Search

Spheroids serve as the building blocks for three-dimensional (3D) bioprinted tissue patches. When larger than 500 μm, the desired size for 3D bioprinting, they tend to have a hypoxic core with necrotic cells. Therefore, it is critical to assess the viability of spheroids in order to ensure the successful fabrication of high-viability patches. However, current viability assays are time-consuming, labor-intensive, require specialized training, or are subject to human bias. In this study, we build a convolutional neural network (CNN) model to efficiently and accurately predict spheroid viability, using a phase-contrast image of a spheroid as its input. A comprehensive dataset of mouse mesenchymal stem cell (mMSC) spheroids of varying sizes with corresponding viability percentages, which was obtained through CCK-8 assays, was established and used to train and validate the model. The model was trained to automatically classify spheroids into one of four distinct categories based on their predicted viability: 0-20%, 20-40%, 40-70%, and 70-100%. The model achieved an average accuracy of 92%, with a consistent loss below 0.2. This deep-learning model offers a non-invasive, efficient, and accurate method to streamline the assessment of spheroid quality, thereby accelerating the development of bioengineered cardiac tissue patches for cardiovascular disease therapies.

Cognitional heart disease is one of the leading causes of mortality among newborns. Tissue-engineered vascular grafts offer the potential to help treat cognitional heart disease through patient-specific vascular grafts. However, current methods often rely on non-personalized designs or involve significant human intervention. This paper presents a computational framework for the automatic shape optimization of patient-specific tissue-engineered vascular grafts for repairing the aortic arch, aimed at reducing the need for manual input and improving current treatment outcomes, which either use non-patient-specific geometry or require extensive human intervention to design the vascular graft. The paper's core innovation lies in an automatic shape optimization pipeline that combines Bayesian optimization techniques with the open-source finite volume solver, OpenFOAM, and a novel graft deformation algorithm. Specifically, our framework begins with Laplacian mode computation and the approximation of a computationally low-cost Gaussian process surrogate model to capture the minimum weighted combination of inlet-outlet pressure drop (PD) and maximum wall shear stress (WSS). Bayesian Optimization then performs a limited number of OpenFOAM simulations to identify the optimal patient-specific shape. We use imaging and flow data obtained from six patients diagnosed with cognitional heart disease to evaluate our approach. Our results showcase the potential of online training and hemodynamic surrogate model optimization for providing optimal graft shapes. These results show how our framework successfully reduces inlet-outlet PD and maximum WSS compared to pre-lofted models that include both the native geometry and human-designed grafts. Furthermore, we compare how the performance of each design optimized under steady-state simulation compares to that design's performance under transient simulation, and to what extent the optimal design remains similar under both conditions. Our findings underscore that the automated designs achieve at least a 16% reduction in blood flow pressure drop in comparison to geometries optimized by humans., Competing Interests: Declaration of competing interest Dr. Axel Krieger and Dr. Xiaolong Liu are founders of and hold Shares of Stock Options in CorFix Medical, Inc. The results of the study discussed in this publication could affect the value of CorFix Medical, Inc. This arrangement has been reviewed and approved by the Johns Hopkins University and Texas Tech University in accordance with its conflict of interest policies., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recent advancements in biotechnology forged the path for clinical trials in dish (CTiDs) to advance as a popular method of experimentation in biomedicine. CTiDs play a fundamental role in translational research through technologies such as induced pluripotent stem cells, whole genome sequencing, and organs-on-a-chip. In this review, we explore advancements that enable these CTiD biotechnologies and their applications in animal testing, disease modeling, and space radiation technologies. Furthermore, this review dissects the advantages and disadvantages of CTiDs, as well as their regulatory considerations. Lastly, we evaluate the challenges that CTiDs pose and the role of CTiDs in future experimentation.

