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Causes of altered ventricular mechanics in hypertrophic cardiomyopathy: an in-silico study
Ekaterina Kovacheva1, Tobias Gerach1, Steffen Schuler1
1Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131, Karlsruhe, Germany.
Insights
This study modeled hypertrophic cardiomyopathy (HCM) mechanisms, revealing how factors like LV hypertrophy and reduced contractility alter heart mechanics. These findings can improve non-invasive diagnosis of HCM by complementing imaging data.
Area of Science:
- Computational modeling and simulation
- Cardiovascular mechanics
- Biomedical engineering
Background:
- Hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by cardiomyocyte disarray, fibrosis, and impaired contractility.
- These pathological changes lead to distinct left ventricular (LV) strain patterns, offering potential for non-invasive diagnosis.
- Current diagnostic methods may involve invasive procedures or contrast agents, highlighting the need for improved non-invasive techniques.
Purpose of the Study:
- To investigate the contribution of individual pathological mechanisms to altered left ventricular (LV) mechanics in hypertrophic cardiomyopathy (HCM).
- To compare in-silico deformation patterns with clinically observed values in HCM patients.
- To understand how variations in tissue properties affect LV function and strain patterns.
Main Methods:
- An in-silico sensitivity study was performed using finite-element modeling of four-chamber heart models.
- Simulations incorporated physiological and pathological mechanisms relevant to HCM, including hypertrophy, reduced contractility, altered stiffness, and fiber disarray.
- A closed-loop circulatory model provided endocardial pressure values, and deformation was evaluated globally and regionally.
Main Results:
- Left ventricular (LV) hypertrophy significantly impacted strain, strain rate, and wall thickening.
- Reduced active force development (40%) decreased overall deformation, with maximal radial strain reducing from 26% to 21%.
- Increased tissue stiffness led to more homogeneous strain distribution, while fiber disarray had minor effects; combined mechanisms reduced LV deformation and halved left atrial (LA) longitudinal shortening.
Conclusions:
- Computer modeling elucidates the impact of HCM-related pathological mechanisms on LV deformation.
- Understanding these mechanical changes can enhance the diagnostic accuracy of HCM when integrated with imaging data.
- This approach offers a pathway to more precise, non-invasive diagnosis of hypertrophic cardiomyopathy.
Background:
Hypertrophic cardiomyopathy (HCM) is typically caused by mutations in sarcomeric genes leading to cardiomyocyte disarray, replacement fibrosis, impaired contractility, and elevated filling pressures. These varying tissue properties are associated with certain strain patterns that may allow to establish a diagnosis by means of non-invasive imaging without the necessity of harmful myocardial biopsies or contrast agent application. With a numerical study, we aim to answer: how the variability in each of these mechanisms contributes to altered mechanics of the left ventricle (LV) and if the deformation obtained in in-silico experiments is comparable to values reported from clinical measurements.
Methods:
We conducted an in-silico sensitivity study on physiological and pathological mechanisms potentially underlying the clinical HCM phenotype. The deformation of the four-chamber heart models was simulated using a finite-element mechanical solver with a sliding boundary condition to mimic the tissue surrounding the heart. Furthermore, a closed-loop circulatory model delivered the pressure values acting on the endocardium. Deformation measures and mechanical behavior of the heart models were evaluated globally and regionally.
Results:
Hypertrophy of the LV affected the course of strain, strain rate, and wall thickening-the root-mean-squared difference of the wall thickening between control (mean thickness 10 mm) and hypertrophic geometries (17 mm) was >10%. A reduction of active force development by 40% led to less overall deformation: maximal radial strain reduced from 26 to 21%. A fivefold increase in tissue stiffness caused a more homogeneous distribution of the strain values among 17 heart segments. Fiber disarray led to minor changes in the circumferential and radial strain. A combination of pathological mechanisms led to reduced and slower deformation of the LV and halved the longitudinal shortening of the LA.
Conclusions:
This study uses a computer model to determine the changes in LV deformation caused by pathological mechanisms that are presumed to underlay HCM. This knowledge can complement imaging-derived information to obtain a more accurate diagnosis of HCM.
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