Patient-specific tissue engineered vascular graft for aortic arch reconstruction.

Objectives: The complexity of aortic arch reconstruction due to diverse 3-dimensional geometrical abnormalities is a major challenge. This study introduces 3-dimensional printed tissue-engineered vascular grafts, which can fit patient-specific dimensions, optimize hemodynamics, exhibit antithrombotic and anti-infective properties, and accommodate growth. Methods: We procured cardiac magnetic resonance imaging with 4-dimensional flow for native porcine anatomy (n = 10), from which we designed tissue-engineered vascular grafts for the distal aortic arch, 4 weeks before surgery. An optimal shape of the curved vascular graft was designed using computer-aided design informed by computational fluid dynamics analysis. Grafts were manufactured and implanted into the distal aortic arch of porcine models, and postoperative cardiac magnetic resonance imaging data were collected. Pre- and postimplant hemodynamic data and histology were analyzed. Results: Postoperative magnetic resonance imaging of all pigs with 1:1 ratio of polycaprolactone and poly-L-lactide-co-ε-caprolactone demonstrated no specific dilatation or stenosis of the graft, revealing a positive growth trend in the graft area from the day after surgery to 3 months later, with maintaining a similar shape. The peak wall shear stress of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft portion did not change significantly between the day after surgery and 3 months later. Immunohistochemistry showed endothelization and smooth muscle layer formation without calcification of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft. Conclusions: Our patient-specific polycaprolactone/poly-L-lactide-co-ε-caprolactone tissue-engineered vascular grafts demonstrated optimal anatomical fit maintaining ideal hemodynamics and neotissue formation in a porcine model. This study provides a proof of concept of patient-specific tissue-engineered vascular grafts for aortic arch reconstruction.

Tetralogy of Fallot regurgitation energetics and kinetics: an intracardiac flow analysis of the right ventricle using computational fluid dynamics.

Repaired Tetralogy of Fallot (rTOF) patients suffer from pulmonary regurgitation and may require pulmonary valve replacement (PVR). Cardiac magnetic resonance imaging (cMRI) guides therapy, but conventional measurements do not quantify the intracardiac flow effects from pulmonary regurgitation or PVR. This study investigates intracardiac flow parameters of the right ventricle (RV) of rTOF by computational fluid dynamics (CFD). cMRI of rTOF patients and controls were retrospectively included. Feature-tracking captured RV endocardial contours from long-axis/short-axis cine. Ventricular motion was reconstructed via diffeomorphic mapping, serving as domain boundary for CFD simulations. Vorticity (1/s), viscous energy loss (ELoss, mJ/L) and turbulent kinetic energy (TKE, mJ/L) were quantified in RV outflow tract (RVOT) and RV inflow. These parameters were normalized against total RV kinetic energy (KE) and RV inflow vorticity to derive dimensionless metrics. Vorticity contours by Q-criterion were qualitatively compared. rTOF patients (n = 15) had mean regurgitant fraction 38 ± 12% and RV size 162 ± 35 mL/m2. Compared to controls (n = 12), rTOF had increased RVOT vorticity (142.6 ± 75.6/s vs. 40.4 ± 11.8/s, p < 0.0001), Eloss (55.6 ± 42.5 vs. 5.2 ± 4.4 mJ/L, p = 0.0004), and TKE (5.7 ± 5.9 vs. 0.84 ± 0.46 mJ/L, p = 0.0003). After PVR, there was decrease in normalized RVOT Eloss/TKE (p = 0.0009, p = 0.029) and increase in normalized tricuspid inflow vorticity/KE (p = 0.0136, p = 0.043), corresponding to reorganization of the "donut"-shaped tricuspid ring-vortex. The intracardiac flow in rTOF patients can be simulated to determine the impact of PVR and improve the clinical indications guided by cardiac imaging.

Discordance interpretation of left ventricular size between echocardiography and cardiac magnetic resonance in pediatric patients with aortic/mitral regurgitation.

