Heart Model Research Articles

Microfluidic organ-on-a-chip models of human lungs and heart: A review

A micro-physiological system is another term for an organ-on-a-chip. Due to the idea's widespread use in drug discovery, precision medicine, and drug screening, interest in it has increased recently. The primary message of this article is to illustrate how artificial drug proof can closely imitate the human body in every regard. Important work for a biomimetic system of physiological organs based on a microfluidic chip using cell biology, engineering, and biomaterials technology. In addition, the use and effectiveness of the gut-on-a-chip, liver-on-a-chip, lung-on-a-chip, and heart-on-a-chip are examined. We have discussed the current status of this project, OOC prospects for the future, and opportunities for microfluidic devices and organs on a chip in this section.

Experience in the development of a system for repeated prosthetic heart valves

The failure of heart valve bioprostheses, requiring repeated intervention to replace them, is a serious drawback that narrows the scope of such devices. The present study demonstrates the experimental investigation of a medical device designed to partially solve the problem of repeated interventions on heart valves, primarily with an emphasis on reducing the duration and trauma of such procedures due to the sutureless balloon implantation method of the «valvein- valve» method.Material and methods. The paper presents a series of in silico, in vitro and in vivo experiments to evaluate various aspects of the device under development. Numerical modeling of the final shape setting to the supporting frame of the heart valve prosthesis to select the most promising concept for prototyping was carried out in the Abaqus/CAE (Dassault Systèmes, France) based on the finite element method. The selected optimal support frame model was prototyped in the form of a series of prosthesis samples of four standard sizes for hydrodynamic studies of quantitative characteristics in vitro. The study was carried out in the Vivitro Labs unit (Vivitro Labs, Canada), imitating the physiological mode of the heart, the prostheses were examined for the mitral position. The developed prototypes of the device were supplemented with related products, an implant holder and a balloon catheter, after which the proposed method of sutureless fixation was validated in an in vitro implantation procedure on a bovine heart model and a series of in vivo (n = 3) chronic experiments on animals.Results. In the course of numerical simulation, it was shown that in Model No. 3 of the supporting frame of the prosthesis, the smallest stresses occur – with an amplitude of up to 490 MPa. For other concepts (Models No. 1 and No. 2), this indicator was significantly higher, 543 and 514 MPa, respectively. Prototypes obtained on the basis of the selected shape of the support frame demonstrated satisfactory hydrodynamic characteristics: effective hole area 190-261 mm2, regurgitation volume 6–9 ml/cycle, average transprosthetic gradient 4.4–6.4 mmHg, depending on size. The study of the technology of sutureless balloon implantation in an in vitro model of the heart and the subsequent chronic experiment on sheep confirmed the main idea of the system – the possibility of a significant reduction in the duration of repeated prosthetics. It has been shown that the time of suture implantation of the “classic” frame prosthesis of the mitral valve is 23–29 minutes, with a total access time of 41–52 minutes. When implanting the experimental device, the sutureless prosthesis itself took 4–6 minutes, access time 24–29 minutes. At the same time, one-month results of an echocardiographic study of the operation of the prosthesis demonstrated satisfactory hemodynamics.Conclusions. This work demonstrates a consistent series of tests of the system being developed for repeated heart valve replacement, which substantiates some design solutions, confirms the effectiveness and viability of the chosen approach to sutureless minimally invasive implantation.

Quantification of Myocardial Contraction Fraction with Three-Dimensional Automated, Machine-Learning-Based Left-Heart-Chamber Metrics: Diagnostic Utility in Hypertrophic Phenotypes and Normal Ejection Fraction.

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA (n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43-67.79%), mean values for MCF were significantly reduced in HCM-48.55% (43.46-54.86% p < 0.001)-and CA-40.92% (36.68-46.84% p < 0.002)-but not in IH-59.35% (53.22-64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R2 = 0.136) and the four study subgroups (healthy adults, R2 = 0.039 IH, R2 = 0.089; HCM, R2 = 0.225; CA, R2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients.

