Value of intravascular ultrasound in guiding coronary interventions.

There has been great effort to improve clinical outcome in percutaneous treatment for coronary artery disease. Complementary to coronary angiography, intravascular ultrasound (IVUS) provides in vivo tomographic anatomic information, enabling to evaluate from the lumen to the vessel wall. As a result, IVUS has had a pivotal role to understand pathophysiology of coronary artery disease and improve clinical outcome. It provides preprocedural information to evaluate stenosis severity and plaque characteristics and helps with optimal stent deployment, minimizing underexpansion and geographic miss that are the major mechanisms of stent failure. Recently, many large-scale clinical trials and meta-analyses with drug-eluting stents have shown the clinical benefits of IVUS-guided percutaneous coronary intervention. Some recent studies have also supported the cost-effectiveness of IVUS-guided PCI especially in high-risk patients. This article will discuss the clinical value of IVUS in contemporary practice.

Randomized trial of stents versus bypass surgery for left main coronary artery disease.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used to treat unprotected left main coronary artery stenosis, although coronary-artery bypass grafting (CABG) has been considered to be the treatment of choice. METHODS: We randomly assigned patients with unprotected left main coronary artery stenosis to undergo CABG (300 patients) or PCI with sirolimus-eluting stents (300 patients). Using a wide margin for noninferiority, we compared the groups with respect to the primary composite end point of major adverse cardiac or cerebrovascular events (death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization) at 1 year. Event rates at 2 years were also compared between the two groups. RESULTS: The primary end point occurred in 26 patients assigned to PCI as compared with 20 patients assigned to CABG (cumulative event rate, 8.7% vs. 6.7%; absolute risk difference, 2.0 percentage points; 95% confidence interval [CI], -1.6 to 5.6; P=0.01 for noninferiority). By 2 years, the primary end point had occurred in 36 patients in the PCI group as compared with 24 in the CABG group (cumulative event rate, 12.2% vs. 8.1%; hazard ratio with PCI, 1.50; 95% CI, 0.90 to 2.52; P=0.12). The composite rate of death, myocardial infarction, or stroke at 2 years occurred in 13 and 14 patients in the two groups, respectively (cumulative event rate, 4.4% and 4.7%, respectively; hazard ratio, 0.92; 95% CI, 0.43 to 1.96; P=0.83). Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group as compared with 12 patients in the CABG group (cumulative event rate, 9.0% vs. 4.2%; hazard ratio, 2.18; 95% CI, 1.10 to 4.32; P=0.02). CONCLUSIONS: In this randomized trial involving patients with unprotected left main coronary artery stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive. (Funded by the Cardiovascular Research Foundation, Seoul, Korea, and others; PRECOMBAT ClinicalTrials.gov number, NCT00422968.).

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.

Impact of angiographic complete revascularization after drug-eluting stent implantation or coronary artery bypass graft surgery for multivessel coronary artery disease.

BACKGROUND: This study sought to evaluate the clinical impact of angiographic complete revascularization (CR) after drug-eluting stent implantation or coronary artery bypass graft surgery for multivessel coronary disease. METHODS AND RESULTS: A total of 1914 consecutive patients with multivessel coronary disease undergoing drug-eluting stent implantation (1400 patients) or coronary artery bypass graft surgery (514 patients) were enrolled. Angiographic CR was defined as revascularization in all diseased segments according to the Synergy Between PCI With Taxus and Cardiac Surgery classification. The outcomes of patients undergoing CR were compared with those undergoing incomplete revascularization (IR) after adjustments with the inverse-probability-of-treatment weighting method. Angiographic CR was performed in 917 patients (47.9%) including 573 percutaneous coronary intervention (40.9%) and 344 coronary artery bypass graft (66.9%) patients. CR patients were younger and had more extensive coronary disease than IR patients. Over 5 years, CR patients had comparable incidences of death (8.9% versus 8.9%; adjusted hazard ratio, 1.04; 95% confidence interval, 0.76 to 1.43; P=0.81), the composite of death, myocardial infarction, and stroke (12.1% versus 11.9%; adjusted hazard ratio, 1.04; 95% confidence interval, 0.79 to 1.36; P=0.80), and the composite of death, myocardial infarction, stroke, and repeat revascularization (22.4% versus 24.9%; adjusted hazard ratio, 0.91; 95% confidence interval, 0.75 to 1.10; P=0.32) compared with IR patients. However, 368 patients (19.2%) with multivessel IR had a greater tendency toward higher risk of death, myocardial infarction, stroke, or repeat revascularization (30.3% versus 22.1%; adjusted hazard ratio, 1.27; 95% confidence interval, 0.97 to 1.66; P=0.079) than those without multivessel IR. CONCLUSIONS: Angiographic CR with drug-eluting stent implantation or coronary artery bypass grafting did not improve long-term clinical outcomes in patients with multivessel disease. This finding supports the strategy of ischemia-guided revascularization.

