Publications by authors named "Lik-Chuan Lee"

39 Publications

Computational Modeling Studies of the Roles of Left Ventricular Geometry, Afterload, and Muscle Contractility on Myocardial Strains in Heart Failure with Preserved Ejection Fraction.

J Cardiovasc Transl Res 2021 Apr 29. Epub 2021 Apr 29.

Department of Mechanical Engineering, Michigan State University, 428 S Shaw Lane, East Lansing, MI, 48824, USA.

Global longitudinal strain and circumferential strain are found to be reduced in HFpEF, which some have interpreted that the global left ventricular (LV) contractility is impaired. This finding is, however, contradicted by a preserved ejection fraction (EF) and confounded by changes in LV geometry and afterload resistance that may also affect the global strains. To reconcile these issues, we used a validated computational framework consisting of a finite element LV model to isolate the effects of HFpEF features in affecting systolic function metrics. Simulations were performed to quantify the effects on myocardial strains due to changes in LV geometry, active tension developed by the tissue, and afterload. We found that only a reduction in myocardial contractility and an increase in afterload can simultaneously reproduce the blood pressures, EF and strains measured in HFpEF patients. This finding suggests that it is likely that the myocardial contractility is reduced in HFpEF patients. Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12265-021-10130-yDOI Listing
April 2021

Inverse modeling framework for characterizing patient-specific microstructural changes in the pulmonary arteries.

J Mech Behav Biomed Mater 2021 Mar 27;119:104448. Epub 2021 Mar 27.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA.

Microstructural changes in the pulmonary arteries associated with pulmonary arterial hypertension (PAH) is not well understood and characterized in humans. To address this issue, we developed and applied a patient-specific inverse finite element (FE) modeling framework to characterize mechanical and structural changes of the micro-constituents in the proximal pulmonary arteries using in-vivo pressure measurements and magnetic resonance images. The framework was applied using data acquired from a pediatric PAH patient and a heart transplant patient with normal pulmonary arterial pressure, which serves as control. Parameters of a constrained mixture model that are associated with the structure and mechanical properties of elastin, collagen fibers and smooth muscle cells were optimized to fit the patient-specific pressure-diameter responses of the main pulmonary artery. Based on the optimized parameters, individual stress and linearized stiffness resultants of the three tissue constituents, as well as their aggregated values, were estimated in the pulmonary artery. Aggregated stress resultant and stiffness are, respectively, 4.6 and 3.4 times higher in the PAH patient than the control subject. Stress and stiffness resultants of each tissue constituent are also higher in the PAH patient. Specifically, the mean stress resultant is highest in elastin (PAH: 69.96, control: 14.42 kPa-mm), followed by those in smooth muscle cell (PAH: 13.95, control: 4.016 kPa-mm) and collagen fibers (PAH: 13.19, control: 2.908 kPa-mm) in both the PAH patient and the control subject. This result implies that elastin may be the key load-bearing constituent in the pulmonary arteries of the PAH patient and the control subject.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmbbm.2021.104448DOI Listing
March 2021

Patient-Specific Computational Analysis of Hemodynamics and Wall Mechanics and Their Interactions in Pulmonary Arterial Hypertension.

Front Bioeng Biotechnol 2020 28;8:611149. Epub 2021 Jan 28.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.

Vascular wall stiffness and hemodynamic parameters are potential biomechanical markers for detecting pulmonary arterial hypertension (PAH). Previous computational analyses, however, have not considered the interaction between blood flow and wall deformation. Here, we applied an established computational framework that utilizes patient-specific measurements of hemodynamics and wall deformation to analyze the coupled fluid-vessel wall interaction in the proximal pulmonary arteries (PA) of six PAH patients and five control subjects. Specifically, we quantified the linearized stiffness (), relative area change (RAC), diastolic diameter (), regurgitant flow, and time-averaged wall shear stress (TAWSS) of the proximal PA, as well as the total arterial resistance ( ) and compliance ( ) at the distal pulmonary vasculature. Results found that the average proximal PA was stiffer [median: 297 kPa, interquartile range (IQR): 202 kPa vs. median: 75 kPa, IQR: 5 kPa; = 0.007] with a larger diameter (median: 32 mm, IQR: 5.25 mm vs. median: 25 mm, IQR: 2 mm; = 0.015) and a reduced RAC (median: 0.22, IQR: 0.10 vs. median: 0.42, IQR: 0.04; = 0.004) in PAH compared to our control group. Also, higher total resistance ( ; median: 6.89 mmHg × min/l, IQR: 2.16 mmHg × min/l vs. median: 3.99 mmHg × min/l, IQR: 1.15 mmHg × min/l; = 0.002) and lower total compliance ( ; median: 0.13 ml/mmHg, IQR: 0.15 ml/mmHg vs. median: 0.85 ml/mmHg, IQR: 0.51 ml/mmHg; = 0.041) were observed in the PAH group. Furthermore, lower TAWSS values were seen at the main PA arteries (MPAs) of PAH patients (median: 0.81 Pa, IQR: 0.47 Pa vs. median: 1.56 Pa, IQR: 0.89 Pa; = 0.026) compared to controls. Correlation analysis within the PAH group found that was directly correlated to the PA regurgitant flow ( = 0.84, = 0.018) and inversely related to TAWSS ( = -0.72, = 0.051). Results suggest that the estimated elastic modulus may be closely related to PAH hemodynamic changes in pulmonary arteries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2020.611149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901991PMC
January 2021

Role of coronary flow regulation and cardiac-coronary coupling in mechanical dyssynchrony associated with right ventricular pacing.

Am J Physiol Heart Circ Physiol 2021 03 24;320(3):H1037-H1054. Epub 2020 Dec 24.

Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan.

