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IntroductionHigh-resolution digitized cardiac anatomical data sets are in huge demand in clinical, basic research and computational settings. They can be leveraged to evaluate intricate anatomical and structural changes in disease pathology, such as myocardial infarction (MI), which is one of the most common causes of heart failure and death. Advancements in high-resolution imaging and anatomical techniques in this field and our laboratory have led to vast improvements in understanding cardiovascular anatomy, especially the cardiac conduction system (CCS) responsible for the electricity of the heart, in healthy/aged/obese post-mortem human hearts. However, the digitized anatomy of the electrical system of the heart within MI hearts remains unexplored.MethodsFive post-mortem non-MI and MI human hearts were obtained by the Visible Heart® Laboratories via LifeSource, Minneapolis, MN, United States (with appropriate ethics and consent): specimens were then transported to Manchester University with an material transfer agreement in place and stored under the HTA 2004, UK. After performing contrast-enhanced micro-CT, a visualization tool (namely Amira) was used for 3D high-resolution anatomical visualizations and reconstruction. Various cardiovascular structures were segmented based on the attenuation difference of micro-CT scans and tissue traceability. The relationship between the CCS and surrounding tissues in MI and non-MI human hearts was obtained. 3D anatomical models were further explored for their use in computational simulations, 3D printing and mix/virtual reality visualization.Results3D segmented cardiovascular structures in the MI hearts elicited diverse macro-/micro- anatomical changes. The key findings are thickened valve leaflets, formation of new coronary arteries, increased or reduced thicknesses of pectinate and papillary muscles and Purkinje fibers, thinner left bundle branches, sinoatrial nodal atrophy, atrioventricular conduction axis fragmentation, and increased epicardial fat in some hearts. The propagation of the excitation impulses can be simulated, and 3D printing can be utilized from the reconstructed and segmented structures.DiscussionHigh-resolution digitized cardiac anatomical datasets offer exciting new tools for medical education, clinical applications, and computational simulation.

Renal denervation to treat arterial hypertension is growing in adoption but still shows inconsistent results. Device improvement is difficult, as there is currently no way to study the immediate success of renal denervation devices in living tissue. In an effort to visualize live renal nerves surrounding their arteries using multiphoton microscopy, kidney pairs were explanted from Yorkshire pigs. They were maintained viable with a pulsatile perfusion apparatus using Visible Kidney™ methodologies, in which blood is replaced by a modified, oxygenated, and warmed (37 °C) Krebs–Henseleit buffer. The block resection allows catheter placement for nerve ablation treatment. Subsequently, the kidney block was disconnected from the perfusion system and underwent multiphoton microscopy (Nikon A1R 1024 MP). A total of three renal blocks were imaged using this model. Using 780 nm excitation for autofluorescence, we were able to selectively image peri-arterial nerves (2.5–23 μm diameter) alongside arteriolar elastin fibers (1.96 ± 0.87 μm; range: 0.3–4.27) at 25× magnification at a pixel size of 1.02 µm). Autofluoresecence was not strong enough to identify nerves at 4× magnification. There was a high but variable signal-to-noise ratio of 52.3 (median, IQR 159). This model may be useful for improving future physician training and innovations in renal denervation technologies.

Abstract Background Percutaneous coronary interventions (PCIs) within left main coronary arteries are high-risk procedures that require optimization of interactions between stent(s) and diseased vessels. Optical Coherence Tomography (OCT) is a widely accepted tool that enhances physicians’ ability to assess proper stent appositions during clinical procedures. The primary aim of this study was to develop complementary post-procedure imaging methodologies to better assess and interpret outcomes of left main PCI procedures, utilizing both reanimated and perfusion-fixed human hearts. Methods PCIs were performed while obtaining OCT scans within the left main anatomies of six human hearts. Subsequently, each heart was scanned with a micro-CT scanner with optimized parameters to achieve resolutions up to 20 µm. Scans were reconstructed and imported into a DICOM segmentation software to generate computational models of implanted stents and associated coronary vessels. 2D images from OCT that were obtained during PCIs were compared to the 3D models generated from micro-CT reconstructions. In addition, the 3D models were utilized to create virtual reality scenes and enlarged 3D prints for development of “mixed reality” tools relative to bifurcation stenting within human left main coronary arteries. Results We developed reproducible methodologies for post-implant analyses of coronary artery stenting procedures. In addition, we generated high-resolution 3D computational models, with ~ 20-micron resolutions, of PCIs performed within reanimated and perfusion-fixed heart specimens. Conclusions Generated computational models of left main PCIs performed in isolated human hearts can be used to obtain detailed measurements that provide further clinical insights on procedural outcomes. The 3D models from these procedures are useful for generating virtual reality scenes and 3D prints for physician training and education.

