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Why Is Infarct Expansion Such an Elusive Therapeutic Target?

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Abstract

Myocardial infarct expansion has been associated with an increased risk of infarct rupture and progression to heart failure, motivating therapies such as infarct restraint and polymer injection that aim to limit infarct expansion. However, an exhaustive review of quantitative studies of infarct remodeling reveals that only half found chronic in-plane expansion, and many reported in-plane compaction. Using a finite element model, we demonstrate that the balance between scar stiffening due to collagen accumulation and increased wall stresses due to infarct thinning can produce either expansion or compaction in the pressurized heart—potentially explaining variability in the literature—and that loaded dimensions are much more sensitive to changes in thickness than in stiffness. Our analysis challenges the concept that in-plane expansion is a central feature of post-infarction remodeling; rather, available data suggest that radial thinning is the dominant process during infarct healing and may be an attractive therapeutic target.

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Abbreviations

MI:

Myocardial infarction

LV:

Left ventricle

FEM:

Finite element model

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No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.

Sources of Funding

The authors gratefully acknowledge funding from the National Institutes of Health (R01HL116449 to JWH, T32HL007284 to WJR), the National Science Foundation (CMMI1332530 to JWH), and the American Heart Association (14POST20460271 to WJR).

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Virginia, Box 800759, Charlottesville, VA, 22908, USA

    William J. Richardson & Jeffrey W. Holmes

  2. Department of Medicine, University of Virginia, Charlottesville, VA, USA

    Jeffrey W. Holmes

  3. Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA

    William J. Richardson & Jeffrey W. Holmes

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Correspondence to William J. Richardson.

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Editor-in-Chief Jennifer L. Hall oversaw the review of this article

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Richardson, W.J., Holmes, J.W. Why Is Infarct Expansion Such an Elusive Therapeutic Target?. J. of Cardiovasc. Trans. Res. 8, 421–430 (2015). https://doi.org/10.1007/s12265-015-9652-2

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  • DOI: https://doi.org/10.1007/s12265-015-9652-2

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