Rate of Change of Initial Intrinsicoid Deflection Predicts Endocardial Versus Epicardial Ventricular Tachycardia.

BACKGROUND: Assessment of origin of ventricular tachycardias (VTs) arising from epicardial vs endocardial sites are largely challenged by the available criteria and etiology of cardiomyopathy. Current electrocardiographic (ECG) criteria based on 12-lead ECG have varying sensitivity and specificity based on site of origin and etiology of cardiomyopathy. OBJECTIVES: This study sought to test the hypothesis that epicardial VT has a slower initial rate of depolarization than endocardial VT. METHODS: We developed a method that takes advantage of the fact that electrical conduction is faster through the cardiac conduction system than the myocardium, and that the conduction system is primarily an endocardial structure. The technique calculated the rate of change in the initial VT depolarization from a signal-averaged 12-lead ECG. We hypothesized that the rate of change of depolarization in endocardial VT would be faster than epicardial. We assessed by applying this technique among 26 patients with VT in nonischemic cardiomyopathy patients. RESULTS: When comparing patients with VTs ablated using epicardial and endocardial approaches, the rate of change of depolarization was found to be significantly slower in epicardial (6.3 ± 3.1 mV/s vs 11.4 ± 3.7 mV/s; P < 0.05). Statistical significance was found when averaging all 12 ECG leads and the limb leads, but not the precordial leads. Follow up analysis by calculation of a receiver-operating characteristic curve demonstrated that this analysis provides a strong prediction if a VT is epicardial in origin (AUC range 0.72-0.88). Slower rate of change of depolarization had high sensitivity and specificity for prediction of epicardial VT. CONCLUSIONS: This study demonstrates that depolarization rate analysis is a potential technique to predict if a VT is epicardial in nature.

Long-term monitoring of stimulated lower leg skeletal muscle forces compared with voluntary contractions in myopathy patients - A five-year follow-up report on 5 adults.

OBJECTIVE: Long-term assessments of lower leg muscle forces in ambulant patients with distal myopathies. METHODS AND MATERIALS: Over a five-year period, we measured involuntary, nerve-stimulated, isometric torques of the ankle dorsiflexors in a group of ambulant patients with myopathies and compared results with voluntary Manual Muscle Tests (MMT). RESULTS: From ten recruited patients, five could finish the five-year protocol. Twenty-seven force measurements sessions (one per year; 1,5 hours duration each) were performed. These patients exhibited low, stable torques or increased minimally (0.2 Newtonmeter, versus 0.1 Nm, ns; 0.7 vs. 1.0, ns; 3.4 vs. 3.5, ns; 0.2 vs. 0.1, ns; 0.8 vs. 1.5, P 0.0004 initial values vs. 5-year values, [norm: 3.9-5.7 Nm]). A 6th patient, eliciting low torque values (0.1 Nm) early passed away. Contraction times inversely correlated with MMT. MMT provided similar overall force abilities. CONCLUSIONS: Long-term monitoring of lower leg muscle forces in ambulant patients is limited by the patient's health status. In a small group of patients, stimulated lower leg forces did not worsen over many years relative to their diagnosed myopathies. Tracking involuntary forces, could be a useful monitoring providing phenotypic information, in addition to MMT. Future devices should be small and be simply self-applying, designed for subjects' domestic use and web-based data transfer. CLINICALTRIALS: gov NCT00735384.

Ventricular Epicardial Adipose Distribution on Human Hearts: 3-Dimensional Reconstructions and Quantitative Assessments.

