Abstract

Aims

Although some recent guidelines recommend an early invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS), several studies have failed to identify any benefit for very early intervention for NSTEACS. The no-reflow phenomenon may inhibit the expected benefit from very early recanalization for NSTEACS subjects. The aim of this study was to investigate whether optical coherence tomography (OCT) could predict no-reflow in patients with NSTEACS.

Methods and results

This study comprised 83 consecutive patients with NSTEACS who underwent OCT and successful emergent primary stenting. On the basis of post-stent TIMI flow, patients were divided into two groups: no-reflow group (n = 14) and reflow group (n = 69). Thin-cap fibroatheroma (TCFA) was defined as a plaque presenting lipid content for >90°, and with thinnest part of the fibrous cap measuring <70 µm. Thin-cap fibroatheroma were more frequently observed in the no-reflow group than in the reflow group (50% vs. 16%, P = 0.005). The frequency of the no-reflow phenomenon increases according to the size of the lipid arc in the culprit plaque. Final TIMI blush grade also deteriorated according to the increase in the lipid arc. A multivariable logistic regression model revealed that lipid arc alone was an independent predictor of no-reflow (odds ratio 1.018; CI 1.004–1.033; P = 0.01).

Conclusion

Optical coherence tomography can predict no-reflow after percutaneous coronary intervention (PCI) in NSTEACS. The lipid contents of a culprit plaque may play a key role in damage to the microcirculation after PCI for NSTEACS. From our results, it is found that OCT is useful tool for stratifying risk for PCI for NSTEACS.

Introduction

There has been much debate about whether patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) should be treated by conservatively or by a strategy of early invasive treatment. In this context, some recently published general consensus guidelines recommend an early invasive strategy, particularly in high-risk patients.1,2 This is, however, despite some large-scale studies having failed to identify a benefit for very early intervention.3–5

The patency of the culprit artery does not always guarantee salvage of myocardium at risk of ischaemia. The phenomenon of microvascular no-reflow is defined as inadequate myocardial perfusion through a given segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction.6,7 It has also been reported that no-reflow is associated with poor functional and clinical patient outcomes when compared with patients with adequate reflow following reperfusion.8,9 Further, recent studies have revealed that distal embolization of thrombus and/or plaque contents are one of the major causes of no-reflow.10–12

It may be critically important, therefore, to be able to predict which lesions are high risk for myocardial no-reflow prior to beginning percutaneous coronary intervention (PCI), especially in patients with NSTEACS not presenting with ongoing myocardial necrosis. However, no study has yet successfully addressed or identified a method for accurately predicting no-reflow in NSTEACS.

The recent development of intravascular optical coherence tomography (OCT) provides a high-resolution imaging modality highly suitable for plaque characterization in vivo.13–17 Optical coherence tomography is an optical analogue of intravascular ultrasound (IVUS) with a resolution of approximately 10–20 µm. Histological studies have shown that OCT can identify the microstructure of atherosclerotic plaques, including lipid core.18,19

The aim of this study was to investigate whether pre-intervention OCT could predict myocardial no-reflow after successful PCI in patients with NSTEACS.

Methods

Study population

We enrolled 90 consecutive NSTACS patients who admitted to Wakayama Medical University Hospital between July 2007 and June 2008. We excluded patients who refused to participate in this study (n = 1), had prior myocardial infarction (n = 3), showed bypass failure (n = 2), and patients in whom adequate OCT and IVUS images at the culprit lesion could not be obtained (n = 1). Finally, we analysed 83 NSTEACS patients who underwent OCT and were successfully recanalized by emergent primary PCI. NSTEACS includes non-ST-segment elevation myocardial infarction and unstable angina for the purposes of this study. Our definition of non-ST-segment elevation myocardial infarction was based on new findings of ST-segment depression <0.1 mm, T-wave inversion of ≥0.4 mm in at least two leads or symptoms consistent with acute myocardial infarction and the presentation of elevated levels of troponin-T (>0.1 ng/mL) in association with any or all of the previous criteria.

Unstable angina was defined as an unstable pattern of chest pain (at rest, new onset, or crescendo angina) coinciding with objective evidence of 201Thallium scintigraphy, dobutamine echocardiography, and/or coronary angiography, demonstrating a >50% coronary stenosis but without any elevation in troponin-T (>0.1 ng/mL).

