Fast Simulation of Mechanical Heterogeneity in the Electrically Asynchronous Heart Using the MultiPatch Module

Cardiac electrical asynchrony occurs as a result of cardiac pacing or conduction disorders such as left bundle-branch block (LBBB). Electrically asynchronous activation causes myocardial contraction heterogeneity that can be detrimental for cardiac function. Computational models provide a tool for understanding pathological consequences of dyssynchronous contraction. Simulations of mechanical dyssynchrony within the heart are typically performed using the finite element method, whose computational intensity may present an obstacle to clinical deployment of patient-specific models. We present an alternative based on the CircAdapt lumped-parameter model of the heart and circulatory system, called the MultiPatch module. Cardiac walls are subdivided into an arbitrary number of patches of homogeneous tissue. Tissue properties and activation time can differ between patches. All patches within a wall share a common wall tension and curvature. Consequently, spatial location within the wall is not required to calculate deformation in a patch. We test the hypothesis that activation time is more important than tissue location for determining mechanical deformation in asynchronous hearts. We perform simulations representing an experimental study of myocardial deformation induced by ventricular pacing, and a patient with LBBB and heart failure using endocardial recordings of electrical activation, wall volumes, and end-diastolic volumes. Direct comparison between simulated and experimental strain patterns shows both qualitative and quantitative agreement between model fibre strain and experimental circumferential strain in terms of shortening and rebound stretch during ejection. Local myofibre strain in the patient simulation shows qualitative agreement with circumferential strain patterns observed in the patient using tagged MRI. We conclude that the MultiPatch module produces realistic regional deformation patterns in the asynchronous heart and that activation time is more important than tissue location within a wall for determining myocardial deformation. The CircAdapt model is therefore capable of fast and realistic simulations of dyssynchronous myocardial deformation embedded within the closed-loop cardiovascular system.     

Tailoring cardiac resynchronization therapy using interventricular asynchrony. Validation of a simple model

This study explores the use of interventricular asynchrony (interVA) for optimizing cardiac resynchronization therapy (CRT), an idea emerging from a simple pathway model of conduction in the ventricles. Measurements were performed in six dogs with chronic left bundle branch block (LBBB) and in 29 patients of the Pacing Therapies for Congestive Heart Failure (PATH-CHF)-I study. In the dogs, intraventricular asynchrony (intraVA) was determined using left ventricular (LV) endocardial activation maps. In dogs and patients, the maximum rate of rise of LV pressure (LV dP/dt(max)) and the pulse pressure (PP) and interVA [time delay between upslope of LV and right ventricular (RV) pressure curves] were measured during LV, RV, and biventricular (BiV) pacing with various atrioventricular (AV) delays. Measurements in the canine hearts supported the pathway model in that optimal resynchronization occurred at approximately 50% reduction of intraVA and at an interVA value halfway that during LBBB and LV pacing. In patients with significant hemodynamic response during pacing (n = 22), intrinsic interVA and interVA at peak improvement (interVA(p)) varied widely between patients (from -83 to -15 ms and from -42 to +31 ms, respectively). However, the model predicted individual interVA(p) accurately (SD of +/-6 ms and +/-12 ms for LV dP/dt(max) and PP, respectively). At equal interVA, LV and BiV pacing produced equal hemodynamic response, but in 11 of 22 responders, BiV pacing reduced interVA insufficiently to reach the maximum hemodynamic response. LV pacing at short AV delay proved to result in better hemodynamics than predicted by the model, indicating that additional factors determine hemodynamics during LV preexcitation. Guided by a simple pathway model, interVA measurements accurately predict optimal hemodynamic performance in individual CRT patients.     

Simulation of stent deployment in a realistic human coronary artery

Background  

The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis.     

Microsatellite evolution in congeneric mammals: domestic and bighorn sheep

We compared genotypes at eight (AC)n microsatellite loci in domestic sheep (Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The domestic sheep had greater genetic variation, higher allele-size variances, and larger allele sizes than the wild sheep. Accumulating evidence from higher taxonomic comparisons shows that these parameters are biased if microsatellite loci are selected in one taxon and used in another. Our results demonstrate similar biases between congeneric species. We compared standard measures of genetic variation, differentiation, and distance within and between species (H, D, FST) to newer measures based on allele-size variance (SW, SB, RST). The size-based distances better detected species-level divergence, but standard measures better distinguished allopatric populations. Empirical calibration of these measures at the subspecies level is needed to establish their useful ranges.      

Olfactory sensitivity in tsetse flies: a daily rhythm

The diurnal tsetse Glossina morsitans morsitans bites especially in early morning and late afternoon; around midday feeding is at a low. In laboratory apparatus that measures the amount of locomotion under constant conditions over the photophase, the flies display a similar patterning of activity levels. The profile of daily rhythms for G. morsitans reported in the literature includes a number of motor and sensory motor systems that fluctuate cophasically. Lacking is a study on the patterning of the senses' response levels. In this paper we present the first instance of a daily modulation in the sense of smell. We stimulated the antennae with concentration series of host-derived odours and measured the spiking rate of cells at different times during the photophase. The concentration-response curves suggest that the sensitivity of antennal olfactory cells flows in parallel with the other daily rhythms. This was also reflected in electroantennograms (EAGs). The electroantennography was extended to G. fuscipes fuscipes, whose level of spontaneous locomotor activity--instead of following a U- shaped pattern--rises gradually over the photophase. Again, the EAGs appeared to parallel the species' locomotor activity. What we believe happens is that the organism tones down the sensitivity of its odour receptors during periods of anticipated inactivity for reasons of economy.      

