Computational modeling and simulation (CM&S) is a powerful tool that can be used to support the development, evaluation, and regulatory authorization of medical devices. CM&S can provide valuable insights into device performance, safety, and effectiveness, as well as reduce the need for animal or human testing. Computational models are, however, idealized digital representations that often have many assumptions and need to be credible before they are used in decision making that could incur patient harm. While the medical device community has made great strides to advance the use of CM&S, a number of challenges remain. To begin addressing these challenges, the US Food and Drug Administration (FDA) and the Medical Device Innovation Consortium (MDIC) co-sponsored theFDA/MDIC Symposium on Computational Modeling and Simulationon April 16-17, 2024 in College Park, Maryland, USA, where attendees from around the world convened to hear from leaders in the field through a unique blend of invited presentations and interactive panel discussions. The symposium agenda covered several major themes, including credibility considerations for CM&S used across the medical device total product life cycle, practical examples of performing model credibility assessment, and the use of CM&S for clinical decision making and the emerging areas ofin silicoclinical trials and digital twins. The objective of this article is to summarize the major takeaways of the symposium. We first provide an overview of the invited presentations followed by summaries of the topics covered during the interactive panel discussions. In doing so, we highlight the main takeaways and identify areas in which panelists had shared perspectives or differences of opinion. Next, we present the results of a survey conducted at the symposium that sought attendees' perspectives on different aspects of medical device CM&S. Finally, we conclude by summarizing the major outcomes of the symposium, including areas where more work and investment are needed to advance the field.

Objective:Patients with a left pulmonary artery (LPA) sling often require surgical reimplantation to address pulmonary flow maldistribution and tracheal compression. We developed a virtual modeling workflow to determine what length of LPA should be retained for reimplantation and provided these data for intraoperative guidance. Methods:From March 2024 to May 2025, 5 patients diagnosed with an LPA sling with (n = 3) or without (n = 2) tracheal stenosis underwent surgical LPA reimplantation with or without slide tracheoplasty at median age 1.8 years [range, 0.4-3.6 years]. All patients had preoperative surgical planning using measurements from a segmented 3-dimensional model using a digital workflow. Model measurements included distances from the main pulmonary artery reimplantation site to nearby landmarks and the length of pressurized, prestretched LPA that should be retained for reimplantation based on the distance between the reimplant site and anticipated extent of distal LPA mobilization. These measurements were used as intraoperative guidance. Results:The planned main pulmonary artery reimplant site varied across surgeons, and recommended LPA length ranged from 42% to 71% of the total native length. Model recommendations were closely followed in all patients with LPA sling. Median hospital length of stay was 7 days [6-15]. At discharge, 3 patients had no/trivial LPA stenosis and 2 had mild (peak gradient 23 mm Hg [20, 26]). At median follow-up of 17.6 months [6.5-22.1], all patients had no/trivial stenosis and were asymptomatic with 100% freedom from reintervention. Postoperative lung-perfusion and computed tomography scans demonstrated left/right split of 40/60% ± 2% (n = 3) and LPA diameter z score of -0.23 [-0.82, +0.31] (n = 2). Conclusions:Three-dimensional models provide a platform for quantitative surgical planning to help achieve targeted reconstruction with good initial clinical follow-up.

Objective: Pediatric aortic valve repair has traditionally been guided by qualitative assessment. In this study, we present our early experience using quantitative guidelines to inform repair. Methods: We present a simple model of normal aortic valve proportions and compare outcomes of valves repaired with and without model-based guidelines. In a secondary analysis of a subset of valves that preoperatively exhibited 2 or 3 distinct leaflets with normal commissures, we assess whether achieving target normal leaflet free edge lengths is associated with less regurgitation. Results: Valve repair aided by modeling exhibited similar rates of aortic regurgitation (AR) and aortic stenosis (AS) on discharge and follow-up echocardiograms to controls. The repair versus replacement rate increased significantly from 57% in controls to 71% during the period in which modeling was used (P = .009), and the proportion of nontricuspid valves and the severity of preoperative AR was higher in the modeling groups than in the controls (P = .049 and P = .001, respectively). In the secondary analysis, operatively changing relative free edge length toward normal target values was associated with significant decreases in AR (P < .001), with a clear boundary separating valves with moderate or severe AR from those with none or trivial. Conclusions: Use of quantitative repair guidelines achieved similar outcomes and higher repair rates despite higher preoperative valve complexity. Among valves with distinct leaflets and normal commissures, changes in AR from preoperation to postoperation closely tracked surgical changes to relative leaflet free edge length. Although initial results are promising, larger numbers and longer follow-up are needed.

