Ventricular anatomical complexity and sex differences impact predictions from electrophysiological computational models.

The aim of this work was to analyze the influence of sex hormones and anatomical details (trabeculations and false tendons) on the electrophysiology of healthy human hearts. Additionally, sex- and anatomy-dependent effects of ventricular tachycardia (VT) inducibility are presented. To this end, four anatomically normal, human, biventricular geometries (two male, two female), with identifiable trabeculations, were obtained from high-resolution, ex-vivo MRI and represented by detailed and smoothed geometrical models (with and without the trabeculations). Additionally one model was augmented by a scar. The electrophysiology finite element model (FEM) simulations were carried out, using O'Hara-Rudy human myocyte model with sex phenotypes of Yang and Clancy. A systematic comparison between detailed vs smooth anatomies, male vs female normal hearts was carried out. The heart with a myocardial infarction was subjected to a programmed stimulus protocol to identify the effects of sex and anatomical detail on ventricular tachycardia inducibility. All female hearts presented QT-interval prolongation however the prolongation interval in comparison to the male phenotypes was anatomy-dependent and was not correlated to the size of the heart. Detailed geometries showed QRS fractionation and increased T-wave magnitude in comparison to the corresponding smoothed geometries. A variety of sustained VTs were obtained in the detailed and smoothed male geometries at different pacing locations, which provide evidence of the geometry-dependent differences regarding the prediction of the locations of reentry channels. In the female phenotype, sustained VTs were induced in both detailed and smooth geometries with RV apex pacing, however no consistent reentry channels were identified. Anatomical and physiological cardiac features play an important role defining risk in cardiac disease. These are often excluded from cardiac electrophysiology simulations. The assumption that the cardiac endocardium is smooth may produce inaccurate predictions towards the location of reentry channels in in-silico tachycardia inducibility studies.

Treatment of coronary bifurcation lesions, part II: implanting two stents. The 16th expert consensus document of the European Bifurcation Club.

The European Bifurcation Club (EBC) supports a continuous review of the field of coronary artery bifurcation interventions and aims to facilitate a scientific discussion and an exchange of ideas on the management of bifurcation disease. The recent focus of meetings and consensus statements has been on the technical issues in bifurcation stenting, recognising that the final result of a bifurcation procedure and the long-term outcome for our patients are strongly influenced by factors, including preprocedural strategy, stenting technique selection, performance of optimal procedural steps, the ability to identify and correct complications and finally, and most important, the overall performance of the operator. Continuous refinement of bifurcation stenting techniques and the promotion of education and training in bifurcation stenting techniques represent a major clinical need. Accordingly, the consensus from the latest EBC meeting in Brussels, October 2021, was to promote education and training in bifurcation stenting based on the EBC principle. Part II of this 16th EBC consensus document aims to provide a step-by-step overview of the pitfalls and technical troubleshooting during the implantation of the second stent either in the provisional stenting (PS) strategy or in upfront 2-stent techniques (e.g., 2-stent PS pathway and double kissing crush stenting). Finally, a detailed overview and discussion of the numerous modalities available to provide continuous education and technical training in bifurcation stenting techniques are discussed, with consideration of their future application in enhancing training and practice in coronary bifurcation lesion treatment.

High-resolution 3D reconstructions of human vasculatures: creation of educational tools and benchtop models for transcatheter devices.

Transcatheter therapies are a common way to treat cardiovascular diseases. These therapies are complicated by significant anatomical patient-to-patient variations that exist in terms of transcatheter vascular pathways. Adding to the complexity of transcatheter procedures, the training tools used for physician education often overlook vast patient-to-patient variations and utilize idealized models of patient anatomy that may be unrealistic. In this study, anatomically accurate models were created from high-resolution images of real patient vasculatures. Using fourteen human cadavers donated for research, we collected high-resolution images to generate 3D computational renderings of various patient anatomies. These models make up the "Transcatheter Pathways Vasculature Database" that can be used for physician education and training, as well as improving transcatheter delivery system design. We performed multiple studies that emphasize the anatomical differences that exist in patient vasculatures. Using 3D printing and virtual reality, we developed educational materials and benchtop models to train physicians using true patient anatomies. These tools can also provide device designers with data to improve their products based on real patient vessels. The "Transcatheter Pathways Vasculature Database" highlights differences between patient vasculatures. By educating and training physicians with patient anatomies that accurately represent significant patient-to-patient variations, learning is more translatable to what is seen in the clinic.

