Fetal heart computational modeling

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2021-2022. Tutor/Director: Director: Patricia Garcia Cañadilla / Tutor: Fàtima Crispi BrillasAmong infants born with cardiac defects, congenital heart disease (CHD) is the leading congenital abnormality and it origins the majority of newborns death in developed countries. The structural malformations in the heart or great vessels it causes increase the postnatal cardiovascular risk and mortality. In particular, the high incidence of tetralogy of Fallot (ToF) in live births make essential to develop new procedures that enable the study and understanding of this cardiac disorder and the hemodynamic changes it induces. That way, fetal medicine has been constantly evolving in the past years, and computational modeling techniques are becoming more established in the clinical practice and are of growing importance. Nowadays, different 0D lumped parameters models have demonstrated to be useful to evaluate complex cardiac defects in order to aid health workers and find the best management for patients. In this project, a 0D lumped model simulating hemodynamic components and parameters of the fetal heart was developed to study the changes occurring in a ToF heart. Specifically, birth defects of ventricular septal defect (VSD) and pulmonary valve stenosis (PVS) were modeled, allowing the analysis of their effects in fetal circulation. Our results suggested that the designed 0D lumped model can reproduce the blood velocities and pressure waveforms of the fetal heart in healthy conditions after adjusting the values of some model parameters. Despite that, the parameters of the ductus arteriosus (DA) should be better fit since we could not completely reproduce its velocity waveform. Regarding the evaluation of hemodynamic changes of cardiac defects, results suggested that the 0D lumped model can simulate the features present in ToF, such as the right-to-left shunt, characteristic of blood flow in VSD, and the increase of the pressure gradient and peak velocity of the pulmonary artery, indicative of PVS. However, more literature and clinical data of cardiac defects should be used in order to verify these outcomes and ensure their reliability

A comprehensive and biophysically detailed computational model of the whole human heart electromechanics

While ventricular electromechanics is extensively studied, four-chamber heart models have only been addressed recently; most of these works however neglect atrial contraction. Indeed, as atria are characterized by a complex physiology influenced by the ventricular function, developing computational models able to capture the physiological atrial function and atrioventricular interaction is very challenging. In this paper, we propose a biophysically detailed electromechanical model of the whole human heart that considers both atrial and ventricular contraction. Our model includes: i) an anatomically accurate whole-heart geometry; ii) a comprehensive myocardial fiber architecture; iii) a biophysically detailed microscale model for the active force generation; iv) a 0D closed-loop model of the circulatory system; v) the fundamental interactions among the different core models; vi) specific constitutive laws and model parameters for each cardiac region. Concerning the numerical discretization, we propose an efficient segregated-intergrid-staggered scheme and we employ recently developed stabilization techniques that are crucial to obtain a stable formulation in a four-chamber scenario. We are able to reproduce the healthy cardiac function for all the heart chambers, in terms of pressure-volume loops, time evolution of pressures, volumes and fluxes, and three-dimensional cardiac deformation, with unprecedented matching (to the best of our knowledge) with the expected physiology. We also show the importance of considering atrial contraction, fibers-stretch-rate feedback and suitable stabilization techniques, by comparing the results obtained with and without these features in the model. The proposed model represents the state-of-the-art electromechanical model of the iHEART ERC project and is a fundamental step toward the building of physics-based digital twins of the human heart

Electro-mechanical whole-heart digital twins: A fully coupled multi-physics approach

Mathematical models of the human heart are evolving to become a cornerstone of precision medicine and support clinical decision making by providing a powerful tool to understand the mechanisms underlying pathophysiological conditions. In this study, we present a detailed mathematical description of a fully coupled multi-scale model of the human heart, including electrophysiology, mechanics, and a closed-loop model of circulation. State-of-the-art models based on human physiology are used to describe membrane kinetics, excitation-contraction coupling and active tension generation in the atria and the ventricles. Furthermore, we highlight ways to adapt this framework to patient specific measurements to build digital twins. The validity of the model is demonstrated through simulations on a personalized whole heart geometry based on magnetic resonance imaging data of a healthy volunteer. Additionally, the fully coupled model was employed to evaluate the effects of a typical atrial ablation scar on the cardiovascular system. With this work, we provide an adaptable multi-scale model that allows a comprehensive personalization from ion channels to the organ level enabling digital twin modeling

