Preclinical Models of Cardiac Disease: A Comprehensive Overview for Clinical Scientists.

For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives.

Virtual reality simulation as a training tool for perfusionists in extracorporeal circulation: Establishing face and content validity.

Objective: We conducted a prospective study to assess the face and content validity of a new virtual reality (VR) extracorporeal circulation simulator (ECC) developed for perfusionists to facilitate training and practice. We evaluated the opinions of students and staff members about the feasibility of the simulation. The 2 groups consisted of experts (qualified perfusionists) and novices (trainee perfusionists). Methods: Perfusionists (n = 12 experts and n = 11 trainees) received instructions on how to use the VR simulator and then proceeded to perform the start of cardiopulmonary bypass in the VR environment. Participants then completed a Usefulness, Satisfaction, and Ease of Use Questionnaire. The questions were rated on a 5-point Likert scale, ranging from 1 (fully disagree) to 5 (fully agree), to assess the face validity and content validity of this simulator. Results: Participants reported a predominantly positive experience with the VR-ECC simulator, with 96% (n = 22) agreeing that the simulator was a useful way of training ECC scenarios. All participants found it easy to interact with the software (100%, n = 23), and 82% of students (n = 9) believed it helped them remember the steps involved with initiating ECC. Finally, (87% [n = 20]) of participants believed the image quality and depth perception were good. Conclusions: Our next-generation simulator was valid for face and content constructs, and almost all participants found it to be a useful way of training for ECC scenarios. This simulator represents a first step toward truly blended digital learning and a new interactive, flexible, and innovative modality for perfusion training.

Sublobar Pulmonary Resection in Children With Congenital Lung Abnormalities: A Systematic Review.

BACKGROUND: Lobectomy is currently the advised resection for symptomatic congenital lung abnormalities (CLA). Sublobar surgery is suggested as an alternative that enables to conserve healthy lung parenchyma. This systematic review aims to explore the outcomes of sublobar surgery in CLA patients as well as the corresponding surgical terminology and techniques. METHODS: A systematic literature search was performed in adherence to PRISMA-P guidelines. The target population consists of children undergoing sublobar pulmonary resection for CLA. All studies were independently assessed by two reviewers, and evaluated by a third reviewer in case of disagreement. RESULTS: The literature search yielded 901 studies of which 18 studies were included, comprising 1167 cases. The median chest tube insertion duration was 3.6 days (range 2.0-6.9 days), the median hospital admission was 4.9 days (range 2.0-14.5 days), and residual disease was diagnosed in 2% - leading to re-operation in 70%. The median incidence of postoperative complications was 15% (range 0-67%). Follow-up imaging was standard-of-care in 2/3 of studies. Due to the absence of standardised terminology, operative details and specification of resection type did not typically relate between studies. CONCLUSIONS: Sublobar resection of CLA lesions could be a viable alternative to lobectomy in certain cases, with the advantage of conserving healthy lung parenchyma. Peri- and postoperative complications are comparable with those reported for conventional lobectomy. The incidence of residual disease following sublobar surgery appears to be lower than commonly stated. To improve comparability between studies, we recommend reporting perioperative characteristics in a structured format. LEVEL OF EVIDENCE: Level IV.

Optimized preoperative planning of double outlet right ventricle patients by 3D printing and virtual reality: a pilot study.

OBJECTIVES: In complex double outlet right ventricle (DORV) patients, the optimal surgical approach may be difficult to assess based on conventional 2-dimensional (2D) ultrasound (US) and computed tomography (CT) imaging. The aim of this study is to assess the added value of 3-dimensional (3D) printed and 3D virtual reality (3D-VR) models of the heart used for surgical planning in DORV patients, supplementary to the gold standard 2D imaging modalities. METHODS: Five patients with different DORV subtypes and high-quality CT scans were selected retrospectively. 3D prints and 3D-VR models were created. Twelve congenital cardiac surgeons and paediatric cardiologists, from 3 different hospitals, were shown 2D-CT first, after which they assessed the 3D print and 3D-VR models in random order. After each imaging method, a questionnaire was filled in on the visibility of essential structures and the surgical plan. RESULTS: Spatial relationships were generally better visualized using 3D methods (3D printing/3D-VR) than in 2D. The feasibility of ventricular septum defect patch closure could be determined best using 3D-VR reconstructions (3D-VR 92%, 3D print 66% and US/CT 46%, P < 0.01). The percentage of proposed surgical plans corresponding to the performed surgical approach was 66% for plans based on US/CT, 78% for plans based on 3D printing and 80% for plans based on 3D-VR visualization. CONCLUSIONS: This study shows that both 3D printing and 3D-VR have additional value for cardiac surgeons and cardiologists over 2D imaging, because of better visualization of spatial relationships. As a result, the proposed surgical plans based on the 3D visualizations matched the actual performed surgery to a greater extent.