The study protocol was approved by the Ethics Committee of Wakayama Medical University. We also obtained written informed consent from all the participants prior to coronary angiography.

Study protocol

Coronary angiography in all patients was performed using a 5F Judkins-type catheter via the femoral approach. All patients received an intravenous bolus injection of 10 000 IU of heparin and intracoronary isosorbide dinitrate (2 mg) before angiography. After completion of diagnostic coronary angiography, OCT was used to observe the culprit coronary artery. A 0.014 in. (distal) OCT catheter (ImageWire®; LightLab Imaging, Westford, MA, USA) was advanced to the distal end of the culprit lesion. If the lesion presented with severe tortuosity, severe stenosis, or a heavy calcium burden, we first advanced a conventional PCI guide wire (0.014 in.) across the lesion before exchanging it for the OCT Imagewire using a microcatheter (Renegade, Boston Scientific, Natick, MA, USA). We used a continuous-flushing (non-occlusive) method for OCT image acquisition, which is a newly developed alternative to the more conventional balloon-occlusion technique. To flush the vessel, we infused a mixture of commercially available Dextran 40 and lactated Ringer's solution (Low Molecular Dextran L Injection®, Otsuka Pharmaceutical Factory, Tokushima, Japan) direct from the guiding catheter at a rate of 2.5–4.5 mL/s using an injector pump (Mark V, Medrad Inc., PA, USA). Regardless of the OCT technique used, in all cases the culprit lesion was imaged using an automatic pullback device travelling at 1 mm/s. The OCT images were digitalized and analysed using the M2CV OCT console.

After completion of OCT explorations and before any intervention, an attempt to perform IVUS was made with all patients. The IVUS catheter (2.9Fr, 20 mHz transducer, Eagle eye, Volcano Corporation, Rancho Cordova, CA, USA) was carefully advanced distal to the lesion under fluoroscopic guidance. Following OCT and IVUS, PCI was performed using a 6F guiding catheter, 0.014 in. guide wire, and a monorail balloon catheter, according to conventional methods. To avoid over-aggressive stent expansion, decision-making on PCI strategy was guided by the results of on-line QCA. Angiographical criteria of <25% residual stenosis were adopted as our definition of successful PCI and the endpoint of the interventional procedure.

A total of 3000 units of unfractionated heparin were administered every hour during the procedure to maintain an activated clotting time of >300 s. After PCI, intravenous infusion of unfractionated heparin was continued for at least 24 h to maintain an activated clotting time of 180–200 s. No IIb/IIIa inhibitors were administrated in this study because these inhibitors have not been approved in Japan. An antiplatelet therapy of aspirin (80 mg/day) prior to coronary angiography and ticlopidine (200 mg/day) following stent implantation was administered.

Angiographic analysis

Coronary angiograms were reviewed separately by two independent observers (H.K. and T.T.) blinded to the OCT findings. Quantitative coronary angiography was performed off-line using the CMS-QCA system (CMS-MEDIS. Medical Imaging Systems, Leiden, Netherlands). Perfusion was evaluated according to TIMI criteria.20 No-reflow phenomenon was defined as post-stent TIMI Grade 0, 1, or 2 flow in the absence of a mechanical obstruction on angiograms. On the basis of post-stent TIMI flow, patients were divided into a no-reflow group and a reflow group. TIMI blush grade was also applied to evaluate myocardial perfusion after PCI.21 Collaterals were graded according to Rentrop's classification,22 with good collateral flow defined as Grade 2 or 3. Angiographic thrombus was defined as a filling defect seen in multiple projections surrounded by contrast in the absence of calcification and >10 mm in length.

