The role of end‐diastolic myocardial fibre stretch on infarct extension

Abstract

Myocardial infarct extension, a process involving the enlargement of infarct and border zone, leads to progressive degeneration of left ventricular (LV) function and eventually gives rise to heart failure. Despite carrying a high risk, the causation of infarct extension is still a subject of much speculation. In this study, patient-specific LV models were developed to investigate the correlation between infarct extension and impaired regional mechanics. Subsequently, sensitivity analysis was performed to examine the causal factors responsible for the impaired regional mechanics observed in regions surrounding the infarct and border zone. From our simulations, fibre strain, fibre stress and fibre stress-strain loop (FSSL) were the key biomechanical variables affected in these regions. Among these variables, only FSSL was correlated with infarct extension, as reflected in its work density dissipation (WDD) index value, with high WDD indices recorded at regions with infarct extension. Impaired FSSL is caused by inadequate contraction force generation during the isovolumic contraction and ejection phases. Our further analysis revealed that the inadequacy in contraction force generation is not necessarily due to impaired myocardial intrinsic contractility, but at least in part, due to inadequate muscle fibre stretch at end-diastole, which depresses the ability of myocardium to generate adequate contraction force in the subsequent systole (according to the Frank-Starling law). Moreover, an excessively stiff infarct may cause its neighbouring myocardium to be understretched at end-diastole, subsequently depressing the systolic contractile force of the neighbouring myocardium, which was found to be correlated with infarct extension.

The role of regional myocardial topography post‐myocardial infarction on infarct extension

“…Deviated FSSL patterns, which involved isovolumic stretching of the RZ during IVC and elevated fibre stress during systole, were observed at some RZ regions surrounding the RZ‐BZ boundaries (e.g., Figure 6, node VI). Similar FSSL patterns were also observed in our previous study at the subendocardial RZ‐BZ boundary, which was linked to the occurrence of infarct extension 10 . The presence of regional IVC fibre stretching was caused by the inability of the myocardium to withstand LV pressure due to inadequate strain during the diastolic phase, which subsequently affected the contractile ability of the myocardium during the systolic phase (the Frank‐Starling law).…”

“…In particular, the presence of severely abnormal FSSL patterns, such as si and cw loops, resulted in nearly zero or negative DREW (Figures 5, 6 and 8) and was associated with infarct extension. This presents an important extension to our previous study, which proposed that work density dissipation (WDD) index, a measure of regional impairment in myocardial mechanics, could be used as a predictor for infarct extension 10 . Our detailed analysis of FSSL throughout the whole LV revealed that the FSSL pattern and loop direction at RZ regions surrounding the RZ‐BZ boundaries was highly varied, depending on the amount of surrounding infarcted tissue.…”

“…Manual tracing of the infarct on cine MRI images by referencing LGE MRI, as in our previous work, 10 is highly susceptible to intra‐ and interobserver variation. Furthermore, in‐plane and through‐plane motion within the LGE image volume and between the LGE and cine image volumes due to patient motion and inconsistent breath‐hold, may also lead to errors in infarct mapping and geometry construction.…”

“…The patient‐specific parameter optimisation and cardiac cycle simulation framework used in this study was the same as we have used previously 10 . Briefly, the optimisation was performed in two stages, that is end‐diastolic optimisation followed by end‐systolic optimisation.…”

“…While Ratcliffe et al 2 proposed that isovolumic BZ stretching was caused by an increase in systolic BZ stress, Guccione et al 9 demonstrated that experimentally observed IVC stretching at the BZ was due to deterioration of intrinsic contractility. This however cannot explain infarct extension at the RZ under normal intrinsic contractility found by Jackson et al 3 In order to further investigate possible mechanisms underlying infarct extension, we previously analysed fibre stress–strain loops (FSSLs) and correlated them to infarct extension using patient‐specific finite element (FE) models 10 . Deviation of FSSL from its ideal rectangular shape was observed at subendocardial regions experiencing infarct extension, and our findings revealed that infarct extension could possibly be initiated by reduced end diastolic fibre strain at the RZ‐BZ boundary, promoting IVC fibre stretching and depressing contractile function of the neighbouring myocardium, resulting in increased myocardial work dissipation which correlated with the occurrence of infarct extension.…”