Objective Supravalvular aortic stenosis (SVAS) repair carries a moderate risk for postoperative aortic regurgitation (AR). This may be related to the targeted sinotubular junction diameter z score (STJDZ) at reconstruction, traditionally sized to zero. We investigated relationships between achieved STJDZ and aortic valve function after repair. Methods Sixty-six children underwent patch repair from 2010 to 2024 at a median age of 1.2 years (interquartile range [IQR], 0.4, 3.5 years) via Brom (n = 53), Doty (n = 9), and McGoon (n = 4) techniques. Relationships between STJDZ and aortic valve function were assessed via Jonckheere-Terpstra nonparametric test for trend over median follow-up of 5.6 years (IQR, 2.4, 8.4 years). Results Preoperatively, AR was none/trivial in 52 (79%), left ventricular outflow tract obstruction (LVOTO) moderate or greater in 54 (82%), and median STJDZ −3.8 (IQR, −4.4, −2.9). At discharge, AR and LVOTO were mild or greater in 45 (68%) and 18 (27%), and median STJDZ was −0.3 (IQR, −1.3, −1.1). STJDZ increased by a median of 3.0 (IQR, 1.6, 4.4) preoperatively to postoperatively. Discharge AR was none/trivial at median STJDZ −1.3 (IQR, −1.8, −0.1) and worsened with increasing diameters (mild: 0.4 [IQR, −1.0, 1.8], mild+: 0.0 [IQR, −1.2, 1.5]; P = .038), with similar results at follow-up (P = .048). LVOTO worsened with lower median STJDZ (none/trivial: 0.2 [IQR, −1.2, 1.5], mild: −1.3 [IQR, −3.2, −0.1]; P = .015). Subanalysis of those with none/trivial preoperative AR (n = 52) showed that increase in STJDZ by ≥4 demonstrated worse follow-up AR (P = .016). Conclusions Achieving STJDZ zero using patch repair techniques to relieve SVAS obstruction demonstrated mild or greater postoperative AR compared with none/trivial regurgitation at median z score −1.3. Mild LVOTO was noted with median z score −1.3. Targeting STJDZ of −1 in pediatric SVAS repair appears appropriate to balance residual regurgitation and LVOTO. Further follow-up is required to understand the long-term impact of this target on aortic growth.

Objective:Patients with single ventricles undergoing bilateral bidirectional Glenn procedures present unique hemodynamic challenges due to distinct flow collisions compared with patients undergoing the unilateral Fontan. Flow-related changes in such patients may result in greater variation in power loss and hepatic flow differential (%) to branch pulmonary arteries that may result in pulmonary arteriovenous malformations and other Fontan-associated complications. This study aimed to analyze power loss and hepatic flow differential (%), along with its associated hemodynamics in patients undergoing the bilateral bidirectional Glenn under different physiological states and to evaluate the impact of a virtual neo-innominate vein connection on blood flow dynamics. Methods:Thirty patients who underwent the bilateral bidirectional Glenn were retrospectively analyzed, and patient-specific 3-dimensional models created using magnetic resonance imaging data were created. Computational fluid dynamic simulations were performed at rest and exercise states. In patients with significantly unbalanced hepatic flow differential (hepatic flow differential to the left pulmonary artery outside a 35% to 65% range), a virtual (neo-innominate) connection was introduced to assess its impact on overall hemodynamics. Results:Nineteen patients exhibited significantly unbalanced hepatic flow differential with median hepatic flow differential to the left pulmonary artery 24%, which improved to 32% after virtual neo-innominate connection, indicating considerable improvement in several patients, although the overall change was not statistically significant (P = .059). Notably, 37% of these showed substantial improvement after neo-innominate creation, highlighting patient specificity. This was accompanied by nonstatistically significant changes in power loss (P = .14), which remained higher than values typically reported for unilateral Fontan configurations. Conclusions:Our study showed that hemodynamics in patients undergoing the bilateral bidirectional Glenn are highly sensitive to anatomy and flow. A neo-innominate surgical modification can restore balanced hepatic flow differential (%) in select patients without a statistically significant increase in power loss but should be implemented selectively based on patient-specific anatomy and flow.

