Predictive value of plaque morphology assessed by frequency-domain optical coherence tomography for impaired microvascular perfusion after elective stent implantation: the intracoronary electrocardiogram study

Predictive value of plaque morphology assessed by frequency-domain optical coherence tomography... Abstract Aims This study was undertaken to assess the association between plaque features at culprit lesions assessed by frequency-domain optical coherence tomography (FD-OCT) and impaired microvascular perfusion estimated by intracoronary electrocardiogram (IcECG) after elective percutaneous coronary intervention (PCI). Furthermore, we investigated whether IcECG could predict future cardiac events. Methods and results This study consisted of 84 patients who underwent both FD-OCT and IcECG during PCI. Patients were classified into two groups based on ST-segment elevation (ST-E) on IcECG after the procedure; ST-E (−) group (n = 53) and ST-E (+) group (n = 31). Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Plaque rupture (7.5% vs. 35.5%, P = 0.001), lipid-rich plaque (75.5% vs. 100%, P < 0.001), the thin cap fibroatheroma (0% vs. 25.8%, P < 0.001) on pre-FD-OCT, protrusion (18.9% vs. 56.7%, P < 0.001), and intra-stent dissection (15.1% vs. 50.0%, P < 0.001) on post-FD-OCT were significantly more frequently found in the ST-E (+) group than in the ST-E (−) group. The incidence of MACE (cardiac death, myocardial infarction, revascularization, hospitalization for heart failure) during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05). Conclusion Plaque features assessed by FD-OCT might be associated with impaired microvascular perfusion and ST-segment elevation on IcECG after the procedure could predict 1-year cardiac events after elective PCI. impaired microvascular perfusion, intracoronary electrocardiogram, frequency domain optical coherence tomography, periprocedural myocardial injury Introduction Percutaneous coronary intervention (PCI) is a well-established therapeutic strategy for patients with stable angina pectoris. However, periprocedural myocardial injury (PMI) after PCI is not uncommon and even a small biomarker increase is significantly associated with an adverse short- and long-term outcome.1 Especially, distal embolization during PCI may deteriorate microvascular perfusion in patients who underwent elective PCI. Numerous efforts have been made to detect high-risk plaque which may cause distal embolization during PCI, using several imaging devices. Of these, frequency-domain optical coherence tomography (FD-OCT) has been recently developed as a high-resolution imaging method to observe culprit lesions more clearly. On the other hand, surface ST-segment change on the electrocardiogram (ECG) reflects myocardial flow and microvascular perfusion after PCI rather than epicardial flow and predicts better myocardial salvage and clinical outcome in acute myocardial infarction patients.2 However, the sensitivity of surface ECG for detecting ischaemia during elective PCI has been disappointing.3 Unipolar intracoronary electrocardiogram (IcECG) which represents local epicardial ECG seemed to be more sensitive than surface ECG for detecting local ischaemia and microvascular perfusion during PCI and persistent ST-segment elevation on IcECG reflects impaired microvascular perfusion after PCI.4 IcECG is a simple, speedy and established method for predicting microvascular perfusion in the catheterization laboratory.4 This study was undertaken to assess the association between plaque features at culprit lesions assessed by FD-OCT on pre- and post-PCI and microvascular perfusion estimated by IcECG. Furthermore, we investigated whether IcECG could predict future cardiac events after elective PCI. Methods Study patient In total, 460 consecutive patients underwent PCI from January 2014 to March 2016 at Hiroshima University Hospital. Of these, we enrolled 84 patients with stable angina pectoris who underwent elective PCI for a single, native, de novo coronary lesion and performed FD-OCT and IcECG both at baseline and after the procedure in this study. A study flow chart is reported in Figure 1. All patients had the presence of anginal chest pain and myocardial ischaemia on myocardial perfusion scintigram or the treadmill exercise test or fractional flow reserve. Patient-related exclusion criteria were: (i) acute coronary syndrome; (ii) elevated pre-procedural cardiac biomarker; (iii) reduced renal function (Estimated glomerular filtration rate <30 mL/min per 1.73 m2). Lesion-related exclusion criteria were the vessels within a myocardial territory of previous myocardial infarction (MI), the left main trunk, ostium lesions, extremely tight lesions or tortuous vessels where we expected difficulty in advancing soft-tip guidewire or the FD-OCT catheter, severe calcified lesions needed for debulking device, target vessel reference diameter of ≥4 mm expected limitation in FD-OCT evaluation and angiographic evidence of coronary dissection or major side branch (>1 mm) occlusion after the procedure. Patients were classified into two groups based on ST-segment elevation (ST-E) on IcECG after the procedure; absence of ST-E [ST-E (−) group: n = 53] and presence of ST-E [ST-E (+) group: n = 31]. Prescription of statins was defined as taking statins at least 7 days before PCI. Multivessel disease was defined as ≥50% stenosis in 1 or more vessels remote from the target artery. Informed consent was obtained from each patient. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the ethical committee of Hiroshima University Graduate School of Biomedical and Health Sciences. Figure 1 View largeDownload slide Study flow chart. PCI, percutaneous coronary intervention; FD-OCT, frequency-domain optical coherence tomography; IcECG, intracoronary electrocardiogram; ST-E, ST-segment elevation. Figure 1 View largeDownload slide Study flow chart. PCI, percutaneous coronary intervention; FD-OCT, frequency-domain optical coherence tomography; IcECG, intracoronary electrocardiogram; ST-E, ST-segment elevation. Study protocol The study protocol was as follows (Figure 2). First, the baseline IcECG (pre-IcECG) was recorded after positioning the guidewire in the distal part of a target vessel. Second, the baseline FD-OCT (pre-FD-OCT) was performed with or without balloon pre-dilatation (1.5 mm noncompliant balloon, 6 atm). Then coronary stent implantation was performed. The post-procedural FD-OCT (post-FD-OCT) was performed with or without balloon post-dilatation. Finally, the post-procedural IcECG (post-IcECG) was recorded after positioning the guidewire in the same part. Blood samples were obtained pre-PCI and at approximately 18 h after PCI to evaluate cardiac biomarkers. A major adverse cardiac event (MACE) was defined as cardiac death, MI, repeat revascularization and/or hospitalization for heart failure. Follow-up angiography was encouraged at 8–10 months after elective PCI or earlier when clinically indicated. Repeat revascularization was identified as any unstaged revascularization after the index procedure. Clinical follow-up was performed for up to 1-year after PCI. Figure 2 View largeDownload slide Study protocol. All patients received dual antiplatelet agents (aspirin 100 mg/day and clopidogrel 75 mg/day, 300 mg loading dose) and statins at least 24 h before the procedure. An intracoronary injection of isosorbide dinitrate 2 mg was performed pre and post PCI. Abbreviations as in Figure 1. Figure 2 View largeDownload slide Study protocol. All patients received dual antiplatelet agents (aspirin 100 mg/day and clopidogrel 75 mg/day, 300 mg loading dose) and statins at least 24 h before the procedure. An intracoronary injection of isosorbide dinitrate 2 mg was performed pre and post PCI. Abbreviations as in Figure 1. PCI and FD-OCT procedures All patients were treated by second or third generation drug-eluting stent without any distal protection device according to standard techniques. All patients received dual antiplatelet agents (aspirin 100 mg/day and clopidogrel 75 mg/day, 300 mg loading dose) and statins at least 24 h before the procedure. 7500 IU of unfractionated heparin was administrated before procedure and an additional bolus of heparin was given during PCI, with a target activated clotting time of >250 s every 30 min. No patient received glycoprotein IIb/IIIa receptor inhibitor. In addition, no patient received other intravenous and intracoronary administration except isosorbide dinitrate. All stents were inflated 3 times to the almost nominal inflation pressure using the stent delivery balloon. The first inflation continued until the stent was angiographically fully expanded; the other 2 lasted 15 to 20 s, respectively. FD-OCT system was a commercially available system (C7 System; LightLab Imaging Inc/St Jude Medical, Westford, MA). The FD-OCT catheter (C7 Dragonfly; LightLab Imaging Inc/St Jude Medical, Westford, MA) was advanced to the distal end of the culprit lesion and contrast media was continuously infused into the coronary artery directly from the guiding catheter. Successful PCI was defined as the achievement of <25% residual stenosis, no angiographic stent edge dissection and final thrombolysis in myocardial infarction (TIMI) flow grade 3. After achieving the angiographic end point, no additional PCI was performed. FD-OCT image analysis Analysis of the FD-OCT images was performed every 0.2 mm interval by 2 reviewers blinded to the results of the IcECG analysis and clinical data. FD-OCT images were analyzed using validated criteria for thrombus characterization, plaque characterization, ruptured plaque, fibrous cap thickness, incomplete stent apposition, tissue protrusion, edge dissection and intra-stent dissection as reported previously.5–7 Lipid was semiquantified as the number of involved quadrants on the cross-sectional FD-OCT image. Lipid-rich plaque was defined as plaque with ≥2 quadrants. Fibrous cap thickness was defined as the minimum distance from the coronary artery lumen to inner border of lipid pool on the cross-sectional FD-OCT image. The length of lipid pool was measured as consecutive longitudinal length of lipid pool at culprit plaque assessed by FD-OCT. The thin cap fibroatheroma (TCFA) was defined as a plaque with lipid content in ≥2 quadrants