An engineering perspective on the development and evolution of implantable cardiac monitors in free-living animals.

The latest technologies associated with implantable physiological monitoring devices can record multiple channels of data (including: heart rates and rhythms, activity, temperature, impedance and posture), and coupled with powerful software applications, have provided novel insights into the physiology of animals in the wild. This perspective details past challenges and lessons learned from the uses and developments of implanted biologgers designed for human clinical application in our research on free-ranging American black bears (Ursus americanus). In addition, we reference other research by colleagues and collaborators who have leveraged these devices in their work, including: brown bears (Ursus arctos), grey wolves (Canis lupus), moose (Alces alces), maned wolves (Chrysocyon brachyurus) and southern elephant seals (Mirounga leonina). We also discuss the potentials for applications of such devices across a range of other species. To date, the devices described have been used in fifteen different wild species, with publications pending in many instances. We have focused our physiological research on the analyses of heart rates and rhythms and thus special attention will be paid to this topic. We then discuss some major expected step changes such as improvements in sensing algorithms, data storage, and the incorporation of next-generation short-range wireless telemetry. The latter provides new avenues for data transfer, and when combined with cloud-based computing, it not only provides means for big data storage but also the ability to readily leverage high-performance computing platforms using artificial intelligence and machine learning algorithms. These advances will dramatically increase both data quantity and quality and will facilitate the development of automated recognition of extreme physiological events or key behaviours of interest in a broad array of environments, thus further aiding wildlife monitoring and management. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.

Assessment of single and double coronary bifurcation stenting techniques using multimodal imaging and 3D modeling in reanimated swine hearts using Visible Heart® methodologies.

Stent implantation in bifurcated coronary lesions is technically challenging so that procedural refinements are continuously investigated. Novel procedure modeling and intracoronary imaging techniques may offer critical insights on stent deformations and stent-wall interactions during bifurcation stenting procedures. Thus, we assessed coronary bifurcation stenting techniques using multimodal imaging and 3D modeling in reanimated swine hearts. Harvested swine hearts were reanimated using Visible Heart® methodologies and (under standard fluoroscopic guidance) used to test 1-stent (provisional and inverted provisional) and 2-stent (culotte, TAP and DK-crush) techniques on bifurcations within various coronary vessels using commercially available devices. Intracoronary angioscopy and frequency-domain optical-coherence-tomography (OCT) were obtained during the procedures. 3D OCT reconstruction and micro-computed tomography 3D modeling (post heart fixations) were used to assess stent deformations and stent-wall interactions. We conducted multiple stenting procedures and collected unique endoscopic and OCT images (and subsequent computational models from micro-CT) to assess stent deformations and device/wall interactions during different steps of bifurcation stenting procedures. Endoscopy, micro-CT and virtual reality processing documented that different 1- and 2-stent techniques, practiced according to experts' recommended steps, achieve optimal post-intervention stent conformation. As compared with intra-procedural endoscopy, software-generated 3D OCT images accurately depicted stent deformations during 1-stent techniques. On the opposite, during more complex 2-stent techniques, some defects were appreciated at 3D OCT reconstruction despite optimal 2D OCT images. This study provided unique insights regarding both stent deformations occurring in the course of bifurcation stenting and the efficacy of OCT to visualize them.

Impact of statin intake on malignant hyperthermia: an in vitro and in vivo swine study.

BACKGROUND: Statin intake is associated with muscular side effects, among which the unmasking of latent myopathies and of malignant hyperthermia (MH) susceptibility have been reported. These findings, together with experimental data in small animals, prompt speculation that statin therapy may compromise the performance of skeletal muscle during diagnostic in vitro contracture tests (IVCT). In addition, statins might reduce triggering thresholds in susceptible individuals (MHS), or exacerbate MH progression. We sought to obtain empirical data to address these questions. METHODS: We compared the responses of 3 different muscles from untreated or simvastatin treated MHS and non-susceptible (MHN) pigs. MHS animals were also invasively monitored for signs of impending MH during sevoflurane anesthesia. RESULTS: Muscles from statin treated MHS pigs responded with enhanced in vitro contractures to halothane, while responses to caffeine were unaltered by the treatment. Neither agent elicited contractures in muscles from statin treated MHN pigs. In vivo, end- tide pCO2, hemodynamic evolution, plasma pH, potassium and lactate concentrations consistently pointed to mild acceleration of MH development in statin-treated pigs, whereas masseter spasm and rigor faded compared to untreated MHS animals. CONCLUSIONS: The diagnostic sensitivity and specificity of the IVCT remains unchanged by a short-term simvastatin treatment in MHS swine. Evidence of modest enhancement in cardiovascular and metabolic signs of MH, as well as masked pathognomonic muscle rigor observed under simvastatin therapy suggest a potentially misleading influence on the clinical presentation of MH. The findings deserve further study to include other statins and therapeutic regimes.