Video-assisted thoracic surgery S7 segmentectomy: use of virtual reality surgical planning and simulated reality intraoperative modelling.

Preoperative planning and perioperative guidance are crucial in anatomical sublobar pulmonary resections. Preoperative virtual reality visualization of the computed tomography scan and intraoperative guidance through a soft-tissue dynamic lung model (simulated reality) can provide better insights into patient-specific anatomy for the surgical team. Using these imaging techniques, we present a right-sided video-assisted thoracoscopic surgery segment 7 resection.

Virtual Reality Simulator versus Conventional Advanced Life Support Training for Cardiopulmonary Resuscitation Post-Cardiac Surgery: A Randomized Controlled Trial.

External chest compressions are often ineffective for patients arresting after cardiac surgery, for whom emergency resternotomy may be required. A single-blinded randomized controlled trial (RCT) was performed, with participants being randomized to a virtual reality (VR) Cardiac Surgical Unit Advanced Life Support (CSU-ALS) simulator training arm or a conventional classroom CSU-ALS training arm. Twenty-eight cardiothoracic surgery (CTS) residents were included and subsequently assessed in a moulage scenario in groups of two, either participating as a leader or surgeon. The primary binary outcomes were two time targets: (1) delivering three stacked shocks within 1 min and (2) resternotomy within 5 min. Secondary outcomes were the number of protocol mistakes made and a questionnaire after the VR simulator. The conventional training group administered stacked shocks within 1 min in 43% (n = 6) of cases, and none in the VR group reached this target, missing it by an average of 25 s. The resternotomy time target was reached in 100% of the cases (n = 14) in the conventional training group and in 83% of the cases (n = 10) in the VR group. The VR group made 11 mistakes in total versus 15 for those who underwent conventional training. Participants reported that the VR simulator was useful and easy to use. The results show that the VR simulator can provide adequate CSU-ALS training. Moreover, VR training results in fewer mistakes suggesting that repetitive practice in an immersive environment improves skills.

Essential Surgical Plan Modifications After Virtual Reality Planning in 50 Consecutive Segmentectomies.

BACKGROUND: Lately, increased interest in pulmonary segmentectomy has been observed. Segmental border identification is extremely difficult on 2-dimensional computed tomography (CT). Preoperative application of virtual reality (VR) can provide better insight into patient-specific anatomy. The aim of this study was to investigate the added clinical value of 3-dimensional (3D) VR using PulmoVR for preoperative planning. METHODS: Patients with an indication for pulmonary segmentectomy were included between June 2020 and September 2021 at the Erasmus Medical Center, Rotterdam, The Netherlands. CT scans were (semi)automatically segmented to visualize lung segments, segmental arteries, veins, and bronchi. Three surgeons made a surgical plan on the basis of the conventional CT scan and subsequently analyzed the VR visualization. The primary outcome was the incidence of critical (ensuring radical resection) preoperative plan modifications. Secondarily, data on observed anatomic variation and perioperative (oncologic) outcomes were collected. RESULTS: A total of 50 patients (median age at surgery, 65 years [interquartile range, 17.25 years]) with an indication for pulmonary segmentectomy were included. After supplemental VR visualization, the surgical plan was adjusted in 52%; the tumor was localized in a different segment in 14%, more lung-sparing resection was planned in 10%, and extended segmentectomy, including 1 lobectomy, was planned in 28%. Pathologic examination confirmed radical resection in 49 patients (98%). CONCLUSIONS: This 3D VR technology showed added clinical value in the first 50 VR-guided segmentectomies because a 52% change of plan with 98% radical resection was observed. Furthermore, 3D VR visualization of the bronchovasculature, including various anatomic variations, provided better insight into patient-specific anatomy and offered lung-sparing possibilities with more certainty.

Immersive 3D Virtual Reality-Based Clip Sizing for Thoracoscopic Left Atrial Appendage Closure.

