Intravascular ultrasound assessment of optimal stent area to prevent in-stent restenosis after zotarolimus-, everolimus-, and sirolimus-eluting stent implantation.

OBJECTIVES AND BACKGROUND: The impact of underexpansion and minimal stent area (MSA) criteria in the second generation drug-eluting stents (DES) has not been addressed yet. METHODS: Using intravascular ultrasound (IVUS), we assessed the optimal cut-off values of post-stenting MSA to prevent in-stent restenosis (ISR). Poststenting IVUS data and 9-month follow-up angiography were available in 912 patients with 990 lesions: 541 sirolimus-eluting stents (SES), 220 zotarolimus-eluting stents (ZES) and 229 everolimus-eluting stents (EES). RESULTS: For the prediction of angiographic ISR, the MSA of each DES was measured. The poststenting MSA was 6.4 ± 1.8 mm(2) in SES, 6.2 ± 2.1 mm(2) in ZES and 6.2 ± 2.1 mm(2) in EES. At the 9-months follow-up, the incidence of angiographic ISR was similar between SES (3.3%) vs. ZES (4.5%) vs. EES. (4.4%), (P = 0.53). Multivariable logistic regression analysis identified the post-stenting MSA as the only independent predictor of angiographic ISR in ZES (Odds ratio 0.722, 95% confidence interval 0.581-0.897, P = 0.001) and in EES (Odds ratio 0.595, 95% confidence interval 0.392-0.904, P = 0.015). The best MSA cut-off value was 5.5 mm(2) for the prediction of SES restenosis (sensitivity 72.2% and specificity 66.3%). For ZES, the optimal MSA predicting ISR was 5.3 mm(2) (sensitivity 56.7% and specificity 61.8%). For EES, the MSA <5.4 mm(2) predicted ISR (sensitivity 60.0% and specificity 60.0%). CONCLUSIONS: As a preventable mechanism of ISR, smaller stent area predicted angiographic restenosis of the second generation DES as well as the first generation. The optimal cut-off values of post-stenting MSA for preventing restenosis were similar between ZES vs. EES vs. SES.

Differential prognostic impact of high on-treatment platelet reactivity among patients with acute coronary syndromes versus stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: High on-treatment platelet reactivity (HTPR) after clopidogrel is associated with a higher risk of cardiovascular events after percutaneous coronary intervention (PCI). However, it remains unclear whether HTPR is of similar prognostic value for different clinical presentations. METHODS: We compared the prognostic impact of HTPR, measured by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA), on outcomes between 1,095 patients with acute coronary syndromes (ACS) and 1,329 patients with stable coronary artery disease (CAD) who were treated with PCI. Before PCI, patients received optimal clopidogrel treatment (75 mg daily for at least 5 days or if <5 days, 300-600 mg loading), and platelet reactivity was measured at 24 to 48 hours after PCI. The primary end point was a composite of death, myocardial infarction, stent thrombosis, or stroke. RESULTS: During follow-up (median, 22.0 months), HTPR was independently associated with higher risks of the primary end point (hazard ratio [HR] 2.03, 95% CI 1.30-3.18, P = .002) and mortality (HR 3.46, 95% CI 1.18-10.18, P = .02) in patients with ACS. By contrast, for patients with stable CAD, HTPR was not associated with adjusted risks of the primary end point (HR 1.00, 95% CI 0.71-1.39, P = .98) or mortality (HR 0.74, 95% CI 0.36-1.51, P = .41). Significant interactions were present between HTPR status and clinical presentations for the primary end point (P = .02) and mortality (P = .04). CONCLUSION: There was a substantial interaction between platelet reactivity on clopidogrel and clinical presentations on cardiovascular events after PCI. High on-treatment platelet reactivity was significantly associated with higher risks of cardiovascular events in ACS patients, whereas this association was absent in stable CAD patients.

Long-term luminal change after drug-eluting stent implantation: serial angiographic follow-up study of the ZEST randomized trial.