and the thinnest part of the fibrous cap measuring <65 μm. Culprit plaque was defined as the plaque at the site of minimum lumen diameter. IcECG recording and analysis IcECG was recorded both at baseline and after the procedure as reported previously.3,4 In brief, a 0.014-inch guidewire (Hi-Torque Balance Middle Weight-Universal, Abbott Vasclar; Santa Clara, California) was passed distal to the culprit lesion and positioned at the distal epicardial position of a target vessel. Pre-IcECG was recorded just after the guidewire passed. At the end of PCI, the guidewire was placed in the same position as pre-IcECG after all procedure and post-IcECG was recorded. ST-segment elevation on IcECG was measured 20 ms after the end of the QRS or QS complexes to the nearest 0.5 mm. Three consecutive QRS complexes were analyzed and mean ST-segment elevation values were calculated. ST-E (+) on IcECG was defined as ST-segment elevation ≥1 mm from baseline.3 Representative case of ST-E (+) on IcECG is shown in Figure 3. Figure 3 View largeDownload slide Representative case of ST-segment elevation on intracoronary electrocardiogram. A, IcECG at baseline (pre-IcECG) B, IcECG after the procedure (post-IcECG). Post-IcECG shows ST-segment elevation compared with pre-IcECG. IcECG, intracoronary electrocardiogram. Figure 3 View largeDownload slide Representative case of ST-segment elevation on intracoronary electrocardiogram. A, IcECG at baseline (pre-IcECG) B, IcECG after the procedure (post-IcECG). Post-IcECG shows ST-segment elevation compared with pre-IcECG. IcECG, intracoronary electrocardiogram. Laboratory measurements Blood samples were collected just before PCI and 18 h after the procedure in the postabsorptive state. Serum troponin-I (TnI) was measured with a commercially available enzyme immunoassay kit (Siemens Healthcare Diagnostics K.K., Tokyo, Japan). The Creatine kinase-MB (CK-MB) activity was measured with the Cica Liquid CK test (Kanto Chemical, Tokyo, Japan). Statistical analysis Standard statistical methods were used in this study. Significant differences were tested using the χ2 test for categorical variables. Normally distributed continuous variables are presented as mean and standard deviation (SD) or median and inter-quartile range (IQR). Unpaired Student’s t-test or Wilcoxon rank-sum test when appropriate was used for continuous variables. Interobserver and intraobserver variabilities of FD-OCT findings and IcECG findings were assessed by the kappa statistic of concordance. Event-free survival curves up to 1-year after PCI were constructed with the Kaplan–Meier method and were compared with the log-rank test. The JMP statistical package (version 11.0, SAS Institute, Inc. Cary, NC, USA) was used for all statistical tests. A significance level of 0.05 was used and two-tailed tests were applied. Results Clinical, angiographic and procedural results No PCI related complications occurred and the procedures were successfully completed in all patients. Thirty-one out of 84 patients (36.9%) represented ST-segment elevation on post-IcECG. The baseline characteristics of the study patients are shown in Table 1. There was no significant difference in all baseline clinical variables except statins at least 7 days before PCI between the two groups. The rate of patients taking statins at least 7 days before PCI was significantly higher in the ST-E (−) group than in the ST-E (+) group (90.6% vs. 74.2%, P < 0.05). Regarding cardiac biomarkers, no significant difference was observed in CK-MB and TnI level before PCI between the two groups. However, CK-MB and TnI after PCI were significantly higher in the ST-E (+) group than in the ST-E (−) group (CK-MB; 8.6 ± 3.2 IU/L vs. 13.8 ± 7.5 IU/L, P < 0.001, TnI; 0.14 ng/mL [IQR 0.07 to 0.42] vs. 0.84 ng/mL [IQR 0.29 to 2.07], P < 0.001). In addition, there was no significant difference in other blood chemical parameters between the two groups. Table 1 Baseline characteristics   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Clinical characteristics   Age, years  67.0 ± 9.2  68.0 ± 10.9  0.57   Male, n (%)  42 (79.3%)  28 (90.3%)  0.19   Hypertension, n (%)  39 (73.6%)  22 (70.9%)  0.80   Dyslipidemia, n (%)  35 (66.0%)  20 (64.5%)  0.89   Diabetes mellitus, n (%)  20 (37.7%)  11 (35.5%)  0.84   Current smoker, n (%)  10 (18.9%)  8 (25.8%)  0.45   Body mass index, kg/m2  24.1 ± 2.8  24.9 ± 4.3  0.21   Medication, n (%)         β-blocker  29 (54.7%)  14 (45.2%)  0.40   Calcium channel blocker  33 (62.3%)  14 (45.2%)  0.13   ACE-I/ARB  32 (60.4%)  18 (58.1%)  0.83   Statin 7 days before PCI  48 (90.6%)  23 (74.2%)  <0.05  Laboratory data   eGFR, mL/min per 1.73 m2  70.77 ± 18.53  64.55 ± 16.15  0.13   HDL cholesterol, mg/dl  51.7 ± 12.9  51.4 ± 14.1  0.80   LDL cholesterol, mg/dl  105.9 ± 39.9  90.6 ± 28.3  0.09   Triglyceride, mg/dl  138.7 ± 79.9  117.8 ± 49.3  0.39   HbA1c, %  6.3 ± 0.7  6.5 ± 0.9  0.48   pre PCI         CK-MB, IU/L  8.5 ± 3.4  9.4 ± 3.6  0.14   Troponin-I, ng/mL  0.01 (0.01–0.02)  0.01 (0.01–0.02)  0.11   post PCI         CK-MB, IU/L  8.6 ± 3.2  13.8 ± 7.5  <0.001   Troponin-I, ng/mL  0.14 (0.07–0.42)  0.84 (0.29–2.07)  <0.001    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Clinical characteristics   Age, years  67.0 ± 9.2  68.0 ± 10.9  0.57   Male, n (%)  42 (79.3%)  28 (90.3%)  0.19   Hypertension, n (%)  39 (73.6%)  22 (70.9%)  0.80   Dyslipidemia, n (%)  35 (66.0%)  20 (64.5%)  0.89   Diabetes mellitus, n (%)  20 (37.7%)  11 (35.5%)  0.84   Current smoker, n (%)  10 (18.9%)  8 (25.8%)  0.45   Body mass index, kg/m2  24.1 ± 2.8  24.9 ± 4.3  0.21   Medication, n (%)         β-blocker  29 (54.7%)  14 (45.2%)  0.40   Calcium channel blocker  33 (62.3%)  14 (45.2%)  0.13   ACE-I/ARB  32 (60.4%)  18 (58.1%)  0.83   Statin 7 days before PCI  48 (90.6%)  23 (74.2%)  <0.05  Laboratory data   eGFR, mL/min per 1.73 m2  70.77 ± 18.53  64.55 ± 16.15  0.13   HDL cholesterol, mg/dl  51.7 ± 12.9  51.4 ± 14.1  0.80   LDL cholesterol, mg/dl  105.9 ± 39.9  90.6 ± 28.3  0.09   Triglyceride, mg/dl  138.7 ± 79.9  117.8 ± 49.3  0.39   HbA1c, %  6.3 ± 0.7  6.5 ± 0.9  0.48   pre PCI         CK-MB, IU/L  8.5 ± 3.4  9.4 ± 3.6  0.14   Troponin-I, ng/mL  0.01 (0.01–0.02)  0.01 (0.01–0.02)  0.11   post PCI         CK-MB, IU/L  8.6 ± 3.2  13.8 ± 7.5  <0.001   Troponin-I, ng/mL  0.14 (0.07–0.42)  0.84 (0.29–2.07)  <0.001  ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; PCI, percutaneous coronary intervention; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HbA1c, haemoglobin A1c; CK-MB, Creatine kinase-MB. Lesion, angiographic and procedural characteristics of the study patients are shown in Table 2. Angiographic final TIMI flow grade 3 was achieved in all patients. There were no patients with ST-segment elevation on surface ECG after the procedure in the two groups. Five out of 84 lesions (6.0%) were predilated before pre-FD-OCT. Post-dilatation after stent deployment was performed in 66 patients (78.6%) and no significant differences in balloon diameter, dilatation pressure and inflation time were observed between the two groups. No patients had received unexpected additional stent implantation because of angiographic stent edge dissection. There was no significant difference in all lesion, angiographic and procedural variables between the two groups. Table 2 Lesion, angiographic and procedural characteristics   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Lesion location, n (%)   Left anterior descending coronary arter  30 (56.6%)  20 (64.5%)  0.48   Left circumflex coronary artery  9 (17.0%)  4 (12.9%)  0.62   Right coronary artery  14 (26.4%)  7 (22.6%)  0.70  Multivessel disease, n (%)  26 (49.1%)  15 (48.4%)  0.95  Collateral flow, n (%)  0 (0%)  0 (0%)  1.00  ACC/AHA classification B2/C, n (%)  24 (45.3%)  15 (48.4%)  0.78  Final TIMI flow grade 3, n (%)  53 (100%)  31 (100%)  1.00  ST-segment elevation on surface ECG, n (%)  0 (0%)  0 (0%)  1.00  QCA         Pre PCI         RD, mm  2.45 ± 0.53  2.53 ± 0.58  0.52   MLD, mm  0.64 ± 0.38  0.72 ± 0.30  0.19   %DS, %  73.6 ± 14.1  71.9 ± 12.5  0.52   Lesion length, mm  18.2 ± 8.1  20.4 ± 9.6  0.45   Post PCI         RD, mm  2.99 ± 0.46  3.09 ± 0.41  0.24   MLD, mm  2.74 ± 0.45  2.77 ± 0.38  0.69   %DS, %  8.61 ± 5.02  10.39 ± 4.88  0.08   Lesion length, mm  19.2 ± 9.9  21.0 ± 11.25  0.55  Stenting         Total stent length, mm  21.6 ± 11.0  22.0 ± 9.2  0.56   Stent diameter, mm  3.18 ± 0.35  3.10 ± 0.34  0.44   Direct stent, n (%)  15 (28.3%)  8 (25.8%)  0.80   Dilatation pressure, atm  11.6 ± 2.8  10.5 ± 2.5  0.16   Inflation time, s  60.6 ± 23.2  59.7 ± 18.5  0.93  Post-dilatation         Balloon post-dilatation, n (%)  42 (79.3%)  24 (77.4%)  0.84   Balloon diameter, mm  3.27 ± 0.40  3.19 ± 0.36  0.46   Dilatation pressure, atm  18.4 ± 4.5  18.3 ± 4.8  0.82   Inflation time, s  40.1 ± 16.2  38.1 ± 20.9  0.43    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Lesion location, n (%)   Left anterior descending coronary arter  30 (56.6%)  20 (64.5%)  0.48   Left circumflex coronary artery  9 (17.0%)  4 (12.9%)  0.62   Right coronary artery  14 (26.4%)  7 (22.6%)  0.70  Multivessel disease, n (%)  26 (49.1%)  15 (48.4%)  0.95  Collateral flow, n (%)  0 (0%)  0 (0%)  1.00  ACC/AHA classification B2/C, n (%)  24 (45.3%)  15 (48.4%)  0.78  Final TIMI flow grade 3, n (%)  53 (100%)  31 (100%)  1.00  ST-segment elevation on surface ECG, n (%)  0 (0%)  0 (0%)  1.00  QCA         Pre PCI         RD, mm  2.45 ± 0.53  2.53 ± 0.58  0.52   MLD, mm  0.64 ± 0.38  0.72 ± 0.30  0.19   %DS, %  73.6 ± 14.1  71.9 ± 12.5  0.52   Lesion length, mm  18.2 ± 8.1  20.4 ± 9.6  0.45   Post PCI         RD, mm  2.99 ± 0.46  3.09 ± 0.41  0.24   MLD, mm  2.74 ± 0.45  2.77 ± 0.38  0.69   %DS, %  8.61 ± 5.02  10.39 ± 4.88  0.08   Lesion length, mm  19.2 ± 9.9  21.0 ± 11.25  0.55  Stenting         Total stent length, mm  21.6 ± 11.0  22.0 ± 9.2  0.56   Stent diameter, mm  3.18 ± 0.35  3.10 ± 0.34  0.44   Direct stent, n (%)  15 (28.3%)  8 (25.8%)  0.80   Dilatation pressure, atm  11.6 ± 2.8  10.5 ± 2.5  0.16   Inflation time, s  60.6 ± 23.2  59.7 ± 18.5  0.93  Post-dilatation         Balloon post-dilatation, n (%)  42 (79.3%)  24 (77.4%)  0.84   Balloon diameter, mm  3.27 ± 0.40  3.19 ± 0.36  0.46   Dilatation pressure, atm  18.4 ± 4.5  18.3 ± 4.8  0.82   Inflation time, s  40.1 ± 16.2  38.1 ± 20.9  0.43  ACC/AHA classification B2/C, American Heart Association/American College of Cardiology classification type B2 or type C; TIMI, thrombolysis in myocardial infarction; ECG, electrocardiogram; QCA, quantitative coronary angiography; PCI, percutaneous coronary intervention; RD, reference diameter; MLD, minimum lumen diameter; %DS, percent diameter stenosis. Pre-and post-FD-OCT findings FD-OCT findings of the study patients are shown in Table 3. Thrombus was observed in 7 patients by pre-FD-OCT and these were all red thrombus. Plaque rupture was significantly more frequently found by pre-FD-OCT in the ST-E (+) group than in the ST-E (−) group (7.5% vs. 35.5%, P = 0.001). Calcification tended to be more frequently found by pre-FD-OCT in the ST-E (+) group than in the ST-E (−) group, but the differences were not statistically significant (32.1% vs. 51.6%, P = 0.08). Relation between minimum fibrous cap thickness and ST-segment elevation on IcECG is shown in Figure 4. Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Lipid-rich plaque and TCFA were significantly more frequently found by pre-FD-OCT in the ST-E (+) group than in the ST-E (−) group (lipid-rich plaque; 75.5% vs. 100%, P < 0.001, TCFA; 0% vs. 25.8%, P < 0.001, respectively). Maximum length of lipid pool was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.58 ± 2.08 mm vs. 7.51 ± 3.31 mm, P < 0.005). Protrusion and intra-stent dissection were significantly more frequently found by post-FD-OCT in the ST-E (+) group than in the ST-E (−) group (protrusion; 18.9% vs. 56.7%, P < 0.001, intra-stent dissection; 15.1% vs. 50.0%, P < 0.001, respectively). Table 3 Frequency-domain optical coherence tomography findings   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Pre PCI   Maximum lumen area, mm2  7.64 ± 2.07  6.99 ± 2.48  0.20   Minimum lumen area, mm2  2.00 ± 1.81  1.67 ± 0.76  0.68   Culprit length, mm  19.4 ± 9.0  21.1 ± 9.5  0.27   Presence of thrombus, n (%)  3 (5.7%)  4 (12.7%)  0.25   Presence of plaque rupture, n (%)  4 (7.5%)  11 (35.5%)  0.001   Presence of calcification, n (%)  17 (32.1%)  16 (51.6%)  0.08   Minimum fibrous cap thickness, μm  240 (180–310)  100 (60–120)  <0.001   Maximum lipid plaque, no. of quadrants         1/2/3/4  13/25/13/2  0/3/18/10  <0.001   Lipid-rich plaque, n (%)  40 (75.5%)  31 (100%)  <0.001   TCFA, n (%)  0 (0%)  8 (25.8%)  <0.001   Maximum length of lipid pool, mm  5.58 ± 2.08  7.51 ± 3.13  0.005  Post PCI   Maximum stent area, mm2  8.21 ± 2.79  7.52 ± 2.10  0.29   Minimum stent area, mm2  5.95 ± 1.83  5.61 ± 1.60  0.39   Stent length, mm  21.0 ± 9.8  22.1 ± 9.9  0.51   Presence of intra-stent thrombus, n (%)  2 (3.8%)  2 (6.7%)  0.55   Presence of incomplete stent apposition, n (%)  4 (7.6%)  3 (10.0%)  0.70   Presence of protrusion, n (%)  10 (18.9%)  17 (56.7%)  <0.001   Presence of stent edge dissection, n (%)  7 (13.2%)  3 (10.0%)  0.67   Presence of intra-stent dissection, n (%)  8 (15.1%)  15 (50.0%)  <0.001    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Pre PCI   Maximum lumen area, mm2  7.64 ± 2.07  6.99 ± 2.48  0.20   Minimum lumen area, mm2  2.00 ± 1.81  1.67 ± 0.76  0.68   Culprit length, mm  19.4 ± 9.0  21.1 ± 9.5  0.27   Presence of thrombus, n (%)  3 (5.7%)  4 (12.7%)  0.25   Presence of plaque rupture, n (%)  4 (7.5%)  11 (35.5%)  0.001   Presence of calcification, n (%)  17 (32.1%)  16 (51.6%)  0.08   Minimum fibrous cap thickness, μm  240 (180–310)  100 (60–120)  <0.001   Maximum lipid plaque, no. of quadrants         1/2/3/4  13/25/13/2  0/3/18/10  <0.001   Lipid-rich plaque, n (%)  40 (75.5%)  31 (100%)  <0.001   TCFA, n (%)  0 (0%)  8 (25.8%)  <0.001   Maximum length of lipid pool, mm  5.58 ± 2.08  7.51 ± 3.13  0.005  Post PCI   Maximum stent area, mm2  8.21 ± 2.79  7.52 ± 2.10  0.29   Minimum stent area, mm2  5.95 ± 1.83  5.61 ± 1.60  0.39   Stent length, mm  21.0 ± 9.8  22.1 ± 9.9  0.51   Presence of intra-stent thrombus, n (%)  2 (3.8%)  2 (6.7%)  0.55   Presence of incomplete stent apposition, n (%)  4 (7.6%)  3 (10.0%)  0.70   Presence of protrusion, n (%)  10 (18.9%)  17 (56.7%)  <0.001   Presence of stent edge dissection, n (%)  7 (13.2%)  3 (10.0%)  0.67   Presence of intra-stent dissection, n (%)  8 (15.1%)  15 (50.0%)  <0.001  PCI, percutaneous coronary intervention; TCFA, thin cap fibroatheroma. Figure 4 View largeDownload slide Relation between fibrous cap thickness and ST-segment elevation on intracoronary electrocardiogram. Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Figure 4 View largeDownload slide Relation between fibrous cap thickness and ST-segment elevation on intracoronary electrocardiogram. Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Prognosis of ST-segment elevation on IcECG The median follow-up period was 365 (IQR 207–365) days. The incidence of each constituent factor of MACE at 1-year is shown in Table 4. One patient in the ST-E (+) group required revascularization for in-stent restenosis. Four patients in the ST-E (−) group and 5 patients in the ST-E (+) group required revascularization for remote lesion. The incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05, Figure 5). Table 4 Cofactors of MACE in the ST-E (−) group and the ST-E (+) group   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  MACE, n (%)  3 (5.7%)  6 (19.4%)  <0.05  Cardiac death, n (%)  0 (0%)  0 (0%)  1.00  Myocardial infarction, n (%)  1 (1.9%)  1 (3.2%)  0.70  Repeat revascularization, n (%)  4 (7.6%)  6 (19.4%)  0.11  Hospitalization for heart failure, n (%)  0 (0%)  2 (6.5%)  0.04    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  MACE, n (%)  3 (5.7%)  6 (19.4%)  <0.05  Cardiac death, n (%)  0 (0%)  0 (0%)  1.00  Myocardial infarction, n (%)  1 (1.9%)  1 (3.2%)  0.70  Repeat revascularization, n (%)  4 (7.6%)  6 (19.4%)  0.11  Hospitalization for heart failure, n (%)  0 (0%)  2 (6.5%)  0.04  MACE, major adverse cardiac event. Figure 5 View largeDownload slide The 1-year cumulative incidence of MACE after PCI in patients with ST-E (−) or ST-E (+) on intracoronary electrocardiogram. The incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05). MACE, major adverse cardiac event; PCI, percutaneous coronary intervention. Figure 5 View largeDownload slide The 1-year cumulative incidence of MACE after PCI in patients with ST-E (−) or ST-E (+) on intracoronary electrocardiogram. The incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05). MACE, major adverse cardiac event; PCI, percutaneous coronary intervention. Intraobserver and interobserver variability Kappa measure of agreement for intraobserver agreement was 1.00 (P < 0.001) for IcECG, 0.83 (P < 0.001) for TCFA, 0.86 (P < 0.001) for lipid-rich plaque. Interobserver variability for IcECG, TCFA and lipid-rich plaque was 0.96 (P < 0.001), 0.80 (P < 0.001) and 0.83 (P < 0.001), respectively. Mean intraobserver difference for the minimum fibrous cap thickness was 9.4 ± 4.1 μm; mean interobserver differences were 10.1 ± 9.0 μm. Mean intraobserver difference for the maximum length of lipid pool was 0.5 ± 0.2 mm; mean interobserver differences were 0.6 ± 0.3 mm. Discussion The major finding of the present study was that minimum fibrous cap thickness on pre-FD-OCT was significantly thinner and maximum length of lipid pool on pre-FD-OCT was significantly higher in the ST-E (+) group than in the ST-E (−) group. In addition, presence of plaque rupture, lipid-rich plaque, TCFA on pre-FD-OCT, protrusion and intra-stent dissection on post-FD-OCT might predict persistent ST-segment elevation on IcECG in patients who underwent successful elective PCI. Furthermore, the incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group. To our knowledge, this is the first report to present a relation between plaque features assessed by FD-OCT and microvascular perfusion estimated by IcECG, and prognosis value on IcECG in patients who underwent successful elective PCI. PMI is caused by procedure-related cell necrosis that occurs during PCI. It is diagnosed when an increase of post-procedural cardiac biomarkers is observed, occurring in between 5% and 44% of PCI.3 PMI have been associated with several factors, which can broadly be categorized as (i) patient-related factors; (ii) lesion-related factors; and (iii) procedure-related factors.8 Lesion-related factors such as plaque burden, calcification, lesion eccentricity, and thrombus which lead to distal embolization of disrupted plaque contents and residual thrombus, predict PMI.9 The most common mechanisms of PMI are distal embolization and side branch occlusion. This study was especially focused on lesion-related factors which lead to distal embolization using FD-OCT. Despite the presence of patent epicardial coronary circulation, microvascular perfusion may fail to be acquired in a substantial portion of the perfusion territory of the treated coronary artery because distal atherothrombotic embolization could trigger abnormalities at the level of the microvasculature.10 Presence of plaque rupture, lipid-rich plaque and TCFA on pre-FD-OCT might predict persistent ST-segment elevation on IcECG in patients who underwent elective PCI, which was consistent with results of previous studies focused on an increase of post-procedural cardiac biomarkers.11,12 TCFA is characterized by a large necrotic core and a thin fibrous cap and associated with positive vessel remodeling.13 Also, TCFA often leads to plaque rupture.14 The necrotic core component contains fragile tissues such as lipid deposition with foam cells, intramural bleeding, and/or cholesterol crystals.15 The presence of plaque rupture, lipid-rich plaque and TCFA correlates with more progressive atherosclerosis and vulnerable plaques and results in distal embolization by disrupted plaque contents during PCI. In addition, in the cavity of plaque rupture, there might be residual lipid plaque and organized thrombus. Previous studies have suggested that large plaque volume and lipid-rich plaque at culprit lesions assessed by intravascular ultrasound may be associated with no-reflow phenomenon, resulting in PMI.16 In this study, maximum length of lipid pool was significantly higher in the ST-E (+) group than in the ST-E (−) group. It might be useful to evaluate longitudinal extent of lipid pool using FD-OCT to quantify the whole plaque burden