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Procedural and clinical outcomes still remain unfavorable for patients with long coronary lesions who undergo percutaneous coronary intervention. The current study, therefore, evaluated 2 innovative drug-eluting stents for the management of long-lesion coronary artery disease.This randomized, multicenter, prospective trial, called the Long Drug-Eluting Stent (LONG-DES) V trial, compared the biodegradable polymer-based biolimus A9-eluting stent (BES) and the durable polymer-based platinum chromium everolimus-eluting stent (PtCr-EES) in 500 patients with long (≥25 mm) coronary lesions. The primary end point of the trial was in-segment late luminal loss at the 9-month angiographic follow-up. The BES and PtCr-EES groups had similar baseline characteristics, with a slightly shorter lesion length in the BES group versus the PtCr-EES group (29.24±12.17 versus 32.27±13.84 mm; P=0.016). In-segment late luminal loss was comparable between the 2 groups at the 9-month angiographic follow-up (BES, 0.14±0.38 versus PtCr-EES, 0.11±0.37 mm; difference, 0.031; 95% confidence interval, -0.053 to 0.091; P=0.03 for a noninferiority margin of 0.11, P=0.45 for superiority), as was in-stent late luminal loss (0.20±0.41 versus 0.24±0.38 mm; P=0.29). The incidence of in-segment (6.1% versus 4.9%; P=0.63) and in-stent (3.7% versus 4.9%; P=0.59) binary restenosis was also similar between the groups. There was no significant between-group difference in the rate of composite outcome of death, myocardial infarction, and target vessel revascularization (41, 16.7% in BES versus 42, 16.5% in PtCr-EES; P=0.94).BES and PtCr-EES implantation showed analogous angiographic and clinical outcomes for patients with de novo long coronary lesions.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186120. [ABSTRACT FROM AUTHOR]

Conflicting data exist regarding the relation between body mass index (BMI) and cardiovascular events and mortality after percutaneous coronary intervention.We performed pooled analyses to evaluate the association between BMI (weight in kilograms divided by the square of the height in meters) and the risks of major cardiovascular events (defined as death from cardiovascular causes, nonfatal myocardial infarction, stent thrombosis, or stroke) and death among 23 181 patients from 11 prospective percutaneous coronary intervention studies. Overall, mean (±SD) BMI was 24.9±3.0. During follow-up (median, 2.1 years), 2381 patients had a major cardiovascular event, and 1004 patients died. After adjusting covariates, there was an inverse relationship between BMI and adverse outcomes. With a BMI of 22.5 to 24.9 as the reference category, the risk of major cardiovascular events was elevated among patients with a lower BMI (by a factor of 1.52 for a BMI <18.5; 1.05 for a BMI of 18.5-19.9; 1.03 for a BMI of 20.0-22.4); by contrast, the risk declined among patients with a higher BMI (by a factor of 0.97 for a BMI of 25.0-27.4; 0.97 for a BMI of 27.5-29.9; and 0.78 for a BMI of ≥30.0). In general, the hazard ratios for deaths were similar.Among patients undergoing percutaneous coronary intervention, a low BMI was associated with increased risks of major cardiovascular events and death. However, there were no excess risks of these events associated with a high BMI. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: The impact of various coronary lesion geometries on fractional flow reserve (FFR) is poorly understood. Methods and Results: A total of 1552 coronary lesions in 1236 patients from a prospective Interventional Cardiology Research In-cooperation Society Fractional Flow Reserve and Intravascular Ultrasound registry were assessed using quantitative coronary angiography, intravascular ultrasound, and FFR. Computational fluid dynamics simulation was performed for theoretical validation. Patients with complex geometries, such as longitudinal eccentricity, cross-sectional eccentricity, and surface roughness, showed significantly lower FFR values. In multivariable analysis, distal longitudinal eccentricity (adjusted odds ratio, 1.55; 95% confidence interval, 1.04–2.87; P=0.031), cross-sectional eccentricity (adjusted odds ratio, 1.65; 95% confidence interval, 1.27–2.14; P<0.001), and surface roughness (adjusted odds ratio, 1.55; 95% confidence interval, 1.04–2.32; P=0.033), as well as male sex, left anterior descending artery territory, proximal location, high degree of diameter stenosis, long lesion, and high plaque burden, were identified as independent predictors for significantly low FFR values (≤0.80). Computational simulation supported the impact of lesion geometry on FFR. Conclusions: The complex coronary lesion geometries were independently associated with reduced FFR values. The visual–functional mismatch between coronary angiography and FFR could be partly attributable to local geometric factors. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01366404. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomographic angiography (CTA) is a reliable modality to detect coronary artery disease. However, CTA generally overestimates stenosis severity compared with invasive angiography, and angiographic stenosis does not necessarily imply hemodynamic relevance when fractional flow reserve (FFR) is used as reference. CTA-based FFR (CT-FFR), using computational fluid dynamics (CFD), improves the correlation with invasive FFR results but is computationally demanding. More recently, a new machine-learning (ML) CT-FFR algorithm has been developed based on a deep learning model, which can be performed on a regular workstation. In this large multicenter cohort, the diagnostic performance ML-based CT-FFR was compared with CTA and CFD-based CT-FFR for detection of functionally obstructive coronary artery disease., Methods and Results: At 5 centers in Europe, Asia, and the United States, 351 patients, including 525 vessels with invasive FFR comparison, were included. ML-based and CFD-based CT-FFR were performed on the CTA data, and diagnostic performance was evaluated using invasive FFR as reference. Correlation between ML-based and CFD-based CT-FFR was excellent ( R =0.997). ML-based (area under curve, 0.84) and CFD-based CT-FFR (0.84) outperformed visual CTA (0.69; P <0.0001). On a per-vessel basis, diagnostic accuracy improved from 58% (95% confidence interval, 54%-63%) by CTA to 78% (75%-82%) by ML-based CT-FFR. The per-patient accuracy improved from 71% (66%-76%) by CTA to 85% (81%-89%) by adding ML-based CT-FFR as 62 of 85 (73%) false-positive CTA results could be correctly reclassified by adding ML-based CT-FFR., Conclusions: On-site CT-FFR based on ML improves the performance of CTA by correctly reclassifying hemodynamically nonsignificant stenosis and performs equally well as CFD-based CT-FFR., (© 2018 American Heart Association, Inc.)