Mechanics of the tricuspid valve: from clinical diagnosis/treatment, in vivo and in vitro investigations, to patient-specific biomechanical modeling

Proper tricuspid valve (TV) function is essential to unidirectional blood flow through the right side of the heart. Alterations to the tricuspid valvular components, such as the TV annulus, may lead to functional tricuspid regurgitation (FTR), where the valve is unable to prevent undesired backflow of blood from the right ventricle into the right atrium during systole. Various treatment options are currently available for FTR; however, research for the tricuspid heart valve, functional tricuspid regurgitation, and the relevant treatment methodologies are limited due to the pervasive expectation among cardiac surgeons and cardiologists that FTR will naturally regress after repair of left-sided heart valve lesions. Recent studies have focused on (i) understanding the function of the TV and the initiation or progression of FTR using both in-vivo and in-vitro methods, (ii) quantifying the biomechanical properties of the tricuspid valve apparatus as well as its surrounding heart tissue, and (iii) performing computational modeling of the TV to provide new insight into its biomechanical and physiological function. This review paper focuses on these advances and summarizes recent research relevant to the TV within the scope of FTR. Moreover, this review also provides future perspectives and extensions critical to enhancing the current understanding of the functioning and remodeling tricuspid valve in both the healthy and pathophysiological states

Entering a new era of surgical training : developing 3-dimensional print models for hands-on surgical training and its introduction into the congenital cardiac surgical curriculum

Congenital heart surgery is a technically challenging subspecialty of cardiothoracic surgery. This is due to a combination of factors including the rarity and variety of pathology and the small patient size. This coupled with the increasing public scrutiny and the expectation of excellent patient outcomes for even the most complex pathologies has led to limitations for surgical trainees to develop their surgical competencies in an efficient manner. Simulation has been used successfully to develop technical skills in other surgical specialities but is limited in congenital heart surgery. The objectives of this work were to develop and integrate hands-on simulation methods into the training of congenital heart surgeons using anatomically accurate 3D-printed heart models and to use validated, objective assessment methods to measure performance. The simulation programme was successfully developed and integrated into the regular training of congenital heart surgeons. The objective assessments demonstrated that there was an improvement in procedural performance and time across multiple complex procedures following deliberate practice and rehearsal. Furthermore, surgeons who had participated in the programme retained their technical skills following a prolonged delay supporting the value of simulation. Overall, there is value in the incorporation of hands-on simulation training into congenital heart surgery and it has the potential to be integrated into training programmes globally

Cardiac resynchronization therapy: mechanisms of action and scope for further improvement in cardiac function.

Aims: Cardiac resynchronization therapy (CRT) may exert its beneficial haemodynamic effect by improving ventricular synchrony and improving atrioventricular (AV) timing. The aim of this study was to establish the relative importance of the mechanisms through which CRT improves cardiac function and explore the potential for additional improvements with improved ventricular resynchronization. Methods and Results: We performed simulations using the CircAdapt haemodynamic model and performed haemodynamic measurements while adjusting AV delay, at low and high heart rates, in 87 patients with CRT devices. We assessed QRS duration, presence of fusion, and haemodynamic response. The simulations suggest that intrinsic PR interval and the magnitude of reduction in ventricular activation determine the relative importance of the mechanisms of benefit. For example, if PR interval is 201 ms and LV activation time is reduced by 25 ms (typical for current CRT methods), then AV delay optimization is responsible for 69% of overall improvement. Reducing LV activation time by an additional 25 ms produced an additional 2.6 mmHg increase in blood pressure (30% of effect size observed with current CRT). In the clinical population, ventricular fusion significantly shortened QRS duration (Δ-27 ± 23 ms, P < 0.001) and improved systolic blood pressure (mean 2.5 mmHg increase). Ventricular fusion was present in 69% of patients, yet in 40% of patients with fusion, shortening AV delay (to a delay where fusion was not present) produced the optimal haemodynamic response. Conclusions: Improving LV preloading by shortening AV delay is an important mechanism through which cardiac function is improved with CRT. There is substantial scope for further improvement if methods for delivering more efficient ventricular resynchronization can be developed. Clinical Trial Registration: Our clinical data were obtained from a subpopulation of the British Randomised Controlled Trial of AV and VV Optimisation (BRAVO), which is a registered clinical trial with unique identifier: NCT01258829, https://clinicaltrials.gov