Epicardial interventions have forged new frontiers in cardiac ablation and device therapies. Healthy human hearts typically present with significant adipose tissue layers superficial to the ventricular myocardium and may hinder success or increase the complexities of epicardial interventions. We quantitatively evaluated the distribution of epicardial adipose tissue on the surface of human hearts and provided high-fidelity 3-dimensional reconstructions of these epicardial adipose tissue layers. The regional thickness of adipose tissues was analyzed at 51 anatomical reference points surrounding both ventricles and compared to specific patient demographics. Adipose deposits on the human hearts displayed characteristic patterns, with the thickest accumulations along the interventricular septa (anterior, 9.01 ± 0.50 mm; posterior, 6.78 ± 0.50 mm) and the right ventricular margin (7.44 ± 0.57 mm). We provide one of the most complete characterizations of human epicardial adipose location and relative layer thickness. These results are considered fundamental for an underlying anatomic understanding when performing procedures within the pericardial space.

The Effects of Interphase and Interpulse Delays and Pulse Widths on Induced Muscle Contractions, Pain and Therapeutic Efficacy in Electroporation-Based Therapies.

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.

Joint engineering-medical school programs prepare physicians for clinical challenges: An observational study.

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.

Determination of lethal electric field threshold for pulsed field ablation in ex vivo perfused porcine and human hearts.

Introduction: Pulsed 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. Methods: In 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. Results: The 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. Discussion: The 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.

A Computational Pipeline for Patient-Specific Prediction of the Postoperative Mitral Valve Functional State.

While mitral valve (MV) repair remains the preferred clinical option for mitral regurgitation (MR) treatment, long-term outcomes remain suboptimal and difficult to predict. Furthermore, pre-operative optimization is complicated by the heterogeneity of MR presentations and the multiplicity of potential repair configurations. In the present work, we established a patient-specific MV computational pipeline based strictly on standard-of-care pre-operative imaging data to quantitatively predict the post-repair MV functional state. First, we established human mitral valve chordae tendinae (MVCT) geometric characteristics obtained from five CT-imaged excised human hearts. From these data, we developed a finite-element model of the full patient-specific MV apparatus that included MVCT papillary muscle origins obtained from both the in vitro study and the pre-operative three-dimensional echocardiography images. To functionally tune the patient-specific MV mechanical behavior, we simulated pre-operative MV closure and iteratively updated the leaflet and MVCT prestrains to minimize the mismatch between the simulated and target end-systolic geometries. Using the resultant fully calibrated MV model, we simulated undersized ring annuloplasty (URA) by defining the annular geometry directly from the ring geometry. In three human cases, the postoperative geometries were predicted to 1 mm of the target, and the MV leaflet strain fields demonstrated close agreement with noninvasive strain estimation technique targets. Interestingly, our model predicted increased posterior leaflet tethering after URA in two recurrent patients, which is the likely driver of long-term MV repair failure. In summary, the present pipeline was able to predict postoperative outcomes from pre-operative clinical data alone. This approach can thus lay the foundation for optimal tailored surgical planning for more durable repair, as well as development of mitral valve digital twins.

A role for ultra-high resolution three-dimensional printed human heart models.

INTRODUCTION: Echocardiography is essential for diagnosing and assessing the severity of perioperative structural and functional heart disease. Yet, educational opportunities to better understand echocardiography-based cardiac anatomy remain limited by the two-dimensional display, lack of anatomic details, variability of heart models, and costs and global access of training. METHODS: We performed micro computed tomography of human heart specimens not suitable for orthotopic transplantation. We created high-resolution computational 3D models of different human hearts, sliced them in the different recommended American Society of Echocardiography views, and 3D printed them using different materials. RESULTS: We scanned, 3D modeled, and 3D printed a variety of human hearts both healthy and diseased. We have made the models available in the cardiac operating rooms and routinely use them for teaching anesthesia residents and cardiothoracic anesthesia fellows about basic and advanced echocardiographic views, cardiopulmonary bypass cannulation strategies, and valvular pathology and planned interventions. CONCLUSION: We have generated a library of 3D printed hearts to display the recommended echocardiographic views as a unique educational tool designed to safely accelerate the understanding of absolute and relative human cardiac anatomy and pathology, especially related to gaining advanced appreciation of clinically employed perioperative echocardiography.

