this study. AP was employed by Thornton Tomasetti, Inc. SK was employed by Exponent, Inc. DH receives gift-in-kind software from several modeling and simulation companies including Dassault Systémes, Ansys, Materialize, and Realize Medical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Aycock, Battisti, Peterson, Yao, Kreuzer, Capelli, Pant, Pathmanathan, Hoganson, Levine and Craven.)

Background: Single ventricle (SV) patients with interrupted inferior vena cava (iIVC) and azygos continuation are at high risk for unbalanced hepatic venous flow (HVF) distribution to the lungs after Fontan completion and subsequent pulmonary arteriovenous malformations (AVMs) formation., Objectives: The aim of the study was to utilize computational fluid dynamics (CFD) analysis to avoid maldistribution of HVF to the lungs after Fontan surgery., Methods: Four SV subjects with iIVC were prospectively studied with a 3-dimensional (3D) modeling workflow with digital 3D models created from segmented magnetic resonance images or computer tomography scans, virtual surgery, and CFD analysis over multiple physiologic states for the evaluation of operative plans to achieve balanced HVF to both lungs. Three of the patients were Fontan revision candidates with existing AVMs. All patients underwent Fontan completion or revision surgery., Results: CFD predicted that existing or proposed Fontan completion in all patients would result in 100% of HVF to one lung. Improved HVF balance was achieved with CFD analysis of alternative surgical approaches resulting in the average distribution of HVF to the right/left pulmonary arteries of 37%/63% ± 10.4%. A hepatoazygos shunt was required in all patients and additional creation of an innominate vein in one. CFD analysis was validated by the comparison of pre-operative predicted and postoperative MRI-measured total right/left pulmonary flow (51%/49% ± 5.4% vs 49%/51% ± 8.5%)., Conclusions: A 3D modeling workflow with CFD simulation for SV patients with iIVC may avoid HVF maldistribution and development of AVMs after Fontan completion., Competing Interests: Gift in-kind software from Dassault Systemes. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Restoring adequate coaptation height is a key principle of mitral valve (MV) repair. This study aimed to evaluate the utility of fiberscope (FS) technology to assess MV coaptation height for intraoperative use., Methods: Ex-vivo testing was performed on five adult porcine hearts. The left atrium (LA) was resected, and the left ventricle (LV) was pressurized retrograde to 27 ± 1mm Hg. An endoscope was inserted into the LV apex, centered under the MV orifice. An FS system (Milliscope II camera, LED light source, and 0.7 mm diameter × 15 cm long) 90° semirigid scope with 1.2 mm focal length) was mounted above the MV annulus in a custom alignment and measuring fixture. Three blinded measurements were taken at two locations on each MV, A2 and P2 segment, from the top of coaptation to the leaflet edge identified by the FS. Accurate positioning was verified using the LV endoscope. A control (metal rod of similar thickness) was used for comparison, with coaptation height recorded when the control was seen via the endoscope., Results: Coaptation heights were similar for the control and FS methods across all hearts at A2 (11.6 ± 2.6 mm control vs 11.8 ± 2.2 mm FS) and P2 (13.3 ±   2.6 mm control vs 13.4 ±   2.9 mm FS) segments, with similar measurement variability (control SD 0.1-1.0 mm; FS SD 0.1-0.9 mm). One outlier was excluded from analysis (n = 19/20). The maximum absolute difference and percent error between measurement methods were less than 1.1 mm (median [IQR], 0.6 [0.3-0.9] mm) and less than 14% (4.1 [2.2-7.6]%)., Conclusions: Utilization of a miniaturized FS enabled precise and accurate quantification of MV coaptation. This technique is promising for evaluating post-repair valve competence and coaptation height.

Background: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling., Methods: SVC and IVC flow from 414 patients with Fontan were collected to establish a relationship between SVC:IVC flow ratio and age. Computational fluid dynamics modeling was performed in 60 (30 extracardiac and 30 lateral tunnel) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively., Results: SVC:IVC flow ratio inverted at ≈8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC, 2, 1, and 0.5 corresponded to ages, 3, 8, and 15+, respectively) was not significant for extracardiac but statistically significant for lateral tunnel cohorts. For all 3 caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2 to 0.5 (age, 3-15+) years, the correlation's strength decreased from 0.87 to 0.64, due to potential flow perturbation as IVC flow momentum increased., Conclusions: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of SVC:IVC variations over time on Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes., Competing Interests: Disclosures Dr Govindarajan reports research funding from the American Heart Association (19TPA34860013), the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH; R01HL161507) and in-kind research support from National Science Foundation (high-performance computing resources from Texas Advanced Computing Center). A. Sahni, E. Eickhoff, and Drs Hoganson, Hammer, and Rathod report research funding from the NHLBI/NIH (R01HL161507). In addition, Dr Govindarajan reports collaborative research funding from Polyvascular Corp, Houston, TX.