PURPOSE: This study investigated discordance between echocardiography (echo) and cardiac magnetic resonance (CMR) measurements of the left ventricle (LV) in pediatric patients with aortic and/or mitral regurgitation (AR/MR). METHODS: Retrospective cohort study of pediatric patients. The cohorts were comprised of patients with AR/MR vs. non-AR/MR. Left ventricular end diastolic volume (LVEDV) by CMR and left ventricular internal diameter diastolic (LVIDd) by echo were obtained from clinical reports then echo images were reviewed to remeasure LVEDV by bullet method. Left ventricular internal diameter systolic (LVIDs) and left ventricular ejection fraction (LVEF) measurements by echo and LVEF by CMR were obtained from clinical reports. Fractional shortening (FS%) was recalculated. Z-scores were calculated using normative data. Correlation between echo and CMR LV measurements was assessed using correlation coefficients. Bland-Altman plots assessed bias between imaging modalities. Receiver operator characteristic (ROC) analysis was performed for detection of LV enlargement and LV dysfunction. RESULTS: AR/MR patients had greater discrepancy in LV size interpretation by Z-score compared to non-AR/MR patients. This discrepancy persisted when the bullet method short axis measurements were incorporated. There was negative bias in echo-based measurements compared to CMR. The diagnostic performance of echo in identifying moderate LV enlargement was worse for AR/MR pediatrics patients. CONCLUSION: The discordant interpretation of LV size by echo compared to CMR is worse in pediatric patients with AR/MR when compared to patients without AR/MR even when short axis measurements are incorporated. This finding suggests non-uniform geometrical changes in the LV as it enlarges due to AR/MR.

Enhanced echocardiographic assessment of intracardiac flow in congenital heart disease.

BACKGROUND: 4D flow magnetic resonance imaging (4D flow MRI) can assess and measure the complex flow patterns of the right ventricle (RV) in congenital heart diseases, but its limited availability makes the broad application of intracardiac flow assessment challenging. Color Doppler imaging velocity reconstruction from conventional echocardiography is an emerging alternative, but its validity against 4D flow MRI needs to be established. OBJECTIVE: To compare intracardiac flow parameters measured by color Doppler velocity reconstruction (DoVeR) against parameters measured from 4D flow MRI. METHODS: We analyzed 20 subjects, including 7 normal RVs and 13 abnormal RVs (10 with repaired Tetralogy of Fallot, and 3 with atrial-level shunts). Intracardiac flow parameters such as relative pressure difference, vortex strength, total kinetic energy, and viscous energy loss were quantified using DoVeR and 4D flow MRI. The agreement between the two methods was determined by comparing the spatial fields and quantifying the cross-correlation and normalized difference between time-series measurements. RESULTS: The hemodynamic parameters obtained from DoVeR and 4D flow MRI showed similar flow characteristics and spatial distributions. The time evolutions of the parameters were also in good agreement between the two methods. The median correlation coefficient between the time-series of any parameter was between 0.87 and 0.92, and the median L2-norm deviation was between 10% to 14%. CONCLUSIONS: Our study shows that DoVeR is a reliable alternative to 4D flow MRI for quantifying intracardiac hemodynamic parameters in the RV.

Aortic arch shape after arch repair predicts exercise capacity: a multicentre analysis.

Aims: Coarctation of the aorta is associated with long-term morbidity including decreased exercise capacity, despite successful repair. In the absence of discrete recoarctation, the haemodynamic mechanism remains unknown. This multicentre study evaluated the relationship between aorta shape, flow, and exercise capacity in patients after arch repair, specifically through the lens of aortic size mismatch and descending aortic (DAo) flow and their association with exercise. Methods and results: Cardiac magnetic resonance, cardiopulmonary exercise test, and echocardiogram data within 1 year were analysed from 58 patients (age 28 ± 10 years, 48% male) across four centres with history of isolated arch repair. Aortic arch measurements were correlated with % predicted VO2max with subgroup analyses of those with residual arch obstruction, bicuspid aortic valve, and hypertension. Ascending aorta (AAo) to DAo diameter ratio (DAAo/DDAo) was negatively correlated with % predicted VO2max. %DAo flow positively correlated with VO2max. Sub-analyses demonstrated that the negative correlation of DAAo/DDAo with VO2max was maintained only in patients without arch obstruction and with a bicuspid aortic valve. Smaller aortic arch measurements were associated with both hypertension and exercise-induced hypertension. Conclusion: Aorta size mismatch, due to AAo dilation or small DAo, and associated decreased %DAo flow, correlated significantly with decreased exercise capacity after aortic arch repair. These correlations were stronger in patients without arch obstruction and with a bicuspid aortic valve. Aorta size mismatch and %DAo flow capture multiple mechanisms of altered haemodynamics beyond blood pressure gradient or discrete obstruction and can inform the definition of a successful repair.

In vitro investigation of axial mechanical support devices implanted in the novel convergent cavopulmonary connection Fontan.