A newborn with hypoplastic left heart syndrome underwent a Norwood procedure with a Sano shunt. A month later, he had an atrial septal defect (ASD) stent placed due to ASD size and flow restriction. Three weeks later, he had sudden bradycardia and cardiac arrest in the intensive care unit. He was resuscitated and cannulated for extracorporeal membrane oxygenation (ECMO) through a right neck approach. An attempt to wean him from ECMO a week later failed due to hypoxia. Echocardiography showed ASD flow restriction and a chest x-ray showed flattening of the left atrial side of the ASD stent from chest compression resulting in a restrictive ASD. The patient underwent surgical removal of the ASD stent with ASD enlargement and was successfully weaned from ECMO after surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: We have developed a tissue engineered cardiac patch derived from a 3-dimensional (3D) myocardial tissue reinforced with extracellular matrix in an effort to enhance in situ myocardial regeneration. The feasibility of the patch was evaluated in a porcine model by various modalities to assess both the constructive and functional aspects of regeneration., Methods: A spheroid-based 3D multicellular tissue was created using a 3D net mold system that incorporated cardiomyocytes and embryonic fibroblast cells. The 3D multicellular tissue was incorporated with extracellular matrix sheets and surgically implanted into the right ventricle of a healthy porcine model (n = 4). After 60 days, the implanted patches were evaluated by cardiac magnetic resonance imaging and electroanatomic mapping studies as well as by post-euthanasia analyses, including measurements of mechanical viscoelasticity., Results: Cardiac magnetic resonance imaging revealed improved regional tissue perfusion in the patch area. Electroanatomic mapping exhibited regenerated electrical conductivity in the patch, as evidenced by relatively preserved voltage regions (1.11 ± 0.8 mV) in comparison to the normal right ventricle (4.7 ± 2.8 mV). Histologic and tissue analyses confirmed repopulation of site-specific host cells, including premature cardiomyocytes and active vasculogenesis. These findings were supported by quantitative reverse transcription-polymerase chain reaction., Conclusions: The tissue engineered cardiac patch effectively facilitated in situ constructive and functional myocardial regeneration, characterized by increased regional tissue perfusion and positive electrical activity in the porcine model., Competing Interests: DISCLOSURES The authors have no conflicts of interest to disclose.

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., Competing Interests: Drs Johnson, Krieger, and Hibino are inventors listed on international patent WO/2017/035500Al (Patient-Specific Tissue Engineered Vascular Graft Utilizing Electrospinning). Dr Johnson is an equity holder in Nanofiber Solutions. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Electrode-based electrical stimulation underpins several clinical bioelectronic devices, including deep-brain stimulators 1,2 and cardiac pacemakers 3 . However, leadless multisite stimulation is constrained by the technical difficulties and spatial-access limitations of electrode arrays. Optogenetics offers optically controlled random access with high spatiotemporal capabilities, but clinical translation poses challenges 4-6 . Here we show tunable spatiotemporal photostimulation of cardiac systems using a non-genetic platform based on semiconductor-enabled biomodulation interfaces. Through spatiotemporal profiling of photoelectrochemical currents, we assess the magnitude, precision, accuracy and resolution of photostimulation in four leadless silicon-based monolithic photoelectrochemical devices. We demonstrate the optoelectronic capabilities of the devices through optical overdrive pacing of cultured cardiomyocytes (CMs) targeting several regions and spatial extents, isolated rat hearts in a Langendorff apparatus, in vivo rat hearts in an ischaemia model and an in vivo mouse heart model with transthoracic optical pacing. We also perform the first, to our knowledge, optical override pacing and multisite pacing of a pig heart in vivo. Our systems are readily adaptable for minimally invasive clinical procedures using our custom endoscopic delivery device, with which we demonstrate closed-thoracic operations and endoscopic optical stimulation. Our results indicate the clinical potential of the leadless, lightweight and multisite photostimulation platform as a pacemaker in cardiac resynchronization therapy (CRT), in which lead-placement complications are common., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Open axillary arterial injury is life-threatening, and upper-extremity reperfusion must be performed within approximately 6 h. We present the case of a patient who underwent reperfusion of the upper limb and nerve reconstruction of the post-ganglionic brachial plexus injury in one stage while maintaining stable vital signs. The injury was an avulsion with no fracture. Nerve grafting was necessary to reconstruct the nerves without tension. Although the sural nerve is commonly used, we decided to sacrifice the ipsilateral ruptured ulnar nerve because it was less likely to recover over a long reinnervation distance. Nine months postoperatively, the patient was able to flex the elbow and rotate the forearm, although finger function was poor. Nevertheless, the patient could use the hand to assist her in performing daily activities and return to the previous workplace as a clerk. J. Med. Invest. 71 : 332-334, August, 2024.

