Ki-Hoon Han

Late stent malapposition after drug-eluting stent implantation: an intravascular ultrasound analysis with long-term follow-up.

Background— Late stent malapposition (LSM) after drug-eluting stent (DES) implantation has not been evaluated sufficiently in real-world practice. Methods and Results— We evaluated the incidence, mechanisms, predictors, and long-term prognosis of LSM after DES implantation in 557 patients (705 native lesions; sirolimus-eluting stent in 538 lesions and paclitaxel-eluting stent in 167 lesions) in whom intravascular ultrasound was performed at index and 6-month follow-up. LSM occurred in 82 patients with 85 lesions (12.1% overall, 95% CI 9.7% to 14.5%, 71 lesions (13.2%) in sirolimus-eluting stents and 14 lesions [8.4%] in paclitaxel-eluting stents, P=0.12]; the incidence was 25.0% (4/16) after directional coronary atherectomy before stenting, 27.5% (14/51) in chronic total occlusion lesions, and 31.8% (7/22) after primary stenting in acute myocardial infarction (P=0.13, P<0.001, and P=0.001, respectively, versus elective stenting with conventional balloon predilation, 9.7% [60/616]). There was an increase of external elastic membrane area (from 17.1±3.6 to 21.4±4.8 mm2, P<0.001) that was greater than the increase in plaque area (from 9.3±2.5 to 10.5±2.7 mm2, P<0.001). Independent predictors of LSM were total stent length, primary stenting in acute myocardial infarction, and chronic total occlusion lesions. Except for 1 death in the non-LSM group, there were no major adverse cardiac events in either LSM or non-LSM patients during a mean 10-month follow-up after detection of LSM. Conclusions— LSM occurs in 12% of cases after DES implantation. The predictors of LSM are total stent length, primary stenting in acute myocardial infarction, and chronic total occlusion lesions. LSM after DES implantation was not associated with any major adverse cardiac events during a subsequent 10-month (mean) follow-up.

Paclitaxel Coating Reduces In-Stent Intimal Hyperplasia in Human Coronary Arteries A Serial Volumetric Intravascular Ultrasound Analysis From the ASian Paclitaxel-Eluting Stent Clinical Trial (ASPECT)

Background—The aim of this study was to use serial volumetric intravascular ultrasound (IVUS) to evaluate the effect of a paclitaxel coating on in-stent intimal hyperplasia (IH). Methods and Results—Patients were randomized to placebo (bare metal stents) or 1 of 2 doses of paclitaxel (low dose: 1.28 &mgr;g/mm2; high dose: 3.10 &mgr;g/mm2). Complete post-stent implantation and follow-up IVUS were available in 81 patients, including 25 control patients and in 28 receiving a low-dose and 28 receiving a high dose. Volumetric analysis of the stented segment and of both reference segments was performed. Baseline stent measurements and both reference measurements were similar among the groups. With increasing doses, there was a stepwise reduction in IH accumulation within the stented segment (31±22 mm3 in control, 18±15 mm3 in low dose, and 13±14 mm3 in high dose, P <0.001). Post hoc analysis showed less IH accumulation when low- and high-dose patients were compared with control (P =0.009 and P <0.001, respectively), but not when low-dose patients were compared with high-dose patients (P =0.2). Focal late malapposition was seen in 1 high-dose patient. With increasing doses, there was no significant change in the reference segments. Conclusions—Paclitaxel-coated stents are effective in reducing in-stent neointimal tissue proliferation in humans. They are not associated with edge restenosis or significant late malapposition.

Incidence, mechanism, predictors, and long-term prognosis of late stent malapposition after bare-metal stent implantation.

