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.

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.

Accuracy of free-breathing multi-parametric SASHA in identifying T1 and T2 elevations in pediatric orthotopic heart transplant patients.

T1/T2 parametric mapping may reveal patterns of elevation ("hotspots") in myocardial diseases, such as rejection in orthotopic heart transplant (OHT) patients. This study aimed to evaluate the diagnostic accuracy of free-breathing (FB) multi-parametric SAturation recovery single-SHot Acquisition (mSASHA) T1/T2 mapping in identifying hotspots present on conventional Breath-held Modified Look-Locker Inversion recovery (BH MOLLI) T1 and T2-prepared balanced steady-state free-precession (BH T2p-bSSFP) maps in pediatric OHT patients. Pediatric OHT patients underwent noncontrast 1.5T CMR with BH MOLLI T1 and T2p-bSSFP and prototype FB mSASHA T1/T2 mapping in 8 short-axis slices. FB and BH T1/T2 hotspots were segmented using semi-automated thresholding (ITK-SNAP) and their 3D coordinate locations were collected (3-Matic, Materialise, Leuven, Belgium). Receiver operator characteristic curve analysis and measures of central tendency were utilized. 40 imaging datasets from 23 pediatric OHT patients were obtained. FB mSASHA yielded a sensitivity of 82.8% for T1 and 80% for T2 maps when compared to the standard BH MOLLI, as well as 100% specificity for both T1 and T2 maps. When identified on both FB and BH maps, hotspots overlapped in all cases, with an average long axis offset between FB and BH hotspot centers of 5.8 mm (IQR 3.5-8.2) on T1 and 5.9 mm (IQR 3.5-8.2) on T2 maps. FB mSASHA T1/T2 maps can identify hotspots present on conventional BH T1/T2 maps in pediatric patients with OHT, with high sensitivity, specificity, and overlap in 3D space. Free-breathing mapping may improve patient comfort and facilitate OHT assessment in younger patient populations.

A phantom for targeted endomyocardial biopsy training.

Endomyocardial biopsy (EMB) of the right ventricular (RV) septal surface during cardiac catheterization is the standard method to assess cardiac allograft rejection, heart failure, or inflammatory cardiomyopathies. We developed methodology using a three-dimensional (3D) printed phantom to provide proof of concept for using biplane overlay technology for targeted EMB. A standard bioptome and steerable sheath were used to discern feasibility of biopsy for seven regions of the RV septum guided by 3D overlay. This novel biopsy phantom can help train operators in biopsy techniques, and biplane overlay technology has the potential to advance targeted EMB in transplant and cardiomyopathy populations.

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.

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.

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.

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.

Altered hemodynamics by 4D flow cardiovascular magnetic resonance predict exercise intolerance in repaired coarctation of the aorta: an in vitro study.

BACKGROUND: Coarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair. Altered flow patterns have been identified due to abnormal aortic arch geometry. Our previous work demonstrated aorta size mismatch to be associated with exercise intolerance in this population. In this study, we studied aortic flow patterns during simulations of exercise in repaired CoA using 4D flow cardiovascular magnetic resonance (CMR) using aortic replicas connected to an in vitro flow pump and correlated findings with exercise stress test results to identify biomarkers of exercise intolerance. METHODS: Patients with CoA repair were retrospectively analyzed after CMR and exercise stress test. Each aorta was manually segmented and 3D printed. Pressure gradient measurements from ascending aorta (AAo) to descending aorta (DAo) and 4D flow CMR were performed during simulations of rest and exercise using a mock circulatory flow loop. Changes in wall shear stress (WSS) and secondary flow formation (vorticity and helicity) from rest to exercise were quantified, as well as estimated DAo Reynolds number. Parameters were correlated with percent predicted peak oxygen consumption (VO2max) and aorta size mismatch (DAAo/DDAo). RESULTS: Fifteen patients were identified (VO2max 47 to 126% predicted). Pressure gradient did not correlate with VO2max at rest or exercise. VO2max correlated positively with the change in peak vorticity (R = 0.55, p = 0.03), peak helicity (R = 0.54, p = 0.04), peak WSS in the AAo (R = 0.68, p = 0.005) and negatively with peak WSS in the DAo (R = - 0.57, p = 0.03) from rest to exercise. DAAo/DDAo correlated strongly with change in vorticity (R = - 0.38, p = 0.01), helicity (R = - 0.66, p = 0.007), and WSS in the AAo (R = - 0.73, p = 0.002) and DAo (R = 0.58, p = 0.02). Estimated DAo Reynolds number negatively correlated with VO2max for exercise (R = - 0.59, p = 0.02), but not rest (R = - 0.28, p = 0.31). Visualization of streamline patterns demonstrated more secondary flow formation in aortic arches with better exercise capacity, larger DAo, and lower Reynolds number. CONCLUSIONS: There are important associations between secondary flow characteristics and exercise capacity in repaired CoA that are not captured by traditional pressure gradient, likely due to increased turbulence and inefficient flow. These 4D flow CMR parameters are a target of investigation to identify optimal aortic arch geometry and improve long term clinical outcomes after CoA repair.

