Author + information
- Received March 12, 2007
- Revision received May 29, 2007
- Accepted June 4, 2007
- Published online October 23, 2007.
- Ren Kawaguchi, MD⁎ (, )
- Shigeru Oshima, MD, PhD,
- Masaaki Jingu, RT,
- Hideki Tsurugaya, MD,
- Takuji Toyama, MD, PhD,
- Hiroshi Hoshizaki, MD, PhD and
- Koichi Taniguchi, MD, PhD
- ↵⁎Reprint requests and correspondence:
Dr. Ren Kawaguchi, Director of Cardiology Division, Gunma Prefectural Cardiovascular Center, 3-12 Kameizumi-Machi, Maebashi, Gunma 371-0004, Japan.
Objectives We aimed to predict the high-risk plaque of distal embolization after stent deployment in patients with acute ST-segment elevation myocardial infarction (STEMI) with Virtual Histology intravascular ultrasound (VH-IVUS) (Volcano Therapeutics, Inc., Rancho Cordova, California).
Background Distal embolization during primary percutaneous coronary intervention (PCI) carries a poor prognosis in patients with STEMI. However, it is unclear which plaque characteristics cause distal embolization after stent deployment.
Methods A total of 71 patients with STEMI were included prospectively. All patients underwent primary PCI within 12 h of symptom onset. After crossing the lesion with a guidewire and performing thrombectomy with an aspiration catheter, VH-IVUS of the infarct-related vessel was performed. Stent deployment was then undertaken without embolic protection. ST-segment re-elevation (STR) was used to evaluate distal embolization. Correlations among plaque characteristics, morphology, and distal embolization were analyzed.
Results The STR after stent deployment was observed in 11 patients (STR group, 15.5%). Necrotic core volume was significantly higher in the STR group than in the non-STR group (32.9 ± 14.1 mm3vs. 20.4 ± 19.1 mm3, p < 0.05). Total plaque volume was similar in both groups. On receiver-operating characteristic analysis, necrotic core volume clearly predicted STR after stent deployment as compared with fibrous, fibro-lipid, dense calcium, and total plaque volumes. The necrotic core volume that was best predictive for STR was 33.4 mm3, with a sensitivity of 81.7% and a specificity of 63.6%.
Conclusions Virtual Histology IVUS is a useful means of predicting the risk of distal embolization after primary stent deployment in patients with STEMI.
Primary stent implantation is an important option in the treatment of patients with ST-segment elevation myocardial infarction (STEMI) (1). However, distal embolization was found in 9% to 15% of patients who underwent primary percutaneous coronary intervention (PCI) for STEMI (2,3). It is well known that distal embolization is associated with poor functional recovery and adverse outcomes (4). A previous study reported that distal embolization during angioplasty for acute myocardial infarction was associated with an 8-fold increase in 5-year mortality (3). High-pressure stent deployment is considered a major cause of distal embolization induced by liberated plaque debris during primary angioplasty (1). However, the plaque composition that leads to distal embolization after stent deployment is yet to be determined.
Virtual Histology intravascular ultrasound (VH-IVUS) (Volcano Therapeutics, Inc., Rancho Cordova, California) has recently become available for routine clinical use. It uses spectral analysis of radiofrequency ultrasound signals to enable detailed assessment of plaque composition. In this study, we aimed to evaluate the composition of culprit plaque in STEMI by VH-IVUS and to predict the risk of distal embolization of plaque after primary stent deployment in patients with STEMI.
Study protocol and patient enrollment
In this prospective, single-center study, 71 patients with de novo STEMI were enrolled from August 2005 to December 2006. The inclusion criteria were as follows: 1) presentation within 12 h of symptom onset; 2) chest pain lasting >30 min and resistant to nitrates; 3) ≥0.2 mV ST-segment elevation in at least 2 contiguous leads on 12-lead electrocardiography (ECG); 4) an infarct-related native artery with a reference lumen diameter >2.5 mm by visual estimation that was deemed suitable for stent placement; and 5) by IVUS, coronary artery occlusion or sub-occlusion (Thrombolysis In Myocardial Infarction [TIMI] flow grade <II on diagnostic angiography). Left main trunk artery lesions were excluded.