Background: The applicability of Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery scores to left main coronary artery disease (CAD) has been questioned. A simplified alternative is needed for guiding decision making., Methods and Results: We evaluated the prognostic value of a simplified angiographic classification in comparison with a Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score-based approach for patients with left main CAD undergoing drug-eluting stent implantation. The proposed approach classified left main CAD as either extensive (n=819), defined as left main bifurcation lesions with an involvement of ostial left circumflex artery or as any left main lesion plus multivessel CAD, or limited (n=453), defined as ostial/midshaft lesions or left main bifurcation lesions without an involvement of ostium of left circumflex artery, alone or plus 1-vessel disease. The databases from 4 prospective Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease studies were pooled, and the primary outcome was a major adverse cardiac event, defined as death, myocardial infarction, or repeat revascularization. During follow-up (median 38 months; interquartile range, 36-61 months), the risk for major adverse cardiac event was significantly higher with extensive than with limited left main CAD (adjusted hazard ratio, 2.13; 95% confidence interval, 1.54-2.94; P <0.001). The risk for a composite outcome of death or myocardial infarction was also higher with extensive left main CAD (adjusted hazard ratio, 1.75; 95% confidence interval, 1.08-2.85; P =0.02). However, Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score tertiles did not effectively stratify these 2 outcome measures., Conclusions: Compared with Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery scores, the simpler angiographic approach provided better discrimination for future cardiovascular events in patients with left main CAD undergoing drug-eluting stent implantation., (© 2018 American Heart Association, Inc.)

Objective: The aim of this study was to determine how trial-based findings of EXCEL and NOBLE might be interpreted and generalizable in 'real-world' settings with comparison of data from the large-scaled, all-comer Interventional Research Incorporation Society-Left MAIN Revascularization (IRIS-MAIN) registry., Patients and Methods: We compared baseline clinical and procedural characteristics and also determined how the relative treatment effect of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) was different in EXCEL and NOBLE, compared with those of the multicenter, IRIS-MAIN registry (n=2481). The primary outcome for between-study comparison was a composite of death, myocardial infarction (MI), or stroke., Results: There were between-study differences in patient risk profiles (age, BMI, diabetes, and clinical presentation), lesion complexities, and procedural characteristics (stent type, the use of off-pump surgery, and radial artery); the proportion of diabetes and acute coronary syndrome was particularly lower in NOBLE than in other studies. Although there was interstudy heterogeneity for the protocol definition of MI, the risks for serious composite outcome of death, MI, or stroke were similar between PCI and CABG in EXCEL [hazard ratio (HR): 1.00; 95% confidence interval (CI): 0.79-1.26; P=0.98] and in the matched cohort of IRIS-MAIN (HR: 1.08; 95%CI: 0.85-1.38; P=0.53), whereas it was significantly higher after PCI than after CABG in NOBLE (HR: 1.47; 95%CI: 1.06-2.05; P=0.02), which was driven by more common MI and stroke after PCI., Conclusion: In the comparison of a large-sized, all-comer registry, the EXCEL trial might represent better generalizability with respect to baseline characteristics and observed clinical outcomes compared with the NOBLE trial.