Transapical electrosurgical laceration and stabilization of mitral clips followed by transcatheter mitral valve replacement—A one-stop shop

ObjectiveElectrosurgical laceration and stabilization of mitral clips (ELASTA-CLIP) is a bail-out technique to recreate a single-orifice mitral valve after transcatheter edge-to-edge repair (TEER) with subsequent transcatheter mitral valve replacement (TMVR). This technique is a novel option for patients with significant residual mitral regurgitation after TEER with high risk for conventional surgery. The original ELASTA CLIP procedure features a transseptal approach, whereas the TMVR with the Tendyne bioprosthesis has a transapical access. Hereby we tested the hypothesis that a modified transapical ELASTA CLIP technique can be safely applied transapically allowing a straightforward one-stop shop access strategy. MethodsWe developed the procedural steps in a porcine passive-beating heart model and applied the modified technique with subsequent TMVR in 2 consecutive patients with severe mitral regurgitation after previous TEER. Patients were followed up to 30 days. ResultsThe modified transapical ELASTA CLIP procedure was successful in both patients. The mean total procedure time was 118 minutes, and the mean fluoroscopy duration 22 minutes. At 30 days’ follow-up, both patients were alive without bleeding complications, reintervention, or prosthetic valve dysfunction. ConclusionsThe modified transapical ELASTA CLIP procedure is technically feasible and safe at 30 days. Procedure times are lower compared with previous reports of the original transseptal approach.

Reducing the Incidence of Post – Myocardial Infarction Heart Failure in an Era of Improved Primary Percutaneous Coronary Intervention through Novel Therapeutics (Protein Kinase C Beta II Inhibitor)

Heart failure (HF) complicating myocardial infarction (MI) remains a major source of morbidity, mortality and a huge health-care burden in the world. The incidence of symptomatic HF after primary percutaneous coronary intervention (PPCI) has been widely reported. PPCI has improved early survival of MI, but its impact on downstream HF is deliberated. Infarct size is the major determinant of the development of HF and prognosis. Efforts to reduce the size will therefore have a significant impact on the incidence of HF after PPCI. Resuscitation of the ischemic myocardium, heavily rests on timely reperfusion. However, cardiomyocyte death still occurs due to ischemic/reperfusion (I/R) injury mediated by oxidative stress. This phenomenon is known to largely contribute to the size of infarct. Activation by protein kinase C-βII (PKCβII) is attributed to the generation of reactive oxygen species (ROS) during this process and inhibition of this drive could salvage the myocardial tissue and subsequently preserve cardiac function. We hypothesized that myristic acid (Myr) and trans-activator of transcription (Tat) conjugated PKCβII inhibitor (Myr-Tat-PKCβII-) will exhibit robust cardioprotective effects in an in vivo porcine model, reflective of our ex vivo rat hearts model. Male Yorkshire pigs underwent regional I/R by occluding the second branch of the left anterior descending artery (LAD). This was achieved in the catheterization laboratory guided by fluoroscopy. A bolus of Myr-Tat-PKCβII- or scrambled control was infused into the LAD during reperfusion. Cardiac function was evaluated by an echocardiogram during the entire procedure, and assessed as the relative change at the end of 3hr reperfusion compared to baseline. Post-reperfused hearts were stained with Evans Blue dye to identify the area a risk and 1% triphenyltetrazolium chloride to delineate the area of necrosis. Infarct size and ejection fraction (EF) were analyzed via Student’s t- test. From mean baseline EF (61.4±0.5%), Myr-Tat-PKCβII- preserved EF with a relative change of 1.2±2.8% compared to 8.9±2.2% in control hearts (p&lt;0.05) at the end of reperfusion. Myr-Tat-PKCβII- reduced infarct size to 13.5±3.9% (n=4) compared to scrambled control hearts (27.5 ±7.9%, n=6). These results suggest Myr-Tat-PKCβII- significantly preserve EF after PPCI and reduce infarct size when given at reperfusion onset. This study gives a solid premise for future examination of Myr-Tat-PKCβII- in an 8 week in-vivo, porcine MI survival study.