Mechanical dyssynchrony (MD) affects left ventricular (LV) mechanics and coronary perfusion. To understand the multifactorial effects of MD, we developed a computational model that bidirectionally couples the systemic circulation with the LV and coronary perfusion with flow regulation. In the model, coronary flow in the left anterior descending (LAD) and left circumflex (LCX) arteries affects the corresponding regional contractility based on a prescribed linear LV contractility-coronary flow relationship. The model is calibrated with experimental measurements of LV pressure and volume, as well as LAD and LCX flow rate waveforms acquired under regulated and fully dilated conditions from a swine under right atrial (RA) pacing. The calibrated model is applied to simulate MD. The model can simultaneously reproduce the reduction in mean LV pressure (39.3%), regulated flow (LAD: 7.9%; LCX: 1.9%), LAD passive flow (21.6%), and increase in LCX passive flow (15.9%). These changes are associated with right ventricular pacing compared with RA pacing measured in the same swine only when LV contractility is affected by flow alterations with a slope of 1.4 mmHg/mL in a contractility-flow relationship. In sensitivity analyses, the model predicts that coronary flow reserve (CFR) decreases and increases in the LAD and LCX with increasing delay in LV free wall contraction. These findings suggest that asynchronous activation associated with MD impacts ) the loading conditions that further affect the coronary flow, which may explain some of the changes in CFR, and ) the coronary flow that reduces global contractility, which contributes to the reduction in LV pressure. A computational model that couples the systemic circulation of the left ventricular (LV) and coronary perfusion with flow regulation is developed to study the effects of mechanical dyssynchrony. The delayed contraction in the LV free wall with respect to the septum has a significant effect on LV function and coronary flow reserve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00549.2020DOI Listing
March 2021

Biomechanics of Human Fetal Hearts with Critical Aortic Stenosis.

Ann Biomed Eng 2021 May 11;49(5):1364-1379. Epub 2020 Nov 11.

Department of Bioengineering, Imperial College London, London, UK.

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10439-020-02683-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058006PMC
May 2021

Effects of Mechanical Dyssynchrony on Coronary Flow: Insights From a Computational Model of Coupled Coronary Perfusion With Systemic Circulation.

Front Physiol 2020 14;11:915. Epub 2020 Aug 14.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.

Mechanical dyssynchrony affects left ventricular (LV) mechanics and coronary perfusion. Due to the confounding effects of their bi-directional interactions, the mechanisms behind these changes are difficult to isolate from experimental and clinical studies alone. Here, we develop and calibrate a closed-loop computational model that couples the systemic circulation, LV mechanics, and coronary perfusion. The model is applied to simulate the impact of mechanical dyssynchrony on coronary flow in the left anterior descending artery (LAD) and left circumflex artery (LCX) territories caused by regional alterations in perfusion pressure and intramyocardial pressure (). We also investigate the effects of regional coronary flow alterations on regional LV contractility in mechanical dyssynchrony based on prescribed contractility-flow relationships without considering autoregulation. The model predicts that LCX and LAD flows are reduced by 7.2%, and increased by 17.1%, respectively, in mechanical dyssynchrony with a systolic dyssynchrony index of 10% when the LAD's is synchronous with the arterial pressure. The LAD flow is reduced by 11.6% only when its is delayed with respect to the arterial pressure by 0.07 s. When contractility is sensitive to coronary flow, mechanical dyssynchrony can affect global LV mechanics, s and contractility that in turn, further affect the coronary flow in a feedback loop that results in a substantial reduction of /, indicative of ischemia. Taken together, these findings imply that regional s play a significant role in affecting regional coronary flows in mechanical dyssynchrony and the changes in regional coronary flow may produce ischemia when contractility is sensitive to the changes in coronary flow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457036PMC
August 2020

Force-dependent recruitment from myosin OFF-state increases end-systolic pressure-volume relationship in left ventricle.

Biomech Model Mechanobiol 2020 Dec 28;19(6):2683-2692. Epub 2020 Apr 28.

Department of Mechanical Engineering, University of Kentucky, 269 Ralph G. Anderson Building, Lexington, KY, 40506-0503, USA.

Finite element (FE) modeling is becoming increasingly prevalent in the world of cardiac mechanics; however, many existing FE models are phenomenological and thus do not capture cellular-level mechanics. This work implements a cellular-level contraction scheme into an existing nonlinear FE code to model ventricular contraction. Specifically, this contraction model incorporates three myosin states: OFF-, ON-, and an attached force-generating state. It has been speculated that force-dependent transitions from the OFF- to ON-state may contribute to length-dependent activation at the cellular level. The current work investigates the contribution of force-dependent recruitment out of the OFF-state to ventricular-level function, specifically the Frank-Starling relationship, as seen through the end-systolic pressure-volume relationship (ESPVR). Five FE models were constructed using geometries of rat left ventricles obtained via cardiac magnetic resonance imaging. FE simulations were conducted to optimize parameters for the cellular contraction model such that the differences between FE predicted ventricular pressures for the models and experimentally measured pressures were minimized. The models were further validated by comparing FE predicted end-systolic strain to experimentally measured strain. Simulations mimicking vena cava occlusion generated descending pressure volume loops from which ESPVRs were calculated. In simulations with the inclusion of the OFF-state, using a force-dependent transition to the ON-state, the ESPVR calculated was steeper than in simulations excluding the OFF-state. Furthermore, the ESPVR was also steeper when compared to models that included the OFF-state without a force-dependent transition. This suggests that the force-dependent recruitment of thick filament heads from the OFF-state at the cellular level contributes to the Frank-Starling relationship observed at the organ level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10237-020-01331-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606253PMC
December 2020

Overview of mathematical modeling of myocardial blood flow regulation.

Am J Physiol Heart Circ Physiol 2020 04 6;318(4):H966-H975. Epub 2020 Mar 6.

The California Medical Innovations Institute Incorporated, San Diego, California.

