Computational modelling for congenital heart disease: how far are we from clinical translation?

Computational models of congenital heart disease (CHD) have become increasingly sophisticated over the last 20 years. They can provide an insight into complex flow phenomena, allow for testing devices into patient-specific anatomies (pre-CHD or post-CHD repair) and generate predictive data. This has been applied to different CHD scenarios, including patients with single ventricle, tetralogy of Fallot, aortic coarctation and transposition of the great arteries. Patient-specific simulations have been shown to be informative for preprocedural planning in complex cases, allowing for virtual stent deployment. Novel techniques such as statistical shape modelling can further aid in the morphological assessment of CHD, risk stratification of patients and possible identification of new 'shape biomarkers'. Cardiovascular statistical shape models can provide valuable insights into phenomena such as ventricular growth in tetralogy of Fallot, or morphological aortic arch differences in repaired coarctation. In a constant move towards more realistic simulations, models can also account for multiscale phenomena (eg, thrombus formation) and importantly include measures of uncertainty (ie, CIs around simulation results). While their potential to aid understanding of CHD, surgical/procedural decision-making and personalisation of treatments is undeniable, important elements are still lacking prior to clinical translation of computational models in the field of CHD, that is, large validation studies, cost-effectiveness evaluation and establishing possible improvements in patient outcomes

'Making the Invisible Visible': an audience response to an art installation representing the complexity of congenital heart disease and heart transplantation

The arts can aid the exploration of individual and collective illness narratives, with empowering effects on both patients and caregivers. The artist, partly acting as conduit, can translate and re-present illness experiences into artwork. But how are these translated experiences received by the viewer-and specifically, how does an audience respond to an art installation themed around paediatric heart transplantation and congenital heart disease? The installation, created by British artist Sofie Layton and titled Making the Invisible Visible, was presented at an arts-and-health event. The piece comprised three-dimensional printed medical models of hearts with different congenital defects displayed under bell jars on a stainless steel table reminiscent of the surgical theatre, surrounded by hospital screens. The installation included a soundscape, where the voice of a mother recounting the journey of her son going through heart transplantation was interwoven with the voice of the artist reading medical terminology. A two-part survey was administered to capture viewers' expectations and their response to the piece. Participants (n=125) expected to acquire new knowledge around heart disease, get a glimpse of patients' experiences and be surprised by the work, while after viewing the piece they mostly felt empathy, surprise, emotion and, for some, a degree of anxiety. Viewers found the installation more effective in communicating the experience of heart transplantation than in depicting the complexity of cardiovascular anatomy (p<0.001, z=7.56). Finally, analysis of open-ended feedback highlighted the intimacy of the installation and the privilege viewers felt in sharing a story, particularly in relation to the soundscape, where the connection to the narrative in the piece was reportedly strengthened by the use of sound. In conclusion, an immersive installation including accurate medical details and real stories narrated by patients can lead to an empathic response and an appreciation of the value of illness narratives

Clinical value of patient-specific three-dimensional printing of congenital heart disease: Quantitative and qualitative assessments

Objective: Current diagnostic assessment tools remain suboptimal in demonstrating complex morphology of congenital heart disease (CHD). This limitation has posed several challenges in preoperative planning, communication in medical practice, and medical education. This study aims to investigate the dimensional accuracy and the clinical value of 3D printed model of CHD in the above three areas. Methods: Using cardiac computed tomography angiography (CCTA) data, a patient-specific 3D model of a 20-month-old boy with double outlet right ventricle was printed in Tango Plus material. Pearson correlation coefficient was used to evaluate correlation of the quantitative measurements taken at analogous anatomical locations between the CCTA images pre- and post-3D printing. Qualitative analysis was conducted by distributing surveys to six health professionals (two radiologists, two cardiologists and two cardiac surgeons) and three medical academics to assess the clinical value of the 3D printed model in these three areas. Results: Excellent correlation (r = 0.99) was noted in the measurements between CCTA and 3D printed model, with a mean difference of 0.23 mm. Four out of six health professionals found the model to be useful in facilitating preoperative planning, while all of them thought that the model would be invaluable in enhancing patient-doctor communication. All three medical academics found the model to be helpful in teaching, and thought that the students will be able to learn the pathology quicker with better understanding. Conclusion: The complex cardiac anatomy can be accurately replicated in flexible material using 3D printing technology. 3D printed heart models could serve as an excellent tool in facilitating preoperative planning, communication in medical practice, and medical education, although further studies with inclusion of more clinical cases are needed

Modeling Single Ventricle Physiology: Review of Engineering Tools to Study First Stage Palliation of Hypoplastic Left Heart Syndrome.

