A successful restoration of epicardial coronary artery blood flow after primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) does not always lead to adequate myocardial perfusion or optimal outcome. Prior studies have shown that microvascular obstruction (MVO) is present in up to 50% of patients with STEMI even after timely reperfusion by PPCI and independently associated with ventricular remodeling and adverse clinical outcomes [
MVO can be identified by cardiac magnetic resonance imaging (MRI), but it can be performed couple of days after PPCI. Therefore, cardiac MRI is not directly helpful in determining whether potential therapies should be applied during revascularization or at early post-PPCI period to reduce adverse effect of MVO. However, measurement of ST-segment changes using electrocardiography (ECG) can not only be easily performed immediately after PPCI but also reflect status of microvascular integrity, infarct size, and prognostic information beyond angiographic findings [
Recently, the index of microvascular resistance (IMR) has been proposed for evaluating the coronary microvascular circulation and providing reliable quantitative values in patients with stable angina [
The study population included 73 consecutive hemodynamically stable patients with the first attack of STEMI who underwent PPCI at Inje University Sanggye-Paik Hospital, Seoul, Korea, between March 2012 and November 2013. The inclusion criteria were as follows: (1) chest pain lasting ≥30 minutes and resistant to nitrates; (2) presentation within 12 hours after symptom onset; (3) persistent ST-segment elevation ≥2 mm in ≥2 contiguous precordial leads or ≥1 mm in ≥2 limb leads on 12-lead electrocardiography (ECG), and elevation of serum creatine kinase-MB (CK-MB) or troponin-I levels to at least twice the upper limit of normal; (4) angiographic evidence of total occlusion that is thrombosis in myocardial infarction (TIMI) flow grade 0 or 1. The exclusion criteria were as follows: (1) prior myocardial infarction, defined by preexisting pathologic Q-wave; (2) non-ST elevation myocardial infarction; (3) left bundle branch block, right bundle branch block, ventricular pacing, or other significant arrhythmia; (4) hemodynamic instability requiring the use of intravenous inotropes or mechanical supports such as intra-aortic balloon pump or percutaneous cardiopulmonary support.
All enrolled patients were treated with successful PPCI (defined as <25% residual epicardial lesion) in achievement of door-to-balloon times of ≤90 minutes and TIMI flow grade ≥2 in final angiography. Prior to PPCI, all patients received aspirin 300 mg, clopidogrel 600 mg, and weight-adjusted heparin (70 units/kg). Use of aspiration thrombectomy catheters or adjunctive pharmacologies such as platelet glycoprotein IIb/IIIa receptor inhibitor was left to the discretion of the primary operator. The study protocol was approved by the Institutional Review Board at our institute (SG-IRB 2010-085), and all participants provided written informed consent.
After successful primary stenting, IMR was measured in all patients. IMR was assessed using a coronary pressure/temperature sensor-tipped guidewire placed distally in the culprit lesion. Hyperemia was induced by 140
For all patients, a standard 12-lead ECG was obtained at initial hospital presentation and at 90 minutes after PPCI. ST-segment elevation was measured 20 ms after the J-point. The sum of ST-segment elevations (sum STE) was measured in leads V1 through V6 for anterior wall infarctions and in leads I, aVL, II, III, aVF, and V4 through V6 for nonanterior wall infarctions. STR was represented by percentage of summed ST-segment reduction between baseline and post-PPCI. The sum of residual ST-segment elevation (residual STE) across all infarct-related leads on the 90-minute post-PPCI ECG was also evaluated. Patients were divided into 2 groups according to the amount of STR: (1) complete STR (≥50%) and (2) incomplete STR (<50%). The ECGs were analyzed by 2 investigators blinded to IMR and angiographic data.