Objectives: Outcome data in tetralogy of Fallot (ToF) and complete atrioventricular canal (CAVC) are limited. We report our experience for over 40 years in this patient population., Methods: Single-centre, retrospective analysis of patients who underwent surgical repair with the diagnosis of ToF-CAVC from 1979 to 2022, divided into 2 different periods and compared., Results: A total of 116 patients were included: 1979-2007 (n = 61) and 2008-2021 (n = 55). Balanced CAVC (80%) and Rastelli type C CAVC (81%) were most common. Patients in the later era were younger (4 vs 14 months, P < 0.001), fewer had trisomy 21 (60% vs 80%, P = 0.019) and fewer had prior palliative prior procedures (31% vs 43%, P < 0.001). In the earlier era, single-patch technique was more common (62% vs 16%, P < 0.001), and in recent era, double-patch technique was more common (84% vs 33%, P < 0.001). In the earlier era, right ventricular outflow tract was most commonly reconstructed with transannular patch (51%), while in more recent era, valve-sparing repairs were more common (69%) (P < 0.001). In-hospital mortality was 4.3%. The median follow-up was 217 and 74 months for the first and second eras. Survival for earlier and later eras at 2-, 5- and 10-year follow-up was (85.1%, 81.5%, 79.6% vs 94.2%, 94.2%, 94.2% respectively, log-rank test P = 0.03)., Conclusions: The surgical approach to ToF-CAVC has evolved over time. More recently, patients tended to receive primary repair at younger ages and had fewer palliative procedures. Improved surgical techniques allowing for earlier and complete repair have shown a decrease in mortality, more valve-sparing procedures without an increase in total reoperations. Presented at the 37th EACTS Annual Meeting, Vienna, Austria., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Optimal aortic sizing during aortic arch reconstruction remains unknown. Negative effects of arch under- or oversizing are well-published. We aimed to characterize longitudinal aortic growth after patch-augmented arch reconstruction to identify the initial reconstructed arch size that results in normal mid-term arch dimensions., Methods: Single-centre, retrospective review of infants undergoing Damus-Kaye-Stansel (DKS) or non-DKS patch-augmented aortic arch reconstruction between 2000 and 2021. Ascending aorta, proximal and distal transverse arch, aortic isthmus (AIsth) and descending aorta dimensions were measured in postoperative echocardiograms (<3 months from index operation) and cross-sectional imaging (>12 months). Longitudinal changes to aortic dimensions and z-scores were analysed. Secondary outcomes included reintervention, valve and ventricular function, mortality and transplantation., Results: Fifty-four patients (16 DKS, 38 non-DKS) were included. At 6.3 [2.2, 12.0]-year follow-up, all aortic segments grew significantly in both groups, while z-scores remained unchanged except for non-DKS proximal and distal transverse arch z-scores, which significantly increased (P < 0.05 each). When stratified by initial postoperative z-score (z < -1, -1 ≤ z ≤ 1, z > 1), non-DKS patients with initial AIsth z-score <-1 had a final z-score significantly smaller than both the targeted z-score zero (P = 0.014) and final z-score in a group with initial postoperative z-score ±1 (P = 0.009). Valve and ventricular function remained stable. Eighteen patients required reintervention, 1 died and 1 underwent transplant., Conclusions: Over mid-term follow-up, aortic growth after arch reconstruction with patch augmentation was proportional when repaired to normal z-score dimensions, aside from proximal transverse arch, which disproportionately dilated. AIsth undersizing prevailed mid-term and trended towards a higher reintervention rate. Initial reconstruction between z-score 0 and +1 resulted in maintenance of that z-score size at mid-term follow-up. Overall, it is crucial to achieve targeted aortic sizing at index operation to maintain appropriate aortic dimensions over time and reduce reintervention risk with specific focus on the AIsth., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: Pulmonary valve (PV) monocusp reconstruction in transannular patch (TAP) right ventricular outflow tract (RVOT) repair for Tetralogy of Fallot has variable clinical outcomes across different surgical approaches. The study purpose was to systematically evaluate how monocusp leaflet design parameters affect valve function in-vitro., Methods: A 3D-printed, disease-specific RVOT model was tested under three infant physiological conditions. Monocusps were sewn into models with the native main pulmonary artery (MPA) forming backwalls that constituted 40% and 50% of the reconstructed circumference for z-score zero PV annulus and MPA diameters (native PV z-score - 3.52 and - 2.99 for BSA 0.32m 2 ). Various leaflet free edge lengths (FEL) (relative to backwall), positions (relative to PV STJ), and scallop depths were investigated across both models. Pressure gradient, regurgitation, and coaptation were analyzed with descriptive statistics and regression models., Results: Increasing FEL beyond 100% of the MPA backwall decreased gradient but mildly increased regurgitation to a peak of 25%. Positioning the free edge 2 mm past the STJ mildly increased gradient for each FEL without significantly changing regurgitation compared to STJ placement. Scalloping leaflets trivially affected performance. Pre-folding leaflets improved mobility and slightly reduced gradient., Conclusions: Balancing gradient, regurgitation, and oversizing for growth, a set of leaflet designs have been selected for pre-clinical evaluation. Designs with leaflet widths 140-160% in the 40% backwall model (110-120% in the 50% backwall), positioned at or 2 mm past the STJ, demonstrated the best results. The next stage of ex-vivo testing will additionally consider native RVOT distensibility, native leaflet interactions, and TAP characteristics., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Neonates with complex congenital heart disease and pulmonary overcirculation have been historically treated surgically. However, subcohorts may benefit from less invasive procedures. Data on transcatheter palliation are limited., Methods: We present our experience with pulmonary flow restrictors (PFRs) for palliation of neonates with congenital heart disease, including procedural feasibility, technical details, and outcomes. We then compared our subcohort of high-risk single ventricle neonates palliated with PFRs with a similar historical cohort who underwent a hybrid Stage 1. Cox regression was used to evaluate the association between palliation strategy and 6-month mortality., Results: From 2021 to 2023, 17 patients (median age, 4 days; interquartile range [IQR], 2-8; median weight, 2.5 kilograms [IQR, 2.1-3.3]) underwent a PFR procedure; 15 (88%) had single ventricle physiology; 15 (88%) were high-risk surgical candidates. All procedures were technically successful. At a median follow-up of 6.2 months (IQR, 4.0-10.8), 13 patients (76%) were successfully bridged to surgery (median time since PFR procedure, 2.6 months [IQR, 1.1-4.4]; median weight, 4.9 kilograms [IQR, 3.4-5.8]). Pulmonary arteries grew adequately for age, and devices were easily removed without complications. The all-cause mortality rate before target surgery was 24% (n=4). Compared with the historical hybrid stage 1 cohort (n=23), after adjustment for main confounding (age, weight, intact/severely restrictive atrial septum or left ventricle to coronary fistulae), the PFR procedure was associated with a significantly lower all-cause 6-month mortality risk (adjusted hazard ratio, 0.26 [95% CI, 0.08-0.82])., Conclusions: Transcatheter palliation with PFR is feasible, safe, and represents an effective strategy for bridging high-risk neonates with congenital heart disease to surgical palliation, complete repair, or transplant while allowing for clinical stabilization and somatic growth., Competing Interests: Disclosures None.