All the patients gave written informed consent for all procedures and our institutional review board approved this research.
Primary PCI and IVUS procedure
Immediately after the angiography, the culprit lesion was crossed with a conventional guidewire. An aspiration catheter was advanced over the guidewire, and the lesion was aspirated. After thrombectomy, intracoronary nitroglycerin (0.1 to 0.2 mg) was administered and TIMI II or III coronary flow was confirmed angiographically. A 20-MHz, 3.2-F phased-array IVUS catheter (Eagle Eye, Volcano Therapeutics) was placed distal to the lesion, and it was pulled back at 0.5 cm/s to the proximal part of the lesion with an auto-motorized pullback system. Stent deployment was performed immediately after IVUS.
The corrected TIMI frame count (CTFC) immediately after stent deployment was estimated in the infarct-related artery as previously reported (5). Assessment for the CTFC was performed separately by 2 independent observers unaware of the IVUS findings. During PCI, heparin sodium was administered to maintain the activated clotting time at 250 to 300 s.
IVUS data analysis
The VH-IVUS data were recorded onto the imaging system hard disk, and analyses were independently performed by experienced analysts who were unaware of the angiographic findings and baseline clinical and lesion characteristics. All measurements were automatically derived from Volcano Invision Gold imaging system software. Lumen and media areas were measured. Plaque area was calculated as the difference between media area and lumen area. The VH-IVUS data analysis was based on gray scale border contour calculation, and the tissue maps were provided by the software (green = fibrous, yellow = fibro-lipid, red = necrotic core, and white = dense calcium). Volumes were automatically determined by the software, a summation of measured cross-sectional areas in all frames of the pullback region based on Simpson’s rule. The individual percentages of plaque components in the total plaque volume were calculated.
Twelve-lead ECGs were continuously recorded during the procedure and assessed before the thrombectomy, just before and immediately after stent deployment. The ST-segment elevation was measured 20 ms after the J point. The ST-segment score was calculated as the sum of ST-segment elevation >0.1 mV for leads V1to V6, I, II, and aVL in anterior infarction and for leads II, III, aVF, V5, and V6in inferior infarction. In true posterior infarction, reciprocal ST-segment depressions >0.1 mV in V1and V2were also included. The ST-segment scores before and after stent deployment were compared to evaluate distal embolization induced by stent deployment. Significant ST-segment re-elevation (STR) was defined as increase in ST-segment score of >2 mm immediately after stent deployment.
Quantitative variables are presented as mean ± SD and categorical variables as percentages. Continuous variables were compared with the Student ttest and categorical data with the Fisher’s exact or chi-square tests, as appropriate. Correlation between total plaque volume and each plaque composition was evaluated by using linear regression models. Receiver-operating characteristic (ROC) analysis was used to determine the optimal cut-off value for each plaque component volume for the prediction of STR after stent deployment. The cut-off point was defined as the greatest sum of the sensitivity and specificity estimates. The area under the ROC curve (AUC) was used as a measure of test accuracy. All statistical analyses were performed with JMP 4.0.5J software (SAS Institute Inc., Cary, North Carolina). All p values <0.05 were considered statistically significant.
Baseline clinical characteristics
The target vessels were the left anterior descending artery (39 cases), left circumflex artery (16 cases), and right coronary artery (16 cases). Primary stenting was successful in all patients. The mean age was 64 ± 12 years. Baseline patient characteristics are shown in Table 1.
A total of 71 coronary lesions underwent VH-IVUS analysis. The mean total plaque volume was 113.0 ± 67.3 mm3. The mean percentages of fibrosis, fibro-lipid, necrotic core, and dense calcium volumes were 63.0 ± 9.1%, 11.5 ± 6.9%, 18.8 ± 8.6%, and 6.6 ± 5.1%, respectively. A strong positive correlation was found between total plaque volume and percentage of dense calcium (r = 0.74, p < 0.0001). A negative correlation between total plaque volume and percentage of fibrosis was found (r = −0.53, p < 0.0001); however, there were no correlations between total plaque volume and percentage of necrotic core or fibro-lipid (Fig. 1).
