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Background: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions., Methods: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance., Conclusion: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients., Competing Interests: Conflict of interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

Importance: The associations between angiographic findings and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and their clinical relevance according to residual functional disease burden have not been thoroughly investigated., Objectives: To evaluate the association of angiographic and physiologic parameters according to residual functional disease burden after drug-eluting stent implantation., Design, Setting, and Participants: This cohort study population was from the International Post-PCI FFR registry, which incorporated 4 registries from Korea, China, and Japan. Patients who underwent angiographically successful second-generation drug-eluting stent implantation and post-PCI FFR measurement were included in the analysis. The patients were divided into 3 groups according to the residual disease burden (post-PCI FFR ≤0.80 [residual ischemia], 0.81-0.86 [suboptimal], and >0.86 [optimal]). The data were collected from August 23, 2018, to June 11, 2019, and the current analysis was performed from January 11, 2022, to October 7, 2023., Exposures: Angiographic parameters and post-PCI FFR., Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization (TVR) at 2 years., Results: In this cohort of 2147 patients, the mean (SD) age was 64.3 (10.0) years, and 1644 patients (76.6%) were men. Based on the post-PCI physiologic status, 269 patients (12.5%) had residual ischemia, 551 (25.7%) had suboptimal results, and 1327 (61.8%) had optimal results. Angiographic parameters had poor correlations with post-PCI FFR (r < 0.20). Post-PCI FFR was isolated from all angiographic parameters in the unsupervised hierarchical cluster analysis. Post-PCI FFR was associated with the occurrence of TVF (adjusted hazard ratio [AHR] per post-PCI FFR 0.01 increase, 0.94 [95% CI, 0.92-0.97]; P < .001), but angiographic parameters were not. The residual ischemia group had a significantly higher rate of TVF than the suboptimal group (AHR, 1.75 [95% CI, 1.08-2.83]; P = .02) and the optimal group (AHR, 2.94 [95% CI, 1.82-4.73]; P < .001). The TVR in the residual ischemia group was predominantly associated with TVR in the nonstented segment (14 [53.8%]), unlike the other 2 groups (3 [10.0%] in the suboptimal group and 13 [30.2%] in the optimal group)., Conclusions and Relevance: In this cohort study of the International Post-PCI FFR registry, a low degree of associations were observed between angiographic and physiologic parameters after PCI. Post-PCI FFR, unlike angiographic parameters, was associated with clinical events and the distribution of clinical events. The current study supports the use of post-PCI FFR as a procedural quality metric and further prospective study is warranted.

Background: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome., Methods: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed., Findings: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups., Interpretation: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone., Funding: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project., Translation: For the Mandarin translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GWS reports speaker fees from Medtronic, Pulnovo, Infraredx, Abiomed, Abbott, Amgen, and Boehringer Ingelheim; has served as a consultant to Daiichi Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, and Oxitope; has equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave paid directly to institution; and his daughter is an employee at IQVIA. S-LC reports speaker fees from Microport, Pulnovo, Boston International Scientific, Medtronic, Sanofi, and BioMed; and grants from the National Scientific Foundation of China. GSM received honorarium from Boston Scientific. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y 12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y 12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE)., Methods: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed., Findings: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; p non-inferiority <0·0001, p superiority =0·89)., Interpretation: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy., Funding: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project., Translation: For the Mandarin translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GWS reports speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Abbott, Amgen, and Boehringer Ingelheim; has served as a consultant to Daiichi Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, and Oxitope; has equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; reports research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave paid directly to institution; and his daughter is an employee at IQVIA. S-LC reports speaker honoraria from Microport, Pulnovo, Boston International Scientific, Medtronic, Sanofi, and BioMed; grants from the National Scientific Foundation of China; and is a Fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. All other authors report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI., Methods and Results: A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; P <0.001), cardiac death (RR, 0.49 [95% CI, 0.34-0.71]; P <0.001), stent thrombosis (RR, 0.63 [95% CI, 0.40-0.99]; P =0.046), target-lesion revascularization (RR, 0.67 [95% CI, 0.49-0.91]; P =0.01), and target-vessel revascularization (RR, 0.60 [95% CI, 0.45-0.80]; P <0.001). In complex lesion subsets, the point estimate for imaging-guided PCI compared with angiography-guided PCI for all-cause death was a RR of 0.75 (95% CI, 0.55-1.02; P =0.07)., Conclusions: In patients undergoing PCI, intravascular imaging is associated with reductions in major adverse cardiac events, cardiac death, stent thrombosis, target-lesion revascularization, and target-vessel revascularization. The magnitude of benefit is large and consistent across all included studies. There may also be benefits in all-cause death, particularly in complex lesion subsets. These results support the use of intravascular imaging as standard of care and updates of clinical guidelines.

Background and Aims: Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) reflects residual atherosclerotic burden and is associated with future events. How much post-PCI FFR can be predicted based on baseline basic information and the clinical relevance have not been investigated., Methods: We compiled a multicenter registry of patients undergoing pre- and post-PCI FFR. Machine-learning (ML) algorithms were designed to predict post-PCI FFR levels from baseline demographics, quantitative coronary angiography, and pre-PCI FFR. FFR deviation was defined as actual minus ML-predicted post-PCI FFR levels, and its association with incident target vessel failure (TVF) was evaluated., Results: Median (IQR) pre- and post-PCI FFR values were 0.71 (0.61, 0.77) and 0.88 (0.84, 0.93), respectively. The Spearman correlation coefficient of the actual and predicted post-PCI FFR was 0.54 (95% CI: 0.52, 0.57). FFR deviation was non-linearly associated with incident TVF (HR [95% CI] with Q3 as reference: 1.65 [1.14, 2.39] in Q1, 1.42 [0.98, 2.08] in Q2, 0.81 [0.53, 1.26] in Q4, and 1.04 [0.69, 1.56] in Q5). A model with polynomial function of continuous FFR deviation indicated increasing TVF risk for FFR deviation ≤0 but plateau risk with FFR deviation >0., Conclusions: An ML-based algorithm using baseline data moderately predicted post-PCI FFR. The deviation of post-PCI FFR from the predicted value was associated with higher vessel-oriented event., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Koo reported receiving grants from Abbott Vascular and Philips Volcano during the conduct of the study. Dr. Tanaka reported receiving personal fees from Abbott Vascular Japan and personal fees from Daiichi-Sankyo Co Ltd during the conduct of the study. Dr. Azzalini received honoraria from Teleflex, Abiomed, Asahi Intecc, Philips, GE Healthcare, Abbott Vascular, and Cardiovascular System, Inc. No other disclosures were reported. Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve measurement after drug-eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target-vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post-PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all P <0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; P =0.03) and vice versa (area under the curve 0.68 versus 0.78; P =0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; P for trend <0.01). Conclusions In patients undergoing drug-eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target-vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04684043. www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42021234748.