Abstract Background and Aims Modern health care faces a plethora of challenges including the delivery of quality and cost‐efficient care. Physicians are first‐hand observers of clinical problems but may lack the requisite training and education to develop innovations that improve patient care. Few medical education programs address innovation, leadership, and transdisciplinary collaboration despite being highlighted by national medical and education organizations including the American Medical Association. The University of Minnesota has implemented the Augustine program over the last 10‐years to produce physicians that are leaders in medical innovation. Methods As a novel joint engineering‐medical school curriculum to educate medical students, residents, and fellows, the Augustine program incorporates engineering coursework, biomedical research, and a multidisciplinary design and business development experience to produce physicians capable of designing and marketing “disruptive technologies.” The Augustine program takes 1‐year to complete in addition to the 4‐year medical education and provides a Master of Biomedical Engineering upon completion. Results Augustine program graduates (n = 6) have reported significant contributions related to the joint engineering‐medical education including peer‐reviewed publications (Median: 13), deployable assets (Median: 2), and intellectual property (Median: 1). Most surveyed graduates (n = 5, 83%) continue to be active contributors to medical innovation and all (n = 6, 100%) utilize their transdisciplinary education to improve patient care. Conclusion Augustine program graduates impact the entire spectrum of innovation and continue to improve patient care. The program will seek to emphasize the inclusion of physician residents and fellows with position expansion. The addition of a multi‐week medical innovation clerkship will provide a more focused experience for students unable to dedicate an entire year to a transdisciplinary experience.

IntroductionPulsed field ablation is an emerging modality for catheter-based cardiac ablation. The main mechanism of action is irreversible electroporation (IRE), a threshold-based phenomenon in which cells die after exposure to intense pulsed electric fields. Lethal electric field threshold for IRE is a tissue property that determines treatment feasibility and enables the development of new devices and therapeutic applications, but it is greatly dependent on the number of pulses and their duration.MethodsIn the study, lesions were generated by applying IRE in porcine and human left ventricles using a pair of parallel needle electrodes at different voltages (500–1500 V) and two different pulse waveforms: a proprietary biphasic waveform (Medtronic) and monophasic 48 × 100 μs pulses. The lethal electric field threshold, anisotropy ratio, and conductivity increase by electroporation were determined by numerical modeling, comparing the model outputs with segmented lesion images.ResultsThe median threshold was 535 V/cm in porcine ((N = 51 lesions in n = 6 hearts) and 416 V/cm in the human donor hearts ((N = 21 lesions in n = 3 hearts) for the biphasic waveform. The median threshold value was 368 V/cm in porcine hearts ((N = 35 lesions in n = 9 hearts) cm for 48 × 100 μs pulses.DiscussionThe values obtained are compared with an extensive literature review of published lethal electric field thresholds in other tissues and were found to be lower than most other tissues, except for skeletal muscle. These findings, albeit preliminary, from a limited number of hearts suggest that treatments in humans with parameters optimized in pigs should result in equal or greater lesions.