accurately. Porto et al.12 reported that presence of intra-stent thrombus and intra-stent dissection on post-FD-OCT might predict Troponin-T elevation in patients treated with second generation drug-eluting stents . In this study, intra-stent dissection was significantly more frequently found by post-FD-OCT in the ST-E (+) group than in the ST-E (−) group. However, there was no significant difference in intra-stent thrombus between the two groups. We guess that this discordance was because intra-stent thrombus were observed in only 4 patients in this study and Porto et al included non-ST elevation myocardial infarction patients. Additionally, protrusion was significantly more frequently found by post-FD-OCT in the ST-E (+) group than in the ST-E (−) group in this study. This finding suggested that thinner fibrous cap and large necrotic cores might be more likely to be destroyed by stent implantation, eventually resulting in impaired microvascular perfusion and tissue protrusion through stent struts reflected this mechanical mechanism. Correspondingly, calcified plaque on pre-FD-OCT might be not easy to be destroyed by stent implantation and introduce distal embolization. Previous studies have reported that ST-segment resolution on IcECG was associated with infarct size assessed by cardiac magnetic resonance imaging (CMR) in MI patients.17 IcECG seemed to assess local myocardial state in the catheterization laboratory.4 Larger stent expansion associated with a higher level of post-procedural CK-MB suggests a tradeoff between optimal stent implantation and PMI.18 Because of monitoring ST-segment changes of IcECG in the catheterization laboratory, evaluation of IcECG might provide useful information on indicating and monitoring of these interventions to optimize stent expansion. To prevent distal embolization during PCI, several trials have been conducted with a variety of embolic distal protection devices. However, The Drug Elution and Distal Protection in ST Elevation Myocardial Infarction (DEDICATION) trial suggested that in primary PCI for ST-segment elevation myocardial infarction, the routine use of distal protection increased the incidence of stent thrombosis and clinically driven target lesion/vessel revascularization because of complexity of use.19 Therefore, it is necessary to determine patients who will suffer from impaired microvascular perfusion without distal protection devices based on these pre-FD-OCT findings. It was reported that pretreatment with statins decreases the incidence of PMI during PCI.20 In this study, the rate of patients taking statins at least 7 days before PCI was significantly higher in the ST-E (−) group than in the ST-E (+) group. It is necessary to administer statins to patients who are planned to undergo PCI earlier than 7 days. Furthermore, ST-segment elevation on IcECG after the procedure might be associated with 1-year MACE. The total of MI, repeat revascularization and hospitalization for heart failure affected 1-year MACE. We think that ST-segment elevation on post-IcECG might be a surrogate marker and patients with ST-segment elevation on post-IcECG might be ‘vulnerable patients which might be prone to cardiac event’. Some studies demonstrated that intravenous nicorandil administration reduced cardiac biomarker elevation after elective PCI.21 More constructive treatment should be needed to these high-risk patients with ST-segment elevation on IcECG after the procedure to reduce future cardiac events. Prospective studies will be advocated to investigate the propriety of FD-OCT-guided use of embolic protection devices and IcECG-guided administration of pharmacological agents to prevent and treat impaired microvascular perfusion during elective PCI. Study limitations Major limitation of this study is small sample size. Because of the invasive nature of this study, only 84 patients were included. In addition, this study was conducted in only a single institution in a non-randomized, retrospective manner. Although all patients achieved final TIMI 3 flow grade in this study, the exclusion of patients with large vessel diameter may have led to all patients achieving final TIMI3 flow grade. Use of other measures, including myocardial blush grade, flow velocity by Doppler wire, microvascular obstruction by CMR and contrast deficit by contrast echocardiography, might have provided additional information on microvascular perfusion. Inability to measure plaque volume is one of the major limitations of FD-OCT. No patient received glycoprotein IIb/IIIa receptor inhibitor because they are not available in Japan. Plaque characteristics and stent status may affect the development of in-stent restenosis. However, only one patient had in-stent restenosis because all patients were treated by second or third generation drug-eluting stent and we excluded patients with reduced renal function, tortuous vessels or severe calcified lesions who are likely to develop in-stent restenosis. So, we could not evaluate predictive value for in-stent restenosis. We did not perform an analysis of the long-term prognostic value of ST-segment elevation on IcECG. Conclusions Plaque features assessed by FD-OCT might be associated with impaired microvascular perfusion and ST-segment elevation on IcECG after the procedure could predict 1-year cardiac events after elective PCI. Further studies should be advocated to investigate the more clinical prognostic value of relation between plaque features at culprit lesions assessed by FD-OCT and IcECG for patients who underwent elective PCI and better therapeutic options to reduce cardiovascular event. Acknowledgements We thank Mr Shingo Kono for his technical support of FD-OCT and Mr Tsukasa Nakao for their technical support of the IcECG recording. Conflict of interest: None declared. References 1 Testa L, Van Gaal WJ, Biondi Zoccai GG, Agostoni P, Latini RA, Bedogni F et al.   Myocardial infarction after percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition. QJM  2009; 102: 369– 78. Google Scholar CrossRef Search ADS PubMed  2 van't Hof AW, Liem A, de Boer MJ, Zijlstra F. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Zwolle Myocardial infarction Study Group. Lancet  1997; 350: 615– 9. Google Scholar CrossRef Search ADS PubMed  3 Balian V, Galli M, Marcassa C, Cecchin G, Child M, Barlocco F et al.   Intracoronary ST-segment shift soon after elective percutaneous coronary intervention accurately predicts periprocedural myocardial injury. Circulation  2006; 114: 1948– 54. Google Scholar CrossRef Search ADS PubMed  4 Uetani T, Amano T, Kumagai S, Ando H, Yokoi K, Yoshida T et al.   Intracoronary electrocardiogram recording with a bare-wire system: perioperative ST-segment elevation in the intracoronary electrocardiogram is associated with myocardial injury after elective coronary stent implantation. JACC Cardiovasc Interv  2009; 2: 127– 35. Google Scholar CrossRef Search ADS PubMed  5 Bezerra HG, Costa MA, Guagliumi G, Rollins AM, Simon DI. Intracoronary optical coherence tomography: a comprehensive review clinical and research applications. JACC Cardiovasc Interv  2009; 2: 1035– 46. Google Scholar CrossRef Search ADS PubMed  6 Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N et al.   In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation  2005; 111: 1551– 5. Google Scholar CrossRef Search ADS PubMed  7 Guagliumi G, Ikejima H, Sirbu V, Bezerra H, Musumeci G, Lortkipanidze N et al.   Impact of drug release kinetics on vascular response to different zotarolimus-eluting stents implanted in patients with long coronary stenoses: the LongOCT study (Optical Coherence Tomography in Long Lesions). JACC Cardiovasc Interv  2011; 4: 778– 85. Google Scholar CrossRef Search ADS PubMed  8 Lansky AJ, Stone GW. Periprocedural myocardial infarction: prevalence, prognosis, and prevention. Circ Cardiovasc Interv  2010; 3: 602– 10. Google Scholar CrossRef Search ADS PubMed  9 Nallamothu BK, Chetcuti S, Mukherjee D, Grossman PM, Kline-Rogers E, Werns SW et al.   Prognostic implication of troponin I elevation after percutaneous coronary intervention. Am J Cardiol  2003; 91: 1272– 4. Google Scholar CrossRef Search ADS PubMed  10 Jaffe R, Dick A, Strauss BH. Prevention and treatment of microvascular obstruction-related myocardial injury and coronary no-reflow following percutaneous coronary intervention: a systematic approach. JACC Cardiovasc Interv  2010; 3: 695– 704. Google Scholar CrossRef Search ADS   11 Lee T, Yonetsu T, Koura K, Hishikari K, Murai T, Iwai T et al.   Impact of coronary plaque morphology assessed by optical coherence tomography on cardiac troponin elevation in patients with elective stent implantation. Circ Cardiovasc Interv  2011; 4: 378– 86. Google Scholar CrossRef Search ADS PubMed  12 Porto I, Di Vito L, Burzotta F, Niccoli G, Trani C, Leone AM et al.   Predictors of periprocedural (type IVa) myocardial infarction, as assessed by frequency-domain optical coherence tomography. Circ Cardiovasc Interv  2012; 5: 89– 96, S1-6. Google Scholar CrossRef Search ADS PubMed  13 Raffel OC, Merchant FM, Tearney GJ, Chia S, Gauthier DD, Pomerantsev E et al.   In vivo association between positive coronary artery remodelling and coronary plaque characteristics assessed by intravascular optical coherence tomography. Eur Heart J  2008; 29: 1721– 8. Google Scholar CrossRef Search ADS PubMed  14 Lee T, Kakuta T, Yonetsu T, Takahashi K, Yamamoto G, Iesaka Y et al.   Assessment of echo-attenuated plaque by optical coherence tomography and its impact on post-procedural creatine kinase-myocardial band elevation in elective stent implantation. JACC Cardiovasc Interv  2011; 4: 483– 91. Google Scholar CrossRef Search ADS PubMed  15 Babu GG, Walker JM, Yellon DM, Hausenloy DJ. Peri-procedural myocardial injury during percutaneous coronary intervention: an important target for cardioprotection. Eur Heart J  2011; 32: 23– 31. Google Scholar CrossRef Search ADS PubMed  16 Uetani T, Amano T, Ando H, Yokoi K, Arai K, Kato M et al.   The correlation between lipid volume in the target lesion, measured by integrated backscatter intravascular ultrasound, and post-procedural myocardial infarction in patients with elective stent implantation. Eur Heart J  2008; 29: 1714– 20. Google Scholar CrossRef Search ADS PubMed  17 Wong DT, Leung MC, Das R, Puri R, Liew GY, Teo KS et al.   Intracoronary ECG ST-segment recovery during primary percutaneous intervention for ST-segment myocardial infarction: insights from a cardiac MRI study. Catheter Cardiovasc Interv  2012; 80: 746– 53. Google Scholar CrossRef Search ADS PubMed  18 Iakovou I, Mintz GS, Dangas G, Abizaid A, Mehran R, Kobayashi Y et al.   Increased CK-MB release is a "trade-off" for optimal stent implantation: an intravascular ultrasound study. J Am Coll Cardiol  2003; 42: 1900– 5. Google Scholar CrossRef Search ADS   19 Kaltoft A, Kelbaek H, Klovgaard L, Terkelsen CJ, Clemmensen P, Helqvist S et al.   Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial. J Am Coll Cardiol  2010; 55: 867– 71. Google Scholar CrossRef Search ADS PubMed  20 Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G et al.   Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study. Circulation  2004; 110: 674– 8. Google Scholar CrossRef Search ADS PubMed  21 Murakami M, Iwasaki K, Kusachi S, Hina K, Hirota M, Hirohata S et al.   Nicorandil reduces the incidence of minor cardiac marker elevation after coronary stenting. Int J Cardiol  2006; 107: 48– 53. Google Scholar CrossRef Search ADS PubMed  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal – Cardiovascular Imaging Oxford University Press