Mapping of epicardial deformation using a video processing technique

A method has been developed to measure deformation of the canine epicardium during the cardiac cycle simultaneously in a number (eight) of small regions (1 X 1 cm2). Approximately 50 white markers (diameter 1.5 mm) are attached to the epicardium and their motion is recorded on tape by a video camera. Marker positions are detected by computer processing of the digitized images. In each region the three deformation parameters are calculated from the displacements of all markers in that region by means of a least-squares criterium. In the experimental situation in the center of the area of the epicardium analyzed the accuracy of measuring circumferential strain, base-to-apex strain and shear is +/- 0.005, +/- 0.005 and +/- 0.002 rad, respectively. The method has been applied in an experiment in which local ischemia of the left ventricular wall was induced by occluding the anterior descending branch of the left coronary artery. Healthy and ischemic regions could clearly be distinguished by the differences in deformation.     

Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation

In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics. Starting out from a reference geometry in which myofiber orientation had no transmural component, two new geometries were defined with either a 27 % decrease in LV short- to long-axis ratio, or a 16 % decrease of RV length, but identical LV and RV cavity and wall volumes. These variations in geometry caused differences in both local myofiber and global pump work below 6 %. Variation of fiber orientation was induced through adaptive myofiber reorientation that caused an average change in fiber orientation of \({\sim }8^\circ \) predominantly through the formation of a component in transmural direction. Reorientation caused a considerable increase in local myofiber work \(({\sim }18\,\%)\) and in global pump work \(({\sim }17\,\%)\) in all three geometries, while differences between geometries were below 5 %. The findings suggest that implementing a realistic myofiber orientation is at least as important as defining a patient-specific geometry. The model for remodeling of myofiber orientation seems a useful approach to estimate myofiber orientation in the absence of accurate patient-specific information.

     

Cardiac resynchronization: insight from experimental and computational models

Cardiac resynchronization therapy (CRT) is a promising therapy for heart failure patients with a conduction disturbance, such as left bundle branch block. The aim of CRT is to resynchronize contraction between and within ventricles. However, about 30% of patients do not respond to this therapy. Therefore, a better understanding is needed for the relation between electrical and mechanical activation. In this paper, we focus on to what extent animal experiments and mathematical models can help in order to understand the pathophysiology of asynchrony to further improve CRT.     

Ultrasonic Vocalizations Emitted by Flying Squirrels

Anecdotal reports of ultrasound use by flying squirrels have existed for decades, yet there has been little detailed analysis of their vocalizations. Here we demonstrate that two species of flying squirrel emit ultrasonic vocalizations. We recorded vocalizations from northern (Glaucomys sabrinus) and southern (G. volans) flying squirrels calling in both the laboratory and at a field site in central Ontario, Canada. We demonstrate that flying squirrels produce ultrasonic emissions through recorded bursts of broadband noise and time-frequency structured frequency modulated (FM) vocalizations, some of which were purely ultrasonic. Squirrels emitted three types of ultrasonic calls in laboratory recordings and one type in the field. The variety of signals that were recorded suggest that flying squirrels may use ultrasonic vocalizations to transfer information. Thus, vocalizations may be an important, although still poorly understood, aspect of flying squirrel social biology.     

Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization

By current guidelines a considerable part of the patients selected for cardiac resynchronization therapy (CRT) do not respond to the therapy. We hypothesized that mechanical discoordination [opposite strain within the left ventricular (LV) wall] predicts reversal of LV remodeling upon CRT better than mechanical dyssynchrony. MRI tagging images were acquired in CRT candidates (n = 19) and in healthy control subjects (n = 9). Circumferential strain (epsilon(cc)) was determined in 160 regions. From epsilon(cc) signals we derived 1) an index of mechanical discoordination [internal stretch fraction (ISF), defined as the ratio of stretch to shortening during ejection] and 2) indexes of mechanical dyssynchrony: the 10-90% width of time to onset of shortening, time to peak shortening, and end-systolic strain. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) were determined before and after 3 mo of CRT. Responders were defined as those patients in whom LVESV decreased by >15%. In responders (n = 10), CRT increased LVEF and decreased LVEDV and LVESV (11 +/- 6%, 21 +/- 16%, and 30 +/- 16%, respectively) significantly more (P < 0.05) than in nonresponders (1 +/- 6%, 3 +/- 4%, and 5 +/- 10%, respectively). Among mechanical indexes, only ISF was different between responders and nonresponders (0.53 +/- 0.25 vs. 0.31 +/- 0.16; P < 0.05). In patients with ISF >0.4 (n = 10), LVESV decreased by 31 +/- 18% vs. 5 +/- 11% in patients with ISF <0.4 (P < 0.05). We conclude that mechanical discoordination, as estimated from ISF, is a better predictor of reverse remodeling after CRT than differences in time to onset and time to peak shortening. Therefore, discoordination rather than dyssynchrony appears to reflect the reserve contractile capacity that can be recruited by CRT.