Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection Fraction
The pathophysiological mechanisms underlying preserved left ventricular (LV) ejection fraction (EF) in patients with heart failure and preserved ejection fraction (HFpEF) remain incompletely understood. We hypothesized that transmural variations in myofiber contractility with existence of subendocar...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.01003/full |
| _version_ | 1818992534948413440 |
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| author | Yaghoub Dabiri Kevin L. Sack Semion Shaul Partho P. Sengupta Julius M. Guccione |
| author_facet | Yaghoub Dabiri Kevin L. Sack Semion Shaul Partho P. Sengupta Julius M. Guccione |
| author_sort | Yaghoub Dabiri |
| collection | DOAJ |
| description | The pathophysiological mechanisms underlying preserved left ventricular (LV) ejection fraction (EF) in patients with heart failure and preserved ejection fraction (HFpEF) remain incompletely understood. We hypothesized that transmural variations in myofiber contractility with existence of subendocardial dysfunction and compensatory increased subepicardial contractility may underlie preservation of LVEF in patients with HFpEF. We quantified alterations in myocardial function in a mathematical model of the human LV that is based on the finite element method. The fiber-reinforced material formulation of the myocardium included passive and active properties. The passive material properties were determined such that the diastolic pressure-volume behavior of the LV was similar to that shown in published clinical studies of pressure-volume curves. To examine changes in active properties, we considered six scenarios: (1) normal properties throughout the LV wall; (2) decreased myocardial contractility in the subendocardium; (3) increased myocardial contractility in the subepicardium; (4) myocardial contractility decreased equally in all layers, (5) myocardial contractility decreased in the midmyocardium and subepicardium, (6) myocardial contractility decreased in the subepicardium. Our results indicate that decreased subendocardial contractility reduced LVEF from 53.2 to 40.5%. Increased contractility in the subepicardium recovered LVEF from 40.5 to 53.2%. Decreased contractility transmurally reduced LVEF and could not be recovered if subepicardial and midmyocardial contractility remained depressed. The computational results simulating the effects of transmural alterations in the ventricular tissue replicate the phenotypic patterns of LV dysfunction observed in clinical practice. In particular, data for LVEF, strain and displacement are consistent with previous clinical observations in patients with HFpEF, and substantiate the hypothesis that increased subepicardial contractility may compensate for subendocardial dysfunction and play a vital role in maintaining LVEF. |
| first_indexed | 2024-12-20T20:27:42Z |
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| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-20T20:27:42Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-25d1fff0f3184dc4ac2df9a60a9cf35b2022-12-21T19:27:25ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-08-01910.3389/fphys.2018.01003350862Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection FractionYaghoub Dabiri0Kevin L. Sack1Semion Shaul2Partho P. Sengupta3Julius M. Guccione4Department of Surgery, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Surgery, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Surgery, University of California, San Francisco, San Francisco, CA, United StatesSection of Cardiology, West Virginia University Heart and Vascular Institute, West Virginia University, Morgantown, WV, United StatesDepartment of Surgery, University of California, San Francisco, San Francisco, CA, United StatesThe pathophysiological mechanisms underlying preserved left ventricular (LV) ejection fraction (EF) in patients with heart failure and preserved ejection fraction (HFpEF) remain incompletely understood. We hypothesized that transmural variations in myofiber contractility with existence of subendocardial dysfunction and compensatory increased subepicardial contractility may underlie preservation of LVEF in patients with HFpEF. We quantified alterations in myocardial function in a mathematical model of the human LV that is based on the finite element method. The fiber-reinforced material formulation of the myocardium included passive and active properties. The passive material properties were determined such that the diastolic pressure-volume behavior of the LV was similar to that shown in published clinical studies of pressure-volume curves. To examine changes in active properties, we considered six scenarios: (1) normal properties throughout the LV wall; (2) decreased myocardial contractility in the subendocardium; (3) increased myocardial contractility in the subepicardium; (4) myocardial contractility decreased equally in all layers, (5) myocardial contractility decreased in the midmyocardium and subepicardium, (6) myocardial contractility decreased in the subepicardium. Our results indicate that decreased subendocardial contractility reduced LVEF from 53.2 to 40.5%. Increased contractility in the subepicardium recovered LVEF from 40.5 to 53.2%. Decreased contractility transmurally reduced LVEF and could not be recovered if subepicardial and midmyocardial contractility remained depressed. The computational results simulating the effects of transmural alterations in the ventricular tissue replicate the phenotypic patterns of LV dysfunction observed in clinical practice. In particular, data for LVEF, strain and displacement are consistent with previous clinical observations in patients with HFpEF, and substantiate the hypothesis that increased subepicardial contractility may compensate for subendocardial dysfunction and play a vital role in maintaining LVEF.https://www.frontiersin.org/article/10.3389/fphys.2018.01003/fullheart failure and preserved ejection fractionleft ventriclemyocardial contractilityfinite element methodsimulation |
| spellingShingle | Yaghoub Dabiri Kevin L. Sack Semion Shaul Partho P. Sengupta Julius M. Guccione Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection Fraction Frontiers in Physiology heart failure and preserved ejection fraction left ventricle myocardial contractility finite element method simulation |
| title | Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection Fraction |
| title_full | Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection Fraction |
| title_fullStr | Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection Fraction |
| title_full_unstemmed | Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection Fraction |
| title_short | Relationship of Transmural Variations in Myofiber Contractility to Left Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype With Preserved Ejection Fraction |
| title_sort | relationship of transmural variations in myofiber contractility to left ventricular ejection fraction implications for modeling heart failure phenotype with preserved ejection fraction |
| topic | heart failure and preserved ejection fraction left ventricle myocardial contractility finite element method simulation |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.01003/full |
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