Objectives: Thick-patch pulmonary homograft, autologous pericardium and CardioCel Neo are common patch materials for aortic arch reconstruction. Insufficient data exist on sutured patch strength and limits of use. We evaluated failure strength of these materials to develop a failure prediction model for clinical guidance., Methods: Patch failure strength was evaluated via sutured uniaxial and burst pressure testing. In sutured uniaxial testing, patches were sutured to aortic or Dacron tabs and pulled to failure. In burst pressure testing, patches were sewn into porcine aortas or Dacron grafts and pressurized to failure. Failure membrane tension was calculated. A prediction model of membrane tension versus vessel diameter was generated to guide clinical patch selection., Results: Combining sutured uniaxial and burst pressure test data, pulmonary homograft failure strength {0.61 [interquartile range (IQR): 0.44, 0.78] N/mm, n = 21} was less than half that of autologous pericardium [2.22 (IQR: 1.65, 2.78) N/mm, n = 15] and CardioCel Neo [1.31 (IQR: 1.20, 1.42) N/mm, n = 20]. Pulmonary homograft burst pressure [245 (IQR: 202, 343) mmHg, n = 7] was significantly lower than autologous pericardium [863 (IQR: 802, 919) mmHg, n = 6] and CardioCel Neo [766 (IQR: 721, 833) mmHg, n = 6]. Our model predicts failure limits for each patch material and outlines safety margins for combinations of aortic diameter and pressure., Conclusions: Sutured failure strength of thick-patch pulmonary homograft was significantly lower than autologous pericardium and CardioCel Neo. Patient selection (predicted postoperative arch diameter and haemodynamics) and blood pressure management must be considered when choosing patch material for arch reconstruction. In older children and adolescents, autologous or bovine pericardium may be more suitable materials for aortic patch augmentation to minimize the risk of postoperative patch failure., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose: Very high-risk, ductal-dependent or complex two-ventricle patients with associated comorbidities often require pulmonary blood flow restriction as bridge to a more definitive procedure, but current surgical options may not be well-tolerated. An evolving alternative utilizes a fenestrated Micro Vascular Plug (MVP) as a transcatheter, internal pulmonary artery band. In this study, we report a case series and an in-vitro evaluation of the MVP to elicit understanding of the challenges faced with device implantation., Methods: Following single-center, retrospective review of eight patients who underwent device placement, an in-vitro flow study was conducted on MVP devices to assess impact of device and fenestration sizing on pulmonary blood flow. A mathematical model was developed to relate migration risk to vessel size. Results of the engineering analysis were compared to the clinical series for validation., Results: At median follow-up of 8 months (range 1-15), survival was 63% (5/8), and 6 (75%) patients underwent subsequent target surgical intervention with relatively low mortality (1/6). Occluder-related challenges included migration (63%) and peri-device flow, which were evaluated in-vitro. The device demonstrated durability over normal and supraphysiologic conditions with minimal change in fenestration size. Smaller vessel size significantly increased pressure gradient due to reduced peri-device flow and smaller effective fenestration size., Conclusion: Device oversizing, with appropriate adjustment to fenestration size, may reduce migration risk and provide a clinically appropriate balance between resulting pressure gradient and Qp:Qs. Our results can guide the interventionalist in appropriately selecting the device and fenestrations based on patient-specific anatomy and desired post-implantation flow characteristics., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objectives: The study objectives were to report on a growing experience of conduction system mapping during complex congenital heart surgery and create a predictive model of conduction anatomy., Methods: Patients undergoing complex cardiac repair with conduction mapping were studied. Intraoperative mapping used a multielectrode catheter to collect His bundle electrograms in the open, decompressed, beating heart. Patient anatomy, operative details, His bundle location, and postoperative conduction status were analyzed. By using classification and regression tree analysis, a predictive model of conduction location was created., Results: A total of 109 patients underwent mapping. Median age and weight were 1.8 years (range, 0.2-14.9) and 10.8 kg (range, 3.5-50.4), respectively. Conduction was identified in 96% (105/109). Median mapping time was 6 minutes (range, 2-33). Anatomy included atrioventricular canal defect, double outlet right ventricle, complex transposition of the great arteries, and multiple ventricular septal defects. By classification and regression tree analysis, ventricular looping and visceroatrial situs were the greatest discriminators of conduction location. A total of 94 of 105 patients (89.5%) were free of complete heart block. Only 1 patient (2.9%) with heterotaxy syndrome developed complete heart block., Conclusions: The precise anatomic location of the conduction system in patients with complex congenital heart defects can be difficult for the surgeon to accurately predict. Intraoperative conduction mapping enables localization of the His bundle and adds to our understanding of the anatomic factors associated with conduction location. Predictive modeling of conduction anatomy may build on what is already known about the conduction system and help surgeons to better anticipate conduction location preoperatively and intraoperatively., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Tetralogy of Fallot and other conditions affecting the right ventricular outflow tract (RVOT) are common in pediatric patients, but there is a lack of quantitative comparison among techniques for repairing or replacing the pulmonary valve. The aim of this study was to develop a robust in vitro system for quantifying flow conditions after various RVOT interventions., Methods: An infant-sized mock circulatory loop that includes a 3D-printed RVOT anatomical model was developed to evaluate flow conditions after different simulated surgical repairs. Physiologically correct flow and pressure were achieved with custom compliant tubing and a tunable flow restrictor. Pressure gradient, flow regurgitation, and coaptation height were measured for two monocusp leaflet designs after tuning the system with a 12 mm Hancock valved conduit., Results: Measurements were repeatable across multiple samples of two different monocusp designs, with the wider leaflet in the 50% backwall model consistently exhibiting lower pressure gradient but higher regurgitation compared to the leaflet in the 40% backwall model. Coaptation height was measured via direct visualization with endoscopic cameras, revealing a shorter area of contact for the wider leaflet (3.3-4.0 mm) compared to the narrower one (4.3 mm)., Conclusion: The 3D-printed RVOT anatomical model and in vitro pulmonary circulatory loop developed in this work provide a platform for planning and evaluating surgical interventions in the pediatric population. Measurements of regurgitation, pressure gradient, and coaptation provide a quantitative basis for comparison among different valve designs and positions., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: In 2012, a global outbreak of invasive Mycobacterium chimaera (M. chimaera) infection was identified in patients after cardiopulmonary bypass surgery. Investigations revealed the source to be heater-cooler unit (HCU) exhaust, with point-source contamination discovered at the LivaNova HCU manufacturing plant (London, UK). We report our experience with affected HCUs at a high-volume pediatric cardiac surgery center in the United States., Methods: A multidisciplinary task force was established for outbreak management, including removing contaminated HCUs from service. Patients identified as exposed to affected HCUs were systematically contacted. A call center was created for patient/family inquiries, and symptomatic patients were assessed using an institutional triage protocol, including laboratory/culture data and infectious diseases consultation., Results: Cardiopulmonary bypass surgeries were performed in 4276 patients (median age: 2.1 years; range: 0-48.4 years) between October 2010 and October 2016. Call center volume was highest in the first 6 weeks after patient notification, totaling 307 calls and yielding 70 clinical patient assessments. Presenting symptoms included fatigue (60%), fever (49%), night sweats (46%), myalgias (34%), and weight loss (24%). Among the 70 assessed patients, echocardiogram (n = 30), cardiac computed tomography (n = 2), cardiac magnetic resonance imaging (n = 1), and pulmonary computed tomography (n = 1) did not reveal abnormalities suggestive of active infection. Infectious diseases consultation occurred in 23 (33%) patients. Acid-fast bacilli blood cultures were obtained in 30 patients; all were negative., Conclusions: Through a highly coordinated outreach effort, no patients have been found to have M. chimaera infection in the 6 years after exposure to contaminated HCUs. Ongoing vigilance for cases that may yet manifest is needed., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Hypoplastic left heart syndrome (HLHS) with aortic atresia (AA) patients are prone to coronary insufficiency due to a small ascending aorta. Prophylactic patch augmentation of the small ascending aorta during the stage I procedure (S1P) may reduce the risk of coronary insufficiency as marked by ventricular dysfunction, need for extracorporeal membrane oxygenator (ECMO) support or mortality., Methods: Retrospective analysis of patients with HLHS with AA who underwent an S1P was completed. Baseline ascending aorta size, right ventricular (RV) function and outcome variables of transplant-free survival, ECMO support after the stage 1 operation and RV function at the time of the bidirectional Glenn and latest follow-up were collected., Results: Between January 2010 and April 2020, 11 patients underwent prophylactic ascending aorta augmentation at the time of the S1P as a planned portion of the procedure. A total of 125 patients underwent S1P during this period as a comparison. Overall survival was 100% for the augmented group and 74% for the control group (P = 0.66). A composite end point of transplant-free survival, no post-S1P ECMO and less than moderate RV dysfunction was created. At the time of BDG, this composite end point was 100% for the augmented group and 61.8% for the control group (P = 0.008) and at most recent follow-up was 100% for the augmented group and 59.3% for control (P = 0.007). Eight patients required a rescue procedure for the clinical evidence of coronary insufficiency following S1P that included ascending aorta patch augmentation or stent placement. When comparing these rescue versus prophylactic ascending aortic augmentations, there were also differences in the composite outcome 100% for augmented and 60% for rescue (P = 0.009) and at the time of most recent follow-up 100% for augmented and 50% for rescue (P = 0.029)., Conclusions: Prophylactic patch augmentation of the ascending aorta in HLHS patients with AA may reduce the risk of mortality, ECMO and reduced RV function. Patients not initially undergoing augmentation but then requiring a rescue procedure have particularly poor outcomes. Patch augmentation for smaller ascending aortic diameters should be considered and further clinical experience may help delineate aorta diameter threshold for augmentation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Postoperative heart block is a significant problem in congenital heart surgery because of the unpredictability and variability of conduction tissue location in complex congenital heart defects. A novel technique for intraoperative conduction system mapping during complex congenital heart surgery is described., Methods: Intraoperative conduction system mapping was performed utilizing a high-density multielectrode grid catheter to collect intracardiac electrograms on open, beating hearts during repair of complex congenital heart defects. Electrograms were interpreted by electrophysiologists, and conduction tissue location was communicated in real time to the surgeon. After localizing conduction tissue, the heart was arrested and the repair was completed taking care to avoid injury to the mapped conduction system., Results: Two patients with complex heterotaxy syndrome underwent intraoperative conduction mapping during biventricular repair. Mapping accurately identified the location of conduction tissue thereby enabling avoidance of conduction system injury during surgery. Notably, conduction was unexpectedly found to be located inferiorly in a patient with L-looped ventricles. Successful biventricular repair was accomplished in both patients without injury to the conduction system., Conclusions: Intraoperative conduction mapping can effectively localize the conduction system during surgery and enable the surgeon to avoid its injury. This can lower the risk of heart block requiring pacemaker in children undergoing complex congenital heart surgery., (© 2022 The Author(s).)

