title: Why Is Infarct Expansion Such an Elusive Therapeutic Target?
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.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Box 800759, Charlottesville, VA, 22908, USA. w.j.rchrdsn@gmail.com.|Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA. w.j.rchrdsn@gmail.com.
authors.forename: William J
authors.initials: WJ
authors.lastname: Richardson
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Box 800759, Charlottesville, VA, 22908, USA.|Department of Medicine, University of Virginia, Charlottesville, VA, USA.|Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Holmes
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D006342:Heart Rupture, Post-Infarction; D006801:Humans; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D009203:Myocardial Infarction / Q000473:pathology* / Q000628:therapy*; D054457:Tissue Scaffolds; D014945:Wound Healing
chemical_list: D003094:Collagen
keywords: Expansion; Fibroblast; Infarction; Mechanics; Remodeling; Wound healing