In vivo assessment of regional mechanics post-myocardial infarction: A focus on the road ahead

Abstract

Cardiovascular disease, particularly the occurrence of myocardial infarction (MI), remains a leading cause of morbidity and mortality (Go et al., Circulation 127: e6-e245, 2013; Go et al. Circulation 129: e28-e292, 2014). There is growing recognition that a key factor for post-MI outcomes is adverse remodeling and changes in the regional structure, composition, and mechanical properties of the MI region itself. However, in vivo assessment of regional mechanics post-MI can be confounded by the species, temporal aspects of MI healing, as well as size, location, and extent of infarction across myocardial wall. Moreover, MI regional mechanics have been assessed over varying phases of the cardiac cycle, and thus, uniform conclusions regarding the material properties of the MI region can be difficult. This review assesses past studies that have performed in vivo measures of MI mechanics and attempts to provide coalescence on key points from these studies, as well as offer potential recommendations for unifying approaches in terms of regional post-MI mechanics. A uniform approach to biophysical measures of import will allow comparisons across studies, as well as provide a basis for potential therapeutic markers.

Keywords: in vivo; myocardial infarction; myocardial mechanics; regional.

Fig. 1.

Species differences. Temporal representation of biological events post-myocardial infarction (MI) in rodents and large mammals, which can affect physical properties of the MI region. A: summary time plot of the rate of collagen accumulation as a function of time post-MI in different species. Figure adapted with permission from Jugdutt et al. (68) with original research (40, 66, 87a, 106). B: relative to large mammals, rodents exhibit accelerated resolution of the inflammatory phase (top), an earlier and abbreviated fibroblast proliferation phase (middle), and rapid collagen deposition and maturation (bottom). The figure was compiled from reported data (33, 34, 38, 43, 44, 64, 66, 67, 78, 136).

Fig. 2.

Strain heterogeneity. A: regional heterogeneity of left ventricular (LV) strain following MI in patients (early post-MI period) was examined using tissue Doppler. Both cyclic longitudinal strain and strain rate exhibited significant variation between the MI and remote regions. The figure was adapted with permission from Edvardsen et al. (36) B: representative strain rate (SR) calculations using tissue Doppler in patients during the early post-MI period (2–6 days post index event), including both peak systolic strain rate (SRs) and early diastolic strain rate (SRe). Trace location is demarcated by line color: Yellow trace denotes basal segment, green trace denotes middle segment, and red trace denotes apical segments. Adapted with permission from Zhang et al. (141) C: representative chord reconstructions of a partial left ventricle in adult sheep, whereby sonomicrometry crystals span the MI, border, and remote regions. Occlusion of the distal segment of the left anterior descending coronary artery yielded an MI within the apical LV region (orange chords). Over time, a significant increase in all these chord lengths was observed. The figure was adapted from Jackson et al. (63) with permission. Although remodeling strain was not calculated, the increases in chord lengths are in line with expected increases in remodeling strains.

Fig. 3.

Extent of infarction across myocardial wall. Top: layer-specific speckle-tracking echocardiography depicting peak strain in a rat MI model with varying degrees of infarction across the myocardial wall. Baseline cyclic strain at systole is nearly homogeneous and depicts contractility (high strain/contractility indicated by blue tones). LV strain maps at 2 wk post-MI of a non-transmural (middle) and completely transmural (bottom) MI depict a reduction in strain magnitudes with contractile loss and uniformity, which is magnified by the depth of infarction across the myocardial wall. The figure was adapted with permission from Bachner-Hinenzon et al. (7).

Fig. 4.

Directional dependence. A: magnetic resonance imaging (MRI) coupled with harmonic phase analysis (HARP) yields LV strain maps from a rat immediately following induction of an MI, with MI location denoted by the red arrows. B: calculated maximal stretch (top) and maximal shortening (bottom) by HARP analysis at distinct anatomical locations (base to apex). E₁ and E₂ represent principal stresses independent of coordinate system. The figure panels were adapted with permission from Liu et al. (84) C: schematic of an experimental MI model in pigs, whereby radio-opaque markers (●) were implanted to allow for directional measurements of strain using biplane cineradiography. D: remodeling strain depends on direction and depth across the LV wall. The figure was adapted with permission from Zimmerman et al. (142).

Fig. 5.

Summary recommendations. Regional and global measurements were recommended for inclusion in future experimental studies. From the data contained in this review, this figure underscores the inverse trends in post-MI changes in local material properties and behavior (MI remodeling strain and stiffness) and global mechanical behavior post-MI (LV chamber stiffness). It is important to note that this figure only shows a general view of these trends, as we have stated throughout this review. Data representing the diastolic phase of the cardiac cycle are not as well reported as the systolic and do not, therefore, allow for a more detailed comparison with respect to the different cardiac phases. Although the specific time course of these changes is animal model-dependent, the trends represented by this figure are universal from the references currently contained in this review (73, 112, 137, 142).

Fig. 6.

In vivo chamber stiffness. Summary of reported LV pressure-volume relationships with passive filling and derived calculations of chamber stiffness following MI. The representation of passive stiffness is not wholly encompassing of mechanics in vivo, as the components of active contractility have been removed. A: in a rat MI model, the passive pressure-volume curves initially shifted to the left (days 0–3) and later to the right (days 5–22) with respect to the referent normal response. Adapted with permission from Raya et al. (105). B: temporal variation in LV chamber stiffness was reported in a rat MI model and was found to depend on the absolute MI size. The figure was adapted with permission from Pfeffer et al. (101).