Effects of Laccase and Transglutaminase on the Physicochemical and Functional Properties of Hybrid Lupin and Whey Protein Powder.

Plant-based protein is considered a sustainable protein source and has increased in demand recently. However, products containing plant-based proteins require further modification to achieve the desired functionalities akin to those present in animal protein products. This study aimed to investigate the effects of enzymes as cross-linking reagents on the physicochemical and functional properties of hybrid plant- and animal-based proteins in which lupin and whey proteins were chosen as representatives, respectively. They were hybridised through enzymatic cross-linking using two laccases (laccase R, derived from Rhus vernicifera and laccase T, derived from Trametes versicolor) and transglutaminase (TG). The cross-linking experiments were conducted by mixing aqueous solutions of lupin flour and whey protein concentrate powder in a ratio of 1:1 of protein content under the conditions of pH 7, 40 °C for 20 h and in the presence of laccase T, laccase R, or TG. The cross-linked mixtures were freeze-dried, and the powders obtained were assessed for their cross-linking pattern, colour, charge distribution (ζ-potential), particle size, thermal stability, morphology, solubility, foaming and emulsifying properties, and total amino acid content. The findings showed that cross-linking with laccase R significantly improved the protein solubility, emulsion stability and foaming ability of the mixture, whereas these functionalities were lower in the TG-treated mixture due to extensive cross-linking. Furthermore, the mixture treated with laccase T turned brownish in colour and showed a decrease in total amino acid content which could be due to the enzyme's oxidative cross-linking mechanism. Also, the occurrence of cross-linking in the lupin and whey mixture was indicated by changes in other investigated parameters such as particle size, ζ-potential, etc., as compared to the control samples. The obtained results suggested that enzymatic cross-linking, depending on the type of enzyme used, could impact the physicochemical and functional properties of hybrid plant- and animal-based proteins, potentially influencing their applications in food.

Provisional stenting with side branch rescue stenting is associated with increased 3-year target lesion failure in patients with acute coronary syndrome and coronary bifurcation lesions.

Background: Provisional stenting (PS) is the main treatment for a majority of coronary bifurcation lesion and includes PS with 1-stent and PS with 2-stent. However, the treatment difference between PS with 1-stent and with 2-stent remains unclear in patients with the acute coronary syndrome (ACS) and coronary bifurcation lesions. Materials and methods: Overall, 820 ACS patients with Medina 1,1,1 or 0,1,1 coronary bifurcation lesion who had completed 3-year follow-up were included and assigned to the PS with 1-stent (n = 519) or the PS with 2-stent (n = 301) according to the use of final stenting technique. The primary endpoint was the target lesion failure (TLF) at 3 years since stenting procedures. Results: At 3-year follow-up, TLF occurred in 85 (16.4%) patients in the PS with 1-stent group and 69 (22.9%) in the PS with 2-stent group (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.06-2.17, p = 0.021), mainly driven by a higher rate of target lesion revascularization (TLR) in the PS with 2-stent group (13.0% vs. 8.3%, HR 1.65, 95% CI 1.04-2.61, p = 0.033). Complex bifurcations, side branch (SB) pretreatment, intravascular imaging guidance, and hyperlipidemia were the four predictors for 3-year TLF. SB pretreatment was associated with increased 3-year TLR, leading to an extremely higher 3-year TLF. Conclusion: Provisional with 2-stent for patients with ACS is associated with a higher rate of 3-year TLF, mainly due to increased requirement of revascularization. SB pretreatment should be avoided for simple bifurcation lesion.

3-Year Outcomes After 2-Stent With Provisional Stenting for Complex Bifurcation Lesions Defined by DEFINITION Criteria.

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).

Rationale and design for comparison of non-compliant balloon with drug-coating balloon angioplasty for side branch after provisional stenting for patients with true coronary bifurcation lesions: a prospective, multicentre and randomised DCB-BIF trial.

INTRODUCTION: Provisional stenting using drug-eluting stent is effective for simple coronary bifurcation lesions. Kissing balloon inflation using conventional non-compliant balloon is the primary treatment of side branch (SB) after main vessel (MV) stenting. Drug-coating balloon (DCB) is reported to be associated with less frequent clinical events in in-stent restenosis and small vessel disease. The importance of DCB in bifurcation treatment is understudied. Accordingly, this trial is designed to investigate the superiority of DCB to non-compliant balloon angioplasty for SB after provisional stenting in patients with true coronary bifurcation lesions. METHODS AND ANALYSIS: The DCB-BIF trial is a prospective, multicentre, randomised, superiority trial including 784 patients with true coronary bifurcation lesions. Patients will be randomised in a 1:1 fashion to receive either DCB or non-compliant balloon angioplasty if SB diameter stenosis >70% after MV stenting. The primary endpoint is the composite of major adverse cardiac event at the 1-year follow-up, including cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularisation. The major secondary endpoints include all-cause death, periprocedural MI, spontaneous MI, clinically driven target vessel revascularisation, in-stent restenosis, stroke and individual component of the primary endpoint. The safety endpoint is the risk of stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been reviewed and approved by the Institutional Review Board of all participating centres. The written informed consent for participation in the trial will be obtained from all participants. The results of this study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT04242134.