OBJECTIVE: To evaluate long-term patterns of luminal changes after implantation of different types of drug-eluting stents (DES), we analyzed the serial angiographic outcomes of patients implanted with zotarolimus-eluting stents (ZES), sirolimus-eluting stents (SES), or paclitaxel-eluting stents (PES). BACKGROUND: Little is known regarding long-term luminal changes after DES implantation. METHODS: As a subgroup analysis of the ZEST trial, we performed complete angiographic evaluation immediately after the procedure and at 9 months and 2 years in 111 patients with 165 lesions (36 patients with ZES, 40 with SES, and 35 with PES). RESULTS: Baseline clinical, angiographic, and procedural characteristics were similar among the three groups. Quantitative angiographic analysis revealed significant decreases in minimal luminal diameter 9 months after stent implantation in the ZES (from 2.71 ± 0.49 to 2.21 ± 0.42 mm, P < 0.001), SES (from 2.79 ± 0.49 to 2.58 ± 0.57 mm, P < 0.001), and PES (from 2.66 ± 0.45 to 2.19 ± 0.52 mm, P < 0.001) groups. However, significant late improvements with different degree in luminal diameter were observed between 9 months and 2 years in the ZES (from 2.21 ± 0.42 to 2.39 ± 0.58 mm, P = 0.001), SES (from 2.58 ± 0.57 to 2.66 ± 0.60 mm, P = 0.039), and PES (from 2.19 ± 0.52 to 2.43 ± 0.52 mm, P < 0.001) groups. CONCLUSION: Serial angiographic follow-up study revealed a biphasic luminal response after DES implantation, characterized by an early progression phase for the first 9 months and a late regression phase from 9 months to 2 years.

Post-PCI Risk Assessment by Inflammation Activity According to Disease Acuity and Time from Procedure.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) has been proposed as an indicator of inflammation and cardiovascular risk. However, little is known of the comparative temporal profile of hs-CRP and its relation to outcomes according to the disease acuity. METHODS: We enrolled 4,263 East Asian patients who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) and stable disease. hs-CRP was measured at baseline and 1 month post-PCI. Major adverse cardiovascular events (MACE: the composite occurrence of death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. RESULT: The AMI group (n = 2,376; 55.7%) had higher hs-CRPbaseline than the non-AMI group (n = 1,887; 44.3%) (median: 1.5 vs. 1.0 mg/L; p < 0.001), which remained higher at 1 month post-PCI (median: 1.0 vs. 0.9 mg/L; p = 0.001). During 1 month, a high inflammatory-risk phenotype (upper tertile: hs-CRPbaseline ≥ 2.4 mg/L) was associated with a greater MACE in the AMI group (adjusted hazard ratio [HRadj]: 7.66; 95% confidence interval [CI]: 2.29-25.59; p < 0.001), but not in the non-AMI group (HRadj: 0.74; 95% CI: 0.12-4.40; p = 0.736). Between 1 month and 4 years, a high inflammatory-risk phenotype (upper tertile: hs-CRP1 month ≥ 1.6 mg/L) was associated with greater MACE compared to the other phenotype in both the AMI (HRadj: 2.40; 95% CI: 1.73-3.45; p < 0.001) and non-AMI groups (HRadj: 2.67; 95% CI: 1.80-3.94; p < 0.001). CONCLUSION: AMI patients have greater inflammation during the early and late phases than non-AMI patients. Risk phenotype of hs-CRPbaseline correlates with 1-month outcomes only in AMI patients. However, the prognostic implications of this risk phenotype appears similar during the late phase, irrespective of the disease acuity.

Mechanism of regular atrial tachyarrhythmias during combined pulomonary vein isolation and complex fractionated electrogram ablation in patients with atrial fibrillation.

BACKGROUND: Atrial tachyarrhythmias (ATA) frequently develop during catheter ablation of atrial fibrillation (AF), but the mechanism of ATA during combined pulmonary vein isolation (PVI) and complex fractionated electrogram-guided ablation (CFEA) has not been reported. METHODS AND RESULTS: This study involved 105 patients with symptomatic, drug-refractory AF. After PVI, CFEA was performed in the left/right atrium if AF remained inducible in paroxysmal AF (PAF) or persisted in persistent AF (PeAF). For the 70 PAF patients, PVI alone rendered AF non-inducible in 29 patients (41.4%), and converted inducible AF into inducible atrial flutter (AFl) in 10 patients (14.3%). For the remaining 31 PAF patients, additional CFEA rendered AF non-inducible in 11 patients (15.7%), whereas only AFl was inducible in 11 patients (15.7%). For 35 PeAF patients, PVI and CFEA converted AF into sinus rhythm in 2 (5.7%) and into AFl in 21 (60.0%) patients, while AF persisted in 12 patients (34.3%). The mechanism of ATA was focal (20/114, 17.5%), roof-dependent (20/114, 17.5%), peri-mitral (33/114, 28.9%), cavotricuspid isthmus-dependent (34/114, 29.8%) AFl or unknown (7/114, 6.1%). Successful ablation was achieved in 93/114 (81.6%) tachycardias. CONCLUSIONS: The major mechanism of ATA during the combined approach of PVI and CFEA is macroreentry around large anatomic obstacles such as the pulmonary vein or the mitral or tricuspid annuli.