Acute aerobic exercise regulation of myocardial calcium homeostasis involves CASQ1, CASQ2, and TRDN.

Exercise maintains cardiac calcium homeostasis and promotes cardiovascular health. This study explored temporal changes of calcium-related myocardial transcriptome changes during the recovery phase following a single bout of moderate-intensity aerobic exercise. Healthy male Sprague-Dawley rats were anesthetized with sodium pentobarbital after moderate-intensity aerobic exercise at four time points (0, 12, 24, and 72 h postexercise). The hearts were removed and RNA-seq and bioinformatics analyses were used to examine temporal transcriptional changes in the myocardium. Casq1, Casq2, and Trdn were identified as key genes in the regulation of calcium homeostasis during myocardial recovery. The highest expression of Casq1, Casq2, and Trdn genes and the proteins they encode occurred 24 h after exercise. An in vitro calcium overload heart model using the Langendorff heart perfusion method was used to examine myocardial calcium buffering capacity. Calcium overload caused the least changes in left ventricular developed pressure, infarct area, Lactate dehydrogenase release, and extent of morphological damage to myocardial cells, with the highest protein expressions of CASQ1, CASQ2, and TRDN at 24 h after acute exercise. This study indicates that maximal myocardial Ca2+ buffering capacity occurs 24 h postexercise in rats. Our study provides insights into exercise-mediated improvements in cardiovascular function and exercise preconditioning.NEW & NOTEWORTHY Acute aerobic exercise upregulates myocardial Casq1, Casq2, and Trdn genes and the proteins they encode in rats. Higher protein levels of CASQ1, CASQ2, and TRDN conferred an improved ability of the myocardium to resist calcium overload. Furthermore, 24 h postexercise is the time point with optimal myocardial calcium buffer capacity.

Thermomechanical stress analyses of nanowarming-assisted recovery from cryopreservation by vitrification in human heart and rat heart models.

This study investigates thermomechanical stress in cryopreservation by vitrification of the heart, while exploring the effects of nanowarming-assisted recovery from cryogenic storage. This study expands upon a recently published study, combining experimental investigation and thermal analysis of cryopreservation on a rat heart model. Specifically, this study focuses on scenarios with variable concentrations of silica-coated iron-oxide nanoparticles (sIONPs), while accounting for loading limitations associated with the heart physiology, as well as the properties of cryoprotective agent (CPA) solution and the geometry of the container. Results of this study suggest that variable sIONP concentration based on the heart physiology will elevate mechanical stresses when compared with the mathematically simplified, uniform distribution case. The most dangerous part of rewarming is below glass transition and at the onset of nanowarming past the glass transition temperature on the way for organ recovery from cryogenic storage. Throughout rewarming, regions that rewarm faster, such as the chambers of the heart (higher sIONP concentration), undergo compressive stresses, while the slower rewarming regions, such as the heart myocardium (low sIONP concentration), undergo tension. Being a brittle material, the vitrified organ is expected to fail under tension in lower stresses than in compression. Unfortunately, the location and magnitude of the maximum stress in the investigated cases varied, while general rules were not identified. This investigation demonstrates the need to tailor the thermal protocol of heart cryopreservation on a case-by-case basis, since the location, orientation, magnitude, and instant at which the maximum mechanical stress is found cannot be predicted a priori. While thermomechanical stress poses a significant risk to organ integrity, careful design of the thermal protocol can be instrumental in reducing the likelihood of structural damage, while taking full advantage of the benefits of nanowarming.