Abstract Preclinical research remains the essential platform in the development and optimization of medical therapies and advancements in translational medicines. However, specifically to animal research, federal laws, and institutional policies require investigators to apply the principles of the 3R's (replacement, reduction, and refinement). The concept of benchtop models utilizing isolated organs, in which multiple variables can be controlled to recreate human function, has been innovative advancements in preclinical research models that adhere to these principles. More specifically, isolated perfused kidney (IPK) models have been invaluable preclinical tools that have led to numerous advancements over the decades, including understanding renal physiology, pharmacologic therapies, and improvements in renal transplantation. However, pre‐existing IPK models are not without their own limitations, leaving areas for improvement. An isolated perfused kidney apparatus was designed to best recreate human use conditions as a preclinical tool. Porcine renal blocks were chosen over the more commonly used rodent models, due to their greater similarities to human anatomies. Sixteen porcine kidney pairs obtained en bloc were extracted and placed onto an apparatus where aortic flows, pressures, and overall systemic temperatures were controlled. Organ viability was assessed in 10 renal blocks (n = 8 fresh and n = 2 previously frozen specimens) via both urinary flows and compositions at timepoints up to 180 min. Multimodality imaging, which included fluoroscopy, ultrasound, optical coherence tomography (OCT), and video scopes, was also employed to capture internal and external images to determine renal artery orientations and dimensions. Anatomical measurements and viability assessments of porcine renal blocks were successfully achieved in our perfusion model. Renal main artery diameters averaged smaller in our sample size than in human anatomy while also having more superior takeoff angles. Yet, the average lengths of each main segment were comparable to human anatomy: 32.09 ± 7.97 mm and 42.23 ± 7.33 mm in the left and right renal main artery, respectively. Urine production and urine composition of the fresh renal blocks, when compared to the frozen blocks and baseline perfusate, showed kidney viabilities of up to 3 h via excretion and retention of various metabolites. In this paper, we described a protocol for an isolated perfused kidney apparatus using large mammalian renal blocks. We believe this protocol to be an improvement from similar pre‐existing models in better representing human physiologic function while allowing for multimodal imaging. The resulting Visible Kidney™ preclinical model, which has shown viability after isolation and reperfusion, can be a fast and reliable tool for the development of medical devices while also reducing the unnecessary use of animals for research.

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.

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requiring use of sedatives or anesthetics. It was previously shown that adjusting pulse parameters may mitigate some of these effects, but not how these adjustments would affect electroporation’s efficacy. We investigated the effect of varying pulse parameters such as interphase and interpulse delay while keeping the duration and number of pulses constant on nerve stimulation, muscle contraction and assessing pain and electroporation efficacy, conducting experiments on human volunteers, tissue samples and cell lines in vitro. Our results show that using specific pulse parameters, particularly short high-frequency biphasic pulses with short interphase and long interpulse delays, reduces muscle contractions and pain sensations in healthy individuals. Higher stimulation thresholds were also observed in experiments on isolated swine phrenic nerves and human esophagus tissues. However, changes in the interphase and interpulse delays did not affect the cell permeability and survival, suggesting that modifying the pulse parameters could minimize adverse effects while preserving therapeutic goals in electroporation.

Abstract The structural morphology of coronary stents (e.g. stent expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically accurate three-dimensional (3D) reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents based on optical coherence tomography (OCT) and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility, and ability to perform computational fluid dynamics (CFD) studies. Our method has the following steps: 3D lumen reconstruction based on OCT and angiography, stent strut segmentation in OCT images, packaging, rotation and straightening of the segmented struts, planar unrolling of the segmented struts, planar stent wireframe reconstruction, rolling back of the planar stent wireframe to the 3D reconstructed lumen, and final stent volume reconstruction. We tested the accuracy and reproducibility of our method in stented patient-specific silicone models using micro-computed tomography (μCT) and stereoscopy as references. The clinical feasibility and CFD studies were performed in clinically stented coronary bifurcations. The experimental and clinical studies showed that our algorithm (1) can reproduce the complex spatial stent configuration with high precision and reproducibility, (2) is feasible in 3D reconstructing stents deployed in bifurcations, and (3) enables CFD studies to assess the local hemodynamic environment within the stent. Notably, the high accuracy of our algorithm was consistent across different stent designs and diameters. Our method coupled with patient-specific CFD studies can lay the ground for optimization of stenting procedures, patient-specific computational stenting simulations, and research and development of new stent scaffolds and stenting techniques.

