First Evidence of Depressed Contractility in the Border Zone of a Human Myocardial Infarction

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States
The Annals of thoracic surgery (Impact Factor: 3.85). 02/2012; 93(4):1188-93. DOI: 10.1016/j.athoracsur.2011.12.066
Source: PubMed

ABSTRACT The temporal progression in extent and severity of regional myofiber contractile dysfunction in normally perfused border zone (BZ) myocardium adjacent to a myocardial infarction (MI) has been shown to be an important pathophysiologic feature of the adverse remodeling process in large animal models. We sought, for the first time, to document the presence of impaired contractility of the myofibers in the human BZ myocardium.
A 62-year-old man who experienced an MI in 1985 and had recently had complete revascularization was studied. Myofiber systolic contractile stress developed in the normally perfused BZ adjacent to the MI (T(max_B)) and that developed in regions remote from the MI (T(max_R)) were quantified using cardiac catheterization, magnetic resonance imaging, and mathematical modeling.
The resulting finite element model of the patient's beating left ventricle was able to simulate the reduced systolic strains measured using magnetic resonance imaging at matching left ventricular pressures and volumes. The T(max_B) (73.1 kPa) was found to be greatly reduced relative to T(max_R) (109.5 kPa). These results were found to be independent of assumptions relating to BZ myofiber orientation.
The results of this study document the presence of impaired contractility of the myofibers in the BZ myocardium and support its role in the post-MI remodeling process in patients. To fully establish this important conclusion serial evaluations beginning at the time of the index MI will need to be performed in a cohort of patients. The current study supports the importance and demonstrates the feasibility of larger and longer-term studies.

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Available from: Robert C. Gorman, Sep 29, 2015
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    • "Fortunately, ex vivo biaxial tissue testing is not required to quantify in vivo regional contractilities for the case of a posterobasal or posterolateral MI because the thickness of the infarcted wall segment is at least 50% of normal [3] [6] [13]. In the previous studies [3] [6] [13], we could measure 3D myocardial strain in the MI. In all three of those studies, however, it was not necessary to use a nonzero T max value in the MI for the LV finiteelement models to predict strain fields as measured with tagged MRI. "
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    ABSTRACT: Heart failure is increasing at an alarming rate, making it a worldwide epidemic. As the population ages and life expectancy increases, this trend is not likely to change. Myocardial infarction (MI)-induced adverse left ventricular (LV) remodeling is responsible for nearly 70% of heart failure cases. The adverse remodeling process involves an extension of the border zone (BZ) adjacent to an MI, which is normally perfused but shows myofiber contractile dysfunction. To improve patient-specific modeling of cardiac mechanics, we sought to create a finite element model of the human LV with BZ and MI morphologies integrated directly from delayed enhancement magnetic resonance (DE-MR) images. Instead of separating the LV into discrete regions (e.g. the MI, BZ and remote regions) with each having a homogeneous myocardial material property, we assumed a functional relation between the DE-MR image pixel intensity and myocardial contractility. The finite element model was then comprehensively validated using measurements obtained from the same patient, namely, 3D strain measurements, using complementary spatial modulation of magnetization magnetic resonance (CSPAMM-MR) images. We demonstrate the utility of our method for quantifying smooth regional variations in myocardial contractility using cardiac DE-MR and CSPAMM-MR images acquired from a 78-year-old woman who experienced an MI approximately one year prior. We found a remote myocardial diastolic stiffness of 0.102 kPa, and a remote myocardial contractility of 146.9 kPa, which are both in the range of previously published normal human values. Moreover, we found a BZ extending over 30% of the normalized pixel intensity maps from the DE-MR images, which is consistent with the literature. Based on these regional myocardial material properties, we used our finite element model to compute unmeasurable patient-specific diastolic and systolic LV myofiber stress distributions. One of the main driving forces for adverse LV remodeling is assumed to be an abnormally high level of ventricular wall stress, and many existing and new treatments for heart failure fundamentally attempt to normalize LV wall stress. Thus, our non-invasive method for estimating smooth regional variations in myocardial contractility should be valuable for optimizing new surgical or medical strategies to limit the chronic evolution from infarction to heart failure.
    Journal of Biomechanical Engineering 11/2014; 137(8). DOI:10.1115/1.4030667 · 1.78 Impact Factor
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    • "The material passive stiffness (C) and the tissue contractility (T max ) were chosen so that the predicted LV volumes (without injection) matched the corresponding EDV (197 ml) and ESV (122 ml) measured from the MR images. All other parameters had values equal to those used in large animal studies (Sun et al., 2009) and human study (Wenk et al., 2012). "
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    ABSTRACT: Injection of biomaterials into diseased myocardium has been associated with decreased myofiber stress, restored left ventricular (LV) geometry and improved LV function. However, its exact mechanism(s) of action remained unclear. In this work, we present the first patient-specific computational model of biomaterial injection that accounts for the possibility of residual strain and stress introduced by this treatment. We show that the presence of residual stress can create more heterogeneous regional myofiber stress and strain fields. Our simulation results show that the treatment generates low stress and stretch areas between injection sites, and high stress and stretch areas between the injections and both the endocardium and epicardium. Globally, these local changes are translated into an increase in average myofiber stress and its standard deviation (from 6.9±4.6 to 11.2±48.8kPa and 30±15 to 35.1±50.9kPa at end-diastole and end-systole, respectively). We also show that the myofiber stress field is sensitive to the void-to-size ratio. For a constant void size, the myofiber stress field became less heterogeneous with decreasing injection volume. These results suggest that the residual stress and strain possibly generated by biomaterial injection treatment can have large effects on the regional myocardial stress and strain fields, which may be important in the remodeling process.
    Journal of Biomechanics 06/2014; 47(12). DOI:10.1016/j.jbiomech.2014.06.026 · 2.75 Impact Factor
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    • "Fig. 4 Cyclical loading in the ELLISPOID and HUMAN models consisting of five high pressure cycles and five low pressure cycles. Every growth step lasts one characteristic time of the growth model which correspond to the values defined in the human modeling study by Wenk et al. (2012). For the growth parameters, we chose τ g = τ rg = 1 s and γ g = γ rg = 1. "
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    ABSTRACT: Ventricular growth is widely considered to be an important feature in the adverse progression of heart diseases, whereas reverse ventricular growth (or reverse remodeling) is often considered to be a favorable response to clinical intervention. In recent years, a number of theoretical models have been proposed to model the process of ventricular growth while little has been done to model its reverse. Based on the framework of volumetric strain-driven finite growth with a homeostatic equilibrium range for the elastic myofiber stretch, we propose here a reversible growth model capable of describing both ventricular growth and its reversal. We used this model to construct a semi-analytical solution based on an idealized cylindrical tube model, as well as numerical solutions based on a truncated ellipsoidal model and a human left ventricular model that was reconstructed from magnetic resonance images. We show that our model is able to predict key features in the end-diastolic pressure-volume relationship that were observed experimentally and clinically during ventricular growth and reverse growth. We also show that the residual stress fields generated as a result of differential growth in the cylindrical tube model are similar to those in other nonidentical models utilizing the same geometry.
    Biomechanics and Modeling in Mechanobiology 06/2014; 14(2). DOI:10.1007/s10237-014-0598-0 · 3.15 Impact Factor
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