Personalized Electromechanical Modeling of the Human Heart : Challenges and Opportunities for the Simulation of Pathophysiological Scenarios

Mathematische Modelle des menschlichen Herzens entwickeln sich zu einem Eckpfeiler der personalisierten Medizin. Sie sind ein nützliches Instrument und helfen klinischen Entscheidungsträgern die zugrundeliegenden Mechanismen von Herzkrankheiten zu erforschen und zu verstehen. Aufgrund der Komplexität des Herzens benötigen derartige Modelle allerdings eine detaillierte Beschreibung der physikalischen Prozesse, welche auf verschiedenen räumlichen und zeitlichen Skalen miteinander interagieren. Aus mathematischer Perspektive stellen vor allem die Entwicklung robuster numerischer Methoden für die Lösung des Modells in Raum und Zeit sowie die Identifizierung von Parametern aus patientenspezifischen Messungen eine Herausforderung dar. In dieser Arbeit wird ein detailliertes mathematisches Modell vorgestellt, welches ein vollgekoppeltes Multiskalenmodell des menschlichen Herzens beschreibt. Das Modell beinhaltet unter anderem die Ausbreitung des elektrischen Signals und die mechanische Verformung des Herzmuskels sowie eine Beschreibung des Herz-Kreislauf-Systems. Basierend auf dem neusten Stand der Technik wurden Modelle der Membrankinetik sowie der Entwicklung der aktiven Kraft zu einem einheitlichen Modell einer Herzmuskelzelle zusammengeführt. Dieses beschreibt die elektromechanische Kopplung in Herzmuskelzellen der Vorhöfe und der Herzkammern basierend auf der Physiologie im Menschen und wurde mit Hilfe von experimentellen Daten aus einzelnen Zellen neu parametrisiert. Um das elektromechanisch gekoppelte Modell des menschlichen Herzens lösen zu können, wurde ein gestaffeltes Lösungsverfahren entwickelt, welches auf bereits existierenden Softwarelösungen der Elektrophysiologie und Mechanik aufbaut. Das neue Modell wurde verwendet, um den Einfluss elektromechanischer Rückkopplungseffekte auf das Herz im Sinusrhythmus zu untersuchen. Die Simulationsergebnisse zeigten, dass elektromechanische Rückkopplungseffekte auf zellulärer Ebene einen wesentlichen Einfluss auf das mechanische Verhalten des Herzens haben. Dahingegen hatte die Verformung des Herzens nur einen geringen Einfluss auf den Diffusionskoeffizienten des elektrischen Signals. Um die verschiedenen Komponenten der Simulationssoftware zu verifizieren, wurden spezielle Probleme definiert, welche die wichtigsten Aspekte der Elektrophysiologie und der Mechanik abdecken. Zusätzlich wurden diese Probleme dazu verwendet, den Einfluss von räumlicher und zeitlicher Diskretisierung auf die numerische Lösung zu bewerten. Die Ergebnisse zeigten, dass Raum- und Zeitdiskretisierung vor allem für das elektrophysiologische Problem die limitierenden Faktoren sind, während die Mechanik hauptsächlich anfällig für volumenversteifende Effekte ist. Weiterhin wurde das Modell verwendet, um zu untersuchen, wie sich eine Verteilung der Faserspannung auf den gesamten Herzmuskel auf die Funktion der linken Herzkammer auswirkt. Hierzu wurde zusätzlich eine Spannung in die Normalenrichtungen der Fasern einer idealisierten linken Herzkammer angewandt. Es zeigte sich, dass insbesondere eine Spannung senkrecht zu den Faserschichten zu einer physiologischeren Kontraktion der Kammer führte. Allerdings konnten diese Ergebnisse auf einem ganzen Herzen nicht vollständig bestätigt werden. In