Coronary stent underexpansion is associated with restenosis and stent thrombosis. In clinical studies of atherosclerosis, high wall shear stress (WSS) has been associated with activation of prothrombotic pathways, upregulation of matrix metalloproteinases, and future myocardial infarction. We hypothesized that stent underexpansion is predictive of high WSS. WSS distribution was investigated in patients enrolled in the prospective randomized controlled study of angulated coronary arteries randomized to undergo percutaneous coronary intervention with R-ZES or X-EES. WSS was calculated from 3D reconstructions of arteries from intravascular ultrasound (IVUS) and angiography using computational fluid dynamics. A logistic regression model investigated the relationship between WSS and underexpansion and the relationship between underexpansion and stent platform. Mean age was 63±11, 78% were male, 35% had diabetes, mean pre-stent angulation was 36.7°±14.7°. Underexpansion was assessed in 83 patients (6,181 IVUS frames). Frames with stent underexpansion were significantly more likely to exhibit high WSS (> 2.5 Pa) compared to those without underexpansion with an OR of 2.197 (95% CI = [1.233-3.913], p = 0.008). There was no significant association between underexpansion and low WSS (< 1.0 Pa) and no significant differences in underexpansion between R-ZES and X-EES. In the Shear Stent randomized controlled study, underexpanded IVUS frames were more than twice as likely to be associated with high WSS than frames without underexpansion., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) for the treatment of coronary bifurcation lesions (CBLs) is still technically demanding, mainly because of higher rates of both acute and chronic complication as compared with non-CBLs. Although provisional stenting (PS) is considered as the preferred strategy for most of the CBLs, a systematic two-stent technique (double kissing [DK] crush) should be considered in patients with complex left main (LM)-CBLs or non-LM-CBLs stratified by the DEFINITION criteria. Intracoronary imaging and/or physiologic evaluation should be used to optimize CBLs intervention. PCI with DES for the treatment of CBLs is technically demanding, mainly because of higher rates of both acute and chronic complication as compared with non-CBLs. PS is a default strategy for most of the CBLs. Double kissing (DK) crush is associated with better clinical outcomes compared with PS in patients with complex LM-CBLs or non-LM-CBLs stratified by the DEFINITION criteria. Intracoronary imaging and/or physiologic evaluation are useful tools to guide the treatment of CBLs. The use of drug-coated balloons in CBLs needs further data to support the clinical benefits., Competing Interests: Disclosure All authors report no relevant conflicts of interest, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is generally considered to reflect residual disease. Yet the clinical relevance of post-PCI FFR after drug-eluting stent (DES) implantation remains unclear., Objective: To evaluate the clinical relevance of post-PCI FFR measurement after DES implantation., Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant published articles from inception to June 18, 2022., Study Selection: Published articles that reported post-PCI FFR after DES implantation and its association with clinical outcomes were included., Data Extraction and Synthesis: Patient-level data were collected from the corresponding authors of 17 cohorts using a standardized spreadsheet. Meta-estimates for primary and secondary outcomes were analyzed per patient and using mixed-effects Cox proportional hazard regression with registry identifiers included as a random effect. All processes followed the Preferred Reporting Items for Systematic Review and Meta-analysis of Individual Participant Data., Main Outcomes and Measures: The primary outcome was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel myocardial infarction (TVMI), and target vessel revascularization (TVR). The secondary outcome was a composite of cardiac death or TVMI at 2 years., Results: Of 2268 articles identified, 29 studies met selection criteria. Of these, 28 articles from 17 cohorts provided data, including a total of 5277 patients with 5869 vessels who underwent FFR measurement after DES implantation. Mean (SD) age was 64.4 (10.1) years and 4141 patients (78.5%) were men. Median (IQR) post-PCI FFR was 0.89 (0.84-0.94) and 690 vessels (11.8%) had a post-PCI FFR of 0.80 or below. The cumulative incidence of TVF was 340 patients (7.2%), with cardiac death or TVMI occurring in 111 patients (2.4%) at 2 years. Lower post-PCI FFR significantly increased the risk of TVF (adjusted hazard ratio [HR] per 0.01 FFR decrease, 1.04; 95% CI, 1.02-1.05; P < .001). The risk of cardiac death or MI also increased inversely with post-PCI FFR (adjusted HR, 1.03; 95% CI, 1.00-1.07, P = .049). These associations were consistent regardless of age, sex, the presence of hypertension or diabetes, and clinical diagnosis., Conclusions and Relevance: Reduced FFR after DES implantation was common and associated with the risks of TVF and of cardiac death or TVMI. These results indicate the prognostic value of post-PCI physiologic assessment after DES implantation.

Bifurcation coronary artery disease is common as the development of atherosclerosis is facilitated by altered endothelial shear stress. Multiple anatomical and physiological factors need to be considered when treating bifurcation lesions. To achieve optimal results, various stenting techniques have been developed, each with benefits and limitations. In this state-of-the-art review we describe technically important characteristics of bifurcation lesions and summarise the evidence supporting contemporary bifurcation techniques.

Background Despite the clinical benefits to intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention (PCI), most patients with coronary artery disease undergo angiography-guided PCI alone in the real-world setting. We sought to investigate the procedural characteristics of IVUS-guided PCI and their clinical outcomes, as compared with angiography-guided PCI. Methods and Results This was a cohort study using patient-level data from the IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) and ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions) clinical trials. A total of 2848 patients with 3872 native coronary lesions were included and procedural characteristics assessed by quantitative coronary angiography (QCA) were compared between IVUS and angiography guidance. Stent-to-reference vessel diameter ratio (ie, QCA stent sizing) was greater (1.11±0.16 versus 1.07±0.14, P <0.001) and high-pressure postdilation was more frequently performed (83.7% versus 75.4%, P <0.001) with IVUS guidance, whereas residual stent edge dissections were more frequent in lesions treated with IVUS guidance (4.6% versus 0.7%, P <0.001). Given the dissection risk, optimal QCA stent sizing for IVUS guidance was a stent-to-QCA reference vessel diameter ratio ≥1.1 to <1.3. Among 1424 patients (1969 lesions) treated with angiography guidance, QCA stent sizing <1.0 was observed in 651 (33.1%) lesions, while QCA stent sizing ≥1.1 to <1.3 was observed in only 526 (26.7%) lesions. Under angiography guidance, patients with both QCA stent sizing ≥1.1 to <1.3 and high-pressure postdilation (235 of 1424, 16.5%) had a lower risk of 3-year target lesion failure compared with others (hazard ratio, 0.532; 95% CI, 0.293-0.966 [ P =0.038]). Conclusions IVUS-guided PCI resulted in larger QCA-assessed stent sizing and more frequent postdilation with high-pressure inflations. These procedures may further improve long-term clinical outcomes in patients undergoing PCI without IVUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01308281 (IVUS-XPL); NCT02215915 (ULTIMATE).

Background: The multicenter and randomized DEFINITION II (Two-Stent vs Provisional Stenting Techniques for Patients With Complex Coronary Bifurcation Lesions) trial showed less 1-year target lesion failure (TLF) after a 2-stent approach for complex coronary bifurcation lesions compared with provisional stenting (PS). The authors report the 3-year clinical outcome of the DEFINITION II trial., Objectives: The aim of the present study was to investigate the difference in TLF at 3 years after a planned 2-stent approach vs PS for complex coronary bifurcation lesions stratified by DEFINITION (Definitions and Impact of Complex Bifurcation Lesions on Clinical Outcomes After Percutaneous Coronary Intervention Using Drug-Eluting Stents) criteria., Methods: A total of 653 patients with complex coronary bifurcation lesions were randomly assigned to either the 2-stent group or the PS group in the DEFINITION II trial and were followed for 3 years. The primary endpoint was the occurrence of TLF at 3 years. Stent thrombosis was the safety endpoint., Results: At 3 years, TLF had occurred in 52 patients (16.0%) in the PS group and in 34 (10.4%) patients in the 2-stent group (HR: 0.63; 95% CI: 0.41-0.97; P = 0.035), driven mainly by increased target vessel myocardial infarction (8.0% vs 3.7%; HR: 0.45; 95% CI: 0.23-0.89; P = 0.022) and target lesion revascularization (8.3% vs 4.3%; HR: 0.50; 95% CI: 0.26-0.96; P = 0.038). There was no difference in TLF between the 2 groups between year 1 and year 3., Conclusions: For patients with complex coronary bifurcations who reach 1-year postprocedure without experiencing endpoint events, there is still a risk for future events. The type of procedure performed initially is no longer a future event risk determinant. (Two-Stent vs Provisional Stenting Techniques for Patients With Complex Coronary Bifurcation Lesions; NCT02284750)., Competing Interests: Funding Support and Author Disclosures This work was funded by the National Science Foundation of China (grants NSFC 81770441 and NSFC 82121001) and jointly supported by the Jiangsu Provincial Special Program of Medical Science (BE2019615), Microport, Sino Medical, and Medtronic. Dr Stone has received speaker or other honoraria from Cook, Terumo, Qool Therapeutics and Orchestra Biomed; serves as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme; and holds equity or options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix. Dr Chen is the developer of the double-kissing crush technique; and is a consultant for Boston International Scientific, Microport, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The risk/benefit tradeoff of dual antiplatelet therapy after percutaneous coronary intervention may vary in East Asian patients as compared with their non-East Asian counterparts., Methods: The double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding; the key secondary end point was the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke., Results: Of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients (13.0%) were enrolled at 27 Chinese sites in this prespecified substudy, of whom 1028 (14.4%) patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor+placebo group between randomization and 1 year (hazard ratio, 0.56 [95% CI, 0.31-0.99]; P =0.048). The key secondary end point occurred in 3.4% of patients in the ticagrelor+aspirin group versus 2.4% in the ticagrelor+placebo group (hazard ratio, 0.70 [95% CI, 0.33-1.46]; P =0.34). There was no interaction between the region of randomization (China versus the rest of the world) and randomized treatment assignment in terms of the primary or key secondary end points., Conclusions: Ticagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02270242.