Standard echocardiography was performed after PPCI in all patients. According to the recommendation of the American Society of Echocardiography, the left ventricle was divided into 16 segments [
The biochemical test was performed to obtain complete blood cell count finding, serum level of cardiac enzyme, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein at the emergency room. CK-MB and troponin-I levels were measured at admission, six hours later, and then twice daily over first 48 hours. Peak CK-MB and peak troponin-I were defined as the highest CK-MB and troponin-I measured. All patients were followed for over 3 years, either by clinic visit or by telephone interview. The major adverse cardiovascular event (MACE) in this study was a composite of cardiac death, nonfatal myocardial infarction, any revascularization, and cerebrovascular accident. Clinical events were defined according to the Academic Research Consortium [
Continuous variables are reported as mean ± standard deviation or median and categorical variables as a percentage. Continuous variables were analyzed using Student’s
Baseline characteristics of the patients according to the degree of STR are summarized in Table
Baseline, angiographic, and procedural characteristics.
All ( |
Incomplete STR ( |
Complete STR ( |
| |
---|---|---|---|---|
Age (years) | 58.4 ± 13.3 | 58.5 ± 13.3 | 58.4 ± 13.5 | 0.972 |
Male, |
62 (84.9) | 20 (87.0) | 42 (84.0) | 0.999 |
Comorbidities, |
||||
Current smoker | 37 | 13 (56.5) | 24 (48.0) | 0.618 |
Hypertension | 41 (56.2) | 13 (56.5) | 28 (56.0) | 0.967 |
Diabetes | 16 (21.9) | 5 (21.7) | 11 (22.0) | 0.980 |
Dyslipidemia | 10 (13.7) | 5 (21.7) | 5 (10.0) | 0.270 |
Stroke | 6 (8.2) | 1 (4.3) | 5 (10.0) | 0.658 |
Electrocardiographic data | ||||
Infarct location, |
||||
Anterior | 33 (54.8) | 17 (73.9) | 23 (46.0) | 0.042 |
Inferior | 28 (38.4) | 4 (17.4) | 24 (48.0) | 0.012 |
Lateral | 5 (6.8) | 2 (8.7) | 3 (6.0) | 0.672 |
Sum of ST-segment elevation (mm) | 10.3 ± 5.6 | 9.2 ± 4.2 | 11.1 ± 6.0 | 0.137 |
ST-segment resolution (%) | 63.8 ± 36.0 | 18.4 ± 22.8 | 84.7 ± 16.1 | <0.001 |
Residual sum of ST-segment elevation (mm) | 3.6 ± 3.5 | 6.6 ± 3.2 | 2.1 ± 2.6 | <0.001 |
Laboratory data | ||||
Absolute neutrophil count (mm3) | 7,959 ± 3,797 | 8,704 ± 3,936 | 7,616 ± 3,722 | 0.259 |
Peak CK-MB (IU/L) | 191.9 ± 130.7 | 215.8 ± 129.4 | 180.8 ± 131.1 | 0.291 |
Peak troponin-I (ng/ml) | 52.0 ± 30.5 | 57.0 ± 29.1 | 49.7 ± 31.1 | 0.340 |
N-terminal pro-BNP (pg/ml) | 585.3 ± 875.4 | 677.0 ± 999.6 | 527.9 ± 805.6 | 0.611 |
hsCRP (mg/L) | 1.41 ± 2.56 | 2.0 ± 3.7 | 1.17 ± 1.92 | 0.368 |
Echocardiography finding | ||||
Ejection fraction (%) | 51.4 ± 10.9 | 45.5 ± 7.8 | 54.2 ± 11.1 | 0.001 |
Ejection fraction <50%, |
32 (43.8) | 17 (73.9) | 15 (30.0) | 0.001 |
RWMSI | 1.32 ± 0.32 | 1.47 ± 0.35 | 1.25 ± 0.27 | 0.005 |
Angiographic data | ||||
LAD culprit, |
33 (54.8) | 17 (73.9) | 23 (46.0) | 0.042 |
Coronary flow before PPCI, |
||||
TIMI flow grade 0 or 1 | 54 (74.0) | 18 (78.3) | 36 (72.0) | 0.775 |