Acute and long-term angiographic outcomes of side branch stenosis after randomized treatment of zotarolimus-, sirolimus-, and paclitaxel-eluting stent for coronary artery stenosis.

This was designed to assess the outcomes of side branch (SB) stenosis after implantation of three drug-eluting stents (DES). From 2,645 patients in the ZEST (Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary Lesions) Trial, 788 patients had 923 bifurcation lesions with SB ≥ 1.5 mm were included. SB was treated in 150 lesions, including 35 (3.8%) receiving SB stenting. Of untreated SB with baseline stenosis < 50%, the incidences of periprocedural SB compromise was similar in the zotarolimus (15.8%), sirolimus (17.2%), and paclitaxel (16.6%) stent groups (P = 0.92). At follow-up angiography, delayed SB compromise occurred in 13.9%, 3.2%, and 9.4% (P = 0.010) of these groups. When classified into four groups (< 50%, 50%-70%, 70%-99%, and 100%), 9.0% of untreated SB were worsened, whereas improvement and stationary were observed in 9.6% and 81.4%. In a multivariable logistic regression model, main branch (MB) stenosis at follow-up (%) was the only independent predictor of SB stenosis worsening (odds ratio, 1.03; 95% confidence interval, 1.01-1.04; P < 0.001). After MB stenting in bifurcation lesions, a minority of SB appears to worsen. DES with strong anti-restenotic efficacy may help maintain SB patency.

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.

[A case of adenosquamous carcinoma of the papilla of Vater].

Adenosquamous carcinoma of the papilla of Vater is a rare tumor and only a few cases have been reported so far. Here, we report a case of adenosquamous carcinoma in a 76-year-old male who presented with jaundice and right upper quadrant abdominal pain. Ultrasonography and enhanced abdominal CT scans showed dilated common bile duct (CBD) and intrahepatic bile duct (IHD) with a suspicious obstructing mass in distal CBD. On endoscopy, obstructing and ulcerated mass was noted on the papilla of Vater. Histopathological inspection of the biopsied specimens from mass showed adenosquamous cell carcinoma of the papilla of Vater. Since the patient refused operation, we inserted a self-expandable metallic stent in distal CBD. This is the first case report on adenosquamous carcinoma of the papilla of Vater in Korea.

Association between bicuspid aortic valve phenotype and patterns of valvular dysfunction and bicuspid aortopathy: comprehensive evaluation using MDCT and echocardiography.

OBJECTIVES: We sought to define the clinical importance of an integrated classification of bicuspid aortic valve (BAV) phenotypes and aortopathy using multidetector computed tomography (MDCT). BACKGROUND: An association between BAV phenotypes and the pattern of valvular dysfunction or bicuspid aortopathy has yet to be definitely established. METHODS: The study cohort included 167 subjects (116 men, age 54.6 ± 14.4 years) who underwent both MDCT and transthoracic echocardiography from 2003 to 2010. Two BAV phenotypes-fusion of the right and left coronary cusps (BAV-AP) and fusion of the right or left coronary cusp and noncoronary cusp (BAV-RL)-were identified. Forty-five patients showed normal aortic dimensions and were classified as type 0. In the remaining patients, hierarchic cluster analysis showed 3 different types of bicuspid aortopathy according to the pattern of aortic dilation: type 1 (aortic enlargement confined to the sinus of Valsalva [n = 34]), type 2 (aortic enlargement involving the tubular portion of the ascending aorta [n = 49]), and type 3 (aortic enlargement extending to the transverse aortic arch [n = 39]). RESULTS: The prevalence of BAV-AP and BAV-RL was 55.7% and 44.3%, respectively. Comparing BAV-AP and BAV-RL, no differences in age or in the prevalence of male sex were determined. However, significant differences in the valvular dysfunction pattern were noted, with moderate-to-severe aortic stenosis predominating in patients with BAV-RL (66.2% vs. 46.2% in BAV-AP; p = 0.01), and moderate-to-severe aortic regurgitation in BAV-AP (32.3% vs. 6.8% in BAV-RL; p < 0.0001). A normal aorta was the most common phenotype in BAV-AP patients (33.3% vs. 18.9% in BAV-RL; p = 0.037), and type 3 aortopathy was the most common phenotype in BAV-RL patients (40.5% vs. 9.7% in BAV-AP; p < 0.0001). CONCLUSIONS: The patterns of valvular dysfunction and bicuspid aortopathy differed significantly between the 2 BAV phenotypes, suggesting the possibility of etiologically different entities.

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.

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.

