Masamichi Takano

Appearance of Lipid-Laden Intima and Neovascularization After Implantation of Bare-Metal Stents: Extended Late-Phase Observation by Intracoronary Optical Coherence Tomography

OBJECTIVES We examined the neointimal characteristics of bare-metal stents (BMS) in extended late phase by the use of optical coherence tomography (OCT). BACKGROUND The long-term neointimal features after BMS implantation have not yet been fully characterized. METHODS Intracoronary OCT observation of BMS segments was performed during the early phase (<6 months, n = 20) and late phase (>or=5 years, n = 21) after implantation. Internal tissue of the BMS was categorized into normal neointima, characterized by a signal-rich band without signal attenuation, or lipid-leaden intima, with marked signal attenuation and a diffuse border. In addition, the presence of disrupted intima and thrombus was evaluated. Neovascularization was defined as small vesicular or tubular structures, and the location of the microvessels was classified into peristent or intraintima. RESULTS Normal neointima proliferated homogeneously, and lipid-laden intima was not observed in the early phase. In the late phase, lipid-laden intima, intimal disruption, and thrombus frequently were found in comparison with the early phase (67% vs. 0%, 38% vs. 0%, and 52% vs. 5%, respectively; p < 0.05). Persistent neovascularization demonstrated a similar incidence between the 2 phases. The appearance of intraintima neovascularization was more prevalent in the late phase than the early phase (62% vs. 0%, respectively; p < 0.01) and in segments with lipid-laden intima than in nonlipidic segments (79% vs. 29%, respectively; p = 0.026). CONCLUSIONS This OCT study suggests that neointima within the BMS often transforms into lipid-laden tissue during an extended period of time and that expansion of neovascularization from peristent to intraintima contributes to atherosclerotic progression of neointima.

Safety and Feasibility of an Intravascular Optical Coherence Tomography Image Wire System in the Clinical Setting

Optical coherence tomography (OCT) is a fiber-optic technology that enables high-resolution intracoronary imaging. The aim of this study was to evaluate the safety and feasibility of intracoronary imaging with OCT in the clinical setting; 76 patients with coronary artery disease from 8 centers were enrolled. The OCT imaging system (ImageWire, Light Imaging Inc., Westford, Massachusetts) consists of a 0.006 inch fiber-optic core that rotates within a 0.016 inch transparent sheath. OCT imaging was performed during occlusion of the artery with a compliant balloon and continuous flushing. Intravascular ultrasound (IVUS) imaging was performed in the same segments. We assessed the safety and feasibility of the OCT imaging, compared with IVUS. Vessel occlusion time was 48.3 +/- 13.5 seconds and occlusion-balloon pressure was 0.4 +/- 0.1 atmospheres. Flushing with lactated Ringers solution was performed at a rate of 0.6 +/- 0.4 ml/s. No significant adverse events, including vessel dissection or fatal arrhythmia, were observed. Procedural success rates were 97.3% by OCT and 94.5% by IVUS. The OCT image wire was able to cross 5 of 6 tight lesions that the IVUS catheter was unable to cross. Of the 98 lesions in which both OCT and IVUS were successfully performed, OCT imaging had an advantage over IVUS for visualization of the lumen border. Minimum lumen diameter and area measurements were significantly correlated between OCT and IVUS imaging (r = 0.91, p <0.0001 and r = 0.95, p <0.0001, respectively). In conclusion, this multicenter study demonstrates the safety and feasibility of OCT imaging in the clinical setting.

