Passive Left Ventricle Research Articles

The Clinical Applications of Left Atrial Strain: A Comprehensive Review

Left atrial (LA) strain imaging, which measures the deformation of the LA using speckle-tracing echocardiography (STE), has emerged recently as an exciting tool to help provide diagnostic and prognostic information for patients with a broad range of cardiovascular (CV) pathologies. Perhaps due to the LA’s relatively thin-walled architecture compared with the more muscular structure of the left ventricle (LV), functional changes in the left atrium often precede changes in the LV, making LA strain (LAS) an earlier marker for underlying pathology than many conventional echocardiographic parameters. LAS imaging is typically divided into three phases according to the stage of the cardiac cycle: reservoir strain, which is characterized by LA filling during systole; conduit strain, which describes LA deformation during passive LV filling; and booster strain, which provides information on the LA atrium during LA systole in late ventricular diastole. While additional large-population studies are still needed to further solidify the role of LAS in routine clinical practice, this review will discuss the current evidence of its use in different pathologies and explore the possibilities of its applications in the future.

CineCT imaging platform for in-vivo and ex-vivo measurement of myocardial biomechanics post myocardial infarction and following intramyocardial delivery of theranostic hydrogel

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health (NIH) Purpose Myocardial infarction (MI) induces acute regional changes in myocardial strain and stiffness in the infarct and the remote areas of the left ventricle (LV), which lead to adverse changes in LV geometry and function. We hypothesize that cineCT imaging could evaluate these biomechanical changes along with the effects of intramyocardial delivery of theranostic hydrogels. Introduction We present an experimental platform to assess changes in the deformation of the LV myocardium using contrast cineCT (CCT) imaging of the beating porcine heart (active deformation) before and after acute MI and intramyocardial delivery of an imageable theranostic hydrogel. We then assess the acute effects of hydrogel delivery early post-MI on biomechanics (passive deformation) using an ex vivo perfused heart preparation. Methods Contrast cineCT imaging was performed using 64-slice CT on 5 Yorkshire pigs without MI (n = 3) or with MI (n = 2). MI pigs had serial imaging performed before and 1 hour after acute surgical coronary occlusion to induce anterolateral MI. One MI pig was also imaged 1 hour after intramyocardial injection of a novel imageable theranostic iodinated hydrogel within the MI region. Post euthanasia, excised hearts were flushed with chilled UW cardioplegic solution and mounted on a custom inflation apparatus for cineCT imaging during LV inflation by external pump. LV pressure was cycled between 10 and 60 mmHg at 35 bpm. Dilute iohexol was injected into aortic root and UW perfusate (15 ml, 1 ml/sec). CineCT image series were reconstructed, contrast enhanced, resampled to the LV long axis (Z), and exported as a series of 10 CT volumes covering 0-90% of the cardiac/inflation cycle. Volumes were registered incrementally using nonlinear image registration (BioImageSuite) and the calculated displacement at each time point was exported at a resolution of 1 mm. A custom Matlab program was used to fit the displacement field to local trilinear polynomials and then calculate the displacement gradients and 3D Lagrangian strains. To estimate the accuracy of this approach, cardiac volumes were also numerically deformed using a 10 pixel translation and 5% triaxial stretch. Results We successfully acquired serial in-vivo and ex-vivo 3D CineCT images for assessment of the active and passive LV myocardial deformation and tracked deformation through the full cardiac/inflation cycle (Figure 2). Numerical deformation tests showed average tracking errors of < 0.2 mm (1/4 pixel) in the X,Y,Z directions of the volume. These resulted in Lagrangian strain errors of < 0.47% for the in-plane strains EXX and EYY (radial and circumferential plane) and < 0.5% for EZZ (long axis). Conclusions We have developed a novel CineCT imaging platform that allows for high resolution in-vivo and ex-vivo measurement of myocardial biomechanics post-MI and following intramyocardial delivery of imageable theranostic hydrogels, which may improve early active and passive biomechanics.