The oxygen consumption by the heart and its extraction from the coronary arterial blood are the highest among all organs. Any increase in oxygen demand due to a change in heart metabolic activity requires an increase in coronary blood flow. This functional requirement of adjustment of coronary blood flow is mediated by coronary flow regulation to meet the oxygen demand without any discomfort, even under strenuous exercise conditions. The goal of this article is to provide an overview of the theoretical and computational models of coronary flow regulation and to reveal insights into the functioning of a complex physiological system that affects the perfusion requirements of the myocardium. Models for three major control mechanisms of myogenic, flow, and metabolic control are presented. These explain how the flow regulation mechanisms operating over multiple spatial scales from the precapillaries to the large coronary arteries yield the myocardial perfusion characteristics of flow reserve, autoregulation, flow dispersion, and self-similarity. The review not only introduces concepts of coronary blood flow regulation but also presents state-of-the-art advances and their potential to impact the assessment of coronary microvascular dysfunction (CMD), cardiac-coronary coupling in metabolic diseases, and therapies for angina and heart failure. Experimentalists and modelers not trained in these models will have exposure through this review such that the nonintuitive and highly nonlinear behavior of coronary physiology can be understood from a different perspective. This survey highlights knowledge gaps, key challenges, future research directions, and novel paradigms in the modeling of coronary flow regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00563.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191499PMC
April 2020

Multiscale Modeling Framework of Ventricular-Arterial Bi-directional Interactions in the Cardiopulmonary Circulation.

Front Physiol 2020 31;11. Epub 2020 Jan 31.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.

Ventricular-arterial coupling plays a key role in the physiologic function of the cardiovascular system. We have previously described a hybrid lumped-finite element (FE) modeling framework of the systemic circulation that couples idealized FE models of the aorta and the left ventricle (LV). Here, we describe an extension of the lumped-FE modeling framework that couples patient-specific FE models of the left and right ventricles, aorta and the large pulmonary arteries in both the systemic and pulmonary circulations. Geometries of the FE models were reconstructed from magnetic resonance (MR) images acquired in a pediatric patient diagnosed with pulmonary arterial hypertension (PAH). The modeling framework was calibrated with pressure waveforms acquired in the heart and arteries by catheterization as well as ventricular volume and arterial diameter waveforms measured from MR images. The calibrated model hemodynamic results match well with the clinically-measured waveforms (volume and pressure) in the LV and right ventricle (RV) as well as with the clinically-measured waveforms (pressure and diameter) in the aorta and main pulmonary artery. The calibrated framework was then used to simulate three cases, namely, (1) an increase in collagen in the large pulmonary arteries, (2) a decrease in RV contractility, and (3) an increase in the total pulmonary arterial resistance, all characteristics of progressive PAH. The key finding from these simulations is that hemodynamics of the pulmonary vasculature and RV wall stress are more sensitive to vasoconstriction with a 10% of reduction in the lumen diameter of the distal vessels than a 67% increase in the proximal vessel's collagen mass.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025512PMC
January 2020

In-silico assessment of the effects of right ventricular assist device on pulmonary arterial hypertension using an image based biventricular modeling framework.

Mech Res Commun 2019 Apr 15;97:101-111. Epub 2019 Apr 15.

Department of mechanical engineering, Michigan State University, East Lansing, Michigan, USA.

Pulmonary arterial hypertension (PAH) is a heart disease that is characterized by an abnormally high pressure in the pulmonary artery (PA). While right ventricular assist device (RVAD) has been considered recently as a treatment option for the end-stage PAH patients, its effects on biventricular mechanics are, however, largely unknown. To address this issue, we developed an image-based modeling framework consisting of a biventricular finite element (FE) model that is coupled to a lumped model describing the pulmonary and systemic circulations in a closed-loop system. The biventricular geometry was reconstructed from the magnetic resonance images of two PAH patients showing different degree of RV remodeling and a normal subject. The framework was calibrated to match patient-specific measurements of the left ventricular (LV) and RV volume and pressure waveforms. An RVAD model was incorporated into the calibrated framework and simulations were performed with different pump speeds. Results showed that RVAD unloads the RV, improves cardiac output and increases septum curvature, which are more pronounced in the PAH patient with severe RV remodeling. These improvements, however, are also accompanied by an adverse increase in the PA pressure. These results suggest that the RVAD implantation may need to be optimized depending on disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mechrescom.2019.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980470PMC
April 2019

Three-dimensional biventricular strains in pulmonary arterial hypertension patients using hyperelastic warping.

Comput Methods Programs Biomed 2020 Jun 17;189:105345. Epub 2020 Jan 17.

National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Duke-NUS Medical School, Singapore. Electronic address:

Background And Objective: Evaluation of biventricular function is an essential component of clinical management in pulmonary arterial hypertension (PAH). This study aims to examine the utility of biventricular strains derived from a model-to-image registration technique in PAH patients in comparison to age- and gender-matched normal controls.

Methods: A three-dimensional (3D) model was reconstructed from cine short- and long-axis cardiac magnetic resonance (CMR) images and subsequently partitioned into right ventricle (RV), left ventricle (LV) and septum. The hyperelastic warping method was used to register the meshed biventricular finite element model throughout the cardiac cycle and obtain the corresponding biventricular circumferential, longitudinal and radial strains.

Results: Intra- and inter-observer reproducibility of biventricular strains was excellent with all intra-class correlation coefficients > 0.84. 3D biventricular longitudinal, circumferential and radial strains for RV, LV and septum were significantly decreased in PAH patients compared with controls. Receiver operating characteristic (ROC) analysis showed that the 3D biventricular strains were better early markers (Area under the ROC curve = 0.96 for RV longitudinal strain) of ventricular dysfunction than conventional parameters such as two-dimensional strains and ejection fraction.

Conclusions: Our highly reproducible methodology holds potential for extending CMR imaging to characterize 3D biventricular strains, eventually leading to deeper understanding of biventricular mechanics in PAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmpb.2020.105345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198336PMC
June 2020

Computational quantification of patient-specific changes in ventricular dynamics associated with pulmonary hypertension.

Am J Physiol Heart Circ Physiol 2019 12 1;317(6):H1363-H1375. Epub 2019 Nov 1.

Simula Research Laboratory, Oslo, Norway.