A Multiscale Computational Model of Skeletal Muscle Electroporation Validated Using In Situ Porcine Experiments.

OBJECTIVE: The goal of our study was to determine the importance of electric field orientation in an anisotropic muscle tissue for the extent of irreversible electroporation damage by means of an experimentally validated mathematical model. METHODS: Electrical pulses were delivered to porcine skeletal muscle in vivo by inserting needle electrodes so that the electric field was applied in direction either parallel or perpendicular to the direction of the muscle fibres. Triphenyl tetrazolium chloride staining was used to determine the shape of the lesions. Next, we used a single cell model to determine the cell-level conductivity during electroporation, and then generalised the calculated conductivity changes to the bulk tissue. Finally, we compared the experimental lesions with the calculated field strength distributions using the Sørensen-Dice similarity coefficient to find the contours of the electric field strength threshold beyond which irreversible damage is thought to occur. RESULTS: Lesions in the parallel group were consistently smaller and narrower than lesions in the perpendicular group. The determined irreversible threshold of electroporation for the selected pulse protocol was 193.4 V/cm with a standard deviation of 42.1 V/cm, and was not dependent on field orientation. CONCLUSION: Muscle anisotropy is of significant importance when considering electric field distribution in electroporation applications. SIGNIFICANCE: The paper presents an important advancement in building up from the current understanding of single cell electroporation to an in silico multiscale model of bulk muscle tissue. The model accounts for anisotropic electrical conductivity and has been validated through experiments in vivo.

Multimodal Imaging of a Culotte Bifurcation Procedure in the Left Main Coronary Artery of a Perfusion-Fixed Human Heart: Step-by-Step with Serial Micro-CT Analyses.

Percutaneous coronary intervention can be a high-risk procedure that would benefit from optimizing device-tissue interactions between stents and coronary vessels. Using a perfusion-fixed human heart with coronary artery disease, we performed a percutaneous coronary intervention of the left main coronary artery bifurcation. This heart was perfused and multimodal imaging was utilized to view the procedure with direct visualization, fluoroscopy, and optical coherence tomography (OCT). We followed the European Bifurcation Club's guidelines to perform a single-stent bifurcation before transitioning to a two-stent Culotte technique. After each procedural step, the heart was removed from the perfusion apparatus and transferred to a micro-CT scanner to obtain unique scans. We conducted apposition analyses of the computational 3D models from micro-CT DICOM datasets, and compared them to the results from direct visualization and commercial OCT's Apposition Indicator software. Additional measurements of resulting coronary anatomic expansions were taken to determine the potential roles of each step in improving procedural outcomes. Micro-CT images show stent deformation during a percutaneous coronary intervention (provisional to Culotte bifurcation procedure) in an isolated diseased human heart.

Preclinical research performed on reanimated/perfused swine kidneys: The Visible Kidney™ methodologies.

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.

Post-procedure micro-CT analyses of coronary artery stenting in left main vessels of reanimated and perfusion-fixed human hearts.

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.

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.

Aortic valve fenestrations: Macroscopic assessment and functional anatomy study.

Aortic valve fenestrations are defined as a loss of aortic valve leaflet tissue. They are a common but overlooked finding with unclear significance. The aim of this study was to investigate the varied functional anatomies of aortic valve fenestrations. A total of 400 formalin-fixed autopsied human hearts were macroscopically assessed and the function of the aortic valve of 16 reanimated human hearts were imaged using Visible Heart® methodologies. Aortic valve leaflet fenestrations were present in 43.0% of autopsied hearts (in one leaflet in 24.0%, in two leaflets 16.0%, in all leaflets 3.0%). Fenestrations were mostly present in left (25.5%) followed by right (23.3%) and noncoronary leaflet (16.3%). In 93.8% of cases, the fenestrations form clusters and were mainly located at the free edge of the leaflet in the commissural area (95.4%). Hearts with aortic valve fenestrations had significantly larger aortic valve diameters and aortic valve areas (p < 0.001). The average surface area sizes of fenestrations were 23.8 ± 16.6 mm2 , and the areas were largest for left followed by right and noncoronary leaflet fenestrations (p < 0.001). The fenestration areas positively correlated with donor age (r = 0.31; p = 0.02). Significant hypermobility and subjective weakening of the leaflet adhesion levels of the fenestrated regions were observed. In conclusion, fenestrations of the aortic leaflets are frequent, and their sizes may be significant. They occur in all age groups, yet their size increase with aging. Fragments of leaflets with fenestrations show different behaviors during the cardiac cycle versus unchanged areas.