TIMI flow grade 2 or 3 | 19 (26.0) | 5 (21.7) | 14 (28.0) | 0.775 |
Coronary flow after PPCI, |
||||
TIMI flow grade 2 | 15 (20.5) | 7 (30.4) | 8 (16.0) | 0.213 |
TIMI flow grade 3 | 58 (79.5) | 16 (69.6) | 42 (84.0) | 0.213 |
TMP grade after PPCI, |
||||
TMP grade 1 | 2 (2.7) | 1 (4.3) | 1 (2.0) | 0.534 |
TMP grade 2 | 29 (39.7) | 11 (47.8) | 18 (36) | 0.337 |
TMP grade 3 | 42 (57.5) | 11 (47.8) | 31 (62) | 0.255 |
Index of microvascular resistance (U) | 24.3 ± 17.6 | 32.6 ± 23.5 | 20.0 ± 11.8 | 0.012 |
Procedure data | ||||
Mean stent diameter (mm) | 3.4 ± 0.5 | 3.3 ± 0.4 | 3.5 ± 0.5 | 0.217 |
Total stent length (mm) | 21.7 ± 6.6 | 22.4 ± 7.8 | 21.3 ± 6.0 | 0.498 |
No reflow, |
3 (4.1) | 1 (4.3) | 2 (4.0) | 0.945 |
Aspiration thrombectomy, |
66 (90.4) | 21 (91.3) | 45 (90.0) | 0.999 |
Use of platelet glycoprotein IIb/IIIa inhibitors, |
35 (47.9) | 11 (47.8) | 24 (48.0) | 0.989 |
BNP: brain natriuretic peptide; CK-MB: creatine kinase-MB; hsCRP: high-sensitivity C-reactive protein; LAD: left anterior descending artery; MACE: major adverse cardiovascular event; PPCI: primary percutaneous coronary intervention; RWMSI: regional wall motion score index; STR: ST-segment elevation resolution; TIMI: thrombosis in myocardial infarction; TMP grade: TIMI myocardial perfusion grade.
Consistent with ECG analysis, angiography showed that LAD was more likely to be an infarct-related artery in the incomplete STR group compared with the complete STR group. However, proportion of TMP grade 1 achievement in the final angiography was not different between 2 groups.
The IMR value was significantly higher in the incomplete STR group patients compared with the complete STR group (Table
Relationship between STR and IMR. IMR: index of microvascular resistance; STR: ST-segment elevation resolution.
Comparison of LAD and non-LAD infarctions.
LAD infarction ( |
Non-LAD infarction ( |
|||||
---|---|---|---|---|---|---|
Incomplete STR ( |
Complete STR ( |
|
Incomplete STR ( |
Complete STR ( |
| |
ST-segment resolution (%) | 24.2 ± 18.4 | 78.1 ± 15.9 | <0.001 | 29.5 ± 40.0 | 90.3 ± 14.3 | 0.013 |
Ejection fraction (%) | 43.4 ± 5.0 | 51.3 ± 13.6 | 0.015 | 51.6 ± 11.5 | 56.8 ± 7.8 | 0.183 |
RWMSI | 1.6 ± 0.4 | 1.4 ± 0.3 | 0.145 | 1.2 ± 0.2 | 1.1 ± 0.1 | 0.133 |
Peak CK-MB (IU/L) | 236.8 ± 130.9 | 197.3 ± 147.0 | 0.382 | 156.3 ± 114.5 | 166.8 ± 116.9 | 0.843 |
Peak troponin-I (ng/ml) | 60.5 ± 28.2 | 49.7 ± 34.5 | 0.281 | 47.2 ± 32.1 | 49.6 ± 28.5 | 0.852 |
TMP grade after PCI | ||||||
1, |
1 (5.9) | 0 | 0.425 | 0 | 1 (3.7) | 0.818 |
2, |
9 (52.9) | 10 (43.5) | 0.554 | 2 (33.3) | 8 (29.6) | 0.858 |
3, |
7 (41.2) | 13 (56.5) | 0.337 | 4 (66.7) | 18 (66.7) | 0.999 |
Index of microvascular resistance (U) | 33.7 ± 25.0 | 20.7 ± 14.4 | 0.046 | 28.8 ± 19.9 | 19.4 ± 8.7 | 0.148 |
CK-MB: creatine kinase-MB; LAD: left anterior descending artery; RWMSI: regional wall motion score index; STR: ST-segment elevation resolution; TMP grade: TIMI myocardial perfusion grade.