Pulmonary arterial hypertension (PAH) causes an increase in the mechanical loading imposed on the right ventricle (RV) that results in progressive changes to its mechanics and function. Here, we quantify the mechanical changes associated with PAH by assimilating clinical data consisting of reconstructed three-dimensional geometry, pressure, and volume waveforms, as well as regional strains measured in patients with PAH ( = 12) and controls ( = 6) within a computational modeling framework of the ventricles. Modeling parameters reflecting regional passive stiffness and load-independent contractility as indexed by the tissue active tension were optimized so that simulation results matched the measurements. The optimized parameters were compared with clinical metrics to find usable indicators associated with the underlying mechanical changes. Peak contractility of the RV free wall (RVFW) γ was found to be strongly correlated and had an inverse relationship with the RV and left ventricle (LV) end-diastolic volume ratio (i.e., RVEDV/LVEDV) (RVEDV/LVEDV)+ 0.44,  = 0.77). Correlation with RV ejection fraction ( = 0.50) and end-diastolic volume index ( = 0.40) were comparatively weaker. Patients with with RVEDV/LVEDV > 1.5 had 25% lower γ ( < 0.05) than that of the control. On average, RVFW passive stiffness progressively increased with the degree of remodeling as indexed by RVEDV/LVEDV. These results suggest a mechanical basis of using RVEDV/LVEDV as a clinical index for delineating disease severity and estimating RVFW contractility in patients with PAH. This article presents patient-specific data assimilation of a patient cohort and physical description of clinical observations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00094.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132315PMC
December 2019

Model of Anisotropic Reverse Cardiac Growth in Mechanical Dyssynchrony.

Sci Rep 2019 09 3;9(1):12670. Epub 2019 Sep 3.

Department of Mechanical Engineering, Michigan State University, East Lansing, USA.

Based on recent single-cell experiments showing that longitudinal myocyte stretch produces both parallel and serial addition of sarcomeres, we developed an anisotropic growth constitutive model with elastic myofiber stretch as the growth stimuli to simulate long-term changes in biventricular geometry associated with alterations in cardiac electromechanics. The constitutive model is developed based on the volumetric growth framework. In the model, local growth evolutions of the myocyte's longitudinal and transverse directions are driven by the deviations of maximum elastic myofiber stretch over a cardiac cycle from its corresponding local homeostatic set point, but with different sensitivities. Local homeostatic set point is determined from a simulation with normal activation pattern. The growth constitutive model is coupled to an electromechanics model and calibrated based on both global and local ventricular geometrical changes associated with chronic left ventricular free wall pacing found in previous animal experiments. We show that the coupled electromechanics-growth model can quantitatively reproduce the following: (1) Thinning and thickening of the ventricular wall respectively at early and late activated regions and (2) Global left ventricular dilation as measured in experiments. These findings reinforce the role of elastic myofiber stretch as a growth stimulant at both cellular level and tissue-level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-48670-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722088PMC
September 2019

Microstructure-based finite element model of left ventricle passive inflation.

Acta Biomater 2019 05 11;90:241-253. Epub 2019 Apr 11.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA. Electronic address:

Isolating the role(s) of microstructural pathological features in affecting diastolic filling is important in developing targeted treatments for heart diseases. We developed a microstructure-based constitutive model of the myocardium and implemented it in an efficient open-source finite element modeling framework to simulate passive inflation of the left ventricle (LV) in a representative 3D geometry based on experimentally measured muscle fiber architecture. The constitutive model was calibrated using previous tissue-level biaxial mechanical test data derived from the canine heart and validated with independent sets of measurements made at both the isolated constituent and organ level. Using the validated model, we investigated the load taken up by each tissue constituent and their effects on LV passive inflation. The model predicts that the LV compliance is sensitive to the collagen ultrastructure, specifically, the collagen fiber azimuthal angle with respect to the local muscle fiber direction and its waviness. The model also predicts that most of the load in the sub-epicardial and sub-endocardial regions is taken up, respectively, by the muscle fibers and collagen fiber network. This result suggests that normalizing LV passive stiffness by altering the collagen fiber network and myocyte stiffness is most effective when applied to the sub-endocardial and sub-epicardial regions, respectively. This finding may have implication for the development of new pharmaceutical treatments targeting individual cardiac tissue constituents to normalize LV filling function in heart diseases. STATEMENT OF SIGNIFICANCE: Current constitutive models describing the tissue mechanical behavior of the myocardium are largely phenomenological. While able to represent the bulk tissue mechanical behavior, these models cannot distinguish the contribution of the tissue constituents and their ultrastructure to heart function. Although microstructure-based constitutive models can be used to isolate the role of tissue ultrastructure, they have not been implemented in a computational framework that can accommodate realistic 3D organ geometry. The present study addresses these issues by developing and validating a microstructure-based computational modeling framework, which is used to investigate the role of tissue constituents and their ultrastructure in affecting heart function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2019.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677579PMC
May 2019

Closing the therapeutic loop.

Arch Biochem Biophys 2019 03 9;663:129-131. Epub 2019 Jan 9.

Department of Mechanical Engineering and Department of Surgery, University of Kentucky, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2019.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377839PMC
March 2019

Quantification of Biventricular Strains in Heart Failure With Preserved Ejection Fraction Patient Using Hyperelastic Warping Method.

Front Physiol 2018 19;9:1295. Epub 2018 Sep 19.

National Heart Centre Singapore, Singapore, Singapore.

