The primary results of this study are: (a) patients with early MVO had a higher prevalence of preexisting hypertension, but apart from that, showed similar risk profiles with regard to age, BMI, lipid status, smoking habits, diabetes and family history. (b) In line with most other MVO studies, a strong correlation between infarct size and early MVO was observed. (c) Early MVO is an independent long-term prognosticator of adverse clinical outcomes, especially recurrent ischemic symptoms, heart failure and repeat hospitalization, in a very long follow-up.
Patient characteristics and microvascular obstruction
MVO is an increasingly recognised phenomenon after pPCI for STEMI. Prevalence between 25%[
19] and 79% [
20] are described in recent literature. In our study, 69% of the patients showed eMVO.
Recently, two studies investigated predictors of late MVO defined by CMR, ECG and angiographic analysis [
18,
35]. Their results suggest an association of MVO with age, diabetes [
35] and hyperglycemia[
18,
36]. Due to the sample size of our study we cannot preclude an impact of diabetes or age on the presence of eMVO only by the lack of statistical significance. Our data, however, is in line with a recent larger studie [
20]. It is likely that the lower age (56.8 yrs
vs. 60 yrs [
35], 63 yrs [
18] and 66 yrs [
20]) and the lower prevalence of diabetes (8.4%
vs. 17% [
35], 16% [
18] and 27% [
20]) can be the explanation for the lack of statistical significance in our study group.
In our study, the prevalence of hypertension was significantly higher in patients with eMVO (65.8%
vs. eMVO- 45.5%) which has, to the best of our knowledge, not been described previously. Data on the effects of hypertension on the cardiac microvasculature suggest impaired endothelial function in hypertensive subjects [
37], which in turn might exaggerate microvascular dysfunction in patients after STEMI[
1]. Interestingly, Husser
et al. observed an inverse association of systolic blood pressure with the presence of MVO, which unfortunately we did not determine. The results of Husser
et al. are explained by the authors as a result of a significant higher Killip class in patients with MVO and the resulting cardiogenic shock [
35].
There was a trend towards a lower number of active smokers among eMVO + patients (69.7%
vs. eMVO- 50.7%, p = 0.052) which was also not observed previously. In analogy with the explanation of Husser
et al. that younger patients may lack ischemic preconditioning and coronary collaterals[
35], we believe that these mechanisms might explain our results despite the lack of statistical significance.
The presence [
20] and extent [
13,
38] of MVO correlates with measures of infarct size as well as with impaired left ventricular function [
20,
35]. The ratio of MVO to infarct size not only correlates with biomarker levels [
14], but is even of superior prognostic value compared to the extent of MVO alone [
38]. Our study is in line with these prior results although the extent of early MVO was not evaluated. Prior results of our study group suggest an additive effect of MVO on myocardial damage [
14] and impaired segmental myocardial function and functional recovery [
39].
Clinical outcomes
These effects of MVO on the cellular and functional level might explain why the prognostic value of early [
19] and late[
38] MVO has frequently been described as superior to that of infarct size alone. The results of the present study extend prior studies by an observation time of 5 years. One limitation of our study, however, is the relatively small sample size, which necessitates the use of a combined primary endpoint.
The question whether early or late MVO is of primary prognostic interest cannot as yet be answered. While deWaha
et al. argue that no hard clinical endpoints occurred in patients with early but no late MVO [
20], the use of early MVO might have an advantage due to a higher sensitivity in detecting the same pathophysiological phenomenon [
40,
41]. Moreover in a subgroup of 40 patients we previously observed that, beside infarct transmurality, eMVO is the most important imaging parameter in predicting regional functional recovery [
39]. On the other hand the use of 3 short-axis slices might underestimate the presence of MVO compared to the six to eight slices acquired on LGE images.
However, we believe that the clinical significance of different results are marginal, especially because the differences in total event-rates are small [
20]. The results of our and other previous studies [
11,
19,
20] suggest a superior prognostic value of MVO compared to that of infarct size and ejection fraction.
Infarct size and left ventricular EF alone have been shown to be significant prognostic parameters after STEMI in large CMR-trials [
42]. In our study group, however, the univariate impact of classical prognostic markers was not statistically significant. One explanation might be the small sample size of our study, which only allows for the most important parameter, namely MVO, to reach a significant number of clinical endpoints.
In our study, eMVO + patients differed from eMVO- patients in the occurrence of recurrent ischemic symptoms (24.7% vs. 6.1%, p < 0.05), congestive heart failure (12.3% vs. 0%, p < 0.05) and hospitalisations of any kind (60.3% vs. 39.4%, p < 0.05). In line with these results, we observed a trend for a higher NYHA class at follow-up (eMVO+: 1.5 ± 0.8 vs. eMVO-: 1.2 ± 0.5, M-W p = 0.072) as well as a trend for a higher number of cardiovascular hospitalisations (46.6% vs. 28.1%, χ2: 3.13, p = 0.077) and atrial fibrillation (8.2% vs. 0%, χ2: 2.88, p = 0.09).
The fact that the presence of MVO leads to a higher rate of recurrent ischemic symptoms during follow-up has not been observed previously. One explanation might be a lower number of coronary collaterals in patients with MVO [
43]. A second explanation might be found on the level of the microvasculature itself. An impaired endothelium-mediated vasodilation or microvascular spasms during the acute event [
44,
45], might represent a microvasculature prone to dysfunction, resulting in a higher number of recurrent ischemic symptoms [
46,
47] and finally MACE [
20].
Early re-admission rates for any cause have been proposed as a quality standard after myocardial infarction and represent not only comorbidities but also cardiovascular disease extent. In general STEMI populations ~10% readmission rates have been reported [
48]. In our study 3 patients were re-admitted within 30 days (2.8%). All of the admissons were of acute cardiovascular nature and occurred in patients with eMVO. The higher number of long-term admission rates in eMVO + patients might represent a higher general and cardiovascular morbidity of eMVO + patients, beside yet evaluated cardiovascular factors[
35].
In the OPTIMAAL trial it has been shown that atrial fibrillation occurs in up to 6-7% of patients within 3 years after first STEMI [
49]. Further the presence of atrial fibrillation after STEMI is associated with worsening prognosis [
50]. To us it seems that atrial fibrillation after STEMI is an important end-point, not only because of prognostic reasons but also because of pathophysiological considerations [
51]. Factors associated with atrial fibrillation after STEMI are age, male gender, history of angina, higher Killip classes, higher diastolic blood pressure, and higher pulse rate during the randomization [
49]. Some of these factors have also been shown to correlate with infarct size or the presence of MVO [
35].
We speculated that adverse remodeling [
52] aggravated by the presence of MVO is responsible for our observations. In conclusion, we believe that in our study population of relatively young (56.8 years) patients, the presence of early MVO leads to a higher cardiovascular morbidity after STEMI during a long term follow-up.