Claudio Capelli

Objectives: Postoperative arrhythmias are frequent after Tetralogy of Fallot (ToF) repair, yet anatomic substrate and preventive strategies remain poorly defined. Using hierarchical phase-contrast tomography (HiP-CT) the atrioventricular conduction system in pediatric ToF specimens was investigated non-destructively and in 3D. Methods: Eighteen whole-heart specimens (11 ToF, 7 controls) were imaged at the European Synchrotron, ESRF. Segmentation and 3D renderings demonstrated gross morphology. Morphology, size, depth and course of the non-branching bundle and right bundle branch (RBB) were quantified using custom computational pipelines. Segmentations were visualized in VheaRts, a Unity3D-based XR platform. Results: The ToF conduction system was more draped than in controls, bilaterally spanning the septum, resembling early embryonic architecture. The RBB was variable in origin, course and morphologic structure with significantly smaller indexed cross-sectional area in native ToF versus controls (0.05 (SD 0.20) vs 0.50 (SD 0.20) mm2, p = 0.005). One anomalous fasciculo-ventricular connection and six dead-end tracts were found. Regions at surgical risk included the posterior-inferior margin of the ventricular septal defect (VSD) and the septal crest along its nadir. The superior margin of the VSD at its intersection with the aortic root was free of conduction tissue. The HiP-CT to VR pipeline enabled interactive 3D visualization of conduction pathways relative to key structures. Conclusions: This first pediatric cardiac HiP-CT series reveals a broader anomalous conduction complex in ToF, including variable RBB origin and hypoplasia, providing insight into preoperative vulnerability, arrhythmia, and surgical risk.

Pediatric hemodialysis is a life-saving treatment for children with chronic kidney diseases. Central venous catheters (CVCs) are the most commonly used vascular access, despite being commonly subject to complications leading to inadequate hemodialysis and catheter replacement. The available CVCs feature various design elements reflecting ongoing efforts to achieve optimal performance. Computational fluid dynamics (CFD) can contribute to analyze the flow dynamics within the CVCs. The aim of this study is to investigate the design parameters that most influence the flow performance of CVCs. A design of experiment (DOE) was set up to assess the CFD of two CVC models of 6.5F and 8F size. Blood flow rates, shear stress, residence time, and platelet lysis index were evaluated. The results showed how the proximal side holes were the most influential geometrical features, influencing both the flow rates ( r > 0.64) and the shear stress of the CVCs (| r | > 0.5). At increased flow rate, the side holes were found to be competing with the tip in terms, especially, of residence time inside the CVC. The findings of this DOE show how CFD can contribute to understand the influence of design parameters and potentially guide the development of optimized pediatric-specific CVC models.

Aortic stenosis (AS) is a common valvular disease becoming more prevalent globally due to the aging of the population. Transcatheter aortic valve implantation (TAVI) is a minimally invasive intervention indicated for AS patients as alternative to surgical replacement. TAVI is to date an established procedure. However, it has been often associated with complications such as paravalvular leakage (PVL) or conduction abnormalities. Evidence of associations between morphological features of the aortic root, valve calcification measurements and suboptimal procedural outcomes have been suggested but the analyses were limited by availability and reproducibility of clinical measurements. In this work, we aim to enrich the characterization of AS patients referred for TAVI by analyzing the clinical findings in conjunction with advanced morphological analysis of the implantation site including aortic root, left ventricular outflow tract and 3D calcification patterns. A population of consecutive patients with AS (n = 130) who underwent TAVI at our clinical centre were retrospectively selected for this study. Demographic and clinical measurements were collected before and after TAVI. Pre-operative CT images were used to reconstruct 3D models of patient-specific anatomies. Statistical shape modelling was carried out and outcomes were analyzed in conjunction with clinical outcomes. The 3D modelling of the valve calcification rate matched previous clinical descriptions; including the crescent shapes visible on each leaflet and the higher calcification rate of the non-coronary cusp. Higher calcification rate was found in larger valves together with a positive association between each coronary height and the calcification of their respective leaflet. Sexual dimorphism, on both shape and calcification, was recorded beyond the size differences with straighter aortas and higher calcification rate at the junction between the left and right coronary leaflets for males compared to females. Morphological differences were significantly associated (p = 0.005) with PVL assessments based on post-operative echocardiograms. Larger aortas and shorter left coronary sinus were associated with less leakage. The outcome distribution appeared to be directly affected by sexual differences and device design. Female phenotypes, smaller and more conic aortic root, were associated with worse outcome. Different patterns in calcification distribution on the leaflets were identified but the association with outcomes is not conclusive. In the future, the presented morphological characterization of patients with AS could contribute to predict post-TAVI PVL and design and test improved TAVI devices.

Assessment of the right ventricular outflow tract and pulmonary arteries (RVOT) for percutaneous pulmonary valve implantation (PPVI) uses discrete measurements (diameters and lengths) from medical images. This multi-centre study identified the 3D RVOT shape features prevalent in patients late after surgical repair of congenital heart disease (CHD). A 3D RVOT statistical shape model (SSM) was computed from 81 retrospectively selected CHD patients (14.7 ± 6.8 years) who required pulmonary valve replacement late after surgical repair. A principal component analysis identified prevalent shape features (modes) within the population which were compared with standard geometric measurements (diameter, length and surface area) and between sub-groups of diagnosis, RVOT type and dysfunction. Shape mode 1 and 2 represented RVOT size and curvature and tapering and length, respectively. Shape modes 3–5 related to branch pulmonary artery calibre, conical vs. bulbous RVOTs and RVOT curvature, respectively. Tetralogy of Fallot, transannular patch type and regurgitant RVOTs were larger and straighter while conduit and stenotic types were longer and more cylindrical than other subgroups. This SSM analysed the main 3D shape features present in a population of RVOTs, exploiting the wide 3D anatomical information provided by routine imaging. This morphological information may have implications for PPVI patient selection and device design.