A Free-Access Online Interactive Simulator to Enhance Perioperative Transesophageal Echocardiography Training Using a High-Fidelity Human Heart 3D Model.

The clinical uses of perioperative transesophageal echocardiography have grown exponentially in recent years for both cardiac and noncardiac surgical patients. Yet, echocardiography is a complex skill that also requires an advanced understanding of human cardiac anatomy. Although simulation has changed the way echocardiography is taught, most available systems are still limited by investment costs, accessibility, and qualities of the input cardiac 3-dimensional models. In this report, the authors discuss the development of an online simulator using a high-resolution human heart scan that accurately represents real cardiac anatomies, and that should be accessible to a wide range of learners without space or time limitations.

Nerve Protection During Prostate Cryosurgery.

Cryosurgery is a minimally invasive approach to the treatment of focal prostate cancer (PCa). A major complication is the cryoinjury to the cavernous nerve in the neurovascular bundle (NVB). This nerve cryoinjury halts conduction of action potentials (APs) and can eventually result in erectile dysfunction and therefore diminished quality of life for the patient. Here, we propose the application of cryoprotective agents (CPA) to the regions of the nerves in the NVB, prior to prostate cryosurgery, to minimize non-recoverable loss of AP conduction. We modeled a cryosurgical procedure based on data taken during a clinical case and applied ex-vivo porcine phrenic nerves and rat sciatic nerve with temperature profile of NVB. The APs were measured before and after the CPA exposures and during 3 h of recovery. Comparisons of AP amplitude recovery with various CPA compositions reveal that certain CPAs (e.g., 5% DMSO + 7.5% Trehalose and 5% M22 for porcine and rat nerves, respectively) showed little or no toxicity and effective cryoprotection from freezing (on average 48% and 30% of recovered AP, respectively). In summary, we demonstrate that neural conduction can be preserved after exposure to freezing conditions if CPAs are properly selected and deployed onto the nerve.

Novel Imaging Technologies for Accurate Assessment of Cardiac Allograft Performance.

Purpose of the Review: The current lack of objective and quantitative assessment techniques to determine cardiac graft relative viability results in risk-averse decision-making, which negatively impact the utilization of cardiac grafts. The purpose of this review is to highlight the current deficiencies in cardiac allograft assessment before focusing on novel cardiac assessment techniques that exploit conventional and emerging imaging modalities, including ultrasound, magnetic resonance, and spectroscopy. Recent Findings: Extensive work is ongoing by the scientific community to identify improved objective metrics and tools for cardiac graft assessment, with the goal to safely increasing the number and proportion of hearts accepted for transplantation. Summary: This review briefly discusses the in situ and ex vivo tools currently available for clinical organ assessment, before focusing on the individual capabilities of ultrasound, magnetic resonance, and spectroscopy to provide insightful, non-invasive information regarding cardiac graft functional and metabolic status that may be used to predict outcome after transplantation.

Multimodal Imaging of a Chimney-Stenting Procedure Performed Simultaneously with a Transcatheter Aortic Valve Replacement (TAVR) in a Reanimated Human Heart including Post-Implant Analyses.

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.

The native aortic valve reduces paravalvular leak in TAVR patients.

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.