Introduction: Among patients with congenital heart disease, those born with only a single working ventricle represent a particularly complex sub-population, typically requiring multiple surgeries and suffering from high levels of mortality and morbidity. Their cardiac care is complex and has evolved considerably since surgical palliation was first introduced more than 50 years ago. Improvements in treatment have been driven both by growing clinical experience and by knowledge gained through experimental and computational studies of blood flow in these patients. The Cardiovascular Fluid Mechanics Lab at the Georgia Institute of Technology, founded 30 years ago by Dr. Ajit Yoganathan, has pioneered work in this field., Methods: In this review, key contributions of Dr. Yoganathan's Cardiovascular Fluid Dynamics Lab are surveyed, including experimental flow loop studies as well as computational fluid dynamics analyses that address many of the critical challenges that cardiologists and surgeons face in treating these patients, including how to reconstruct cardiovascular anatomy to minimize power loss, balance blood flow distribution at key bifurcation points, and avoid other unfavorable hemodynamic conditions., Conclusions: Among many contributions in this field, work from the Cardiovascular Fluid Mechanics Lab has led to novel medical devices and patient-specific computational modeling workflows and software tools. These key contributions from this group have enhanced our understanding of the physiology and management of single-ventricle patients., (© 2021. Biomedical Engineering Society.)