Objective: Patients with previous stroke are increasing among patients receiving percutaneous coronary intervention (PCI) with drug-eluting stents (DES); however, data about the influence of previous stroke on patient outcomes are limited. We evaluated whether previous stroke is associated with increased risk for mortality in coronary artery disease., Patients and Methods: A total of 18 650 patients with coronary artery disease undergoing PCI with DES were enrolled. Databases from three real-world PCI registries were merged for a patient-level meta-analysis. The primary outcome was death from any cause. The secondary outcomes were death from a cardiac cause, myocardial infarction, stent thrombosis, stroke, or repeat revascularization., Results: Patients with previous stroke (n=1361), compared with those without previous stroke (n=17 289), were older and had a higher prevalence of risk factors or comorbidities. At a median follow-up of 47.0 months, patients with previous stroke had a higher risk for death from any cause [adjusted hazard ratio (HR)=1.623; 95% confidence interval (CI): 1.342-1.962; P<0.001], death from a cardiac cause (adjusted HR=1.686; 95% CI: 1.339-2.124; P<0.001), and stroke (adjusted HR=2.456; 95% CI: 1.853-3.255; P<0.001). There were no significant differences in the risks for myocardial infarction, stent thrombosis, or repeat revascularization., Conclusion: Patients with previous stroke showed higher risks for all-cause death and stroke after PCI with DES than those without stroke. Previous stroke should be considered a risk factor for all-cause death and stroke in this patient population.

Background: Diabetes mellitus (DM), low ejection fraction (EF), and the extent of coronary artery disease (CAD) have all been identified as predictors of cardiovascular events in multivessel disease, but their comparative contributions to future risk remain unclear in patients with unprotected left main coronary artery (ULMCA) disease. Through this study we aimed to categorize the risk for cardiovascular events in patients with ULMCA disease using simple clinical descriptors., Patients and Methods: Our study included a total of 5975 patients with ULMCA disease from the Interventional Research Incorporation Society-Left MAIN Revascularization registry who were treated with percutaneous coronary intervention (n=2850), coronary artery bypass grafting (n=2337), or medical therapy alone (n=608). We categorized the risk for cardiovascular events using simple clinical descriptors (DM, low EF, and the extent of CAD). The primary outcome was a major adverse cardiac or cerebrovascular event (MACCE) (i.e. death from any cause, stroke, myocardial infarction, or repeat revascularization)., Results: Overall, the 5-year rate of MACCE was highest in the medical group, lower in the percutaneous coronary intervention group, and lowest in the coronary artery bypass grafting group (42.5, 25.7, and 19.9%, respectively; P<0.001). In multivariable modeling, the presence of DM [hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.12-1.40; P<0.001], low EF of 40% or less (HR: 1.83; 95% CI: 1.56-2.15; P<0.001), and the extent of CAD (HR: 1.14; 95% CI: 1.08-1.21; P<0.001) were independent predictors of MACCE; in addition, these factors were consistently associated with a significantly higher risk for MACCE, regardless of index treatment strategies., Conclusion: Simple clinical descriptors can assist clinicians in identifying high-risk patients and in predicting future cardiovascular events within the broad range of risk factors for ULMCA disease.