OBJECTIVES: The 2 opposing inflows and 2 outflows in a total cavopulmonary connection make mechanical circulatory support (MCS) extremely challenging. We have previously reported a novel convergent cavopulmonary connection (CCPC) Fontan design that improves baseline characteristics and provides a single inflow and outflow, thus simplifying MCS. This study aims to assess the feasibility of MCS of this novel configuration using axial flow pumps in an in vitro benchtop model. METHODS: Three-dimensional segmentations of 12 single-ventricle patients (body surface area 0.5-1.75 m2) were generated from cardiovascular magnetic resonance images. The CCPC models were designed by connecting the inferior vena cava and superior vena cava to a shared conduit ascending to the pulmonary arteries, optimized in silico. The 12 total cavopulmonary connection and their corresponding CCPC models underwent in vitro benchtop characterization. Two MCS devices were used, the Impella RP® and the PediPump. RESULTS: MCS successfully and symmetrically reduced the pressure in both vena cavae by >20 mmHg. The devices improved the hepatic flow distribution balance of all CCPC models (Impella RP®P = 0.045, PediPump P = 0.055). CONCLUSIONS: The CCPC Fontan design provides a feasible MCS solution for a failing Fontan by balancing hepatic flow distribution and symmetrically decompressing the central venous pressure. Cardiac index may also improve with MCS. Additional studies are needed to evaluate this concept for managing Fontan failure.

Congenital Heart Disease Illustrated: Use of Cross-sectional Imaging in Pediatric Cardiology.

In the modern era of cardiac imaging, there is increasing use of cardiac computed tomography and cardiac magnetic resonance for visualization of congenital heart disease (CHD). Advanced visualization techniques such as virtual dissection, 3-dimensional modeling, and 4-dimensional flow are also commonly used in clinical practice. This review highlights such methods in five common forms of CHD, including double outlet right ventricle, common arterial trunk, sinus venosus defects, Tetralogy of Fallot variants, and heterotaxy, providing visualizations of pathology in both conventional and novel formats.

Virtual Planning and Patient-Specific Graft Design for Aortic Repairs.

PURPOSE: Patients presenting with coarctation of the aorta (CoA) may also suffer from co-existing transverse arch hypoplasia (TAH). Depending on the risks associated with the surgery and the severity of TAH, clinicians may decide to repair only CoA, and monitor the TAH to see if it improves as the patient grows. While acutely successful, eventually hemodynamics may become suboptimal if TAH is left untreated. The objective of this work aims to develop a patient-specific surgical planning framework for predicting and assessing postoperative outcomes of simple CoA repair and comprehensive repair of CoA and TAH. METHODS: The surgical planning framework consisted of virtual clamp placement, stenosis resection, and design and optimization of patient-specific aortic grafts that involved geometrical modeling of the graft and computational fluid dynamics (CFD) simulation for evaluating various surgical plans. Time-dependent CFD simulations were performed using Windkessel boundary conditions at the outlets that were obtained from patient-specific non-invasive pressure and flow data to predict hemodynamics before and after the virtual repairs. We applied the proposed framework to investigate optimal repairs for six patients (n = 6) diagnosed with both CoA and TAH. Design optimization was performed by creating a combination of a tubular graft and a waterslide patch to reconstruct the aortic arch. The surfaces of the designed graft were parameterized to optimize the shape. RESULTS: Peak systolic pressure drop (PSPD) and time-averaged wall shear stress (TAWSS) were used as performance metrics to evaluate surgical outcomes of various graft designs and implantation. The average PSPD improvements were 28% and 44% after the isolated CoA repair and comprehensive repair, respectively. Maximum values of TAWSS were decreased by 60% after CoA repair and further improved by 22% after the comprehensive repair. The oscillatory shear index was calculated and the values were confirmed to be in the normal range after the repairs. CONCLUSION: The results showed that the comprehensive repair outperforms the simple CoA repair and may be more advantageous in the long term in some patients. We demonstrated that the surgical planning and patient-specific flow simulations could potentially affect the selection and outcomes of aorta repairs.

The current state and potential innovation of fetal cardiac MRI.

Fetal cardiac MRI is a rapidly evolving form of diagnostic testing with utility as a complementary imaging modality for the diagnosis of congenital heart disease and assessment of the fetal cardiovascular system. Previous technical limitations without cardiac gating for the fetal heart rate has been overcome with recent technology. There is potential utility of fetal electrocardiography for direct cardiac gating. In addition to anatomic assessment, innovative technology has allowed for assessment of blood flow, 3D datasets, and 4D flow, providing important insight into fetal cardiovascular physiology. Despite remaining technical barriers, with increased use of fCMR worldwide, it will become an important clinical tool to improve the prenatal care of fetuses with CHD.

Cardiac evaluation of hospitalized children with 2019 coronavirus (COVID-19) infection at a single large quaternary center.