Objective: Surgical left atrial appendage (LAA) closure using epicardial clips has become popular in stroke prevention in patients with atrial fibrillation. Optimal placement of the clip is essential to achieve complete LAA occlusion and to prevent complications due to compression of the circumflex artery. We determine the added value of immersive virtual reality (VR) in accurately assessing LAA base size and selection of an appropriately sized clip. Methods: We studied the feasibility of measuring the LAA base using VR and conventional computed tomography (CT). A retrospective analysis was performed of LAA base measurements in 15 patients who had undergone thoracoscopic LAA clipping. Subsequently, we compared the placed clip size with imaging-acquired LAA base size to retrospectively evaluate intraprocedural sizing. Results: We successfully applied a VR platform to measure LAA base size. The median LAA base size measured in CT (23.8 mm, interquartile range [IQR] 22.3 to 26.4 mm) and intracardial virtual reality (23.4 mm, IQR 21.6 to 25.5 mm) did not differ significantly (P = 0.416). VR measurements of the LAA base in surgeon's view (25.7 mm, IQR 24.2 to 29.2) were significantly higher than those of 2-dimensional CT (P = 0.037) and intracardial 3-dimensional (3D) VR (P < 0.05) measurements. All measurements differed significantly with placed clip sizes (P < 0.05). There were no clip malpositioning-related events. Conclusions: Immersive VR is a feasible method for obtaining anatomical information on LAA base size. In this retrospective analysis, CT and VR-based measurements of LAA base size differed significantly from intraoperatively placed LAA clips, indicating potential oversizing when measured intraoperatively. Using intuitive 3D VR-based imaging might be a useful method to assist in accurate preprocedural sizing of LAA base and can potentially prevent oversizing.

Virtual Reality Simulation Training for Cardiopulmonary Resuscitation After Cardiac Surgery: Face and Content Validity Study.

BACKGROUND: Cardiac arrest after cardiac surgery commonly has a reversible cause, where emergency resternotomy is often required for treatment, as recommended by international guidelines. We have developed a virtual reality (VR) simulation for training of cardiopulmonary resuscitation (CPR) and emergency resternotomy procedures after cardiac surgery, the Cardiopulmonary Resuscitation Virtual Reality Simulator (CPVR-sim). Two fictive clinical scenarios were used: one case of pulseless electrical activity (PEA) and a combined case of PEA and ventricular fibrillation. In this prospective study, we researched the face validity and content validity of the CPVR-sim. OBJECTIVE: We designed a prospective study to assess the feasibility and to establish the face and content validity of two clinical scenarios (shockable and nonshockable cardiac arrest) of the CPVR-sim partly divided into a group of novices and experts in performing CPR and emergency resternotomies in patients after cardiac surgery. METHODS: Clinicians (staff cardiothoracic surgeons, physicians, surgical residents, nurse practitioners, and medical students) participated in this study and performed two different scenarios, either PEA or combined PEA and ventricular fibrillation. All participants (N=41) performed a simulation and completed the questionnaire rating the simulator's usefulness, satisfaction, ease of use, effectiveness, and immersiveness to assess face validity and content validity. RESULTS: Responses toward face validity and content validity were predominantly positive in both groups. Most participants in the PEA scenario (n=26, 87%) felt actively involved in the simulation, and 23 (77%) participants felt in charge of the situation. The participants thought it was easy to learn how to interact with the software (n=24, 80%) and thought that the software responded adequately (n=21, 70%). All 15 (100%) expert participants preferred VR training as an addition to conventional training. Moreover, 13 (87%) of the expert participants would recommend VR training to other colleagues, and 14 (93%) of the expert participants thought the CPVR-sim was a useful method to train for infrequent post-cardiac surgery emergencies requiring CPR. Additionally, 10 (91%) of the participants thought it was easy to move in the VR environment, and that the CPVR-sim responded adequately in this scenario. CONCLUSIONS: We developed a proof-of-concept VR simulation for CPR training with two scenarios of a patient after cardiac surgery, which participants found was immersive and useful. By proving the face validity and content validity of the CPVR-sim, we present the first step toward a cardiothoracic surgery VR training platform.

Virtual Reality in the Preoperative Planning of Adult Aortic Surgery: A Feasibility Study.

Background: Complex aortic anatomy needs careful preoperative planning in which a patient-tailored approach with novel immersive techniques could serve as a valuable addition to current preoperative imaging. This pilot study aimed to investigate the technical feasibility of virtual reality (VR) as an additional imaging tool for preoperative planning in ascending aortic surgery. Methods: Ten cardiothoracic surgeons were presented with six patients who had each undergone a recent repair of the ascending aorta. Two-dimensional computed tomography images of each patient were assessed prior to the VR session. After three-dimensional (3D) VR rendering and 3D segmentation of the ascending aorta and aortic arch, the reconstructions were analyzed by each surgeon in VR via a head-mounted display. Each cardiothoracic surgeon completed a questionnaire after each planning procedure. The results of their assessments were compared to the performed operations. The primary endpoint of the present study was a change of surgical approach from open to clamped distal anastomosis, and vice versa. Results: Compared with conventional imaging, 80% of surgeons found that VR prepared them better for surgery. In 33% of cases (two out of six), the preoperative decision was adjusted due to the 3D VR-based evaluation of the anatomy. Surgeons rated CardioVR usefulness, user-friendliness, and satisfaction with median scores of 3.8 (IQR: 3.5-4.1), 4.2 (IQR: 3.8-4.6,) and 4.1 (IQR: 3.8-4.7) on a five-point Likert scale, respectively. Conclusions: Three-dimensional VR imaging was associated with improved anatomical understanding among surgeons and could be helpful in the future preoperative planning of ascending aortic surgery.