Analysis of intravascular ultrasound images

The IVUS images were interpreted by two independent experienced observers (M.K. and N.N.) unfamiliar with the OCT data according to the American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies.23 A lipid pool-like image was defined as a pooling of low-echoic material or echolucent material covered with a high-echoic layer.11

Analysis of optical coherence tomography images

The OCT findings were interpreted by two independent experienced observers (M.M. and A.T.) unfamiliar with the angiographic and clinical data. When there was any discordance between the observers, a consensus reading was obtained. OCT images were analysed using previously validated criteria for plaque characterization and fibrous cap thickness was determined as reported previously.18,19 Lipid was semi-quantified by measuring the lipid arc. When the lipid arc stretched for >90°, the plaque was deemed to be lipid-rich. For each patient, the cross-sectional image with the largest of lipid arc and the thinnest fibrous cap thickness were used for analysis. Thin-cap fibroatheroma (TCFA) was defined as a plaque presenting lipid content for >90°, and with thinnest part of the fibrous cap measuring <70 µm (Figure 1, C-OCT). Plaque rupture was defined as the presence of fibrous cap discontinuity and a cavity formation in the plaque (Figure 1, D-OCT). Intracoronary thrombus was identified as a mass protruding into the vessel lumen from the surface of the vessel wall.

Figure 1

Representative pre-percutaneous coronary intervention optical coherence tomography (OCT) images. (A) An initial angiogram of a case presenting no-reflow. Severe stenosis and complex lesion located in the mid portion of left circumflex artery. (B) The angiogram during no-reflow. (C-OCT) Pre-percutaneous coronary intervention optical coherence tomography images of culprit lesion (indicating C in angiogram). Optical coherence tomography presents thin-capped fibroatheroma. The lipid arc was 276° and the fibrous cap thickness was 40 µm. (D-OCT) A ruptured plaque adjacent to thin-capped fibroatheroma (indicating D in angiogram). Broken fibrous cap thickness was 30 µm. (C-IVUS) Intravascular ultrasound image of thin-cap fibroatheroma (C-OCT). A low-echoic and eccentric plaque is observed. (D-IVUS) Intravascular ultrasound image of ruptured plaque (D-OCT). Intravascular ultrasound also revealed the ruptured plaque.

Figure 1

Representative pre-percutaneous coronary intervention optical coherence tomography (OCT) images. (A) An initial angiogram of a case presenting no-reflow. Severe stenosis and complex lesion located in the mid portion of left circumflex artery. (B) The angiogram during no-reflow. (C-OCT) Pre-percutaneous coronary intervention optical coherence tomography images of culprit lesion (indicating C in angiogram). Optical coherence tomography presents thin-capped fibroatheroma. The lipid arc was 276° and the fibrous cap thickness was 40 µm. (D-OCT) A ruptured plaque adjacent to thin-capped fibroatheroma (indicating D in angiogram). Broken fibrous cap thickness was 30 µm. (C-IVUS) Intravascular ultrasound image of thin-cap fibroatheroma (C-OCT). A low-echoic and eccentric plaque is observed. (D-IVUS) Intravascular ultrasound image of ruptured plaque (D-OCT). Intravascular ultrasound also revealed the ruptured plaque.

Statistical analysis

Results were expressed as mean value ± SD or median [Q1–Q3] for continuous variables. Qualitative data are presented as numbers (%). Continuous variables were compared using Student's t-test or Mann–Whitney U test, and categorical data using χ2 test or Fisher's exact test, as appropriate. A multivariable logistic regression model was used to determine predictors of no-reflow. Those variables that had shown P < 0.05 in univariate analysis (lipid pool-like image, per cent plaque area, presence of TCFA, lipid arc) and clinically meaningful factors for no-reflow (male gender, history of diabetes mellitus) were included into the multivariable logistic analysis. A likelihood ratio test, with linearity as the null hypothesis, was performed to determine whether the linearity assumption was valid. A P-value of <0.05 was considered statistically significant.

Results

Patient characteristics and clinical results

Patient characteristics and clinical results for both groups are summarized in Table 1. There were no differences in the incidence of classical coronary risk factors between the two groups. Peak creatine kinase-MB levels after PCI was significantly higher in the no-reflow group than in the reflow group (50 [190] vs. 12 [30] IU/L, P < 0.01).

