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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.
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.
A computational framework is developed to consider the concurrent growth and remodelling (G&R) processes occurring in the large pulmonary artery (PA) and right ventricle (RV), as well as ...ventricular-vascular interactions during the progression of pulmonary arterial hypertension (PAH). This computational framework couples the RV and the proximal PA in a closed-loop circulatory system that operates in a short timescale of a cardiac cycle, and evolves over a long timescale due to G&R processes in the PA and RV. The framework predicts changes in haemodynamics (e.g. 68.2% increase in mean PA pressure), RV geometry (e.g. 38% increase in RV end-diastolic volume) and PA tissue microstructure (e.g. 90% increase in collagen mass) that are consistent with clinical and experimental measurements of PAH. The framework also predicts that a reduction in RV contractility is associated with long-term RV chamber dilation, a common biomarker observed in the late-stage PAH. Sensitivity analyses on the G&R rate constants show that large PA stiffening (both short and long term) is affected by RV remodelling more than the reverse. This framework can serve as a foundation for the future development of a more predictive and comprehensive cardiovascular G&R model with realistic heart and vascular geometries.
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.
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.
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.
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.
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.
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 CT and resistance RT 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.
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.
Hypertrophic cardiomyopathy (HCM) is a genetic heart disease that is associated with many pathological features, such as a reduction in global longitudinal strain (GLS), myofiber disarray and ...hypertrophy. The effects of these features on left ventricle (LV) function are, however, not clear in two phenotypes of HCM, namely, obstructive and non-obstructive. To address this issue, we developed patient-specific computational models of the LV using clinical measurements from 2 female HCM patients and a control subject. Left ventricular mechanics was described using an active stress formulation and myofiber disarray was described using a structural tensor in the constitutive models. Unloaded LV configuration for each subject was first determined from their respective end-diastole LV geometries segmented from the cardiac magnetic resonance images, and an empirical single-beat estimation of the end-diastolic pressure volume relationship. The LV was then connected to a closed-loop circulatory model and calibrated using the clinically measured LV pressure and volume waveforms, peak GLS and blood pressure. Without consideration of myofiber disarray, peak myofiber tension was found to be lowest in the obstructive HCM subject (60 kPa), followed by the non-obstructive subject (242 kPa) and the control subject (375 kPa). With increasing myofiber disarray, we found that peak tension has to increase in the HCM models to match the clinical measurements. In the obstructive HCM patient, however, peak tension was still depressed (cf. normal subject) at the largest degree of myofiber disarray found in the clinic. The computational modeling workflow proposed here can be used in future studies with more HCM patient data.
Myocardial supply changes to accommodate the variation of myocardial demand across the heart wall to maintain normal cardiac function. A computational framework that couples the systemic circulation ...of a left ventricular (LV) finite element model and coronary perfusion in a closed loop is developed to investigate the transmural distribution of the myocardial demand (work density) and supply (perfusion) ratio. Calibrated and validated against measurements of LV mechanics and coronary perfusion, the model is applied to investigate changes in the transmural distribution of passive coronary perfusion, myocardial work density, and their ratio in response to changes in LV contractility, preload, afterload, wall thickness, and cavity volume. The model predicts the following:
Total passive coronary flow varies from a minimum value at the endocardium to a maximum value at the epicardium transmurally that is consistent with the transmural distribution of IMP;
Total passive coronary flow at different transmural locations is increased with an increase in either contractility, afterload, or preload of the LV, whereas is reduced with an increase in wall thickness or cavity volume;
Myocardial work density at different transmural locations is increased transmurally with an increase in either contractility, afterload, preload or cavity volume of the LV, but is reduced with an increase in wall thickness;
Myocardial work density-perfusion mismatch ratio at different transmural locations is increased with an increase in contractility, preload, wall thickness or cavity volume of the LV, and the ratio is higher at the endocardium than the epicardium. These results suggest that an increase in either contractility, preload, wall thickness, or cavity volume of the LV can increase the vulnerability of the subendocardial region to ischemia.
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.
•Image-based finite element model is developed to study vascular changes in pulmonary arterial hypertension (PAH) in humans.•Stress and stiffness resultants are estimated for the vascular constituents.•Elastin is the primary load-bearing constituent in the pulmonary arteries.•Total stress and stiffness resultants are higher in the (PAH) patient than in the control subject.
Closing the therapeutic loop Campbell, Kenneth S.; Yengo, Christopher M.; Lee, Lik-Chuan ...
Archives of biochemistry and biophysics,
03/2019, Volume:
663
Journal Article
PDF