Predictive value of plaque morphology assessed by frequency-domain optical coherence tomography for impaired microvascular perfusion after elective stent implantation: the intracoronary electrocardiogram study

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Abstract

Abstract Aims This study was undertaken to assess the association between plaque features at culprit lesions assessed by frequency-domain optical coherence tomography (FD-OCT) and impaired microvascular perfusion estimated by intracoronary electrocardiogram (IcECG) after elective percutaneous coronary intervention (PCI). Furthermore, we investigated whether IcECG could predict future cardiac events. Methods and results This study consisted of 84 patients who underwent both FD-OCT and IcECG during PCI. Patients were classified into two groups based on ST-segment elevation (ST-E) on IcECG after the procedure; ST-E (−) group (n = 53) and ST-E (+) group (n = 31). Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Plaque rupture (7.5% vs. 35.5%, P = 0.001), lipid-rich plaque (75.5% vs. 100%, P < 0.001), the thin cap fibroatheroma (0% vs. 25.8%, P < 0.001) on pre-FD-OCT, protrusion (18.9% vs. 56.7%, P < 0.001), and intra-stent dissection (15.1% vs. 50.0%, P < 0.001) on post-FD-OCT were significantly more frequently found in the ST-E (+) group than in the ST-E (−) group. The incidence of MACE (cardiac death, myocardial infarction, revascularization, hospitalization for heart failure) during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05). Conclusion Plaque features assessed by FD-OCT might be associated with impaired microvascular perfusion and ST-segment elevation on IcECG after the procedure could predict 1-year cardiac events after elective PCI. impaired microvascular perfusion, intracoronary electrocardiogram, frequency domain optical coherence tomography, periprocedural myocardial injury Introduction Percutaneous coronary intervention (PCI) is a well-established therapeutic strategy for patients with stable angina pectoris. However, periprocedural myocardial injury (PMI) after PCI is not uncommon and even a small biomarker increase is significantly associated with an adverse short- and long-term outcome.1 Especially, distal embolization during PCI may deteriorate microvascular perfusion in patients who underwent elective PCI. Numerous efforts have been made to detect high-risk plaque which may cause distal embolization during PCI, using several imaging devices. Of these, frequency-domain optical coherence tomography (FD-OCT) has been recently developed as a high-resolution imaging method to observe culprit lesions more clearly. On the other hand, surface ST-segment change on the electrocardiogram (ECG) reflects myocardial flow and microvascular perfusion after PCI rather than epicardial flow and predicts better myocardial salvage and clinical outcome in acute myocardial infarction patients.2 However, the sensitivity of surface ECG for detecting ischaemia during elective PCI has been disappointing.3 Unipolar intracoronary electrocardiogram (IcECG) which represents local epicardial ECG seemed to be more sensitive than surface ECG for detecting local ischaemia and microvascular perfusion during PCI and persistent ST-segment elevation on IcECG reflects impaired microvascular perfusion after PCI.4 IcECG is a simple, speedy and established method for predicting microvascular perfusion in the catheterization laboratory.4 This study was undertaken to assess the association between plaque features at culprit lesions assessed by FD-OCT on pre- and post-PCI and microvascular perfusion estimated by IcECG. Furthermore, we investigated whether IcECG could predict future cardiac events after elective PCI. Methods Study patient In total, 460 consecutive patients underwent PCI from January 2014 to March 2016 at Hiroshima University Hospital. Of these, we enrolled 84 patients with stable angina pectoris who underwent elective PCI for a single, native, de novo coronary lesion and performed FD-OCT and IcECG both at baseline and after the procedure in this study. A study flow chart is reported in Figure 1. All patients had the presence of anginal chest pain and myocardial ischaemia on myocardial perfusion scintigram or the treadmill exercise test or fractional flow reserve. Patient-related exclusion criteria were: (i) acute coronary syndrome; (ii) elevated pre-procedural cardiac biomarker; (iii) reduced renal function (Estimated glomerular filtration rate <30 mL/min per 1.73 m2). Lesion-related exclusion criteria were the vessels within a myocardial territory of previous myocardial infarction (MI), the left main trunk, ostium lesions, extremely tight lesions or tortuous vessels where we expected difficulty in advancing soft-tip guidewire or the FD-OCT catheter, severe calcified lesions needed for debulking device, target vessel reference diameter of ≥4 mm expected limitation in FD-OCT evaluation and angiographic evidence of coronary dissection or major side branch (>1 mm) occlusion after the procedure. Patients were classified into two groups based on ST-segment elevation (ST-E) on IcECG after the procedure; absence of ST-E [ST-E (−) group: n = 53] and presence of ST-E [ST-E (+) group: n = 31]. Prescription of statins was defined as taking statins at least 7 days before PCI. Multivessel disease was defined as ≥50% stenosis in 1 or more vessels remote from the target artery. Informed consent was obtained from each patient. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the ethical committee of Hiroshima University Graduate School of Biomedical and Health Sciences. Figure 1 View largeDownload slide Study flow chart. PCI, percutaneous coronary intervention; FD-OCT, frequency-domain optical coherence tomography; IcECG, intracoronary electrocardiogram; ST-E, ST-segment elevation. Figure 1 View largeDownload slide Study flow chart. PCI, percutaneous coronary intervention; FD-OCT, frequency-domain optical coherence tomography; IcECG, intracoronary electrocardiogram; ST-E, ST-segment elevation. Study protocol The study protocol was as follows (Figure 2). First, the baseline IcECG (pre-IcECG) was recorded after positioning the guidewire in the distal part of a target vessel. Second, the baseline FD-OCT (pre-FD-OCT) was performed with or without balloon pre-dilatation (1.5 mm noncompliant balloon, 6 atm). Then coronary stent implantation was performed. The post-procedural FD-OCT (post-FD-OCT) was performed with or without balloon post-dilatation. Finally, the post-procedural IcECG (post-IcECG) was recorded after positioning the guidewire in the same part. Blood samples were obtained pre-PCI and at approximately 18 h after PCI to evaluate cardiac biomarkers. A major adverse cardiac event (MACE) was defined as cardiac death, MI, repeat revascularization and/or hospitalization for heart failure. Follow-up angiography was encouraged at 8–10 months after elective PCI or earlier when clinically indicated. Repeat revascularization was identified as any unstaged revascularization after the index procedure. Clinical follow-up was performed for up to 1-year after PCI. Figure 2 View largeDownload slide Study protocol. All patients received dual antiplatelet agents (aspirin 100 mg/day and clopidogrel 75 mg/day, 300 mg loading dose) and statins at least 24 h before the procedure. An intracoronary injection of isosorbide dinitrate 2 mg was performed pre and post PCI. Abbreviations as in Figure 1. Figure 2 View largeDownload slide Study protocol. All patients received dual antiplatelet agents (aspirin 100 mg/day and clopidogrel 75 mg/day, 300 mg loading dose) and statins at least 24 h before the procedure. An intracoronary injection of isosorbide dinitrate 2 mg was performed pre and post PCI. Abbreviations as in Figure 1. PCI and FD-OCT procedures All patients were treated by second or third generation drug-eluting stent without any distal protection device according to standard techniques. All patients received dual antiplatelet agents (aspirin 100 mg/day and clopidogrel 75 mg/day, 300 mg loading dose) and statins at least 24 h before the procedure. 