Background: Identifying predictive factors for major cardiovascular events and death in patients with unprotected left main coronary artery disease is of great clinical value for risk stratification and possible guidance for tailored preventive strategies., Methods and Results: The Interventional Research Incorporation Society-Left MAIN Revascularization registry included 5795 patients with unprotected left main coronary artery disease (percutaneous coronary intervention, n=2850; coronary-artery bypass grafting, n=2337; medication alone, n=608). We analyzed the incidence and independent predictors of major adverse cardiac and cerebrovascular events (MACCE; a composite of death, MI, stroke, or repeat revascularization) and all-cause mortality in each treatment stratum. During follow-up (median, 4.3 years), the rates of MACCE and death were substantially higher in the medical group than in the percutaneous coronary intervention and coronary-artery bypass grafting groups ( P <0.001). In the percutaneous coronary intervention group, the 3 strongest predictors for MACCE were chronic renal failure, old age (≥65 years), and previous heart failure; those for all-cause mortality were chronic renal failure, old age, and low ejection fraction. In the coronary-artery bypass grafting group, old age, chronic renal failure, and low ejection fraction were the 3 strongest predictors of MACCE and death. In the medication group, old age, low ejection fraction, and diabetes mellitus were the 3 strongest predictors of MACCE and death., Conclusions: Among patients with unprotected left main coronary artery disease, the key clinical predictors for MACCE and death were generally similar regardless of index treatment. This study provides effect estimates for clinically relevant predictors of long-term clinical outcomes in real-world left main coronary artery patients, providing possible guidance for tailored preventive strategies., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01341327., (© 2017 American Heart Association, Inc.)

Background: The mechanism of statin for atheroma stabilization remains unclear. We aimed to assess the relationship between on-treatment changes in serum inflammatory biomarker levels and plaque composition in differed nonculprit coronary lesions., Methods and Results: The changes in serum biochemical values, and intravascular ultrasound data were evaluated in 218 patients with virtual histology (VH)-intravascular ultrasound-defined fibroatheroma-containing segments after 12-month rosuvastatin treatment. When stratifying patients into quartiles according to the change in high-sensitivity C-reactive protein (hsCRP), there was a significant positive linear relationship for the changes in %necrotic core (coefficient, 1.31; standard error, 0.54) and %dense calcium volumes (coefficient, 0.80; standard error, 0.27), but a negative linear relationship for the changes in %fibrous (coefficient, -0.94; standard error, 0.45) and %fibrofatty volumes (coefficient, -1.17; standard error, 0.56; all P <0.05). The decrease in hsCRP (-1.2±3.9 versus 0.5±3.4 mg/L; P =0.02) was greater in those without VH-defined thin-cap fibroatheroma (TCFA, defined as >30° of necrotic core abutting the lumen in 3 consecutive slices) than those with VH-TCFA at follow-up. Diabetes mellitus, a larger normalized total atheroma volume, and the presence of VH-TCFA at baseline predicted the presence of VH-TCFA at follow-up (odds ratio, 4.01, 1.18, and 9.21, respectively; all P <0.05), whereas the change in hsCRP showed a trend (odds ratio, 1.19; P =0.07). The change in low-density lipoprotein-cholesterol had no relationship with the changes in hsCRP or plaque compositions., Conclusions: With 12-month rosuvastatin therapy, a greater hsCRP reduction (not low-density lipoprotein-cholesterol) was associated with a greater decrease in %necrotic core volume and the absence of VH-TCFA, indicating a link between the anti-inflammatory action of statin and plaque stabilization by reducing NC and reinforcing fibrous cap., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00997880., (© 2017 American Heart Association, Inc.)

Background: We evaluated the prognosis of deferred and revascularized coronary stenoses after fractional flow reserve (FFR) measurement to assess its revascularization threshold in clinical practice., Methods: The IRIS-FFR registry (Interventional Cardiology Research In-cooperation Society Fractional Flow Reserve) prospectively enrolled 5846 patients with ≥1coronary lesion with FFR measurement. Revascularization was deferred in 6468 lesions and performed in 2165 lesions after FFR assessment. The primary end point was major adverse cardiac events (cardiac death, myocardial infarction, and repeat revascularization) at a median follow-up of 1.9 years and analyzed on a per-lesion basis. A marginal Cox model accounted for correlated data in patients with multiple lesions, and a model to predict per-lesion outcomes was adjusted for confounding factors., Results: For deferred lesions, the risk of major adverse cardiac events demonstrated a significant, inverse relationship with FFR (adjusted hazard ratio, 1.06; 95% confidence interval, 1.05-1.08; P <0.001). However, this relationship was not observed in revascularized lesions (adjusted hazard ratio, 1.00; 95% confidence interval, 0.98-1.02; P =0.70). For lesions with FFR ≥0.76, the risk of major adverse cardiac events was not significantly different between deferred and revascularized lesions. Conversely, in lesions with FFR ≤0.75, the risk of major adverse cardiac events was significantly lower in revascularized lesions than in deferred lesions (for FFR 0.71-0.75, adjusted hazard ratio, 0.47; 95% confidence interval, 0.24-0.89; P =0.021; for FFR ≤0.70, adjusted hazard ratio 0.47; 95% confidence interval, 0.26-0.84; P =0.012)., Conclusions: This large, prospective registry showed that the FFR value was linearly associated with the risk of cardiac events in deferred lesions. In addition, revascularization for coronary artery stenosis with a low FFR (≤0.75) was associated with better outcomes than the deferral, whereas for a stenosis with a high FFR (≥0.76), medical treatment would be a reasonable and safe treatment strategy., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01366404., (© 2017 American Heart Association, Inc.)