Changes in coronary plaque color and morphology by lipid-lowering therapy with atorvastatin: serial evaluation by coronary angioscopy

OBJECTIVES Changes in coronary plaque color and morphology by statin therapy were evaluated using coronary angioscopy. BACKGROUND Coronary plaque stabilization by statin therapy has not been clarified in humans. METHODS Thirty-one patients with coronary artery disease were divided into either the comparison group (n = 16) or the atorvastatin group (n = 15). Before treatment and 12 months after, the color and complexity of 145 coronary plaques were determined according to angioscopic findings. The yellow score of the plaque was defined as 0 (white), 1 (light yellow), 2 (yellow), or 3 (dark yellow), and its disrupted score was defined as 0 (smooth surface) or 1 (irregular surface) and as 0 (without thrombus) or 1 (with thrombus). In each patient, the mean yellow score and mean disrupted score were calculated. RESULTS Mean low-density lipoprotein cholesterol (LDL-C) decreased by 45% in the atorvastatin group, whereas an increase of 9% was seen in the comparison group. The mean yellow score decreased from 2.03 to 1.13 in the atorvastatin group, whereas it increased from 1.67 to 1.99 in the comparison group. There was a good correlation between the change in the mean yellow score and the change in LDL-C levels (r = 0.81, p < 0.0001). The change in the mean yellow score and mean disrupted score differed significantly between the two groups (p = 0.002 and p = 0.03, respectively). CONCLUSIONS This is the first report clarifying detailed changes in coronary plaque by statin in humans. This study indicated that lipid-lowering therapy changes plaque color and morphology and should then lead to coronary plaque stabilization.

Elevated Troponin T Levels and Lesion Characteristics in Non–ST-Elevation Acute Coronary Syndromes

Background—Elevated troponin T levels in non–ST-elevation acute coronary syndromes (NSTE-ACS) have been shown to predict an adverse outcome. Furthermore, it has been reported that troponin T could help improve the effectiveness of such new antithrombotic drugs as platelet GPIIb/IIIa antagonists and low-molecular-weight heparins. We hypothesized that such elevated troponin T levels in NSTE-ACS indicate the presence of thrombus at culprit lesions, and this hypothesis was verified through the use of coronary angioscopy. Methods and Results—We studied 57 consecutive patients with NSTE-ACS who underwent preinterventional angioscopy. Before catheterization, we obtained blood samples to determine troponin positivity, and the patients were then classified as either troponin-positive or troponin-negative groups (diagnostic threshold, 0.1 ng/mL). Using angioscopy at the culprit lesions, we examined the presence of coronary thrombus, yellow plaque, and complex plaque. Moreover, we compared the preinterventional angiographic parameters (thrombus and complexity of the culprit lesion, and TIMI flow) between the two groups. Twenty-two patients were troponin-positive and 35 patients were troponin-negative. Univariate analyses indicated that the TIMI flow and the incidence of coronary thrombus detected with angioscopy correlate with the elevated troponin T levels. A multivariate logistic regression analysis showed the presence of coronary thrombus detected with angioscopy to be the only independent factor associated with elevated troponin T levels in patients with NSTE-ACS (odds ratio, 22.1; 95% CI, 2.59 to 188.42; P =0.0046). Conclusions—Using angioscopy, the elevated troponin T levels in NSTE-ACS were confirmed to be strongly associated with the presence of coronary thrombus.

In Vivo Comparison of Optical Coherence Tomography and Angioscopy for the Evaluation of Coronary Plaque Characteristics

Atherosclerotic yellow plaques identified by coronary angioscopy are considered as vulnerable plaques. However, characteristics of yellow plaques are not well understood. Optical coherence tomography (OCT) provides accurate tissue characterization in vivo and has the capability to measure fibrous cap thickness covering a lipid plaque. Characteristics of yellow plaques identified by angioscopy were evaluated by OCT. We examined 205 plaques of 41 coronary arteries in 26 patients. In OCT analysis, plaques were classified as fibrous or lipid. Minimal lumen area of the plaque, arch of the lipid, and fibrous cap thickness on the lipid plaque were measured. Yellow grade of the plaque was defined as 0 (white), 1 (light yellow), 2 (medium yellow), or 3 (dark yellow) based on the angioscopy. A total of 149 plaques were diagnosed as lipid plaques. Neither the minimal lumen area nor the arch of the lipid was related to the yellow grade. There was an inverse relationship between color grade and the fibrous cap thickness (grade 0 [n = 45] 218 +/- 89 microm, grade 1 [n = 40] 101 +/- 8 microm, grade 2 [n = 46] 72 +/- 10 microm, and grade 3 [n = 18] 40 +/- 14 microm; p <0.05). Sensitivity and specificity of the angioscopy-identified yellow plaque for having a thin fibrous cap (thickness <or=110 microm) were 98% and 96%, respectively. In conclusion, angioscopy-identified yellow plaques frequently were lipid tissue with an overlying thin fibrous cap. Fibrous caps of the intense yellow plaques were very thin, and these plaques might be structurally vulnerable.