Background: Cardiac complications of serious SARS-CoV-2 infections, especially Multisystem Inflammatory Syndrome of Children (MIS-C) are well described, however current studies have not considered pediatric patients hospitalized with no cardiac concerns. We established a protocol for cardiac evaluation of all admitted COVID-19 patients three weeks post-discharge, irrespective of cardiac concerns. We assessed cardiovascular outcomes and hypothesized that patients with absent cardiac concerns are at lower risk for cardiac abnormalities. Methods: This was a retrospective study of 160 patients admitted for COVID-19 (excluding MIS-C) between March 2020 and September 2021 with subsequent echocardiogram(s) performed at our center. Patients were divided into 4 subgroups: Group 1 included patients with absent cardiac concerns, admitted to acute care (1a) and intensive care unit (ICU) (1 b). Group 2 included patients with cardiac concerns, admitted to acute care (2a) and ICU (2 b). Groups were compared based on clinical endpoints and echocardiographic measurements, including tissue Doppler imaging (TDI) assessment of diastolic function (z-score of septal Mitral E/TDI E' and lateral E/TDI E'). Chi-squared, Fisher's exact, and Kruskal-Wallis tests were used. Results: Traditional cardiac abnormalities varied significantly between the groups; with Group 2 b having the most (n = 8, 21%), but still found in Group 1a (n = 2, 3%) and Group 1 b (n = 1, 5%). No patients in Group 1 demonstrated abnormal systolic function, compared to Group 2a (n = 1, 3%) and Group 2 b (n = 3, 9%, p = 0.07). When including TDI assessment of diastolic function, the total incidence of abnormalities found on echocardiogram was increased in all groups. Conclusion: Cardiac abnormalities were found in pediatric patients admitted with COVID-19, even those without apparent cardiovascular concerns. The risk was greatest in ICU-admitted patients with cardiac concerns. The clinical significance of diastolic function assessment in these patients remains unknown. Further studies are needed to assess long-term cardiovascular sequelae of children with COVID-19, irrespective of cardiac concerns.

The convergent cavopulmonary connection: A novel and efficient configuration of Fontan to accommodate mechanical support.

Objective: The current total cavopulmonary connection Fontan has competing inflows and outflows, creating hemodynamic inefficiencies that contribute to Fontan failure and complicate placement and efficiency of mechanical circulatory support. We propose a novel convergent cavopulmonary connection (CCPC) Fontan design to create a single, converged venous outflow to the pulmonary arteries, thus increasing efficiency and mechanical circulatory support access. We then evaluate the feasibility and hemodynamic performance of the CCPC in various patient sizes using computational fluid dynamic assessments of computer-aided designs. Methods: Cardiac magnetic resonance imaging data from 12 patients with single ventricle (10 total cavopulmonary connection, 2 Glenn) physiology (body surface area, 0.5-2.0 m2) were segmented to create 3-dimensional replicas of all thoracic structures. Surgically feasible CCPC shapes within constraints of anatomy were created using iterative computational fluid dynamic and clinician input. Designs varied based on superior and inferior vena cava conduit sizes, coronal attachment height, coronal entry angle, and axial entry angle of the superior vena cava to the inferior vena cava. CCPC designs were optimized based on efficiency (indexed power loss), risk of arteriovenous malformations (hepatic flow distribution), and risk of flow stasis (% nonphysiologic wall shear stress). Results: All CCPC designs met hemodynamic performance thresholds for indexed power loss and hepatic flow distribution. CCPC designs showed improvements in reducing % nonphysiologic wall shear stress and balancing HFD. Conclusions: CCPC is physiologically and surgically feasible in various patient sizes using validated computational fluid dynamic models. CCPC configuration has analogous indexed power loss, hepatic flow distribution, and % nonphysiologic wall shear stress compared with total cavopulmonary connection, and the single inflow and outflow may ease mechanical circulatory support therapies. Further studies are required for design optimization and mechanical circulatory support institution.

Intracardiac Flow Analysis of the Right Ventricle in Pediatric Patients With Repaired Tetralogy of Fallot Using a Novel Color Doppler Velocity Reconstruction.