Background: Five definitions of peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) are used in clinical trials; their clinical relevance in coronary bifurcation stenting remains unclear., Objectives: To understand the correlation between PMI and mortality in bifurcation lesions from the DKCRUSH studies., Methods: PMI was defined using serum creatine kinase-myocardial band (CK-MB) values within 48 h of PCI according to the SYNTAX, Fourth Universal Definition of MI (4th UDMI), ISCHEMIA, SCAI, and EXCEL definitions. Overall, 1300 patients with both CK and CK-MB measurements pre- and post-stenting were evaluated. The association of each PMI type and all-cause death or cardiac death at a median of 5.58 years of follow-up was analyzed using Cox regression., Results: In total, 56 (4.3%) patients had PMI. According to SYNTAX, 4th UDMI or ISCHEMIA, SCAI, and EXCEL definitions, PMI occurred in 21 (1.6%), 56 (4.3%), 29 (2.2%), and 32 (2.5%) patients, respectively. All definitions were significantly correlated with unadjusted mortality at the end of follow-up but not at 30 days or 1-year after stenting. PMI using SYNTAX, SCAI, and EXCEL definitions rather than 4th UDMI definition was strongly associated with adjusted all-cause death. By adjusted analysis, PMI according to 4th UDMI, SCAI, and EXCEL definitions but not SYNTAX definition was positively correlated with cardiac death at a median of 5.58 years of follow-up. CK-MB ≥ 5 x UNL strongly enhanced the correlation of CK-MB values with mortality., Conclusions: PMI rate varies with the definition following stenting for bifurcation lesions. PMI defined by SCAI and EXCEL definitions is strongly correlates with adjusted all-cause and cardiac death., (© 2021 Wiley Periodicals LLC.)

Objectives: The present study aimed to evaluate long-term cardiac survival benefit for intravascular ultrasound (IVUS)- versus angiography-guided long drug-eluting stent (DES) implantation., Background: Although the long-term benefit of IVUS guidance for DES implantation has been reported from recent randomized trials, this benefit was primarily driven by the reduction in repeat revascularization. Thus, it remains uncertain whether IVUS guidance improved survival during long-term follow-up., Methods: We pooled the data of 2 randomized trials (IVUS-XPL [Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions] and ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions]) and compared IVUS guidance versus angiography guidance in 2,577 patients with long lesions treated with an implanted stent length ≥28 mm. The primary end point was cardiac death at 3 years., Results: A 3-year clinical follow-up was completed in 96%. The primary end point of cardiac death occurred in 12 patients (1.0%) in the IVUS-guided group vs 28 patients (2.2%) in the angiography-guided group (HR: 0.43; 95% CI: 0.22-0.84; P = 0.011). In addition, target lesion-related myocardial infarction occurred in 3 patients (0.2%) in the IVUS-guided group and in 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95% CI: 0.09-1.22; P = 0.081), stent thrombosis developed in 3 patients (0.2%) in the IVUS-guided group and 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95% CI: 0.09-1.23; P = 0.082), and ischemia-driven target lesion revascularization was observed in 47 patients (3.8%) in the IVUS-guided group and 80 patients (6.5%) in the angiography-guided group (HR: 0.57; 95% CI: 0.40-0.82; P = 0.002)., Conclusions: In this post hoc pooled patient-level analysis, the use of IVUS-guided long DES implantation compared with angiography-guided stent implantation improved long-term patient cardiac survival., Competing Interests: Funding Support and Author Disclosures Supported by the Cardiovascular Research Center, Seoul, Korea. Dr Mintz has received honoraria (lecture fees) from Boston Scientific, Philips/Volcano, Abiomed, and Medtronic. Dr Chen has received lecture fees from Microport, Boston Scientific, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There are 2 competing approaches to optimize drug-eluting stent implantation: angiography-guided routine postdilation or intravascular ultrasound (IVUS) guidance., Methods: From the pooled data of 2 randomized trials, IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) and ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions), that compared IVUS- versus angiography-guided drug-eluting stent implantation, we compared 1037 patients (1265 lesions) with IVUS-guided postdilation, 905 patients (1170 lesions) with angiography-guided postdilation, and 383 patients (397 lesions) with angiography-guided drug-eluting stent implantation without postdilation as a reference group; all patients required ≥28 mm long stents. The primary end point was composite of cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 3 years., Results: Postintervention quantitative coronary angiography-based minimum lumen diameter was not different between the angiography guidance with postdilation versus the angiography guidance without postdilation group (2.5±0.4 mm versus 2.5±0.4 mm; P =0.367). However, it was larger in the IVUS guidance with postdilation versus the angiography guidance without postdilation group (2.6±0.5 mm versus 2.5±0.4 mm; P =0.046), and also in the IVUS guidance with postdilation versus the angiography guidance with postdilation group (2.6±0.5 mm versus 2.5±0.4 mm; P <0.001). The rate of the primary end point was not different between the angiography guidance with postdilation versus the angiography guidance without postdilation group (8.6% versus 9.8%; hazard ratio, 0.86 [95% CI, 0.58-1.29]; P =0.473). However, it was lower after IVUS guidance with postdilation versus angiography guidance without postdilation (4.5% versus 9.8%; hazard ratio, 0.44 [95% CI, 0.28-0.68]; P <0.001) and also after IVUS guidance with postdilation versus angiography guidance with postdilation (4.5% versus 8.6%; hazard ratio, 0.51 [95% CI, 0.35-0.74]; P <0.001)., Conclusions: In patients undergoing long drug-eluting stent implantation, IVUS-guided postdilation was associated with improved long-term clinical outcomes, unlike angiography-guided postdilation.

[Figure: see text].

Abstract: Percutaneous coronary intervention has become the main revascularization strategy for coronary artery disease. Compared with early percutaneous coronary angioplasty and the extensive clinical application of bare metal stents, drug-eluting stents can significantly reduce the stenosis caused by the elastic retraction of plaque and neoatherosclerosis (NA), but there is still a high incidence of in-stent restenosis (ISR), which restricts the clinical efficacy of stent implantation. In-stent neoatherosclerosis (ISNA), defined as atherosclerotic lesions in the neointima, is one of the main causes of late stent failure. ISNA plays an important role in stent thrombosis and ISR. The rate of target lesion revascularization and in-stent thrombosis is high when NA arises. Therefore, it is of great clinical significance to explore the occurrence of NA and its development mechanism after stent implantation to prevent ISR and improve stent implantation efficacy and associated clinical prognosis. In this article, we systematically reviewed the existing clinical research on ISNA and the role of optical coherence tomography in its evaluation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor., Methods: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population., Conclusion: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Coronary bifurcations exhibit localised turbulent flow and an enhanced propensity for atherothrombosis, platelet deposition and plaque rupture. Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with an increased risk of thrombotic events. Such risk is modulated by anatomical complexity, intraprocedural factors and pharmacological therapy. There is no consensus on the appropriate PCI strategy or the optimal regimen and duration of antithrombotic treatment in order to decrease the risk of ischaemic and bleeding complications in the setting of coronary bifurcation. A uniform therapeutic approach meets a clinical need. The present initiative, promoted by the European Bifurcation Club (EBC), involves opinion leaders from Europe, America, and Asia with the aim of analysing the currently available evidence. Although mainly derived from small dedicated studies, substudies of large trials or from authors' opinions, an algorithm for the optimal management of patients undergoing bifurcation PCI, developed on the basis of clinical presentation, bleeding risk, and intraprocedural strategy, is proposed here.