A 1-year old male patient with Williams syndrome and multiple prior interventions presented for surgical repair of his descending aorta (DA) through a left thoracotomy. Concerns for significant bleeding and spinal cord protection led the care team to consider a left heart bypass (LHB) circuit with options for pump sucker use, heat exchange capacity, and the possibility of converting to traditional cardiopulmonary bypass (CPB). A traditional CPB circuit with a roller-head arterial pump was assembled with a bypass line around the cardiotomy venous reservoir (CVR). Excluding the CVR with this line allowed for a closed LHB circuit. A second pump head was integrated to both recirculate the CVR volume and to serve as a means for controlled volume administration to the closed LHB circuit. Pump sucker return directed to the CVR could easily be transfused back to the patient. The patient was placed on the hybrid LHB circuit and cooled to 32°C. DA clamps were placed. Upper body dynamic blood pressure was managed for a target mean of 50 mmHg, the left atrial pressure (LAP) was maintained in the 5-7 mmHg range, and the nonpulsatile lower body blood pressure was targeted at 40-50 mmHg. Cerebral near-infrared spectroscopy (NIRS) helped guide volume and pressure management. The surgeons placed two long-segment patches on the DA, moving clamps as needed. The patient was rewarmed and separated from the hybrid LHB circuit after 82 minutes. Closed circuit LHB can be provided with a roller-head hybrid circuit incorporating an oxygenator for gas exchange, central cooling and warming, and arterial line filtration along with a CVR for pump sucker use and controlled transfusion to the patient., (© Copyright 2021 AMSECT.)

Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP. The ESHP circuit consists of an oxygenator, a heart-lung machine, a heater-cooler unit, an anesthesia gas blender, and a collection funnel. Female Yorkshire pig hearts (n = 10) had del Nido cardioplegia (4°C) administered, excised, and attached to the perfusion system. Hearts were perfused retrogradely into the aortic root for 2 hours before converting the system to an isovolumic mode or a working mode for further 2 hours. Blood samples were analyzed to measure metabolic parameters. During the isovolumic mode (n = 5), a balloon inserted in the left ventricular (LV) cavity was inflated so that an end-diastolic pressure of 6-8 mmHg was reached. During the working mode (n = 5), perfusion in the aortic root was redirected into left atrium (LA) using a compliance chamber which maintained an LA pressure of 6-8 mmHg. Another compliance chamber was used to provide an afterload of 40-50 mmHg. Hemodynamic and metabolic conditions remained stable and consistent for a period of 4 hours of ESHP in both isovolumic mode (LV developed pressure: 101.0 ± 3.5 vs. 99.7 ± 6.8 mmHg, p = .979, at 2 and 4 hours, respectively) and working mode (LV developed pressure: 91.0 ± 2.6 vs. 90.7 ± 2.5 mmHg, p = .942, at 2 and 4 hours, respectively). The present study proposed a novel ESHP system that enables comprehensive functional and metabolic assessment of large mammalian hearts. This system allowed for stable myocardial function for up to 4 hours of perfusion, which would offer great potential for the development of translational therapeutic protocols to improve dysfunctional donated hearts., (© Copyright 2020 AMSECT.)