einem zweiten Projekt wurde mit Hilfe eines Modells der linken Herzkammer untersucht, wie sich das Rotationsmuster der Kammer unter Modifikation der lokalen elektromechanischen Eigenschaften verändert. Hierzu wurden in vivo Daten elektromechanischer Parameter von 30 Patienten mit Herzversagen und Linksschenkelblock in das Modell integriert, simuliert und ausgewertet. Die Ergebnisse konnten die klinisch aufgestellte Hypothese nicht bestätigen und es zeigte sich keine Korrelation zwischen den elektromechanischen Parametern und dem Rotationsverhalten. Die Auswirkungen von standardisierten Ablationsstrategien zur Behandlung von Vorhofflimmern in Bezug auf die kardiovaskuläre Leistung wurde in einem Modell des ganzen Herzens untersucht. Aufgrund der Narben im linken Vorhof wurde die elektrische Aktivierung und die Steifigkeit des Herzmuskels verändert. Dies führte zu einem reduzierten Auswurfvolumen, welches in direktem Zusammenhang mit dem inaktiven Gewebe steht. Abhängig von der Steifigkeit der Narben hat sich zusätzlich der Druck im linken Vorhof erhöht. Die linke Herzkammer war nur wenig beeinflusst. Zu guter Letzt wurden schrittweise pathologische Mechanismen in das Herzmodell integriert, welche in Zusammenhang mit Herzversagen stehen und in Patienten mit dilatativer Kardiomyopathie zu beobachten sind. Die Simulationen zeigten, dass vor allem zelluläre Veränderungen bezüglich der elektrophysiologischen Eigenschaften für die schlechte mechanische Aktivtät des Herzens verantwortlich sind. Weiterhin zeigte sich, dass strukturelle Veränderungen der Anatomie und die erhöhte Steifigkeit des Herzmuskels und die damit einhergehenden Anpassungen des Herz-Kreislauf-Systems nötig sind, um in vivo Messungen zu reproduzieren. In dieser Arbeit wurde eine Simulationsumgebung vorgestellt, welche die Berechnung der elektromechanischen Aktivität des Herzens und des Herz-Kreislauf-Systems ermöglicht. Die Simulationsumgebung wurde mit Hilfe von einfachen Beispielen verifiziert und unter Einbeziehung von Daten aus der Magnetresonanztomographie validiert. Zu guter Letzt wurde die Simulationsumgebung genutzt, um klinische Fragen zu beantworten, welche andernfalls im Dunkeln blieben

Modelling and robust estimation of AV node function during AF

Objective: The purpose of the present thesis is to enrich the robustness of a statistical atrioventricular (AV) node model during atrial Fibrillation (AF). The model takes into account electrophysiological properties as the two pathways, their refractory periods and concealed conduction; these pathways are located between sinoatrial (SA) and AV node. It is highly desirable understanding of the AV node function, in order to achieve optimal arrhythmia management for those patients affected by AF, which is the most common arrhythmia. Methods: The simulation has been improved by introducing a new parameter that represents the probability of an impulse choosing either one of the two pathways. Exploration data has been conducted keeping fixed a set of parameters while varying one of them. Results: The model concerns a relationship between the probability of an atrial impulse passing through (output parameter, a) and choosing (input parameter, g) either one of two pathway. To test its accuracy and precision mean absolute error (MAE) and root mean square error (RMSE) have been calculated for different g, obtaining, MAE = 3:8_8:2023_1