7500 IU of unfractionated heparin was administrated before procedure and an additional bolus of heparin was given during PCI, with a target activated clotting time of >250 s every 30 min. No patient received glycoprotein IIb/IIIa receptor inhibitor. In addition, no patient received other intravenous and intracoronary administration except isosorbide dinitrate. All stents were inflated 3 times to the almost nominal inflation pressure using the stent delivery balloon. The first inflation continued until the stent was angiographically fully expanded; the other 2 lasted 15 to 20 s, respectively. FD-OCT system was a commercially available system (C7 System; LightLab Imaging Inc/St Jude Medical, Westford, MA). The FD-OCT catheter (C7 Dragonfly; LightLab Imaging Inc/St Jude Medical, Westford, MA) was advanced to the distal end of the culprit lesion and contrast media was continuously infused into the coronary artery directly from the guiding catheter. Successful PCI was defined as the achievement of <25% residual stenosis, no angiographic stent edge dissection and final thrombolysis in myocardial infarction (TIMI) flow grade 3. After achieving the angiographic end point, no additional PCI was performed. FD-OCT image analysis Analysis of the FD-OCT images was performed every 0.2 mm interval by 2 reviewers blinded to the results of the IcECG analysis and clinical data. FD-OCT images were analyzed using validated criteria for thrombus characterization, plaque characterization, ruptured plaque, fibrous cap thickness, incomplete stent apposition, tissue protrusion, edge dissection and intra-stent dissection as reported previously.5–7 Lipid was semiquantified as the number of involved quadrants on the cross-sectional FD-OCT image. Lipid-rich plaque was defined as plaque with ≥2 quadrants. Fibrous cap thickness was defined as the minimum distance from the coronary artery lumen to inner border of lipid pool on the cross-sectional FD-OCT image. The length of lipid pool was measured as consecutive longitudinal length of lipid pool at culprit plaque assessed by FD-OCT. The thin cap fibroatheroma (TCFA) was defined as a plaque with lipid content in ≥2 quadrants and the thinnest part of the fibrous cap measuring <65 μm. Culprit plaque was defined as the plaque at the site of minimum lumen diameter. IcECG recording and analysis IcECG was recorded both at baseline and after the procedure as reported previously.3,4 In brief, a 0.014-inch guidewire (Hi-Torque Balance Middle Weight-Universal, Abbott Vasclar; Santa Clara, California) was passed distal to the culprit lesion and positioned at the distal epicardial position of a target vessel. Pre-IcECG was recorded just after the guidewire passed. At the end of PCI, the guidewire was placed in the same position as pre-IcECG after all procedure and post-IcECG was recorded. ST-segment elevation on IcECG was measured 20 ms after the end of the QRS or QS complexes to the nearest 0.5 mm. Three consecutive QRS complexes were analyzed and mean ST-segment elevation values were calculated. ST-E (+) on IcECG was defined as ST-segment elevation ≥1 mm from baseline.3 Representative case of ST-E (+) on IcECG is shown in Figure 3. Figure 3 View largeDownload slide Representative case of ST-segment elevation on intracoronary electrocardiogram. A, IcECG at baseline (pre-IcECG) B, IcECG after the procedure (post-IcECG). Post-IcECG shows ST-segment elevation compared with pre-IcECG. IcECG, intracoronary electrocardiogram. Figure 3 View largeDownload slide Representative case of ST-segment elevation on intracoronary electrocardiogram. A, IcECG at baseline (pre-IcECG) B, IcECG after the procedure (post-IcECG). Post-IcECG shows ST-segment elevation compared with pre-IcECG. IcECG, intracoronary electrocardiogram. Laboratory measurements Blood samples were collected just before PCI and 18 h after the procedure in the postabsorptive state. Serum troponin-I (TnI) was measured with a commercially available enzyme immunoassay kit (Siemens Healthcare Diagnostics K.K., Tokyo, Japan). The Creatine kinase-MB (CK-MB) activity was measured with the Cica Liquid CK test (Kanto Chemical, Tokyo, Japan). Statistical analysis Standard statistical methods were used in this study. Significant differences were tested using the χ2 test for categorical variables. Normally distributed continuous variables are presented as mean and standard deviation (SD) or median and inter-quartile range (IQR). Unpaired Student’s t-test or Wilcoxon rank-sum test when appropriate was used for continuous variables. Interobserver and intraobserver variabilities of FD-OCT findings and IcECG findings were assessed by the kappa statistic of concordance. Event-free survival curves up to 1-year after PCI were constructed with the Kaplan–Meier method and were compared with the log-rank test. The JMP statistical package (version 11.0, SAS Institute, Inc. Cary, NC, USA) was used for all statistical tests. A significance level of 0.05 was used and two-tailed tests were applied. Results Clinical, angiographic and procedural results No PCI related complications occurred and the procedures were successfully completed in all patients. Thirty-one out of 84 patients (36.9%) represented ST-segment elevation on post-IcECG. The baseline characteristics of the study patients are shown in Table 1. There was no significant difference in all baseline clinical variables except statins at least 7 days before PCI between the two groups. The rate of patients taking statins at least 7 days before PCI was significantly higher in the ST-E (−) group than in the ST-E (+) group (90.6% vs. 74.2%, P < 0.05). Regarding cardiac biomarkers, no significant difference was observed in CK-MB and TnI level before PCI between the two groups. However, CK-MB and TnI after PCI were significantly higher in the ST-E (+) group than in the ST-E (−) group (CK-MB; 8.6 ± 3.2 IU/L vs. 13.8 ± 7.5 IU/L, P < 0.001, TnI; 0.14 ng/mL [IQR 0.07 to 0.42] vs. 0.84 ng/mL [IQR 0.29 to 2.07], P < 0.001). In addition, there was no significant difference in other blood chemical parameters between the two groups. Table 1 Baseline characteristics   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Clinical characteristics   Age, years  67.0 ± 9.2  68.0 ± 10.9  0.57   Male, n (%)  42 (79.3%)  28 (90.3%)  0.19   Hypertension, n (%)  39 (73.6%)  22 (70.9%)  0.80   Dyslipidemia, n (%)  35 (66.0%)  20 (64.5%)  0.89   Diabetes mellitus, n (%)  20 (37.7%)  11 (35.5%)  0.84   Current smoker, n (%)  10 (18.9%)  8 (25.8%)  0.45   Body mass index, kg/m2  24.1 ± 2.8  24.9 ± 4.3  0.21   Medication, n (%)         β-blocker  29 (54.7%)  14 (45.2%)  0.40   Calcium channel blocker  33 (62.3%)  14 (45.2%)  0.13   ACE-I/ARB  32 (60.4%)  18 (58.1%)  0.83   Statin 7 days before PCI  48 (90.6%)  23 (74.2%)  <0.05  Laboratory data   eGFR, mL/min per 1.73 m2  70.77 ± 18.53  64.55 ± 16.15  0.13   HDL cholesterol, mg/dl  51.7 ± 12.9  51.4 ± 14.1  0.80   LDL cholesterol, mg/dl  105.9 ± 39.9  90.6 ± 28.3  0.09   Triglyceride, mg/dl  138.7 ± 79.9  117.8 ± 49.3  0.39   HbA1c, %  6.3 ± 0.7  6.5 ± 0.9  0.48   pre PCI         CK-MB, IU/L  8.5 ± 3.4  9.4 ± 3.6  0.14   Troponin-I, ng/mL  0.01 (0.01–0.02)  0.01 (0.01–0.02)  0.11   post PCI         CK-MB, IU/L  8.6 ± 3.2  13.8 ± 7.5  <0.001   Troponin-I, ng/mL  0.14 (0.07–0.42)  0.84 (0.29–2.07)  <0.001    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Clinical characteristics   Age, years  67.0 ± 9.2  68.0 ± 10.9  0.57   Male, n (%)  42 (79.3%)  28 (90.3%)  0.19   Hypertension, n (%)  39 (73.6%)  22 (70.9%)  0.80   Dyslipidemia, n (%)  35 (66.0%)  20 (64.5%)  0.89   Diabetes mellitus, n (%)  20 (37.7%)  11 (35.5%)  0.84   Current smoker, n (%)  10 (18.9%)  8 (25.8%)  0.45   Body mass index, kg/m2  24.1 ± 2.8  24.9 ± 4.3  0.21   Medication, n (%)         β-blocker  29 (54.7%)  14 (45.2%)  0.40   Calcium channel blocker  33 (62.3%)  14 (45.2%)  0.13   ACE-I/ARB  32 (60.4%)  18 (58.1%)  0.83   Statin 7 days before PCI  48 (90.6%)  23 (74.2%)  <0.05  Laboratory data   eGFR, mL/min per 1.73 m2  70.77 ± 18.53  64.55 ± 16.15  0.13   HDL cholesterol, mg/dl  51.7 ± 12.9  51.4 ± 14.1  0.80   LDL cholesterol, mg/dl  105.9 ± 39.9  90.6 ± 28.3  0.09   Triglyceride, mg/dl  138.7 ± 79.9  117.8 ± 49.3  0.39   HbA1c, %  6.3 ± 0.7  6.5 ± 0.9  0.48   pre PCI         CK-MB, IU/L  8.5 ± 3.4  9.4 ± 3.6  0.14   Troponin-I, ng/mL  0.01 (0.01–0.02)  0.01 (0.01–0.02)  0.11   post PCI         CK-MB, IU/L  8.6 ± 3.2  13.8 ± 7.5  <0.001   Troponin-I, ng/mL  0.14 (0.07–0.42)  0.84 (0.29–2.07)  <0.001  ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; PCI, percutaneous coronary intervention; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HbA1c, haemoglobin A1c; CK-MB, Creatine kinase-MB. Lesion, angiographic and procedural characteristics of the study patients are shown in Table 2. Angiographic final TIMI flow grade 3 was achieved in all patients. There were no patients with ST-segment elevation on surface ECG after the procedure in the two groups. Five out of 84 lesions (6.0%) were predilated before pre-FD-OCT. Post-dilatation after stent deployment was performed in 66 patients (78.6%) and no significant differences in balloon diameter, dilatation pressure and inflation time were observed between the two groups. No patients had received unexpected additional stent implantation because of angiographic stent edge dissection. There was no significant difference in all lesion, angiographic and procedural variables between the two groups. Table 2 Lesion, angiographic and procedural characteristics   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Lesion location, n (%)   Left anterior descending coronary arter  30 (56.6%)  20 (64.5%)  0.48   Left circumflex coronary artery  9 (17.0%)  4 (12.9%)  0.62   Right coronary artery  14 (26.4%)  7 (22.6%)  0.70  Multivessel disease, n (%)  26 (49.1%)  15 (48.4%)  0.95  Collateral flow, n (%)  0 (0%)  0 (0%)  1.00  ACC/AHA classification B2/C, n (%)  24 (45.3%)  15 (48.4%)  0.78  Final TIMI flow grade 3, n (%)  53 (100%)  31 (100%)  1.00  ST-segment elevation on surface ECG, n (%)  0 (0%)  0 (0%)  1.00  QCA         Pre PCI         RD, mm  2.45 ± 0.53  2.53 ± 0.58  0.52   MLD, mm  0.64 ± 0.38  0.72 ± 0.30  0.19   %DS, %  73.6 ± 14.1  71.9 ± 12.5  0.52   Lesion length, mm  18.2 ± 8.1  20.4 ± 9.6  0.45   Post PCI         RD, mm  2.99 ± 0.46  3.09 ± 0.41  0.24   MLD, mm  2.74 ± 0.45  2.77 ± 0.38  0.69   %DS, %  8.61 ± 5.02  10.39 ± 4.88  0.08   Lesion length, mm  19.2 ± 9.9  21.0 ± 11.25  0.55  Stenting         Total stent length, mm  21.6 ± 11.0  22.0 ± 9.2  0.56   Stent diameter, mm  3.18 ± 0.35  3.10 ± 0.34  0.44   Direct stent, n (%)  15 (28.3%)  8 (25.8%)  0.80   Dilatation pressure, atm  11.6 ± 2.8  10.5 ± 2.5  0.16   Inflation time, s  60.6 ± 23.2  59.7 ± 18.5  0.93  Post-dilatation         Balloon post-dilatation, n (%)  42 (79.3%)  24 (77.4%)  0.84   Balloon diameter, mm  3.27 ± 0.40  3.19 ± 0.36  0.46   Dilatation pressure, atm  18.4 ± 4.5  18.3 ± 4.8  0.82   Inflation time, s  40.1 ± 16.2  38.1 ± 20.9  0.43    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Lesion location, n (%)   Left anterior descending coronary arter  30 (56.6%)  20 (64.5%)  0.48   Left circumflex coronary artery  9 (17.0%)  4 (12.9%)  0.62   Right coronary artery  14 (26.4%)  7 (22.6%)  0.70  Multivessel disease, n (%)  26 (49.1%)  15 (48.4%)  0.95  Collateral flow, n (%)  0 (0%)  0 (0%)  1.00  ACC/AHA classification B2/C, n (%)  24 (45.3%)  15 (48.4%)  0.78  Final TIMI flow grade 3, n (%)  53 (100%)  31 (100%)  1.00  ST-segment elevation on surface ECG, n (%)  0 (0%)  0 (0%)  1.00  QCA         Pre PCI         RD, mm  2.45 ± 0.53  2.53 ± 0.58  0.52   MLD, mm  0.64 ± 0.38  0.72 ± 0.30  0.19   %DS, %  73.6 ± 14.1  71.9 ± 12.5  0.52   Lesion length, mm  18.2 ± 8.1  20.4 ± 9.6  0.45   Post PCI         RD, mm  2.99 ± 0.46  3.09 ± 0.41  0.24   MLD, mm  2.74 ± 0.45  2.77 ± 0.38  0.69   %DS, %  8.61 ± 5.02  10.39 ± 4.88  0.08   Lesion length, mm  19.2 ± 9.9  21.0 ± 11.25  0.55  Stenting         Total stent length, mm  21.6 ± 11.0  22.0 ± 9.2  0.56   Stent diameter, mm  3.18 ± 0.35  3.10 ± 0.34  0.44   Direct stent, n (%)  15 (28.3%)  8 (25.8%)  0.80   Dilatation pressure, atm  11.6 ± 2.8  10.5 ± 2.5  0.16   Inflation time, s  60.6 ± 23.2  59.7 ± 18.5  0.93  Post-dilatation         Balloon post-dilatation, n (%)  42 (79.3%)  24 (77.4%)  0.84   Balloon diameter, mm  3.27 ± 0.40  3.19 ± 0.36  0.46   Dilatation pressure, atm  18.4 ± 4.5  18.3 ± 4.8  0.82   Inflation time, s  40.1 ± 16.2  38.1 ± 20.9  0.43  ACC/AHA classification B2/C, American Heart Association/American College of Cardiology classification type B2 or type C; TIMI, thrombolysis in myocardial infarction; ECG, electrocardiogram; QCA, quantitative coronary angiography; PCI, percutaneous coronary intervention; RD, reference diameter; MLD, minimum lumen diameter; %DS, percent diameter stenosis. Pre-and post-FD-OCT findings FD-OCT findings of the study patients are shown in Table 3. Thrombus was observed in 7 patients by pre-FD-OCT and these were all red thrombus. Plaque rupture was significantly more frequently found by pre-FD-OCT in the ST-E (+) group than in the ST-E (−) group (7.5% vs. 35.5%, P = 0.001). Calcification tended to be more frequently found by pre-FD-OCT in the ST-E (+) group than in the ST-E (−) group, but the differences were not statistically significant (32.1% vs. 51.6%, P = 0.08). Relation between minimum fibrous cap thickness and ST-segment elevation on IcECG is shown in Figure 4. Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Lipid-rich plaque and TCFA were significantly more frequently found by pre-FD-OCT in the ST-E (+) group than in the ST-E (−) group (lipid-rich plaque; 75.5% vs. 100%, P < 0.001, TCFA; 0% vs. 25.8%, P < 0.001, respectively). Maximum length of lipid pool was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.58 ± 2.08 mm vs. 7.51 ± 3.31 mm, P < 0.005). Protrusion and intra-stent dissection were significantly more frequently found by post-FD-OCT in the ST-E (+) group than in the ST-E (−) group (protrusion; 18.9% vs. 56.7%, P < 0.001, intra-stent dissection; 15.1% vs. 50.0%, P < 0.001, respectively). Table 3 Frequency-domain optical coherence tomography findings   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Pre PCI   Maximum lumen area, mm2  7.64 ± 2.07  6.99 ± 2.48  0.20   Minimum lumen area, mm2  2.00 ± 1.81  1.67 ± 0.76  0.68   Culprit length, mm  19.4 ± 9.0  21.1 ± 9.5  0.27   Presence of thrombus, n (%)  3 (5.7%)  4 (12.7%)  0.25   Presence of plaque rupture, n (%)  4 (7.5%)  11 (35.5%)  0.001   Presence of calcification, n (%)  17 (32.1%)  16 (51.6%)  0.08   Minimum fibrous cap thickness, μm  240 (180–310)  100 (60–120)  <0.001   Maximum lipid plaque, no. of quadrants         1/2/3/4  13/25/13/2  0/3/18/10  <0.001   Lipid-rich plaque, n (%)  40 (75.5%)  31 (100%)  <0.001   TCFA, n (%)  0 (0%)  8 (25.8%)  <0.001   Maximum length of lipid pool, mm  5.58 ± 2.08  7.51 ± 3.13  0.005  Post PCI   Maximum stent area, mm2  8.21 ± 2.79  7.52 ± 2.10  0.29   Minimum stent area, mm2  5.95 ± 1.83  5.61 ± 1.60  0.39   Stent length, mm  21.0 ± 9.8  22.1 ± 9.9  0.51   Presence of intra-stent thrombus, n (%)  2 (3.8%)  2 (6.7%)  0.55   Presence of incomplete stent apposition, n (%)  4 (7.6%)  3 (10.0%)  0.70   Presence of protrusion, n (%)  10 (18.9%)  17 (56.7%)  <0.001   Presence of stent edge dissection, n (%)  7 (13.2%)  3 (10.0%)  0.67   Presence of intra-stent dissection, n (%)  8 (15.1%)  15 (50.0%)  <0.001    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  Pre PCI   Maximum lumen area, mm2  7.64 ± 2.07  6.99 ± 2.48  0.20   Minimum lumen area, mm2  2.00 ± 1.81  1.67 ± 0.76  0.68   Culprit length, mm  19.4 ± 9.0  21.1 ± 9.5  0.27   Presence of thrombus, n (%)  3 (5.7%)  4 (12.7%)  0.25   Presence of plaque rupture, n (%)  4 (7.5%)  11 (35.5%)  0.001   Presence of calcification, n (%)  17 (32.1%)  16 (51.6%)  0.08   Minimum fibrous cap thickness, μm  240 (180–310)  100 (60–120)  <0.001   Maximum lipid plaque, no. of quadrants         1/2/3/4  13/25/13/2  0/3/18/10  <0.001   Lipid-rich plaque, n (%)  40 (75.5%)  31 (100%)  <0.001   TCFA, n (%)  0 (0%)  8 (25.8%)  <0.001   Maximum length of lipid pool, mm  5.58 ± 2.08  7.51 ± 3.13  0.005  Post PCI   Maximum stent area, mm2  8.21 ± 2.79  7.52 ± 2.10  0.29   Minimum stent area, mm2  5.95 ± 1.83  5.61 ± 1.60  0.39   Stent length, mm  21.0 ± 9.8  22.1 ± 9.9  0.51   Presence of intra-stent thrombus, n (%)  2 (3.8%)  2 (6.7%)  0.55   Presence of incomplete stent apposition, n (%)  4 (7.6%)  3 (10.0%)  0.70   Presence of protrusion, n (%)  10 (18.9%)  17 (56.7%)  <0.001   Presence of stent edge dissection, n (%)  7 (13.2%)  3 (10.0%)  0.67   Presence of intra-stent dissection, n (%)  8 (15.1%)  15 (50.0%)  <0.001  PCI, percutaneous coronary intervention; TCFA, thin cap fibroatheroma. Figure 4 View largeDownload slide Relation between fibrous cap thickness and ST-segment elevation on intracoronary electrocardiogram. Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Figure 4 View largeDownload slide Relation between fibrous cap thickness and ST-segment elevation on intracoronary electrocardiogram. Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (−) group (240 μm [IQR 180 to 310] vs. 100 μm [IQR 60 to 120], P < 0.001). Prognosis of ST-segment elevation on IcECG The median follow-up period was 365 (IQR 207–365) days. The incidence of each constituent factor of MACE at 1-year is shown in Table 4. One patient in the ST-E (+) group required revascularization for in-stent restenosis. Four patients in the ST-E (−) group and 5 patients in the ST-E (+) group required revascularization for remote lesion. The incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05, Figure 5). Table 4 Cofactors of MACE in the ST-E (−) group and the ST-E (+) group   ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  MACE, n (%)  3 (5.7%)  6 (19.4%)  <0.05  Cardiac death, n (%)  0 (0%)  0 (0%)  1.00  Myocardial infarction, n (%)  1 (1.9%)  1 (3.2%)  0.70  Repeat revascularization, n (%)  4 (7.6%)  6 (19.4%)  0.11  Hospitalization for heart failure, n (%)  0 (0%)  2 (6.5%)  0.04    ST-E (−)  ST-E (+)    Variables  (n = 53)  (n = 31)  P-value  MACE, n (%)  3 (5.7%)  6 (19.4%)  <0.05  Cardiac death, n (%)  0 (0%)  0 (0%)  1.00  Myocardial infarction, n (%)  1 (1.9%)  1 (3.2%)  0.70  Repeat revascularization, n (%)  4 (7.6%)  6 (19.4%)  0.11  Hospitalization for heart failure, n (%)  0 (0%)  2 (6.5%)  0.04  MACE, major adverse cardiac event. Figure 5 View largeDownload slide The 1-year cumulative incidence of MACE after PCI in patients with ST-E (−) or ST-E (+) on intracoronary electrocardiogram. The incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05). MACE, major adverse cardiac event; PCI, percutaneous coronary intervention. Figure 5 View largeDownload slide The 1-year cumulative incidence of MACE after PCI in patients with ST-E (−) or ST-E (+) on intracoronary electrocardiogram. The incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group (5.7% vs. 19.4%, P < 0.05). MACE, major adverse cardiac event; PCI, percutaneous coronary intervention. Intraobserver and interobserver variability Kappa measure of agreement for intraobserver agreement was 1.00 (P < 0.001) for IcECG, 0.83 (P < 0.001) for TCFA, 0.86 (P < 0.001) for lipid-rich plaque. Interobserver variability for IcECG, TCFA and lipid-rich plaque was 0.96 (P < 0.001), 0.80 (P < 0.001) and 0.83 (P < 0.001), respectively. Mean intraobserver difference for the minimum fibrous cap thickness was 9.4 ± 4.1 μm; mean interobserver differences were 10.1 ± 9.0 μm. Mean intraobserver difference for the maximum length of lipid pool was 0.5 ± 0.2 mm; mean interobserver differences were 0.6 ± 0.3 mm. Discussion The major finding of the present study was that minimum fibrous cap thickness on pre-FD-OCT was significantly thinner and maximum length of lipid pool on pre-FD-OCT was significantly higher in the ST-E (+) group than in the ST-E (−) group. In addition, presence of plaque rupture, lipid-rich plaque, TCFA on pre-FD-OCT, protrusion and intra-stent dissection on post-FD-OCT might predict persistent ST-segment elevation on IcECG in patients who underwent successful elective PCI. Furthermore, the incidence of MACE during 1-year was significantly higher in the ST-E (+) group than in the ST-E (−) group. To our knowledge, this is the first report to present a relation between plaque features assessed by FD-OCT and microvascular perfusion estimated by IcECG, and prognosis value on IcECG in patients who underwent successful elective PCI. PMI is caused by procedure-related cell necrosis that occurs during PCI. It is diagnosed when an increase of post-procedural cardiac biomarkers is observed, occurring in between 5% and 44% of PCI.3 PMI have been associated with several factors, which can broadly be categorized as (i) patient-related factors; (ii) lesion-related factors; and (iii) procedure-related factors.8 Lesion-related factors such as plaque burden, calcification, lesion eccentricity, and thrombus which lead to distal embolization of disrupted plaque contents and residual thrombus, predict PMI.9 The most common mechanisms of PMI are distal embolization and side branch occlusion. This study was especially focused on lesion-related factors which lead to distal embolization using FD-OCT. Despite the presence of patent epicardial coronary circulation, microvascular perfusion may fail to be acquired in a substantial portion of the perfusion territory of the treated coronary artery because distal