Abstract PS3-21: Predicting cardiac dysfunction in breast cancer patients undergoing aromatase inhibitor treatment using biomechanical model-based elasticity imaging

Abstract Introduction Premenopausal women with intermediate-high risk HR+ breast cancer often receive near-complete estrogen deprivation with ovarian function suppression concurrent with an AI. Hypoestrogenemia is associated with cardiotoxicity, but the cardiovascular impact of this newer breast cancer treatment is largely unknown. With increases in survival rates and younger women being diagnosed, methods to monitor and predict cardiac damage due to OFS+AI therapy are needed. Left ventricle (LV) ejection fraction is currently used for monitoring cancer treatment-related cardiovascular degradation, and can detect major heart defects, but is insensitive to subclinical left ventricle function. Emerging methods include T1 mapping and estimation of myocardial strain to indicate fibrosis. We propose an extension of these methods by estimating cardiac tissue elasticity using LV wall deformation to drive a biomechanical model. Elasticity is a more functional and direct measurement of tissue response based on structural mechanics driven by patient-specific cardiac magnetic resonance imaging (CMR) data. Elasticity measurements may serve as a predictive biomarker of early AI-induced cardiac changes.MethodsThis study is a retrospective initial proof-of-concept correlative imaging study to an existing clinical study for the use of CMR to detect cardiovascular damage (ESPRIT). Two cohorts of premenopausal breast cancer patients either: (1) undergoing OFS+AI for HR+ breast cancer or (2) triple negative breast cancer (TNBC) patients that have already received chemotherapy, were imaged twice, 3-6 months apart using CINE CMR. TNBC patients serve as the control, with no expectation of further cancer treatment-related cardiac damage. Time steps during passive ventricular diastole were visually selected from CINE CMRs. Each slice was non-rigidly registered to estimate LV deformation during passive filling. Deformation was simulated on a finite element mesh of the LV based on linear elastic transverse isotropic mechanical equilibrium. Using an inverse problem formulation, simulated deformation was compared to model-calculated deformation to estimate the spatial tissue longitudinal and transverse elasticity. Elasticity maps of the LV at initial and final points are compared to determine regional stiffening of the LV wall, to be used as early biomarkers for LV fibrosis. ResultsIn this initial investigation, elasticity maps were analyzed for four patients (n=2 from each cohort). Passive LV tissue stiffening was observed in each AI patient, with 100% and 25% relative increases observed for longitudinal elasticity and 50% increases for transverse elasticity in the basal inferior region, and mid anterior region of the LV in each patient, respectively. No increases in stiffness of the LV were observed for TNBC patients. Ejection fraction remained consistent for all patients. ConclusionIn this proof-of-concept study, we demonstrate that elasticity maps indicate local stiffening of the LV using a biomechanical model-based elasticity imaging method that could be used to indicate cardiac dysfunction in breast cancer patients receiving AIs. Spatial elasticity mapping allows direct observation of structural mechanics to reveal specific areas of LV stiffening. Moving beyond traditional strain imaging, our method yields a functional measure of tissue stiffness to directly indicate cardiac fibrosis. This study demonstrates the use of biomechanical models to interpret CMR and provides potential for use of more advanced constitutive models. Our non-invasive biomechanical model-based elasticity imaging method shows significant promise to indicate early cardiac function deterioration, critical for premenopausal women undergoing extended cancer therapies. Citation Format: Caroline Elizabeth Miller, Jennifer Jordan, Alexandra Thomas, Jared Weis. Predicting cardiac dysfunction in breast cancer patients undergoing aromatase inhibitor treatment using biomechanical model-based elasticity imaging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-21.

Simulation of Left Ventricular Dynamics Using a Low-Order Mathematical Model

The eventual goal of this study is to develop methods for estimating dynamic stresses in the left ventricle (LV) that could be used on-line in clinical settings, based on routinely available measurements. Toward this goal, a low-order theoretical model is presented, in which LV shape is represented using a small number of parameters, allowing rapid computational simulations of LV dynamics. The LV is represented as a thick-walled prolate spheroid containing helical muscle fibers with nonlinear passive and time-dependent active contractile properties. The displacement field during the cardiac cycle is described by three time-dependent parameters, using a family of volume-preserving mappings based on prolate spheroidal coordinates. Stress equilibrium is imposed in weak form and the resulting force balance equations are coupled to a lumped-parameter model of the circulation, leading to a system of differential–algebraic equations, whose numerical solution yields predictions of LV pressure and volume, together with spatial distributions of stresses and strains throughout the cardiac cycle. When static loading of the passive LV is assumed, this approach yields displacement and stress fields that closely match results from a standard finite-element approach. When dynamic motion with active contraction is simulated, substantial variations of fiber stress and strain through the myocardium are predicted. This approach allows simulations of LV dynamics that run faster than real time, and could be used to determine patient-specific parameters of LV performance on-line from clinically available measurements, with the eventual goal of real-time, patient-specific analysis of cardiac parameters.