The Concept of Spiritual Personality Based on the Sound Heart Model

The theory of Sound Heart in spiritual health was investigated in 2019 in "Chair of Behavioral Sciences" in Shahid Beheshti University by psychology professors. Then it was investigated in the "Chair of Transcendental Sciences" by the clerics of the seminary. It received the permission to perform the "Pre-Semitism". The model was investigated with the presence of ten judges, critics and observers of the "Supreme Council of Cultural Revolution" in the meeting of 2022. Asadzandi, the theorist of the Sound heart model by implementing the suggestions of professors, completed the theory according to the criteria of writing theorizing plans in the "Support Board for Theorizing, Criticism and Scientific Debate Chairs of the Supreme Council of the Cultural Revolution". The final meeting was held in 2023. Sound Heart Model was approved by this important scientific-executive center in Iran. The following content is part of the topics discussed in that meeting.

CREB-binding protein and HIF-1α/β-catenin to upregulate miR-322 and alleviate myocardial ischemia-reperfusion injury.

Myocardial ischemia/reperfusion injury (MIRI) is a prevalent condition associated with numerous critical clinical conditions. miR-322 has been implicated in MIRI through poorly understood mechanisms. Our preliminary analysis indicated potential interaction of CREB-binding protein (CBP), a transcriptional coactivator and acetyltransferase, with HIF-1α/β-catenin, which might regulate miR-322 expression. We, therefore, hypothesized that CBP/HIF-1α/β-catenin/miR-322 axis might play a role in MIRI. Rat cardiomyocytes subjected to oxygen-glucose deprivation /reperfusion (OGD/R) and Langendorff perfused heart model were used to model MIRI in vitro and in vivo, respectively. We used various techniques such as CCK-8 assay, transferase dUTP nick end labeling staining, western blotting, RT-qPCR, chromatin immunoprecipitation (ChIP), dual-luciferase assay, co-immunoprecipitation (Co-IP), hematoxylin and eosin staining, and TTC staining to assess cell viability, apoptosis, and the levels of CBP, HIF-1α, β-catenin, miR-322, and acetylation. Our results indicate that OGD/R in cardiomyocytes decreased CBP/HIF-1α/β-catenin/miR-322 expression, increased cell apoptosis and cytokines, and reduced cell viability. However, overexpression of CBP or miR-322 suppressed OGD/R-induced cell injury, while knockdown of HIF-1α/β-catenin further exacerbated the damage. HIF-1α/β-catenin bound to miR-322 promoter to promote its expression, while CBP acetylated HIF-1α/β-catenin for stabilization. Overexpression of CBP attenuated MIRI in rats by acetylating HIF-1α/β-catenin to stabilize their expression, resulting in stronger binding of HIF-1α/β-catenin with the miR-322 promoter and subsequent increased miR-322 levels. Therefore, activating CBP/HIF-1α/β-catenin/miR-322 signaling may be a potential approach to treat MIRI.

Is N-methylacetazolamide a possible new therapy against ischemia-reperfusion injury?

The increase of intracellular Ca2+ concentration, produced principally by its influx through the L-type Ca2+ channels, is one of the major contributors to the ischemia-reperfusion injury. The inhibition of those channels in different experimental models was effective to ameliorate the post-ischemic damage. However, at a clinical level, the results were contradictory. Recent results of our group obtained in an ¨ex vivo¨ heart model demonstrated that a chemical derived from acetazolamide, the N-methylacetazolamide (NMA) protected the heart against ischemia-reperfusion injury, diminishing the infarct size and improving the post-ischemic recovery of myocardial function and mitochondrial dynamic. A significant inhibitory action on L-type Ca2+ channels was also detected after NMA treatment, suggesting this action as responsible for the beneficial effects on myocardium exerted by this compound. Although these results were promising, the effectiveness of NMA in the treatment of ischemic heart disease in humans as well as the advantages or disadvantages in comparison to the classic calcium antagonists needs to be investigated.

Prespecialist perceptions of three-dimensional heart models in anatomical education.