Comparison of effects of atorvastatin (20 mg) versus rosuvastatin (10 mg) therapy on mild coronary atherosclerotic plaques (from the ARTMAP trial).

High-dose rosuvastatin induces regression of coronary atherosclerosis, but it remains uncertain whether usual-dose statin has similar effects. We compared the effects of atorvastatin 20 mg/day versus rosuvastatin 10 mg/day on mild coronary atherosclerotic plaques (20% to 50% luminal narrowing and lesion length >10 mm) using intravascular ultrasound (IVUS). Three hundred fifty statin-naive patients with mild coronary atherosclerotic plaques were randomized to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. IVUS examinations were performed at baseline and 6-month follow-up. Primary end point was percent change in total atheroma volume (TAV) defined as (TAV at 6 months - TAV at baseline)/(TAV at baseline) × 100. Evaluable IVUS was obtained for 271 patients (atorvastatin in 143, rosuvastatin in 128). Clinical characteristics, lipid levels, and IVUS measurements at baseline were similar between the 2 groups. At 6-month follow-up, percent change in TAV was significantly less in the atorvastatin group than in the rosuvastatin group (-3.9 ± 11.9% vs -7.4 ± 10.6%, respectively, p = 0.018). In contrast, change in percent atheroma volume was not different between the 2 groups (-0.3 ± 4.2 vs -1.1 ± 3.5, respectively, p = 0.157). Compared to baseline, TAV and TAV at the most diseased 10-mm subsegment were significantly decreased in the 2 groups (p <0.001). Changes in lipid profiles at 6-month follow-up were similar between the 2 groups. In conclusion, usual doses of atorvastatin and rosuvastatin induced significant regression of coronary atherosclerosis in statin-naive patients, with a greater decrease in favor of rosuvastatin.

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.

Long-term outcome of stents versus bypass surgery in diabetic and nondiabetic patients with multivessel or left main coronary artery disease: a pooled analysis of 5775 individual patient data.

BACKGROUND: Coronary artery bypass grafting and percutaneous coronary intervention (PCI) are alternative treatments for complex multivessel or left main disease. However, the relative treatment effects in diabetic and nondiabetic patients remain uncertain. METHODS AND RESULTS: We performed a pooled analysis of 5775 patients from 3 clinical studies comparing PCI and coronary artery bypass grafting for multivessel or left main disease and compared adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and repeat revascularization) according to the diabetic status. Over a median follow-up of 5.5 years, risk-adjusted mortality after PCI relative to coronary artery bypass grafting was not different in diabetic (hazard ratio [HR], 1.15; 95% CI, 0.88-1.51) and nondiabetic (HR, 1.15; 95% CI, 0.88-1.50) patients. The adjusted risks of the composite outcome of death, Q-wave myocardial infarction, or stroke were also not different in diabetic (HR, 1.00; 95% CI, 0.79-1.26) and nondiabetic (HR, 0.99; 95% CI, 0.78-1.26) patients. However, PCI was significantly associated with higher risk of repeat revascularization both in diabetic (HR, 3.56; 95% CI, 2.62-4.83) and in nondiabetic (HR, 3.55; 95% CI, 2.61-4.83) patients. Significant interactions were absent between diabetic status and revascularization strategies for death (P=0.27), composite outcome of death, Q-wave myocardial infarction, or stroke (P=0.97), and repeat revascularization (P=0.08). CONCLUSIONS: For multivessel or left main disease, the long-term risks of mortality and composite serious outcomes were not different between PCI and coronary artery bypass grafting in diabetic and nondiabetic patients, but PCI was associated with higher risk of repeat revascularization. These relative treatment effects were not modified by diabetic status. These results are hypothesis generating and should be addressed in a randomized trial.

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.

Impact of ischemia-guided revascularization with myocardial perfusion imaging for patients with multivessel coronary disease.

OBJECTIVES: The aim of this study was to evaluate the impact of ischemia-guided (IG) revascularization. BACKGROUND: The importance of IG revascularization has not been well-determined. METHODS: The outcomes of IG revascularization, in which revascularization was performed in the matched coronary artery with the perfusion abnormality on myocardial perfusion image (MPI), were retrospectively compared with those of non-IG revascularization in a registry of 5,340 patients with multivessel coronary disease comprising 2,587 percutaneous coronary interventions (PCIs) with drug-eluting stents and 2,753 coronary artery bypass graft (CABG) surgeries after adjustment with inverse-probability-of-treatment weighting. RESULTS: The MPI was performed in 42.3% of patients, and IG revascularization was performed in 17.3%, including 12.4% in PCI and 21.8% in CABG patients (p < 0.001). The incidence of major adverse cardiac and cerebrovascular events (MACCE) including death, myocardial infarction, stroke, or repeat revascularization was significantly lower in the IG than in the non-IG group (16.2% vs. 20.7%; adjusted hazard ratio [aHR]: 0.73; 95% confidence interval [CI]: 0.60 to 0.88; p = 0.001), primarily driven by the lower repeat revascularization rate (9.9% vs. 22.8%; aHR: 0.66; 95% CI: 0.49 to 0.90; p = 0.009). Subgroup analysis showed that IG reduced the risk of MACCE in PCI (17.4% vs. 22.8%; aHR: 0.59; 95% CI: 0.43 to 0.81; p = 0.001) but not in CABG (16.0% vs. 18.5%; aHR: 0.87; 95% CI: 0.67 to 1.14; p = 0.31) patients. CONCLUSIONS: Ischemia-guided revascularization with MPI, particularly in PCI-treated patients, seems to decrease the risk of repeat revascularization and MACCE for patients with multivessel disease.