Multidisciplinary Virtual Three-Dimensional Planning of a Forequarter Amputation With Chest Wall Resection.

We present the case of a 74-year-old man with a history of a squamous cell carcinoma in the left axilla. The patient underwent a multidisciplinary surgical resection through an extended forequarter amputation with thoracic wall resection and reconstruction. With regard to the complexity of the case, three-dimensional virtual reality-based patient-specific reconstructions were used as a supplemental tool to conventional computed tomography imaging to plan the procedure. With this report, we aim to stimulate further research to improve and automate the workflow and to bring virtual and augmented reality reconstructions into the surgical theater of the future.

Current and Future Applications of Virtual, Augmented, and Mixed Reality in Cardiothoracic Surgery.

BACKGROUND: This review aims to examine the existing literature to address currently used virtual, augmented, and mixed reality modalities in the areas of preoperative surgical planning, intraoperative guidance, and postoperative management in the field of cardiothoracic surgery. In addition this innovative technology provides future perspectives and potential benefits for cardiothoracic surgeons, trainees, and patients. METHODS: A targeted, nonsystematic literature assessment was performed within the Medline and Google Scholar databases to help identify current trends and to provide better understanding of the current state-of-the-art extended reality (XR) modalities in cardiothoracic surgery. Related articles published up to July 2020 were included in the review. RESULTS: XR is a novel technique gaining increasing application in cardiothoracic surgery. It provides a 3-dimensional and realistic view of structures and environments and offers the user the ability to interact with digital projections of surgical targets. Recent studies showed the validity and benefits of XR applications in cardiothoracic surgery. Examples include XR-guided preoperative planning, intraoperative guidance and navigation, postoperative pain and rehabilitation management, surgical simulation, and patient education. CONCLUSIONS: XR is gaining interest in the field of cardiothoracic surgery. In particular there are promising roles for XR applications in televirtuality, surgical planning, surgical simulation, and perioperative management. However future refinement and research are needed to further implement XR in the aforementioned settings within cardiothoracic surgery.

Preoperative visualization of congenital lung abnormalities: hybridizing artificial intelligence and virtual reality.

OBJECTIVES: When surgical resection is indicated for a congenital lung abnormality (CLA), lobectomy is often preferred over segmentectomy, mostly because the latter is associated with more residual disease. Presumably, this occurs in children because sublobar surgery often does not adhere to anatomical borders (wedge resection instead of segmentectomy), thus increasing the risk of residual disease. This study investigated the feasibility of identifying eligible cases for anatomical segmentectomy by combining virtual reality (VR) and artificial intelligence (AI). METHODS: Semi-automated segmentation of bronchovascular structures and lesions were visualized with VR and AI technology. Two specialists independently evaluated via a questionnaire the informative value of regular computed tomography versus three-dimensional (3D) VR images. RESULTS: Five asymptomatic, non-operated cases were selected. Bronchovascular segmentation, volume calculation and image visualization in the VR environment were successful in all cases. Based on the computed tomography images, assignment of the CLA lesion to specific lung segments matched between the consulted specialists in only 1 out of the cases. Based on the three 3D VR images, however, the localization matched in 3 of the 5 cases. If the patients would have been operated, adding the 3D VR tool to the preoperative workup would have resulted in changing the surgical strategy (i.e. lobectomy versus segmentectomy) in 4 cases. CONCLUSIONS: This study demonstrated the technical feasibility of a hybridized AI-VR visualization of segment-level lung anatomy in patients with CLA. Further exploration of the value of 3D VR in identifying eligible cases for anatomical segmentectomy is therefore warranted.

3D Virtual Reality Imaging of Major Aortopulmonary Collateral Arteries: A Novel Diagnostic Modality.