OBJECTIVES:To characterize longitudinal changes in lateral tunnel (LT) and extracardiac conduit (EC) Fontan pathway geometry and flow dynamics and to investigate whether these parameters mediate differences in outcomes by Fontan type. METHODS:Patients who underwent Fontan at our institution between 2000 and 2017 and were evaluated with post-Fontan computed tomography (CT)/magnetic resonance imaging (MRI) were reviewed retrospectively. Three-dimensional segmentations of the Fontan pathways were generated. Indexed power loss (iPL) was estimated using computational fluid dynamics in the context of patient-specific flow measurements and segmentations. Fontan failure was defined as a composite of mortality, heart transplantation, chylothorax, protein-losing enteropathy, plastic bronchitis, and hepatic dysfunction. RESULTS:Of 207 patients (LT, 166; EC, 41) who met the study criteria, 69 (LT, 54; EC, 15) had multiple post-Fontan CT/MRI examinations. Fontan pathway volume increased significantly within the LT cohort (1.6 mL/year; P < .001), but there was no significant change in the volume of EC Fontans (0.4 mL/year; P = .07). When adjusting for body surface area, LT Fontans continued to display increased volume (P = .006), while EC Fontans showed marked decreases (P = .026). The iPL of LT Fontans remained stable; however, there was a significant increase in iPL for patients in the EC cohort (P = .018). LT patients had lower rates of Fontan failure compared to EC patients (P = .002, log-rank test). Mediation analysis revealed that volume mediated ∼20% of the protective effects of the LT technique on the occurrence of Fontan failure at 10 years. CONCLUSIONS:LT Fontan pathways exhibited superior growth characteristics and sustained flow efficiency compared to EC Fontan pathways. The LT technique also was associated with improved outcomes, a finding that may be attributable to favorable geometry.

Patients with interrupted inferior vena cava (I-IVC) and azygos continuation who undergo Fontan completion via hepatoazygos shunting exhibit unique hemodynamic challenges. This study evaluates age-related shifts in systemic venous return dominance, hepatic flow distribution (HFD), power loss (PL), and flow disturbances using patient-specific computational fluid dynamics (CFD). Data analysis from 95 patients with I-IVC showed a nonlinear shift in upper-to-lower body systemic flow dominance with ratios of 2, 1, and 0.5 (correlating to ages ∼3, ∼10, and ∼20, respectively). CFD simulations for 17 selected patients revealed a trend of increasing HFD toward the right pulmonary artery, with median splits of 45%-49%, 48%-52%, and 40%-60% for the respective flow ratios. Power loss increased significantly with lower-body flow dominance. Median values for absolute PL were 4.75 mW (ratio 2), 16.5 mW (ratio 1), and 33.7 mW (ratio 0.5). Indexed PL showed a similar trend, rising from 0.04 mW/m2 to 0.11 mW/m2 across the flow ratios. Vorticity and viscous dissipation rates, key metrics of flow disturbances, also increased with lower-body flow dominance, showing strong correlations with PL (R = 0.58-0.76). Kruskal-Wallis-based statistical analysis identified significant statistical differences in absolute PL (P = 0.0045) and flow disturbances (P < 0.001), emphasizing the impact of age-related flow dynamics on Fontan efficiency. Our findings emphasize the need for targeted interventions in patients with I-IVC with azygos continuation to mitigate evolving hemodynamic inefficiencies and optimize Fontan outcomes during critical growth periods.NEW & NOTEWORTHY Evaluate how age-driven changes in patients with interrupted inferior vena cava impact Fontan efficiency. Using patient-specific computational fluid dynamics, our study reveals nonlinear flow dynamics, increasing power loss, and evolving hepatic flow distribution, emphasizing the need for tailored interventions to optimize outcomes.