Long-Term Follow-Up Evaluation After Sirolimus-Eluting Stent Implantation by Optical Coherence Tomography: Do Uncovered Struts Persist?

To the Editor: Presently, occurrence of late stent thrombosis (LST) after drug-eluting stent implantation is a major clinical concern. Although LST is an infrequent complication, LST can lead to serious results. A long-term follow-up study revealed recently that LST occurs at a constant rate of 0.6

Comparison of neointimal coverage by optical coherence tomography of a sirolimus-eluting stent versus a bare-metal stent three months after implantation.

No detailed data regarding neointimal coverage of bare-metal stents (BMSs) at 3 months after implantation was reported to date. This investigation was designed to evaluate the neointimal coverage of BMSs compared with sirolimus-eluting stents (SESs) using optical coherence tomography. A prospective optical coherence tomographic follow-up examination was performed 3 months after stent implantation for patients who underwent BMS (n = 16) or SES implantation (n = 24). Neointimal hyperplasia (NIH) thickness on each stent strut and percentage of NIH area in each cross section were measured. Malapposition of stent struts to the vessel wall and the existence of in-stent thrombi were also evaluated. There were 5,076 struts of SESs and 2,875 struts of BMSs identified. NIH thickness and percentage of NIH area in the BMS group were higher than in the SES group (351 +/- 248 vs 31 +/- 39 mum; p <0.0001; 45.0 +/- 14% vs 10.0 +/- 4%; p <0.0001, respectively). The frequency of uncovered struts was higher in the SES group than the BMS group (15% vs 0.1%; p <0.0001). Malapposed struts were observed more frequently in the SES group than the BMS group (15% vs 1.1%; p <0.0001). In conclusion, there was no difference in incidence of in-stent thrombus between the 2 groups (14% vs 0%; p = 0.23). The present study showed almost all BMS struts to be well covered at a 3-month follow-up, suggesting that patients receiving BMS stents may not require dual-antiplatelet therapy >3 months after implantation.

Serial long-term evaluation of neointimal stent coverage and thrombus after sirolimus-eluting stent implantation by use of coronary angioscopy

Objective: Progression of neointimal stent coverage (NSC) and changes in thrombus were evaluated serially by coronary angioscopy for up to 2 years after sirolimus-eluting stent (SES) implantation. Methods: Serial angioscopic observations were performed in 20 segments of 20 patients at baseline, at 6 months and at 2 years after SES implantation. NSC was classified as follows: 0, uncovered struts; 1, visible struts through thin neointima; or 2, no visible struts. In each patient, maximum and minimum NSC was evaluated. Existence of thrombus was also examined. Results: The maximum NSC increased from 6 months to 2 years (mean (SD) 1.2 (0.4) vs 1.8 (0.4), respectively, p = 0.005), while the minimum NSC did not change (0.7 (0.5) vs 0.8 (0.4), respectively, p = 0.25). The prevalence of patients with uncovered struts did not decrease from 6 months to 2 years (35% vs 20%, respectively, p = 0.29). Although there were no thrombus-related adverse events, new thrombus formation was found in 5% of 6-month, and in 20% of 2-year follow-up evaluations. The prevalence of thrombus inside the SES at baseline, 6 months and 2 years was similar (40%, 40% and 30%, respectively; p = NS). Conclusions: Neointimal growth inside the SES progressed heterogeneously. Uncovered struts persisted in 20% of the patients for up to 2 years and subclinical thrombus formation was not uncommon.