Heart failure (HF) imposes a major global health care burden on society and suffering on the individual. About 50% of HF patients have preserved ejection fraction (HFpEF). More intricate and comprehensive measurement-focused imaging of multiple strain components may aid in the diagnosis and elucidation of this disease. Here, we describe the development of a semi-automated hyperelastic warping method for rapid comprehensive assessment of biventricular circumferential, longitudinal, and radial strains that is physiological meaningful and reproducible. We recruited and performed cardiac magnetic resonance (CMR) imaging on 30 subjects [10 HFpEF, 10 HF with reduced ejection fraction patients (HFrEF) and 10 healthy controls]. In each subject, a three-dimensional heart model including left ventricle (LV), right ventricle (RV), and septum was reconstructed from CMR images. The hyperelastic warping method was used to reference the segmented model with the target images and biventricular circumferential, longitudinal, and radial strain-time curves were obtained. The peak systolic strains are then measured and analyzed in this study. Intra- and inter-observer reproducibility of the biventricular peak systolic strains was excellent with all ICCs > 0.92. LV peak systolic circumferential, longitudinal, and radial strain, respectively, exhibited a progressive decrease in magnitude from healthy control→HFpEF→HFrEF: control (-15.5 ± 1.90, -15.6 ± 2.06, 41.4 ± 12.2%); HFpEF (-9.37 ± 3.23, -11.3 ± 1.76, 22.8 ± 13.1%); HFrEF (-4.75 ± 2.74, -7.55 ± 1.75, 10.8 ± 4.61%). A similar progressive decrease in magnitude was observed for RV peak systolic circumferential, longitudinal and radial strain: control (-9.91 ± 2.25, -14.5 ± 2.63, 26.8 ± 7.16%); HFpEF (-7.38 ± 3.17, -12.0 ± 2.45, 21.5 ± 10.0%); HFrEF (-5.92 ± 3.13, -8.63 ± 2.79, 15.2 ± 6.33%). Furthermore, septum peak systolic circumferential, longitudinal, and radial strain magnitude decreased gradually from healthy control to HFrEF: control (-7.11 ± 1.81, 16.3 ± 3.23, 18.5 ± 8.64%); HFpEF (-6.11 ± 3.98, -13.4 ± 3.02, 12.5 ± 6.38%); HFrEF (-1.42 ± 1.36, -8.99 ± 2.96, 3.35 ± 2.95%). The ROC analysis indicated LV peak systolic circumferential strain to be the most sensitive marker for differentiating HFpEF from healthy controls. Our results suggest that the hyperelastic warping method with the CMR-derived strains may reveal subtle impairment in HF biventricular mechanics, in particular despite a "normal" ventricular ejection fraction in HFpEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2018.01295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156386PMC
September 2018

High Spatial Resolution Multi-Organ Finite Element Modeling of Ventricular-Arterial Coupling.

Front Physiol 2018 2;9:119. Epub 2018 Mar 2.

Department of Mechanical Engineering, Michigan State University, East Lansing, MI, United States.

While it has long been recognized that bi-directional interaction between the heart and the vasculature plays a critical role in the proper functioning of the cardiovascular system, a comprehensive study of this interaction has largely been hampered by a lack of modeling framework capable of simultaneously accommodating high-resolution models of the heart and vasculature. Here, we address this issue and present a computational modeling framework that couples finite element (FE) models of the left ventricle (LV) and aorta to elucidate ventricular-arterial coupling in the systemic circulation. We show in a baseline simulation that the framework predictions of (1) LV pressure-volume loop, (2) aorta pressure-diameter relationship, (3) pressure-waveforms of the aorta, LV, and left atrium (LA) over the cardiac cycle are consistent with the physiological measurements found in healthy human. To develop insights of ventricular-arterial interactions, the framework was then used to simulate how alterations in the geometrical or, material parameter(s) of the aorta affect the LV and vice versa. We show that changing the geometry and microstructure of the aorta model in the framework led to changes in the functional behaviors of both LV and aorta that are consistent with experimental observations. On the other hand, changing contractility and passive stiffness of the LV model in the framework also produced changes in both the LV and aorta functional behaviors that are consistent with physiology principles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2018.00119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841309PMC
March 2018

Efficient estimation of personalized biventricular mechanical function employing gradient-based optimization.

Int J Numer Method Biomed Eng 2018 07 22;34(7):e2982. Epub 2018 Apr 22.

Simula Research Laboratory, 1325, Lysaker, Norway.

Individually personalized computational models of heart mechanics can be used to estimate important physiological and clinically-relevant quantities that are difficult, if not impossible, to directly measure in the beating heart. Here, we present a novel and efficient framework for creating patient-specific biventricular models using a gradient-based data assimilation method for evaluating regional myocardial contractility and estimating myofiber stress. These simulations can be performed on a regular laptop in less than 2 h and produce excellent fit between measured and simulated volume and strain data through the entire cardiac cycle. By applying the framework using data obtained from 3 healthy human biventricles, we extracted clinically important quantities as well as explored the role of fiber angles on heart function. Our results show that steep fiber angles at the endocardium and epicardium are required to produce simulated motion compatible with measured strain and volume data. We also find that the contraction and subsequent systolic stresses in the right ventricle are significantly lower than that in the left ventricle. Variability of the estimated quantities with respect to both patient data and modeling choices are also found to be low. Because of its high efficiency, this framework may be applicable to modeling of patient specific cardiac mechanics for diagnostic purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cnm.2982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043386PMC
July 2018

Contribution of left ventricular residual stress by myocytes and collagen: existence of inter-constituent mechanical interaction.

Biomech Model Mechanobiol 2018 Aug 24;17(4):985-999. Epub 2018 Feb 24.

Michigan State University, 428 S. Shaw Lane, East Lansing, MI, 48824, USA.

We quantify the contribution of myocytes, collagen fibers and their interactions to the residual stress field found in the left ventricle (LV) using both experimental and theoretical methods. Ring tissue samples extracted from normal rat, male and female, LV were treated with collagenase and decellularization to isolate myocytes and collagen fibers, respectively. Opening angle tests were then performed on these samples as well as intact tissue samples containing both constituents that served as control. Our results show that the collagen fibers are the main contributor to the residual stress fields found in the LV. Specifically, opening angle measured in collagen-only samples (106.45[Formula: see text] ± 23.02[Formula: see text]) and myocytes-only samples (21.00[Formula: see text] ± 4.37[Formula: see text]) was significantly higher and lower than that of the control (57.88[Formula: see text] ± 12.29[Formula: see text]), respectively. A constrained mixture (CM) modeling framework was then used to infer these experimental results. We show that the framework cannot reproduce the opening angle found in the intact tissue with measurements made on the collagen-only and myocytes-only samples. Given that the CM framework assumes that each constituent contributes to the overall mechanics simply by their mere presence, this result suggests the existence of some myocyte-collagen mechanical interaction that cannot be ignored in the LV. We then propose an extended CM formulation that takes into account of the inter-constituent mechanical interaction in which constituents are deformed additionally when they are physically combined into a mixture. We show that the intact tissue opening angle can be recovered in this framework.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10237-018-1007-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050161PMC
August 2018

Image-based computational assessment of vascular wall mechanics and hemodynamics in pulmonary arterial hypertension patients.