atherothrombotic embolization could trigger abnormalities at the level of the microvasculature.10 Presence of plaque rupture, lipid-rich plaque and TCFA on pre-FD-OCT might predict persistent ST-segment elevation on IcECG in patients who underwent elective PCI, which was consistent with results of previous studies focused on an increase of post-procedural cardiac biomarkers.11,12 TCFA is characterized by a large necrotic core and a thin fibrous cap and associated with positive vessel remodeling.13 Also, TCFA often leads to plaque rupture.14 The necrotic core component contains fragile tissues such as lipid deposition with foam cells, intramural bleeding, and/or cholesterol crystals.15 The presence of plaque rupture, lipid-rich plaque and TCFA correlates with more progressive atherosclerosis and vulnerable plaques and results in distal embolization by disrupted plaque contents during PCI. In addition, in the cavity of plaque rupture, there might be residual lipid plaque and organized thrombus. Previous studies have suggested that large plaque volume and lipid-rich plaque at culprit lesions assessed by intravascular ultrasound may be associated with no-reflow phenomenon, resulting in PMI.16 In this study, maximum length of lipid pool was significantly higher in the ST-E (+) group than in the ST-E (−) group. It might be useful to evaluate longitudinal extent of lipid pool using FD-OCT to quantify the whole plaque burden accurately. Porto et al.12 reported that presence of intra-stent thrombus and intra-stent dissection on post-FD-OCT might predict Troponin-T elevation in patients treated with second generation drug-eluting stents . In this study, intra-stent dissection was significantly more frequently found by post-FD-OCT in the ST-E (+) group than in the ST-E (−) group. However, there was no significant difference in intra-stent thrombus between the two groups. We guess that this discordance was because intra-stent thrombus were observed in only 4 patients in this study and Porto et al included non-ST elevation myocardial infarction patients. Additionally, protrusion was significantly more frequently found by post-FD-OCT in the ST-E (+) group than in the ST-E (−) group in this study. This finding suggested that thinner fibrous cap and large necrotic cores might be more likely to be destroyed by stent implantation, eventually resulting in impaired microvascular perfusion and tissue protrusion through stent struts reflected this mechanical mechanism. Correspondingly, calcified plaque on pre-FD-OCT might be not easy to be destroyed by stent implantation and introduce distal embolization. Previous studies have reported that ST-segment resolution on IcECG was associated with infarct size assessed by cardiac magnetic resonance imaging (CMR) in MI patients.17 IcECG seemed to assess local myocardial state in the catheterization laboratory.4 Larger stent expansion associated with a higher level of post-procedural CK-MB suggests a tradeoff between optimal stent implantation and PMI.18 Because of monitoring ST-segment changes of IcECG in the catheterization laboratory, evaluation of IcECG might provide useful information on indicating and monitoring of these interventions to optimize stent expansion. To prevent distal embolization during PCI, several trials have been conducted with a variety of embolic distal protection devices. However, The Drug Elution and Distal Protection in ST Elevation Myocardial Infarction (DEDICATION) trial suggested that in primary PCI for ST-segment elevation myocardial infarction, the routine use of distal protection increased the incidence of stent thrombosis and clinically driven target lesion/vessel revascularization because of complexity of use.19 Therefore, it is necessary to determine patients who will suffer from impaired microvascular perfusion without distal protection devices based on these pre-FD-OCT findings. It was reported that pretreatment with statins decreases the incidence of PMI during PCI.20 In this study, the rate of patients taking statins at least 7 days before PCI was significantly higher in the ST-E (−) group than in the ST-E (+) group. It is necessary to administer statins to patients who are planned to undergo PCI earlier than 7 days. Furthermore, ST-segment elevation on IcECG after the procedure might be associated with 1-year MACE. The total of MI, repeat revascularization and hospitalization for heart failure affected 1-year MACE. We think that ST-segment elevation on post-IcECG might be a surrogate marker and patients with ST-segment elevation on post-IcECG might be ‘vulnerable patients which might be prone to cardiac event’. Some studies demonstrated that intravenous nicorandil administration reduced cardiac biomarker elevation after elective PCI.21 More constructive treatment should be needed to these high-risk patients with ST-segment elevation on IcECG after the procedure to reduce future cardiac events. Prospective studies will be advocated to investigate the propriety of FD-OCT-guided use of embolic protection devices and IcECG-guided administration of pharmacological agents to prevent and treat impaired microvascular perfusion during elective PCI. Study limitations Major limitation of this study is small sample size. Because of the invasive nature of this study, only 84 patients were included. In addition, this study was conducted in only a single institution in a non-randomized, retrospective manner. Although all patients achieved final TIMI 3 flow grade in this study, the exclusion of patients with large vessel diameter may have led to all patients achieving final TIMI3 flow grade. Use of other measures, including myocardial blush grade, flow velocity by Doppler wire, microvascular obstruction by CMR and contrast deficit by contrast echocardiography, might have provided additional information on microvascular perfusion. Inability to measure plaque volume is one of the major limitations of FD-OCT. No patient received glycoprotein IIb/IIIa receptor inhibitor because they are not available in Japan. Plaque characteristics and stent status may affect the development of in-stent restenosis. However, only one patient had in-stent restenosis because all patients were treated by second or third generation drug-eluting stent and we excluded patients with reduced renal function, tortuous vessels or severe calcified lesions who are likely to develop in-stent restenosis. So, we could not evaluate predictive value for in-stent restenosis. We did not perform an analysis of the long-term prognostic value of ST-segment elevation on IcECG. Conclusions Plaque features assessed by FD-OCT might be associated with impaired microvascular perfusion and ST-segment elevation on IcECG after the procedure could predict 1-year cardiac events after elective PCI. Further studies should be advocated to investigate the more clinical prognostic value of relation between plaque features at culprit lesions assessed by FD-OCT and IcECG for patients who underwent elective PCI and better therapeutic options to reduce cardiovascular event. Acknowledgements We thank Mr Shingo Kono for his technical support of FD-OCT and Mr Tsukasa Nakao for their technical support of the IcECG recording. Conflict of interest: None declared. References 1 Testa L, Van Gaal WJ, Biondi Zoccai GG, Agostoni P, Latini RA, Bedogni F et al.   Myocardial infarction after percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition. QJM  2009; 102: 369– 78. Google Scholar CrossRef Search ADS PubMed  2 van't Hof AW, Liem A, de Boer MJ, Zijlstra F. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Zwolle Myocardial infarction Study Group. Lancet  1997; 350: 615– 9. Google Scholar CrossRef Search ADS PubMed  3 Balian V, Galli M, Marcassa C, Cecchin G, Child M, Barlocco F et al.   Intracoronary ST-segment shift soon after elective percutaneous coronary intervention accurately predicts periprocedural myocardial injury. 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Google Scholar CrossRef Search ADS PubMed  7 Guagliumi G, Ikejima H, Sirbu V, Bezerra H, Musumeci G, Lortkipanidze N et al.   Impact of drug release kinetics on vascular response to different zotarolimus-eluting stents implanted in patients with long coronary stenoses: the LongOCT study (Optical Coherence Tomography in Long Lesions). JACC Cardiovasc Interv  2011; 4: 778– 85. Google Scholar CrossRef Search ADS PubMed  8 Lansky AJ, Stone GW. Periprocedural myocardial infarction: prevalence, prognosis, and prevention. Circ Cardiovasc Interv  2010; 3: 602– 10. Google Scholar CrossRef Search ADS PubMed  9 Nallamothu BK, Chetcuti S, Mukherjee D, Grossman PM, Kline-Rogers E, Werns SW et al.   Prognostic implication of troponin I elevation after percutaneous coronary intervention. Am J Cardiol  2003; 91: 1272– 4. Google Scholar CrossRef Search ADS PubMed  10 Jaffe R, Dick A, Strauss BH. Prevention and treatment of microvascular obstruction-related myocardial injury and coronary no-reflow following percutaneous coronary intervention: a systematic approach. JACC Cardiovasc Interv  2010; 3: 695– 704. Google Scholar CrossRef Search ADS   11 Lee T, Yonetsu T, Koura K, Hishikari K, Murai T, Iwai T et al.   Impact of coronary plaque morphology assessed by optical coherence tomography on cardiac troponin elevation in patients with elective stent implantation. Circ Cardiovasc Interv  2011; 4: 378– 86. Google Scholar CrossRef Search ADS PubMed  12 Porto I, Di Vito L, Burzotta F, Niccoli G, Trani C, Leone AM et al.   Predictors of periprocedural (type IVa) myocardial infarction, as assessed by frequency-domain optical coherence tomography. Circ Cardiovasc Interv  2012; 5: 89– 96, S1-6. 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Google Scholar CrossRef Search ADS   19 Kaltoft A, Kelbaek H, Klovgaard L, Terkelsen CJ, Clemmensen P, Helqvist S et al.   Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial. J Am Coll Cardiol  2010; 55: 867– 71. Google Scholar CrossRef Search ADS PubMed  20 Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G et al.   Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study. Circulation  2004; 110: 674– 8. 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European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Mar 1, 2018

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