Extended Follow-Up by Serial Angioscopic Observation for Bare-Metal Stents in Native Coronary Arteries: From Healing Response to Atherosclerotic Transformation of Neointima

Background— Although coronary angiograms after bare-metal stent (BMS) implantation show late luminal narrowing beyond 4 years, the detailed changes inside the BMS have not yet been fully elucidated. Methods and Results— Serial angiographic and angioscopic examinations were performed immediately (baseline), 6 to 12 months (first follow-up), and ≥4 years (second follow-up) after stenting without target lesion revascularization in 26 segments of 26 patients who received BMS deployment for their native coronary arteries. Angioscopic observation showed atherosclerotic yellow plaque crushed out by stent struts in 22 patients (85%) and mural thrombus in 21 patients (81%) at baseline. At first follow-up, white neointimal hyperplasia was almost completely buried inside the struts, and both yellow plaque and thrombus had decreased in comparison with baseline (12% and 4%, respectively; P <0.001). The frequencies of yellow plaque and thrombus increased from the first to second follow-ups (58% and 31%, respectively; P <0.05). All of the yellow plaques in the second follow-up were located not exterior to the struts but protruding from the vessel wall into the lumen. Late luminal narrowing, defined as an increasing of percent diameter stenosis between the first and second follow-ups, was greater in segments with yellow plaque than in those without yellow plaque (18.4±17.3% versus 3.6±4.2%, respectively; P =0.011). Conclusions— This angiographic and angioscopic study suggests that white neointima of the BMS may often change into yellow plaque over an extended period of time, and atherosclerotic progression inside the BMS may contribute to late luminal narrowing. Received January 29, 2009; accepted April 15, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Although coronary angiograms after bare-metal stent (BMS) implantation show late luminal narrowing beyond 4 years, the detailed changes inside the BMS have not yet been fully elucidated. Methods and Results—Serial angiographic and angioscopic examinations were performed immediately (baseline), 6 to 12 months (first follow-up), and ≥4 years (second follow-up) after stenting without target lesion revascularization in 26 segments of 26 patients who received BMS deployment for their native coronary arteries. Angioscopic observation showed atherosclerotic yellow plaque crushed out by stent struts in 22 patients (85%) and mural thrombus in 21 patients (81%) at baseline. At first follow-up, white neointimal hyperplasia was almost completely buried inside the struts, and both yellow plaque and thrombus had decreased in comparison with baseline (12% and 4%, respectively; P<0.001). The frequencies of yellow plaque and thrombus increased from the first to second follow-ups (58% and 31%, respectively; P<0.05). All of the yellow plaques in the second follow-up were located not exterior to the struts but protruding from the vessel wall into the lumen. Late luminal narrowing, defined as an increasing of percent diameter stenosis between the first and second follow-ups, was greater in segments with yellow plaque than in those without yellow plaque (18.4±17.3% versus 3.6±4.2%, respectively; P=0.011). Conclusions—This angiographic and angioscopic study suggests that white neointima of the BMS may often change into yellow plaque over an extended period of time, and atherosclerotic progression inside the BMS may contribute to late luminal narrowing.

Late Vascular Responses From 2 to 4 Years After Implantation of Sirolimus-Eluting Stents: Serial Observations by Intracoronary Optical Coherence Tomography

Background—Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings. Methods and Results—Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 &mgr;m versus 123.0±102.5 &mgr;m; P<0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P=0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P=1.0), the cross sections with ESL increased (9.6% versus 15.2%; P=0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm2 versus 0.62±0.68 mm2 and 16.6±5.4° versus 65.1±38.4°; P<0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P=1.0). All thrombi were identified in patients who had cross sections with ESL. Conclusions—The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.Background— Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings. Methods and Results— Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 μm versus 123.0±102.5 μm; P <0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P =0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P =1.0), the cross sections with ESL increased (9.6% versus 15.2%; P =0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm2 versus 0.62±0.68 mm2 and 16.6±5.4° versus 65.1±38.4°; P <0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P =1.0). All thrombi were identified in patients who had cross sections with ESL. Conclusions— The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.