OCT analysis in patients with very late stent thrombosis.

OBJECTIVES: We report optical coherence tomography (OCT) findings in 33 patients who presented with very late stent thrombosis (VLST) after either drug-eluting stent (DES) or bare-metal stent (BMS) implantation. BACKGROUND: VLST is a potentially life-threatening complication, but the underlying mechanisms remain unclear. METHODS: In 33 patients (27 DES- and 6 BMS-treated lesions) with definite VLST, OCT images were acquired before either thrombus aspiration or intravascular ultrasonography (IVUS) imaging. RESULTS: The median duration from implantation was 61.5 months in the DES group and 109.1 months in the BMS group. In the overall cohort, combining DES and BMS, 94% showed intraluminal thrombi. VLST was associated with in-stent neointimal rupture in 23 patients (70%); 22 had thrombi near the site of neointimal rupture. Stent malapposition was observed in 14 (42%) lesions, but only 9 of them showed thrombi at the site of stent malapposition; moreover, 6 (18%) stented segments with malapposition also had neointimal rupture. Only 2 (6%) lesions had no evidence of neointimal rupture or malapposition. Stent fracture was detected in 3 DES-treated lesions, all with concomitant neointimal rupture. Compared with lesions without neointimal rupture, lesions with neointimal rupture showed a higher frequency of ST-segment elevation myocardial infarction (65% vs. 20%, respectively, p = 0.040) as well as a higher peak creatine kinase-myocardial band level (163.1 ng/ml vs. 15.7 ng/ml, respectively, p = 0.017). CONCLUSIONS: OCT imaging indicated that advanced neoatherosclerosis with neointimal rupture and thrombosis was the most common mechanism of definite VLST and was associated with a high frequency of ST-segment elevation myocardial infarction.

Functional assessment of jailed side branches in coronary bifurcation lesions using fractional flow reserve.

OBJECTIVES: This study was designed to assess the functional significance of side branches after stent implantation in main vessels using fractional flow reserve (FFR). BACKGROUND: Little is known about the functional significance of side branches after stent implantation in main vessels in coronary bifurcation lesions. METHODS: Between May 2007 and January 2011, 230 side branches in 230 patients after stent implantation in main vessels were assessed by FFR and were consecutively enrolled. RESULTS: Median FFR at the side branch was 0.91 (interquartile range: 0.85 to 0.95). There was a negative correlation between the diameter stenosis (DS) by quantitative coronary angiography (QCA) and FFR of side branch (r=-0.21, p=0.002), but only 41 (17.8%) side branches were functionally significant after stent implantation in the main vessel. Among 67 side branches with >50% DS by QCA, 19 (28.4%) had FFR≤0.80, and among 163 side branches with ≤50% DS by QCA, 22 (13.5%) had FFR≤0.80 after stent implantation in main vessels. On the basis of receiver-operating characteristic curves, the optimal cutoff value of DS by QCA of the side branch was 54.9%, and the area under the curve was 0.64 (95% confidence interval [CI]: 0.58 to 0.71, p<0.001) with a 41.5% sensitivity, an 83.1% specificity, a 34.7% positive predictive value, an 86.3% negative predictive value, and a 75.7% accuracy. Multivariate binary logistic regression analysis identified DS by QCA (odds ratio [OR]: 1.04, 95% CI: 1.02 to 1.06, p=0.001) and reference vessel diameter (OR: 0.28, 95% CI: 0.10 to 0.77, p=0.014) before stent implantation as independent predictors of the side branches with FFR≤0.80 after stent implantation. CONCLUSIONS: Most side branch lesions do not have functional significance after stent implantation in the main vessel, and quantitative coronary angiography is unreliable in assessing the functional severity of these lesions.

Usefulness of minimal luminal coronary area determined by intravascular ultrasound to predict functional significance in stable and unstable angina pectoris.