Background: . Mitral transcatheter edge-to-edge repair (m-TEER) is a minimally invasive procedure for treating mitral regurgitation (MR). m-TEER is a highly technical procedure, and a steep learning curve needs to be overcome for operators to ensure optimal patient outcomes and minimise procedural complications. Training via online simulation and observation of procedures is not sufficient to establish operator confidence; thus, advanced hands-on training modalities need to be explored and developed. Methods: . In this study, a novel anatomical simulator for m-TEER training was evaluated in comparison to a standard model. The proposed simulator resembled the anatomical features of the right and left atrium, left ventricle and mitral valve apparatus. Participants in the questionnaire (n = 18) were recruited across 4 centres in London with (n = 8) and without (n = 10) prior experience in m-TEER. Participants were asked to simulate procedures on both an idealised, routinely used simulator and the newly proposed anatomical model. The questionnaire was designed to assess (i) participants’ confidence before and after training and (ii) the realism of the model in the context of the m-TEER procedure. The results of the questionnaires were collected, and statistical analysis (t-test) was performed. Results: . Both models were equally beneficial in increasing operator confidence before and after the simulation of the intervention (P = 0.43). However, increased confidence after training with the anatomical model was recorded (P = 0.02). Participants with prior experience with m-TEER therapy were significantly more confident about the procedure after training with the anatomical model than participants who had no prior experience (P = 0.002). On average, all participants thought that the anatomical model was effective as a training simulator (P = 0.013) and should be integrated into routine training (P = 0.015)). Participants with experience thought that the anatomical model was more effective at reproducing the m-TEER procedure than the idealised model (P = 0.03). Conclusions: . This study showed how a more realistic simulator can be used to improve the effectiveness of m-TEER procedural training. Such pilot results suggest planning future and large investigations to evaluate improvements in clinical practice.

In silico trials are a promising way to increase the efficiency of the development, and the time to market of cardiovascular implantable devices. The development of transcatheter aortic valve implantation (TAVI) devices, could benefit from in silico trials to overcome frequently occurring complications such as paravalvular leakage and conduction problems. To be able to perform in silico TAVI trials virtual cohorts of TAVI patients are required. In a virtual cohort, individual patients are represented by computer models that usually require patient‐specific aortic valve geometries. This study aimed to develop a virtual cohort generator that generates anatomically plausible, synthetic aortic valve stenosis geometries for in silico TAVI trials and allows for the selection of specific anatomical features that influence the occurrence of complications. To build the generator, a combination of non‐parametrical statistical shape modeling and sampling from a copula distribution was used. The developed virtual cohort generator successfully generated synthetic aortic valve stenosis geometries that are comparable with a real cohort, and therefore, are considered as being anatomically plausible. Furthermore, we were able to select specific anatomical features with a sensitivity of around 90%. The virtual cohort generator has the potential to be used by TAVI manufacturers to test their devices. Future work will involve including calcifications to the synthetic geometries, and applying high‐fidelity fluid–structure‐interaction models to perform in silico trials.

In silico medicine describes the application of computational modelling and simulation (CM&S) to the study, diagnosis, treatment or prevention of a disease. Tremendous research advances have been achieved to facilitate the use of CM&S in clinical applications. Nevertheless, the uptake of CM&S in clinical practice is not always timely and accurately reflected in the literature. A clear view on the current awareness, actual usage and opinions from the clinicians is needed to identify barriers and opportunities for the future of in silico medicine. The aim of this study was capturing the state of CM&S in clinics by means of a survey toward the clinical community. Responses were collected online using the Virtual Physiological Human institute communication channels, engagement with clinical societies, hospitals and individual contacts, between 2020 and 2021. Statistical analyses were done with R. Participants (n = 163) responded from all over the world. Clinicians were mostly aged between 35 and 64 years-old, with heterogeneous levels of experience and areas of expertise (i.e., 48% cardiology, 13% musculoskeletal, 8% general surgery, 5% paediatrics). The CM&S terms “Personalised medicine” and “Patient-specific modelling” were the most well-known within the respondents. “In silico clinical trials” and “Digital Twin” were the least known. The familiarity with different methods depended on the medical specialty. CM&S was used in clinics mostly to plan interventions. To date, the usage frequency is still scarce. A well-recognized benefit associated to CM&S is the increased trust in planning procedures. Overall, the recorded level of trust for CM&S is high and not proportional to awareness level. The main barriers appear to be access to computing resources, perception that CM&S is slow. Importantly, clinicians see a role for CM&S expertise in their team in the future. This survey offers a snapshot of the current situation of CM&S in clinics. Although the sample size and representativity could be increased, the results provide the community with actionable data to build a responsible strategy for accelerating a positive uptake of in silico medicine. New iterations and follow-up activities will track the evolution of responses over time and contribute to strengthen the engagement with the medical community.