Left atrium passive ejection fraction is the most sensitive index of type 2 diabetes mellitus-related cardiac changes.

The aims of this study were to use cardiovascular magnetic resonance (CMR) cine to assess left atrium (LA) and left ventricle (LV) function and structure in normotensive type 2 diabetes mellitus (T2DM) patients and to identify the most sensitive index of those T2DM-related cardiac changes. Fifty T2DM patients with normotension (25 males, age 54.7 ± 8.7 years, duration of diabetes: 7.5 ± 5.1 years) and 35 controls (16 males, age: 52.2 ± 13.2 years) were prospectively enrolled. All patients were scanned using CMR four- and two-chamber long-axis cine to assess LA and LV structure and function. Normotensive T2DM patients were associated with decreased LA total ejection fraction (EF), passive EF and LV end diastolic volume, normal LA active EF and LV myocardial mass and increased LV mass/volume (M/V). LA total EF and passive EF correlated with body mass index, duration of diabetes and M/V. To differentiate between diabetic patients and healthy controls, area under the receiver operating characteristic (ROC) curve (AUC) values were calculated to be 0.763, 0.706, 0.647 and 0.649 for LA passive EF, total EF, LVEDV and M/V, respectively. The addition of LA total EF, LVEDV, M/V and the combination thereof did not significantly improve AUC values in a model containing LA passive EF. Normotensive T2DM patients were associated with LA decreased total ejection fraction, decreased passive EF and LV concentric remodeling. Among these indices, LA passive EF was the most sensitive to T2DM-related LA function changes.

Bench Models for Assessing the Mechanics of Mitral Valve Repair and Percutaneous Surgery.

Rapid preclinical evaluations of mitral valve (MV) mechanics are currently best facilitated by bench models of the left ventricle (LV). This review aims to provide a comprehensive assessment of these models to aid interpretation of their resulting data, inform future experimental evaluations, and further the translation of results to procedure and device development. For this review, two types of experimental bench models were evaluated. Rigid LV models were characterized as fluid-mechanical systems capable of testing explanted MVs under static and or pulsatile left heart hemodynamics. Passive LV models were characterized as explanted hearts whose left side is placed in series with a static or pulsatile flow-loop. In both systems, MV function and mechanics can be quantitatively evaluated. Rigid and passive LV models were characterized and evaluated. The materials and methods involved in their construction, function, quantitative capabilities, and disease modeling were described. The advantages and disadvantages of each model are compared to aid the interpretation of their resulting data and inform future experimental evaluations. Repair and percutaneous studies completed in these models were additionally summarized with perspective on future advances discussed. Bench models of the LV provide excellent platforms for quantifying MV repair mechanics and function. While exceptional work has been reported, more research and development is necessary to improve techniques and devices for repair and percutaneous surgery. Continuing efforts in this field will significantly contribute to the further development of procedures and devices, predictions of long-term performance, and patient safety.

Numerical investigation of the effect of cannula placement on thrombosis

Despite the rapid advancement of left ventricular assist devices (LVADs), adverse events leading to deaths have been frequently reported in patients implanted with LVADs, including bleeding, infection, thromboembolism, neurological dysfunction and hemolysis.Cannulation forms an important component with regards to thrombus formation in assisted patients by varying the intraventricular flow distribution in the left ventricle (LV). To investigate the correlation between LVAD cannula placement and potential for thrombus formation, detailed analysis of the intraventricular flow field was carried out in the present study using a two way fluid structure interaction (FSI), axisymmetric model of a passive LV incorporating an inflow cannula. Three different cannula placements were simulated, with device insertion near the LV apex, penetrating one-fourth and mid-way into the LV long axis. The risk of thrombus formation is assessed by analyzing the intraventricular vorticity distribution and its associated vortex intensity, amount of stagnation flow in the ventricle as well as the level of wall shear stress. Our results show that the one-fourth placement of the cannula into the LV achieves the best performance in reducing the risk of thrombus formation. Compared to cannula placement near the apex, higher vortex intensity is achieved at the one-fourth placement, thus increasing wash out of platelets at the ventricular wall. One-fourth LV penetration produced negligible stagnation flow region near the apical wall region, helping to reduce platelet deposition on the surface of the cannula and the ventricular wall.

