Transmural APD heterogeneity determines ventricular arrhythmogenesis in LQT8 syndrome: Insights from Bidomain computational modeling.

Long QT Syndrome type 8 (LQT8) is a cardiac arrhythmic disorder associated with Timothy Syndrome, stemming from mutations in the CACNA1C gene, particularly the G406R mutation. While prior studies hint at CACNA1C mutations' role in ventricular arrhythmia genesis, the mechanisms, especially in G406R presence, are not fully understood. This computational study explores how the G406R mutation, causing increased transmural dispersion of repolarization, induces and sustains reentrant ventricular arrhythmias.

Epicardial Dispersion of Repolarization Promotes the Onset of Reentry in Brugada Syndrome: A Numerical Simulation Study.

The Brugada syndrome (BrS) is a cardiac arrhythmic disorder responsible for sudden cardiac death associated with the onset of ventricular arrhythmias, such as reentrant ventricular tachycardia and fibrillation. The mechanisms which lead to the onset of such electrical disorders in patients affected by BrS are not completely understood, yet. The aim of the present study is to investigate by means of numerical simulations the electrophysiological mechanisms at the basis of the morphology of electrocardiogram (ECG) and the onset of reentry associated with BrS.

Role of Scar and Border Zone Geometry on the Genesis and Maintenance of Re-Entrant Ventricular Tachycardia in Patients With Previous Myocardial Infarction.

In patients with healed myocardial infarction, the left ventricular ejection fraction is characterized by low sensitivity and specificity in the prediction of future malignant arrhythmias. Thus, there is the need for new parameters in daily practice to perform arrhythmic risk stratification. The aim of this study is to identify some features of proarrhythmic geometric configurations of scars and border zones (BZ), by means of numerical simulations based on left ventricular models derived from post myocardial infarction patients.

Numerical evaluation of cardiac mechanical markers as estimators of the electrical activation time.

Recent advances in the development of noninvasive cardiac imaging technologies have made it possible to measure longitudinal and circumferential strains at a high spatial resolution also at intramural level. Local mechanical activation times derived from these strains can be used as noninvasive estimates of electrical activation, in order to determine, eg, the origin of premature ectopic beats during focal arrhythmias or the pathway of reentrant circuits. The aim of this work is to assess the reliability of mechanical activation time markers derived from longitudinal and circumferential strains, denoted by AT and AT , respectively, by means of three-dimensional cardiac electromechanical simulations.

Electromechanical effects of concentric hypertrophy on the left ventricle: A simulation study.

In this work, we analyze the way concentric hypertrophy, triggered by mild aortic stenosis, affects the electromechanical activity of the left ventricle during a cardiac cycle by employing a 3D finite-element strongly-coupled model. Three mechanical feedbacks on electrophysiology are considered: the conduction feedback, acting on conductivity tensors, the convection feedback, dependent on the deformation rate, and the mechanoelectric feedback due to stretch-activated membrane channels. In case of a multiple endocardial electrical stimulation for a healthy ventricle, the convection feedback raises the values of action potential duration APD while modifying the corresponding distribution patterns, mainly in the latest activated regions.

A Numerical Study of Scalable Cardiac Electro-Mechanical Solvers on HPC Architectures.

We introduce and study some scalable domain decomposition preconditioners for cardiac electro-mechanical 3D simulations on parallel HPC (High Performance Computing) architectures. The electro-mechanical model of the cardiac tissue is composed of four coupled sub-models: (1) the static finite elasticity equations for the transversely isotropic deformation of the cardiac tissue; (2) the active tension model describing the dynamics of the intracellular calcium, cross-bridge binding and myofilament tension; (3) the anisotropic Bidomain model describing the evolution of the intra- and extra-cellular potentials in the deforming cardiac tissue; and (4) the ionic membrane model describing the dynamics of ionic currents, gating variables, ionic concentrations and stretch-activated channels. This strongly coupled electro-mechanical model is discretized in time with a splitting semi-implicit technique and in space with isoparametric finite elements.

Cardiac kinematic parameters computed from video of in situ beating heart.

Mechanical function of the heart during open-chest cardiac surgery is exclusively monitored by echocardiographic techniques. However, little is known about local kinematics, particularly for the reperfused regions after ischemic events. We report a novel imaging modality, which extracts local and global kinematic parameters from videos of in situ beating hearts, displaying live video cardiograms of the contraction events.

Simulating the effects of growth and fiber dispersion on the electromechanical response of a cardiac ventricular wedge affected from concentric hypertrophy.

In this paper, we analyze the epicardial electromechanical response of an in silico cardiac ventricular wedge under both healthy and concentric hypertrophic conditions. This is achieved by taking into account the growth of the wedge thickness and the fiber dispersion that may follow. The electromechanical response is described in terms of some macroscopic measures, i.

In silico modelling and analysis of the electrical and mechanical properties of in vitro cardiac cultures with different fiber architectures.

Today, in vitro cardiac cultures are widely exploited to investigate several aspects of the electromechanical behavior of the cardiac tissue. Thus, new forecasts may derive from modelling their properties. In particular, in this paper, we focus on the fiber architecture of cultures, i.

Modelling the effect of thickness on the electromechanical properties of in vitro cardiac cultures: A simulation study.

Nowadays, in vitro cardiac cultures offer a valid tool to study the bioelectrical activity and the biomechanics of the heart tissue. Modelling their properties could be helpful for researchers involved in this field. In this paper, we develop a three-dimensional electromechanical model to study how thickness affects the bioelectrical and biomechanical performances of an in vitro culture made of ventricular cells.

Effects of premature anodal stimulations on cardiac transmembrane potential and intracellular calcium distributions computed by anisotropic Bidomain models.

Aims: Cardiac unipolar electrode stimulations induce a particular structure of the transmembrane potential distribution (Vm), called virtual electrode polarization (VEP), which plays an important role in the mechanisms of cardiac excitation, reentry induction, and ventricular defibrillation. Recent experimental studies, based on the optical mapping techniques, have shown that premature stimulations also induce significant changes in the intracellular calcium (Cai) spatial distribution. The aim of this work is to investigate and compare by means of numerical simulations the morphology of the Vm and Cai patterns, generated by applying an S1-S2 stimulation protocol with a premature S2 anodal pulse.

Intramural activation and repolarization sequences in canine ventricles. Experimental and simulation studies.

Background: There are no published data showing the three-dimensional sequence of repolarization and the associated potential fields in the ventricles. Knowledge of the sequence of repolarization has medical relevance because high spatial dispersion of recovery times and action potential durations favors cardiac arrhythmias. In this study we describe measured and simulated 3-D excitation and recovery sequences and activation-recovery intervals (ARIs) (measured) or action potential durations (APDs) (simulated) in the ventricular walls.

Modeling ventricular excitation: axial and orthotropic anisotropy effects on wavefronts and potentials.

By applying the eikonal approximation to the bidomain model of the cardiac tissue we investigate the influence of the axially isotropic and orthotropic conductivity tensors on the propagation of the excitation wavefronts and on the associated potential distribution and electrograms.