Little is known about the intravascular ultrasound (IVUS) minimal lumen area (MLA) criteria and their accuracy in lesion subsets assorted according to vessel type, lesion location, vessel size, and clinical settings. We therefore assessed the accuracy of subgroup-specific cut-off values in predicting fractional flow reserve (FFR) <0.80. In total 692 consecutive patients with 784 coronary lesions were assessed by IVUS and FFR before intervention. All patients had ≥1 target vessel with a de novo lesion (30% to 90% diameter stenosis). For prediction of FFR <0.80 in the group overall, the best cut-off value of MLA was 2.4 mm(2) (sensitivity 84% and specificity 63%). Overall diagnostic accuracy was only 69%. In the subgroup analysis, the MLA cutoff was 2.4 mm(2) for the left anterior descending coronary artery, 1.6 mm(2) for the left circumflex coronary artery, and 2.4 mm(2) for the right coronary artery. By lesion location, the optimal cutoff was 2.6 mm(2) for proximal, 2.3 mm(2) for mid, and 1.9 mm(2) for distal segments. Furthermore, the cutoffs were 3.2 mm(2) in lesions with a larger RLD >3.5 mm and 1.9 mm(2) in lesions with a smaller RLD <2.75 mm. Nevertheless, diagnostic accuracies of all subgroup-specific criteria were <80%. In conclusion, because IVUS-measured MLA is only 1 of many factors affecting coronary flow hemodynamics, even subgroup-specific criteria were inaccurate in identifying ischemia-inducible stenosis. In conclusion, direct functional assessment is therefore essential in guiding treatment strategies for coronary lesions.

OCT findings in patients with recanalization of organized thrombi in coronary arteries.

OBJECTIVES: The purpose of this study was to determine the angiographic and optical coherence tomographic (OCT) characteristics of coronary lesions with recanalized thrombi. BACKGROUND: Although spontaneous recanalization of thrombi has been reported pathologically, it is rarely recognized in clinical practice. METHODS: Based on histopathologic features, recanalization of thrombi was defined by characteristics on OCT. RESULTS: Recanalization of thrombi was identified in 6 patients (3 male, 3 female; median age 63 years; age range 54 to 72 years). Based on symptoms, 3 patients were diagnosed with unstable angina; 2 were diagnosed with stable angina; and 1, who had mitral stenosis and huge left atrial thrombi, was diagnosed with post-infarct angina. All had normal serum concentrations of cardiac markers at admission. Angiography showed irregular linear filling defects and haziness. Two patients with near total occlusion had Thrombolysis In Myocardial Infarction (TIMI) flow grade 1 and collaterals, whereas 4 patients had TIMI flow grade 3 and no collaterals. All patients showed OCT findings consistent with recanalized thrombi, which consisted of signal-rich, high backscattered septa that divided the lumen into multiple small cavities communicating with each other. These structures, which had smooth inner borders, created a "Swiss cheese" appearance. Percutaneous coronary intervention was performed in 5 patients with angiographic slow flow or inducible-ischemia as documented by invasive or noninvasive stress tests. The remaining 1 patient with restored coronary flow underwent mitral valve surgery and left atrial thrombectomy. CONCLUSIONS: OCT provided details on the characteristics of the organization of thrombi in both chronic total occlusion and subtotal narrowing. Coronary lesions containing recanalized thrombi were characterized by multiple small channels, with most showing functional significance.

Effect of substrate modification in catheter ablation of paroxysmal atrial fibrillation: pulmonary vein isolation alone or with complex fractionated electrogram ablation.

Catheter ablation of atrial fibrillation that targets complex fractionated electrogram sites has been widely applied in the management of persistent atrial fibrillation. The clinical outcomes of pulmonary vein isolation alone and pulmonary vein isolation plus the use of complex fractionated electrogram-guided ablation (CFEA) have not been fully compared in patients with paroxysmal atrial fibrillation.This prospective study included 70 patients with symptomatic paroxysmal atrial fibrillation that remained inducible after pulmonary vein isolation. For radio-frequency catheter ablation, patients were nonrandomly assigned to a control group (pulmonary vein isolation alone, Group 1, n=35) or a CFEA group (pulmonary vein isolation plus additional CFEA, Group 2, n=35). The times to first recurrence of atrial tachyarrhythmias were compared between the 2 groups.In Group 2, CFEA rendered atrial fibrillation noninducible in 16 patients (45.7%) and converted inducible atrial fibrillation into inducible atrial flutters in 12 patients (34.3%). Atrial fibrillation remained inducible in 7 patients (20%) after the combined ablation procedures. After a mean follow-up of 23 months, freedom from recurrence of atrial tachyarrhythmias was significantly higher in Group 2 than in Group 1 (P=0.037). In Group 1, all of the recurrent tachyarrhythmias were atrial fibrillation, whereas regular tachycardia was the major mechanism of recurrent arrhythmias in Group 2 (atrial tachycardia or atrial flutter in 5 of 6 patients and atrial fibrillation in 1 patient).We found that CFEA after pulmonary vein isolation significantly reduced recurrent atrial tachyarrhythmia and might modify the pattern of arrhythmia recurrence in patients with paroxysmal atrial fibrillation.