Background: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion., Trial Design: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure., Conclusions: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: This study was to analyze the incidence of definite stent thrombosis (ST) after the implantation of drug-eluting stents (DESs) and cutoff value of overlapping length for predicting definite ST. An overlapping stent is associated with a high rate of clinical events after DES implantation compared with a non-overlapping stent. However, the rates of definite ST and clinical outcomes from a large patient population remain underreported., Methods: A total of 15,561 patients with 24,183 lesions who underwent DES implantation from January 2005 to February 2017 were retrospectively included in 5 tertiary hospitals in China. The main endpoint was the incidence of definite ST after procedures., Results: With a median of 1932 (IQR = 1194-2929) days, clinical follow-up was available in 7484 patients in the overlap group and in 8077 patients in the non-overlap group. The rates of definite ST were 3.1% in the overlap group and 1.2% in the non-overlap group (HR: 2.67 (95% CI: 2.11-3.38), p < 0.001). Of the 24,183 treated lesions, the incidences of definite ST were 2.4% in the overlap group and 0.9% in the non-overlap group (HR: 2.96 (95% CI: 2.38-3.69), p < 0.001). Stent overlap was associated with a higher rate of target lesion revascularization (TLR) (9.4%) compared with stent non-overlap (6.4%, p < 0.001). The length of overlapping stent ≥ 2.93 mm strongly correlated with definite ST., Conclusion: The present study shows that overlapping DES increases definite ST and revascularization in patients during long-term follow-up. In addition, the longer overlapping zone was associated with worse clinical outcomes.

Coronary artery bypass surgery has been the accepted treatment for left main coronary artery disease for over 50 years. Balloon angioplasty was later used then abandoned because of deaths likely due to restenosis or thrombotic occlusion. However, rapid innovations in drug-eluting stent designs leading to more biocompatible thin strut platforms with optimal drug elution profiles and further advances in modern pharmacotherapy involving potent P2Y 12 inhibitors combined with utilization of intracoronary imaging and physiologic assessment for procedural planning and optimization have transformed percutaneous interventions into successful alternatives to coronary artery bypass graft surgery (CABG) in selected LM anatomic territories. Herein, we provide an evidence-based practical guide on how to approach and perform LM percutaneous interventions (PCI)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization., Methods: A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1-RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1-5, and >5) and post-PCI FFR (≥0.94, 0.87-0.93, and ≤0.86)., Results: After PCI, SYNTAX score was changed from 10.0 (Q1-Q3, 7.0-16.0) to 0.0 (Q1-Q3, 0.0-5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank P =0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank P =0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032-1.153]; P =0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898-1.045]; P =0.417)., Conclusions: Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04012281.

Importance: The prognostic value of pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) may be associated with the post-PCI FFR and their interaction. To correctly interpret the prognostic value of pre-PCI FFR, it is essential to understand to what extent the association of pre-PCI FFR with clinical outcomes is explained by post-PCI FFR., Objective: To investigate the extent to which post-PCI FFR mediates the association of pre-PCI FFR with vessel-related outcomes using an international, multicenter collaboration registry., Design, Setting, and Participants: This cohort study used pooled patient data from 4 international FFR registries. A total of 1488 patients with pre-PCI FFR of 0.80 or less who underwent elective PCI were included. Data collection was conducted from November 2011 to August 2019, and analysis was conducted from September 2019 to July 2020., Main Outcomes and Measures: The primary outcome was target vessel failure (TVF) during 2 years of follow-up. The extent to which post-PCI FFR of less than 0.90 mediated the association of pre-PCI FFR less than 0.75 (vs pre-PCI FFR of 0.75 or greater) with TVF was evaluated using a mediation analysis in a counterfactual framework., Results: Among 1488 patients, the mean (SD) age was 63.5 (9.9) years and 1161 patients (78.0%) were men. The median (interquartile range) pre-PCI and post-PCI FFR were 0.71 (0.62-0.76) and 0.88 (0.83-0.92), respectively. The direct association of low pre-PCI FFR (ie, <0.75) with TVF was significant (odds ratio, 1.81; 95% CI, 1.03-3.17; P = .04), while the mediation by post-PCI FFR level of less than 0.90 was not (indirect association: odds ratio, 1.03; 95% CI, 0.98-1.09; P = .24). In sensitivity analyses using several pre-PCI cutoffs, the mediations by post-PCI FFR were consistently weak., Conclusions and Relevance: In this study, the association of pre-PCI FFR with TVF was not significantly mediated by post-PCI FFR. Poor prognosis due to progressed atherosclerosis, represented as low FFR, may not be reversed by successful PCI that increases FFR. Therefore, the prognostic value of pre-PCI FFR may mainly reflect the global atherosclerotic burden, not the extent of the modifiable epicardial stenosis.

Objectives: The aim of this study was to develop a risk model incorporating clinical, angiographic, and physiological parameters to predict future clinical events after drug-eluting stent implantation., Background: Prognostic factors after coronary stenting have not been comprehensively investigated., Methods: A risk model to predict target vessel failure (TVF) at 2 years was developed from 2,200 patients who underwent second-generation drug-eluting stent implantation and post-stent fractional flow reserve (FFR) measurement. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. A random survival forest model with automatic feature selection by minimal depth analysis was used for risk model development., Results: During 2 years of follow-up, the cumulative incidence of TVF was 5.9%. From clinical, angiographic, and physiological parameters, 6 variables were selected for the risk model in order of importance within the model as follows: total stent length, post-stent FFR, age, post-stent percentage diameter stenosis, reference vessel diameter, and diabetes mellitus. Harrell's C index of the random survival forest model was 0.72 (95% confidence interval [CI]: 0.62 to 0.82). This risk model showed better prediction ability than models with clinical risk factors alone (Harrell's C index = 0.55; 95% CI: 0.41 to 0.59; p for comparison = 0.005) and with clinical risk factors and angiographic parameters (Harrell's C index = 0.65; 95% CI: 0.52 to 0.77; p for comparison = 0.045). When the patients were divided into 2 groups according to the median of total stent length (30 mm), post-stent FFR and total stent length showed the highest variable importance in the short- and long-stent groups, respectively., Conclusions: A risk model incorporating clinical, angiographic, and physiological predictors can help predict the risk for TVF at 2 years after coronary stenting. Total stent length and post-stent FFR were the most important predictors. (International Post PCI FFR Registry; NCT04012281)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions., Methods and Results: In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20-0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19-1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31-2.37; P = 0.772)., Conclusion: For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting., Study Registration: http://www.clinicaltrials.com; Identifier: NCT02284750., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of this study was to compare clinical outcomes of different bifurcation percutaneous coronary intervention (PCI) techniques., Background: Despite several randomized trials, the optimal PCI technique for bifurcation lesions remains a matter of debate. Provisional stenting has been recommended as the default technique for most bifurcation lesions. Emerging data support double-kissing crush (DK-crush) as a 2-stent technique., Methods: PubMed and Scopus were searched for randomized controlled trials comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE). Secondary outcomes of interest were cardiac death, myocardial infarction, target vessel or lesion revascularization, and stent thrombosis. Summary odds ratios (ORs) were estimated using Bayesian network meta-analysis., Results: Twenty-one randomized controlled trials including 5,711 patients treated using 5 bifurcation PCI techniques were included. Investigated techniques were provisional stenting, T stenting/T and protrusion, crush, culotte, and DK-crush. Median follow-up duration was 12 months (interquartile range: 9 to 36 months). When all techniques were considered, patients treated using the DK-crush technique had less occurrence of MACE (OR: 0.39; 95% credible interval: 0.26 to 0.55) compared with those treated using provisional stenting, driven by a reduction in target lesion revascularization (OR: 0.36; 95% credible interval: 0.22 to 0.57). No differences were found in cardiac death, myocardial infarction, or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed among provisional stenting, culotte, T stenting/T and protrusion, and crush. In non-left main bifurcations, DK-crush reduced MACE (OR: 0.42; 95% credible interval: 0.24 to 0.66)., Conclusions: In this network meta-analysis, DK-crush was associated with fewer MACE, driven by lower rates of repeat revascularization, whereas no significant differences among techniques were observed for cardiac death, myocardial infarction, and stent thrombosis. A clinical benefit of 2-stent techniques was observed over provisional stenting in bifurcation with side branch lesion length ≥10 mm., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Reports showed no change of 7-day mortality after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) between 2001 and 2011 in China. National rolling one-year interventional standardized training programme began in September 2009. However, the improvement in clinical outcome following STEMI PCI after 2011 remains unclear., Methods and Results: This multicentre MOODY registry study aimed to analyse the clinical improvement after STEMI PCI. Of a total of 9265 acute MI patients registered from 24 centres, 3142 STEMIs having a first medical contact time ≤12 hours and undergoing primary PCI were assigned to the Pre Group (n = 1014, between March 1999 and October 2010) or the Post Group (n = 2128, between 2010 November and 2016 October). The primary endpoint was in-hospital cardiac death. Study endpoints were also compared between trained and untrained operators and between experienced (≥50 primary PCIs/year) and inexperienced personnel. In-hospital death after PCI was 3.0% in the Pre Group, significantly higher than 1.6% in the Post Group (P = .035). The improvements in clinical outcome after PCI between the 2016 and Pre Groups were stably sustained through one-year follow-up. The significant reduction for in-hospital death was noted when primary PCI was performed by trained (1.4% vs 5.4%, P < .001) or experienced (2.7% vs 4.8%, P = .001) operators, compared to untrained or inexperienced operators, respectively. Inclusion of the untrained operator into the conventional risk model strongly enhanced the prediction for endpoints. Age, Killip Class 3, diabetes, trans-radial approach and system delay were five predictors of in-hospital death after primary PCI., Conclusion: PCI for STEMI by a trained and experienced operator was associated with significant reduction of in-hospital death. Our results strongly warrant the need for promoting the current system response and patient education., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation.)