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 VO2 max with subgroup analyses of those with residual arch obstruction, bicuspid aortic valve, and hypertension. Ascending aorta (AAo) to DAo diameter ratio (D AAo /D DAo ) was negatively correlated with % predicted VO2 max . %DAo flow positively correlated with VO2 max . Sub-analyses demonstrated that the negative correlation of D AAo /D DAo with VO2 max 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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Fibrosing mediastinitis (FM) is a rare, potentially progressive disease resulting from an idiosyncratic immune response to a variety of stimuli that lead to fibrous infiltration of the mediastinum and possible narrowing of the bronchovascular structures. We report an unusual case of FM in a pediatric patient presenting as myopericarditis and progressing to pericardial thickening and encasement of the mediastinal vascular structures needing surgical intervention. Imaging, including transthoracic echocardiography, cardiac computed tomography, and cardiac magnetic resonance played a crucial role in the diagnosis, assessment, and follow-up. Contrast-enhanced computed tomography can be especially helpful to demonstrate potential findings associated with FM., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Aortic thrombus formation in children is uncommon, particularly in an otherwise healthy pediatric patient. Thromboembolism of such thrombi resulting in subsequent ST-segment elevation myocardial infarction is, thus, exceedingly rare. ( Level of Difficulty: Intermediate. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Hypoplastic left heart syndrome (HLHS) is a deadly congenital heart disease that arises when the left ventricle and outflow tract fail to develop appropriately, inhibiting the adequate perfusion of the rest of the body. Historically, this disease has been treated via a series of surgeries that allows the heart to use a single ventricle. These surgeries are often a palliative measure, and heart transplantation is the only definitive therapy that exists for this condition. It has been hypothesized that stem cell-based regenerative therapies could have a role in promoting cardiac tissue regeneration in HLHS patients who are undergoing palliative surgery. Several clinical trials have demonstrated that introducing pluripotent cells into the heart is safe, feasible, and capable of improving right ventricular ejection fraction (RVEF). However, while these approaches show great promise, there is still room for development. There is a substantial body of pre-clinical work that is focused on generating increasingly large and complex pieces of cardiac tissue in the form of cardiac patches, with the idea that these could be used to rebuild and strengthen the heart in a robust and long-lasting manner. In total, stem cell-based therapies have much to offer when it comes to improving the treatment of HLHS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-127/coif). The column “Pediatric Heart” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Tricuspid atresia with common arterial trunk is a very rare association in complex CHD. This association has even more infrequently been documented concomitantly with interrupted aortic arch. We present the diagnosis and initial surgical management of an infant with a fetal diagnosis of tricuspid atresia and common arterial trunk, with additional postnatal finding of interrupted aortic arch with interruption between the left common carotid and left subclavian artery. Due to the infant's small size, she was initially palliated with bilateral pulmonary artery bands and a ductal stent. This was followed by septation of the common arterial trunk and interrupted aortic arch repair and 4 mm right subclavian artery to main pulmonary artery shunt placement at two months of age. She was discharged home on day of life 81.

Background: Patient-specific, 3-dimensional printed, tissue engineered vascular grafts (3DTEVGs) are manufactured to optimize hemodynamic performance and to accommodate growth. We evaluate growth outcomes of 3DTEVGs compared with standard grafts for pulmonary artery reconstruction in porcine models., Methods: Magnetic resonance imaging (MRI) with 4-dimensional flow data was acquired in porcine models (n = 8). 3DTEVGs guided in design by computational flow dynamics were implanted (n = 4), with polytetrafluorethylene grafts used as controls (n = 4). Postoperative MRI and histologic features of explanted grafts were evaluated after 10 weeks., Results: All pigs survived, with evidence of patent grafts on postoperative MRI. Graft inner diameter changes were 0.47 ± 2.31 mm in 3DTEVGs and -4.61 ± 2.15 mm in controls ( P  = .018). Mean main pulmonary artery wall shear stress was significantly lower in 3DTEVGs (7.12 ± 4.21 Pa) than in controls (18.15 ± 8.37 Pa; P  = .0396). Histologic evaluation of 3DTEVGs showed a single layer of endothelial cells, an organized smooth muscle layer, and collagen deposition with a remaining scaffold area of 21.37% ± 20.46%., Conclusions: Our patient-specific 3DTEVGs demonstrated optimal anatomic fit while maintaining ideal flow dynamics and promoting appropriate neovessel formation., (© 2023 The Authors.)

In the world of clinic treatments, 3D-printed tissue constructs have emerged as a less invasive treatment method for various ailments. Printing processes, scaffold and scaffold free materials, cells used, and imaging for analysis are all factors that must be observed in order to develop successful 3D tissue constructs for clinical applications. However, current research in 3D bioprinting model development lacks diverse methods of successful vascularization as a result of issues with scaling, size, and variations in printing method. This study analyzes the methods of printing, bioinks used, and analysis techniques in 3D bioprinting for vascularization. These methods are discussed and evaluated to determine the most optimal strategies of 3D bioprinting for successful vascularization. Integrating stem and endothelial cells in prints, selecting the type of bioink according to its physical properties, and choosing a printing method according to physical properties of the desired printed tissue are steps that will aid in the successful development of a bioprinted tissue and its vascularization.