OBJECTIVE:To determine whether prenatal palliative care (PC) utilization for patients with critical congenital heart disease (CCHD) at our institution is less than 10%, in spite of improvements in shared decision-making, communication, and family stress afforded by subspecialty PC consultation. STUDY DESIGN:A retrospective study of prenatal CCHD diagnoses at a tertiary center from January 2020 to December 2023. Initial hospitalization characteristics, presence and timing of PC, and survival or mechanism of death were collected. Early PC was defined as occurring prenatally or more than 30 days prior to death. Clinical characteristics were compared between patients with early, late, or no PC consultation. RESULTS:CCHD was diagnosed prenatally in 506 patients. Only 12% (n = 61) had a PC consultation, with 4 performed prenatally. Compared with those who received late or no PC, early PC consultation occurred more frequently for patients with genetic diagnoses (61% [n = 27] vs 35% [n = 6] vs 26% [n = 117], P < .001) or noncardiac congenital anomalies (61% [n = 27] vs 29% [n = 5] vs 35% [n = 154], P < .001). Of patients undergoing the highest complexity neonatal surgeries, 18% (n = 41) had subspecialty PC consultation. Overall, 12% (n = 60) of these patients died. CONCLUSIONS:Patients with CCHD experience significant morbidity and mortality. Given the underutilization of subspecialty PC upon prenatal diagnosis of CCHD, implementation of routine PC consultation for high-risk patients could enhance PC involvement in this cohort.

OBJECTIVE:The impact of early age on outcomes for repair of complete atrioventricular canal defects (CAVCs) remains poorly defined. We evaluated young infants with CAVC, comparing those who underwent primary repair versus primary pulmonary artery banding (PAB) and results related to left atrioventricular valve (AVV) reintervention and survival. METHODS:Patients (age <60 days) with CAVC were evaluated (January 2005 to April 2022) at a single institution. Patients were categorized as having primary CAVC repair or PAB. Patients with complex unbalanced CAVC and severely hypoplastic ventricles and those not undergoing CAVC repair after PAB were excluded. Outcome measures included total number of operations, reoperation on the left AVV, hospital length of stay, and mortality. RESULTS:CAVC was identified in 135 patients, mean age 33 ± 19 days and weight 3.4 ± 0.7 kg at primary operation. Additional diagnosis included transposition of the great arteries (n = 4), tetralogy of Fallot (n = 9), transposition of the great arteries (n = 13), and total and partial anomalous pulmonary venous return (n = 7). Thirty-three patients required preoperative respiratory support. Primary CAVC repair was performed in 101 patients at 38 ± 16.6 days and 3.5 ± 0.7 kg, and primary PAB was performed in 34 patients at 16 ± 15 days and 3.2 ± 0.7 kg, of whom 62% (n = 21) underwent subsequent CAVC repair at 6.9 ± 4.7 months and 6.6 ± 2.3 kg. When we compared patients undergoing primary CAVC versus PAB; 55% versus 48% had preoperative mild and 39% versus 29% mild-moderate or greater atrioventricular valve regurgitation (AVVR). In patients who underwent CAVC repair, a 2-patch repair was used in 66% of cases and posterior left AVV annuloplasty in 34%. Predischarge reoperation for left AVVR was required in 13% (n = 14/101) patients whereas in patients who underwent PAB, it was required in 14% (n = 3/21). Hospital length of stay was shorter for primary CAVC (25 vs 41 days). Overall, median follow-up was 4.5 years. Patients undergoing primary CAVC had fewer total number of operations (1.3 vs 2.5, P < .001) and fewer reoperations on the left AVV (18% vs 24%, P = .56). Overall, freedom from reoperation in primary CAVC for left AVVR at 1 and 5 years was 85% and 82% compared with patients who underwent PAB (89% and 69%). At follow-up, 88% of patients undergoing primary CAVC repair had mild or less left AVVR, whereas 82% undergoing initial PAB had mild or less left AVVR. There were 10 deaths; overall mortality was 6% in patients who underwent primary CAVC and 19% in patients who underwent PAB. Similarly, follow-up rates of significant AVVR and mortality did not differ significantly between groups (P > .05). CONCLUSIONS:Definitive CAVC repair at ≤60 days can be performed with acceptable midterm survival. Primary CAVC repair versus primary PAB for young patients undergoing CAVC has a trend toward fewer total operations, fewer reoperations for AVVR, decreased hospital LOS, and less mortality. However, reoperation rates for AVVR and mortality were not statistically different, and pacemaker implantation occurred in 10% of patients who underwent primary repair. These results underscore the need for cautious interpretation, given the limitations of statistical power. Reoperation for left AVVR remains a challenge and occurs early after repair. Evolving surgical techniques to avoid postoperative left AVV dysfunction should further reduce early postoperative morbidity and hospital resource use.