J Biomech 2018 02 27;68:84-92. Epub 2017 Dec 27.

Department of Mechanical Engineering, Michigan State University, 2555 Engineering Building, East Lansing, MI 48824, USA. Electronic address:

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevated pulmonary arterial (PA) pressure. While several computational hemodynamic models of the pulmonary vasculature have been developed to understand PAH, they are lacking in some aspects, such as the vessel wall deformation and its lack of calibration against measurements in humans. Here, we describe a computational modeling framework that addresses these limitations. Specifically, computational models describing the coupling of hemodynamics and vessel wall mechanics in the pulmonary vasculature of a PAH patient and a normal subject were developed. Model parameters, consisting of linearized stiffness E of the large vessels and Windkessel parameters for each outflow branch, were calibrated against in vivo measurements of pressure, flow and vessel wall deformation obtained, respectively, from right-heart catheterization, phase-contrast and cine magnetic resonance images. Calibrated stiffness E of the proximal PA was 2.0 and 0.5 MPa for the PAH and normal models, respectively. Calibrated total compliance C and resistance R of the distal vessels were, respectively, 0.32 ml/mmHg and 11.3 mmHg∗min/l for the PAH model, and 2.93 ml/mmHg and 2.6 mmHg∗min/l for the normal model. These results were consistent with previous findings that the pulmonary vasculature is stiffer with more constricted distal vessels in PAH patients. Individual effects on PA pressure due to remodeling of the distal and proximal compartments of the pulmonary vasculature were also investigated in a sensitivity analysis. The analysis suggests that the remodeling of distal vasculature contributes more to the increase in PA pressure than the remodeling of proximal vasculature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiomech.2017.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783768PMC
February 2018

Organ-level validation of a cross-bridge cycling descriptor in a left ventricular finite element model: effects of ventricular loading on myocardial strains.

Physiol Rep 2017 Nov;5(21)

Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan

Although detailed cell-based descriptors of cross-bridge cycling have been applied in finite element (FE) heart models to describe ventricular mechanics, these multiscale models have never been tested rigorously to determine if these descriptors, when scaled up to the organ-level, are able to reproduce well-established organ-level physiological behaviors. To address this void, we here validate a left ventricular (LV) FE model that is driven by a cell-based cross-bridge cycling descriptor against key organ-level heart physiology. The LV FE model was coupled to a closed-loop lumped parameter circulatory model to simulate different ventricular loading conditions (preload and afterload) and contractilities. We show that our model is able to reproduce a linear end-systolic pressure volume relationship, a curvilinear end-diastolic pressure volume relationship and a linear relationship between myocardial oxygen consumption and pressurevolume area. We also show that the validated model can predict realistic LV strain-time profiles in the longitudinal, circumferential, and radial directions. The predicted strain-time profiles display key features that are consistent with those measured in humans, such as having similar peak strains, time-to-peak-strain, and a rapid change in strain during atrial contraction at late-diastole. Our model shows that the myocardial strains are sensitive to not only LV contractility, but also to the LV loading conditions, especially to a change in afterload. This result suggests that caution must be exercised when associating changes in myocardial strain with changes in LV contractility. The methodically validated multiscale model will be used in future studies to understand human heart diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.13392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688770PMC
November 2017

Characterization of patient-specific biventricular mechanics in heart failure with preserved ejection fraction: Hyperelastic warping.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:4149-4152

Heart failure with preserved ejection fraction (HFPEF) is considered as a major public health problem. Traditionally, HFPEF is diagnosed based on a "normal" EF, but the studies have explored the potential role of left ventricular mechanics. Furthermore, right ventricular mechanics and bi-ventricular interaction in HFPEF is currently not well understood. In this study, we aim to develop a framework using a hyperelastic warping approach to quantify bi-ventricular and septum strains from cardiac magnetic resonance (CMR) images. Whole heart models were reconstructed in HFPEF, HF with reduced EF (HFREF) and normal control patients, and a Laplace-Dirichlet Rule-Based (LDRB) algorithm was employed to assign circumferential orientation. The LV circumferential strain was 10.56% in normal control, and decreased to 5.90% in HFPEF and 1.66% in HFREF. Interestingly, the RV circumferential strain was 7.29% in normal control, but increased to 8.93% in HFPEF, and decreased to 2.16% in HFREF. The septum circumferential strain was comparable between HFPEF and normal control. Heart failure with preserved ejection fraction demonstrated augmented right ventricular strain and comparable septum strain to maintain its "normal" ejection fraction. This might unveil a new mechanism of bi-ventricular interaction and compensation in heart failure with preserved ejection fraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC.2016.7591640DOI Listing
August 2016

Patient-Specific Computational Analysis of Ventricular Mechanics in Pulmonary Arterial Hypertension.