Algorithm for the analysis of pre-extraction computed tomographic images to evaluate implanted lead-lead interactions and lead-vascular attachments.

BACKGROUND: The number of lead extractions is growing because of the greater population and increasing age of individuals with a cardiac implantable electronic device. Lead extraction procedures can be complex undertakings with risk of significant mortality, and vascular tears in the superior vena cava are of greatest concern. OBJECTIVE: The purpose of this study was to study whether a novel algorithm that analyzes pre-extraction computed tomographic (CT) images can determine the likelihood and location of lead-lead interactions and lead-vessel attachment within patients' venous vasculatures. This information can be used to identify potential case challenges in the planning stages. METHODS: We developed an algorithm to estimate the presence and position of lead-lead interactions and lead-vessel adherences by tracking distance between the leads and distance between the lead and superior vena cava in a sample of 12 patients referred to the United Heart and Vascular Clinic for lead extractions due to infection (n = 5), lead failure (n = 5), and tricuspid regurgitation (n = 2). RESULTS: Preliminary results indicate that the developed algorithm successfully identified lead-lead and lead-vascular attachments compared to review of CT images by medical experts. CONCLUSION: With future validation and clinical implementation, this algorithm could aid physician preparedness by minimizing intraprocedural emergencies and may improve patient outcomes.

First Successful Open-Heart Surgery Utilizing Cross-Circulation in 1954.

A pioneering surgeon at the University of Minnesota, Dr C. Walton Lillehei, is still considered the "father of open-heart surgery". Dr Lillehei and his surgical team performed the first open-heart operations utilizing cross-circulation, including the first successful ventricular septal defect closure on a 3-year-old boy. Before his death at age 67, this patient arranged to donate his body to the University of Minnesota's Anatomy Bequest program. We describe this patient's medical history, and present unique images of internal/external cardiac anatomies and implanted devices obtained via direct visualizations, computed tomography, and fluoroscopy post-mortem. Additionally, we present computational models and 3-dimensional printed models.

Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion.

Many lung donor offers are refused despite increasing demand. Portable normothermic ex vivo lung perfusion (EVLP) could increase donor yield by monitoring and reconditioning extended criteria donor (ECD) lungs. We report its use in human lungs declined for clinical transplantation. Ten sets of such lungs were procured from brain-dead donors and underwent 24 hours of normothermic EVLP using a perfusate based on donor whole blood. Hemodynamic and ventilatory data and P:F ratios were measured. Advanced donor age and borderline oxygenation (donor mean P:F 228 ± 73) were the most commonly cited reasons for refusal for transplantation. There was no significant worsening of pulmonary hemodynamics or compliance or significant P:F decline during preservation in the overall cohort. Mean P:F ratio in the overall cohort was 315 ± 88 mm Hg after 24 hours EVLP. At EVLP termination 5/10 lung blocks met standard EVLP thresholds for acceptability for transplant. Eventual EVLP performance was poorly predicted by donor P:F ratio but well predicted by data gathered early in EVLP. Portable normothermic EVLP is useful for transportation, monitoring, and reconditioning of ECD lungs. Early EVLP measurements are more effective than preprocurement donor P:F in predicting eventual allograft performance. We advocate an aggressive strategy of evaluation of ECD lungs using blood-based EVLP.

Multimodal functional and still imaging of a transplanted human heart reanimated using Visible Heart® methodologies.

BACKGROUND: Our research team obtained a human heart with the right lung attached from a recent transplantation patient via a research collaboration with LifeSource, a local organ procurement organization. The heart and lungs were not viable for transplant given the patient's medical history and were subsequently offered to the University of Minnesota for research purposes. METHODS: Using Visible Heart® methodologies, we reanimated the specimen en bloc and collected multimodal direct visualization from inside the cardiac chambers and great vessels of the functioning heart. RESULTS: Video footage, using videoscopic and fluoroscopic imaging, was captured and is presented in this report as supporting material. Multiple still images highlight the surgical suture sites of the transplantation procedures. CONCLUSIONS: This multimodal imaging offers unique educational value for medical students, clinicians, and medical device designers for improving transplantation techniques and patient outcomes.