Background: Paravalvular leak (PVL) is a frequent TAVR complication. Prospective identification of patients who are likely to develop PVL after TAVR would likely lead to improved outcomes. Prior studies have used geometric characteristics to predict the likelihood of PVL development, but prediction and quantification has not been done. One of the reasons is that it is difficult to predict the mechanical deformation of the native diseased aortic valve prior to implantation of the prosthetic valve, as existing calcifications likely contribute to the seal between the prosthetic valve and the aortic annulus. However, the relatively amount the native valve plays in preventing PVL is unknown.Methods: A retrospective chart review was conducted identifying patients with mild or greater PVL. One patient who had substantial PVL was identified and a 3D printed (pre-TAVR) aortic root was created. Balloon-expandable TAVR stent frames were implanted within the 3D printed root and a new model was created. Using this geometry, computational fluid dynamics (CFD) simulations were done to quantify PVL. The PVL flow path was iteratively decreased to simulate the space occupied by a crushed native aortic valve and PVL was quantified.Results: PVL was found to decrease as the space occupying the PVL area increased, demonstrating that the native aortic valve contributes to reducing regurgitation. CFD simulations demonstrated that within the patient analyzed, the native valve occupies between 3–40% of the PVL pathway.Conclusion:A priori techniques that predict the development of post TAVR PVL should account for the native diseased valve as our simulations demonstrate that it plays a role in reducing PVL.

Abstract 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.

Abstract Background Defects in α-dystroglycan (DG) glycosylation characterize a group of muscular dystrophies known as dystroglycanopathies. One of the key effectors in the α-DG glycosylation pathway is the glycosyltransferase fukutin-related protein (FKRP). Mutations in FKRP lead to a large spectrum of muscular dystrophies, including limb girdle muscular dystrophy 2I (LGMD2I). It remains unknown whether stem cell transplantation can promote muscle regeneration and ameliorate the muscle wasting phenotype associated with FKRP mutations. Results Here we transplanted murine and human pluripotent stem cell-derived myogenic progenitors into a novel immunodeficient FKRP-mutant mouse model by intra-muscular injection. Upon both mouse and human cell transplantation, we observe the presence of donor-derived myofibers even in absence of pre-injury, and the rescue of α-DG functional glycosylation, as shown by IIH6 immunoreactivity. The presence of donor-derived cells expressing Pax7 under the basal lamina is indicative of satellite cell engraftment, and therefore, long-term repopulation potential. Functional assays performed in the mouse-to-mouse cohort revealed enhanced specific force in transplanted muscles compared to PBS-injected controls. Conclusions Altogether, our data demonstrate for the first time the suitability of a cell-based therapeutic approach to improve the muscle phenotype of dystrophic FKRP-mutant mice.

Research purpose: The cardiac conduction system (CCS) regulates electrical impulses across the heart and cardiac arrhythmias cause structural remodelling of the CCS. Since its discovery over a century ago, the precise anatomy and differences between the human CCS in healthy, aged, and obese human hearts has remained relatively unknown. Using iodine potassium-iodide (I2KI) and graphene oxide (GO) as contrast agents for high-resolution micro-computed tomography (micro-CT), we explored and identified the anatomies of whole healthy, aged, and obese hearts, including their CCS. Basic procedures: Human specimens were obtained from 5 post-mortem hearts, under local ethical rules and stored in the Dobrzynski laboratory, under the Human Tissue Act 2004. Specimens were stained with I2KI or GO contrast agents before scanning with micro-CT. Data obtained from micro-CT was uploaded onto Amira v6.5 software for analysis, 3-dimensional reconstructions, and segmentation of relevant structures. Following micro-CT analyses, tissue blocks were cryosectioned and stained for histological assessments. Main findings: There are obvious anatomical structural differences between the healthy, aged and obese hearts. Compared to the healthy heart, the aged heart and obese heart had larger chambers; thicker myocardial walls; thicker blood vessels; more extensive nodal regions and connective tissue; more epicardial fat; and fewer Purkinje fibres.Our use of I2KI and GO as contrast agents for high-resolution micro-CT scanning contribute to - and expands - the current understanding of CCS structural variations between healthy, aged and obese human hearts.These current and novel techniques can have key impacts on our anatomical understandings for current treatments for cardiovascular disease and the development of mathematical models of aged and diseased hearts. Thus ultimately aiding in the reduction of cardiac morbidities and reduction of patient death rate.