Randomized trial of optimal treatment strategies for in-stent restenosis after drug-eluting stent implantation.

OBJECTIVES: The purpose of this study is to compare the efficacy of the treatment strategies for in-stent restenosis (ISR) of drug-eluting stents (DES) according to the morphologic pattern of restenosis. BACKGROUND: Optimal treatment strategies for ISR within DES have not been adequately addressed yet. METHODS: Patients with ISR of DES were randomized according to the lesion length to compare outcomes of sirolimus-eluting stent (SES) versus cutting balloon angioplasty for focal type (≤10 mm) and SES versus everolimus-eluting stent (EES) for diffuse type (>10 mm). The primary endpoint was in-segment late loss at 9 months. Overall 162 patients, 96 with focal ISR and 66 with diffuse ISR, were enrolled. RESULTS: In focal lesions, in-segment late loss was significantly higher in the cutting balloon group (n = 48) than in the SES group (n = 48; 0.25 mm, interquartile range [IQR]: -0.01 to 0.68 mm vs. 0.06 mm, IQR: -0.08 to 0.17 mm; p = 0.04). Consequently, in-segment restenosis rate tended to be higher in the cutting balloon group than in the SES group (20.7% vs. 3.1%, p = 0.06) with comparable incidences of the composite of death, myocardial infarction, or target vessel revascularization at 12 months of clinical follow up (6.3% vs. 6.3%, p > 0.99). In 66 cases of diffuse ISR, in-segment late loss (0.11 mm, IQR: -0.02 to 0.30 mm; vs. 0.00 mm, IQR: -0.08 to 0.25 mm; p = 0.64), in-segment restenosis rate (5.0% vs. 14.3%, p = 0.32), and the composite incidence of death, myocardial infarction, or target lesion revascularization (9.6% vs. 8.8%, p > 0.99) did not differ between SES group (n = 32) and EES group (n = 34). CONCLUSIONS: For lesions of focal DES restenosis, repeat implantation of SES is more effective in reducing late luminal loss and subsequent restenosis rate than cutting balloon angioplasty. For diffuse DES restenosis, implantation of SES or EES is comparably effective in terms of angiographic and clinical outcomes.

Validation of functional state of coronary tandem lesions using computational flow dynamics.

Functional lesion assessment for coronary tandem lesions and its clinical applications have not been thoroughly studied. The aim of this study was to test the hypothesis that the fractional flow reserve (FFR) gradient across an individual stenosis (ΔFFR) during pressure-wire pullback is a surrogate of the relative functional severity of each stenosis in coronary tandem lesions. For in vitro validation, computational flow dynamic modeling of coronary tandem lesion with various degree of stenosis was constructed. For clinical validation, a total of 52 patients (104 lesions) with coronary tandem lesions (2 stenoses along 1 coronary artery) were consecutively enrolled, and tailored stent procedures based on ΔFFR was performed, at first treating the lesion with large ΔFFR and then subsequently reassessing the FFR for the remaining lesion. The coronary stenosis was considered functionally significant and stenting was performed when the FFR of a lesion was ≤0.80. Using in vitro computational flow dynamic modeling, the lesion with the large ΔFFR of the coronary tandem lesion was indicated as the lesion with the greater degree of simulated diameter stenosis. In the clinical cohort, 28 patients (53.8%) had only single-lesion treatment, and stent implantation for 28 lesions (26.9%) was deferred according to the proposed strategy. During the 9-month follow-up period, only 1 repeat revascularization occurred among the deferred lesions. In conclusion, for the treatment of coronary tandem lesions, ΔFFR may be a useful index for prioritizing the treatment sequence and optimizing the stenting procedure. In this way, unnecessary stent implantation can be avoided, with the achievement of favorable functional and clinical outcomes.

