Myocardial adaptation and exercise performance in patients with pulmonary arterial hypertension assessed with patient-specific computer simulations

2021 ◽  
Vol 321 (5) ◽  
pp. H865-H880
Author(s):  
Niels Thue Olsen ◽  
Christoffer Göransson ◽  
Niels Vejlstrup ◽  
Jørn Carlsen
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Computer Simulations ◽  
Patient Specific ◽  
Limiting Factor ◽  
Myocardial Mechanics ◽  
Use Of Data ◽  
Pulmonary Arterial ◽  
Myocardial Adaptation ◽  
Rest And Exercise

Computer simulations of the myocardial mechanics and hemodynamics of rest and exercise were performed in nine patients with pulmonary arterial hypertension and 10 control subjects, with the use of data from invasive catheterization and from cardiac magnetic resonance. This approach allowed a detailed analysis of myocardial adaptation to pulmonary arterial hypertension and showed how reduction in right ventricular inotropic reserve is the important limiting factor for an increase in cardiac output during exercise.

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

2016 ◽  
Vol 138 (11) ◽  
Author(s):  
Ce Xi ◽  
Candace Latnie ◽  
Xiaodan Zhao ◽  
Ju Le Tan ◽  
Samuel T. Wall ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Left Ventricle ◽  
Arterial Hypertension ◽  
Pressure Gradient ◽  
Circumferential Strain ◽  
Patient Specific ◽  
Free Wall ◽  
Mr Images ◽  
Ventricular Mechanics ◽  
Pulmonary Arterial

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.

scholarly journals Identification of a common Wnt-associated genetic signature across multiple cell types in pulmonary arterial hypertension

2014 ◽  
Vol 307 (5) ◽  
pp. C415-C430 ◽  
Author(s):  
James D. West ◽  
Eric D. Austin ◽  
Christa Gaskill ◽  
Shennea Marriott ◽  
Rubin Baskir ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Wnt Signaling Pathway ◽  
Cell Types ◽  
Patient Specific ◽  
Molecular Defect ◽  
Expression Array ◽  
Genetic Signature ◽  
Multiple Cell ◽  
Pulmonary Arterial

Understanding differences in gene expression that increase risk for pulmonary arterial hypertension (PAH) is essential to understanding the molecular basis for disease. Previous studies on patient samples were limited by end-stage disease effects or by use of nonadherent cells, which are not ideal to model vascular cells in vivo. These studies addressed the hypothesis that pathological processes associated with PAH may be identified via a genetic signature common across multiple cell types. Expression array experiments were initially conducted to analyze cell types at different stages of vascular differentiation (mesenchymal stromal and endothelial) derived from PAH patient-specific induced pluripotent stem (iPS) cells. Molecular pathways that were altered in the PAH cell lines were then compared with those in fibroblasts from 21 patients, including those with idiopathic and heritable PAH. Wnt was identified as a target pathway and was validated in vitro using primary patient mesenchymal and endothelial cells. Taken together, our data suggest that the molecular lesions that cause PAH are present in all cell types evaluated, regardless of origin, and that stimulation of the Wnt signaling pathway was a common molecular defect in both heritable and idiopathic PAH.

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

2021 ◽  
Vol 8 ◽  
Author(s):  
Byron A. Zambrano ◽  
Nathan McLean ◽  
Xiaodan Zhao ◽  
Ju-Le Tan ◽  
Liang Zhong ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arteries ◽  
Patient Specific ◽  
Pulmonary Vasculature ◽  
Control Group ◽  
Regurgitant Flow ◽  
Wall Stiffness ◽  
Wall Deformation ◽  
Pulmonary Arterial

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 (E), relative area change (RAC), diastolic diameter (D), regurgitant flow, and time-averaged wall shear stress (TAWSS) of the proximal PA, as well as the total arterial resistance (Rt) and compliance (Ct) 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; P = 0.007] with a larger diameter (median: 32 mm, IQR: 5.25 mm vs. median: 25 mm, IQR: 2 mm; P = 0.015) and a reduced RAC (median: 0.22, IQR: 0.10 vs. median: 0.42, IQR: 0.04; P = 0.004) in PAH compared to our control group. Also, higher total resistance (Rt; 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; P = 0.002) and lower total compliance (Ct; median: 0.13 ml/mmHg, IQR: 0.15 ml/mmHg vs. median: 0.85 ml/mmHg, IQR: 0.51 ml/mmHg; P = 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; P = 0.026) compared to controls. Correlation analysis within the PAH group found that E was directly correlated to the PA regurgitant flow (r = 0.84, P = 0.018) and inversely related to TAWSS (r = −0.72, P = 0.051). Results suggest that the estimated elastic modulus E may be closely related to PAH hemodynamic changes in pulmonary arteries.

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