Adaptation of a Rabbit Myocardium Material Model for Use in a Canine Left Ventricle Simulation Study

The myocardium of the left ventricle (LV) of the heart comprises layers of muscle fibers whose orientation varies through the heart wall. Because of these fibers, accurate modeling of the myocardium stress-strain behavior requires models that are nonlinear, anisotropic, and time-varying. This article describes the development and testing of a material model of the canine LV myocardium, which will be used in ongoing simulations of the mechanics of the LV with fluid-structure interaction. The model assumes that myocardium deformation has two extreme states: one during which the muscle fibers are fully relaxed, and another during which the muscle fibers are fully contracted. During the second state, the "total" stresses are assumed to be the sum of "passive" stresses, which represent the fully relaxed muscle fibers, and "active" stresses, which are additional stresses due to the contraction of the muscle fibers. The canine LV myocardium is modeled as a transversely isotropic material for which material properties vary in the fiber and cross-fiber directions. The material behavior is considered to be hyperelastic and is modeled by a strain-energy density function in a manner that is an adaptation of an approach based on measurements of the stress-strain behavior of rabbit LV myocardia. A numerical method has been developed to calculate suitable parameter values for the passive material model using previous passive canine LV myocardium stress measurements and taking into account existing physical and numerical constraints. In the absence of published measurements of total canine LV myocardium stresses, a method has been developed to estimate these stresses from available passive and total rabbit LV myocardium stresses and then to calculate active material parameter values. Material parameter values were calculated for passive and active canine LV myocardium. Passive stresses calculated using the model compare well to previous stress measurements while active stresses calculated using the model compare well with those approximated from rabbit measurements. The adapted material model of the canine LV myocardium is deemed to be suitable for use in simulations of the operation of both idealized and realistic canine hearts. The estimated model parameter values can be easily revised to more appropriate ones if measurements of active canine LV myocardium stresses become available. The extension of this material model to a fully orthotropic one is also possible but determination of its parameters would require stress-stretch measurements in the fiber and both cross-fiber directions.

Adaptation of Passive Rat Left Ventricle in Diastolic Dysfunction

This article deals with providing a theoretical explanation for quantitative changes in the geometry, the opening angle and the deformation parameters of the rat ventricular wall during adaptation of the passive left ventricle in diastolic dysfunction. A large deformation theory is applied to analyse transmural stress and strain distribution in the left ventricular wall considering it to be made of homogeneous, incompressible, transversely isotropic, non-linear elastic material. The basic assumptions made for computing stress distributions are that the average circumferential stress and strain for the adaptive ventricle is equal to the average circumferential stress and strain in the normotensive ventricle, respectively.All the relevant parameters, such as opening angle, twist per unit length, axial extension, internal and external radii and others, in the stress-free, unloaded and loaded states of normotensive, hypertensive and adaptive left ventricle are determined. The circumferential stress and strain distribution through the ventricular wall are also computed. Our analysis predicts that during adaptation, wall thickness and wall mass of the ventricle increase. These results are consistent with experimental findings and are the indications of initiation of congestive heart failure.

Ras-dependent pathways induce obstructive hypertrophy in echo-selected transgenic mice.