First stage palliation of hypoplastic left heart syndrome, i.e., the Norwood operation, results in a complex physiological arrangement, involving different shunting options (modified Blalock-Taussig, RV-PA conduit, central shunt from the ascending aorta) and enlargement of the hypoplastic ascending aorta. Engineering techniques, both computational and experimental, can aid in the understanding of the Norwood physiology and their correct implementation can potentially lead to refinement of the decision-making process, by means of patient-specific simulations. This paper presents some of the available tools that can corroborate clinical evidence by providing detailed insight into the fluid dynamics of the Norwood circulation as well as alternative surgical scenarios (i.e., virtual surgery). Patient-specific anatomies can be manufactured by means of rapid prototyping and such models can be inserted in experimental set-ups (mock circulatory loops) that can provide a valuable source of validation data as well as hydrodynamic information. Such models can be tuned to respond to differing the patient physiologies. Experimental set-ups can also be compatible with visualization techniques, like particle image velocimetry and cardiovascular magnetic resonance, further adding to the knowledge of the local fluid dynamics. Multi-scale computational models include detailed three-dimensional (3D) anatomical information coupled to a lumped parameter network representing the remainder of the circulation. These models output both overall hemodynamic parameters while also enabling to investigate the local fluid dynamics of the aortic arch or the shunt. As an alternative, pure lumped parameter models can also be employed to model Stage 1 palliation, taking advantage of a much lower computational cost, albeit missing the 3D anatomical component. Finally, analytical techniques, such as wave intensity analysis, can be employed to study the Norwood physiology, providing a mechanistic perspective on the ventriculo-arterial coupling for this specific surgical scenario

Three-dimensional printing in congenital heart disease: Considerations on training and clinical implementation from a teaching session

In light of growing interest for three-dimensional printing technology in the cardiovascular community, this study focused on exploring the possibilities of providing training for cardiovascular three-dimensional printing in the context of a relevant international congress and providing considerations on the delivery of such courses. As a second objective, the study sought to capture preferences in relation to three-dimensional printing uses and set-ups from those attending the training session. A survey was administered to n = 30 professionals involved or interested in three-dimensional printing cardiovascular models following a specialised teaching session. Survey results suggest the potential for split training sessions, with a broader introduction for those with no prior experience in three-dimensional printing followed by a more in-depth and hands-on session. All participants agreed on the potential of the technology in all its applications, particularly for aiding decision-making around complex surgical or interventional cases. When exploring setting up an in-house three-dimensional printing service, the majority of participants reported that their centre was already equipped with an in-house facility or expressed a desire that such a facility should be available, with a minority preferring consigning models to an external third party for printing

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity

Beyond apical ballooning: computational modelling reveals morphological features of Takotsubo cardiomyopathy

Takotsubo cardiomyopathy (TCM) is characterized by transient myocardial dysfunction, typically at the left ventricular (LV) apex. Its pathophysiology and recovery mechanisms remain unknown. We investigated LV morphology and deformation in n = 28 TCM patients. Patients with MRI within 5 days from admission ("early TCM") showed reduced LVEF and higher ventricular volumes, but no differences in ECG, global strains or myocardial oedema. Statistical shape modelling described LV size (Mode 1), apical sphericity (Mode 2) and height (Mode 3). Significant differences in Mode 1 suggest that "early TCM" LV remodeling is mainly influenced by a change in ventricular size rather than apical sphericity

Robust Revascularization in Models of Limb Ischemia Using a Clinically Translatable Human Stem Cell-Derived Endothelial Cell Product

Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was identified as mostly endothelial (60% CD31+/CD144+), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers. Cell tracking using MRI, PET, and qPCR in a murine model of limb ischemia demonstrated that hESC-ECP was detectable up to day 7 following injection. Efficacy in several murine models of limb ischemia (immunocompromised/immunocompetent mice and mice with either type I/II diabetes mellitus) demonstrated significantly increased blood perfusion and capillary density. Overall, we demonstrate a GMP-compatible hESC-ECP that improved ischemic limb perfusion and increased local angiogenesis without engraftment, paving the way for translation of this therapy