Background: Rates of reintervention (RI) after patch-augmented reconstruction for hypoplastic aortic arch (HAA) 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 between 2000 and 2021 at median age of 6 days (interquartile range [IQR], 4-13 days) and a median weight of 3.2 kg (IQR, 2.8-3.7 kg). Surgical technique was patch augmentation with coarctectomy with or without interdigitation in 269 patients (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 3.9 years (IQR, 1.1-8.0 years), 35 patients (10.4%) required reintervention (endovascular, n = 30; surgical, n = 12; both, n = 7). The 10-year cumulative incidence of death/transplant was 10% (95% confidence interval [CI], 4%-20%), and that of and reintervention was 13% (95% CI, 8%-20%). On univariate analysis, isolated patch aortoplasty (P = .002), aortic homograft patch material (P = .006), and postoperative aortic size z-score <=-2 for each segment were associated with greater risk of reintervention: ascending aorta (P = .006), proximal (P = .001) and distal (P = .005) transverse arches, and aortic isthmus (P < .001). On multivariable analysis, aortic homograft (hazard ratio [HR], 6.29; 95% CI, 1.94-20.5; P = .002) and postoperative isthmus z-score <=-2 (HR, 10.5; 95% CI, 5.15-21.5; P < .001) remained significant. Patients with a repaired isthmus z-score <=-2 had a 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 a z-score >-2. Conclusions: Aortic undersizing during patch-augmented reconstruction of HAA results in a >10% rate of reintervention at mid-term follow-up. Achieving adequate postoperative arch size is critical for preventing reintervention, with aortic isthmus size of utmost importance.

Branch pulmonary artery (BPA) reconstruction is associated with high reintervention rates. We present in vitro validation of a patch-planning workflow accounting for vessel prestretch, tissue properties, and suture uptake, to achieve targeted reconstructed dimensions. Two physiologically compliant, centrally stenosed BPA silicone models were created to represent neonatal and child-age repairs. Preoperative CTs were segmented to create 3D models for virtual planning. Patches were designed to restore stenotic regions to target diameters under two physiological pressure extremes, accounting for model and patch material distensibility. Finite-element simulation determined the loaded flat patch configuration. Analytical transformation produced unloaded designs for patches planned at high pressure. Designs were laser projected onto patch surfaces, patches sutured, and postoperative CTs acquired (n ≥ 3 per model/pressure/material). Virtual model credibility was evaluated following a recent credibility assessment framework. Patches designed for low vs. high pressure differed in size by up to 25

Background: Assessing left ventricular (LV) preparedness in congenitally-corrected transposition of the great arteries/intact ventricular septum (ccTGA/IVS) prior to the double switch operation (DSO) remains challenging. Subpulmonary LV Pressure-Volume Area (PVA) - a comprehensive metric of ventricular workload - when compared to systemic right ventricular (RV) PVA as a benchmark, may be a good index of adequacy. Aims: Determine (1) if LV PVA can be estimated from simple catheterization and imaging parameters, using conductance-catheter derived PVA as reference, and (2) if LV:RV ePVA ratio predicts outcomes after DSO. Methods: Subpulmonary LV PVA was measured using conductance catheters and compared to estimated PVA (ePVA) calculated with simple catheterization and volumetric variables. Then, in a retrospective cohort, LV:RV ePVA ratio and other clinical variables were evaluated as predictors for a composite adverse outcome of moderate LV dysfunction, transplant, or death post-DSO. Results: ePVA yielded high agreement and low bias compared to measured PVA by conductance catheter (n=20). In the retrospective cohort, 6/42 patients (14%) experienced the outcome. Low LV:RV ePVA and pressure ratios were the only significant predictors, while LV mass and mass-to-volume ratio were not. Amongst 8 patients with borderline pressure ratios, ePVA ratio was an excellent discriminator five with ePVA ratio <0.67 had adverse outcome, whereas three with ePVA ratio 0.67 did not. Conclusions: Estimation of subpulmonary LV PVA using simple imaging and catheterization data was reliable compared to gold standard techniques. LV:RV ePVA ratio 0.67 was a strong and novel predictor of LV preparedness for DSO in patients with ccTGA/IVS. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No external funding was received in the performance of the work and the preparation of the manuscript ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Boston Children's Hospital Institutional Review Board. The requirement for individual patient consent was waived. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data relevant to the manuscript are available upon reasonable request from the authors

