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Appendix METHODS This study was performed according to the recommendations specified in the Cochrane Handbook for Systematic Reviews of Interventions(1). Eligibility criteria Studies performing IMR (index of microvascular resistance) using the thermodilution principle at the end of the primary percutaneous coronary intervention (PPCI) procedure and had a cardiovascular magnetic resonance (CMR) performed within a week of the STEMI were screened. Only studies reporting mean IMR ± standard deviation (SD) were included. Search strategy We searched MEDLINE and EMBASE databases up to June 2016. Additionally, we screened editorials and web-based sources of information to gain access to potential data from newly available or retrieved studies. The following search terms were used: “primary percutaneous coronary intervention”, “index of microvascular resistance”, “microvascular obstruction”, “cardiovascular magnetic resonance” and “ST-segment elevation myocardial infarction”. Data extraction Figure 1 shows the process of study selection as per preferred reporting items for systematic reviews and meta-analyses (PRISMA)(2). 6 studies(3-8) were identified and 2 reviewers performed data extraction independently. The study characteristics including IMR values are shown in Table 1 and table 2. Data synthesis and analysis RevMan 5.2 (Nordic Cochrane Centre) was used to conduct a fixed-effect meta-analysis for the weighted mean and weighted mean difference with 99% confidence intervals. All reported P values are two-sided, with significance set at P<0.05. Heterogeneity among trials was quantified using I2 statistics with I2 of 0-25%, 25-50% and 50-75% considered as low, moderate and high heterogeneity, respectively. Excluded studies McGeoch 2010(9): Reported median IMR in group with and without MVO Payne 2012(10): Did not report on IMR in the group with and without MVO. References 1. 2. 3. 4. 5. 6. Higgins JP, Altman DG, Gotzsche PC et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. Bmj 2011;343:d5928. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Bmj 2009;339:b2535. Yoo SH, Yoo TK, Lim HS, Kim MY, Koh JH. Index of microcirculatory resistance as predictor for microvascular functional recovery in patients with anterior myocardial infarction. Journal of Korean medical science 2012;27:1044-50. Ahn SG, Lee SH, Lee JH et al. Efficacy of combination treatment with intracoronary abciximab and aspiration thrombectomy on myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary coronary stenting. Yonsei Med J 2014;55:606-16. Cuculi F, De Maria GL, Meier P et al. Impact of Microvascular Obstruction on the Assessment of Coronary Flow Reserve, Index of Microcirculatory Resistance, and Fractional Flow Reserve After ST-Segment Elevation Myocardial Infarction. Journal of the American College of Cardiology 2014;64:1894-904. Fukunaga M, Fujii K, Kawasaki D et al. Thermodilution-derived coronary blood flow pattern immediately after coronary intervention as a predictor of microcirculatory damage and midterm clinical outcomes in patients with ST-segment-elevation myocardial infarction. Circulation Cardiovascular interventions 2014;7:149-55. 7. 8. 9. 10. Hoole SP, Jaworski C, Brown AJ et al. Serial assessment of the index of microcirculatory resistance during primary percutaneous coronary intervention comparing manual aspiration catheter thrombectomy with balloon angioplasty (IMPACT study): a randomised controlled pilot study. Open Heart 2015;2:e000238. Ahn SG, Hung OY, Lee JW et al. Combination of the Thermodilution-Derived Index of Microcirculatory Resistance and Coronary Flow Reserve Is Highly Predictive of Microvascular Obstruction on Cardiac Magnetic Resonance Imaging After STSegment Elevation Myocardial Infarction. JACC Cardiovascular interventions 2016;9:793-801. McGeoch R, Watkins S, Berry C et al. The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with ST-segment elevation myocardial infarction. JACC Cardiovascular interventions 2010;3:715-22. Payne AR, Berry C, Doolin O et al. Microvascular Resistance Predicts Myocardial Salvage and Infarct Characteristics in ST-Elevation Myocardial Infarction. Journal of the American Heart Association 2012;1:e002246. Table 1: Characteristics of the 6 included studies Study N Timing of IMR measurement Timing of CMR Primary Objective Outcome Yoo 2012 (3) 34 Anterior STEMI Immediately post PPCI 6±4 days To assess the micro-vascular dysfunction by IMR and predicting microvascular functional recovery in patients with AMI who underwent PPCI The extent of MVO by CMR correlated with IMR. IMR was significantly correlated with change in regional wall motion score index and change in left ventricular ejection fraction. 40 STEMI Immediately post PPCI Day 5 (range 3-9) To assess whether a combination of IC abciximab and aspiration thrombectomy is superior to each treatment alone in terms of improving MVO Combination of IC abciximab with aspiration thrombectomy improved IMR and reduced frequency of MVO 45 STEMI Immediately post PPCI, at day 1 and at 6 months Day 1day To describe how invasive coronary microcirculation indices evolve and are influenced by the presence of MVO. Patients with MVO had lower CFR immediately post PPCI and at 24 hours and a trend towards higher IMR. There were no significant differences seen both in IMR and CFR at 6 months between those who developed MVO and those who did not. Fukunaga 2014 (6) 88 STEMI Immediately post PPCI 7.4±3.2 days To evaluate whether CBF and IMR values immediately after PPCI predict early microvascular damage Patients in the “bimodal group” had higher prevalence of MVO on CMR when compared to those in the “narrow unimodal” and “wide unimodal groups” and were at higher risk of death and rehospitalization for heart failure. Hoole 2015(7) 41 STEMI Immediately post PPCI 48 hours To investigate whether manual thrombectomy would change microvascular function measured by IMR, compared with balloon angioplasty (BA) Manual thrombectomy was not superior to balloon angioplasty to improve IMR and reduce MVO Ahn 2012(4) Cuculi 2014(5) MVO: 12-15 minutes post gadolinium MVO: 10-15 minutes post gadolinium MVO: 10-15 minutes post gadolinium MVO: 15 minutes post gadolinium Early MVO: following first pass perfusion Late MVO: 5-10 minutes post gadolinium Ahn 2016(8) 40 Immediately post PPCI Median 7 days (range 5 to 11) MVO: 10-15 minutes post gadolinium To investigate the incremental predictive values of the IMR, CFR, and the combination of both to detect MVO on CMR in patients treated with primary PCI for STEMI Increased coronary microvascular resistance assessed by invasive physiological indexes (a high IMR and low CFR) was associated with MVO on CMR after reperfused STEMI. Table 2: IMR in STEMI patients with and without MVO by CMR Study Patients with MVO Patients without MVO N with CMR data IMR immediately post PPCI N with CMR data IMR immediately post PPCI Yoo 2012(3) 18 38.1±16.7 16 16.7±12.4 Ahn 2014(4) 15 53.4±44.3 16 21.5±5.2 Cuculi 2014(5) 21 42.9±24.4 22 31.3±16.0 Fukunaga 2014(6) 40 58.2±41.8 28 28.8±30.6 Hoole 2015(7) 13 53.8±37.3 17 38.9±28.4 Ahn 2016 23 42.0±20.0 17 20.0±8.0 Total 130 49.1 (99% CI 41.4 to 56.8) 116 26.8 (99% CI 21.6 to 32.0) Figure 1: PRISMA 2009 flow diagram This figure shows the process via which 6 studies were selected for inclusion in this meta-analysis