Table 1

Clinical characteristics and clinical results

 No-reflow group Reflow group P-value 
Number of patients 14 69  
Age (years) 65 ± 14 66 ± 11 0.77 
Male 13 (93) 51 (74) 0.17 

 
Coronary risk factors 
 Systemic hypertension 10 (71) 44 (64) 0.76 
 Diabetes mellitus 7 (50) 24 (35) 0.37 
 Hypercholesterolemia ( >220 mg/dL) 8 (57) 33 (48) 0.57 
 Smoking 10 (71) 32 (46) 0.14 

 
Time from hospitalization to angiography (h) 6 [2.5–46] 9 [4–45] 0.38 
CK-MB levels after PCI (IU/L) 50 [21–211] 12 [6.8–37] 0.003 
 No-reflow group Reflow group P-value 
Number of patients 14 69  
Age (years) 65 ± 14 66 ± 11 0.77 
Male 13 (93) 51 (74) 0.17 

 
Coronary risk factors 
 Systemic hypertension 10 (71) 44 (64) 0.76 
 Diabetes mellitus 7 (50) 24 (35) 0.37 
 Hypercholesterolemia ( >220 mg/dL) 8 (57) 33 (48) 0.57 
 Smoking 10 (71) 32 (46) 0.14 

 
Time from hospitalization to angiography (h) 6 [2.5–46] 9 [4–45] 0.38 
CK-MB levels after PCI (IU/L) 50 [21–211] 12 [6.8–37] 0.003 

Data presented are mean value ± SD, median [Q1–Q3], or number (%).

Angiographical findings

Percutaneous coronary intervention was successful in all patients and without any serious complications. Mean time to catheterization was 29 ± 26 h. Bare metal stents were used in all patients (n = 83, 100%) patients. Our angiographical findings are summarized in Table 2. Angiographical no-reflow phenomenon after stent implantation was seen in 14 patients (17%). After usage of intraaortic balloon pumping (IABP), aspiration, and/or intracoronary injection of nicorandil, 81 patients achieved TIMI 3 flow, except two patients showing TIMI 2 flow. IABP was more frequently used in the no-reflow group than in the reflow group (21% vs. 1%, P = 0.01). Procedural factors such as inflation pressure, stent size, or stent to artery ratio were similar between the groups.

Table 2

Angiographical findings

 No-reflow group (n = 14) Reflow group (n = 69) P-value 
Culprit artery 
 Left descending artery 6 (43) 34 (49) 0.89 
 Left circumflex artery 2 (14) 10 (14)  
 Right coronary artery 6 (43) 25 (36)  

 
TIMI flow grade at initial angiogram 
 0 4 (29) 11 (17) 0.61 
 1 2 (3)  
 2 3 (21) 17 (25)  
 3 7 (50) 39 (56)  

 
Angiographical thrombus 0 (0) 3 (3) 0.99 
Good collateral flow 2 (14) 8 (12) 0.67 
Reference diameter (mm) 3.4 ± 0.6 3.2 ± 0.7 0.45 
Minimal lumen diameter (mm) 0.68 ± 0.7 0.61 ± 0.6 0.73 
% diameter stenosis 82.6 ± 17.3 86.5 ± 14.2 0.40 
IABP use 3 (21) 1 (1) 0.01 
Number of stents used 1.1 ± 0.3 1.1 ± 0.4 0.67 
Stent size (mm) 3.4 ± 0.4 3.4 ± 0.5 0.77 
Stent to artery ratio 1.03 ± 0.11 0.97 ± 0.35 0.50 
Stent length (mm) 16.3 ± 2.1 17.4 ± 8.2 0.77 
Final inflation pressure (atm) 12.6 ± 2.1 12.3 ± 1.5 0.55 
 No-reflow group (n = 14) Reflow group (n = 69) P-value 
Culprit artery 
 Left descending artery 6 (43) 34 (49) 0.89 
 Left circumflex artery 2 (14) 10 (14)  
 Right coronary artery 6 (43) 25 (36)  

 
TIMI flow grade at initial angiogram 
 0 4 (29) 11 (17) 0.61 
 1 2 (3)  
 2 3 (21) 17 (25)  
 3 7 (50) 39 (56)  

 
Angiographical thrombus 0 (0) 3 (3) 0.99 
Good collateral flow 2 (14) 8 (12) 0.67 
Reference diameter (mm) 3.4 ± 0.6 3.2 ± 0.7 0.45 
Minimal lumen diameter (mm) 0.68 ± 0.7 0.61 ± 0.6 0.73 
% diameter stenosis 82.6 ± 17.3 86.5 ± 14.2 0.40 
IABP use 3 (21) 1 (1) 0.01 
Number of stents used 1.1 ± 0.3 1.1 ± 0.4 0.67 
Stent size (mm) 3.4 ± 0.4 3.4 ± 0.5 0.77 
Stent to artery ratio 1.03 ± 0.11 0.97 ± 0.35 0.50 
Stent length (mm) 16.3 ± 2.1 17.4 ± 8.2 0.77 
Final inflation pressure (atm) 12.6 ± 2.1 12.3 ± 1.5 0.55 

Data presented are mean value ± SD or number (%).

