Shigenobu Inami

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.

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

Development of a Novel Prohealing Stent Designed to Deliver Sirolimus From a Biodegradable Abluminal Matrix

Background—We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. Methods and Results—Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 &mgr;g sirolimus/mm] and full-dose sirolimus [Combo, 5 &mgr;g sirolimus/mm). These Combo stents and the Cypher stent (10 &mgr;g sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50% total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience V=8, Cypher=8, Genous bioengineered R stent=6, LD-Combo=14, and Combo=14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173±0.088 mm) compared with Cypher (0.358±0.225 mm), LD-Combo (0.316±0.228 mm), and Xience V (0.305±0.252 mm; P<0.00001). Immunohistochemical analysis of endothelialization showed that Genous bioengineered R stent had the highest degree of platelet endothelial cell adhesion molecule expression (87%) followed by the Combo (75%), LD-Combo (65%), and Cypher (58%). Conclusions—Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation.

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.

Impact of Prediabetic Status on Coronary Atherosclerosis A multivessel angioscopic study

OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself.

Lack of association between large angiographic late loss and low risk of in-stent thrombus: angioscopic comparison between paclitaxel- and sirolimus-eluting stents.

Background— It recently has been hypothesized that a larger late loss may have a protective role against stent thrombosis. The relationship between angiographic late loss and the presence of thrombus based on angioscopic findings within paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) was investigated in this study. Methods and Results— Prospective 6-month follow-up angiographic and angioscopic examinations were performed on 18 patients for PES and on 20 patients for SES. Late loss was measured by quantitative coronary angiography. Angioscopic neointimal stent coverage (NSC) grade was classified as follows: 0=uncovered struts without neointima, 1=visible struts through thin neointima, and 2=no visible struts. In each patient, maximum NSC, minimum NSC, and the existence of thrombus were evaluated. Late loss and maximum NSC were greater in PES than in SES (0.38±0.43 versus 0.10±0.23 mm; P =0.02 and P =0.0004, respectively). Late loss was correlated with maximum NSC (grade 0, 0.06±0.01 mm; grade 1, 0.10±0.05 mm; and grade 2, 0.48±0.46 mm), whereas there was no correlation between late loss and minimum NSC. The prevalence of patients with uncovered struts did not differ (44% of PES, 40% of SES; P =0.78). In-stent thrombus was found more frequently in PES than in SES (72% versus 40%, P =0.046) despite no occurrence of stent thrombosis. Only within PES were thrombi found in the segments of NSC grade 2 associated with large late loss. Conclusion— The present study suggests that angiographic large late loss was not associated with a low risk of in-stent thrombus. Received January 27, 2008; accepted May 30, 2008. # CLINICAL PERSPECTIVE {#article-title-2}Background—It recently has been hypothesized that a larger late loss may have a protective role against stent thrombosis. The relationship between angiographic late loss and the presence of thrombus based on angioscopic findings within paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) was investigated in this study. Methods and Results—Prospective 6-month follow-up angiographic and angioscopic examinations were performed on 18 patients for PES and on 20 patients for SES. Late loss was measured by quantitative coronary angiography. Angioscopic neointimal stent coverage (NSC) grade was classified as follows: 0=uncovered struts without neointima, 1=visible struts through thin neointima, and 2=no visible struts. In each patient, maximum NSC, minimum NSC, and the existence of thrombus were evaluated. Late loss and maximum NSC were greater in PES than in SES (0.38±0.43 versus 0.10±0.23 mm; P=0.02 and P=0.0004, respectively). Late loss was correlated with maximum NSC (grade 0, 0.06±0.01 mm; grade 1, 0.10±0.05 mm; and grade 2, 0.48±0.46 mm), whereas there was no correlation between late loss and minimum NSC. The prevalence of patients with uncovered struts did not differ (44% of PES, 40% of SES; P=0.78). In-stent thrombus was found more frequently in PES than in SES (72% versus 40%, P=0.046) despite no occurrence of stent thrombosis. Only within PES were thrombi found in the segments of NSC grade 2 associated with large late loss. Conclusion—The present study suggests that angiographic large late loss was not associated with a low risk of in-stent thrombus.

Relationship between neointimal coverage of sirolimus-eluting stents and lesion characteristics: A study with serial coronary angioscopy

BACKGROUND Delayed neointimal coverage after the implantation of a drug-eluting stent (DES) is thought to be related to their potential for developing late-stent thrombosis. However, few studies have shown which factor affects the neointimal coverage after DES implantation. We hypothesized that the extent of neointimal coverage after DES implantation is affected by the underlying lesion characteristics because arterial wall components are reported to determine the transport and distribution of the drugs. METHODS Thirty-seven coronary artery lesions treated with a single sirolimus-eluting stent (SES) were evaluated in 37 patients with stable coronary artery disease. Angioscopy was performed before, immediately after, and 6 months after stenting to examine the existence of yellow plaque, thrombus, complex plaque, and intramural hemorrhage and the degree of neointimal coverage at 6-month follow-up. This was classified either as a noncoverage group (stent struts were predominantly exposed or visible through a thin neointima) or as a coverage group (stent struts were predominantly covered by neointimal hyperplasia and thus invisible). RESULTS Twenty-one lesions were classified into the noncoverage group, and 16 lesions the coverage group. The frequency of preexistent yellow plaques was significantly higher in the noncoverage group than that in the coverage group (67% vs 19%, P = .007). A multivariate logistic regression analysis showed the preexistence of yellow plaque was the only independent factor behind less neointimal coverage at 6 months after SES implantation (odds ratio 19.5, 95% confidence interval 1.58-240.50, P = .020). CONCLUSIONS The preexistence of yellow plaque may be associated with decreased neointimal coverage of SES.