To overcome the genetic and interindividual variability frequently noted in complex phenotypes, we used echocardiographic selection to develop a substrain of myosin light chain (MLC)-Ras (RAS) transgenic mice with an enhanced ventricular hypertrophic phenotype. These echo-selected mice were then compared with wild-type (WT) animals and a pressure overload hypertrophy model (transverse aortic constriction; TAC). Echocardiography demonstrated increased wall thickness in RAS compared with the other groups. We developed novel miniaturized physiological technology to quantitatively identify in vivo intraventricular gradients; increased systolic Doppler velocity was seen in the left ventricle (LV) in 69% of RAS vs. none of WT or TAC. Intracavitary pressure gradients were present in 3 of 10 RAS vs. none of TAC or WT. Passive diastolic LV stiffness was not different among the three groups. Myofibrillar disarray was present in all RAS animals and was significantly more extensive (21.7% area fraction) than in TAC (1.5%) or WT (0.0%). RAS mice had selective induction of natriuretic peptide genes in the LV, a pattern distinct from that induced by pressure overload. Juvenile mortality was significantly increased in the offspring of echo-selected RAS parents. We conclude that adaptation of echocardiography to the mouse permits selection for cardiac phenotypes, and that selectively inbred MLC-Ras transgenic mice faithfully reproduce the molecular, physiological, and pathological features of human hypertrophic cardiomyopathy (HCM). Because previous studies support the concept that hypertrophy in human HCM is secondary to dysfunction created by sarcomeric protein mutations, the current studies suggest that Ras-dependent pathways might play a similar role in forms of human HCM.

STRESSES AND STRAINS IN THE PASSIVE LEFT VENTRICLE

In this paper, we estimate the stresses and strains from the equatorial region down to the apex of the heart by modeling the passive left ventricle as a frustrum of a thick hollow cone. Large deformation theory has been employed in this analysis. Furthermore, the effects of residual stresses and the anisotropy due to muscle fiber orientation have been included. It is observed that circumferential stress, which is the most important physiologically, decreases considerably at the endocardium and is more evenly distributed through the wall when residual stresses are taken into account. The stresses also decrease as we go from the equatorial region to the apex. Because heart muscles physically have residual stresses, the consequent lower stress gradient through the wall enhances the diastolic function of the left ventricle.

Effects of pressure overload on the passive mechanics of the rat left ventricle.

Both myocyte growth and changes in the extracellular matrix may affect the passive mechanics of the left ventricle (LV). Pressure-volume (PV) relationships and midwall two-dimensional strains versus passive loading were measured in isolated rat hearts 2 and 6 weeks after ascending aortic banding. Collagen area fractions and perimysial fibril orientations were determined with picrosirius-polarization microscopy, and the equatorial region of the LV was modeled with finite element analysis of a transversely isotropic cylinder with the same material properties in hypertrophy and control. Compared with weight-matched shams, heart weight increased at 2 (19%) and 6 (22%) weeks, as did LV wall thickness (6% and 31%, respectively). The PV curve became less compliant with hypertrophy; only circumferential strain decreased after hypertrophy. Collagen area fractions were not different at either subendocardium or subepicardium (3.37 +/- 1.06 versus 3.96 +/- 0.76 at 2 weeks and 3.61 +/- 1.30 versus 4.22 +/- 1.50 at 6 weeks for banded and sham, respectively; subendocardium). Collagen and muscle fiber orientations also did not change with hypertrophy. The finite element model predicted trends in the strains similar to those found experimentally. Thus, in this model of pressure-overload hypertrophy, the decreases in compliance and circumferential strain of the passive LV are not due to changes in the percentage of extracellular matrix, but rather to global geometric changes.

Effect of residual stress on transmural sarcomere length distributions in rat left ventricle.

It has been previously shown that the myocardium in the walls of the unloaded passive left ventricle (LV) is not stress free. To assess the functional significance of residual stress in the ventricular wall, we compared the transmural distributions of sarcomere length (SL) in specimens of rat LV myocardium fixed in the unloaded (residually stressed) and stress-free states. When a cross-sectional ring cut from the equatorial region of the freshly arrested rat hearts was cut radially to relieve residual stress, it sprang open into an arc with a mean opening angle of 45 +/- 15 degrees (SD) (n = 8). During immersion fixation in glutaraldehyde, the opening angle increased 9.3 +/- 7.1 degrees (SD) overall. SLs were measured at 16 equally spaced transmural locations from the free wall in the stress-free tissue sections and were compared with control measurements from adjacent cross-sectional rings in which residual stress had not been relieved. Average SL for the stress-free tissue (n = 11) was 1.84 +/- 0.05 (SD) microns and for the unloaded tissue was 1.83 +/- 0.06 (SD) microns. However, analysis of covariance on the pooled data showed that the transmural distributions were significantly different (P < 0.0001). Whereas SL was uniform across the wall in the stress-free state with a mean gradient of -0.014 +/- 0.044 (SD) microns/total wall thickness, there was a significant decrease (P = 0.001) in SL from epicardium to endocardium in the intact unloaded tissue [slope = -0.114 +/- 0.054 (SD) microns/total wall thickness].(ABSTRACT TRUNCATED AT 250 WORDS)