Background:Aortic valve repair (AVr) exhibits acceptable outcomes in children with adequate native tissue. With deficient leaflets, patch augmentation is often required. Autologous pericardium (AP) calcification precipitates cusp immobility and high failure rates. Alternatively, the use of aortic wall (AW) as leaflet patch material was assessed. Methods:Between January 2023 and July 2024, 38 children underwent AVr using bicuspidization (n = 29; 76%) or another technique with AW (n = 19) or AP (n = 19) patches. Concurrent reduction ascending aortoplasty was performed more often in AW (n = 18 [95%] vs 10 [53%] for AP; P = .008). Primary endpoints were AoV reoperation and/or recurrent >mild aortic regurgitation (AR). Results:Hospital stay, complications, and predischarge reoperation (3 AW, 2 AP) were similar in the 2 groups. There were no deaths in either group. At discharge, the AW and AP groups had a similar rate of >mild AR (19% vs 6%; P = .34), but the AW group had a >30% lower incidence of >trivial AR (25% vs 59% for AP; P = .08). At a median follow-up of 10.2 months, there were no additional reoperations in the AW group but 3 (16%) in the AP group (P = .61). On follow-up echocardiography at a median of 5.4 months, the rate of >mild AR was 23% in the AW group versus 24% in the AP group (P = .59). At 8 months postoperatively, for the AW and AP groups, freedom from reoperation was 84.2% versus 79.0% (P = .61), recurrent >mild AR was 82.8% versus 78.6% (P = .45), and the composite of reoperation and recurrent AR was 68.4 versus 73.7% (P = .61). Conclusions:Pediatric AVr using AW as leaflet patch material has similar short-term outcomes as AP. Given the potential advantages of using a living autologous cardiovascular material, AW patches for AVr may demonstrate superior valve performance and durability with longer-term follow-up and expand options for valves previously thought to be unrepairable.

Background: Patients with hypoplastic left ventricles (LV) who undergo volume-loading procedures (recruitment, biventricular [BIV] repair) are at risk for adverse outcomes, including heart failure and death. We investigated pre-BIV LV shape as a predictor of outcome after BIV repair in patients with hypoplastic LVs. Methods: Baseline and post-recruitment cardiac magnetic resonance imaging and computed tomography data were analyzed in patients with hypoplastic LV (<50 mL/m(2)). Statistical shape modeling (SSM) was utilized to generate a model of the shape and variability of LVs. Traditional measures of LV sphericity and eccentricity were also measured. Major adverse cardiovascular events (MACE) included heart failure, transplant, and death. Results: Of 95 patients with baseline mean LV volume 29 +/- 13 mL/m(2), 45/95 (47%) had a right dominant atrioventricular canal defect, 31/95 (33%) had a variant of hypoplastic left heart syndrome, and 18/95 (19%) had endocardial fibroelastosis (EFE). A wide variation in LV shape was found by SSM, and shape modes were associated with right ventricle (RV) and LV size, and diagnosis. BIV repair was achieved in 74/95 (78%) patients; 13/74 (18%) of BIV patients had MACE. Predictors of MACE following BIV repair included EFE, higher RV mass index, and higher RV end-diastolic volume index. No baseline or post-recruitment LV shape parameter was associated with the outcome after BIV repair. Conclusion: The shape model of hypoplastic LVs demonstrated a wide array of LV shapes. LVs gained sphericity and size and lost eccentricity with recruitment. Though the ventricles changed shape with recruitment, no specific LV shape characteristic at the baseline or post-recruitment stage was predictive of decision to proceed with BIV repair or outcome. Higher RV mass and volume may represent new biomarkers that predict outcomes following BIV repair in patients with hypoplastic LV. Further investigation could determine the reproducibility of these findings.

