Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure

Abstract

To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 +/- 2 wk (means +/- SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 +/- 0.030; P <0.05), whereas the apical site did not [P=not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 +/- 0.003 at 2 wk and 0.054 +/- 0.021 at final; both P <0.05), which contributed to a significant increase in wall thickness at the final study (0.181 +/- 0.047; P < 0.05), whereas the apical site did not (P=NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.

Fig. 1

A: schematic representation of the heart. LV, left ventricle; RV, right ventricle; X₁, circumferential axis; X₂, longitudinal axis; X₃, radial axis; LAD, left anterior descending coronary artery; LCx, left circumflex coronary artery; and m₁, m₂: intramyocardial markers implanted at the level of the basal bead set in the LV lateral wall (m₁) and the septum (m₂). B: schematic representation of local fiber-sheet axes. X_f, fiber axis; X_s, sheet axis; and X_n, axis oriented normal to the sheet plane. The X_f, X_s, and X_n axes present a Cartesian system.

Fig. 2

Schematic representation of fiber-sheet remodeling strains. Each cylinder represents a myofiber. Myofibers are organized into laminar “sheets,” which are approximately four cells thick and roughly stacked from apex to base (15). Sheet angle (β) is measured with reference to the positive X₃, with a positive angle defined as rotation toward the positive cross-fiber axis (X_cf). Therefore, the sheet angle is negative in this diagram (β < 0). Positive E_ff, E_sn, and E_ss represent fiber elongation, sheet shear, and sheet extension, respectively. Because the sheet angle is negative (β < 0), a positive sheet shear (E_sn > 0) is associated with reduction in radial remodeling strain or wall thinning (E₃₃ < 0). Sheet extension (E_ss > 0) may be accounted for by myofiber rearrangement within the sheet plane, or interdigitation, in addition to an increase in myocyte diameter (7), and is associated with increase in radial remodeling strain, or wall thickening (E₃₃ > 0). Endo, endocardium; epi, epicardium.

Fig. 3

Transmural fiber and sheet angles. Values are means ± SE (n = 6). Fiber angles were transmurally linear in both apex and base sites, however, regionally variable. Sheet angles were transmurally and regionally variable in both sites. Neither fiber nor sheet angles significantly changed from the control to the final study (P = NS).

Fig. 4

Time-dependent remodeling of myofiber and sheet structures. Values are means ± SE (n = 6). E₁₁, circumferential strain; E₂₂, longitudinal strain; and E₃₃, radial strain. *P < 0.05 vs. 0; +P < 0.05 vs. apex.

Fig. 5

Schematic account of fiber-sheet remodeling from Fig. 4. Apex: because the initial sheet angle is predominantly negative (β < 0), a positive sheet shear (E_sn > 0) is associated with reduction in radial strain (E₃₃ < 0), or wall thinning. Sheet extension (E_ss > 0) is associated with increase in radial strain (E₃₃ > 0), or wall thickening. The net effect is no change in wall thickness (E₃₃ ~ 0). Base: initial sheet angle is predominantly positive (β > 0); therefore, a positive sheet shear (E_sn > 0) is associated with increase in radial strain (E₃₃ > 0), or wall thickening. Because sheet extension is also associated with increase in radial strain, the net effect is significant increase in wall thickness (E₃₃ > 0).

Fig. 6

Time-dependent changes in LV geometry in chronic volume overload. A: normal LV geometry is ellipsoidal. B: during the early period (2–3 wk) of chronic volume overload, LV geometry becomes conoidal due to increases in basal dimensions. C: LV geometry in the late period (6–9 wk) becomes spherical due to increases in both apical and basal dimensions.

Fig. 7

Comparison of E_sn in acute vs. chronic volume loading. A: negative sheet angle (β < 0): In both acute and chronic responses to volume loading, sheet shear remodeling occurs in the positive direction (E_sn > 0), which is associated with a decrease in radial remodeling strain, or wall thinning (E₃₃ < 0). B: positive sheet angle (β > 0): In acute volume loading, similar to the case when the sheet angle is negative, sheet shear remodeling occurs in the negative direction (E_sn < 0), which is associated with wall thinning (E₃₃ < 0). In contrast, in chronic volume loading, sheet shear remodeling occurs in the positive direction (E_sn > 0), which is associated with an increase in radial remodeling strain, or wall thickening (E₃₃ < 0). Data for acute volume loading are based on Takayama et al. (27). Only sheet shear changes are represented in this diagram.

Fig. 8

Sheet angle change and radial remodeling. This diagram illustrates the relationship between the initial sheet angle and radial remodeling in a case of positive initial sheet angle. As the sheet angle decreases from positive (A) to zero (B), radial remodeling increases and the wall thickens (E₃₃ > 0). When the sheet angle becomes negative (C), a decrease in the sheet angle is associated with a decrease in radial remodeling and the wall thins (E₃₃ < 0). Only angle changes are represented in this diagram.