Background—Predictors and long-term prognosis of late stent malapposition (LSM) after bare-metal stent (BMS) implantation are unknown. Methods and Results—We evaluated the incidence, mechanisms, predictors, and long-term prognosis of LSM after BMS implantation in 881 patients (992 native lesions) in whom intravascular ultrasound was performed at index and 6-month follow-up. LSM was defined as a separation of stent struts from the intimal surface of the arterial wall that was not presented at stent implantation. LSM occurred in 54 patients with 54 lesions (5.4% overall); the incidence was 10.3% (9 of 87) after directional coronary atherectomy (DCA) before stenting and 11.5% (11 of 96) after primary stenting in acute myocardial infarction (P =0.031 and P =0.007, respectively, versus elective stenting with conventional balloon pre-dilation, 4.3% [30 of 692]). There was an increase of external elastic membrane area (18.9±3.9 to 24.5±5.1 mm2, P <0.001) that was greater than the increase in plaque area (9.6±3.0 to 11.4±2.9 mm2, P <0.001). Independent predictors of LSM were primary stenting in acute myocardial infarction (P =0.023, OR=2.55, 95% CI=1.14 to 5.69) and DCA before stenting (P =0.025, OR=3.02, 95% CI=1.15 to 7.96). There were no significant differences in major adverse cardiac events between LSM and non-LSM groups during mean 3-year follow-up (1.9% versus 1.8%, respectively, P =NS). Conclusions—LSM occurs in ≈5% after BMS implantation. The predictors of LSM are primary stenting in acute myocardial infarction and DCA before stenting. Compared with complete stent apposition at follow-up, LSM after BMS implantation is not associated with any major adverse cardiac events during a mean 3-year follow-up after detection of LSM.

Tissue Characterization of In-Stent Neointima Using Intravascular Ultrasound Radiofrequency Data Analysis

Using virtual histology and intravascular ultrasound (VH-IVUS), tissue characterization of restenotic in-stent neointima after drug-eluting stent (DES) and bare metal stent (BMS) implantation was assessed. VH-IVUS was performed in 117 lesions (70 treated with DESs and 47 treated with BMSs) with angiographic in-stent restenosis and intimal hyperplasia (IH) > 50% of the stent area. The region of interest was placed between the luminal border and the inner border of the struts and tissue composition was reported as percentages of IH area (percent fibrous, percent fibrofatty, percent necrotic core, percent dense calcium) at the 2 sites of maximal percent IH and maximal percent necrotic core. Mean follow-up times between stent implantation and VH-IVUS study were 43.5 ± 33.8 months for BMS-treated lesions and 11.1 ± 7.8 months for DES-treated lesions (p < 0.001). The 2 groups had greater percent necrotic core and percent dense calcium at maximal percent IH and maximal percent necrotic core sites, especially in stents that had been implanted for longer periods. In conclusion, this VH-IVUS analysis showed that BMS- and DES-treated lesions develop in-stent necrotic core and dense calcium, suggesting the development of in-stent neoatherosclerosis.

Effect of intravascular ultrasound findings on long-term repeat revascularization in patients undergoing drug-eluting stent implantation for severe unprotected left main bifurcation narrowing.

We studied the effect of the preprocedural intravascular ultrasound findings on stent expansion and the pre- and postprocedural findings on the long-term clinical outcomes in patients undergoing drug-eluting stent implantation for unprotected left main (LM) bifurcation disease. Using a left anterior descending (LAD) pullback, we evaluated the ostial LAD artery (3 mm distal to the carina), the polygon of confluence (POC; the confluent zone of the LAD artery and left circumflex artery), and the distal LM artery (3 mm just proximal to the POC). The measurements included the minimum lumen area (MLA) and minimum stent area within each segment. In 168 LM bifurcations, the preprocedural MLA and post-stenting minimum stent area within the LM artery were located within the POC in 41% and 70%, respectively. Independent predictors for the post-stent minimum stent area within the distal portion of LM artery above the LAD carina were the preprocedural lumen area of the LAD carina (β = 0.253, 95% confidence interval [CI] 0.10 to 0.36, p = 0.001) and preprocedural MLA within the POC (β = 0.205, 95% CI 0.04 to 0.23, p = 0.008). During the 41.8 ± 18.0-month follow-up period, 26 patients experienced cardiac events. In the multivariate Cox model, female gender (adjusted hazard ratio 2.56, 95% CI 1.173 to 5.594, p = 0.018) and preprocedural MLA within the POC (adjusted hazard ratio 0.829, 95% CI 0.708 to 0.971, p = 0.020) were independent predictors for the occurrence of events at 3 years of follow-up. In conclusion, as assessed by the LAD pullback, the preprocedural MLA within the POC was a surrogate reflecting the overall severity of LM bifurcation disease, contributed to the post-stent minimum stent area within the distal segment of LM bifurcation, and was a predictor of clinical events during follow-up.

Long-Term Vascular Changes After Drug-Eluting Stent Implantation Assessed by Serial Volumetric Intravascular Ultrasound Analysis

Using serial volumetric intravascular ultrasonography, we evaluated the predictors of late intimal hyperplasia (IH) increases after drug-eluting stent implantation. All eligible patients who underwent 6-month angiography without visual restenosis were requested to undergo a 2-year follow-up examination. Complete serial (after stenting and early [6-month], and late [2-year] follow-up) angiographic and intravascular ultrasound data were available for 135 patients with 143 lesions: 99 sirolimus-eluting stents and 44 paclitaxel-eluting stents. The external elastic membrane, stent, lumen, and peri-stent plaque volumes (external elastic membrane minus stent) were normalized by stent length. The percentage of IH volume was calculated as IH volume/stent volume x 100. The early reduction in the minimum lumen area was greater than the late reduction in the minimum lumen area (-0.8 +/- 0.8 vs -0.2 +/- 0.5 mm(2), p <0.001). A progressive increase occurred in the percentage of IH volume: 8.1 +/- 7.1% from baseline to 6 months and 2.4 +/- 3.9% from 6 months to 2 years (p <0.001, between the early and late increases in the percentage of IH). The use of paclitaxel-eluting stents was the only independent predictor for the percentage of IH volume at 6 months (beta = 0.419, p <0.001). The use of paclitaxel-eluting stents (beta = 0.365, p <0.001, 95% confidence interval 3.7 to 9.7) and the post-stenting normalized plaque and media volume (beta = 0.195, p = 0.020, 95% confidence interval 0.1 to 1.6) were the only independent predictors for the percentage of IH volume at 2 years. However, when the percentage of IH at 6 months was forced into the model, the percentage of IH at 6 months and the post-stenting normalized plaque and media volume, not paclitaxel-eluting stent use, predicted the 2-year percentage of IH. In conclusion, although IH continued to increase beyond 6 months, the growth rate of intima and luminal loss attenuated with time.

Late and Very Late Drug-Eluting Stent Malapposition Serial 2-Year Quantitative IVUS Analysis

Background—The long-term natural history of acquired malapposition continues to be the subject of debate. Methods and Results—Using volumetric intravascular ultrasound analyses, we evaluated serial (poststenting, 6-month, and 2-year follow-up) changes in drug-eluting stent–treated vascular segments with acquired malapposition. External elastic membrane, stent, lumen, malapposition, and peristent plaque+media (P+M=external elastic membrane −stent− malapposition) areas were measured; and volumes were calculated and divided by stent length (normalized volume). Among 250 lesions in which complete serial intravascular ultrasound data were available, stent malapposition was identified in 19 lesions (7.6%) at 6 months, and an additional 13 malapposition lesions were newly detected at 2 years (5.2%). Because no malapposition sites resolved, the malapposition rate at 2 years was 12.8%. Malapposition areas and volumes were correlated to the increases in external elastic membrane (positive remodeling) throughout the study period, from immediately after stenting to 6 months and from 6 months to 2 years, both in the group that developed malapposition at 6 months and in the group that developed malapposition at 2 years. Clinical follow-up beyond the 2 year intravascular ultrasound study was done in all patients. Overall, there were 2 cardiac deaths and 1 noncardiac death. Two patients presented with acute myocardial infarction associated with very late stent thrombosis (1 definite stent thrombosis, 1 probable stent thrombosis). Three patients underwent repeat revascularization owing to in-stent restenosis developed after the 2-year follow-up. Conclusions—Expansive vascular remodeling may play a role in the development and dynamic progression of acquired drug-eluting stent malapposition, not only during the first 6 months after implantation but thereafter.Background— The long-term natural history of acquired malapposition continues to be the subject of debate. Methods and Results— Using volumetric intravascular ultrasound analyses, we evaluated serial (poststenting, 6-month, and 2-year follow-up) changes in drug-eluting stent–treated vascular segments with acquired malapposition. External elastic membrane, stent, lumen, malapposition, and peristent plaque+media (P+M=external elastic membrane −stent− malapposition) areas were measured; and volumes were calculated and divided by stent length (normalized volume). Among 250 lesions in which complete serial intravascular ultrasound data were available, stent malapposition was identified in 19 lesions (7.6%) at 6 months, and an additional 13 malapposition lesions were newly detected at 2 years (5.2%). Because no malapposition sites resolved, the malapposition rate at 2 years was 12.8%. Malapposition areas and volumes were correlated to the increases in external elastic membrane (positive remodeling) throughout the study period, from immediately after stenting to 6 months and from 6 months to 2 years, both in the group that developed malapposition at 6 months and in the group that developed malapposition at 2 years. Clinical follow-up beyond the 2 year intravascular ultrasound study was done in all patients. Overall, there were 2 cardiac deaths and 1 noncardiac death. Two patients presented with acute myocardial infarction associated with very late stent thrombosis (1 definite stent thrombosis, 1 probable stent thrombosis). Three patients underwent repeat revascularization owing to in-stent restenosis developed after the 2-year follow-up. Conclusions— Expansive vascular remodeling may play a role in the development and dynamic progression of acquired drug-eluting stent malapposition, not only during the first 6 months after implantation but thereafter.

Two-Year Follow-Up Intravascular Ultrasound Analysis After Bare Metal Stent Implantation in 120 Lesions

The objective of this study was to examine long‐term changes after bare metal stent implantation in a relatively large number of patients. There are few reports of intravascular ultrasound (IVUS) studies performed on stented and nonstented (reference) segments beyond 6 months after bare metal stenting. Using IVUS, we evaluated serial changes in stented and reference segments between 6 and 24 months after stent implantation in 110 patients with 120 lesions. Serial IVUS images were acquired at five equidistant intrastent sites and at two different reference segment sites. Measurements were made of the external elastic membrane (EEM), stent, lumen, and intimal hyperplasia (IH = stent − lumen) area. For the whole patient group, between 6 and 24 months, the mean IH area in stented segments decreased from 2.6 ± 1.0 to 2.3 36± 0.9 mm2 (P < 0.001), and the mean lumen area increased from 6.2 ± 2.0 to 6.5 ± 1.9 mm2 (P < 0.001). The mean IH area decreased in 91 lesions (76%) and increased in 29 lesions (24%) between 6 and 24 months. There were no significant changes in EEM or lumen area in the reference segments. Late angiographic restenosis (diameter stenosis ≥ 50%) occurred in three lesions between 6 and 24 months. A late target lesion revascularization was performed for one lesion. In the period of time between 6 and 24 months after stenting, IH regression occurred in most (76%) stent lesions, resulting in late lumen increase. However, IH progression was observed in 24% of in‐stent lesions. No significant changes of EEM or lumen area occurred in the reference segments.

Late Intravascular Ultrasound Findings of Patients Treated With Brachytherapy for Diffuse In-Stent Restenosis

This study aimed at evaluating long‐term (24‐month) effects of β‐irradiation (188Re‐MAG3‐filled balloon) using intravascular ultrasound (IVUS) in patients with in‐stent restenosis (ISR). Long‐term effects of β‐irradiation on intimal hyperplasia (IH) within the stented segment and vessel and lumen dimensions of nonstented adjacent segments in patients with ISR have not been sufficiently evaluated. Two‐year follow‐up IVUS was performed in 30 patients with patent ISR segments at 6‐month follow‐up angiography. Serial IVUS images were acquired at five equidistant intrastent sites and at three different reference segment sites. IH burden (%) was defined as 100 × (IH/stent area). Mean intrastent IH area and IH burden significantly increased between 6 and 24 months, from 2.1 ± 1.1 to 2.6 ± 1.4 mm2 (P < 0.001) and from 26% ± 10% to 33% ± 14% (P < 0.001), respectively. There was a significant decrease of mean external elastic membrane (from 10.1 ± 3.9 to 9.7 ± 3.9 mm2; P = 0.015) and lumen area (from 5.6 ± 2.3 to 5.1 ± 2.3 mm2; P = 0.021) within distal reference segments between 6 and 24 months. Target lesion revascularization (TLR) was performed in six patients (20%) between 6 and 24 months after β‐irradiation therapy. There were no significant differences between TLR and non‐TLR groups except for a smaller minimum lumen area at 24 months in the TLR group. Because of a small amount of late loss between 6 and 24 months, most irradiated ISR vessel segments remained stable for up to 2 years. However, quantitative evidence of late catch‐up was evident in most patients and was significantly associated with 24‐month TLR in some patients. Catheter Cardiovasc Interv 2004;63:208–214.