Intravascular ultrasound findings

Intravascular ultrasound transducer could not pass the tight (n = 9), heavily calcified (n = 3), or bent (n = 4) lesions. Ultimately, only 67 (80%) of 84 culprit lesions could be observed by this IVUS system before pre-dilatation, while OCT was able to observe 83 (99%) of 84 culprit lesions (IVUS 80% vs. OCT 99%, P < 0.001). The OCT findings are summarized in Table 3.

Table 3

Intravascular ultrasound findings

 No-reflow group (n = 14) Reflow group (n = 53) P-value 
Plaque rupture 8 (57%) 23 (38%) 0.36 
Lipid pool-like image 7 (50%) 7 (13%) 0.01 
Positive remodelling 9 (64%) 25 (47%) 0.37 
Lesion lumen cross sectional area (mm23.3 ± 1.5 3.5 ± 1.3 0.75 
Lesion external elastic membrane cross sectional area (mm215.3 ± 3.0 13.9 ± 4.0 0.23 
Plaque area (%) 83.0 ± 14 73.6 ± 11 0.01 
 No-reflow group (n = 14) Reflow group (n = 53) P-value 
Plaque rupture 8 (57%) 23 (38%) 0.36 
Lipid pool-like image 7 (50%) 7 (13%) 0.01 
Positive remodelling 9 (64%) 25 (47%) 0.37 
Lesion lumen cross sectional area (mm23.3 ± 1.5 3.5 ± 1.3 0.75 
Lesion external elastic membrane cross sectional area (mm215.3 ± 3.0 13.9 ± 4.0 0.23 
Plaque area (%) 83.0 ± 14 73.6 ± 11 0.01 

Data presented are mean value ± SD or number (%).

Optical coherence tomography findings

Culprit lesions were successfully observed with OCT without any serious procedural complications. No patients presented with any worsening of coronary flow or haziness at the culprit lesion after the OCT procedure. An inter-observer agreement for qualitative analysis of 95.1% was achieved in this study. The OCT findings are summarized in Table 4. Plaque rupture was seen in 43 (52%) of all patients. TCFA were more frequently observed in the no-reflow group than in the reflow group (50% vs. 16%, P < 0.01). We also observed that the frequency of no-reflow increases according to the lipid arc at the culprit plaque (Figure 2). Although all patients without lipid plaques (34 of 34, 100%) achieved good reflow, 46% of patients with lipid-rich plaque (13 of 28, 46%) presented no-reflow after PCI. Final TIMI blush grade also was more likely to be poor as the lipid arc increased (Figure 3). In this study, 30 (88%) of 34 patients with no lipid arc achieved good myocardial perfusion (TIMI blush grade 3), only 11 of 28 (39%) patients with a lipid-rich plaque (lipid arc >90°), by our definitions, achieved good myocardial perfusion. Representative pre-intervention OCT images of no-reflow are shown in Figure 1.

Figure 2

Frequency of no-reflow and lipid arc. The frequency of no-reflow increases according to the lipid arc at the culprit plaque. Although all patients without lipid plaques (34 of 34, 100%) achieved good reflow, 46% of patients with lipid-rich plaque (13 of 28, 46%) presented no-reflow after percutaneous coronary intervention.

Figure 2

Frequency of no-reflow and lipid arc. The frequency of no-reflow increases according to the lipid arc at the culprit plaque. Although all patients without lipid plaques (34 of 34, 100%) achieved good reflow, 46% of patients with lipid-rich plaque (13 of 28, 46%) presented no-reflow after percutaneous coronary intervention.