Background: Tracheobronchomalacia and airway obstruction from severely dilated pulmonary arteries in tetralogy of Fallot with absent pulmonary valve (TOF-APV) has been associated with high rates of respiratory failure and mortality (15% to 25%). It is not known whether aggressive pulmonary artery (PA) or direct airway intervention during early definitive cardiac repair improves outcomes., Methods: A retrospective observational study was made of all patients undergoing surgical repair for TOF-APV at our center between 2006 and 2018., Results: Twenty patients underwent repair at a median age of 51 days and PA Z-scores of 8.1. Twelve patients had a valve implanted, 6 of whom required reoperation for valve replacement at a median of 9 months (range, 3 to 28) compared with 8 who had initial transannular patch, and only 1 patient required subsequent valve replacement (P < .05). Seven patients had central PAs replaced with thin-walled Gore-Tex (WL Gore, Flagstaff, AZ) grafts; none of these required PA reoperation during a median follow-up of 26.5 months, whereas 3 of 13 patients who did not have PA replacement with Gore-Tex required subsequent PA reoperation (P < .05). Concomitant airway interventions (eg, tracheobronchopexy/plasty) were performed in 4 patients and none required subsequent airway interventions, whereas 2 patients not having initial airway intervention required subsequent tracheopexy (P < .05). Three patients in the cohort eventually required tracheostomy (15%), and 2 patients died (10%; on postoperative days 30 and 326); none had received initial airway intervention., Conclusions: Pulmonary artery replacement and aggressive direct airway management at initial definitive repair of cardiac TOF-APV can be performed safely with acceptable survival outcomes and low rates of airway and PA reintervention., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Donation after circulatory death (DCD) offers an additional source of cardiac allografts, potentially allowing expansion of the donor pool, but is limited owing to the effects of ischemia. In this study, we investigated the efficacy of mitochondrial transplantation to enhance myocardial function of DCD hearts., Methods: Circulatory death was induced in Yorkshire pigs (40-50 kg, n = 29) by a cessation of mechanical ventilation. After 20 minutes of warm ischemia, cardioplegia was administered. The hearts were then reperfused on an ex-situ blood perfusion system. After 15 minutes of reperfusion, hearts received either vehicle alone (vehicle [VEH], 10 ml; n = 8) or vehicle containing autologous mitochondria (vehicle with mitochondria as a single injection [MT], 5 × 10 9 in 10 ml, n = 8). Another group of hearts (serial injection of mitochondria [MT S ]; n = 6) received a second injection of mitochondria (5 × 10 9 in 10 ml) after 2 hours of ex-situ heart perfusion and reperfused for an additional 2 hours. A Sham group (sham hearts; n = 6) did not undergo any warm ischemia., Results: At the end of 4 hours of reperfusion, MT and MT S groups showed a significantly increased left ventricle/ventricular peak developed pressure (p = 0.002), maximal left ventricle/ventricular pressure rise (p < 0.001), fractional shortening (p < 0.001), and myocardial oxygen consumption (p = 0.004) compared with VEH. Infarct size was significantly decreased in MT and MT S groups compared with VEH (p < 0.001). No differences were found in arterial lactate levels among or within groups throughout reperfusion., Conclusions: Mitochondrial transplantation significantly preserves myocardial function and oxygen consumption in DCD hearts, thus providing a possible option for expanding the heart donor pool., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Autologous pericardium, fixed in glutaraldehyde, is a common patch material used in heart valve reconstruction. Competence of a reconstructed valve depends on patch dimensions and also on how much the patch deforms when the closed valve is pressurized. In this study, we used biaxial testing to evaluate the deformability of fixed autologous pericardium, and several commercial alternatives, under typical cardiac loads. We found that deformability of fixed autologous pericardium varies predictably with fixation time. This information can be used by surgeons in designing patches for valve repair., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Left main coronary artery (LMCA) stenosis is present in approximately 5% of patients with congenital supravalvular aortic stenosis (SVAS) (Fig. 1) 1 and is associated with an increased risk of sudden cardiac death. 2 However, patients undergoing coronary artery intervention at the time of SVAS repair are at the highest risk of experiencing major adverse cardiac events. 3 Literature reports of surgical techniques and outcomes of concomitant coronary artery repair in these high-risk patients are diverse and inconsistently described. We have recently adopted a standardized surgical technique for management of this complex pathology by combining extended LMCA patch augmentation with a 3-patch aortic root reconstruction (Brom's technique). In this report, we describe our contemporary surgical technique of 3-patch aortic root reconstruction with extended LMCA patch augmentation for patients with congenital SVAS with ostial LMCA stenosis and bilateral outflow tract obstruction. Institutional review board approval was obtained for retrospective review of patient charts., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Extracellular matrix materials mechanically dissociated into submillimeter particles have a larger surface area than sheet materials and enhanced cellular attachment. Decellularized porcine mesothelial extracellular matrix microparticles were seeded with bone marrow-derived mesenchymal stromal cells and cultured in a rotating bioreactor. The mesenchymal stromal cells attached and grew to confluency on the microparticles. The cell-seeded microparticles were then encapsulated in varying concentrations of fibrin glue, and the cells migrated rapidly off the microparticles. The combination of microparticles and mesenchymal stromal cells was then applied to a splinted full-thickness cutaneous in vivo wound model. There was evidence of increased cell infiltration and collagen deposition in mesenchymal stromal cells-treated wounds. Cell-seeded microparticles have potential as a cell delivery and paracrine therapy in impaired healing environments.

Interrupted right aortic arch is a rare congenital cardiovascular anomaly typically associated with other forms of congenital heart disease. We report two cases of interrupted right aortic arch associated with isolated left pulmonary artery and bilateral ductus arteriosus in the first case and with truncus arteriosus in the second case. Computed tomography was complementary to echocardiography in delineating the anatomic details in both cases, informing surgical repair with reconstruction of a left aortic arch in the first case and right arch in the second case., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Following stage 1 palliation, delayed sternal closure may be used as a technique to enhance thoracic compliance but may also prolong the length of stay and increase the risk of infection., Methods: We reviewed all neonates undergoing stage 1 palliation at our institution between 2010 and 2017 to describe the effects of delayed sternal closure., Results: During the study period, 193 patients underwent stage 1 palliation, of whom 12 died before an attempt at sternal closure. Among the 25 patients who underwent primary sternal closure, 4 (16%) had sternal reopening within 24 hours. Among the 156 infants who underwent delayed sternal closure at 4 [3,6] days post-operatively, 11 (7.1%) had one or more failed attempts at sternal closure. Patients undergoing primary sternal closure had a shorter duration of mechanical ventilation and intensive care unit length of stay. Patients who failed delayed sternal closure had a longer aortic cross-clamp time (123±42 versus 99±35 minutes, p=0.029) and circulatory arrest time (39±28 versus 19±17 minutes, p=0.0009) than those who did not fail. Failure of delayed sternal closure was also closely associated with Technical Performance Score: 1.3% of patients with a score of 1 failed sternal closure compared with 18.9% of patients with a score of 3 (p=0.0028). Among the haemodynamic and ventilatory parameters studied, only superior caval vein saturation following sternal closure was different between patients who did and did not fail sternal closure (30±7 versus 42±10%, p=0.002). All patients who failed sternal closure did so within 24 hours owing to hypoxaemia, hypercarbia, or haemodynamic impairment., Conclusion: When performed according to our current clinical practice, sternal closure causes transient and mild changes in haemodynamic and ventilatory parameters. Monitoring of SvO2 following sternal closure may permit early identification of patients at risk for failure.