Background: Transcatheter-based annuloplasty therapies for tricuspid regurgitation have demonstrated significant development over recent years. However, the tricuspid valve and neighboring vasculature and conductive tissue regions can present anatomical and device deployment challenges. This present study investigated the anatomical dimensions and spatial relationships of the cardiac structures essential to percutaneous annuloplasty procedures: the tricuspid annulus (TA), right coronary artery (RCA), and triangle of Koch border region. Methods: Measurements were derived from computational three-dimensional reconstructions of static magnetic resonance imaging scans of perfusion-fixed human hearts (n = 82) with preserved right-sided heart anatomies. This specimen set included heart samples presenting with prediagnosed atrioventricular valvular regurgitation. Results: Our anatomical assessments demonstrated that the TA to RCA proximities were intensified with the presence of atrioventricular valvular regurgitation, compared with healthy heart specimens. The minimal distances were frequently located between the lateral and posterior annular points. This annular region corresponds to the RCA distal segments and posterior descending branch origins. Greater portions and incidences of the RCA coursing parallel or inferior to the TA plane were recorded for these diseased hearts. Patient demographic variables (gender, age, and body mass index) were insignificant determinants of change for a majority of our results. Conclusions: These three-dimensional reconstructions provide insights to guide the development and future iterations of transcatheter tricuspid valve annuloplasty systems with regards to device anchoring, annular geometry, tissue proximities, and implantation considerations.

Transcatheter aortic valve replacement (TAVR) has become a popular treatment option for severe aortic stenosis for patients with a high risk for mortality with surgical aortic valve replacement (SAVR). Coronary artery occlusion (CAO) following the implantation of the device is a potential and sometimes devastating complication of this procedure, that provokes a sudden deterioration of hemodynamic status followed by cardiogenic shock and electrical instability. With patients that present a high risk for coronary obstruction, coronary protection with a chimney stenting technique is an effective strategy that can ensure coronary perfusion during TAVR in case of acute CAO. Utilizing Visible Heart® methodologies, a human heart was reanimated. A chimney stenting technique was implemented simultaneously with the deployment of a Medtronic Evolut™ Pro+ valve (Medtronic PLC; Minneapolis, MN, USA). The entire procedure was recorded utilizing endoscopic cameras, fluoroscopy, optical coherence tomography, and echocardiography. In addition to these procedural visualizations, post-procedural micro-computed tomography (micro-CT) was conducted to provide post-implantation imaging with approximately 60-micron resolution. Utilizing these imaging modalities in a reanimated human heart allows for the unique opportunity to collect data for TAVR procedures in real human anatomies for the subsequent educational uses by the physicians treating aortic valvular disease and/or the designers of future TAVR technologies and procedures.

Skeletal muscle relies on coordination between myogenic and non-myogenic interstitial cells for homeostasis and for regeneration and response to injury. Fibroadipogenic progenitors (FAPs) have recently been recognized as key modulators of signaling to promote myogenesis following injury. FAPs are also responsible for the fibrosis and fatty replacement of muscle tissue seen in many diseased states. While extensive use of surface markers to purify FAPs has been undertaken in the mouse system, in particular PDGFRA, markers for human FAPs are less well understood. Here, we show that CD73 can be used as a single positive marker to purify FAPs from the lineage-negative (CD45-neg, CD31-neg) fraction of skeletal muscle mononuclear cells. Although CD73 was previously found to be expressed in cultured myogenic cells, we find that this marker is only acquired upon culture and that the CD73+ fraction of human skeletal muscle has no myogenic activity. We show that Lin-neg CD73+ cells from human muscle undergo fat differentiation as well as fibrogenesis when exposed to appropriate activating signals in vitro. This simple single positive marker approach effectively enables isolation of human FAPs from fresh human skeletal muscle biopsies.