Influence of diabetes mellitus on long-term (five-year) outcomes of drug-eluting stents and coronary artery bypass grafting for multivessel coronary revascularization.

Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and for diffuse and progressive atherosclerosis. We evaluated the outcomes of drug-eluting stent (DES) placement and coronary artery bypass grafting (CABG) in 891 diabetic patients (489 for DES implantation and 402 for CABG) and 2,151 nondiabetic patients (1,058 for DES implantation and 1,093 for CABG) with multivessel CAD treated from January 2003 through December 2005 and followed up for a median 5.6 years. Outcomes of interest included death; the composite outcome of death, myocardial infarction (MI), or stroke; and repeat revascularization. In diabetic patients, after adjusting for baseline covariates, 5-year risk of death (hazard ratio 1.01, 95% confidence interval 0.77 to 1.33, p = 0.96) and the composite of death, MI, or stroke (hazard ratio 1.03, 95% confidence interval 0.80 to 1.31, p = 0.91) were similar in patients undergoing DES or CABG. However, rate of repeat revascularization was significantly higher in the DES group (hazard ratio 3.69, 95% confidence interval 2.64 to 5.17, p <0.001). These trends were consistent in nondiabetic patients (hazard ratio 0.80, 95% confidence interval 0.55 to 1.16, p = 0.23 for death; hazard ratio 0.77, 95% confidence interval 0.56 to 1.05, p = 0.10 for composite of death, MI, or stroke; hazard ratio 2.77, 95% CI 1.95 to 3.91, p <0.001 for repeat revascularization). There was no significant interaction between diabetic status and treatment strategy on clinical outcomes (p for interaction = 0.36 for death; 0.20 for the composite of death, MI, or stroke; and 0.40 for repeat revascularization). In conclusion, there was no significant prognostic influence of diabetes on long-term treatment with DES or CABG in patients with multivessel CAD.

Everolimus-eluting stent implantation for unprotected left main coronary artery stenosis. The PRECOMBAT-2 (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) study.

OBJECTIVES: This study sought to evaluate the safety and efficacy of second-generation drug-eluting stents (DES) for patients with unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND: The clinical benefit of second-generation DES for ULMCA stenosis has not been determined. METHODS: The authors assessed 334 consecutive patients who received everolimus-eluting stents (EES) for ULMCA stenosis between 2009 and 2010. The 18-month incidence rates of major adverse cardiac or cerebrovascular events (MACCE), including death, myocardial infarction (MI), stroke, or ischemia-driven target vessel revascularization (TVR), were compared with those of a randomized study comparing patients who received sirolimus-eluting stents (SES) (n = 327) or coronary artery bypass grafts (CABG) (n = 272). RESULTS: EES (8.9%) showed a comparable incidence of MACCE as SES (10.8%; adjusted hazard ratio [aHR] of EES: 0.84; 95% confidence interval [CI]: 0.51 to 1.40; p = 0.51) and CABG (6.7%, aHR of EES: 1.40; 95% CI: 0.78 to 2.54; p = 0.26). The composite incidence of death, MI, or stroke also did not differ among patients receiving EES (3.3%), SES (3.7%; aHR of EES: 0.63; 95% CI: 0.27 to 1.47; p = 0.29), and CABG (4.8%; aHR of EES: 0.67; 95% CI: 0.29 to 1.54; p = 0.34). However, the incidence of ischemia-driven TVR in the EES group (6.5%) was higher than in the CABG group (2.6%, aHR of EES: 2.77; 95% CI: 1.17 to 6.58; p = 0.02), but comparable to SES (8.2%, aHR of EES: 1.14; 95% CI: 0.64 to 2.06; p = 0.65). Angiographic restenosis rates were similar in the SES and EES groups (13.8% vs. 9.2%, p = 0.16). CONCLUSIONS: Second-generation EES had a similar 18-month risk of MACCE for ULMCA stenosis as first-generation SES or CABG.

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.