Objectives: The present study aimed to investigate the difference in target lesion failure (TLF) at 3 years after double kissing (DK) crush stenting versus provisional stenting (PS) for unprotected left main distal bifurcation (UPLMb) lesions., Background: The multicenter and randomized DKCRUSH-V (Double Kissing Crush versus Provisional Stenting for Left Main Distal Bifurcation Lesions: The DKCRUSH-V Randomized Trial) study showed fewer 1-year TLF after DK crush for UPLMb lesions compared with PS. The study reports the 3-year clinical outcome of the DKCRUSH-V study., Methods: A total of 482 patients with UPLMb lesions who were randomly assigned to either the DK crush group (DK group) or PS group in the DKCRUSH-V study were followed for 3 years. The primary endpoint was the occurrence of a TLF at 3 years. Stent thrombosis (ST) was the safety endpoint. Patients were classified by lesion's complexity and NERS (New Risk Stratification) II or SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) score., Results: At 3 years, TLF occurred in 41 (16.9%) patients in the PS group and in 20 (8.3%) patients in the DK group (p = 0.005), mainly driven by increased target vessel myocardial infarction (5.8% vs. 1.7%; p = 0.017) and target lesion revascularization (10.3% vs. 5.0%; p = 0.029). Definite or probable ST rate at 3 years was 4.1% in the PS group and 0.4% in the DK group (p = 0.006). Notably, DK crush was associated with a significant reduction in both primary and secondary endpoints for patients with complex lesions or at high risk., Conclusions: Provisional stenting for UPLMb lesions was associated with significantly increased rates of TLF and ST over 3 years of follow-up. Further randomized study is warranted to confirm the benefits of DK crush stenting for complex UPLMb lesions. (Double Kissing and Double Crush versus Provisional T Stenting Technique for the Treatment of Unprotected Distal Left Main True Bifurcation Lesions: A Randomized, International, Multi-center Clinical Trial; ChiCTR-TRC-11001213)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the impacts of intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation on patients with chronic kidney disease (CKD) based on the ULTIMATE trial., Background: IVUS-guided DES implantation improves clinical outcomes in complex lesions. However, routine IVUS guidance in patients with CKD remains controversial., Methods: CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL min -1 1.73 m -2 . The primary end point was target vessel failure (TVF) at 12 months, including cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization., Results: eGFR was available in 1,443 patients, of whom 723 were in the IVUS guidance group, and 720 were in the angiography guidance group. Finally, CKD was present in 349 (24.2%) patients. At 12 months, TVF in the CKD group was 7.2%, which was significantly higher than 3.2% in the non-CKD group (p = .001). Moreover, there were 25 TVFs in the CKD patients, with 7 (3.9%) TVFs in the IVUS group and 18 (10.7%) TVFs in the angiography group (hazard ratio [HR]: 0.35; 95% confidence interval [CI]: 0.15-0.84; p = .01), whereas 35 TVFs occurred in patients without CKD, with 14 (2.6%) TVFs in the IVUS group and 21 (3.8%) TVFs in the angiography group (HR: 0.67; 95% CI: 0.34-1.32; p = .25; p for interaction = .24)., Conclusions: This study demonstrated that CKD patients undergoing DES implantations were associated with a higher risk of TVF at 12 months. More importantly, the risk of TVF in the CKD patients could be significantly decreased through IVUS guidance., Clinical Trial: NCT02215915., (© 2019 Wiley Periodicals, Inc.)

Intravascular ultrasound (IVUS) guidance is not routinely performed in real-word clinical practice partly because the benefit of IVUS guidance is not well established. This updated meta-analysis aims to compare IVUS-guided and angiography-guided drug-eluting stent (DES) implantation, simultaneously stressing the value of an optimal IVUS-defined procedure. Medline, Scopus, Google Scholar, and Cochrane Controlled Trials Registry were searched for the randomized trials comparing IVUS-guided and angiography-guided DES implantation. Nine eligible randomized trials including 4,724 patients were identified. At a mean follow-up of 16.7 months, IVUS guidance was associated with a significant lower risk of major adverse cardiovascular events (MACE) [5.4% vs. 9.0%; relative risks (RR): 0.61, 95% confident interval (CI) 0.49-0.74, p < 0.001], cardiac death (0.6% vs. 1.2%; RR: 0.49, 95% CI 0.26-0.92, p = 0.03), target vessel revascularization (3.5% vs .6.1%; RR: 0.58, 95% CI 0.42-0.80, p = 0.001), target lesion revascularization (3.1% vs. 5.2%; RR: 0.59, 95% CI 0.44-0.80, p = 0.001), and definite/probable stent thrombosis (0.5% vs .1.1%; RR: 0.45, 95% CI 0.23-0.87, p = 0.02) compared with angiography guidance. No significant differences in all cause death and myocardial infarction were noted between the two groups. Subgroup analysis showed that patients who met the optimal criteria had a lower rate of MACE than those with IVUS-defined suboptimal procedure (RR: 0.33, 95% CI 0.06-0.60, p = 0.02). The present meta-analysis with the largest sample size to date demonstrates that IVUS-guided DES implantation significantly reduces cardiac death, coronary revascularization and stent thrombosis, particularly for patients with IVUS-defined optimal procedures compared with angiography guidance.