Cardiac patient-specific three-dimensional models as surgical planning tools.

BACKGROUND: Three-dimensional printing is an additive manufacturing method that builds objects from digitally generated computational models. Core technologies behind three-dimensional printing are evolving rapidly with major advances in materials, resolution, and speed that enable greater realism and higher accuracy. These improvements have led to novel applications of these processes in the medical field. METHODS: The process of going from a medical image data set (computed tomography, magnetic resonance imaging, ultrasound) to a physical three-dimensional print includes several steps that are described. Medical images originate from Digital Imaging and Communications in Medicine files or data sets, the current standard for storing and transmitting medical images. Via Digital Imaging and Communications in Medicine manipulation software packages, a segmentation process, and manual intervention by an expert user, three-dimensional digital and printed models can be constructed in great detail. RESULTS: Cardiovascular medicine is one of the fastest growing applications for medical three-dimensional printing. The technology is more frequently being used for patient and clinician education, preprocedural planning, and medical device design and prototyping. We report on three case studies, describing how our three-dimensional printing has contributed to the care of cardiac patients at the University of Minnesota. CONCLUSION: Medical applications of computational three-dimensional modeling and printing are already extensive and growing rapidly and are routinely used for visualizing complex anatomies from patient imaging files to plan surgeries and create surgical simulators. Studies are needed to determine whether three-dimensional printed models are cost effective and can consistently improve clinical outcomes before they become part of routine clinical practice.

Identification of Radiofrequency Ablation Catheter Parameters That May Induce Intracardiac Steam Pops: Direct Visualization of Elicitation in Reanimated Swine Hearts.

Radiofrequency, a common ablation modality, is used clinically to terminate cardiac arrhythmias. With excessive heating, complications sometimes occur when the applied energy generates steam pops, which cause release of energy in the form of tissue and/or air emboli. In this study, we investigated numerous parameters potentially associated with intracardiac steam pops including (1) wattage, (2) catheter tip temperature, (3) catheter irrigation, (4) anatomic site, and (5) repeat ablations at a given site. Using unique Visible Heart® methodologies in reanimated swine hearts, we visualized 539 ablations; steam pops developed in 140 of these ablations. The incidence of steam pops significantly increased for both nonirrigated and irrigated ablations at 40 W (p < 0.005), and for nonirrigated ablations with catheter contact angles perpendicular to the tissue or that encompassed larger surface areas (p < 0.05). To minimize the incidence of steam pops, clinicians performing radiofrequency ablations must consider catheter parameters.

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations.

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches use smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band, and papillary muscles. Four paired detailed and smoothed RV endocardium models (2 male and 2 female) were reconstructed from ex vivo human hearts high-resolution magnetic resonance images. Detailed models include structures with ≥1 mm2 cross-sectional area. Haemodynamic characterisation was done by computational fluid dynamics simulations with steady and transient inflows, using high-performance computing. The differences between the flows in smoothed and detailed models were assessed using Q-criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress. Results demonstrated that detailed endocardial structures increase the degree of intra-ventricular pressure drop, decrease the wall shear stress, and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity.

Left Ventricular Trabeculations Decrease the Wall Shear Stress and Increase the Intra-Ventricular Pressure Drop in CFD Simulations.

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10-2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.

Investigating the physiological effects of 10.5 Tesla static field exposure on anesthetized swine.

PURPOSE: In this work, we investigated the relative effects of static magnetic field exposure (10.5 Tesla [T]) on two physiological parameters; blood pressure (BP) and heart rate (HR). METHODS: In vivo, we recorded both BP and HR in 4 swine (3 female, 1 male) while they were positioned within a 10.5T magnet. All measurements were performed invasively within these anesthetized animals by the placement of pressure catheters into their carotid arteries. RESULTS: We measured average increases of 2.0 mm Hg (standard deviation [SD], 6.9) in systolic BP and an increase of 4.5 mm Hg (SD, 13.7) in the diastolic BPs: We also noted an average increase of 1.2 beats per minute (SD, 2.5) in the HRs during such. CONCLUSION: Data regarding changes in BP and HR in anesthetized swine attributed to whole-body 10.5T exposure are reported. Magn Reson Med 79:511-514, 2018. © 2017 International Society for Magnetic Resonance in Medicine.