STR, CTFC, and plaque composition
Mean ST-segment elevation scores were 11.0 ± 9.5 before stent deployment and 9.8 ± 8.6 afterward. An STR immediately after stent deployment was observed in 11 patients (15.5%). The necrotic core volume was significantly higher in the STR group compared with the non-STR group (32.9 ± 14.1 mm3vs. 20.4 ± 19.1 mm3, p = 0.0439). However, there was no difference in total plaque volume, fibrous volume, fibro-lipid volume, and dense calcium volume between the 2 groups. Lesion length, vessel diameter, and lumen diameter also showed no differences between the 2 groups. The CTFC was significantly higher in the STR group than in the non-STR group (37.5 ± 16.6 vs. 21.2 ± 5.8, p < 0.0001). Infarct-related artery showed no differences between the 2 groups (Table 2).The STR group contained a significantly higher number of patients with hyperlipidemia (STR group vs. non-STR group = 81.8% vs. 45.0%, p = 0.0457) and a smaller number of patients with diabetes (STR group vs. non-STR group = 9.1% vs. 41.7%, p = 0.0463). There was no difference in the number of patients with hypertension (STR group vs. non-STR group = 81.8% vs. 68.3%, p = 0.4877), current smoking (STR group vs. non-STR group = 45.5% vs. 56.7%, p = 0.5274), body mass index (STR group vs. non-STR group = 22.9 ± 3.0 kg/m2vs. 23.9 ± 3.4 kg/m2, p = 0.3702), and time from symptoms to PCI (STR group vs. non-STR group = 6.7 ± 2.3 h vs. 5.7 ± 2.7 h, p = 0.2417) between the STR group and the non-STR group.
ROC analysis of plaque composition volume for prediction of STR after stent deployment
We performed ROC analysis of the plaque composition volume (Fig. 2).Necrotic core volume clearly predicted STR after stent deployment compared with fibrous, fibro-lipid, dense calcium, and total plaque volume. The AUC in ROC analysis of necrotic core volume was 0.756 and highest among the analyzed variables. The best cut-off value of necrotic core volume for prediction of STR was 33.4 mm3, with a sensitivity of 81.7% and a specificity of 63.6%. Necrotic core volume >33.4 mm3was observed in 26.8% of all the patients. The VH-IVUS image examples of STR case and non-STR case are shown in Figure 3.
This is the first trial specifically designed to evaluate the efficacy of VH-IVUS in predicting the risk of distal embolization during primary PCI in patients with STEMI. The major novel findings in the present study were as follows: 1) a high necrotic core volume shown by VH-IVUS is predictive of distal embolization as assessed by STR after stent deployment; 2) the best cut-off value of necrotic core volume for prediction of distal embolization was 33.4 mm3, with a sensitivity of 81.7% and a specificity of 63.6%; and 3) total plaque volume was not related to distal embolization after primary stent deployment.
Liberation of plaque debris by iatrogenic plaque disruption is a mechanism of distal embolization during primary PCI (6). An STR during PCI and a higher CTFC are recognized as predictors of the no-reflow phenomenon (5,7). In the no-reflow cases, distal embolization of plaque or thrombus from the lesion site is the likely mechanism (7). On the basis of these findings, we adopted the STR as an index of distal embolization, although STR after stent deployment might be caused by microvascular dysfunction induced by various mechanisms (8–10). However, in this study, stent deployment was performed after thrombectomy and coronary flow (TIMI II or III) was observed before stent deployment in all cases. Therefore, distal embolization of plaque or thrombus from the lesion site induced by stent deployment is the probable cause of STR. In addition, STR after thrombectomy was observed in 13 patients. Of these patients, STR after stent deployment was observed in 1 patient. These data suggest that STR after stent deployment is not attributable to thrombectomy but to stent deployment.