Background: Intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation is associated with fewer major adverse cardiovascular events compared with angiography guidance for patients with individual lesion subset. However, the beneficial effect on major adverse cardiovascular event outcome of IVUS guidance over angiography guidance in all-comers who undergo DES implantation still remains understudied., Objectives: This study aimed to determine the benefits of IVUS guidance over angiography guidance during DES implantation in all-comer patients., Methods: A total of 1,448 all-comer patients who required DES implantation were randomly assigned (1:1 ratio) to either an IVUS guidance or angiography guidance group. The primary endpoint was target-vessel failure (TVF) at 12 months, including cardiac death, target-vessel myocardial infarction, and clinically driven target-vessel revascularization (TVR). The procedure was defined as a success if all IVUS-defined optimal criteria were met., Results: At 12 months follow-up, 60 TVFs (4.2%) occurred, with 21 (2.9%) in the IVUS group and 39 (5.4%) in the angiography group (hazard ratio [HR]: 0.530; 95% confidence interval [CI]: 0.312 to 0.901; p = 0.019). In the IVUS group, TVF was recorded in 1.6% of patients with successful procedures, compared with 4.4% in patients who failed to achieve all optimal criteria (HR: 0.349; 95% CI: 0.135 to 0.898; p = 0.029). The significant reduction of clinically driven target-lesion revascularization or definite stent thrombosis (HR: 0.407; 95% CI: 0.188 to 0.880; p = 0.018) based on lesion-level analysis by IVUS guidance was not achieved when the patient-level analysis was performed., Conclusions: The present study demonstrates that IVUS-guided DES implantation significantly improved clinical outcome in all-comers, particularly for patients who had an IVUS-defined optimal procedure, compared with angiography guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions [ULTIMATE]; NCT02215915)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Stenting coronary artery bifurcation lesion is associated with suboptimal clinical results. Clinical improvement by intravascular ultrasound (IVUS) guided bifurcation stenting is controversial because small-side-branch (SB), low-risk patients and false bifurcations were included in previous studies that had no exact IVUS criteria for optimal stent expansion. We sought determine whether IVUS guidance is superior to angiography guidance for patients with true and complex bifurcation lesions. Between July 2006 and July 2012, 1465 patients with unstable angina and Medina 1,1,1 or 0,1,1 coronary bifurcation lesions were prospectively studied. 310 patients in the IVUS guidance (defined as stent symmetry index > 0.7, stent expansion index > 0.9, well apposition, and no Type B/C dissection) group were paired with 620 patients in the angiography group by propensity score-matching. The primary endpoint was the rate of composite major adverse cardiac events (MACE) (cardiac death, myocardial infarction (MI), or clinically-driven target vessel revascularization) at 1-year and at the end of study after indexed procedure. Use of IVUS guidance was mainly driven by stenting technique selection and identification of lesions' specificities. IVUS criteria for optimal stent expansion were achieved in 82.9% of patients which contribute to IVUS group data assessment and the rest did not meet optimal criteria. MACE occurred in 10.0% of patients at 1-year follow-up and 15.2% at the 7-year follow-up in the IVUS group, significantly different from 15.0% (p = 0.036) and 22.4% (p = 0.01) in the angiography group, respectively. Compared to angiography guidance, IVUS guidance also resulted in a lower 7-year cardiac death rate (6.5 versus 1.3%, p = 0.002) and MI (8.4 versus 2.3%, P < 0.001). Any revascularization was also statistically lower in the IVUS group through whole study period, compared to the angiography group. Lower MACE rates were observed in IVUS guidance group in a 7-year follow-up compared with angiography guidance alone.

Background: Very few data have been reported for ST-segment elevation myocardial infarction (STEMI) caused by unprotected left main coronary artery (ULMCA) occlusion, and very little is known about the results of this subgroup of patients who underwent primary percutaneous coronary intervention (PCI). The aim of this study was to determine the clinical features and outcomes of patients with STEMI who underwent primary PCI for acute ULMCA occlusion., Methods: From January 2000 to February 2014, 372 patients with STEMI caused by ULMCA acute occlusion (ULMCA-STEMI) who underwent primary PCI at one of two centers were enrolled. The 230 patients with non-ST-segment elevation MI (NSTEMI) caused by ULMCA lesion (ULMCA-NSTEMI) who underwent emergency PCI were designated the control group. The main indexes were the major adverse cardiac events (MACEs) in-hospital, at 1 month, and at 1 year., Results: Compared to the NSTEMI patients, the patients with STEMI had significantly higher rates of Killip class≥III (21.2% vs. 3.5%, χ 2 = 36.253, P < 0.001) and cardiac arrest (8.3% vs. 3.5%, χ 2 = 5.529, P = 0.019). For both groups, the proportions of one-year cardiac death in the patients with a post-procedure thrombolysis in myocardial infarction (TIMI) flow grade<3 were significantly higher than those in the patients with a TIMI flow grade of 3 (STEMI group: 51.7% [15/29] vs. 4.1% [14/343], P < 0.001; NSTEMI group: 33.3% [3/9] vs. 13.6% [3/221], P = 0.001; respectively]. Landmark analysis showed that the patients in STEMI group were associated with higher risks of MACE (16.7% vs. 9.1%, P = 0.009) and cardiac death (5.4% vs. 1.3%, P = 0.011) compared with NSTEMI patients at 1 month. Meanwhile, in patients with ULMCA, the landmark analysis for incidences of MACE and cardiac death was similar between the STEMI and NSTEMI (all P = 0.72) in the intervals of 1-12 months. However, patients who were diagnosed with STEMI or NSTEMI had no significant difference in reinfarction (all P > 0.05) and TVR (all P > 0.05) in the intervals of 0-1 month as well as 1 month to 1 year. The results of Cox regression analysis showed that the differences in the independent predictors for MACE included the variables of Killip class ≥ III and intra-aortic balloon pump support for the STEMI patients and the variables of previous MI, ULMCA distal bifurcation, and 2-stent for distal ULMCA lesions for the NSTEMI patients., Conclusions: Compared to the NSTEMI patients, the patients with STEMI and ULMCA lesions still remain at a much higher risk for adverse events at 1 year, especially on 1 month. If a successful PCI procedure is performed, the 1-year outcomes in those patients might improve., Competing Interests: There are no conflicts of interest

Background: The relationship between platelet reactivity and long-term clinical outcomes remains controversial. The present prospective study was designed to explore the association between high platelet reactivity (HPR) on clopidogrel and long-term clinical outcomes following implantation of drug eluting stents (DES)., Methods: A total of 1769 consecutive patients assessed by Aggrestar (PL-11) were enrolled at our center from February 2011 to December 2017. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE), defined as definite or probable stent thrombosis, spontaneous myocardial infarction, all cause death, clinically driven target vessel revascularization (TVR), or ischemic stroke. Bleeding served as the safety endpoint. Propensity score matching (PSM) analysis was performed to adjust for baseline differences in the overall cohort., Results: Finally, 409 patients (23.1%) were identified with HPR on clopidogrel. At a median follow-up of 4.1 years (interquartile range, 1.8 years), the occurrence of MACCE was significantly higher in HPR on clopidogrel group than normal platelet reactivity (NPR) on clopidogrel group (15.6% vs. 5.4%, p < 0.001). After PSM, 395 paired patients were matched, and the difference in MACCE between HPR (15.7%) versus NPR (9.4%) on clopidogrel groups remained significant (P < 0.001), mainly driven by increased all cause death (5.3% vs. 1.8%, p < 0.001), and clinically driven TVR (8.1% vs. 6.3%, p = 0.019) in the HPR group. The risk of bleeding between two groups was similar., Conclusions: This prospective study confirms the relationship between HPR on clopidogrel and long-term adverse cardiovascular events after coronary stenting.

Type 2 diabetes correlates with clinical events after the implantation of a second-generation drug-eluting stent (DES). The rate and prognostic value of stent fracture (SF) in patients with diabetes who underwent DES implantation remain unknown. A total of 1160 patients with- and 2251 without- diabetes, who underwent surveillance angiography at 1 year after DES implantation between June 2004 and August 2014, were prospectively studied. The primary endpoints included the incidence of SF and a composite major adverse cardiac event [MACE, including myocardial infarction (MI), cardiac death, and target-vessel revascularization (TVR)] at 1-year follow-up and at the end of follow-up for overall patients, and target lesion failure [TLF, including cardiac death, target vessel myocardial infarction (TVMI) and target lesion revascularization (TLR)] at the end of study for SF patients. In general, diabetes was associated with a higher rate of MACE at 1-year (18.4 vs. 12.9%) and end of follow-up (24.0 vs. 18.6%, all p < 0.001), compared with those in patients who did not have diabetes. The 1-year SF rate was comparable among patients with diabetes (n = 153, 13.2%) and non-diabetic patients (n = 273, 12.1%, p > 0.05). Diabetic patients with SF had a 2.6-fold increase of SF-related cardiac death at the end of study and threefold increase of re-repeat TLR when compared with non-diabetic patients with SF (5.9 vs. 2.2%, p = 0.040; 6.5 vs. 2.2%, p = 0.032), respectively. Given the fact that diabetes is correlated with increased MACE rate, SF in diabetic patients translates into differences in mortality and re-repeat TLR compared with the non-diabetic group.