Background: Changes over time in revascularization strategies and outcomes among patients with unprotected left main coronary artery stenosis remain largely unknown., Methods and Results: A total of 2618 consecutive patients with unprotected left main coronary artery stenosis who underwent revascularization were identified from the ASAN Medical Center-Left MAIN Revascularization registry and classified by time periods: bare metal stent (wave 1, 1995-1998), early drug-eluting stents (wave 2, 2003-2006), and late drug-eluting stents (wave 3, 2007-2010). Primary end point was major adverse cerebrocardiovascular events (the composite of death, myocardial infarction, repeat revascularization, and stroke). During the study period, 1124 patients underwent percutaneous coronary intervention (PCI) and 1494 patients underwent coronary artery bypass grafting. The proportion of PCI significantly increased from 35% to 52% between waves 1 and 3. In patients receiving PCI, the risk-adjusted incidence rate of major adverse cerebro-cardiovascular events decreased from 20.18 cases per 100 person-years in wave 1 to 6.77 cases per 100 person-years in wave 3 (P<0.001 for trend). Death, the composite of death, myocardial infarction, stroke, and repeat revascularization were also significantly decreased by 40%, 35%, and 46%, respectively. The risk-adjusted incidence rate of major adverse cerebrocardiovascular events did not change in patients receiving coronary artery bypass grafting. The difference major adverse cerebrocardiovascular events risk between PCI and coronary artery bypass grafting progressively reduced (adjusted hazard ratio [95% confidence interval], 0.33 [0.23-0.47]; 0.53 [0.35-0.80]; and 1.01 [0.68-1.49] from wave 1 to wave 3., Conclusions: The outcomes of unprotected left main coronary artery PCI have significantly improved over time. In addition, more patients received PCI for unprotected left main coronary artery stenosis in recent years., (© 2015 American Heart Association, Inc.)

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.

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.

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.

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.

Background: Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus., Methods and Results: This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23 ± 0.27 versus 0.37 ± 0.52 mm; difference, -0.13 mm; 95% confidence interval, -0.25 to -0.02; upper 1-sided 95% confidence interval, -0.04; P<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%; P=0.029) and in-segment restenosis (0.9% versus 6.5%; P=0.035). However, in-stent late loss (0.11 ± 0.26 versus 0.20 ± 0.49 mm; P=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%; P=0.317), death (1.3% versus 3.3%; P=0.448), and myocardial infarction (0% versus 1.3%; P=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%; P=0.218), were also not statistically different between the 2 groups., Conclusion: Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease.

Background: We assessed geometric changes responsible for acute lumen loss at the left circumflex coronary artery (LCX) ostium after crossover stenting from the left anterior descending coronary artery (LAD) to the left main artery., Methods and Results: Twenty-three left main artery bifurcation lesions with a preprocedural angiographic diameter stenosis <50% at the LCX ostium were evaluated using prestenting and poststenting intravascular ultrasound pullbacks from both the LAD and the LCX. At the minimal lumen area (MLA) sites within the LCX ostium and at the LCX carina, the lumen, stent, plaque+media (P+M), and external elastic membrane (EEM) areas were measured; the EEM eccentricity was calculated at the LCX carina. The change in MLA within the LCX ostium (ΔL), the change in EEM area at the MLA site (ΔV), and the change in P+M area at the MLA site (ΔP) were calculated. The MLA within the LCX ostium significantly decreased from 5.4 mm(2) (first and third quartiles, 4.3 mm(2), 7.2 mm(2)) prestenting to 4.0 mm(2) (3.0 mm(2), 4.8 mm(2)) poststenting (P<0.001). The percent change in MLA within the LCX ostium correlated with changes in EEM eccentricity (r=-0.414, P=0.049) and percent change in EEM area at the MLA site (r=0.626, P=0.001). A smaller distal carina angle between the LAD and the LCX before stenting was associated with a greater percent reduction in lumen (r=0.472, P=0.023) and EEM (r=0.402, P=0.048) after stenting. In 18 lesions with >10% reduction of MLA within the LCX ostium despite the lack of direct relationship between ΔL and ΔP at the MLA site, ΔP closely correlated with the ratio of ΔV to ΔL (r=-0.953, P<0.001), suggesting that an increase in plaque at the LCX ostium contributed to the MLA loss relative to the decrease in EEM area., Conclusions: Lumen loss at the LCX ostium frequently occurred after crossover stenting from the distal LM to the LAD. The main mechanism was carina shift that was associated with a narrow angle between the LAD and LCX.