Visual-functional mismatch between coronary angiography and fractional flow reserve.

OBJECTIVES: The goal of this study was to identify clinical and lesion-specific local factors affecting visual-functional mismatch. BACKGROUND: Although lesion severity determined by coronary angiography has not been well correlated with physiological significance, the mechanism of the discordance remains poorly understood. METHODS: The authors assessed quantitative coronary angiography, intravascular ultrasound (IVUS), and fractional flow reserve (FFR) in a prospective cohort of 1,000 patients with 1,129 coronary lesions. Three-dimensional computational simulation studies were performed. RESULTS: Lesions with angiographic diameter stenosis (DS) ≥50% and FFR >0.80 ("mismatches") were seen in 57% of non-left main lesions and in 35% of the left main lesions, respectively (p = 0.032). Conversely, among the lesions with DS <50% and FFR <0.80 ("reverse mismatches") 16% were found in the non-left main lesions and 40% in the left main lesions (p < 0.001). The independent predictors for mismatch were advanced age, non-left anterior descending artery location, absence of plaque rupture, short lesion length, large minimal lumen area, smaller plaque burden, and greater minimal lumen diameter. Conversely, reverse mismatch was independently associated with younger age, left anterior descending artery location, the presence of plaque rupture, a smaller minimal lumen area, and larger plaque burden. In a computational simulation study, FFR was influenced by DS, lesion length, different lesion shape, plaque eccentricity, surface roughness, and various shapes of plaque rupture. CONCLUSIONS: There were high frequencies of visual-functional mismatch between angiography and FFR. The discrepancy was related to the clinical and lesion-specific factors frequently unrecognizable by angiography, thus suggesting that coronary angiography cannot accurately predict FFR. (Natural History of FFR-Guided Deferred Coronary Lesions [IRIS FFR-DEFER]; NCT01366404).

Comparison of resolute zotarolimus-eluting stents and sirolimus-eluting stents in patients with de novo long coronary artery lesions: a randomized LONG-DES IV trial.

BACKGROUND: Procedural and clinical outcomes still remain unfavorable for patients with long coronary lesions who undergo stent-based coronary interventions. Therefore, we compared the relative efficacy and safety of resolute zotarolimus-eluting stents (R-ZES) and sirolimus-eluting stents (SES) for patients with de novo long coronary lesions. METHODS AND RESULTS: This randomized, multicenter, prospective trial, called the Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-IV (LONG-DES IV) trial, compared long R-ZES and SES in 500 patients with long (≥25 mm) native coronary lesions. The primary end point of the trial was in-segment late luminal loss at 9-month angiographic follow-up. The baseline characteristics were not different between R-ZES and SES groups, including lesion lengths (32.4±13.5 mm versus 31.0±13.5 mm, P=0.27). At 9-month angiographic follow-up, the R-ZES was noninferior to the SES with respect to in-segment late luminal loss, the primary study end point (0.14±0.38 mm versus 0.12±0.43 mm, P for noninferiority=0.03, P for superiority=0.68). In addition, in-stent late luminal loss (0.26±0.36 mm versus 0.24±0.42 mm, P=0.78) and the rates of in-segment (5.2% versus 7.2%, P=0.44) and in-stent (4.0% versus 6.0%, P=0.41) binary restenosis were not significantly different between the 2 groups. There were no significant between-group differences in the rate of adverse clinical events (death, myocardial infarction, stent thrombosis, target-lesion revascularization, and composite outcomes). CONCLUSIONS: For patients with de novo long coronary artery disease, R-ZES implantation showed noninferior angiographic outcomes as compared with SES implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186094.

Outcomes after unrestricted use of everolimus-eluting and sirolimus-eluting stents in routine clinical practice: a multicenter, prospective cohort study.