Background: The use of a valved right ventricular to pulmonary artery shunt (RVPAS) has been reported by some to improve pulmonary artery growth after stage 1 palliation (S1P)., Methods: We retrospectively reviewed all patients undergoing an S1P with an RVPAS between January 2013 and May 2017, stratified by RVPAS type: a ring-reinforced polytetrafluoroethylene (PTFE) graft or a composite graft that included a distal valved femoral or saphenous vein homograft. We examined the association of RVPAS type on postoperative hemodynamics, time to reintervention, pulmonary artery growth, and survival., Results: Among 94 infants, 56 (60%) underwent PTFE-only shunt, 24 (25%) underwent femoral vein homograft, and 14 (15%) underwent saphenous vein homograft, and no relevant risk factor differences were found between the groups. Arterial saturation was 2.3% higher (p = 0.014) and serum lactic acid was 1.24 mg/dL lower (p = 0.03) in the femoral vein homograft group than in the PTFE-only group, although venous saturation was similar. By 60 days, 50% of patients with saphenous vein homograft had a reintervention compared with 5% with PTFE graft (p < 0.0001) and 12% with femoral vein homograft (p = 0.2 versus PTFE). At the time of stage 2 palliation, no differences were found in pulmonary artery size or growth over time by either echocardiogram or angiography or in the density of aortopulmonary collaterals or degree of tricuspid regurgitation. The 12-month survival was similar between the groups., Conclusions: The use of an interposition femoral vein homograft into the RVPAS may enhance perioperative stability, but it does not substantially improve interstage growth of the pulmonary arteries. Use of saphenous vein homograft is associated with earlier time to reintervention after S1P., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Synthetic graft materials are commonly used for shunts and cardiovascular reconstruction in neonates, but are prone to thrombosis and scarring. The umbilical vein is a potential source of autologous, endothelialized tissue for neonatal shunts and tissue reconstruction, but requires preservation before implantation., Methods: Umbilical cords were collected in UW solution with antibiotics at 4°C until dissection. Umbilical vein segments were tested for burst pressure before and after 2 weeks of preservation. Umbilical veins segments were preserved under static or flow conditions at 4°C in UW solution with 5% human plasma lysate for 7 days. Veins were evaluated with histopathology, scanning electron microscopy, and platelet adhesion testing., Results: Umbilical veins have no difference in burst pressure at harvest (n = 16) compared with 2 weeks of preservation (n = 11; 431 ± 229 versus 438 ± 244 mm Hg). After 1 week, static and flow-preserved veins showed viability of the vessel segments with endothelium staining positive for CD31, von Willebrand factor, and endothelial nitric oxide synthase. Scanning electron microscopy demonstrated preservation of normal endothelial morphology and flow alignment in the flow-preserved samples compared with cobblestone endothelial appearance and some endothelial cell loss in the static samples. Static samples had significantly more platelet adhesion than flow-preserved samples did., Conclusions: Umbilical veins have adequate burst strength to function at neonatal systemic pressures. Preservation under flow conditions demonstrated normal endothelial and overall vascular morphology with less platelet adhesion compared with static samples. Preserved autologous umbilical veins are potential source for endothelialized shunts or cardiovascular repair tissue for neonates., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In pre-clinical safety studies, drug-induced vascular injury (DIVI) is defined as an adverse response to a drug characterized by degenerative and hyperplastic changes of endothelial cells and vascular smooth muscle cells. Inflammation may also be seen, along with extravasation of red blood cells into the smooth muscle layer (i.e., hemorrhage). Drugs that cause DIVI are often discontinued from development after considerable cost has occurred. An in vitro vascular model has been developed using endothelial and smooth muscle cells in co-culture across a porous membrane mimicking the internal elastic lamina. Arterial flow rates of perfusion media within the endothelial chamber of the model induce physiologic endothelial cell alignment. Pilot testing with a drug known to cause DIVI induced extravasation of red blood cells into the smooth muscle layer in all devices with no extravasation seen in control devices. This engineered vascular model offers the potential to evaluate candidate drugs for DIVI early in the discovery process. The physiologic flow within the co-culture model also makes it candidate for a wide variety of vascular biology investigations.

Extracellular matrix (ECM) materials from animal and human sources have become important materials for soft tissue repair. Microparticles of ECM materials have increased surface area and exposed binding sites compared to sheet materials. Decellularized porcine peritoneum was mechanically dissociated into 200 µm microparticles, seeded with fibroblasts and cultured in a low gravity rotating bioreactor. The cells avidly attached and maintained excellent viability on the microparticles. When the seeded microparticles were placed in a collagen gel, the cells quickly migrated off the microparticles and through the gel. Cells from seeded microparticles migrated to and across an in vitro anastomosis model, increasing the tensile strength of the model. Cell seeded microparticles of ECM material have potential for paracrine and cellular delivery therapies when delivered in a gel carrier. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1728-1735, 2016., (© 2016 Wiley Periodicals, Inc.)

Background Aims: The use of bone marrow-derived mesenchymal stromal cells (MSCs) in cell-based therapies is currently being developed for a number of diseases. Thus far, the clinical results have been inconclusive and variable, in part because of the variety of cell isolation procedures and culture conditions used in each study. A new isolation technique that streamlines the method of concentration and demands less time and attention could provide clinical and economic advantages compared with current methodologies. In this study, we evaluated the concentrating capability of an integrated centrifuge-based technology compared with standard Ficoll isolation., Methods: MSCs were concentrated from bone marrow aspirate using the new device and the Ficoll method. The isolation capabilities of the device and the growth characteristics, secretome production, and differentiation capacity of the derived cells were determined., Results: The new MSC isolation device concentrated the bone marrow in 90 seconds and resulted in a mononuclear cell yield 10-fold higher and with a twofold increase in cell retention compared with Ficoll. The cells isolated using the device were shown to exhibit similar morphology and functional activity as assessed by growth curves and secretome production compared to the Ficoll-isolated cells. The surface marker and trilineage differentiation profile of the device-isolated cells was consistent with the known profile of MSCs., Discussion: The faster time to isolation and greater cell yield of the integrated centrifuge-based technology may make this an improved approach for MSC isolation from bone marrow aspirates., (Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The management of decompensating critically ill children with severe PH is extremely challenging and requires a multidisciplinary approach. Unfortunately, even with optimal care, these children might continue to deteriorate and develop inadequate systemic perfusion and at times cardiac arrest secondary to a pulmonary hypertensive crisis. Tools to support these children are limited, and at times, the team should proceed with offering extracorporeal support, especially in newly diagnosed patients who have not benefitted from medical therapy prior to their acute deterioration, in patients with severe pulmonary venous disease and in patients with alveolar capillary dysplasia. Currently, the only approved mode for extracorporeal support in pediatric patients with PH eligible for lung transplantation is ECMO. To decrease the risks associated with ECMO, and offer potential for increased duration of support, extubation, and rehabilitation, we transitioned four small children with refractory PH from ECMO to a device comprising an oxygenator interposed between the PA and LA. This work describes in great detail our experience with this mode of support with emphasis on exclusion criteria, the implantation procedure, and the post-implantation management., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.