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.

Background: As a substudy of the large, randomized ZEST (Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary Lesions) trial comparing first- and second-generation drug-eluting stents, we evaluated intimal hyperplasia (IH) and vascular changes using volumetric intravascular ultrasound analysis., Methods and Results: Complete angiographic and volumetric intravascular ultrasound data immediately after stenting and at 9-month follow-up were available in 162 patients with 183 lesions: 61 sirolimus-eluting stents (SES), 64 paclitaxel-eluting stents (PES), and 58 zotarolimus-eluting stents (ZES). External elastic membrane, stent, lumen, and peristent plaque volumes (external elastic membrane minus stent) were normalized by stent length. Percent IH volumes were calculated as [IH volume/stent volume]×100, %. Reduction of minimal luminal area) was greater in PES than SES (-1.4±1.5 mm(2) versus -0.7±0.9 mm(2), P=0.003), whereas minimal luminal area change in ZES was not significantly different from SES (-1.2±1.0 mm(2) versus -0.7±0.9 mm(2), P=0.055). Percent IH volume was less in SES compared with PES (9.8±6.0% versus 17.5±11.2%, P=0.002) or with ZES (9.8±6.0% versus 18.2±7.6%, P=0.005). Comparing ZES versus PES, there were no significant differences in %IH volume (17.5±11.2% versus 18.2±7.6%, P=0.779) or changes in normalized lumen volume (-1.2±1.3 mm(2) versus -1.1±0.8 mm(2), P=0.452). Late stent malapposition was identified in 8 (13%) SES and 2 (3%) PES but in no ZES (P=0.050). Angiographic restenosis was detected in 6 lesions (3 PES and 3 ZES)., Conclusions: The degree of neointimal growth in ZES was similar to that in PES but less than that in SES. ZES had no late stent malappositions., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00418067., (© 2011 American Heart Association, Inc.)

Background: We used intravascular ultrasound (IVUS) to (1) clarify the mechanisms of luminal loss after drug-eluting stent (DES) implantation and (2) classify morphological patterns of in-stent restenosis (ISR)., Methods and Results: On the basis of IVUS-identified luminal narrowing (in-stent minimum lumen area <4 mm(2)), IVUS-defined ISR was classified as focal (luminal narrowing ≤10 mm in length), multifocal (≥1 focal lesions), and diffuse (luminal narrowing >10 mm in length) with or without stent edge involvement. Significant intimal hyperplasia (IH) was defined as IH area >50% of stent. Overall, 76 lesions had IVUS-defined ISR; 32 (42%) had stent underexpansion (minimal stent area <5 mm(2)); and 71 (93%) had IH area >50% of stent. Total stent length negatively correlated with minimal stent area (r=-0.613, P<0.001) as well as with stent area at the minimum lumen site (r=-0.436, P<0.001) but not with minimum lumen area (r=-0.084, P=0.472). Underexpansion was present at the minimum lumen site in 15 of 43 (35%) lesions with stent length >28 mm, even though there was significant IH in 34 (79%) lesions; conversely, in 32 of 33 (97%) lesions with stent length ≤28 mm, the minimum lumen site was not associated with stent underexpansion but significant IH. IVUS-defined focal ISR was most common (47%). Compared with focal ISR, normalized vessel, stent, lumen, and plaque volumes were smaller in diffuse and multifocal than focal ISR, with no difference in IH extent., Conclusions: In most DES restenosis, IH was the dominant mechanism of ISR. Nevertheless, underexpansion associated with longer stent length remained an important preventable mechanism of ISR.