BACKGROUND: Repaired tetralogy of Fallot (RTOF) patients will develop right ventricular (RV) dysfunction from chronic pulmonary regurgitation (PR). Cardiac magnetic resonance sequences such as four-dimensional flow can demonstrate altered vorticity and flow energy loss (FEL); however, they are not as available as conventional echocardiography (echo). The study determined whether a novel, vendor-independent Doppler velocity reconstruction (DoVeR) could measure RV intracardiac flow in conventional echo of RTOF patients. The primary hypothesis was that DoVeR could detect increased vorticity and diastolic FEL in RTOF patients. METHODS: Repaired tetralogy of Fallot patients with echo were retrospectively paired with age-/size-matched controls. Doppler velocity reconstruction employed the stream function-vorticity equation to approximate intracardiac flow fields from color Doppler. A velocity field of the right ventricle was reconstructed from the apical 4-chamber view. Vortex strength (VS, area integral of vorticity) and FEL were derived from DoVeR. Cardiac magnetic resonance and exercise stress parameters (performed within 1 year of echo) were collected for analysis. RESULTS: Twenty RTOF patients and age-matched controls were included in the study. Mean regurgitant fraction was 40.5% ± 7.6%, and indexed RV end-diastolic volume was 158 ± 36 mL/m2. Repaired tetralogy of Fallot patients had higher total, mean diastolic, and peak diastolic VS (P = .0013, P = .0012, P = .0032, respectively) and higher total, mean diastolic, and peak diastolic body surface area-indexed FEL (P = .0016, P = .0022, P < .001, respectively). Peak diastolic indexed FEL and peak diastolic VS had weak-to-moderate negative correlation with RV ejection fraction (r = -0.52 [P = .019] and r = -0.49 [P = .030], respectively) and left ventricular ejection fraction (r = -0.47 [P = .034] and r = -0.64 [P = .002], respectively). Mean diastolic indexed FEL and VS had moderate-to-strong negative correlation with percent predicted maximal oxygen consumption (r = -0.69 [P = .012] and r = -0.75 [P = .006], respectively). CONCLUSIONS: DoVeR can detect alterations to intracardiac flow in RTOF patients from conventional color Doppler imaging. Echo-based measures of diastolic VS and FEL correlated with ventricular function. DoVeR has the potential to provide serial evaluation of abnormal flow dynamics in RTOF patients.

Impact of ferumoxytol vs gadolinium on 4D flow cardiovascular magnetic resonance measurements in small children with congenital heart disease.

BACKGROUND: Cardiovascular magnetic resonance (CMR) allows for time-resolved three-dimensional phase-contrast (4D Flow) analysis of congenital heart disease (CHD). Higher spatial resolution in small infants requires thinner slices, which can degrade the signal. Particularly in infants, the choice of contrast agent (ferumoxytol vs. gadolinium) may influence 4D Flow CMR accuracy. Thus, we investigated the accuracy of 4D Flow CMR measurements compared to gold standard 2D flow phase contrast (PC) measurements in ferumoxytol vs. gadolinium-enhanced CMR of small CHD patients with shunt lesions. METHODS: This was a retrospective study consisting of CMR studies from complex CHD patients less than 20 kg who had ferumoxytol or gadolinium-enhanced 4D Flow and standard two-dimensional phase contrast (2D-PC) flow collected. 4D Flow clinical software (Arterys) was used to measure flow in great vessels, systemic veins, and pulmonary veins. 4D Flow accuracy was defined as percent difference or correlation against conventional measurements (2D-PC) from the same vessels. Subgroup analysis was performed on two-ventricular vs single-ventricular CHD, arterial vs venous flow, as well as low flows (defined as < 1.5 L/min) in 1V CHD. RESULTS: Twenty-one ferumoxytol-enhanced and 23 gadolinium-enhanced CMR studies were included, with no difference in age (2.1 ± 1.6 vs. 2.3 ± 1.9 years, p = 0.70), patient body surface area (0.50 ± 0.2 vs. 0.52 ± 0.2 m2, p = 0.67), or vessel diameter (11.4 ± 5.2 vs. 12.4 ± 5.6 mm, p = 0.22). Ten CMR studies with single ventricular CHD were included. Overall, ferumoxytol-enhanced 4D flow CMR measurements demonstrated less percent difference to 2D-PC when compared to gadolinium-enhanced 4D Flow CMR studies. In subgroup analyses of arterial vs. venous flows (high velocity vs. low velocity) and low flow in single ventricle CHD, ferumoxytol-enhanced 4D Flow CMR measurements had stronger correlation to 2D-PC CMR. The contrast-to-noise ratio (CNR) in ferumoxytol-enhanced studies was higher than the CNR in gadolinium-enhanced studies. CONCLUSIONS: Ferumoxytol-enhanced 4D Flow CMR has improved accuracy when compared to gadolinium 4D Flow CMR, particularly for infants with small vessels in CHD.