Receiver operator characteristic analysis to predict incomplete STR from the IMR value. The best cutoff value for IMR to predict incomplete STR was 27.3. AUC: area under the curve; IMR: index of microvascular resistance; STR: ST-segment elevation resolution.
Univariate and multivariate regression analyses for predicting high IMR (IMR ≥27.3).
Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|
HR (95% CI) |
|
HR (95% CI) |
| |
Age, per year | 1.01 (0.97–1.06) | 0.545 | ||
Male | 0.76 (0.16–3.59) | 0.727 | ||
Hypertension | 1.53 (0.50–4.75) | 0.458 | ||
Diabetes mellitus | 1.25 (0.33–4.70) | 0.741 | ||
Dyslipidemia | 1.70 (0.34–8.55) | 0.520 | ||
Current smoking | 2.06 (0.65–6.51) | 0.217 | ||
Incomplete STR | 4.03 (1.22–13.28) | 0.022 | 4.80 (1.06–21.69) | 0.042 |
Peak CK-MB | 1.01 (1.00–1.01) | 0.060 | 1.00 (1.00–1.01) | 0.265 |
Peak troponin-I | 1.02 (1.00–1.04) | 0.070 | 1.01 (0.98–1.05) | 0.534 |
hsCRP | 1.05 (0.85–1.30) | 0.659 | ||
Ejection fraction | 0.94 (0.87–1.01) | 0.091 | 1.00 (0.91–1.11) | 0.878 |
Aspiration thrombectomy | 0.48 (0.07–3.44) | 0.500 | ||
Stent length | 1.05 (0.96–1.15) | 0.255 |
CI: confidence interval; CK-MB: creatine kinase-MB; HR: hazard ratio; IMR: index of microvascular resistance; STR: ST-segment elevation resolution.
Kaplan–Meier curve between the high and low IMR group. IMR: index of microvascular resistance.
Despite the lack of a correlation of the degree of STR with the peak CK-MB and peak TnI, a strong relationship was identified between sum STE and the peak CK-MB (
The present study has shown that the lack of STR early after STEMI treated with successful PPCI is linked with microvascular dysfunction assessed by IMR and left ventricular systolic dysfunction. To the best of our knowledge, this is the first study to demonstrate the association between STR and IMR after PPCI. Furthermore, the significant relationship between incomplete STR and higher IMR was observed in patients with LAD infarction, but not in those with non-LAD infarction. The cutoff value of IMR for predicting incomplete STR was 27.3, and patients with high IMR based on this value experienced more frequent incidence of MACE than those with low IMR.
Consistent with other studies [
In the fibrinolysis era, STR was a well-established marker of the infarct-related artery (IRA) patency. Therefore, most of the previous fibrinolytic studies have shown the relation between a lack of STR and the large infarct size or poor clinical outcomes [
In the present study, patients with incomplete STR were more likely to have LAD infarction, similar to previous studies [
According to our findings and previous studies, the degree of STR and IMR measurement may offer complementary information about microcirculatory dysfunction at the very earliest stage of STEMI management, so they may assist operator’s early decision making to select patients who may benefit from adjunctive or more intensive therapy.
The present study has several limitations. First, this was a prospective single-center observational study with a small study population. Second, we did not obtain follow-up echocardiography in all patients; therefore, we could not assess the interval change of ventricular function according to the degree of STR or IMR. At last, we excluded hemodynamically unstable patients who needed catecholamine or mechanical support because they could not be able to measure IMR. Therefore, only patients who had relatively small infarct area might be enrolled.
The degree of STR had an inverse relationship with the IMR value and was well correlated with LVEF. Incomplete STR early after PPCI for STEMI might be a surrogate marker for microvascular as well as left ventricular dysfunction, especially in patients with LAD infarction.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that there are no conflicts of interest.
Byung Gyu Kim and Sung Woo Cho contributed equally to this work.
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A3B03034465) and the 2017 Inje University research grant.