Background: We assessed optimal intravascular ultrasound (IVUS) criteria for predicting functional significance of intermediate coronary lesions., Methods and Results: Overall, 201 patients with 236 coronary lesions underwent IVUS and invasive physiological assessment before intervention. Fractional flow reserve (FFR) was measured at maximal hyperemia induced by intravenous adenosine infusion. FFR <0.80 at maximum hyperemia was seen in 49 (21%) of the overall 236 lesions. The independent determinants of FFR were minimal lumen area (MLA; β=0.020; 95% confidence interval [CI], 0.008 to 0.031; P=0.032), plaque burden (β=-0.002; 95% CI, -0.003 to 0.001; P=0.001), lesion length with a lumen area <3.0 mm(2) (β=-0.003; 95% CI, -0.005 to -0.001; P=0.005), and left anterior descending artery location (β=-0.035; 95% CI, -0.055 to -0.016; P=0.001). The best cutoff value (with a maximal accuracy) of the MLA to predict FFR <0.80 was <2.4 mm(2), with a diagnostic accuracy of 68% (90% sensitivity, 60% specificity, and area under the curve=0.800; 95% CI, 0.742 to 0.848; P<0.001). The cutoff value of plaque burden to predict FFR <0.80 was ≥79% (69% sensitivity, 72% specificity, and area under the curve=0.756; 95% CI, 0.696 to 0.810; P<0.001). The cutoff value of lesion length with a lumen area <3.0 mm(2) was 3.1 mm (84%sensitivity, 63%specificity, and area under the curve=0.765; 95% CI, 0.706 to 0.818; P<0.001). Among 117 lesions with an MLA ≥2.4 mm(2), 112 (96%) had an FFR ≥0.80,; and all but 1 showed FFR ≥0.75. Conversely, 44 (37%) lesions with an MLA <2.4 mm(2) had an FFR <0.80., Conclusions: IVUS-derived MLA ≥2.4 mm(2) may be useful to exclude FFR <0.80, but poor specificity limits its value for physiological assessment of lesions with MLA <2.4 mm(2). Thus, FFR or stress tests may be necessary to accurately identify ischemia-inducible intermediate stenoses.

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

Background: The clinical characteristics that identify high-risk subsets of patients with unprotected left main coronary artery disease undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have not been well established., Methods and Results: Between January 2000 and June 2006, 2240 patients with unprotected left main coronary artery disease underwent PCI (n=1102) or CABG (n=1138). Twenty-six preprocedural parameters were evaluated by univariate and multivariate Cox regression analysis to identify independent predictors of all-cause mortality and target-vessel revascularization. Interaction tests were performed to compare heterogeneities of effects of preprocedural parameters depending on the revascularization methods. During follow-up (median of 3.1 years), 187 patients died (78 PCI and 109 CABG) and 149 patients had target-vessel revascularization (121 PCI and 28 CABG). EuroSCORE > or =6 was an independent predictor of death in both groups. Additional independent predictors were chronic renal failure and previous congestive heart failure in the PCI group and age > or =75 years, atrial fibrillation, right coronary artery disease, and left main distal bifurcation disease in the CABG group. Interaction analysis showed no heterogeneities of the effects of variables depending on the revascularization methods. Independent predictors of target-vessel revascularization were acute coronary syndrome and left main distal bifurcation disease in the PCI group and history of coronary intervention in the CABG group. The interaction between previous PCI and treatment remained after adjustment for all independent predictors of target-vessel revascularization (interaction P=0.0345)., Conclusions: Several clinical characteristics were identified as important preprocedural predictors of long-term adverse outcomes after percutaneous or surgical revascularization in patients with unprotected left main coronary artery disease.