This article aims to discuss the use of three-dimensional (3D) printed models of vascular variation cases as an educational tool for undergraduate and postgraduate anatomy students. This advanced study involved ten anatomy assistants who were provided with five distinct cases of congenital cardiovascular variations, each accompanied by a computed tomography angiography (CT-A) and 1:1 solid model format. The residents were asked to generate perceptions for both formats and then compare these perceptions based on identifying the variation, defining the structural features, and evaluating relevant educational perspectives. The vascular origin measurement values compared to the statistically evaluated real values of the related cases showed that models were 1:1 identical copies. Qualitative assessment feedback from five stations supported the usefulness of 3D models as educational tools for organ anatomy, simulation of variational structures, and overall medical education and anatomy training. Models showcasing different anatomical variations such as aortic arch with Type 2 pattern, a right-sided aortic arch with Type 2 pattern, an aberrant right subclavian artery, arteria lusoria in thorax, and a left coronary artery originating from pulmonary trunk in an Alcapa type pattern allow for better analysis due to their complex anatomies, thus optimizing the study of variation-specific anatomy. The perception level in the 3D model contained higher points in all of the nine parameters, namely identification of cardiovascular variations, defining the vessel with anomaly, aortic arch branch count and appearance order, feasibility of using it in peers and student education. 3D models received a score 9.1 points, while CT-A images were rated at 4.8 out of 10. 3D printed anatomical models of variational cardiovascular anatomy serve as essential components of anatomy training and postgraduate clinical perception by granting demonstrative feedback and a superior comprehension of the visuospatial relationship between the anatomical structures.

An FSEI approach for the assessment of stenotic aortic valve effects on the left heart hemodynamics

Fluid–structure-electrophysiology interaction (FSEI) deals with (i) the active contraction of the myocardium, (ii) the complex blood motion and (iii) the related deformation of the cardiac tissues. This three-way coupled approach is key for obtaining predictive cardiac information as the tissue kinematics comes as a part of the solution, rather than being imposed as a boundary condition. FSEI is here applied to study the effects induced by aortic valve stenosis on the hemodynamics. This pathology, typically occurring in elderly individuals, is caused by the stiffening of the valve leaflets, thus impairing the valve functioning and reducing the pumping efficiency of the heart. The disease severity is gradually increased within a high-fidelity model for the left heart, while keeping the same geometrical, elastic and electrophysiological properties of the cardiac system, which would be impossible with in-vivo experiments. We observe an increase of the transvalvular pressure drop and of the peak velocity of the systolic jet velocity along with a reduction of the cardiac ejection fraction. Furthermore, a stenotic aortic valve significantly alters the wall shear stresses and their spatial distribution over the aortic arch and valve leaflets, which may induce a remodeling process of the ventricular myocardium. The numerical results from the multi-physics model are fully consistent with the clinical experience, thus further opening the way for computational engineering aided medical diagnostic.

Utility of late gadolinium enhancement on magnetic resonance imaging in hypertrophic cardiomyopathy patients in an Indian cohort

This prospective observational study sought to correlate segmental late gadolinium enhancement (LGE) seen in cardiac magnetic resonance imaging with occurrence of ventricular arrhythmias (VAs) in patients with hypertrophic cardiomyopathy. LGE was assessed in a 17-segmental model of heart. Of 57 patients, VAs were present in 26.3% of patients and 10.5% had sustained ventricular tachycardia. LGE was present in 43.9% of patients. Presence of LGE in 4 or more segments was associated with VAs with a sensitivity of 73% and specificity of 76% with area under curve of 0.733 in C-statistics.

Three-Dimensional Bioprinting in Cardiovascular Disease: Current Status and Future Directions.

Three-dimensional (3D) printing plays an important role in cardiovascular disease through the use of personalised models that replicate the normal anatomy and its pathology with high accuracy and reliability. While 3D printed heart and vascular models have been shown to improve medical education, preoperative planning and simulation of cardiac procedures, as well as to enhance communication with patients, 3D bioprinting represents a potential advancement of 3D printing technology by allowing the printing of cellular or biological components, functional tissues and organs that can be used in a variety of applications in cardiovascular disease. Recent advances in bioprinting technology have shown the ability to support vascularisation of large-scale constructs with enhanced biocompatibility and structural stability, thus creating opportunities to replace damaged tissues or organs. In this review, we provide an overview of the use of 3D bioprinting in cardiovascular disease with a focus on technologies and applications in cardiac tissues, vascular constructs and grafts, heart valves and myocardium. Limitations and future research directions are highlighted.