Background: Provisional stenting (PS) is the most common technique used to treat distal left main (LM) bifurcation lesions in patients with unprotected LM coronary artery disease undergoing percutaneous coronary intervention. The double kissing (DK) crush planned 2-stent technique has been shown to improve clinical outcomes in non-LM bifurcations compared with PS, and in LM bifurcations compared with culotte stenting, but has never been compared with PS in LM bifurcation lesions., Objectives: The authors sought to determine whether a planned DK crush 2-stent technique is superior to PS for patients with true distal LM bifurcation lesions., Methods: The authors randomized 482 patients from 26 centers in 5 countries with true distal LM bifurcation lesions (Medina 1,1,1 or 0,1,1) to PS (n = 242) or DK crush stenting (n = 240). The primary endpoint was the 1-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Routine 13-month angiographic follow-up was scheduled after ascertainment of the primary endpoint., Results: TLF within 1 year occurred in 26 patients (10.7%) assigned to PS, and in 12 patients (5.0%) assigned to DK crush (hazard ratio: 0.42; 95% confidence interval: 0.21 to 0.85; p = 0.02). Compared with PS, DK crush also resulted in lower rates of target vessel myocardial infarction I (2.9% vs. 0.4%; p = 0.03) and definite or probable stent thrombosis (3.3% vs. 0.4%; p = 0.02). Clinically driven target lesion revascularization (7.9% vs. 3.8%; p = 0.06) and angiographic restenosis within the LM complex (14.6% vs. 7.1%; p = 0.10) also tended to be less frequent with DK crush compared with PS. There was no significant difference in cardiac death between the groups., Conclusions: In the present multicenter randomized trial, percutaneous coronary intervention of true distal LM bifurcation lesions using a planned DK crush 2-stent strategy resulted in a lower rate of TLF at 1 year than a PS strategy. (Double Kissing and Double Crush Versus Provisional T Stenting Technique for the Treatment of Unprotected Distal Left Main True Bifurcation Lesions: A Randomized, International, Multi-Center Clinical Trial [DKCRUSH-V]; ChiCTR-TRC-11001213)., (Copyright © 2017 American College of Cardiology Foundation. All rights reserved.)

Objectives: This study aimed to investigate the cutoff of post-drug-eluting stent (DES) fractional flow reserve (FFR) for prediction of 1- to 3-year target vessel failure (TVF)., Background: FFR immediately after a DES implantation correlates with clinical events. However, the cutoff of post-DES FFR for predicting long-term clinical events remains understudied., Methods: Between May 2012 and September 2013, a total of 1,476 patients who had FFR <0.8 at maximal and at baseline underwent DES implantation were prospectively studied in 9 centers. Post-DES FFR was repeat measured. The primary endpoint was the 1-year TVF rate after procedures. Receiver-operating characteristic curves were used to calculate the post-DES FFR value for TVF, then patients were classified on the basis of this value and followed up for 3 years., Results: By the end of the first year, 88 (6.0%) TVFs were recorded. A post-DES FFR ≤0.88 strongly correlated with TVF. Disease in the left anterior descending coronary artery (LAD), stent length, and stent diameter were independent factors of impaired post-DES FFR, whereas post-procedure FFR ≤0.88 was the only predictor of TVF, with 40 (4.0%) TVFs in the FFR >0.88 and 48 (8.0%) in the FFR ≤0.88 group (p = 0.001), mainly driven by target vessel revascularization (3.8% vs. 8.8%; p = 0.005) and cardiac death (0.2% vs. 1.3%; p = 0.017). The difference in TVF between 2 groups was maintained through 3-year follow-up (p = 0.002). For patients with LAD lesions, a post-DES FFR ≤0.905 predicted 1-year TVF., Conclusions: Post-DES FFR strongly correlated with TVF rate. Mechanisms attributed to and treatments for impaired FFR after stenting should be studied in future studies. (Post-DES FFR Predicts the Clinical Outcomes: DK CRUSH-VII, A Prospective, Multicenter, Registry Study [DK CRUSH-VII]; ChiCTR-PRCH-12001976)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Contemporary clinical trials, registries, and meta-analyses, supported by recent results from the EXCEL (Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease) and NOBLE (Percutaneous Coronary Angioplasty Versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis) trials, have established percutaneous coronary intervention of left main coronary stenosis as a safe alternative to coronary artery bypass grafting in patients with low and intermediate SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) scores. As left main percutaneous coronary intervention gains acceptance, it is imperative to increase awareness for patient selection, risk scoring, intracoronary imaging, vessel preparation, and choice of stenting techniques that will optimize procedural and patient outcomes., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The association of platelet reactivity and clinical outcomes, especially stent thrombosis, was not so clear. We sought to investigate whether high platelet reactivity affects clinical outcomes of patients with drug eluting stents (DESs) implantation., Methods: All enrolled individuals treated with DESs implantation were evaluated by PL-11, using sequentially platelet counting method. The primary end point was the occurrence of definite and probable stent thrombosis at 2 years. The secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all cause death, spontaneous myocardial infarction (MI), target vessel revascularization (TVR), and ischemic stroke., Results: A total of 1331consecutive patients were enrolled at our center. There were 91 patients (6.8 %) identified with high platelet reactivity (HPR) on aspirin, and 437 patients (32.9 %) with HPR on clopidogrel. At 2-year follow-up, the incidence of stent thrombosis was significantly higher in patients with HPR on aspirin (9.9 % vs. 0.4 %, p < 0.001), and HPR on clopidogrel (3.0 % vs. 0.1 %, p < 0.001). There were increased MACCE in the HPR on aspirin group (16.5 % vs. 8.5 %, p = 0.021), mainly driven by the higher all cause death (7.7 % vs. 1.6 %, p = 0.002) and MI (9.9 % vs. 1.9 %, p < 0.001) in the HPR on aspirin group. Similarly, the rate of MACCE was higher in the HPR on clopidogrel group (12.4 % vs. 7.4 %, p = 0.004). No differences in all bleeding and hemorrhagic stroke were observed., Conclusions: The present study demonstrated that high platelet reactivity on both aspirin and clopidogrel were associated with incremental stent thrombosis following DESs implantation.

Aims: The study aimed to examine five-year clinical outcomes of complete (CR), partially complete (PCR), and incomplete revascularisation (ICR) in patients with unprotected left main coronary artery (ULMCA) disease treated with drug-eluting stents (DES). Completeness of revascularisation, defined as revascularisation of all vessels ≥1.5 or 2.5 mm in diameter, has been shown to correlate with outcomes after percutaneous coronary intervention (PCI). There are no data to compare revascularisation strategies on long-term clinical outcomes in patients undergoing PCI of ULMCA disease., Methods and Results: This prospective registry enrolled 910 consecutive patients with ULMCA disease undergoing PCI with DES implantation. CR included patients who had a successful revascularisation of all diseased segments with diameter ≥1.5 mm. PCR included patients who had successful revascularisation of all diseased segments with diameter ≥2.5 mm. ICR included patients who did not achieve revascularisation for all diseased segments of diameter ≥2.5 mm. The primary endpoint was the incidence of major adverse cardiac events (MACE: a composite of cardiac death, myocardial infarction and repeat revascularisation) at five-year follow-up. CR was achieved in 386 (42.4%), PCR in 227 (25.0%), and ICR in 297 (32.6%) patients. Patients with ICR had a significantly higher rate of MACE (29.6% vs. 22.5% and 15.5%, p<0.001) and all-cause mortality (12.5% vs. 7.0% and 6.2%; p=0.006) than those with CR and PCR at five-year follow-up. After propensity score matching, patients with CR vs. PCR had similar incidences of MACE (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 0.78-1.74, p=0.46), mortality (HR: 1.27, 95% CI: 0.61-2.63, p=0.53), and cardiac death (1.8% vs. 4.5%; HR: 2.56, 95% CI: 0.80-8.17, p=0.11). On multivariable logistic regression analysis, ICR appears to be an outcome of poor clinical characteristics, comorbidities and complex coronary anatomy., Conclusions: In the treatment of patients with ULMCA disease, ICR was associated with worse long-term clinical outcomes than CR and PCR. PCR has clinical outcomes similar to CR in patients with ULMCA disease treated with DES.