BACKGROUND: It remains unclear whether there are differences in the safety and efficacy outcomes between everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in contemporary practice. METHODS AND RESULTS: We prospectively enrolled 6166 consecutive patients who received EES (3081 patients) and SES (3085 patients) between April 2008 and June 2010, using data from the Interventional Cardiology Research In-Cooperation Society-Drug-Eluting Stents Registry. The primary end point was a composite of death, nonfatal myocardial infarction (MI), or target-vessel revascularization (TVR). At 2 years of follow-up, the 2 study groups did not differ significantly in crude risk of the primary end point (12.1% for EES versus 12.4% for SES; HR, 0.97; 95% CI, 0.84-1.12, P=0.66). After adjustment for differences in baseline risk factors, the adjusted risk for the primary end point remained similar for the 2 stent types (HR, 0.96; 95% CI, 0.82-1.12, P=0.60). There were also no differences between the stent groups in the adjusted risks of the individual component of death (HR, 0.93; 95% CI, 0.67-1.30, P=0.68), MI (HR, 0.97; 95% CI, 0.79-1.18, P=0.74), and TVR (HR, 1.10; 95% CI, 0.82-1.49, P=0.51). The adjusted risk of stent thrombosis also was similar (HR, 1.16; 95% CI, 0.47-2.84, P=0.75). CONCLUSIONS: In contemporary practice of percutaneous coronary intervention procedures, the unrestricted use of EES and SES showed similar rates of safety and efficacy outcomes with regard to death, MI, sent thrombosis, and TVR. Future longer-term follow-up is needed to better define the relative benefits of these drug-eluting stents. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01070420.

Comprehensive intravascular ultrasound assessment of stent area and its impact on restenosis and adverse cardiac events in 403 patients with unprotected left main disease.

BACKGROUND: We assessed the optimal intravascular ultrasound (IVUS) stent area to predict angiographic in-stent restenosis (ISR) after sirolimus-eluting stent implantation for unprotected left main coronary artery (LM) disease. METHODS AND RESULTS: A total of 403 patients treated with single- or 2-stent strategies (crushing and T-stent) had immediate poststenting IVUS and 9-month follow-up angiography. Poststenting minimal stent area (MSA) was measured in each of 4 segments: ostial left anterior descending (LAD), ostial left circumflex (LCX) polygon of confluence (POC, confluence zone of LAD and LCX), and proximal LM above the POC. Overall, 46 (11.4%) showed angiographic restenosis at 9 months: 3 of 67 (4.5%) nonbifurcation lesions treated with a single-stent, 14 of 222 (6.3%) bifurcation lesions treated with single-stent crossover, and 29 of 114 (25.4%) of bifurcation lesions treated with 2 stents. The MSA cutoffs that best predicted ISR on a segmental basis were 5.0 mm(2) (ostial LCX ISR), 6.3 mm(2) (ostial LAD ISR), 7.2 mm(2) (ISR within the POC), and 8.2 mm(2) (ISR within the LM above the POC). Using these criteria, 133 (33.8%) had underexpansion of at least 1 segment. Angiographic ISR (at any location) was more frequent in lesions with underexpansion of at least 1 segment versus lesions with no underexpansion (24.1% versus 5.4%, P<0.001). Two-year major adverse coronary event-free survival rate was significantly lower in patients with underexpansion of at least 1 segment versus lesions with no underexpansion (90±3% versus 98±1%, log-rank P<0.001), and poststenting underexpansion was an independent predictor for major adverse cardiac events (adjusted hazard ratio, 5.56; 95% confidence interval, 1.99-15.49; P=0.001). CONCLUSIONS: With these criteria, IVUS optimization during LMCA stenting procedures may improve clinical outcomes.

Impact of bleeding on subsequent early and late mortality after drug-eluting stent implantation.

OBJECTIVES: The aim of this study was to assess the impact of early and late bleeding on subsequent mortality after drug-eluting stent (DES) implantation. BACKGROUND: Little is known about the impact of late bleeding after DES implantation. METHODS: With a time-updated Cox model, the impact of bleeding and myocardial infarction (MI) on 3-year mortality was analyzed in 3,148 consecutive patients who underwent DES implantation for coronary disease. RESULTS: Bleeding, defined according to STEEPLE (Safety and Efficacy of Enoxaparin in PCI Patients, an International Randomized Evaluation) minor or major criteria, occurred in 6.5% of patients over 3 years. Patients with bleeding were older; were more likely to be female; had higher rates of diabetes mellitus, hypertension, and extensive coronary disease and lower ventricular function; and underwent more complex procedures than those without bleeding. The 3-year adjusted hazard ratios (HRs) for mortality were 5.81 (95% confidence interval [CI]: 3.92 to 8.60; p < 0.001) for patients with bleeding and 2.53 (95% CI: 1.62 to 3.96; p < 0.001) for patients with MI. When the timings of events were separated, the HRs for mortality were 4.89 (95% CI: 3.08 to 7.78; p < 0.001) and 7.81 (95% CI: 4.39 to 13.89; p < 0.001) for patients with bleeding within and after 30 days, respectively. By contrast, the HRs for mortality were 1.85 (95% CI: 1.09 to 3.14, p = 0.022) and 10.33 (95% CI: 4.91 to 21.75, p < 0.001) for patients with MI within and after 30 days, respectively. CONCLUSIONS: Bleeding is closely associated with mortality during both the early and late periods after DES implantation. Therefore, in addition to carefully assessing bleeding after stenting, evidence-based treatment should be implemented to offer the best balance of benefit and harm.

