Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients

Abstract 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...

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Main Authors: Joy Mojumder, Lei Fan, Thuy Nguyen, Kenneth S. Campbell, Jonathan F. Wenk, Julius M. Guccione, Theodore Abraham, Lik Chuan Lee
Format: Article
Language:English
Published: Nature Portfolio 2023-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-28037-w
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author Joy Mojumder
Lei Fan
Thuy Nguyen
Kenneth S. Campbell
Jonathan F. Wenk
Julius M. Guccione
Theodore Abraham
Lik Chuan Lee
author_facet Joy Mojumder
Lei Fan
Thuy Nguyen
Kenneth S. Campbell
Jonathan F. Wenk
Julius M. Guccione
Theodore Abraham
Lik Chuan Lee
author_sort Joy Mojumder
collection DOAJ
description Abstract 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.
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spelling doaj.art-ba78ed35645a457ab6c00892b266e9542023-01-22T12:10:34ZengNature PortfolioScientific Reports2045-23222023-01-0113111710.1038/s41598-023-28037-wComputational analysis of ventricular mechanics in hypertrophic cardiomyopathy patientsJoy Mojumder0Lei Fan1Thuy Nguyen2Kenneth S. Campbell3Jonathan F. Wenk4Julius M. Guccione5Theodore Abraham6Lik Chuan Lee7Department of Mechanical Engineering, Michigan State UniversityDepartment of Mechanical Engineering, Michigan State UniversityDepartment of Cardiology, University of California San FranciscoDepartment of Physiology & Division of Cardiovascular Medicine, University of KentuckyDepartment of Mechanical Engineering, University of KentuckyDepartment of Surgery, University of California San FranciscoDepartment of Cardiology, University of California San FranciscoDepartment of Mechanical Engineering, Michigan State UniversityAbstract 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.https://doi.org/10.1038/s41598-023-28037-w
spellingShingle Joy Mojumder
Lei Fan
Thuy Nguyen
Kenneth S. Campbell
Jonathan F. Wenk
Julius M. Guccione
Theodore Abraham
Lik Chuan Lee
Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
Scientific Reports
title Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
title_full Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
title_fullStr Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
title_full_unstemmed Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
title_short Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
title_sort computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
url https://doi.org/10.1038/s41598-023-28037-w
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