Changes in overall ventricular myocardial architecture in the setting of a porcine animal model of right ventricular dilation

Abstract

Background: Chronic pulmonary regurgitation often leads to myocardial dysfunction and heart failure. It is not fully known why secondary hypertrophy cannot fully protect against the increase in wall stress brought about by the increased end-diastolic volume in ventricular dilation. It has been assumed that mural architecture is not deranged in this situation, but we hypothesised that there might be a change in the pattern of orientation of the aggregations of cardiomyocytes, which would contribute to contractile impairment.

Methods: We created pulmonary valvular regurgitation by open chest, surgical suturing of its leaflets in seven piglets, performing sham operations in seven control animals. Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we demonstrated significantly increased right ventricular volumes in the test group. After sacrifice, diffusion tensor imaging of their hearts permitted measurement of the orientation of the cardiomyocytes.

Results: The helical angles in the right ventricle approached a more circumferential orientation in the setting of right ventricular RV dilation (p = 0.007), with an increased proportion of surface-parallel cardiomyocytes. In contrast, this proportion decreased in the left ventricle. Also in the left ventricle a higher proportion of E3 angles with a value around zero was found, and conversely a lower proportion of angles was found with a numerical higher value. In the dilated right ventricle the proportion of E3 angles around -90° is increased, while the proportion around 90° is decreased.

Conclusion: Contrary to traditional views, there is a change in the orientation of both the left ventricular and right ventricular cardiomyocytes subsequent to right ventricular dilation. This will change their direction of contraction and hinder the achievement of normalisation of cardiomyocytic strain, affecting overall contractility. We suggest that the aetiology of the cardiac failure induced by right vetricular dilation may be partly explained by morphological changes in the myocardium itself.

Keywords: Congenital heart disease; Diffusion tensor imaging; Heart failure; Myocardial remodeling.

Fig. 1

Diffusion tensor and eigenvectors. The shape of the diffusion tensor in an ordered fibrous environment such as the myocardium. Panel a depicts the schematic ordering of the cardiomyocytes while panel b shows the coherent shape of the diffusion tensor, the primary (e1), secondary (e2) and tertiary (e3) eigenvectors are shown along with their relationship in panel c. Panel d shows a schematic representation of the left ventricle with the local orthogonal planes aligned relative to the epicardium. Panel e shows the local set of orthogonal planes as superimposed in every voxel. Plane A (red) is the circumferential-longitudinal plane parallel to the epicardial tangential plane and plane B (blue) is the radial-longitudinal plane parallel to the left ventricular long axis and orthogonal to plane A. Plane C, the local “horizontal” plane, is the circumferential-radial plane orthogonal to planes A and B. The helical angle is the angle between the cardiomyocyte and plane C. The intrusion angle is the angle between the cardiomyocyte and plane A. Panel f shows the E3 angle as measured using the tertiary eigenvector (e3) relative to plane B. The aggregation of cardiomyocytes is depicted as a flat square, which is a gross oversimplification

Fig. 2

The epicardial tangential plane. Calculation of the epicardial tangential plane. The short axis circumference of the ventricle was subdivided into 64 parts of equal size as imaged. The area of interest as outlined in bold was exported with its corresponding parts 2 mm above and below as outlined in dashed lines. Three points P1, P2, and P3 were selected in the epicardium as shown and from these the epicardial tangential plane was calculated

Fig. 3

Angle histograms. Pooled results of angle calculations from the basal, equatorial and apical regions presented as histograms. Left column: Left ventricle. Middle column: Interventricular septum. Right column: Right ventricle. Top row: Results of helical angle distributions. Middle row: Results of intrusion angle distribution. Bottom row: Results of E3 angle distribution. Results are shown as medians with interquartile range. Asterisk indicates statistical significance in individual bins in post-hoc testing using Mann-Whitney U-test. Within each plot the distributions of the two groups are compared using the Kolmogorov-Smirnov test of the equality of distributions. Resulting p-values are as follows: Left Ventricle: Helical angle; p = 0.06, Intrusion angle; p = 0.04, E3 angle; p < 0.001. Septum: Helical angle; p = 0.71, Intrusion angle; p = 0.12, E3 angle; p = 0.56. Right Ventricle: Helical angle; p = 0.03, Intrusion angle; p = 0.007, E3 angle; p = 0.018

Fig. 4

Results of helical and intrusion angles as a function of myocardial depth in percent. 0% is the sub-endocardium, 100% is the sub-epicardium. In the interventricular septum 100% is the right ventricular sub-endocardium. Results are shown as medians with interquartile range. Asterisk indicates statistical significance in individual areas in post-hoc testing using Mann-Whitney U-test

Fig. 5

Surface plots of helical, intrusion and unit angles in control heart (left) versus heart with pulmonary regurgitation and right ventricular dilation (right). The subdivision of the myocardium into smaller parts is obvious when calculating intrusion angles since this particular angle is highly sensitive to inhomogeneities in the epicardial surface

Fig. 6

Detailed regional analysis based on data from individual zones in the entire heart. Transmural analyses of helical angles from sub-endocardium (0) to sub-epicardium (100). Asterisk indicates statistical significance in individual areas using Mann-Whitney U-test. In the down right corner a schematic representation of the zones is presented for reference

Fig. 7

Detailed regional analysis based on data from individual zones in the entire heart. Transmural analyses of intrusion angles from sub-endocardium (0) to sub-epicardium (100). Asterisk indicates statistical significance in individual areas using Mann-Whitney U-test. In the down right corner a schematic representation of the zones is presented for reference

Fig. 8

Regional analyses of E3-angles are shown in histograms. In the down right corner a schematic representation of the zones is presented for reference. Asterisk indicates statistical significance in individual areas using Mann-Whitney U-test

Fig. 9

Tractography images of cardiomyocytes in the free wall of the right ventricle in controls (a) and right ventricular dilation (b). The tracks are limited to a length of 4 cm for the ease of interpretation. The colour code of the tracks does not represent any anatomical or physiological properties, but are added as a visual aid enabling the reader to distinguish between individual tracks. The helical angles of the tracts are approaching a more circumferential orientation in the dilated right ventricle (b)

Fig. 10

The wicker basket analogy. When the basket is dilated in the right panel the angle, between the wickers decreases from approximately 100° to 80°. In this basket the angle between the wickers decrease when the basket is dilated in exactly the same way as seen in the dilating right ventricle. The figure is not to be understood as a model of mural architecture and it is not to be interpreted as an image of how the myocardium is constructed. Contrary, the purpose of the figure is to illustrate the concept of what happens to the helical angles, depicted by the angles between the wickers, when the cavity dilates. No conclusions on E3 or intrusion angles can be made from this model