A Study of the Dynamics of Cardiac Ischemia using Experimental and Modeling Approaches

The dynamics of cardiac ischemia was investigated using experimental studies and computer simulations. An experimental model consisting of an isolated and perfused canine heart with full control over blood flow rate to a targeted coronary artery was used in the experimental study and a realistically shaped computer model of a canine heart, incorporating anisotropic conductivity and realistic fiber orientation, was used in the simulation study. The phenomena investigated were: (1) the influence of fiber rotation on the epicardial potentials during ischemia and (2) the effect of conductivity changes during a period of sustained ischemia. Comparison of preliminary experimental and computer simulation results suggest that as the ischemic region grows from the endocardium towards the epicardium, the epicardial potential patterns follow the rotating fiber orientation in the myocardium. Secondly, in the experimental studies it was observed that prolonged ischemia caused a subsequent reduction in the magnitude of epicardial potentials. Similar results were obtained from the computer model when the conductivity of the tissue in the ischemic region was reduce

Cardiac re-entry dynamics & self-termination in DT-MRI based model of Human Foetal Heart

The effect of heart geometry and anisotropy on cardiac re-entry dynamics and self-termination is studied here in anatomically realistic computer simulations of human foetal heart. 20 weeks of gestational age human foetal heart isotropic and anisotropic anatomy models from diffusion tensor MRI data sets are used in the computer simulations. The fibre orientation angles of the heart were obtained from the DT-MRI primary eigenvalues. In a spatially homogeneous electrophysiological mono domain model with the DT-MRI based heart geometries, we initiate simplified Fitz-Hugh-Nagumo kinetics cardiac re-entry at a prescribed location in a 2D slice, and in the full 3D anatomy model. In a slice of the heart, the MRI based fibre anisotropy changes the re-entry dynamics from pinned to anatomical re-entry. In the full 3D MRI based model, the foetal heart fibre anisotropy changes the re-entry dynamics from a persistent re-entry to the re-entry self-termination

Cardiac re-entry dynamics and self-termination in DT-MRI based model of Human Foetal Heart

The effect of human fetal heart geometry and anisotropy on anatomy induced drift and self-termination of cardiac re-entry is studied here in MRI based 2D slice and 3D whole heart computer simulations. Isotropic and anisotropic models of 20 weeks of gestational age human fetal heart obtained from 100 μm voxel diffusion tensor MRI data sets were used in the computer simulations. The fiber orientation angles of the heart were obtained from the orientation of the DT-MRI primary eigenvectors. In a spatially homogeneous electrophysiological monodomain model with the DT-MRI based heart geometries, cardiac re-entry was initiated at a prescribed location in a 2D slice, and in the 3D whole heart anatomy models. Excitation was described by simplified FitzHugh-Nagumo kinetics. In a slice of the heart, with propagation velocity twice as fast along the fibers than across the fibers, DT-MRI based fiber anisotropy changes the re-entry dynamics from pinned to an anatomical re-entry. In the 3D whole heart models, the fiber anisotropy changes cardiac re-entry dynamics from a persistent re-entry to the re-entry self-termination. The self-termination time depends on the re-entry's initial position. In all the simulations with the DT-MRI based cardiac geometry, the anisotropy of the myocardial tissue shortens the time to re-entry self-termination several folds. The numerical simulations depend on the validity of the DT-MRI data set used. The ventricular wall showed the characteristic transmural rotation of the helix angle of the developed mammalian heart, while the fiber orientation in the atria was irregula

Computational modeling of acute myocardial infarction

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Computer Methods in Biomechanics and Biomedical Engineering on October, 2016, available online at: http://www.tandfonline.com/10.1080/10255842.2015.1105965Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size.Peer ReviewedPostprint (author's final draft

3D/2D Registration of Mapping Catheter Images for Arrhythmia Interventional Assistance

Radiofrequency (RF) catheter ablation has transformed treatment for tachyarrhythmias and has become first-line therapy for some tachycardias. The precise localization of the arrhythmogenic site and the positioning of the RF catheter over that site are problematic: they can impair the efficiency of the procedure and are time consuming (several hours). Electroanatomic mapping technologies are available that enable the display of the cardiac chambers and the relative position of ablation lesions. However, these are expensive and use custom-made catheters. The proposed methodology makes use of standard catheters and inexpensive technology in order to create a 3D volume of the heart chamber affected by the arrhythmia. Further, we propose a novel method that uses a priori 3D information of the mapping catheter in order to estimate the 3D locations of multiple electrodes across single view C-arm images. The monoplane algorithm is tested for feasibility on computer simulations and initial canine data.Comment: International Journal of Computer Science Issues, IJCSI, Volume 4, Issue 2, pp10-19, September 200

A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

How left-right patterning drives asymmetric morphogenesis is unclear. Here, we have quantified shape changes during mouse heart looping, from 3D reconstructions by HREM. In combination with cell labelling and computer simulations, we propose a novel model of heart looping. Buckling, when the cardiac tube grows between fixed poles, is modulated by the progressive breakdown of the dorsal mesocardium. We have identified sequential left-right asymmetries at the poles, which bias the buckling in opposite directions, thus leading to a helical shape. Our predictive model is useful to explore the parameter space generating shape variations. The role of the dorsal mesocardium was validated in Shh-/- mutants, which recapitulate heart shape changes expected from a persistent dorsal mesocardium. Our computer and quantitative tools provide novel insight into the mechanism of heart looping and the contribution of different factors, beyond the simple description of looping direction. This is relevant to congenital heart defects

Calculating Unknown Eigenvalues with a Quantum Algorithm

Quantum algorithms are able to solve particular problems exponentially faster than conventional algorithms, when implemented on a quantum computer. However, all demonstrations to date have required already knowing the answer to construct the algorithm. We have implemented the complete quantum phase estimation algorithm for a single qubit unitary in which the answer is calculated by the algorithm. We use a new approach to implementing the controlled-unitary operations that lie at the heart of the majority of quantum algorithms that is more efficient and does not require the eigenvalues of the unitary to be known. These results point the way to efficient quantum simulations and quantum metrology applications in the near term, and to factoring large numbers in the longer term. This approach is architecture independent and thus can be used in other physical implementations

Pacing therapy for atrioventricular dromotropathy: A combined computational-experimental-clinical study

AIMS: Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational-experimental-clinical study. METHODS AND RESULTS: Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction \u3c35%) with prolonged PR interval (\u3e230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10-15%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34 ± 40% and 26 ± 31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation. CONCLUSION: Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval