Drug-eluting stent thrombosis.

When compared to bare metal stents (BMS), drug-eluting stents (DES) are associated with a dramatic reduction in restenosis and target lesion revascularization. However, the benefit of DES is limited to restenosis, and DES utilization does not translate into reductions in death or myocardial infarction. Additionally, concern exists regarding the long-term safety of DES, as there appears to be a small but real increase in late (LST) and very late stent thrombosis (VLST), seen particularly after the discontinuation of antiplatelet therapy. The specter of LST and VLST has curtailed enthusiasm for widespread DES utilization mandating critical appraisal of DES and the optimal role they play in percutaneous coronary intervention. The incidence of DES thrombosis is debated and varies somewhat by definition. The mechanisms are multifactorial, and involve patient, lesion, stent and physician related factors. Some of these factors are modifiable at the physician-patient level, while others are not. This review focuses on DES thrombosis, with particular attention paid to the definitions, incidence, mechanisms and clinical implications.

Mechanism of lumen enlargement during intracoronary stent implantation: an intravascular ultrasound study.

BACKGROUND: Intravascular ultrasound analysis has assessed mechanisms of lumen enlargement after nonstent interventions, but not after stenting. METHODS AND RESULTS: Preintervention and postintervention intravascular ultrasound was used to study 25 de novo native coronary lesions treated with single MultiLink stents without preatheroablation. External elastic membrane, lumen, and plaque and media (P&M) areas were measured every 1 mm to include the lesion and reference segments that were 5 mm proximal and distal to it. Lesion mean lumen area increased from 4.0+/-1.0 mm(2) before the intervention to 8.8+/-2.0 mm(2) after the intervention (P<0.0001) as a result of an increase in mean external elastic membrane area (14. 2+/-2.7 to 16.1+/-3.0 mm(2), P<0.0001) and a decrease in mean P&M area (10.2+/-2.2 to 7.2+/-1.8 mm(2), P<0.0001). The decrease in lesion P&M was accompanied by an increase in both proximal reference mean P&M (7.0+/-1.9 to 8.4+/-2.0 mm(2), P<0.0001) and distal reference mean P&M (5.8+/-2.1 to 7.2+/-2.1 mm(2), P<0.0001). Volumetric analysis showed an axial redistribution of plaque away from the center of the lesion toward the reference segments to increase the plaque burden in both the proximal and distal reference segments. Total (lesion plus reference) mean P&M decreased from 8. 6+/-2.1 to 7.5+/-1.8 mm(2) (P<0.0001). CONCLUSIONS: The mechanisms of lumen enlargement after stenting involved (1) significant axial redistribution of plaque from the lesion into the reference segments, (2) vessel expansion, and (3) either plaque embolization or compression.

Safety of intracoronary gamma-radiation on uninjured reference segments during the first 6 months after treatment of in-stent restenosis: a serial intravascular ultrasound study.

BACKGROUND: The effects of endovascular irradiation on uninjured reference segments during the treatment of in-stent restenosis are unknown. METHODS AND RESULTS: In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized (blinded) to receive either gamma-irradiation ((192)Ir) or a placebo (dummy seeds). We identified all patients in whom the active (n=19) or dummy seeds (n=19) extended >10 mm proximal and distal to the in-stent restenosis lesion. Serial (postirradiation and follow-up) external elastic membrane (EEM), lumen, and plaque and media (EEM-lumen) areas were measured (using intravascular ultrasound) every 1 mm over 5-mm-long reference segments that were 6 to 10 mm proximal and distal to the in-stent restenosis lesion. During follow-up, a similar small increase occurred in the plaque and media area in the proximal and distal reference segments in both (192)Ir and placebo patients. However, in the (192)Ir patients, an increase in both proximal and distal EEM area occurred; as a result, no change in lumen area occurred. Conversely, in the placebo patients, the proximal reference EEM area decreased, and no change occurred in the distal reference EEM area; this contributed to a decrease in lumen area. CONCLUSIONS: There was no evidence of a deleterious effect of gamma-irradiation on angiographically normal uninjured reference segments in the first 6 months after the treatment of in-stent restenosis.

Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions : intravascular ultrasound study of 2256 patients.

BACKGROUND: Elevation of serum creatine kinase MB fraction (CK-MB) after percutaneous coronary interventions has been associated with early and late mortality; however, the pathogenesis of CK-MB elevation is still unknown. We hypothesized that CK-MB elevation was related to atherosclerotic plaque burden as assessed by preintervention intravascular ultrasound (IVUS). METHODS AND RESULTS: We studied 2256 consecutive patients who underwent intervention of 2780 native coronary lesions and had complete high-quality preintervention IVUS imaging in the era before routine use of platelet glycoprotein IIb/IIIa inhibitors. Patients were divided into 3 groups: CK-MB within normal range (1675 patients; 2061 lesions); CK-MB elevation 1 to 5 times upper limit of normal (292 patients; 355 lesions); and CK-MB elevation > or = 5 times upper limit of normal (289 patients; 364 lesions). Qualitative angiographic lesion morphology and quantitative analysis were similar among the 3 groups. On preintervention IVUS, progressively more reference segment and lesion site plaque burden and lesion site calcium occurred in the groups with CK-MB elevation. Positive remodeling was more common in lesions with CK-MB elevation. As levels of CK-MB increased, cross-sectional narrowing (percentage plaque burden) increased, both at the reference site (mean cross-sectional narrowing values were 45.1%, <49.3%, and <52.2% for normal CK-MB, 1 to 5 times upper limit of normal, and > or =5 times upper limit of normal groups, respectively; P=0.03) and at the lesion site (81.9%, <85.4%, and <87.1%, respectively; P=0.04). Multivariate analysis indicated that de novo lesions, atheroablative technique, plaque burden at the lesion and reference segments, and final minimal lumen diameter were independent predictors of CK-MB elevation. CONCLUSIONS: CK-MB elevation correlates with a greater atherosclerotic plaque burden. CK-MB elevation after intervention may be a marker of diffuse atherosclerotic disease or a consequence of catheter-based intervention in more diseased arteries or both.

Preintervention arterial remodeling as an independent predictor of target-lesion revascularization after nonstent coronary intervention: an analysis of 777 lesions with intravascular ultrasound imaging.

BACKGROUND: Pathological and intravascular ultrasound (IVUS) studies have documented arterial remodeling during atherogenesis. However, the impact of this remodeling process on the long-term outcome after percutaneous intervention is unknown. METHODS AND RESULTS: We used preintervention IVUS to define positive and negative/intermediate remodeling in a total of 777 lesions in 715 patients treated with nonstent techniques. Positive remodeling (lesion external elastic membrane area greater than average reference) was present in 313 lesions; intermediate/negative remodeling (lesion external elastic membrane area less than or equal to reference) was present in the other 464. Baseline clinical and angiographic characteristics were similar, except for a slightly higher percentage of insulin-dependent diabetic patients (10.2% versus 6.1%; P=0.054) in the negative/intermediate-remodeling group. Angiographic success and in-hospital and short-term complications were comparable in the 2 groups. There was no significant correlation between remodeling (as a continuous variable) and final lumen area (r=0.06) or final lesion plaque burden (r=0.17). At 18+/-13 months of clinical follow-up, both groups had similar rates of death and Q-wave myocardial infarction: 3.4% and 2.5% for the negative/intermediate-remodeling group versus 2.7% and 2.7% for the positive-remodeling group. However, the target-lesion revascularization (TLR) rate was 20.2% for the negative/intermediate-remodeling group versus 31.2% for the positive-remodeling group (P=0.007), and remodeling, as a continuous variable, was strongly correlated with probability of TLR (P=0.0001). By multivariable logistic regression analysis, diabetes (OR=2.3), left anterior descending artery location (OR=1.8), and remodeling (OR=5.9) were independent predictors of TLR. CONCLUSIONS: Positive lesion-site remodeling is associated with a higher long-term TLR after a nonstent interventional procedure. Thus, long-term clinical outcome appears to be determined in part by preintervention lesion characteristics.

Serial intravascular ultrasound assessment of the efficacy of intracoronary gamma-radiation therapy for preventing recurrence in very long, diffuse, in-stent restenosis lesions.

BACKGROUND: The efficacy of coronary gamma-irradiation in preventing recurrent in-stent restenosis (ISR) is well established. However, brachytherapy may be less effective in very long, diffuse ISR lesions. METHODS AND RESULTS: We used serial intravascular ultrasound (IVUS) to study patients with long, diffuse ISR lesions (length, 36 to 80 mm) who were enrolled in (1) Long WRIST (Washington Radiation In-Stent Restenosis Trial), a double-blind, placebo-controlled trial of intracoronary gamma-irradiation (15 Gy at 2 mm from the source) and (2) high-dose (HD) Long WRIST, a registry that used a dose prescription of 18 Gy at 2 mm from the source. IVUS was performed using automated pullback (0.5 mm/s). Stent, lumen, and intimal hyperplasia were measured at 2-mm intervals. Complete postintervention and follow-up IVUS imaging was available in 30 irradiated and 34 placebo patients from Long WRIST and in 25 patients from HD Long WRIST. Stent length was longer in HD Long WRIST than in placebo or treated patients in Long WRIST (P=0.0064 and P=0.0125, respectively). Otherwise, baseline measurements were similar. At follow-up, the minimum lumen area was largest in the HD Long WRIST patients (4.0+/-1.4 mm(2)); areas were 2.9+/-1.0 mm(2) in irradiated patients in Long WRIST and 1.9+/-1.1 mm(2) in placebo patients in Long WRIST (P<0.005 for all comparisons). CONCLUSIONS: - Serial IVUS analysis shows that gamma-irradiation reduces recurrent in-stent neointimal hyperplasia in long, diffuse ISR lesions; however, it is even more effective when given at a higher dose.

Treatment of in-stent restenosis with excimer laser coronary angioplasty versus rotational atherectomy: comparative mechanisms and results.

BACKGROUND: Atheroablation yields improved clinical results for balloon angioplasty (percutaneous transluminal coronary angioplasty, PTCA) in the treatment of diffuse in-stent restenosis (ISR). METHODS AND RESULTS: We compared the mechanisms and clinical results of excimer laser coronary angioplasty (ELCA) versus rotational atherectomy (RA), both followed by adjunct PTCA; 119 patients (158 ISR lesions) were treated with ELCA+PTCA and 130 patients (161 ISR lesions) were treated with RA+PTCA. Quantitative coronary angiographic and planar intravascular ultrasound (IVUS) measurements were performed routinely. In addition, volumetric IVUS analysis to compare the mechanisms of lumen enlargement was performed in 28 patients with 30 lesions (16 ELCA+PTCA, 14 RA+PTCA). There were no significant between-group differences in preintervention or final postintervention quantitative coronary angiographic or planar IVUS measurements of luminal dimensions. Angiographic success and major in-hospital complications with the 2 techniques were also similar. Volumetric IVUS analysis showed significantly greater reduction in intimal hyperplasia volume after RA than after ELCA (43+/-14 versus 19+/-10 mm(3), P<0.001) because of a significantly higher ablation efficiency (90+/-10% versus 76+/-12%, P = 0.004). However, both interventional strategies had similar long-term clinical outcome; 1-year target lesion revascularization rate was 26% with ELCA+PTCA versus 28% with RA+PTCA (P = NS). CONCLUSIONS: Despite certain differences in the mechanisms of lumen enlargement, both ELCA+PTCA and RA+PTCA can be used to treat diffuse ISR with similar clinical results.

Intracoronary beta-radiation therapy inhibits recurrence of in-stent restenosis.

BACKGROUND: Intracoronary gamma-radiation therapy reduces recurrent in-stent restenosis (ISR). This study, BETA WRIST (Washington Radiation for In-Stent restenosis Trial) was designed to examine the efficacy and safety of the beta-emitter 90-yttrium for the prevention of recurrent ISR. METHODS AND RESULTS: A total of 50 consecutive patients with ISR in native coronaries underwent percutaneous transluminal coronary angioplasty, laser angioplasty, rotational atherectomy, and/or stent implantation. Afterward, a segmented balloon catheter was positioned and automatically loaded with a 90-yttrium, 0.014-inch source wire that was 29 mm in length to deliver a dose of 20.6 Gy at 1.0 mm from the balloon surface. In 17 patients, manual stepping of the radiation catheter was necessary for lesions >25 mm in length. The radiation was delivered successfully to all patients, with a mean dwell time of 3.0+/-0.4 minutes. Fractionation of the dose due to ischemia was required in 11 patients. At 6 months, the binary angiographic restenosis rate was 22%, the target lesion revascularization rate was 26%, and the target vessel revascularization rate was 34%; all rates were significantly lower than those of the placebo group of gamma-WRIST. CONCLUSIONS: beta-Radiation with a 90-yttrium source used as adjunct therapy for patients with ISR results in a lower-than-expected rate of angiographic and clinical restenosis.

Long-term follow-up after percutaneous transluminal coronary angioplasty was not performed based on intravascular ultrasound findings: importance of lumen dimensions.

BACKGROUND: Angiography is limited in determining the anatomic severity of coronary artery stenoses. Clinical decision-making in patients with symptoms and intermediate lesions remains challenging. METHODS AND RESULTS: The current analysis included 300 patients (357 intermediate native artery lesions) in whom intervention was deferred based on intravascular ultrasound (IVUS) findings. Standard clinical, angiographic, and IVUS parameters were collected. Patients were followed for >1 year. Events occurred in 24 patients (8%). They included 2 cardiac deaths, 4 myocardial infarctions, and 18 target-lesion revascularizations (TLR; 12 percutaneous transluminal coronary angiographies and 6 coronary artery bypass grafts; only 3 TLRs occurred within 6 months after the IVUS study). All significant univariate clinical, angiographic, and IVUS parameters (P<0.05) were tested in multivariate models. These included diabetes mellitus, IVUS lesion lumen area, maximum lumen diameter, minimum lumen diameter, plaque area, plaque burden, and area stenosis (AS). No angiographic measurement was significant at P<0.05. The only independent predictors of an event (death, myocardial infarction, or TLR) were IVUS minimum lumen area and AS. The only independent predictors of TLR were diabetes mellitus, IVUS minimum lumen area, and AS. In 248 lesions with a minimum lumen area >/=4.0 mm(2), the event rate was only 4.4% and the TLR rate 2.8%. CONCLUSIONS: Long-term follow-up after IVUS-guided deferred interventions in patients with de novo intermediate native artery lesions showed a low event rate. In patients with a minimum lumen area >/=4.0 mm(2), the event rate was especially low. IVUS imaging is an acceptable alternative to physiological assessment in these patients.

Creatine kinase-MB enzyme elevation following successful saphenous vein graft intervention is associated with late mortality.

BACKGROUND: Although the risk for development of creatine kinase (CK-MB) elevation after saphenous vein graft (SVG) intervention is high, its prognostic significance remains unknown. This study evaluated the impact of periprocedural CK-MB elevation on late clinical events following successful SVG angioplasty. METHODS AND RESULTS: We studied 1056 consecutive patients with successful (defined by angiographic success and absence of major complications) intervention of 1693 SVG lesions. These patients were grouped as normal CK-MB (n=556), minor CK-MB rise (CK-MB 1 to 5 times normal, n=339), and major CK-MB rise (CK-MB >5 times normal, n=161). There were no differences in major clinical events at 30-day follow-up among the 3 groups. However, 1-year mortality was 4.8%, 6.5%, and 11. 7%, respectively, P<0.05 (ANOVA). Even within a population without any intraprocedure or in-hospital complications (n=727, 69% of the overall cohort), 1-year mortality remained significantly higher with CK-MB elevation: 2.4%, 5.5%, and 10.7%, respectively, P<0.05 (ANOVA). Multivariate analysis revealed major CK-MB elevation as the strongest independent predictor of late mortality (odds ratio 3.3, with 95% CI 1.7 to 6.2), followed by diabetes mellitus (odds ratio 2. 6, with 95% CI 1.5 to 4.5). CONCLUSIONS: Major CK-MB elevation occurs after 15% of otherwise successful SVG interventions and is associated with increased late mortality.

Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome.

BACKGROUND: The angiographic presentation of in-stent restenosis (ISR) may convey prognostic information on subsequent target vessel revascularizations (TLR). METHODS AND RESULTS: We developed an angiographic classification of ISR according to the geographic distribution of intimal hyperplasia in reference to the implanted stent. Pattern I includes focal (< or =10 mm in length) lesions, pattern II is ISR>10 mm within the stent, pattern III includes ISR>10 mm extending outside the stent, and pattern IV is totally occluded ISR. We classified a total of 288 ISR lesions in 245 patients and verified the angiographic accuracy of the classification by intravascular ultrasound. Pattern I was found in 42% of patients, pattern II in 21%, pattern III in 30%, and pattern IV in 7%. Previously recurrent ISR was more frequent with increasing grades of classification (9%, 20%, 34%, and 50% for classes I to IV, respectively; P=0.0001), as was diabetes (28%, 32%, 39%, and 48% in classes I to IV, respectively; P<0.01). Angioplasty and stenting were used predominantly in classes I and II, whereas classes III and IV were treated with atheroablation. Final diameter stenosis ranged between 21% and 28% (P=NS among ISR patterns). TLR increased with increasing ISR class; it was 19%, 35%, 50%, and 83% in classes I to IV, respectively (P<0.001). Multivariate analysis showed that diabetes (odds ratio, 2.8), previously recurrent ISR (odds ratio, 2. 7), and ISR class (odds ratio, 1.7) were independent predictors of TLR. CONCLUSIONS: The introduced angiographic classification is prognostically important, and it may be used for appropriate and early patient triage for clinical and investigational purposes.

Prolonged antiplatelet therapy to prevent late thrombosis after intracoronary gamma-radiation in patients with in-stent restenosis: Washington Radiation for In-Stent Restenosis Trial plus 6 months of clopidogrel (WRIST PLUS).

BACKGROUND: Intracoronary gamma-radiation reduces recurrent in-stent restenosis. Late thrombosis (>30 days after radiation therapy) is identified as a serious complication. The Washington Radiation for In-Stent Restenosis Trial (WRIST) PLUS, which involved 6 months of treatment with clopidogrel and aspirin, was designed to examine the efficacy and safety of prolonged antiplatelet therapy for the prevention of late thrombosis. METHODS AND RESULTS: A total of 120 consecutive patients with diffuse in-stent restenosis in native coronary arteries and vein grafts with lesions <80 mm underwent percutaneous coronary transluminal angioplasty, laser ablation, and/or rotational atherectomy. Additional stents were placed in 34 patients (28.3%). After the intervention, a closed-end lumen catheter was introduced into the artery, a ribbon with different trains of radioactive (192)Ir seeds was positioned to cover the treated site, and a dose of 14 Gy to 2 mm was prescribed. Patients were discharged with clopidogrel and aspirin for 6 months and followed angiographically and clinically. All patients but one tolerated the clopidogrel. The late occlusion and thrombosis rates were compared with the gamma-radiation-treated (n=125) and the placebo patients (n=126) from the WRIST and LONG WRIST studies (which involved only 1 month of antiplatelet therapy). At 6 months, the group receiving prolonged antiplatelet therapy had total occlusion and late thrombosis rates of 5.8% and 2.5%, respectively; these rates were lower than those in the active gamma-radiation group and similar to those in the placebo historical control group. CONCLUSIONS: Six months of clopidogrel and aspirin and a reduction in re-stenting for patients with in-stent restenosis treated with gamma-radiation is well tolerated and associated with a reduction in the late thrombosis rate compared with a similar cohort treated with only 1 month of clopidogrel and aspirin.

Comparative efficacy of gamma-irradiation for treatment of in-stent restenosis in saphenous vein graft versus native coronary artery in-stent restenosis: An intravascular ultrasound study.

BACKGROUND: We used serial volumetric (post-irradiation and follow-up) intravascular ultrasound (IVUS) to compare the effectiveness of gamma-irradiation ((192)Ir) in saphenous vein graft (SVG) versus native coronary artery in-stent restenosis (ISR). METHODS AND RESULTS: The study population consisted of 47 patients with native coronary artery ISR from WRIST (Washington Radiation for In-Stent Restenosis Trial) and 31 patients with SVG ISR (12 from the WRIST and 19 from SVGWRIST). After irradiation and at 6-month follow-up, stent, lumen, and intimal hyperplasia (IH, stent minus lumen) areas were measured every 1 mm. ISR length was similar in the 2 groups (29+/-12 versus 29+/-14 mm, P=0.9). Post-intervention measurements of stent (280+/-154 versus 324+/-270 mm(3), P=0.4), lumen (184+/-91 versus 214+/-172 mm(3), P=0.3), and IH (96+/-77 versus 109+/-119 mm(3), P=0.5) volumes were similar in the 2 groups. The post-intervention minimum lumen cross sectional areas tended to be smaller in native artery ISR lesions (4.7+/-1.7 versus 5.4+/-1.6 mm(2), P=0.11). During follow-up, there was a slight increase in IH volume (9+/-38 mm(3)) in native artery ISR lesions and a slight decrease in IH volume in SVG ISR lesions (-9+/-32 mm(3), P=0.0463). There was also a slight decrease in minimum lumen area in the native artery ISR lesions versus a slight increase in minimum lumen area in the SVG ISR lesions (-0.8+/-1.7 versus 0.2+/-1.1, P=0.0087). As a result, the follow-up minimum lumen area in native artery lesions was smaller than in SVG ISR lesions (4.1+/-2.1 mm(2) versus 5.6+/-2.2 mm(2), P=0.0067). CONCLUSION: gamma-Irradiation with (192)Ir brachytherapy appears to be as effective in SVGs as it is in native artery ISR lesions.

Intracoronary gamma-radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis.

BACKGROUND: Treatment of in-stent restenosis presents a critical limitation of intracoronary stent implantation. Ionizing radiation has been shown to decrease neointimal formation within stents in animal models and in initial clinical trials. We studied the effects of intracoronary gamma-radiation therapy versus placebo on the clinical and angiographic outcomes of patients with in-stent restenosis. METHODS AND RESULTS: One hundred thirty patients with in-stent restenosis underwent successful coronary intervention and were then blindly randomized to receive either intracoronary gamma-radiation with (192)Ir (15 Gy) or placebo. Four independent core laboratories blinded to the treatment protocol analyzed the angiographic and intravascular ultrasound end points of restenosis. Procedural success and in-hospital and 30-day complications were similar among the groups. At 6 months, patients assigned to radiation therapy required less target lesion revascularization and target vessel revascularization (9 [13.8%] and 17 [26.2%], respectively) compared with patients assigned to placebo (41 [63.1%, P=0.0001] and 44 [67.7%, P=0.0001], respectively). Binary angiographic restenosis was lower in the irradiated group (19% versus 58% for placebo, P=0.001). Freedom from major cardiac events was lower in the radiation group (29.2% versus 67.7% for placebo, P<0.001). CONCLUSIONS: Intracoronary gamma-radiation used as adjunct therapy for patients with in-stent restenosis significantly reduces both angiographic and clinical restenosis.

Myocardial salvage after failed coronary angioplasty.

UNLABELLED: Patients undergoing coronary angioplasty have a 2% to 7% risk of requiring emergency coronary artery bypass graft surgery for impending infarction. These patients provide a unique model of early reperfusion because the exact time of compromise to blood flow and the composition of the reperfusion solution are known. However, the amount of myocardium salvaged is unknown. Between December 1981 and September 1985, 859 patients underwent coronary angioplasty. Forty-two patients had emergency surgery for objective evidence of impending infarction. Five patients died. Thirty-six patients were contacted for follow-up; 21 (58%) of 36 had a radionuclide ventriculogram performed at a mean of 39 +/- 13 months after surgery. These radionuclide studies were compared with the patient's preangioplasty contrast ventriculogram. One patient had a myocardial infarction 3 years after surgery. Eleven (55%) of the remaining 20 patients had a normal radionuclide ventriculogram at follow-up study (ejection fraction 65 +/- 9%). Five (25%) of the 20 patients had a depressed ejection fraction (46 +/- 4%) with wall motion abnormalities, but these were unchanged from the preangioplasty studies. Four patients (20%) had a significant decrease in ejection fraction over baseline (37 +/- 10%) with new wall motion abnormalities. IN CONCLUSION: 1) there is an 80% chance that left ventricular function will be unchanged at 3 year follow-up study in patients surviving emergency bypass grafting for failed angioplasty; 2) these data suggest that early revascularization for impending infarction in this setting is associated with a good late outcome; and 3) this patient group offers a unique opportunity to study the effects of early reperfusion in a human model.

Late total occlusion after intracoronary brachytherapy for patients with in-stent restenosis.

OBJECTIVES: The study sought to determine the incidence and predictors of late total occlusion (LTO, >30 days) in-patients with in-stent restenosis who were treated with intracoronary radiation. BACKGROUND: Intracoronary radiation both with beta and gamma emitters has been shown to reduce recurrent in-stent restenosis. METHODS: We reviewed the records of 473 patients who presented with in-stent restenosis and who were enrolled in various radiation protocols, whether randomized to placebo versus radiation or entered into registries. There were 165 placebo and 308 radiated patients, including both gamma and beta emitters. Maximum dose to the vessel wall was 30 to 55 Gy. Following radiation, all patients received antiplatelet therapy with aspirin and either ticlopidine or clopidogrel for one month. All patients completed at least six months of angiographic follow-up. RESULTS: The LTO was documented in 28 patients (9.1%) from the irradiated group versus 2 placebo patients (1.2%), p < 0.0001. The LTO rates were similar across studies and emitters. In the irradiated group, LTO presented as acute myocardial infarction in 12 patients (43%), unstable angina in 14 (50%), and asymptotic in 2 (7%). Mean time to LTO was 5.4 +/- 3.2 months in the irradiated group versus 4.5 +/- 2.1 in placebo patients (p = NS). The overall rate of restenting for the entire study group at the time of radiation was 48.6%. Importantly, new stents were placed in 82% of the irradiated and in 100% of the placebo patients who presented with LTO. Multivariate analysis determined that new stenting was the main predictor of LTO. CONCLUSIONS: Intracoronary radiation for patients with in-stent restenosis is associated with a high rate of LTO. Restenting may contribute late thrombosis. Prolonged antiplatelet therapy (up to six months) should be considered for these patients.

Multivariate predictors of intravascular ultrasound end points after directional coronary atherectomy.

OBJECTIVES: This study attempted to identify the clinical, angiographic, procedural and intravascular ultrasound predictors of directional atherectomy results assessed by intravascular ultrasound. BACKGROUND: Several angiographic and intravascular ultrasound variables have been associated with the outcome of directional coronary atherectomy. No study has incorporated both modalities into a predictive model. METHODS: One hundred seventy patients were analyzed using preintervention and postintervention intravascular ultrasound and quantitative angiography. Clinical and procedural variables were collected by independent chart review. Quantitative and qualitative angiographic analysis was performed by a core laboratory in blinded manner. Intravascular ultrasound was performed using a transducer-tipped catheter, rotating within a stationary imaging sheath, and withdrawn automatically at 0.5 mm/s. Clinical, procedural, angiographic and ultrasound variables were tested in a multivariate linear regression model. Dependent ultrasound variables included postatherectomy lumen cross-sectional area and percent cross-sectional narrowing (plaque plus media/external elastic membrane cross-sectional area) and, in a subgroup of 47 patients studied using volumetric analysis, percent plaque volume removal. RESULTS: By multivariate stepwise linear regression analysis, predictors of residual lumen cross-sectional area (correcting for reference lumen area) included arc of calcium and preatherectomy plaque plus media cross-sectional area; predictors of residual cross-sectional narrowing were arc of calcium, preatherectomy plaque plus media cross-sectional area and lesion length; and predictors of percent plaque volume removal were arc of calcium and atherectomy device size. CONCLUSIONS: The preintervention lesion arc of calcium measured by intravascular ultrasound is the most consistent predictor of the effectiveness and results of directional coronary atherectomy.

Mechanisms and immediate and long-term results of adjunct directional coronary atherectomy after rotational atherectomy.

