Author + information
- S1936879816313231-b6144efcd714d95ca8816c158f3cbdc8Heerajnarain Bulluck, MBBS∗ (, )
- S1936879816313231-9a64a4063f9506cbd38b72ba422accd8Nicolas Foin, PhD,
- S1936879816313231-616035a5987afde0ab2d446a8b86e138Hector A. Cabrera-Fuentes, PhD,
- S1936879816313231-60d04cfb6daf2a9f8c331c502da98478Khung K. Yeo, MBBS,
- S1936879816313231-fc38127bce6fdd6faaec7563eefc5de1Aaron S. Wong, MBBS,
- S1936879816313231-730a42f0930780eaa114be34da2327bbJiang M. Fam, MBBS,
- S1936879816313231-20e3dbefa8cd31e5174f5e36d79c0781Philip E. Wong, MBBS,
- S1936879816313231-4c95dc255f17684295465c70a7034173Jack W. Tan, MBBS,
- S1936879816313231-046b2f5173699d7aaba53507e8e713beAdrian F. Low, MBBS and
- S1936879816313231-fd0fc812126c35527c1ae4bc9f6f2128Derek J. Hausenloy, PhD
- ↵∗The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, WC1E 6HX, United Kingdom
Despite timely reperfusion by primary percutaneous coronary intervention (PPCI), microvascular obstruction (MVO) occurs in up to 50% of patients with ST-segment elevation myocardial infarction (STEMI) (1). Its presence is associated with adverse left ventricular remodeling and worse clinical outcomes (1), and there is currently no effective therapy for reducing its burden. MVO can be detected by cardiovascular magnetic resonance (CMR), but this can only be performed after PPCI, when it may be too late to implement potential therapies to minimize its deleterious effect.
In this regard, the index of microvascular resistance (IMR, defined as the product of the distal pressure and mean transit time of a saline bolus during maximum hyperemia using a dual temperature and pressure wire) has been introduced as a method for evaluating the coronary microvascular circulation at the time of PPCI. However, not all studies have consistently shown a significant difference in IMR between those with and without MVO and were likely due to being underpowered. Therefore, we conducted a meta-analysis to investigate the role of IMR in detecting the presence of MVO at the time of PPCI in reperfused STEMI patients.
We searched MEDLINE and EMBASE databases up to June 2016. The inclusion criteria were those studies undertaking both IMR at the end of PPCI in STEMI patients and performing CMR to detect MVO. We only included studies reporting the mean IMR in patients with and without MVO. Further details of the studies included in this meta-analysis are available in the Online Appendix.
Six studies were included in the meta-analysis, comprising a total of 288 patients (2–7). Further details of the 6 included studies are available in the Online Appendix. MVO data by CMR was available for 246 patients. MVO was present in 130 of 246 patients (53%). The weighted mean IMR of the whole cohort was 38.6 ± 30.6 U (99% confidence interval [CI]: 33.5 to 43.6 U). The weighted mean IMR in the 130 patients with MVO was 49.1 ± 33.6 U (99% CI: 41.4 to 56.8 U), whereas it was 26.7 ± 21.5 U (99% CI: 21.6 to 32.0 U; p < 0.0001; heterogeneity; chi-square = 4.31; df = 5; p = 0.51; I2 = 0%) in 116 patients without MVO. The weighted mean difference in IMR between these 2 groups was 20.9 U (99% CI: 14.0 to 27.8 U; I2 = 0%; p < 0.00001; Figure 1).
This study suggests that patients with a weighted mean IMR of <32 U (upper limit of the 99% CI in the group without MVO) were far less likely to have MVO, whereas patients with a weighted mean IMR of >41 U (lower limit of the 99% CI in the group with MVO) were much more likely to have MVO. Interestingly, a median IMR value of >40 U was previously shown to be an independent predictor of death in a large study of 253 patients with STEMI (hazard ratio: 4.3; p = 0.02) after a median follow-up of 2.8 years (8). This IMR value was very close to the cutoff value we obtained from this meta-analysis using MVO by CMR as a surrogate.
Therefore, we would propose that when investigating a novel intervention for minimizing the burden of MVO, selecting patients with an IMR of >41 U may help to identify, at the time of PPCI, those very likely to have MVO and at risk of worse outcomes. This approach would identify those most likely to benefit from promising therapies such as an infusion of glycoprotein IIb/IIIa inhibitors and intracoronary thrombolysis. Furthermore, by only targeting those with an IMR of >41 U at the end of the PPCI procedure, those at lower risk of MVO (IMR ≤41U) will not be subjected to unnecessary risk of adverse events such as bleeding.
The main limitations of this study are patient-level data were not available to report on sensitivity and specificity of IMR to detect MVO. The SDs reported in some of these studies were quite wide and this highlights the heterogeneity present when measuring IMR. It is highly probable that the sensitivity and specificity of IMR to detect MVO would be affected as a result. However, our study is not suggesting that IMR measurement can dichotomize those with and without MVO, but is providing an approach to identify those at high risk of having MVO in the cardiac catheterization laboratory and could be targeted in future studies. The interval between PPCI and CMR was different in each study and could have affected the detection of MVO. MVO was assessed on late gadolinium enhancement performed between 10 and 15 min post contrast in the majority of the studies, but 1 study performed late gadolinium enhancement imaging between 5 and 10 min post-contrast (6) and may have led to a higher incidence of MVO in the latter.
In conclusion, IMR at the time of PPCI can identify those patients with MVO, allowing the implementation of treatment to minimize this complication. We provide weighted mean IMR values in patients with MVO (49 ± 33 U) and without MVO (27 ± 22 U), information that may be used to estimate sample sizes when planning future studies to assess the efficacy of novel therapies for reducing its burden.
For an expanded Methods section, please see the online version of this article.
Please note: Dr. Yeo received honoraria from Boston Scientific, Abbott Vascular, and St. Jude Medical; is a consultant for Boston Scientific; is a proctor for Abbott Vascular; received research grant support from Medtronic; and received speaker fees from St. Jude Medical. Dr. Tan is an employee of the National Heart Center Singapore and has received honoraria and research grants. Dr. Wong is a Senior Consultant at the National Heart Center Singapore and is the CEO/CTO of Innoheart Pre-clinical CRO Singapore. All other authors reported that they have no relationships relevant to the contents of this article to disclose.
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