Congenital TrainHeart: development of a fully 3D printed simulator for hands-on surgical training

RIASSUNTO Introduzione: Con la crescente aspettativa di un perfetto outcome per i pazienti sottoposti a interventi di cardiochirurgia, risulta fondamentale sviluppare e utilizzare nuove modalità per la formazione dei giovani chirurghi. Tuttavia, ad oggi, l’organizzazione di corsi di simulazione risulta dispendioso sia in termini di risorse economiche che di personale. Proprio per questo, il crescente interesse collettivo verso la stampa 3D ha permesso di sviluppare nuove tecnologie che possono essere efficacemente utilizzate nell’ambito della simulazione cardiochirurgica. Obiettivo dello studio: Questa tesi descrive lo sviluppo di un simulatore a basso costo stampato in 3D che può essere utilizzato sia nell’ambito delle cardiopatie congenite che di quelle acquisite Materiali e metodi: Il simulatore è stato sviluppato in modo tale da simulare posizione, visuale ed esposizione del cuore all’interno del torace in diversi approcci chirurgici. Tutte le componenti del simulatore sono state progettate tramite un software di modellazione 3D e stampati con stampante 3D a stereolitografia. I modellini da inserire all’interno dello stesso simulatore sono stati a loro volta sviluppati o tramite l’utilizzo dello stesso software o sfruttando tecniche di ricostruzione 3D a partenza da immagini TC o RMN. Risultati: Il simulatore si compone di una struttura che simula la cavità toracica con una apertura ellittica nella parte superiore atta a simulare una sternotomia mediana. Il simulatore può essere fissato ad un treppiede permettendo aggiustamenti per quanto concerne l’altezza, nonché movimenti di inclinazione e rotazione. In aggiunta, sono state realizzate quattro cover che permettono di modificare l’apertura sulla parte superiore del simulatore, al fine di simulare accessi di tipo mininvasivo. I modellini sono stati invece stampati con una resina elastica che, date le sue caratteristiche, può essere tagliata e suturata. Conclusioni: Il nuovo simulatore stampabile in 3D che è stato sviluppato potrebbe rappresentare uno strumento estremamente valido per le simulazioni cardiochirurgiche ad alta fedeltà e per il planning personalizzato di una procedura.Background: With the growing expectation of a perfect outcome for patients undergoing cardiac surgery, it is now imperative to find alternative surgical training methods for residents and fellows. However, surgical simulation usually requires a fair amount of funds and manpower to establish a reliable program. For this reason, the increasing interest in the 3D printing field allowed the development of new technologies that found immediate application in surgical simulation. Aim of the study: This thesis illustrates the development of a low-cost 3D printed simulator for congenital and acquired cardiac surgery. Materials and methods: A simulator was designed to replicate position, view, and exposure of the heart within the chest wall using different approaches (median sternotomy, mini-sternotomy, subaxillary, and posterior mini-thoracotomy). All components were designed using a 3D modeling software and printed using a stereolithography 3D printer. All models that come with the simulator were designed using the same CAD software used for the chest simulator or using 3D reconstruction software for CT or MRI scans. Results: The simulator consists of a chest wall cavity with an oval opening on the top simulating a median sternotomy. The simulator can be attached to a tripod, allowing for height adjustments and pitch-and-roll movements. In addition, five different covers were designed to modify the opening, thus allowing to replicate minimally-invasive surgical approaches. The fully printed design made it possible to significantly reduce the cost of the entire product. All models are printed with a special elastic resin which makes it possible to cut and suture all structures. Conclusion: A novel low-cost fully 3D printed simulator was developed. This may represent a valid tool for high fidelity simulation programs in congenital and acquired cardiac surgery in addition to a patient-specific surgical planning