A point-of-care platelet function assay and C-reactive protein for prediction of major cardiovascular events after drug-eluting stent implantation.

OBJECTIVES: This study sought to investigate clinical utility of on-site platelet function test and C-reactive protein (CRP) in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Data on long-term prognostic value of high on-treatment platelet reactivity (HTPR) on clopidogrel after PCI are limited. As a distinct biological pathway, CRP has been suggested to be associated with post-PCI atherothrombotic events. METHODS: We evaluated 2,849 patients who received drug-eluting stents (DES) and had post-PCI VerifyNow P2Y12 assays (Accumetrics, San Diego, California) performed. Among them, baseline CRP measurement was available in 2,546 patients. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, stent thrombosis, and stroke. RESULTS: During follow-up (median, 2.2 years), the occurrence of the primary endpoint did not significantly differ among patients with and without HTPR (2.8% vs. 2.4% at 2 years; hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.88 to 2.01; p = 0.18). By contrast, patients with elevated CRP levels were at significantly higher risk for the primary endpoint, as compared with those with nonelevated CRP levels (5.6% vs. 1.7% at 2 years; HR: 2.81, 95% CI:, 1.83 to 4.31; p < 0.001). The VerifyNow test had no incremental usefulness to classify long-term risk. However, the incorporation of CRP into a model with conventional clinical and procedural risk factors significantly improved the C-statistic for the prediction of the primary endpoint (0.729 to 0.759; p = 0.03). CONCLUSIONS: We failed to identify that HTPR measured by VerifyNow P2Y12 assay was significantly associated with long-term atherothrombotic risks in patients receiving DES. However, elevated CRP levels were significantly associated with worse outcomes and had incremental predictive values over conventional risk factors.

Long-term comparison of drug-eluting stents and coronary artery bypass grafting for multivessel coronary revascularization: 5-year outcomes from the Asan Medical Center-Multivessel Revascularization Registry.

OBJECTIVES: We performed the long-term (5-year) follow-up of a large cohort of patients who underwent drug-eluting stent (DES) or coronary artery bypass graft (CABG) surgery for multivessel revascularization. BACKGROUND: Limited information is available on very long-term outcomes after multivessel DES treatment relative to CABG. METHODS: We evaluated 3,042 patients with multivessel disease who received DES (n = 1,547) or underwent CABG (n = 1,495) between January 2003 and December 2005, and for whom complete follow-up data were available for a median 5.6 years (interquartile range: 4.6 to 6.3 years). We compared adverse outcomes (death; a composite outcome of death, myocardial infarction, or stroke; and repeat revascularization). RESULTS: After adjustment for differences in baseline risk factors, 5-year risk of death (hazard ratio [HR]: 1.00; 95% confidence interval [CI]: 0.76 to 1.32, p = 0.99) and the combined risk of death, myocardial infarction, or stroke (HR: 0.97; 95% CI: 0.76 to 1.24, p = 0.81) were similar between the DES group and the CABG group. However, the rates of revascularization were significantly higher in the DES group (HR: 2.93; 95% CI: 2.20 to 3.90, p < 0.001). Similar results were obtained in comparisons of DES with CABG for high-risk clinical and anatomic subgroups with diabetes mellitus, abnormal ventricular function, age 65 years or more, and 3-vessel and left main disease. However, mortality benefit with DES implantation relative to CABG was noted in patients with 2-vessel disease (HR: 0.57; 95% CI: 0.36 to 0.92, p = 0.02). CONCLUSIONS: For patients with multivessel disease, DES treatment, compared with CABG, showed similar rates of mortality and of the composite safety outcomes, but higher rates of revascularization up to 5 years.