In patients with failed Fontan circulation, end-stage heart failure can develop or Fontan physiology failure requiring transplantation. Experience with ventricular assist device support for these patients as a bridge to heart transplantation has been limited and often not resulted in successful hospital discharge. We report the successful use of the Berlin Heart EXCOR (Berlin Heart, The Woodlands, TX) ventricular assist device in bridging a child with Fontan circulation and systolic dysfunction to heart transplantation and discharge home., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Communication is essential to the safe conduct of any critical task including cardiac surgery. After inspiration by airline crew resource management training, a communication system for the care plans of pediatric cardiac patients was developed and refined over time that encompasses the entire heart center team. Five distinct communication points are used to ensure preoperative, intraoperative, and postoperative care, which is transitioned efficiently and maintained at the highest level., (© The Author(s) 2014.)

Purpose: Stenosis in a vascular access circuit is the predominant cause of access dysfunction. Hemodynamic significance of a stenosis identified by angiography in an access circuit is uncertain. This study utilizes computational fluid dynamics (CFD) to model flow through arteriovenous fistula to predict the functional significance of stenosis in vascular access circuits., Methods: Three-dimensional models of fistulas were created with a range of clinically relevant stenoses using SolidWorks. Stenoses diameters ranged from 1.0 to 3.0 mm and lengths from 5 to 60 mm within a fistula diameter of 7 mm. CFD analyses were performed using a blood model over a range of blood pressures. Eight patient-specific stenoses were also modeled and analyzed with CFD and the resulting blood flow calculations were validated by comparison with brachial artery flow measured by duplex ultrasound., Results: Predicted flow rates were derived from CFD analysis of a range of stenoses. These stenoses were modeled by CFD and correlated with the ultrasound measured flow rate through the fistula of eight patients. The calculated flow rate using CFD correlated within 20% of ultrasound measured flow for five of eight patients. The mean difference was 17.2% (ranged from 1.3% to 30.1%)., Conclusions: CFD analysis-generated flow rate tables provide valuable information to assess the functional significance of stenosis detected during imaging studies. The CFD study can help in determining the clinical relevance of a stenosis in access dysfunction and guide the need for intervention.

Mesenchymal bone marrow stromal cells may be a source of cells to preseed decellularized biologic mesh materials for improved cellularization and promote a more physiologic tissue after remodeling. Spontaneous differentiation of mesenchymal stromal cells on the decellularized material would be undesirable. Conversely, induced differentiation of mesenchymal stem cells (MSC) on the material would suggest that these materials may have promise as scaffold materials for bone, cartilage, or adipocyte formation. Two sources of mesenchymal cells were evaluated for induced differentiation in control wells. These MSCs were also evaluated for spontaneous or induced differentiation on decellularized porcine dermis and mesothelium materials. Primarily harvested bone marrow MSCs and commercially obtained MSCs were induced into osteoblasts and adipocytes on decellularized dermis and mesothelium materials. The MSCs were able to be induced into chondrocytes in pellet form but not when grown as a monolayer on the materials. The MSCs did not undergo spontaneous differentiation when grown on the materials for up to four weeks. MSC grown on decellularized porcine dermis or mesothelium do not spontaneously differentiate and may serve as a source of autologous cells for preseeding these extracellular matrix materials prior to implantation., (© 2013 Wiley Periodicals, Inc.)

Lung tissue engineering is an emerging field focused on the development of lung replacement devices and tissue to treat patients with end stage lung disease. Microfluidic based lung assist devices have been developed that have biomimetically designed vascular networks that achieve physiologic blood flow. Gas exchange in these devices occurs across a thin respiratory membrane. Designed for intrathoracic implantation as a bridge to transplant or destination therapy, these lung assist devices will allow ambulation and hospital discharge for patients with end stage lung disease. Decellularized lungs subsequently recellularized with epithelial and endothelial cells have been implanted in small animal models with demonstration of initial gas exchange. Further development of these tissues and scaling to large animal models will validate this approach and may be an organ source for lung transplantation. Initial clinical success has been achieved with decellularized tracheal implants using autologous stem cells. Development of microfluidic lung models using similar architecture to the lung assist device technology allows study of lung biology and diseases with manipulation of lung cells and respiratory membrane strain.

Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼ 1-3 cm(3)) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To evaluate paracorporeal lung assist devices to treat neonates and children with decompensated respiratory failure as a bridge to recovery or lung transplantation., Methods: One neonate (23 days old) and 3 young children (aged 2, 9, and 23 months) presented with primary lung disease with pulmonary hypertension, including alveolar capillary dysplasia in 2 and right pulmonary hypoplasia and primary pulmonary hypertension in 1. The patients were listed for lung transplantation but decompensated and required extracorporeal membrane oxygenation (ECMO). The patients were transitioned from ECMO to a pumpless paracorporeal lung assist device (Maquet Quadrox-iD oxygenator in 3, Novalung in 1) with inflow from the pulmonary artery and return to the left atrium., Results: The patients were weaned from ECMO and supported by the device for 44 ± 29 days (range, 5-74). Three patients were extubated while supported by the device (after 9, 15, and 72 days). One patient was bridged to lung transplant (9 months old, with alveolar capillary dysplasia, supported 5 days). One patient was bridged to recovery with maximal medical therapy (23 months old, with primary pulmonary hypertension, supported 23 days). Two patients died while awaiting a suitable lung donor after a support time of 54 and 72 days., Conclusions: Pediatric patients bridged from ECMO to lung transplantation have poor results. An alternative method for longer term respiratory support was necessary as a bridge for these patients. The use of a paracorporeal lung assist device successfully supported 4 patients to recovery, lung transplantation, or past the average wait time for pediatric donor lungs (27 days). This therapy has the potential to bridge children with decompensated respiratory failure to lung transplantation., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)