Association of peri-procedural myocardial infarction with mortality after stenting true coronary bifurcation lesions: A pooled individual participant data analysis from four randomized controlled trials.

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.

Asian Pacific Society of Cardiology Consensus Recommendations on the Use of MitraClip for Mitral Regurgitation.

Transcatheter mitral valve repair with the MitraClip, a catheter-based percutaneous edge-to-edge repair technique to correct mitral regurgitation (MR), has been demonstrated in Western studies to be an effective and safe MR treatment strategy. However, randomised clinical trial data on its use in Asian-Pacific patients is limited. Hence, the Asian Pacific Society of Cardiology convened an expert panel to review the available literature on MitraClip and to develop consensus recommendations to guide clinicians in the region. The panel developed statements on the use of MitraClip for the management of degenerative MR, functional MR, and other less common indications, such as acute MR, dynamic MR, hypertrophic obstructive cardiomyopathy, and MR after failed surgical repair. Each statement was voted on by each panel member and consensus was reached when 80% of experts voted 'agree' or 'neutral'. This consensus-building process resulted in 10 consensus recommendations to guide general cardiologists in the evaluation and management of patients in whom MitraClip treatment is being contemplated.

Left atrial appendage occlusion for ischemic stroke prevention in patients with non-valvular atrial fibrillation: clinical expert opinion and consensus statement for the Asian-Pacific region.

PURPOSE: To develop a consensus statement for left atrial appendage occlusion (LAAO) in Asian-Pacific patients with non-valvular atrial fibrillation (NVAF) at risk of ischemic stroke. The need for such a region-specific consensus was indicated by the relative paucity of clinical evidence for LAAO and oral anticoagulation therapy obtained in Asian-Pacific populations and the specific stroke and bleeding characteristics of this population. METHODS: Consensus was developed by discussion and evaluation of available evidence and expert opinions during a 2-day meeting attended by clinical experts from the Asian-Pacific regions. RESULTS: The consensus statement arrived at provides recommendations based on available evidence and expert opinions regarding LAAO in Asian-Pacific patients. Gaps in the evidence and other areas requiring further research were identified. CONCLUSION: LAAO is an alternative device-based therapy in carefully selected patients with NVAF at risk of ischemic stroke. However, evidence for LAAO is primarily obtained from Caucasian populations, and data on LAAO in Asian-Pacific patients are scarce. While the present consensus statement addresses several therapy-related aspects based on careful interpretation of available evidence and expert opinions, other areas require additional evidence derived from Asian-Pacific populations.

Imaging and 2-year clinical outcomes of thin strut sirolimus-eluting bioresorbable vascular scaffold: The MeRes-1 extend trial.

OBJECTIVES: This study explores the safety and efficacy of thin strut MeRes100 sirolimus-eluting bioresorbable vascular scaffold (BRS) in patients with de novo coronary artery lesions. BACKGROUND: In interventional cardiology, the emergence of BRS technology is catalyzing the next paradigm shift. METHODS: The MeRes-1 Extend was a multicenter, prospective, single-arm, open-label study enrolling 64 patients in Spain, Macedonia, Brazil, South Africa, Malaysia, and Indonesia. The safety endpoint was major adverse cardiac events (MACE) which composed of cardiac death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (ID-TLR). The imaging efficacy endpoint was mean in-scaffold late lumen loss (LLL) evaluated by quantitative coronary angiography (QCA). Optical coherence tomography (OCT) imaging was performed at baseline and 6-month follow-up. RESULTS: A total of 69 target lesions were identified in 64 enrolled patients (mean age 58.30 ± 9.02 years). Of the treated lesions, 49 (71.01%) lesions were of type B2/C. Procedural and device success was achieved in 64 and 62 patients, respectively. At 2-year follow-up, MACE was reported in one patient (1.61%) in the form of ID-TLR. There was no case of MI, cardiac death or scaffold thrombosis through 2-year. In a subset of 32 patients, paired QCA showed mean in-scaffold LLL of 0.18 ± 0.31 mm at 6-month follow-up. In a subset of 21 patients, OCT revealed 97.95 ± 3.69% strut coverage with mean scaffold area of 7.56 ± 1.79 mm2 and no evidence of strut malapposition. CONCLUSIONS: The clinical and imaging outcomes of MeRes-1 Extend trial demonstrated favorable safety and efficacy of MeRes100 sirolimus-eluting BRS in patients with de novo coronary artery lesions.

Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial.

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.

3-Year Outcomes of the DKCRUSH-V Trial Comparing DK Crush With Provisional Stenting for Left Main Bifurcation Lesions.

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).

Left atrial appendage closure with WATCHMAN in Asian patients: 2 year outcomes from the WASP registry.

BACKGROUND: Left atrial appendage closure is a non-pharmacological alternative for stroke prevention in high-risk non-valvular atrial fibrillation patients, but has not been widely studied in Asian patients. The prospective WASP registry assessed real-world outcomes for patients undergoing WATCHMAN implant in the Asia-Pacific region. METHODS: Data were collected from consecutive patients across 9 centres. Major endpoints included procedural success, safety and long-term outcomes including occurrence of bleeding, stroke/transient ischaemic attack/systemic embolism and all-cause mortality. RESULTS: Subjects (n = 201) had a mean age of 70.8 ±â€¯9.4 years, high stroke risk (CHA2DS2-VASc: 3.9 ±â€¯1.7), elevated bleeding risk (HAS-BLED: 2.1 ±â€¯1.2) with 53% patients from Asian countries. Successful implantation occurred in 98.5% of patients; 7-day device/procedure-related SAE rate was 3.0%. After 2 years of follow-up, the rates of ischaemic stroke/TIA/SE and major bleeding were 1.9 and 2.2 per 100-PY, respectively, representing relative reductions of 77% and 49% versus expected rates per risk scores. The relative risk reductions versus expected rates were more pronounced in Asians vs. Non-Asians (89% vs 62%; 77% vs 14%). Other significant findings included larger mean LAA ostium diameter for Asians vs. Non-Asians (23.4 ±â€¯4.1 mm vs. 21.2 ±â€¯3.2 mm, p < 0.001) and hence requirement for larger median device size (27 mm for Asians, 24 mm for non-Asians [p < 0.0001]). CONCLUSION: Real-world experience of left atrial appendage closure with WATCHMAN has demonstrated low peri-procedural risk, and long-term efficacy for stroke and bleeding prevention in a primarily Asian cohort.

Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion.

BACKGROUND: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials. METHODS: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator. The primary end point was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life was assessed at baseline and at 1, 6, 12, 24, and 36 months. Because of slow recruitment, the trial was stopped before completion of the 1284 planned enrollments. RESULTS: Between March 2010 and September 2016, 834 patients were randomly assigned to the CTO-PCI (n=417) or no CTO-PCI (n=398) strategy. Among the patients assigned to the no CTO-PCI strategy, 78 (19.6%) crossed over to receive staged CTO-PCI within 3 days of randomization. The overall CTO-PCI success rate was 90.6%. Serious nonfatal complications associated with CTO-PCI occurred in 3 patients (1 stroke, 1 cardiac tamponade, and 1 patient with recurrent episodes of ventricular tachyarrhythmia induced by intracoronary thrombus). Approximately half of the patients in each group underwent PCI for an average of 1.3 non-CTO lesions, resulting in a comparable residual SYNTAX score (Synergy Between PCI With TAXUS and Cardiac Surgery; 3.7±5.4 versus 4.0±5.9, P=0.42) confined to non-CTO vessels. During a median follow-up of 4.0 years (interquartile range, 2.4 to 5.1 years), there was no significant difference between the CTO-PCI and the no CTO-PCI strategies in the incidence of the primary end point (22.3% versus 22.4%, hazard ratio, 1.03; 95% CI, 0.77 to 1.37; P=0.86). Both CTO-PCI and no CTO-PCI strategy were associated with significant improvements but without between-group differences in disease-specific health status that was sustained through 36 months. CONCLUSIONS: CTO-PCI was feasible with high success rates. There was no difference in the incidence of major adverse cardiovascular events with CTO-PCI versus no CTO-PCI, but the study was limited by low power for clinical end points and high crossover rates between groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01078051.

Treatment effects of systematic two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: rationale and design of a prospective, randomised and multicentre DEFINITION II trial.