Abstract Biologgers can be used to monitor both human and animal physiology and behaviors, activity patterns, and/or environmental stressors. Monitoring of heart rates and rhythms, respiratory patterns, and activity in free-ranging bears can provide unique insights into physiological mechanisms. Such research can also influence the conservation of wildlife, the management of human–wildlife conflicts, and potentially human medicine. Here we describe our experiences with the development and utilization of three generations of implantable biologgers in American black and Eurasian brown bears (Ursus americanus and Ursus arctos arctos). These devices have enabled novel investigations into the underlying mechanisms for winter survival, including the discovery of an extreme respiratory sinus arrhythmias that acts to conserve energy while providing adequate circulation to maintain alertness (i.e., “fight or flight” behaviors). Extreme variations in heart rate have also been documented, including a 33.8 s asystole and a 261 beats/min sinus tachycardia in black bears and a 39.4 s asystole and a 240 beats/min sinus tachycardia in brown bears. Long-term data recording has also identified annual trends in heart rates and activity in both species. Combining physiological data with concurrent GPS collar locations provided insights into the impacts of human and environmental stressors (hunting, predation by other bears, road crossings, drones), which would not have been apparent through spatial data analysis alone. More recently, short-range wireless telemetry has allowed for real-time streaming of data via telemetry stations placed in remote den locations. Future iterations include transponders for biomonitoring and as an early warning system to aid in the prevention of poaching in free-ranging animals. In this review, we discuss the primary experimental capabilities of the current and next-generation systems. We highlight device evolution in terms of new physiological measurements (e.g., temperature, activity, impedance, posture), increased data storage capacity, improved wireless capabilities, and miniaturization to reduce the invasiveness of implantation procedures. These biologgers are now being applied to other species, and the possibilities seem limitless as technologies continue to advance.

Abstract Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees.

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.

Changes in cardiac tissue properties following the application of various ablation modalities may lead to the development of an array of associated complications. The application of either radio frequency (RF) or cryothermal ablations will alter the biomechanical properties of various cardiac tissues in a differential manner; in some cases, this may be attributable to increased incidences of cardiac tamponade, pulmonary vein stenosis, and/or atrial-esophageal fistula. Thus, a greater understanding of the underlying changes in tissue properties induced by ablative therapies will ultimately promote safer and more efficacious procedures. The effects of applied RF or cryothermal energies on the biomechanical properties of the pulmonary vein, left atrial, or right atrial samples (n=369 ) were examined from fresh excised porcine (n=35) and donated human tissue (n=11). RF ablations were found to reduce the tensile strength of the porcine cardiac specimens (p

The use of therapeutic ablation in patients with atrial fibrillation has become a mainstay in the treatment of this disease, yet often these individuals require multiple procedures. In other words, successful first time treatments are impacted by challenges, including the generation of linear lesions in certain anatomies like the mitral isthmus of the left atrium. Hence, there is a need to find ways to address the presence of unwanted conduction gaps at the time of lesion creation. In this paper, we describe a novel approach to examine conduction gaps, by using a proof of concept device to examine local electrical activation within the cardiac areas of an applied lesion, i.e., to locate gaps in the lesion set. To accomplish this, both epicardial and endocardial linear ablation lines composed of spot lesions with conduction gaps were created in a porcine model. The forces necessary to elicit monophasic action potentials (MAP) were collected from >200 measurements on the epicardium of the right ventricle. Ablations were then performed on the ventricular epicardium and left atrial mitral isthmus endocardially, while recording MAPs. We were able to successfully demonstrate the use of a proof of concept device to identify conduction gaps in linear lesion sets; furthermore, we were able to determine required contact forces to appropriately determine focal electrical changes of the underlying tissues. New catheter designs that incorporate capabilities to record focal MAPs could be employed clinically to better assess a given lesion quality and/or to determine the existence of an undesired conduction gap.

Data relative to anatomical measurements, spatial relationships, and device−tissue interaction are invaluable to medical device designers. However, obtaining these datasets from a wide range of anatomical specimens can be difficult and time consuming, forcing designers to make decisions on the requisite shapes and sizes of a device from a restricted number of specimens. The Visible Heart® Laboratories have a unique library of over 500 perfusion-fixed human cardiac specimens from organ donors whose hearts (and or lungs) were not deemed viable for transplantation. These hearts encompass a wide variety of pathologies, patient demographics, surgical repairs, and/or interventional procedures. Further, these specimens are an important resource for anatomical study, and their utility may be augmented via generation of 3D computational anatomical models, i.e., from obtained post-fixation magnetic resonance imaging (MRI) scans. In order to optimize device designs and procedural developments, computer generated models of medical devices and delivery tools can be computationally positioned within any of the generated anatomical models. The resulting co-registered 3D models can be 3D printed and analyzed to better understand relative interfaces between a specific device and cardiac tissues within a large number of diverse cardiac specimens that would be otherwise unattainable.