Background: The preferred surgical approach for aortic coarctation with hypoplastic aortic arch remains controversial. Perception exists that performing a sternotomy imposes a significant recovery burden. We analyzed perioperative outcomes of coarctation repair to compare approaches. Methods: Excluding genetic disorders and single-ventricle anatomy, 320 patients ± hypoplastic arch underwent coarctation repair by thoracotomy (n = 281) or sternotomy (n = 39) from 2012 to 2023 at median (IQR) age 22 days (7-383) and weight 3.9 kg (3.2-9.0). Primary endpoints were postoperative intensive care unit (ICU) and hospital length of stay (LOS) and ventilation duration. Secondary outcomes included mortality and reintervention. Stratification by preoperative distal transverse arch (DTA) z-score was performed to assess the impact of arch hypoplasia on hospital course. Results: Sternotomy patients had longer median (IQR) ICU LOS (4.9 days [2.8-7.7] vs 2.0 days [1.3-3.3]), hospital LOS (11.3 days [6.1-16.3] vs 5.4 days [4.2-8.6]), and ventilation duration (2 days [1-4] vs 1 day [0-1]) than thoracotomy patients by 2.9, 5.9, and 1 day (P < .001 each). Thoracotomy patients had higher rates of antihypertensive medications at discharge (51% vs 33%, P = .042). At 2.2 years follow-up, there was one mortality. Although not statistically significant, of all reinterventions performed within each group, thoracotomy patients had a higher proportion within 90 days of repair (45% vs 0%, P = .49); eight-year freedom from reintervention was 93.0% for sternotomy and 88.5% for thoracotomy (P = .65). In a subgroup analysis of patients with DTA z-score ≤ -3, hospital LOS was similar between approaches (P = .063). Conclusions: Children undergoing coarctation repair via sternotomy had a longer hospital course than those undergoing thoracotomy, although differences diminished among those with DTA z-score ≤ -3. Either approach can be considered in patients with mild-to-moderate arch hypoplasia given minor numeric differences in perioperative outcomes; however, sternotomy may provide more complete relief of obstruction to mitigate risks associated with residual elevated arch resistance.

Background: Double switch operation (DSO) for congenitally corrected transposition of the great arteries with intact ventricular septum (ccTGA) has a high rate of post-DSO LV dysfunction. Hypothesis: LV pressure-volume area (PVA), a surrogate of myocardial O 2 consumption, is a superior marker of LV preparedness and is associated with adverse outcomes after DSO. Aims: 1. Derive a mathematical relationship to estimate LV PVA (ePVA) from catheterization (pressure) and imaging (volumetric) data, using directly measured PVA (mPVA) as reference 2. Assess if lower ratio of LV ePVA to RV ePVA (as an internal control) is associated with adverse outcome after DSO. Methods: Aim 1: Using conductance catheter derived invasive subpulmonary LV PV loops, mPVA was recorded as the sum of stroke work (SW) and potential energy (PE). A mathematical relationship was established with standard catheterization/imaging data to estimate ePVA. Aim 2: In a retrospective cohort, LV:RV ePVA ratio was calculated as above, and along with standard clinical metrics, assessed for relationship with a composite outcome of ≥ moderate LV dysfunction, transplant, or death post-DSO. Results: Aim 1: In 20 PV loop studies in 18 pre-DSO patients, there was a strong linear correlation between measured and estimated SW and PE (R 2 > 0.9 and p<0.0001 for both). ePVA yielded high agreement and low bias compared to mPVA (mean bias 0.5±11%). Aim 2: Composite outcome occurred in 6/42 DSO patients (14%). LV:RV ePVA ratio (0.57 [0.49, 0.61] vs 0.90 [0.73, 1.1], p<0.001) and LV:RV pressure ratio (0.80 [0.77, 0.87] vs 1.13 [1.01, 1.23], p<0.001) were lower in those with adverse outcome. There were no differences in other pre-operative parameters. On time to event analysis, lower LV:RV ePVA ratio was the strongest determinant (HR 39, 95% CI 15-100; C Index 0.94), while lower LV:RV pressure ratio was the only other predictor (HR 24, 95% CI 13-42; C Index 0.88). In 8 patients with borderline pressure ratios of 0.77-0.88, ePVA ratio was an excellent discriminator - 3 patients with ePVA ratio of ≥0.67 had good outcomes, whereas 5 patients with ePVA ratio <0.67 had adverse outcomes. Conclusion: LV:RV ePVA ratio >0.67 is a strong and novel predictor of LV preparedness for DSO in patients with ccTGA.

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.