The use of intravascular ultrasound (IVUS) guidance for drug-eluting stent (DES) optimization is limited by the number of adequately powered randomized control trials (RCTs). We performed an updated meta-analysis, including data from recently published RCTs and observational studies, by reviewing the literature in Medline and the Cochrane Library to identify studies that compared clinical outcomes between IVUS-guided and angiography-guided DES implantation from January 1995 to January 2016. This meta-analysis included 25 eligible studies, including 31,283 patients, of whom 3192 patients were enrolled in 7 RCTs. In an analysis of all 25 studies, the summary results for all the events analyzed were significantly in favor of IVUS-guided DES implantation [major adverse cardiac events (MACE, odds ratio [OR] 0.76, 95% confidence intervals [CI]: 0.70-0.82, P<0.001); death (OR 0.62, 95% CI: 0.54-0.72, P<0.001); myocardial infarction (OR 0.67, 95% CI: 0.56-0.80, P<0.001); stent thrombosis (OR 0.58, 95% CI: 0.47-0.73, P<0.001); target lesion revascularization (TLR, OR 0.77, 95% CI: 0.67-0.89, P=0.005); target vessel revascularization (TVR, OR 0.85, 95% CI: 0.76-0.95, P<0.001)]. However, in a separate analysis of RCTs, a favorable result for IVUS-guided DES implantation was found only for MACE (OR 0.66, 95% CI: 0.52-0.84, P=0.001), TLR (OR 0.61, 95% CI: 0.43-0.87, P=0.006), and TVR (OR 0.61, 95% CI: 0.41-0.90, P=0.013). IVUS-guided percutaneous coronary intervention was associated with better overall clinical outcomes than angiography-guided DES implantation. However, in a solely RCT meta-analysis, this benefit was mainly driven by reduced rates of revascularizations., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objectives: The present study aimed to analyze the incidence of SF and its correlation with clinical events after DES implantation and the outcome of re-intervention for symptomatic in-stent restenosis (ISR) induced by stent fracture (SF)., Background: SF is associated with a high rate of clinical events after the implantation of drug-eluting stents (DES). However, the chronological rate of SF and the effect of SF on clinical outcomes from a large patient population remain underreported., Methods: A total of 6,555 patients with 16482 DES in 10751 diseased vessels and surveillance angiography between November 2003 and January 2014 were prospectively studied. The primary endpoints included the incidence of SF, in-stent restenosis (ISR), target lesion revascularization (TLR), and definite stent thrombosis (ST) at the end of follow-up before and after propensity score matching. Clinical outcomes after TLR were also followed up., Results: The SF rate was detected in 803 (12.3%) patients, 3,630 (22.0%) stents, and 1,852 (17.2%) diseased vessels. SF increased over time. SF was associated with higher unadjusted rates of ISR (42.1%), TLR (24.8%, n = 379), and definite ST (4.6%) compared with stents without fracture (10.7%, 6.6%, and 1.03%, all p < 0.001), and the differences remained significant after propensity score matching (all p < 0.05). There was no significant difference in any-cause or cardiac mortality between patients with and without SF. After 1,523 days of follow-up since the first surveillance angiography, repeat ISR was detected in 90 of 379 (23.8%) stents after reintervention, and 6 (7.5%) stents required repeat TLR., Conclusions: SF is more frequently observed after DES implantation. TLR was required in almost one-fourth of fractured stents. Increased events in the SF group did not translate into a difference in mortality compared with the non-SF group. Reintervention was associated with acceptable clinical results., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention., Methods and Results: The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10-2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension., Conclusions: OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526., (© 2016 American Heart Association, Inc.)

Introduction: N-acetylcysteine (NAC) and sodium bicarbonate (SOB) therapies may prevent contrast-induced nephropathy (CIN). However, the efficacy of using combination over individual therapies was not established, and there was no large randomised study comparing abbreviated SOB therapy with conventional sustained saline pre-hydration with oral NAC., Methods: In a multi-centre, open-label, randomised, controlled trial (NCT00497328), we prospectively enrolled 548 patients with at least moderate renal impairment undergoing cardiac catheterisation with or without percutaneous coronary intervention. Patients were randomly assigned to 3 groups: 1) NAC: 154 mEq/L sustained sodium chloride regime (1 mL/kg/h 12 h before, during and 6h after the procedure) with oral NAC at 1.2g bid for 3 days (n=185); 2) SOB: 154 mEq/L abbreviated SOB regime at 3 mL/kg/h 1h before the procedure, and 1 mL/kg/h during and 6h after the procedure (n=182); and 3) COM: combination of abbreviated SOB regime and oral NAC (n=181). The primary end point was incidence of CIN. The secondary end points were rise in serum creatinine, hospitalisation duration, haemodialysis, morbidity and mortality within 30 days., Results: The 3 groups had similar baseline characteristics: age 68 ± 10 years, 76% male, 48% diabetic and baseline glomerular filtration rate (GFR) 47.7 ± 13.0 mL/min. There were 41 (8.8%) patients with GFR<30. The CIN incidences were NAC 6.5%, SOB 12.8% and COM 10.6%. The COM regimen was not superior to either the NAC (relative risk (RR)=1.61, 95% confidence interval (CI): 0.76 to 3.45, p=0.225) or SOB (RR=0.83, 95% CI: 0.44 to 1.56, p=0.593) regimens. The CIN incidence was lower in the NAC group than the SOB group (adjusted odds ratio (OR)=0.40, 95% CI: 0.17 to 0.92; p=0.032). Multivariate analysis showed contrast volume (OR=1.99, 95% CI: 1.33 to 2.96, p<0.001 per 100mL), female (OR=2.47, 95% CI: 1.22 to 5.00, p=0.012) and diabetes (OR=2.03, 95% CI: 1.03 to 3.99, p=0.041) were independent risk predictors. There were no differences in the secondary outcomes among the 3 groups., Conclusion: The combination regimen was not superior to individual regimens in preventing CIN in patients with baseline renal impairment. There was a trend suggesting that the 12-hour sustained sodium chloride pre-hydration regimen was more protective than the 1-hour abbreviated SOB regimen., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The study sought to compare long-term optical coherence tomography (OCT)-based in-stent vascular response between the abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) and the durable polymer everolimus-eluting stent (EES) in the TARGET I trial. The TARGET I trial was a prospective, multicenter, randomized clinical trial which enrolled 458 patients with single de novo lesions treated by abluminal groove-filled biodegradable polymer SES and EES. A subset of 43 patients underwent angiography and OCT examinations at 3 years. All OCT images were analyzed at 0.4 mm intervals. A similar increase in angiographic late lumen loss was observed in SES and EES (from 0.05 ± 0.05 vs. 0.05 ± 0.05 mm [p = 0.84] at 9 months to 0.25 ± 0.37 vs. 0.26 ± 0.19 mm [p = 0.99] at 3 years, respectively), without significant differences at 3 years in mean neointimal thickness of stent struts (SES: 0.13 ± 0.02 mm vs. EES: 0.13 ± 0.02 mm, p = 0.80); mean percentage of covered struts (SES: 99.2 % vs. EES: 99.3 %, p = 0.53), or malapposed strut rates (SES: 0.08 % vs. EES: 0.06 %, p = 0.15). The OCT-based in-stent vascular response evaluation found similar vascular healing for the two studied devices, indicating that the luminal loss in EES from 9 months to 3 years cannot be imputed on its coated biocompatible polymer.