Figure 3

TIMI blush grade and lipid arc. Final TIMI blush grade was more likely to be poor as the lipid arc increased. In this study, 30 (88%) of 34 patients with no lipid arc achieved good myocardial perfusion (TIMI blush grade 3), only 11 of 28 (39%) patients with a lipid-rich plaque (lipid arc >90°) achieved good myocardial perfusion.

Figure 3

TIMI blush grade and lipid arc. Final TIMI blush grade was more likely to be poor as the lipid arc increased. In this study, 30 (88%) of 34 patients with no lipid arc achieved good myocardial perfusion (TIMI blush grade 3), only 11 of 28 (39%) patients with a lipid-rich plaque (lipid arc >90°) achieved good myocardial perfusion.

Table 4

Intravascular optical coherence tomography findings

 No-reflow group (n = 14) Reflow group (n = 69) P-value 
Plaque rupture 10 (71) 33 (48) 0.15 
Thrombus 11 (79) 55 (80) 0.99 
Thin-cap fibroatheroma  7 (50) 11 (16) 0.005 
Lipid arc (degree) 166 ± 60 44 ± 63 <0.001 
 No-reflow group (n = 14) Reflow group (n = 69) P-value 
Plaque rupture 10 (71) 33 (48) 0.15 
Thrombus 11 (79) 55 (80) 0.99 
Thin-cap fibroatheroma  7 (50) 11 (16) 0.005 
Lipid arc (degree) 166 ± 60 44 ± 63 <0.001 

Data presented are mean value ± SD or number (%).

Multivariable logistic regression model for no-reflow

Our multivariable logistic regression model revealed that only lipid arc degree was an independent predictor of no-reflow (odds ratio 1.018, CI 1.004–1.033, P = 0.01). These data are summarized in Table 5.

Table 5

Multivariable logistic regression model for no-reflow

 P-value Odds ratio 95% CI 
Gender 0.46 2.67 0.198–35.882 
History of diabetes mellitus, years 0.12 4.13 0.688–24.743 
Lipid pool-like image, years 0.39 2.26 0.357–14.252 
Plaque area, % 0.07 1.07 0.994–1.144 
Thin-cap fibroatheroma, years 0.98 0.98 0.116–8.191 
Lipid arc 0.01 1.018 1.004–1.033 
 P-value Odds ratio 95% CI 
Gender 0.46 2.67 0.198–35.882 
History of diabetes mellitus, years 0.12 4.13 0.688–24.743 
Lipid pool-like image, years 0.39 2.26 0.357–14.252 
Plaque area, % 0.07 1.07 0.994–1.144 
Thin-cap fibroatheroma, years 0.98 0.98 0.116–8.191 
Lipid arc 0.01 1.018 1.004–1.033 

Discussion

Lipid contents and myocardial no-reflow

It is well known that the angiographic no-reflow phenomenon occurs after intervention in degenerated saphenous vein grafts. In these cases, distal embolization of plaque and/or thrombus from the lesion site is the likely mechanism.24–26

Our IVUS study revealed that the presence of lipid-pool-like images is associated with the no-reflow phenomenon and that decreased plaque volume inversely correlated with coronary flow after PCI.11,27 In acute myocardial infarction subjects, Kotani et al.10 have reported that plaque debris consisting of a necrotic core, inflammatory cells, cholesterol debris, and old and fresh thrombi are often retrieved from the distal portions of infarct-related arteries after direct angioplasty. Okura et al.12 reported that suspicious necrotic core component might be related to liberation of small embolic particles during coronary stenting. However, it remains unclear which components of thrombosed-plaque contribute most to the development for no-reflow. In this study, we have shown that lipid content from culprit plaques are directly associated with no-reflow after PCI in the setting of NSTEACS. Furthermore, lipid content also affects the myocardial microcirculation. Even where epicardial flow appears to be normal, the embolization of lipid content may have occurred at the level of the myocardial tissue.

It has been reported that high numbers of macrophages are present in the lipid contents of plaque and contain large amounts of tissue factor.28,29 One experimental study showed that the shedding of active tissue factors alone can cause the no-reflow phenomenon.30 We suspect that the mechanical destruction of lipid-rich plaques by PCI, especially thin-cap atheroma that can easily be disrupted, may induce an outflow of active tissue factor into the coronary flow and that this blood-born active tissue factor may cause no-reflow after PCI.