BACKGROUND: Major aortopulmonary collateral arteries (MAPCAs), as seen in patients with pulmonary atresia, are arteries that supply blood from the aorta to the lungs and often require surgical intervention. To achieve complete repair in the least number of interventions, optimal imaging of the pulmonary arterial anatomy and MAPCAs is critical. 3D virtual reality (3D-VR) is a promising and upcoming new technology that could potentially ameliorate current imaging shortcomings. METHODS: A retrospective, proof-of-concept study was performed of all operated patients with pulmonary atresia and MAPCAs at our center between 2010 and 2020 with a preoperative computed tomography (CT) scan. CT images were reviewed by two congenital cardiac surgeons in 3D-VR to determine additional value of VR for MAPCA imaging compared to conventional CT and for preoperative planning of MAPCA repair. RESULTS: 3D-VR visualizations were reconstructed from CT scans of seven newborns where the enhanced topographic anatomy resulted in improved visualization of MAPCA. In addition, surgical planning was improved since new observations or different preoperative plans were apparent in 4 out of 7 cases. After the initial setup, VR software and hardware was reported to be easy and intuitive to use. CONCLUSIONS: This study showed technical feasibility of 3D-VR reconstruction of children with immersive visualization of topographic anatomy in an easy-to-use format leading to an improved surgical planning of MAPCA surgery. Future prospective studies are required to investigate the clinical benefits in larger populations.

Social Non-profit Bioentrepreneurship: Current Status and Future Impact on Global Health.

For-profit biotechnological and pharmaceutical companies have played an essential role in the research and development (R&D) of innovative medical products and drugs for many decades and embody a trillion-dollar industry. The past decades have been marked by an increase in growth of social non-profit biotechnology companies and organizations led by entrepreneurs committed to solve (global) health issues. In this review, we define the concept of social bioentrepreneurship and consider the potential impact of such ventures on global health. We analyse the current status of non-profit biotechnology and clarify the strategy, motivation, funding, and marketing techniques of these enterprises. We find that these non-profit ventures mainly focus on neglected and rare diseases by using different but also similar funding, marketing, and business strategy approaches to for-profit biotechnology enterprises. We also identify good leadership, multidisciplinary teams, and public awareness as key components to achieve long-term survival and higher success rates. Challenges faced by bioentrepreneurs include the lack of a clearly defined regulatory environment or governmental incentives to support their endeavors. Overall, with this qualitative data review and market analysis we draw a promising picture of social non-profit bioentrepreneurship and underscore its current and future impact on global health issues.

Conventional open harvesting of the radial artery as a conduit for coronary artery bypass grafting.

This video tutorial summarizes the main steps of the conventional open surgical technique for harvesting the radial artery as a coronary artery bypass graft, taking anatomic and surgical aspects into account.

Virtual reality and artificial intelligence for 3-dimensional planning of lung segmentectomies.

BACKGROUND: There has been an increasing trend toward pulmonary segmentectomies to treat early-stage lung cancer, small intrapulmonary metastases, and localized benign pathology. A complete preoperative understanding of pulmonary anatomy is essential for accurate surgical planning and case selection. Identifying intersegmental divisions is extremely difficult when performed on computed tomography. For the preoperative planning of segmentectomies, virtual reality (VR) and artificial intelligence could allow 3-dimensional visualization of the complex anatomy of pulmonary segmental divisions, vascular arborization, and bronchial anatomy. This technology can be applied by surgeons preoperatively to gain better insight into a patient's anatomy for planning segmentectomy. METHODS: In this prospective observational pilot study, we aim to assess and demonstrate the technical feasibility and clinical applicability of the first dedicated artificial intelligence-based and immersive 3-dimensional-VR platform (PulmoVR; jointly developed and manufactured by Department of Cardiothoracic Surgery [Erasmus Medical Center, Rotterdam, The Netherlands], MedicalVR [Amsterdam, The Netherlands], EVOCS Medical Image Communication [Fysicon BV, Oss, The Netherlands], and Thirona [Nijmegen, The Netherlands]) for preoperative planning of video-assisted thoracoscopic segmentectomies. RESULTS: A total of 10 eligible patients for segmentectomy were included in this study after referral through the institutional thoracic oncology multidisciplinary team. PulmoVR was successfully applied as a supplementary imaging tool to perform video-assisted thoracoscopic segmentectomies. In 40% of the cases, the surgical strategy was adjusted due to the 3-dimensional-VR-based evaluation of anatomy. This underlines the potential benefit of additional VR-guided planning of segmentectomy for both surgeon and patient. CONCLUSIONS: Our study demonstrates the successful development and clinical application of the first dedicated artificial intelligence and VR platform for the planning of pulmonary segmentectomy. This is the first study that shows an immersive virtual reality-based application for preoperative planning of segmentectomy to the best of our knowledge.