Moving beyond size: vorticity and energy loss are correlated with right ventricular dysfunction and exercise intolerance in repaired Tetralogy of Fallot.

BACKGROUND: The global effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dilation and dysfunction in repaired Tetralogy of Fallot (rTOF) patients is well studied by cardiovascular magnetic resonance (CMR). However, the links between PR in the RV outflow tract (RVOT), RV dysfunction and exercise intolerance are not clarified by conventional measurements. Not all patients with RV dilation share the same intracardiac flow characteristics, now measurable by time resolved three-dimensional phase contrast imaging (4D flow). In our study, we quantified regional vorticity and energy loss in rTOF patients and correlated these parameters with RV dysfunction and exercise capacity. METHODS: rTOF patients with 4D flow datasets were retrospectively analyzed, including those with transannular/infundibular repair and conduit repair. Normal controls and RV dilation patients with atrial-level shunts (Qp:Qs > 1.2:1) were included for comparison. 4D flow was post-processed using IT Flow (Cardioflow, Japan). Systolic/diastolic vorticity (ω, 1/s) and viscous energy loss (VEL, mW) in the RVOT and RV inflow were measured. To characterize the relative influence of diastolic vorticity in the two regions, an RV Diastolic Vorticity Quotient (ωRVOT-Diastole/ωRV Inflow-Diastole, RV-DVQ) was calculated. Additionally, RVOT Vorticity Quotient (ωRVOT-Diastole/ωRVOT-Systole, RVOT-VQ) and RVOT Energy Quotient (VELRVOT-Diastole/VELRVOT-Systole, RVOT-EQ) was calculated. In rTOF, measurements were correlated against conventional CMR and exercise stress test results. RESULTS: 58 rTOF patients, 28 RV dilation patients and 12 controls were included. RV-DVQ, RVOT-VQ, and RVOT-EQ were highest in rTOF patients with severe PR compared to rTOF patients with non-severe PR, RV dilation and controls (p < 0.001). RV-DVQ positively correlated with RV end-diastolic volume (0.683, p < 0.001), PR fraction (0.774, p < 0.001) and negatively with RV ejection fraction (- 0.521, p = 0.003). Both RVOT-VQ, RVOT-EQ negatively correlated with VO2-max (- 0.587, p = 0.008 and - 0.617, p = 0.005) and % predicted VO2-max (- 0.678, p = 0.016 and - 0.690, p = 0.001). CONCLUSIONS: In rTOF patients, vorticity and energy loss dominate the RVOT compared to tricuspid inflow, correlating with RV dysfunction and exercise intolerance. These 4D flow-based measurements may be sensitive biomarkers to guide surgical management of rTOF patients.

Aorta size mismatch predicts decreased exercise capacity in patients with successfully repaired coarctation of the aorta.

OBJECTIVE: Coarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair with no residual stenosis; however, the hemodynamic mechanism remains unknown. This study aims to correlate aortic arch geometry with exercise capacity in patients with successfully repaired CoA and explain hemodynamic changes using 3-dimensional-printed aorta models in a mock circulatory flow loop. METHODS: A retrospective chart review identified patients with CoA repair who had cardiac magnetic resonance imaging and an exercise stress test. Measurements included aorta diameters, arch height to diameter ratio, left ventricular function, and percent descending aorta (%DAo) flow. Each aorta was printed 3-dimensionally for the flow loop. Flow and pressure were measured at the ascending aorta (AAo) and DAo during simulated rest and exercise. Measurements were correlated with percent predicted peak oxygen consumption (VO2 max). RESULTS: Fifteen patients (mean age 26.8 ± 8.6 years) had a VO2 max between 47% and 126% predicted (mean 92 ± 20%) with normal left ventricular function. DAo diameter and %DAo flow positively correlated with VO2 (P = .007 and P = .04, respectively). AAo to DAo diameter ratio (DAAo/DDAo) negatively correlated with VO2 (P < .001). From flow loop simulations, the ratio of %DAo flow in exercise to rest negatively correlated with VO2 (P = .02) and positively correlated with DAAo/DDAo (P < .01). CONCLUSIONS: This study suggests aorta size mismatch (DAAo/DDAo) is a novel, clinically important measurement predicting exercise capacity in patients with successful CoA repair, likely due to increased resistance and altered flow distribution. Aorta size mismatch and %DAo flow are targets for further clinical evaluation in repaired CoA.