Although some previous studies have shown that the coronary aspiration improves myocardial reperfusion in patients with STEMI (11–13), the issue of mechanical liberation of plaque debris induced by stent deployment remains unresolved. Moreover, it is still unclear which characteristics of the plaque cause distal embolization after stent deployment. Previous studies showed that a greater atherosclerotic plaque burden was correlated with distal embolization in patients with stable or unstable angina pectoris (14,15). In our results, however, total plaque volume was unrelated; moreover, it was found that necrotic core volume was the strong risk factor for distal embolization. This conflicting finding might depend on the differences in plaque characteristics, because acute coronary syndromes are usually caused by rupture or erosion of fibrous caps covering the lipid-rich necrotic cores of vulnerable and usually small-sized plaques (16,17). We demonstrated a correlation between total plaque volume and the percentage of dense calcium (r = 0.74, p < 0.0001) and of fibrosis (r = −0.53, p < 0.0001), although there was no correlation between the percentage of necrotic core and total plaque volume. These findings suggest that even if a small sized plaque is observed after thrombectomy in STEMI, the risk of distal embolization is not low.
Although no difference was observed in dense calcium volume between STR group and non-STR group, no significant difference was observed between AUC for dense calcium volume (0.664) and that for the necrotic core volume (0.756) in the ROC analysis of the plaque component volume and STR (p = 0.4024). In addition, a strong positive correlation (r = 0.81, p < 0.0001) was observed between the necrotic core volume and dense calcium volumes in the present study. These findings might suggest that dense calcium is also concerned in STR after stent deployment. Moreover, because our observations are preliminary, extensive additional validation might be required.
Various embolic protection devices are now available, and visible debris that otherwise would have entered the distal circulation can be removed in patients with STEMI (18). Although routine use of embolic protection devices in patients with STEMI cannot be advocated (18,19), they are expected to be effective in decreasing myocardial damage in selected patients at high risk of distal embolization.
In the present study, the major predictor of distal embolization induced by stent deployment was necrotic core volume determined by VH-IVUS. The best cut-off value was 33.4 mm3, with a sensitivity of 81.7% and a specificity of 63.6%. Embolic protection devices are expected to be effective in these carefully selected STEMI patients with high risk of distal embolization.
Although VH-IVUS has been validated in human coronary arteries (20–23), recent data from a porcine model have shown that VH-IVUS was not accurate in detecting the relative amounts of specific plaque components compared with the corresponding histological specimens (24). Thus, the necrotic core detected by VH-IVUS might not necessarily be a pathological one. However, the aim of this study was to identify the relationship between VH-IVUS data and distal embolization, and no mention is made of pathological plaque composition. Moreover, even though all the patients underwent thrombectomy via an aspiration catheter, the presence of residual thrombus in culprit lesions might have confounded the results for plaque component assessment. A glycoprotein IIb/IIIa inhibitor was not used in the present study, because of its unavailability in our country. In addition, because clopidogrel still has an off-label use for patients with STEMI in our country, none of the patients were given clopidogrel in this study. Lastly, we need to prospectively validate our measurements in another cohort to see how the predictive algorithm correlates with STR.
Virtual Histology IVUS is a useful means of predicting the risk of distal embolization after primary stent deployment in patients with STEMI.
The authors thank Hideki Futamatsu, MD, PhD, for his helpful advice in reviewing this study and the entire staff of the catheterization laboratory in Gunma Prefectural Cardiovascular Center for their enthusiasm during the study.
- Abbreviations and Acronyms
- corrected Thrombolysis In Myocardial Infarction frame count
- intravascular ultrasound
- percutaneous coronary intervention
- receiver-operating characteristic
- ST-segment elevation myocardial infarction
- ST-segment re-elevation
- Thrombolysis In Myocardial Infarction
- Virtual Histology
- Received March 12, 2007.
- Revision received May 29, 2007.
- Accepted June 4, 2007.
- American College of Cardiology Foundation
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