Parameter subset reduction for patient-specific modelling of arrhythmogenic cardiomyopathy-related mutation carriers in the CircAdapt model

Osta, N Van; Lyon, Aurore; Kirkels, Feddo P.; Koopsen, Tijmen; Loon, Tim van; Teske, Arco J.; Delhaas, Tammo; Huberts, Wouter; Lumens, Joost

doi:10.1098/rsta.2019.0347

Cited by 15 publications

(56 citation statements)

References 32 publications

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“…Non-personalized simulations representing subgroups of AC mutation carriers showed that at least some degree of local mechanical dysfunction was needed to reproduce the measured RV deformation abnormalities. A recently published sensitivity analysis 8 confirmed that model parameters related to both activation delay and mechanical dysfunction are essential to reproduce myocardial deformation using the CircAdapt model. 8 The current study extends this previous work by estimating patient-specific myocardial substrates in all three RVfw segments and by including the LV mechanics for a more realistic approach of the patient’s haemodynamics.…”

Section: Discussionmentioning

confidence: 83%

“…A recently published sensitivity analysis 8 confirmed that model parameters related to both activation delay and mechanical dysfunction are essential to reproduce myocardial deformation using the CircAdapt model. 8 The current study extends this previous work by estimating patient-specific myocardial substrates in all three RVfw segments and by including the LV mechanics for a more realistic approach of the patient’s haemodynamics. These patient-specific simulations confirmed hypothesis that abnormal deformation patterns are related to increased regional heterogeneity in contractility and compliance without a heterogeneity in activation delay.…”

Section: Discussionmentioning

confidence: 83%

“…A parameter subset with 21 parameters essential for modelling regional RVfw, IVS, and LVfw deformation in AC mutation carriers was previously identified. 8 CO and heart rate (HR) were direct input parameters of the model and thereby set from the measurements. The former was obtained from CMR data, while the latter was obtained from the RV focused four-chamber view.…”

Section: Methodsmentioning

confidence: 99%

“…Parameters were individually estimated using a parameter estimation framework previously described in more detail. 8 This framework estimates model parameters using the clinical data as described above and results in a virtual subject that reproduces the clinical data. In brief, the parameter estimation framework consisted of two steps.…”

Section: Methodsmentioning

confidence: 99%

“…The aim of this study is to non-invasively estimate the pathophysiological substrates underlying regional deformation abnormalities in the individual AC mutation carrier, using imaging-based patient-specific computer simulations. We use a parameter estimation protocol based on a previously established framework 8 which simulates myocardial deformation to identify regional tissue properties.…”

Section: Introductionmentioning

confidence: 99%

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Electromechanical substrate characterization in arrhythmogenic cardiomyopathy using imaging-based patient-specific computer simulations

et al. 2021

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Aims Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease, characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. The aim of this study is to use computer simulations to non-invasively estimate the individual patient’s myocardial tissue substrates underlying regional right ventricular (RV) deformation abnormalities in a cohort of AC mutation carriers. Methods and results In 68 AC mutation carriers and 20 control subjects, regional longitudinal deformation patterns of the RV free wall (RVfw), interventricular septum (IVS), and left ventricular free wall (LVfw) were obtained using speckle-tracking echocardiography. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects. Using the individual’s deformation data as model input, this protocol automatically estimated regional RVfw and global IVS and LVfw tissue properties. The computational model was able to reproduce clinically measured regional deformation patterns for all subjects, with highly reproducible parameter estimations. Simulations revealed that regional RVfw heterogeneity of both contractile function and compliance were increased in subjects with clinically advanced disease compared to mutation carriers without clinically established disease (17 ± 13% vs. 8 ± 4%, P = 0.01 and 18 ± 11% vs. 10 ± 7%, P < 0.01, respectively). No significant difference in activation delay was found. Conclusion Regional RV deformation abnormalities in AC mutation carriers were related to reduced regional contractile function and tissue compliance. In clinically advanced disease stages, a characteristic apex-to-base heterogeneity of tissue abnormalities was present in the majority of the subjects, with most pronounced disease in the basal region of the RVfw.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electromechanical substrate characterization in arrhythmogenic cardiomyopathy using imaging-based patient-specific computer simulations

et al. 2021

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Towards a Mathematical Understanding of Ventilator-Induced Lung Injury in Preterm Rat Pups

Luke,

Kelly,

Stoner

et al. 2024

Mathematical Modeling for Women’s Health

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Approximately 1% of infants are born extremely preterm and underweight and are prone to respiratory distress and subsequent morbidity. Typical treatments for respiratory distress in late preterm and term infants, such as non-invasive pressure support, are less effective in preterm infants. Invasive mechanical ventilation applied as a last resort causes trauma, leading to ventilator-induced lung injury (VILI). Maternal infection, such as chorioamnionitis, can cause prenatal and neonatal lung infection, inflammation, and often very preterm birth. Inflammation is expected to stiffen the lungs with increased resistance and lowered compliance, but exceptions occur. A complete picture of the mechanisms of stiffening remains unknown. In an attempt to elucidate this information, we applied custom parameter inference and image analysis procedures to a neonatal rat model of chorioamnionitis and VILI, incorporating subject-specific pressure-volume measurements and histology. Numerical optimizations on a nonlinear compartmental model identified key parameter differences between healthy and unhealthy groups that may suggest mechanisms of VILI in infected respiratory systems. Combined analyses of the two strategies identified new correlations between model parameters, imaging metrics, and inflammatory markers from the data, suggesting that mathematical approaches provide an important path towards understanding VILI and infection.

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Biventricular Interaction During Acute Left Ventricular Ischemia in Mice: A Combined In-Vivo and In-Silico Approach

et al. 2023

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Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure–volume loop data (n = 3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure–volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems-level cardiovascular dynamics can quantitatively reproduce in-vivo data and qualitatively match prior findings from animal studies on LV ischemia.

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Parameter subset reduction for patient-specific modelling of arrhythmogenic cardiomyopathy-related mutation carriers in the CircAdapt model

Cited by 15 publications

References 32 publications

Electromechanical substrate characterization in arrhythmogenic cardiomyopathy using imaging-based patient-specific computer simulations

Electromechanical substrate characterization in arrhythmogenic cardiomyopathy using imaging-based patient-specific computer simulations

Towards a Mathematical Understanding of Ventilator-Induced Lung Injury in Preterm Rat Pups

Biventricular Interaction During Acute Left Ventricular Ischemia in Mice: A Combined In-Vivo and In-Silico Approach

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