Submillimeter Multifunctional Ferromagnetic Fiber Robots for Navigation, Sensing, and Modulation.

Small-scale robots capable of remote active steering and navigation offer great potential for biomedical applications. However, the current design and manufacturing procedure impede their miniaturization and integration of various diagnostic and therapeutic functionalities. Herein, submillimeter fiber robots that can integrate navigation, sensing, and modulation functions are presented. These fiber robots are fabricated through a scalable thermal drawing process at a speed of 4 meters per minute, which enables the integration of ferromagnetic, electrical, optical, and microfluidic composite with an overall diameter of as small as 250µm and a length of as long as 150m. The fiber tip deflection angle can reach up to 54o under a uniform magnetic field of 45 mT. These fiber robots can navigate through complex and constrained environments, such as artificial vessels and brain phantoms. Moreover, Langendorff mouse hearts model, glioblastoma micro platforms, and in vivo mouse models are utilized to demonstrate the capabilities of sensing electrophysiology signals and performing a localized treatment. Additionally, it is demonstrated that the fiber robots can serve as endoscopes with embedded waveguides. These fiber robots provide a versatile platform for targeted multimodal detection and treatment at hard-to-reach locations in a minimally invasive and remotely controllable manner.

Biotechnological advances and applications of human pluripotent stem cell-derived heart models.

In recent years, significant biotechnological advancements have been made in engineering human cardiac tissues and organ-like models. This field of research is crucial for both basic and translational research due to cardiovascular disease being the leading cause of death in the developed world. Additionally, drug-associated cardiotoxicity poses a major challenge for drug development in the pharmaceutical and biotechnological industries. Progress in three-dimensional cell culture and microfluidic devices has enabled the generation of human cardiac models that faithfully recapitulate key aspects of human physiology. In this review, we will discuss 3D pluripotent stem cell (PSC)-models of the human heart, such as engineered heart tissues and organoids, and their applications in disease modeling and drug screening.

Evaluation of biological activity of some pyridine derivatives on perfusion pressure and their interaction with the M2 muscarinic receptor

AbstractThe aim of this study was to evaluate the biological activity of some pyridine derivatives (compounds 1 to 15) on perfusion pressure in an isolated rat heart model. Furthermore, theoretical interaction of pyridine derivatives with the M2 muscarinic receptor was determined using acetylcholine, AF‐DX 116 and the 3uon protein as theoretical tools in a docking model. Results showed that pyridine derivatives 6, 9, and 13 decreased perfusion pressure compared to control conditions and compounds 1‐5, 7, 8, 10‐12, 14, and 15. Furthermore, theoretical data indicates that different amino acid residues are involved in the interaction of pyridine derivatives with the protein surface. Other data indicate that the inhibition constant was lower for compounds 6, 9 and 13 compared to acetylcholine and AF‐DX 116. In conclusion, all these data suggest that pyridine derivatives 6, 9 and 13 can produce changes in perfusion pressure possibly through activation of the M2 muscarinic receptor, and this phenomenon could depend on the different functional groups involved in its chemical structure.