OBJECTIVES: The purpose of this study was to confirm the mechanisms and the immediate and long-term results of rotational atherectomy and adjunct directional coronary atherectomy. BACKGROUND: Rotational atherectomy is best suited for treating calcific stenoses, but the ability of rotational atherectomy alone to optimize lumen dimensions in large vessels is limited; this is only partly improved by adjunct balloon angioplasty. METHODS: We treated 165 lesions in 163 patients by use of rotational atherectomy and adjunct directional coronary atherectomy. Quantitative angiography and intravascular ultrasound were used for lesion analysis. A matched comparison with 208 lesions treated with rotational atherectomy and adjunct coronary angioplasty was performed. Patients were then followed up for at least 9 months, and target-lesion revascularization was assessed. RESULTS: In the 61 lesions imaged sequentially, lumen area increased from 1.7 +/- 0.8 (mean +/- 1 SD) to 3.9 +/- 1.1 mm(2) after rotational atherectomy, owing to a decrease in plaque plus media area from 16.8 +/- 5.0 to 15.2 +/- 5.2 mm(2) (both p < 0.0001). After adjunct directional coronary atherectomy, lumen area increased even more to 6.7 +/- 2.0 mm(2) (vs. 5.1 +/- 1.4 mm(2) after adjunct coronary angioplasty, p < 0.0001) as a result of both vessel expansion (18.8 +/ 5.3 to 20.8 +/- 5.7 mm(2)) and additional plaque removal (to 14.1 +/- 5.0 mm(2), all p < 0.0001). The total arcs of calcium decreased from 207 +/- 107 degrees to 166 +/- 93 degrees after rotational atherectomy and to 145 +/- 87 degrees after directional coronary atherectomy. Overall, procedural success was 96%, and final diameter stenosis was 15 +/- 17%. Target-lesion revascularization was 23%. The only independent predictor of target-lesion revascularization was a larger overall atherectomy index (84% vs. 59%, p = 0.048). CONCLUSIONS: There is a synergistic relationship between rotational atherectomy and directional coronary atherectomy in the treatment of calcific lesions. The immediate results show a high procedural success--lumen dimensions were larger and late target-lesion revascularization was lower in lesions treated with rotational atherectomy and directional coronary atherectomy than in those treated with rotational atherectomy and adjunct balloon angioplasty.

Arterial responses to balloon coronary angioplasty: an intravascular ultrasound study.

OBJECTIVES: The purpose of this study was to examine the coronary artery response to percutaneous transluminal coronary angioplasty by using intravascular ultrasound. BACKGROUND: The immediate effects of coronary angioplasty on arterial wall geometry and surface appearance are understood poorly. Most of the available data are derived from small necropsy series, inferred from animal models or extrapolated from in vitro studies. High frequency intravascular ultrasound provides transmural images of coronary arteries in vivo. METHODS: We used intravascular ultrasound to study 29 patients before or after, or both, successful coronary angioplasty. RESULTS: The angiographic diameter narrowing was 72 +/- 13% before and improved to 19 +/- 11% after angioplasty. Calcium was visualized in 7 (24%) of the 29 angioplasty sites by fluoroscopy versus 15 (52%) of sites by intravascular ultrasound (p = 0.022). Arterial dissection after angioplasty was observed in 8 (27%) of cases by contrast angiography versus 24 (83%) by intravascular ultrasound (p less than 0.001). Intravascular ultrasound detected extensive dissection at the angioplasty site in 11 (73%) of the 15 calcified plaques and in only 3 (21%) of the 14 noncalcified plaques (p = 0.024). Arterial expansion (defined as the area within the external elastic membrane at the angioplasty site greater than that of the proximal reference segment) occurred in 29% of calcified plaques compared with 86% of noncalcified plaques (p = 0.007). CONCLUSIONS: Intravascular ultrasound is more sensitive than angiography for identifying arterial calcium and dissection at the site of angioplasty. At the site of angioplasty, arterial dissection occurred more frequently in calcified plaques whereas arterial expansion occurred more frequently in noncalcified plaques. Successful angioplasty causes a continuum of arterial responses that vary importantly with plaque composition.