J Biomech Eng 2016 11;138(11)

Department of Mechanical Engineering, Michigan State University, East Lansing, MI 48824-1226 e-mail:

Patient-specific biventricular computational models associated with a normal subject and a pulmonary arterial hypertension (PAH) patient were developed to investigate the disease effects on ventricular mechanics. These models were developed using geometry reconstructed from magnetic resonance (MR) images, and constitutive descriptors of passive and active mechanics in cardiac tissues. Model parameter values associated with ventricular mechanical properties and myofiber architecture were obtained by fitting the models with measured pressure-volume loops and circumferential strain calculated from MR images using a hyperelastic warping method. Results show that the peak right ventricle (RV) pressure was substantially higher in the PAH patient (65 mmHg versus 20 mmHg), who also has a significantly reduced ejection fraction (EF) in both ventricles (left ventricle (LV): 39% versus 66% and RV: 18% versus 64%). Peak systolic circumferential strain was comparatively lower in both the left ventricle (LV) and RV free wall (RVFW) of the PAH patient (LV: -6.8% versus -13.2% and RVFW: -2.1% versus -9.4%). Passive stiffness, contractility, and myofiber stress in the PAH patient were all found to be substantially increased in both ventricles, whereas septum wall in the PAH patient possessed a smaller curvature than that in the LV free wall. Simulations using the PAH model revealed an approximately linear relationship between the septum curvature and the transseptal pressure gradient at both early-diastole and end-systole. These findings suggest that PAH can induce LV remodeling, and septum curvature measurements may be useful in quantifying transseptal pressure gradient in PAH patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1115/1.4034559DOI Listing
November 2016

An integrated electromechanical-growth heart model for simulating cardiac therapies.

Biomech Model Mechanobiol 2016 08 16;15(4):791-803. Epub 2015 Sep 16.

Simula Research Laboratory, Oslo, Norway.

An emerging class of models has been developed in recent years to predict cardiac growth and remodeling (G&R). We recently developed a cardiac G&R constitutive model that predicts remodeling in response to elevated hemodynamics loading, and a subsequent reversal of the remodeling process when the loading is reduced. Here, we describe the integration of this G&R model to an existing strongly coupled electromechanical model of the heart. A separation of timescale between growth deformation and elastic deformation was invoked in this integrated electromechanical-growth heart model. To test our model, we applied the G&R scheme to simulate the effects of myocardial infarction in a realistic left ventricular (LV) geometry using the finite element method. We also simulate the effects of a novel therapy that is based on alteration of the infarct mechanical properties. We show that our proposed model is able to predict key features that are consistent with experiments. Specifically, we show that the presence of a non-contractile infarct leads to a dilation of the left ventricle that results in a rightward shift of the pressure volume loop. Our model also predicts that G&R is attenuated by a reduction in LV dilation when the infarct stiffness is increased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10237-015-0723-8DOI Listing
August 2016

A Novel Method for Quantifying Smooth Regional Variations in Myocardial Contractility Within an Infarcted Human Left Ventricle Based on Delay-Enhanced Magnetic Resonance Imaging.

J Biomech Eng 2015 Aug 16;137(8):081009. Epub 2015 Jun 16.

Heart failure is increasing at an alarming rate, making it a worldwide epidemic. As the population ages and life expectancy increases, this trend is not likely to change. Myocardial infarction (MI)-induced adverse left ventricular (LV) remodeling is responsible for nearly 70% of heart failure cases. The adverse remodeling process involves an extension of the border zone (BZ) adjacent to an MI, which is normally perfused but shows myofiber contractile dysfunction. To improve patient-specific modeling of cardiac mechanics, we sought to create a finite element model of the human LV with BZ and MI morphologies integrated directly from delayed-enhancement magnetic resonance (DE-MR) images. Instead of separating the LV into discrete regions (e.g., the MI, BZ, and remote regions) with each having a homogeneous myocardial material property, we assumed a functional relation between the DE-MR image pixel intensity and myocardial stiffness and contractility--we considered a linear variation of material properties as a function of DE-MR image pixel intensity, which is known to improve the accuracy of the model's response. The finite element model was then calibrated using measurements obtained from the same patient--namely, 3D strain measurements-using complementary spatial modulation of magnetization magnetic resonance (CSPAMM-MR) images. This led to an average circumferential strain error of 8.9% across all American Heart Association (AHA) segments. We demonstrate the utility of our method for quantifying smooth regional variations in myocardial contractility using cardiac DE-MR and CSPAMM-MR images acquired from a 78-yr-old woman who experienced an MI approximately 1 yr prior. We found a remote myocardial diastolic stiffness of C(0) = 0.102 kPa, and a remote myocardial contractility of T(max) = 146.9 kPa, which are both in the range of previously published normal human values. Moreover, we found a normalized pixel intensity range of 30% for the BZ, which is consistent with the literature. Based on these regional myocardial material properties, we used our finite element model to compute patient-specific diastolic and systolic LV myofiber stress distributions, which cannot be measured directly. One of the main driving forces for adverse LV remodeling is assumed to be an abnormally high level of ventricular wall stress, and many existing and new treatments for heart failure fundamentally attempt to normalize LV wall stress. Thus, our noninvasive method for estimating smooth regional variations in myocardial contractility should be valuable for optimizing new surgical or medical strategies to limit the chronic evolution from infarction to heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1115/1.4030667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476031PMC
August 2015

Human Cardiac Function Simulator for the Optimal Design of a Novel Annuloplasty Ring with a Sub-valvular Element for Correction of Ischemic Mitral Regurgitation.

Cardiovasc Eng Technol 2015 Jun 7;6(2):105-16. Epub 2015 Feb 7.

Department of Surgery, University of California at San Francisco, San Francisco, USA ; Division of Adult Cardiothoracic Surgery, Department of Surgery, School of Medicine, Mount Zion Harold Brunn Institute for Cardiovascular Research, UCSF, 1657 Scott St., Room 219, San Francisco, CA 94143 USA.

Ischemic mitral regurgitation is associated with substantial risk of death. We sought to: (1) detail significant recent improvements to the Dassault Systèmes human cardiac function simulator (HCFS); (2) use the HCFS to simulate normal cardiac function as well as pathologic function in the setting of posterior left ventricular (LV) papillary muscle infarction; and (3) debut our novel device for correction of ischemic mitral regurgitation. We synthesized two recent studies of human myocardial mechanics. The first study presented the robust and integrative finite element HCFS. Its primary limitation was its poor diastolic performance with an LV ejection fraction below 20% caused by overly stiff ex vivo porcine tissue parameters. The second study derived improved diastolic myocardial material parameters using in vivo MRI data from five normal human subjects. We combined these models to simulate ischemic mitral regurgitation by computationally infarcting an LV region including the posterior papillary muscle. Contact between our novel device and the mitral valve apparatus was simulated using Dassault Systèmes SIMULIA software. Incorporating improved cardiac geometry and diastolic myocardial material properties in the HCFS resulted in a realistic LV ejection fraction of 55%. Simulating infarction of posterior papillary muscle caused regurgitant mitral valve mechanics. Implementation of our novel device corrected valve dysfunction. Improvements in the current study to the HCFS permit increasingly accurate study of myocardial mechanics. The first application of this simulator to abnormal human cardiac function suggests that our novel annuloplasty ring with a sub-valvular element will correct ischemic mitral regurgitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13239-015-0216-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427655PMC
June 2015

Utility of high-resolution electroanatomic mapping of the left ventricle using a multispline basket catheter in a swine model of chronic myocardial infarction.