Background: Although C-reactive protein (CRP) has been proposed as a useful biomarker for predicting atherothrombosis, the association between CRP and stent thrombosis after drug-eluting stent implantation has not been defined., Methods and Results: We prospectively evaluated 2691 patients treated with drug-eluting stents who had a baseline CRP measurement. The primary outcome was stent thrombosis; secondary outcomes were death, myocardial infarction (MI), death or MI, and target vessel revascularization. During follow-up (median, 3.9 years), 32 patients had definite or probable stent thrombosis, 137 patients died, 227 had an MI, and 195 underwent target vessel revascularization. In multivariable Cox proportional-hazards models, elevated levels of CRP were significantly associated with increased risk of stent thrombosis (hazard ratio, 3.86; 95% confidence interval, 1.82 to 8.18; P<0.001). Elevated CRP levels also significantly predicted the risks of death (hazard ratio, 1.61; 95% confidence interval, 1.13 to 2.28; P=0.008), MI (hazard ratio, 1.63; 95% confidence interval, 1.25 to 2.12; P=0.001), and death or MI (hazard ratio, 1.61; 95% confidence interval, 1.29 to 2.00; P<0.001) but not target vessel revascularization (hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; P=0.21). The incorporation of CRP into a model with patient, lesion, and procedural factors resulted in a significant increase in the C statistic for the prediction of stent thrombosis, MI, and the composite of death or MI., Conclusions: Elevated CRP levels were significantly associated with increased risks of stent thrombosis, death, and MI in patients receiving drug-eluting stents, suggesting the usefulness of inflammatory risk assessment with CRP. Given the relatively infrequent occurrence of stent thrombosis, death, and MI, larger studies with longer-term follow-up are required to confirm the novel relationship.

Background: Limited information is available on long-term outcomes for patients with unprotected left main coronary artery disease who received drug-eluting stents (DES)., Methods and Results: In the multicenter registry evaluating outcomes among patients with unprotected left main coronary artery stenosis undergoing stenting with either bare metal stents (BMS) or DES, 1217 consecutive patients were divided into 2 groups: 353 who received only BMS and 864 who received at least 1 DES. The 3-year outcomes were compared by use of the adjustment of inverse-probability-of-treatment-weighted method. Patients receiving DES were older and had a higher prevalence of diabetes mellitus, hypertension, hyperlipidemia, and multivessel disease. In the overall population, with the use of DES, the 3-year adjusted risk of death (8.0% versus 9.5%; hazard ratio, 0.71; 95% confidence interval, 0.36 to 1.40; P=0.976) or death or myocardial infarction (14.3% versus 14.9%; hazard ratio, 0.83; 95% confidence interval, 0.49 to 1.40; P=0.479) was similar compared with BMS. However, the risk of target lesion revascularization was significantly lower with the use of DES than BMS (5.4% versus 12.1%; hazard ratio, 0.40; 95% confidence interval, 0.22 to 0.73; P=0.003). When patients were classified according to lesion location, DES was still associated with lower risk of target lesion revascularization in patients with bifurcation (6.9% versus 16.3%; hazard ratio, 0.38; 95% confidence interval, 0.18 to 0.78; P=0.009) or nonbifurcation (3.4% versus 10.3%; hazard ratio, 0.39; 95% confidence interval, 0.17 to 0.88; P=0.024) lesions with a comparable risk of death or myocardial infarction., Conclusions: Compared with BMS, DES was associated with a reduction in the need for repeat revascularization without increasing the risk of death or myocardial infarction for patients with unprotected left main coronary artery stenosis.

Background: Although intravascular ultrasound (IVUS) guidance has been useful in stenting for unprotected left main coronary artery stenosis, its impact on long-term mortality is still unclear., Methods and Results: In the MAIN-COMPARE registry, patients with unprotected left main coronary artery stenosis in a hemodynamically stable condition underwent elective stenting under the guidance of IVUS (756 patients) or conventional angiography (219 patients). Patients with acute myocardial infarction were excluded. The 3-year outcomes between the 2 groups were primarily compared using propensity-score matching in the entire and separate populations according to stent type. In 201 matched pairs of the overall population, there was a tendency of lower risk of 3-year morality with IVUS guidance compared with angiography guidance (6.0% versus 13.6%, log-rank P=0.063; hazard ratio, 0.54; 95% CI, 0.28 to 1.03; Cox-model P=0.061). In particular, in 145 matched pairs of patients receiving drug-eluting stent, the 3-year incidence of mortality was lower with IVUS guidance as compared with angiography guidance (4.7% versus 16.0%, log-rank P=0.048; hazard ratio, 0.39; 95% CI, 0.15 to 1.02; Cox model P=0.055). In contrast, the use of IVUS guidance did not reduce the risk of mortality in 47 matched pairs of patients receiving bare-metal stent (8.6% versus 10.8%, log-rank P=0.35; hazard ratio, 0.59; 95% CI, 0.18 to 1.91; Cox model P=0.38). The risk of myocardial infarction or target vessel revascularization was not associated with the use of IVUS guidance., Conclusions: Elective stenting with IVUS guidance, especially in the placement of drug-eluting stent, may reduce the long-term mortality rate for unprotected left main coronary artery stenosis when compared with conventional angiography guidance.