Background: While the pledget suture technique has been the standard for surgical aortic. valve replacement (AVR), discussion continues regarding the possibility of the nonpledget suture technique to produce superior structural and hemodynamic parameters. This study aims to assess the effectiveness of the figure-of-eight suture technique in AVR, as determined by the incidence of prosthesis-patient mismatch (PPM)., Methods: We reviewed records of patients (N = 629) who underwent a surgical AVR procedure between January 2011 and July 2018 at a single institution. Indexed effective orifice area values and PPM incidence were calculated from implanted valve size and patient body surface area. Incidence of none, moderate, and severe PPM was compared across AVR suture techniques., Results: A total of 570 pledget and 59 figure-of-eight patients were compared for incidence of PPM. Patients who received AVR with the pledget suture technique had significantly lower echocardiographic measurements of baseline ejection fraction than patients who had received AVR with the figure-of-eight suture technique (p = 0.003). Patients who received the figure-of eight suture had a 14% decrease in moderate PPM compared to patients who received the pledget suture (p = 0.022). Patients who received the figure-of-eight suture also had a significantly higher rate of no PPM (p = 0.044)., Conclusions: The use of the figure-of-eight suture technique in AVR can reduce the incidence of moderate PPM. While the pledget suture is the standard technique in AVR, the figure-of-eight suture technique may offer better structural and hemodynamic outcomes, especially for patients with a smaller aortic annulus., (© 2023. The Author(s).)

Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation., Methods and Results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-treatment ( P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling., Conclusion: Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway.Trial registration number NCT03525418., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Post-operative complications of vascular anastomosis procedures remain a significant clinical challenge and health burden globally. Each year, millions of anastomosis procedures connect arteries and/or veins in vascular bypass, vascular access, organ transplant, and reconstructive surgeries, generally via suturing. Dysfunction of these anastomoses, primarily due to neointimal hyperplasia and the resulting narrowing of the vessel lumen, results in failure rates of up to 50% and billions of dollars in costs to the healthcare system. Non-absorbable sutures are the gold standard for vessel anastomosis; however, damage from the surgical procedure and closure itself causes an inflammatory cascade that leads to neointimal hyperplasia at the anastomosis site. Here, we demonstrate the development of a novel, scalable manufacturing system for fabrication of high strength sutures with nanofiber-based coatings composed of generally regarded as safe (GRAS) polymers and either sirolimus, tacrolimus, everolimus, or pimecrolimus. These sutures provided sufficient tensile strength for maintenance of the vascular anastomosis and sustained drug delivery at the site of the anastomosis. Tacrolimus-eluting sutures provided a significant reduction in neointimal hyperplasia in rats over a period of 14 days with similar vessel endothelialization in comparison to conventional nylon sutures. In contrast, systemically delivered tacrolimus caused significant weight loss and mortality due to toxicity. Thus, drug-eluting sutures provide a promising platform to improve the outcomes of vascular interventions without modifying the clinical workflow and without the risks associated with systemic drug delivery., Competing Interests: Declaration of Competing Interest KSP, JH, and LE have filed patent applications regarding the subject matter of this manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Congenital heart disease (CHD) is the most common congenital anomaly in newborns. Current treatment for cyanotic CHD largely relies on the surgical intervention; however, significant morbidity and mortality for patients with CHD remain. Recent research to explore new avenues of treating CHD includes the utility of stem cells within the field. Stem cells have since been used to both model and potentially treat CHD. Most clinical applications to date have focused on hypoplastic left heart syndrome. Here, we examine the current role of stem cells in CHD and discuss future applications within the field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Tetralogy of Fallot (TOF) repair is a frequent procedure, and although valve-sparing (VS) repair is preferred, determining which patients can successfully undergo this operation remains controversial. We sought to identify parameters to determine a selective, accurate indication for VS repair., Methods: We reviewed 71 patients (82%) undergoing VS repair. We analyzed hemodynamic data, intraoperative reports, and follow-up echocardiography results to identify acceptable indications. Patients requiring pulmonary valve (PV) reintervention versus no reintervention were compared., Results: PV annulus size at repair was z-score of -2.0 (-5.3, 1.3). Approximately half (51%) had a z-score less than -2. Cox regression results showed this was not a risk factor for reintervention (p = .59). Overall, 1-, 3-, 5-, and 10-year freedom from PV reintervention rates were 95.8%, 92.8%, 91% and 77.8%, respectively. Residual pulmonary stenosis (PS) at initial repair was relatively higher in the reintervention group compared with no reintervention group (40 [28, 51] mmHg vs. 30 [22, 37] mmHg; p = .08). For patients with residual PS, pressure gradient (PG) was consistent over time across both groups (PV reintervention: -3 [-15, 8] mmHg vs. no reintervention: 0 [-9, 8] mmHg). The risk of PV reintervention is 3.7-fold higher when the PG from intraoperative TEE is greater than 45 mmHg (p = .04)., Conclusions: Our review of the midterm outcomes of expanded indication for VS suggests intraoperative decision to convert to transannular patch is warranted if intraoperative postprocedure TEE PG is greater than 45 mmHg or RV pressure is higher than half of systemic pressure to prevent reintervention., (© 2022 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)