From optimal timing to optimal lesion for early percutaneous coronary intervention in NSTEACS

Hoenig et al.31 reported that the composite end-point of death, non-fatal myocardial infarction, or the incidences of refractory angina were significantly decreased by the invasive strategy compared with the conservative strategy. Simultaneously, they also reported that the invasive strategy was associated with a two-fold increase in the relative risk of peri-procedural myocardial infarction.31 Recently published general consensus guidelines recommend the early invasive strategy, particularly in high-risk patients.1,2 To the best of our knowledge, few studies discuss which lesions are best suited for early PCI in NSTEACS. One randomized, controlled study showed that prolonged antithrombotic pre-treatment does not improve the outcome.32 This result suggests that modifying the thrombus existing at the culprit lesion does not improve the prognosis of NSTEACS or reduce complications after PCI in this setting. Our results similarly show that lipid content plays a key role in the development of no-reflow and impaired tissue circulation. TIMI blush grade is directly related to higher risk of mortality; normal epicardial flow and normal tissue level perfusion (TIMI blush grade 3) have an extremely low risk of mortality.20 Our patients without lipid arc showed good epicardial flow and normal tissue level perfusion. We consider that these lesions are suitable for very early PCI in NSTEACS to achieve favourable clinical outcomes. Elevated creatine kinase after PCI is reported as a predictor for poor outcomes after PCI.33 Lower levels of creatine kinase-MB after PCI in the reflow group may support the above recommendations. Before altering clinical practice based on these results, it would be necessary to undertake an adequately randomized trial in which patients with OCT defined large lipid content would be deferred for PCI for some days or weeks. However, setting up such a trial in a large number of patients would be costly and difficult with regard to patient recruitment.

Clinical implications

Patients with NSEACS are not faced with ongoing myocardial necrosis. Therefore, we should not always hurry to perform PCI in early phase as like STEACS in order to salvage myocardium at risk. This would allow for the accurate stratification of risk and encourage PCI only for optimal lesions. The recently published guidelines recommend early angiography as a way of evaluating the overall risk.1,2 No-reflow after reperfusion in patients with NSTEACS will be encountered in the cath-lab. OCT for NSTEACS subjects can be performed promptly and safely in the setting of the cath-lab adjacent to angiography. We believe that OCT can be used in the setting of NSTEACS for the evaluation of the lesion, to determine which lesion is suitable for early PCI, conducted while taking advantage of techniques for distal protection for preventing the no-reflow phenomenon. Since recently, admissions for NSTEACS have come to outnumber admissions for STEMI by nearly a 4:1 margin,34 risk stratification for NSTEACS by OCT may be of great benefit for a large number of patients.

Study limitations

A number of limitations can be said to be associated with this study. To the best of our knowledge, there are few data regarding the precise frequency of no-reflow in emergent PCI for NSEACS in stent era. Kotani et al.10 reported that no-reflow occurs in 19% of ACS patients. This frequency is very similar to our present study. However, we did not use IIb/IIIa inhibitors in this study. This might strongly affect the frequency of no-reflow. Many mechanisms have been postulated for microvascular dysfunction, including free radicals,35–37 cardiac sympathetic reflexes with resulting α-adrenergic macrovascular and microvascular constriction,38 regional changes in angiotensin II receptor density,39 and selectin-regulated interactions between activated poly-morphonuclear leucocytes, and the endothelium.40 These diverse data suggest that no-reflow may be induced by multifactorial causes. OCT can only provide information about surface morphologies of coronary plaques.

We applied the lipid arc for semi-quantitative assessment for lipid contents. However, plaque volume is also an important factor for no-reflow.11,27 The maximum penetration depth of OCT is about 2 mm. This limited penetration depth does not permit us to evaluate plaque volume or positive remodelling of atheromatous plaques.

Equally, the presence of thrombus at a culprit site may disturb the assessment by OCT, as thrombus further limits the penetration of the device.

Conclusion

Optical coherence tomography can predict no-reflow and impaired microcirculation after PCI in the setting of NSTEACS. Lipid content from a culprit plaque may play a key role in damage to the microcirculation following PCI for NSTEACS. Our results suggest OCT is a useful coronary imaging modality for stratifying risk for early PCI in NSTEACS.

Conflict of interest: none declared.

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