scholarly journals Uncertainty Quantification of Regional Cardiac Tissue Properties in Arrhythmogenic Cardiomyopathy Using Adaptive Multiple Importance Sampling

2021 ◽  
Vol 12 ◽  
Author(s):  
Nick van Osta ◽  
Feddo P. Kirkels ◽  
Tim van Loon ◽  
Tijmen Koopsen ◽  
Aurore Lyon ◽  
...  
Keyword(s):  
Uncertainty Quantification ◽  
Importance Sampling ◽  
Left Ventricular ◽  
Patient Specific ◽  
Intraobserver Variability ◽  
Posterior Distributions ◽  
Arrhythmogenic Cardiomyopathy ◽  
True Parameter ◽  
Tissue Properties ◽  
Multiple Importance Sampling

Introduction: Computational models of the cardiovascular system are widely used to simulate cardiac (dys)function. Personalization of such models for patient-specific simulation of cardiac function remains challenging. Measurement uncertainty affects accuracy of parameter estimations. In this study, we present a methodology for patient-specific estimation and uncertainty quantification of parameters in the closed-loop CircAdapt model of the human heart and circulation using echocardiographic deformation imaging. Based on patient-specific estimated parameters we aim to reveal the mechanical substrate underlying deformation abnormalities in patients with arrhythmogenic cardiomyopathy (AC).Methods: We used adaptive multiple importance sampling to estimate the posterior distribution of regional myocardial tissue properties. This methodology is implemented in the CircAdapt cardiovascular modeling platform and applied to estimate active and passive tissue properties underlying regional deformation patterns, left ventricular volumes, and right ventricular diameter. First, we tested the accuracy of this method and its inter- and intraobserver variability using nine datasets obtained in AC patients. Second, we tested the trueness of the estimation using nine in silico generated virtual patient datasets representative for various stages of AC. Finally, we applied this method to two longitudinal series of echocardiograms of two pathogenic mutation carriers without established myocardial disease at baseline.Results: Tissue characteristics of virtual patients were accurately estimated with a highest density interval containing the true parameter value of 9% (95% CI [0–79]). Variances of estimated posterior distributions in patient data and virtual data were comparable, supporting the reliability of the patient estimations. Estimations were highly reproducible with an overlap in posterior distributions of 89.9% (95% CI [60.1–95.9]). Clinically measured deformation, ejection fraction, and end-diastolic volume were accurately simulated. In presence of worsening of deformation over time, estimated tissue properties also revealed functional deterioration.Conclusion: This method facilitates patient-specific simulation-based estimation of regional ventricular tissue properties from non-invasive imaging data, taking into account both measurement and model uncertainties. Two proof-of-principle case studies suggested that this cardiac digital twin technology enables quantitative monitoring of AC disease progression in early stages of disease.

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

2020 ◽  
Vol 378 (2173) ◽  
pp. 20190347 ◽  
Author(s):  
Nick van Osta ◽  
Aurore Lyon ◽  
Feddo Kirkels ◽  
Tijmen Koopsen ◽  
Tim van Loon ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Computational Models ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Patient Specific ◽  
Model Parameters ◽  
Arrhythmogenic Cardiomyopathy ◽  
Tissue Properties ◽  
Myocardial Disease ◽  
Deformation Patterns

Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease, clinically characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Patient-specific computational models could help understand the disease progression and may help in clinical decision-making. We propose an inverse modelling approach using the CircAdapt model to estimate patient-specific regional abnormalities in tissue properties in AC subjects. However, the number of parameters ( n  = 110) and their complex interactions make personalized parameter estimation challenging. The goal of this study is to develop a framework for parameter reduction and estimation combining Morris screening, quasi-Monte Carlo (qMC) simulations and particle swarm optimization (PSO). This framework identifies the best subset of tissue properties based on clinical measurements allowing patient-specific identification of right ventricular tissue abnormalities. We applied this framework on 15 AC genotype-positive subjects with varying degrees of myocardial disease. Cohort studies have shown that atypical regional right ventricular (RV) deformation patterns reveal an early-stage AC disease. The CircAdapt model of cardiovascular mechanics and haemodynamics has already demonstrated its ability to capture typical deformation patterns of AC subjects. We, therefore, use clinically measured cardiac deformation patterns to estimate model parameters describing myocardial disease substrates underlying these AC-related RV deformation abnormalities. Morris screening reduced the subset to 48 parameters. qMC and PSO further reduced the subset to a final selection of 16 parameters, including regional tissue contractility, passive stiffness, activation delay and wall reference area. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

scholarly journals Uncertainty quantification and sensitivity analysis of left ventricular function during the full cardiac cycle