Heart Rhythm 2015 Jan 27;12(1):144-54. Epub 2014 Aug 27.

Department of Medicine, Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco, California. Electronic address:

Background: Standard electroanatomic mapping systems use a single catheter to perform left ventricular substrate mapping. A new mapping system uses a 64-electrode mini-basket catheter to perform rapid automated acquisition of chamber geometry, voltage, and activation.

Objective: The aim of this study was to compare the accuracy of electroanatomic mapping using the basket catheter with that of mapping using a standard linear catheter in a swine model of chronic myocardial infarction.

Methods: Ten swine underwent left anterior descending coronary artery occlusion to create an anteroseptal myocardial infarction. Animals underwent delayed-enhancement magnetic resonance imaging (MRI) and then detailed left ventricular voltage mapping with both the basket and the linear catheter. Map characteristics and scar area were compared between the basket catheter, linear catheter, and MRI. Induced ventricular tachycardia (VT) was mapped with the basket catheter.

Results: More points were acquired with the basket catheter than with the standard catheter (8762 ± 3164 vs 1712 ± 551; P < .001). The fifth percentile of normal bipolar voltage distribution with the basket catheter was 1.54 mV. Using a bipolar voltage cutoff of 1.5 mV, the total infarct areas measured using the basket catheter, linear catheter, and MRI were similar (17.8 cm(2) vs 20.9 cm(2) vs 17.5 cm(2); P = .69); however, the correlation between MRI and catheter scar area measurement was best for the basket catheter (basket vs linear: r = .76 vs r = .71). In 3 animals, sustained poorly tolerated VT was initiated and the circuit mapped successfully with the basket catheter in <5 minutes.

Conclusion: Rapid substrate and activation mapping using a 64-electrode mini-basket catheter allows detailed voltage and activation mapping in postinfarction cardiomyopathy. This system may be useful for substrate and VT mapping in human postinfarction cardiomyopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrthm.2014.08.036DOI Listing
January 2015

Bioinjection treatment: effects of post-injection residual stress on left ventricular wall stress.

J Biomech 2014 Sep 25;47(12):3115-9. Epub 2014 Jun 25.

Department of Surgery, University of California, San Francisco, CA, USA; Department of Bioengineering, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA.

Injection of biomaterials into diseased myocardium has been associated with decreased myofiber stress, restored left ventricular (LV) geometry and improved LV function. However, its exact mechanism(s) of action remained unclear. In this work, we present the first patient-specific computational model of biomaterial injection that accounts for the possibility of residual strain and stress introduced by this treatment. We show that the presence of residual stress can create more heterogeneous regional myofiber stress and strain fields. Our simulation results show that the treatment generates low stress and stretch areas between injection sites, and high stress and stretch areas between the injections and both the endocardium and epicardium. Globally, these local changes are translated into an increase in average myofiber stress and its standard deviation (from 6.9 ± 4.6 to 11.2 ± 48.8 kPa and 30 ± 15 to 35.1 ± 50.9 kPa at end-diastole and end-systole, respectively). We also show that the myofiber stress field is sensitive to the void-to-size ratio. For a constant void size, the myofiber stress field became less heterogeneous with decreasing injection volume. These results suggest that the residual stress and strain possibly generated by biomaterial injection treatment can have large effects on the regional myocardial stress and strain fields, which may be important in the remodeling process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiomech.2014.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163117PMC
September 2014

Invited commentary.

Ann Thorac Surg 2014 Jul;98(1):80

Department of Surgery, University of California-San Francisco, 1657 Scott St, Brunn Bldg, Rm 219, San Francisco, CA 94143. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2014.04.032DOI Listing
July 2014

Distribution of normal human left ventricular myofiber stress at end diastole and end systole: a target for in silico design of heart failure treatments.

J Appl Physiol (1985) 2014 Jul 29;117(2):142-52. Epub 2014 May 29.

Surgery Department, University of California at San Francisco, San Francisco, California;

Ventricular wall stress is believed to be responsible for many physical mechanisms taking place in the human heart, including ventricular remodeling, which is frequently associated with heart failure. Therefore, normalization of ventricular wall stress is the cornerstone of many existing and new treatments for heart failure. In this paper, we sought to construct reference maps of normal ventricular wall stress in humans that could be used as a target for in silico optimization studies of existing and potential new treatments for heart failure. To do so, we constructed personalized computational models of the left ventricles of five normal human subjects using magnetic resonance images and the finite-element method. These models were calibrated using left ventricular volume data extracted from magnetic resonance imaging (MRI) and validated through comparison with strain measurements from tagged MRI (950 ± 170 strain comparisons/subject). The calibrated passive material parameter values were C0 = 0.115 ± 0.008 kPa and B0 = 14.4 ± 3.18; the active material parameter value was Tmax = 143 ± 11.1 kPa. These values could serve as a reference for future construction of normal human left ventricular computational models. The differences between the predicted and the measured circumferential and longitudinal strains in each subject were 3.4 ± 6.3 and 0.5 ± 5.9%, respectively. The predicted end-diastolic and end-systolic myofiber stress fields for the five subjects were 2.21 ± 0.58 and 16.54 ± 4.73 kPa, respectively. Thus these stresses could serve as targets for in silico design of heart failure treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/japplphysiol.00255.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101610PMC
July 2014