Abnormal Diastolic Hemodynamic Forces: A Link Between Right Ventricular Wall Motion, Intracardiac Flow, and Pulmonary Regurgitation in Repaired Tetralogy of Fallot.

Background and Objective: The effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dysfunction in repaired Tetralogy of Fallot (RTOF) patients is well recognized by cardiac magnetic resonance (CMR). However, the link between RV wall motion, intracardiac flow and PR has not been established. Hemodynamic force (HDF) represents the global force exchanged between intracardiac blood volume and endocardium, measurable by 4D flow or by a novel mathematical model of wall motion. In our study, we used this novel methodology to derive HDF in a cohort of RTOF patients, exclusively using routine CMR imaging. Methods: RTOF patients and controls with CMR imaging were retrospectively included. Three-dimensional (3D) models of RV were segmented, including RV outflow tract (RVOT). Feature-tracking software (QStrain 2.0, Medis Medical Imaging Systems, Leiden, Netherlands) captured endocardial contours from long/short-axis cine and used to reconstruct RV wall motion. A global HDF vector was computed from the moving surface, then decomposed into amplitude/impulse of three directional components based on reference (Apical-to-Basal, Septal-to-Free Wall and Diaphragm-to-RVOT direction). HDF were compared and correlated against CMR and exercise stress test parameters. A subset of RTOF patients had 4D flow that was used to derive vorticity (for correlation) and HDF (for comparison against cine method). Results: 68 RTOF patients and 20 controls were included. RTOF patients had increased diastolic HDF amplitude in all three directions (p<0.05). PR% correlated with Diaphragm-RVOT HDF amplitude/impulse (r = 0.578, p<0.0001, r = 0.508, p < 0.0001, respectively). RV ejection fraction modestly correlated with global HDF amplitude (r = 0.2916, p = 0.031). VO2-max correlated with Septal-to-Free Wall HDF impulse (r = 0.536, p = 0.007). Diaphragm-to-RVOT HDF correlated with RVOT vorticity (r = 0.4997, p = 0.001). There was no significant measurement bias between Cine-derived HDF and 4D flow-derived HDF by Bland-Altman analysis. Conclusion: RTOF patients have abnormal diastolic HDF that is correlated to PR, RV function, exercise capacity and vorticity. HDF can be derived from conventional cine, and is a potential link between RV wall motion and intracardiac flow from PR in RTOF patients.

Statistical shape modeling reveals the link between right ventricular shape, hemodynamic force, and myocardial function in patients with repaired tetralogy of Fallot.

Patients with repaired tetralogy of Fallot (rTOF) can develop chronic pulmonary insufficiency (PI) with right ventricular (RV) dilation, progressive RV dysfunction, and decreased exercise capacity. Pulmonary valve replacement (PVR) can help reduce the amount of PI and RV dilation; however, optimal timing remains controversial; a better understanding of rTOF pathophysiology is of fundamental importance to inform clinical management of patients with rTOF and optimal timing of PVR. In this study, we hypothesize a tight interplay between RV shape, intracardiac biomechanics, and ventricular function in patients with rTOF. To explore this hypothesis and derive quantitative measures, we combined statistical shape modeling with physics-based analysis of in vivo 4D flow data in 36 patients with rTOF. Our study demonstrated for the first time a correlation between regional RV shape variations, hemodynamic forces (HDF), and clinical dysfunction in patients with rTOF. The main findings of this work include 1) general increase in RV size, due to both volume overload and physiological growth, correlated with decrease in strain magnitude in the respective directions, and with increased QRS; 2) regional PI-induced remodeling accounted for ∼10% of the shape variability of the population, and was associated with increased diastolic HDF along the diaphragm-to-right ventricular outflow tract (RVOT) direction, resulting in a net RV deformation along the same direction and decreased tricuspid annular plane systolic excursion (TAPSE); and 3) three shape modes independently correlated with systolic HDF and exercise capacity. Identification of patients based on the shape variations described in this study could help identify those at risk for irreversible dysfunction and guide optimal timing of PVR.NEW & NOTEWORTHY We combine statistical shape modeling with physics-based analysis of 4D flow data to elucidate the interplay between RV shape, hemodynamic forces, and clinical dysfunction in repaired tetralogy of Fallot. We are the first to show that ventricular remodeling is related to hemodynamic force magnitude and direction, global and regional functional parameters, and exercise intolerance. Identification of patients based on the shape variations described in this study could help identify those at risk for irreversible dysfunction.

Virtual Reality Cardiac Surgical Planning Software (CorFix) for Designing Patient-Specific Vascular Grafts: Development and Pilot Usability Study.

