Discussion
The findings of our study can be summarised as follows: (1) MVO and IMH are frequently observed in reperfused AMI using T2W and LGE CMR, (2) IMH and MVO are strongly related phenomena, (3) patients with MVO and IMH have pre-PCI TIMI 3 flow less often, and (4) infarct size, once adjusted for MVO and IMH presence, remained the sole independent predictor of LV remodelling.
T2W CMR is capable of detecting myocardial oedema as regions of increased signal intensity due to prolongation of T2 relaxation time as a consequences of increased tissue free water content [18]. IMH is thought to be caused by leakage of blood out of severely injured microvasculature into the interstitium that can be depicted as a central area of low signal intensity (SI) within the oedematous area on T2W CMR. This low SI is explained by local field heterogeneities due to the paramagnetic effects of blood degradation products such as deoxyhaemoglobin, which shorten the T2 relaxation time [10]. In two case reports, Basso et al. demonstrated a good correlation among the location, spatial extent, and shape of IMH on CMR and histopathology [8]. Because of its excellent spatial resolution and high contrast, LGE CMR accurately assesses the extent of infarction and MVO [19]. Combined with T2W CMR, it is now possible to gain novel insights into the pathophysiology of IMH and MVO in vivo and evaluate their clinical significance.
Previous studies have shown that MVO infarcts show a lack of regional and global functional recovery compared with non-MVO infarcts; however, it remains unclear whether MVO provides independent prognostic information [11, 12]. Despite the strong relation of MVO with IS, some studies indicated that MVO is an important determinant of LV recovery and prognosis, even after controlling for IS, whereas others have reported that MVO loses its predictive power after adjusting for IS [13, 14, 20, 21]. Persistence of MVO, but not MVO that disappeared at 1 week after infarction, was associated with attenuated infarct healing and subsequent adverse remodelling, indicating that the timing of MVO imaging is important [22]. In that study and similar to our findings, IS remained the major determinant of LV remodelling in a multivariate model.
Our clinical observation that MVO and IMH occur in the central portions of the infarct and not in patients with pre-PCI TIMI 3 flow is in line with experimental studies showing the association of IMH with markedly depressed flow before reperfusion and severe ischaemia [5]. Our finding that IMH was also observed in 10% of patients with post-PCI TIMI flow <3 supports experimental observations that IMH does not depend on the magnitude of early reflow [6, 23]. Conflicting results on the clinical significance of IMH have been reported. Our data are in contrast to those of Ganame et al., who found that LVEF did not improve in patients with haemorrhagic infarcts as opposed to patients with non-haemorrhagic infarcts [16]. IMH and infarct size were the strongest independent predictors of adverse LV remodelling in that study. Our results are in accordance with those from Beek et al., who showed that IMH did not have prognostic significance beyond the presence of MVO [15].
The underlying pathophysiological mechanisms of MVO and IMH are complex and remain only partially understood. Irreversible ischaemic myocardial cell injury progresses as a ‘wave front’ from the endocardium to the epicardium, with endothelial cell injury occurring after myocardial cell injury [1, 3]. After varying periods of ischaemia, sequential changes of the microvasculature occur. Endothelial protrusion by cell swelling together with capillary plugging by neutrophils, red blood cells and platelets and swelling of surrounding myocytes compressing capillaries may all cause MVO. As ischaemic injury progresses, endothelial cell death causes loss of capillary integrity with resultant IMH in cases of myocardial reperfusion. Our data show that MVO and IMH are strongly related phenomena and suggest that IMH is a sign of severely injured microvasculature that easily leaks blood into the interstitial space. Furthermore, our results suggest that microvascular injury is predominantly a reflection of extensive myocardial necrosis rather than a separate entity identifying patients at higher risk.
Despite having MVO, IMH was absent in ten patients in our study. We postulate that, for some patients in the MVO(+)/IMH(−) group, the ischaemic threshold for IMH may not have been reached yet. This could explain the discrepancy between the predicted IMH values and the negative findings at CMR. Lending support to this concept was the finding that all measured parameters, including MVO size, were in between the average values of the two other groups. It is therefore likely that the groups reflect a gradation of the severity of ischaemic damage.