Passive Material Properties of Intact Ventricular Myocardium Determined From a Cylindrical Model

The equatorial region of the canine left ventricle was modeled as a thick-walled cylinder consisting of an incompressible hyperelastic material with homogeneous exponential properties. The anisotropic properties of the passive myocardium were assumed to be locally transversely isotropic with respect to a fiber axis whose orientation varied linearly across the wall. Simultaneous inflation, extension, and torsion were applied to the cylinder to produce epicardial strains that were measured previously in the potassium-arrested dog heart. Residual stress in the unloaded state was included by considering the stress-free configuration to be a warped cylindrical arc. In the special case of isotropic material properties, torsion and residual stress both significantly reduced the high circumferential stress peaks predicted at the endocardium by previous models. However, a resultant axial force and moment were necessary to cause the observed epicardial deformations. Therefore, the anisotropic material parameters were found that minimized these resultants and allowed the prescribed displacements to occur subject to the known ventricular pressure loads. The global minimum solution of this parameter optimization problem indicated that the stiffness of passive myocardium (defined for a 20 percent equibiaxial extension) would be 2.4 to 6.6 times greater in the fiber direction than in the transverse plane for a broad range of assumed fiber angle distributions and residual stresses. This agrees with the results of biaxial tissue testing. The predicted transmural distributions of fiber stress were relatively flat with slight peaks in the subepicardium, and the fiber strain profiles agreed closely with experimentally observed sarcomere length distributions. The results indicate that torsion, residual stress and material anisotropy associated with the fiber architecture all can act to reduce endocardial stress gradients in the passive left ventricle.

A two-phase finite element model of the diastolic left ventricle

A porous medium finite element model of the passive left ventricle is presented. The model is axisymmetric and allows for finite deformation, including torsion about the axis of symmetry. An anisotropic quasi-linear viscoelastic constitutive relation is implemented in the model. The model accounts for changing fibre orientation across the myocardial wall. During passive filling, the apex rotates in a clockwise direction relative to the base for an observer looking from apex to base. within an intraventricular pressure range of 0–3 kPa the rotation angle of all nodes remained below 0.1 rad. Diastolic viscoelasticity of myocardial tissue is shown to reduce transmural differences of preload-induced sarcomere stretch and to generate residual stresses in an unloaded ventricular wall, consistent with the observation of opening angles seen when the heart is slit open. It is shown that the ventricular model stiffens following an increase of the intracoronary blood volume. At a given left ventricular volume, left ventricular pressure increases from 1.5 to 2.0 kPa when raising the intracoronary blood volume from 9 to 14 ml (100 g) −1 left ventricle.

Constitutive relations and finite deformations of passive cardiac tissue II: stress analysis in the left ventricle.

We present a new approach for estimation of transmural distributions of stress and strain in the equatorial region of a passive left ventricle. We employ a thick-walled cylindrical geometry, assume that myocardium is incompressible, and use a three-dimensional constitutive relation that yields a material symmetry consistent with observed transmural variations in muscle fiber orientations. Moreover, we consider finite deformations including inflation, extension, twist, and transmural shearing and suggest a new method for determination of the requisite deformation parameters directly from experimental strain data. We show representative transmural distributions of stress and strain, and perform a parametric study to illustrate differing predictions of stress induced by varying boundary conditions, muscle fiber orientations, or modes of deformation. Our analysis can be used to guide and check future predictions of cardiac stresses, and to guide experimentalists by suggesting the accuracy of measurements essential for stress analysis in the heart.

Stress in a model of the passive left ventricle

Stress in a model of the passive left ventricle

A non-linear, viscoelastic, axisymmetric, two-phase finite element model of the passive left ventricle

A non-linear, viscoelastic, axisymmetric, two-phase finite element model of the passive left ventricle