2020 ◽  
Vol 378 (2173) ◽  
pp. 20190381 ◽  
Author(s):  
J. O. Campos ◽  
J. Sundnes ◽  
R. W. dos Santos ◽  
B. M. Rocha
Keyword(s):  
Uncertainty Quantification ◽  
Wall Thickness ◽  
Cardiac Cycle ◽  
Fibre Orientation ◽  
Left Ventricular ◽  
Sensitivity Analyses ◽  
Patient Specific ◽  
Model Parameters ◽  
Fibre Direction ◽  
Active Stress

Patient-specific computer simulations can be a powerful tool in clinical applications, helping in diagnostics and the development of new treatments. However, its practical use depends on the reliability of the models. The construction of cardiac simulations involves several steps with inherent uncertainties, including model parameters, the generation of personalized geometry and fibre orientation assignment, which are semi-manual processes subject to errors. Thus, it is important to quantify how these uncertainties impact model predictions. The present work performs uncertainty quantification and sensitivity analyses to assess the variability in important quantities of interest (QoI). Clinical quantities are analysed in terms of overall variability and to identify which parameters are the major contributors. The analyses are performed for simulations of the left ventricle function during the entire cardiac cycle. Uncertainties are incorporated in several model parameters, including regional wall thickness, fibre orientation, passive material parameters, active stress and the circulatory model. The results show that the QoI are very sensitive to active stress, wall thickness and fibre direction, where ejection fraction and ventricular torsion are the most impacted outputs. Thus, to improve the precision of models of cardiac mechanics, new methods should be considered to decrease uncertainties associated with geometrical reconstruction, estimation of active stress and of fibre orientation. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

Arrhythmogenic cardiomyopathy is characterized by apex-to-base heterogeneity of right ventricular myocardial contractility and stiffness: an imaging-based patient-specific modeling study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Van Osta ◽  
A Lyon ◽  
F Kirkels ◽  
T Koopsen ◽  
T.A.M Van Loon ◽  
...  
Keyword(s):  
Disease Progression ◽  
Patient Specific ◽  
Funding Source ◽  
Free Wall ◽  
Longitudinal Deformation ◽  
Arrhythmogenic Cardiomyopathy ◽  
Tissue Properties ◽  
Specific Parameter ◽  
Structural Stage ◽  
Modelling Approach

Abstract Introduction Arrhythmogenic Cardiomyopathy (AC) is an inherited cardiac disease, clinically characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Geno-positive subjects with and without symptoms may suffer from sudden cardiac death. Therefore, early disease expression and risk stratification is important. It has been shown that right ventricular (RV) longitudinal deformation abnormalities in early stages is related to disease progression. We propose an inverse patient-specific computer modelling approach, combined with clinical imaging data, to non-invasively quantify regional ventricular tissue abnormalities in AC mutation carriers. Purpose To non-invasively reveal the individual myocardial substrate underlying the regional RV deformation abnormalities in AC mutation carriers. Methods In 74 individuals carrying a plakophilin-2 or desmoglein-2 mutation, 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 (Figure: left column). This cohort was subdivided into 3 consecutive clinical stages i.e. subclinical (concealed, n=19) with no abnormalities, electrical stage (n=13) with only electrocardiographic abnormalities, and structural stage (n=42) with both electrical and structural abnormalities defined by the 2010 Task Force AC criteria. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects (Figure: middle column). Using the individuals' RV strain patterns as model input, this protocol automatically estimated regional RV tissue properties, such as myocardial contractility and stiffness. Results The computational model was able to reproduce the deformation as clinically measured. Patient-specific parameter estimation results (Figure: right column) revealed that clinical AC disease progression is characterized by an increase of base-to-apex heterogeneity in contractility and stiffness of the RV myocardial tissue, with a decreased contractility and an increased stiffness in the basal segment compared to the apex. Although this heterogeneity was most severe in the structural stage group, it was already present in many of the subjects in the subclinical stage. No clear apex-to-base heterogeneity of mechanical activation delay was found in this cohort. Conclusion Our patient-specific modelling approach showed that early abnormalities in RV longitudinal strain are most likely caused by increased heterogeneity in local tissue properties. Strain abnormalities are predominantly caused by decreased basal tissue contractility and increased basal tissue stiffness. Abnormalities in tissue properties may be found already in the subclinical stage. Future studies will investigate how these abnormalities relate to disease progression and arrhythmogenic risk. Characterization of AC Disease Substrate Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.

scholarly journals Arrhythmogenic cardiomyopathy is characterized by apex-to-base heterogeneity of right ventricular myocardial contractility, stiffness, and mechanical delay: a patient-specific modeling study