Piglet Model for Modified Blalock-Taussig-Thomas Shunt Training

BackgroundThe Blalock-Taussig-Thomas shunt is one of the milestone procedures in cardiac surgery and a crucial operation for palliating blue babies. It is currently impractical to train new surgeons on infants even under the supervision of their mentors. A realistic training model for location, exposure, tissue toughness, and texture is required. The objective of this study was to determine whether the model is realistic and practical and to evaluate the quality of anastomosis performed by surgical trainees. MethodsPiglet heart and lung models were selected from piglets of 3 to 5 kg. Six cardiothoracic surgical residents participated in the program and performed the procedure. Subsequently, every trainee answered a standard questionnaire in terms of satisfaction in reality and practicality; the trainers evaluated the quality of the anastomosis. The median score of each item was analyzed and described. The quality of anastomosis was evaluated and analyzed similarly. ResultsMedian scores of satisfaction (14 questions) were 9, 10, 9, 9.5, 10, 9.5, 10, 9.5, 10, 8.5, 10, 8.5, 10, and 8. Median challenge scores (6 questions) were 10, 10, 10, 10, 10, 9.5, and 10. The median anastomosis evaluation score from 6 trainees was 25 (24-25). ConclusionsOur heart-lung simulation model is perhaps 1 of the most realistic simulations in practicality, visualization, exposure of the related structures, similar scenes to the real operation, and sense of touch and texture. Realistic models should be developed, but they should be inexpensive.

Combination of personalized computational modeling and machine learning for optimization of left ventricular pacing site in cardiac resynchronization therapy.

Introduction: The 30-50% non-response rate to cardiac resynchronization therapy (CRT) calls for improved patient selection and optimized pacing lead placement. The study aimed to develop a novel technique using patient-specific cardiac models and machine learning (ML) to predict an optimal left ventricular (LV) pacing site (ML-PS) that maximizes the likelihood of LV ejection fraction (LVEF) improvement in a given CRT candidate. To validate the approach, we evaluated whether the distance DPS between the clinical LV pacing site (ref-PS) and ML-PS is associated with improved response rate and magnitude. Materials and methods: We reviewed retrospective data for 57 CRT recipients. A positive response was defined as a more than 10% LVEF improvement. Personalized models of ventricular activation and ECG were created from MRI and CT images. The characteristics of ventricular activation during intrinsic rhythm and biventricular (BiV) pacing with ref-PS were derived from the models and used in combination with clinical data to train supervised ML classifiers. The best logistic regression model classified CRT responders with a high accuracy of 0.77 (ROC AUC = 0.84). The LR classifier, model simulations and Bayesian optimization with Gaussian process regression were combined to identify an optimal ML-PS that maximizes the ML-score of CRT response over the LV surface in each patient. Results: The optimal ML-PS improved the ML-score by 17 ± 14% over the ref-PS. Twenty percent of the non-responders were reclassified as positive at ML-PS. Selection of positive patients with a max ML-score >0.5 demonstrated an improved clinical response rate. The distance DPS was shorter in the responders. The max ML-score and DPS were found to be strong predictors of CRT response (ROC AUC = 0.85). In the group with max ML-score > 0.5 and DPS< 30 mm, the response rate was 83% compared to 14% in the rest of the cohort. LVEF improvement in this group was higher than in the other patients (16 ± 8% vs. 7 ± 8%). Conclusion: A new technique combining clinical data, personalized heart modelling and supervised ML demonstrates the potential for use in clinical practice to assist in optimizing patient selection and predicting optimal LV pacing lead position in HF candidates for CRT.

Soft, bioresorbable, transparent microelectrode arrays for multimodal spatiotemporal mapping and modulation of cardiac physiology

Transparent microelectrode arrays (MEAs) that allow multimodal investigation of the spatiotemporal cardiac characteristics are important in studying and treating heart disease. Existing implantable devices, however, are designed to support chronic operational lifetimes and require surgical extraction when they malfunction or are no longer needed. Meanwhile, bioresorbable systems that can self-eliminate after performing temporary functions are increasingly attractive because they avoid the costs/risks of surgical extraction. We report the design, fabrication, characterization, and validation of a soft, fully bioresorbable, and transparent MEA platform for bidirectional cardiac interfacing over a clinically relevant period. The MEA provides multiparametric electrical/optical mapping of cardiac dynamics and on-demand site-specific pacing to investigate and treat cardiac dysfunctions in rat and human heart models. The bioresorption dynamics and biocompatibility are investigated. The device designs serve as the basis for bioresorbable cardiac technologies for potential postsurgical monitoring and treating temporary patient pathological conditions in certain clinical scenarios, such as myocardial infarction, ischemia, and transcatheter aortic valve replacement.