BACKGROUND: Patients with single ventricle heart defects receive 3 stages of operations culminating in the Fontan procedure. During the Fontan procedure, a vascular graft is sutured between the inferior vena cava and pulmonary artery to divert deoxygenated blood flow to the lungs via passive flow. Customizing the graft configuration can maximize the long-term benefits. However, planning patient-specific procedures has several challenges, including the ability for physicians to customize grafts and evaluate their hemodynamic performance. OBJECTIVE: The aim of this study was to develop a virtual reality (VR) Fontan graft modeling and evaluation software for physicians. A user study was performed to achieve 2 additional goals: (1) to evaluate the software when used by medical doctors and engineers, and (2) to explore the impact of viewing hemodynamic simulation results in numerical and graphical formats. METHODS: A total of 5 medical professionals including 4 physicians (1 fourth-year resident, 1 third-year cardiac fellow, 1 pediatric intensivist, and 1 pediatric cardiac surgeon) and 1 biomedical engineer voluntarily participated in the study. The study was pre-scripted to minimize the variability of the interactions between the experimenter and the participants. All participants were trained to use the VR gear and our software, CorFix. Each participant designed 1 bifurcated and 1 tube-shaped Fontan graft for a single patient. A hemodynamic performance evaluation was then completed, allowing the participants to further modify their tube-shaped design. The design time and hemodynamic performance for each graft design were recorded. At the end of the study, all participants were provided surveys to evaluate the usability and learnability of the software and rate the intensity of VR sickness. RESULTS: The average times for creating 1 bifurcated and 1 tube-shaped graft after a single 10-minute training session were 13.40 and 5.49 minutes, respectively, with 3 out 5 bifurcated and 1 out of 5 tube-shaped graft designs being in the benchmark range of hepatic flow distribution. Reviewing hemodynamic performance results and modifying the tube-shaped design took an average time of 2.92 minutes. Participants who modified their tube-shaped graft designs were able to improve the nonphysiologic wall shear stress (WSS) percentage by 7.02%. All tube-shaped graft designs improved the WSS percentage compared to the native surgical case of the patient. None of the designs met the benchmark indexed power loss. CONCLUSIONS: VR graft design software can quickly be taught to physicians with no engineering background or VR experience. Improving the CorFix system could improve performance of the users in customizing and optimizing grafts for patients. With graphical visualization, physicians were able to improve WSS percentage of a tube-shaped graft, lowering the chance of thrombosis. Bifurcated graft designs showed potential strength in better flow split to the lungs, reducing the risk for pulmonary arteriovenous malformations.

Computational Fontan Analysis: Preserving Accuracy While Expediting Workflow.

Background: Postoperative outcomes of the Fontan operation have been linked to geometry of the cavopulmonary pathway, including graft shape after implantation. Computational fluid dynamics (CFD) simulations are used to explore different surgical options. The objective of this study is to perform a systematic in vitro validation for investigating the accuracy and efficiency of CFD simulation to predict Fontan hemodynamics. Methods: CFD simulations were performed to measure indexed power loss (iPL) and hepatic flow distribution (HFD) in 10 patient-specific Fontan models, with varying mesh and numerical solvers. The results were compared with a novel in vitro flow loop setup with 3D printed Fontan models. A high-resolution differential pressure sensor was used to measure the pressure drop for validating iPL predictions. Microparticles with particle filtering system were used to measure HFD. The computational time was measured for a representative Fontan model with different mesh sizes and numerical solvers. Results: When compared to in vitro setup, variations in CFD mesh sizes had significant effect on HFD (P = .0002) but no significant impact on iPL (P = .069). Numerical solvers had no significant impact in both iPL (P = .50) and HFD (P = .55). A transient solver with 0.5 mm mesh size requires computational time 100 times more than a steady solver with 2.5 mm mesh size to generate similar results. Conclusions: The predictive value of CFD for Fontan planning can be validated against an in vitro flow loop. The prediction accuracy can be affected by the mesh size, model shape complexity, and flow competition.

Surgical Planning and Optimization of Patient-Specific Fontan Grafts With Uncertain Post-Operative Boundary Conditions and Anastomosis Displacement.