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
N Van Osta ◽  
F Kirkels ◽  
A Lyon ◽  
T Koopsen ◽  
TAM Van Loon ◽  
...  
Keyword(s):  
Parameter Estimation ◽  
Patient Specific ◽  
Myocardial Tissue ◽  
Free Wall ◽  
Longitudinal Deformation ◽  
Arrhythmogenic Cardiomyopathy ◽  
Tissue Properties ◽  
Specific Parameter ◽  
Deformation Patterns ◽  
Modelling Approach

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO-ZonMw, VIDI grant 016.176.340 Dutch Heart Foundation (2015T082) Introduction Arrhythmogenic Cardiomyopathy (AC) is an inherited cardiac disease, characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Geno-positive subjects with and without symptoms may suffer from sudden cardiac death. Therefore, early disease detection and risk stratification is important. Right ventricular (RV) longitudinal deformation abnormalities in early stages of disease have been shown to be of prognostic value. We propose an imaging-based patient-specific computer modelling approach for non-invasive quantification of regional ventricular tissue abnormalities. Purpose To non-invasively reveal the individual patient’s myocardial tissue substrates underlying the regional RV deformation abnormalities in AC mutation carriers. Methods In 65 individuals carrying a plakophilin-2 or desmoglein-2 mutation 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 (Figure: left). This cohort was subdivided into 3 consecutive clinical stages i.e. subclinical (concealed, n = 18) with no abnormalities, electrical stage (n = 13) with only electrocardiographic abnormalities, and structural stage (n = 34) with both electrical and structural abnormalities defined by the 2010 Task Force AC criteria. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects (Figure: middle). Using the individuals’ RVfw, IVS, and LVfw strain patterns as model input, this protocol automatically estimated regional RV and global IVS and LVfw tissue properties, such as myocardial contractility, stiffness, and activation delay. Results The computational model was able to reproduce the regional deformation patterns as measured clinically. Patient-specific parameter estimation results (Figure: right) revealed that clinical AC disease progression is characterized by a decrease in contractility and an increase in stiffness and mechanical delay of the RV myocardial tissue in the basal segment compared to the apex. The subclinical stage subjects showed tissue properties comparable to the control group, including a small apex-to-base heterogeneity in tissue properties. Conclusion Our patient-specific modelling approach is able to reveal individual myocardial substrates underlying the regional RV deformation abnormalities. Early abnormalities in RV longitudinal strain are most likely caused by increased heterogeneity in local tissue properties, such as an apex-to-base decrease of contractility, increased of myocardial stiffness, and time to peak stress. Abnormalities in tissue properties may be found already in the subclinical stage. In future studies, this artificial intelligence approach will be used to investigate how these abnormalities relate to disease progression and arrhythmogenic risk. Abstract Figure. Characterization of AC Disease Substrate

Cardiac Resynchronisation Therapy – Evolving Strategies to Enhance Response

2010 ◽  
Vol 6 (1) ◽  
pp. 83
Author(s):  
Jagmeet P Singh ◽  
Keyword(s):  
Heart Failure ◽  
Systolic Heart Failure ◽  
Cardiac Resynchronisation Therapy ◽  
Left Ventricular ◽  
Patient Specific ◽  
Cardiac Resynchronisation ◽  
Clinical Benefits ◽  
Pacing Lead ◽  
Resynchronisation Therapy ◽  
Physiological Impact

Cardiac resynchronisation therapy (CRT) has gained widespread acceptance as a safe and effective therapeutic strategy for congestive heart failure (CHF) refractory to optimal medical therapy. The use of implantable devices has substantially altered the natural history of systolic heart failure. These devices exert their physiological impact through ventricular remodelling, associated with a reduction in left ventricular (LV) volumes and an improvement in ejection fraction (EF). Several prospective randomised studies have shown that this in turn translates into long-term clinical benefits such as improved quality of life, increased functional capacity and reduction in hospitalisation for heart failure and overall mortality. Despite these obvious benefits, there remain more than a few unresolved concerns, the most important being that up to one-third of patients treated with CRT do not derive any detectable benefit. There are several determinants of successful delivery and response to CRT, including selecting the appropriate patient, patient-specific optimal LV pacing lead placement and appropriate post-implant device care and follow-up. This article highlights the importance of collectively working on all of these aspects of CRT to enhance and maximise response.

scholarly journals B-PO02-124 NONISCHEMIC LEFT VENTRICULAR CARDIOMYOPATHY WITH PRESERVED LEFT VENTRICULAR FUNCTION: A TYPE OF ARRHYTHMOGENIC CARDIOMYOPATHY

Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S148
Author(s):  
Ikutaro Nakajima ◽  
Kenichi Tokutake ◽  
Asad A. Aboud ◽  
Oluwaseun Adeola ◽  
Travis D. Richardson ◽  
...  
Keyword(s):  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Arrhythmogenic Cardiomyopathy ◽  
Ventricular Cardiomyopathy

scholarly journals Cardiomyopathies: An Overview

2021 ◽  
Vol 22 (14) ◽  
pp. 7722
Author(s):  
Tiziana Ciarambino ◽  
Giovanni Menna ◽  
Gennaro Sansone ◽  
Mauro Giordano
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Dilated Cardiomyopathy ◽  
Sudden Cardiac Arrest ◽  
Restrictive Cardiomyopathy ◽  
The United States ◽  
Abrupt Onset ◽  
Left Ventricular ◽  
Arrhythmogenic Cardiomyopathy ◽  
Athletic Field ◽  
Fibrofatty Tissue

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were “cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome”. Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological.

scholarly journals Sustained ventricular tachycardia of left, right or both bundle branch block morphology in patients with Arrhythmogenic Cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Milman ◽  
M Laredo ◽  
R Roudijk ◽  
G Peretto ◽  
A Andorin ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Right Bundle Branch Block ◽  
Left Bundle Branch Block ◽  
Clinical Course ◽  
Left Ventricular ◽  
Funding Source ◽  
Arrhythmogenic Cardiomyopathy ◽  
Icd Implantation ◽  
Bundle Branch Block ◽  
Group 3

Abstract Aims In arrhythmogenic cardiomyopathy (ACM) sustained monomorphic ventricular tachycardia (VT) typically displays left bundle branch block (LBBB) morphology. Sustained VT with right bundle branch block (RBBB) morphology is very rare despite the frequent left ventricular involvement. The present study sought to assess the prevalence of spontaneous sustained LBBB-VT, RBBB-VT or both as well as clinical and genetic differences associated with these VT types. Methods and results Twenty-six centers from 11 European countries provided information on 952 patients with ACM and >1 episode of sustained VT observed during the patients' clinical course. VT was classified as: LBBB-VT; RBBB-VT or LBBB+RBBB-VT. Among 952 patients, 881 (92.5%) had LBBB-VT alone, 71 (7.5%) had RBBB-VT [alone in 42 (4.4%) patients or with LBBB-VT in 29 (3.0%) patients]. Male prevalence was 90.5%, 79.2% and 55.9% in the RBBB-VT, LBBB-VT and LBBB+RBBB-VT groups, respectively (P=0.001). Patients' age at first VT did not differ amongst the 3 VT groups. ICD implantation was more frequent for the RBBB-VT and the LBBB+RBBB groups (≈90% each) vs. 67.9% for the LBBB-VT group (P=0.001). Death incidence (9.5%–17.2%) was not significantly different between the 3 groups (P=0.425). Plakophylin-2 mutations predominated in the LBBB-VT and LBBB-VT+RBBB-VT groups (47.2% and 27.3%, respectively) and Desmoplakin mutations in the RBBB-VT group (36.7%). Conclusion This large European survey demonstrates: 1) Sustained RBBB-VT is documented in 7.5% patients with ACM; 2) Males markedly predominate in the RBBB-VT and LBBB-VT groups but not in the LBBB+RBBB VT group; 3) Distribution of desmosomal mutations appears to be different in the 3 VT groups. Funding Acknowledgement Type of funding source: None

scholarly journals Drone Ground Impact Footprints with Importance Sampling: Estimation and Sensitivity Analysis

2021 ◽  
Vol 11 (9) ◽  
pp. 3871
Author(s):  
Jérôme Morio ◽  
Baptiste Levasseur ◽  
Sylvain Bertrand
Keyword(s):  
Sensitivity Analysis ◽  
Monte Carlo ◽  
Importance Sampling ◽  
Loss Of Control ◽  
Minimum Volume ◽  
Multiple Importance Sampling ◽  
Impact Position ◽  
Engine Failure ◽  
Main Engine ◽  
Ground Impact

This paper addresses the estimation of accurate extreme ground impact footprints and probabilistic maps due to a total loss of control of fixed-wing unmanned aerial vehicles after a main engine failure. In this paper, we focus on the ground impact footprints that contains 95%, 99% and 99.9% of the drone impacts. These regions are defined here with density minimum volume sets and may be estimated by Monte Carlo methods. As Monte Carlo approaches lead to an underestimation of extreme ground impact footprints, we consider in this article multiple importance sampling to evaluate them. Then, we perform a reliability oriented sensitivity analysis, to estimate the most influential uncertain parameters on the ground impact position. We show the results of these estimations on a realistic drone flight scenario.

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