OBJECTIVE: Fontan surgical planning involves designing grafts to perform optimized hemodynamic performance for the patient's long-term health benefit. The uncertainty of post-operative boundary conditions (BC) and graft anastomosis displacements can significantly affect optimized graft designs and lead to undesirable outcomes, especially for hepatic flow distribution (HFD). We aim to develop a computation framework to automatically optimize patient-specific Fontan grafts with the maximized possibility of keeping post-operative results within clinical acceptable thresholds. METHODS: The uncertainties of BC and anastomosis displacements were modeled using Gaussian distributions according to prior research studies. By parameterizing the Fontan grafts, we built surrogate models of hemodynamic parameters taking the design parameters and BC as input. A two-phase reliability-based robust optimization (RBRO) strategy was developed by combining deterministic optimization (DO) and optimization under uncertainty (OUU) to reduce computational cost. RESULTS: We evaluated the performance of the RBRO framework by comparing it with the DO method in four cases of Fontan patients. The results showed that the surgical plans computed from the proposed method yield up to 79.2% improvement in the reliability of the HFD than those of the DO method ( ). The mean values of indexed power loss (iPL) and the percentage of non-physiologic wall shear stress (%WSS) for the optimized surgical plans met the clinically acceptable thresholds. CONCLUSION: This study demonstrated the effectiveness of our RBRO framework to address the uncertainties of BC and anastomosis displacements for Fontan surgical planning. SIGNIFICANCE: The technique developed in this paper demonstrates a significant improvement in the reliability of the predicted post-operative outcomes for Fontan surgical planning. This planning technique is immediately applicable as a building block to enable technology for optimal long-term outcomes for pediatric Fontan patients and can also be used in other pediatric and adult cardiac surgeries.

Location matters: Offset in tissue-engineered vascular graft implantation location affects wall shear stress in porcine models.

Objective: Although surgical simulation using computational fluid dynamics has advanced, little is known about the accuracy of cardiac surgical procedures after patient-specific design. We evaluated the effects of discrepancies in location for patient-specific simulation and actual implantation on hemodynamic performance of patient-specific tissue-engineered vascular grafts (TEVGs) in porcine models. Methods: Magnetic resonance angiography and 4-dimensional (4D) flow data were acquired in porcine models (n = 11) to create individualized TEVGs. Graft shapes were optimized and manufactured by electrospinning bioresorbable material onto a metal mandrel. TEVGs were implanted 1 or 3 months postimaging, and postoperative magnetic resonance angiography and 4D flow data were obtained and segmented. Displacement between intended and observed TEVG position was determined through center of mass analysis. Hemodynamic data were obtained from 4D flow analysis. Displacement and hemodynamic data were compared using linear regression. Results: Patient-specific TEVGs were displaced between 1 and 8 mm during implantation compared with their surgically simulated, intended locations. Greater offset between intended and observed position correlated with greater wall shear stress (WSS) in postoperative vasculature (P < .01). Grafts that were implanted closer to their intended locations showed decreased WSS. Conclusions: Patient-specific TEVGs are designed for precise locations to help optimize hemodynamic performance. However, if TEVGs were implanted far from their intended location, worse WSS was observed. This underscores the importance of not only patient-specific design but also precision-guided implantation to optimize hemodynamics in cardiac surgery and increase reproducibility of surgical simulation.

Right ventricular afterload in repaired D-TGA is associated with inefficient flow patterns, rather than stenosis alone.

Treatment of D- transposition of great arteries (DTGA) involves the Arterial Switch Operation (ASO), which can create PA branch stenosis (PABS) and alter PA blood flow energetics. This altered PA flow may contribute to elevated right ventricular (RV) afterload more significantly than stenosis alone. Our aim was to correlate RV afterload and PA flow characteristics using 4D flow cardiac magnetic resonance (CMR) imaging of a mock circulatory system (MCS) incorporating 3D printed replicas. CMR imaging and clinical characteristics were analyzed from 22 ASO patients (age 11.9 ± 8.7 years, 68% male). Segmentation was performed to create 3D printed PA replicas that were mounted in an MRI-compatible MCS. Pressure drop across the PA replica was recorded and 4D flow CMR acquisitions were analyzed for blood flow inefficiency (energy loss, vorticity). In post-ASO patients, there is no difference in RV mass (p = 0.07), nor RV systolic pressure (p = 0.26) in the presence or absence of PABS. 4D flow analysis of MCS shows energy loss is correlated to RV mass (p = 0.01, r = 0.67) and MCS pressure differential (p = 0.02, r = 0.57). Receiver operating characteristic curve shows energy loss detects elevated RV mass above 30 g/m2 (p = 0.02, AUC 0.88) while index of PA dimensions (Nakata) does not (p = 0.09, AUC 0.79). PABS alone does not account for differences in RV mass or afterload in post-ASO patients. In MCS simulations, energy loss is correlated with both RV mass and PA pressure, and can moderately detect elevated RV mass. Inefficient PA flow may be an important predictor of RV afterload in this population.