INTRODUCTION: Provisional stenting (PS) for simple coronary bifurcation lesions is the mainstay of treatment. A systematic two-stent approach is widely used for complex bifurcation lesions (CBLs). However, a randomised comparison of PS and two-stent techniques for CBLs has never been studied. Accordingly, the present study is designed to elucidate the benefits of two-stent treatment over PS in patients with CBLs. METHODS AND ANALYSIS: This DEFINITION II study is a prospective, multinational, randomised, endpoint-driven trial to compare the benefits of the two-stent technique with PS for CBLs. A total of 660 patients with CBLs will be randomised in a 1:1 fashion to receive either PS or the two-stent technique. The primary endpoint is the rate of 12-month target lesion failure defined as the composite of cardiac death, target vessel myocardial infarction (MI) and clinically driven target lesion revascularisation. The major secondary endpoints include all causes of death, MI, target vessel revascularisation, in-stent restenosis, stroke and each individual component of the primary endpoints. The safety endpoint is the occurrence of definite or probable stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been approved by the Institutional Review Board of Nanjing First Hospital, and accepted by each participating centre. Written informed consent was obtained from all enrolled patients. Findings of the study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT02284750; Pre-results.

Hemodynamic analysis of a novel bioresorbable scaffold in porcine coronary artery model.

BACKGROUND: The shear stress distribution assessment can provide useful insights for the hemodynamic performance of the implanted stent/scaffold. Our aim was to investigate the effect of a novel bioresorbable scaffold, Mirage on local hemodynamics in animal models. METHOD: The main epicardial coronary arteries of 7 healthy mini-pigs were implanted with 11 Mirage Microfiber sirolimus-eluting Bioresorbable Scaffolds (MMSES). Optical coherence tomography (OCT) was performed post scaffold implantation and the obtained images were fused with angiographic data to reconstruct the coronary artery anatomy. Blood flow simulation was performed and Endothelial Shear Stress(ESS) distribution was estimated for each of the 11 scaffolds. ESS data were extracted in each circumferential 5-degree subunit of each cross-section in the scaffolded segment. The generalized linear mixed-effect analysis was implemented for the comparison of ESS in two scaffold groups; 150-µm strut thickness MMSES and 125-µm strut thickness MMSES. RESULTS: ESS was significantly higher in MMSES (150 µm) [0.85(0.49-1.40) Pa], compared to MMSES (125 µm) [0.68(0.35-1.18) Pa]. Both MMSES (150 µm) and MMSES (125 µm) revealed low recirculation zone percentages per luminal surface area [3.17% ± 1.97% in MMSES (150 µm), 2.71% ± 1.32% in MMSES (125 µm)]. CONCLUSION: Thinner strut Mirage scaffolds induced lower shear stress due to the small size vessels treated as compared to the thick strut version of the Mirage which was implanted in relatively bigger size vessels. Vessel size should be taken into account in planning BRS implantation. Small vessels may not get benefit from BRS implantation even with a streamlined strut profile. This pilot study warrants comparative assessment with commercially available bioresorbable scaffolds.

Double Kissing Crush Versus Provisional Stenting for Left Main Distal Bifurcation Lesions: DKCRUSH-V Randomized Trial.

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).

Cutoff Value and Long-Term Prediction of Clinical Events by FFR Measured Immediately After Implantation of a Drug-Eluting Stent in Patients With Coronary Artery Disease: 1- to 3-Year Results From the DKCRUSH VII Registry Study.

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).

Randomized Comparison of Absorb Bioresorbable Vascular Scaffold and Mirage Microfiber Sirolimus-Eluting Scaffold Using Multimodality Imaging.

OBJECTIVES: The primary objective of this study was to evaluate the safety and effectiveness of the Mirage (Manli Cardiology, Singapore) bioresorbable microfiber sirolimus-eluting scaffold compared with the Absorb (Abbott Vascular, Santa Clara, California) bioresorbable vascular scaffold in the treatment of stenotic target lesions located in native coronary arteries, ranging from ≥2.25 to ≤4.0 mm in diameter. Secondary objectives were to establish the medium-term safety, effectiveness, and performance of the Mirage device. BACKGROUND: The current generation of bioresorbable scaffolds has several limitations, such as thick square struts with large footprints that preclude their deep embedment into the vessel wall, resulting in protrusion into the lumen with microdisturbance of flow. The Mirage sirolimus-eluting bioresorbable microfiber scaffold is designed to address these concerns. METHODS: In this prospective, single-blind trial, 60 patients were randomly allocated in a 1:1 ratio to treatment with a Mirage sirolimus-eluting bioresorbable microfiber scaffold or an Absorb bioresorbable vascular scaffold. The clinical endpoints were assessed at 30 days and at 6 and 12 months. In-device angiographic late loss at 12 months was quantified. Secondary optical coherence tomographic endpoints were assessed post-scaffold implantation at 6 and 12 months. RESULTS: Median angiographic post-procedural in-scaffold minimal luminal diameters of the Mirage and Absorb devices were 2.38 mm (interquartile range [IQR]: 2.06 to 2.62 mm) and 2.55 mm (IQR: 2.26 to 2.71 mm), respectively; the effect size (d) was -0.29. At 12 months, median angiographic in-scaffold minimal luminal diameters of the Mirage and Absorb devices were not statistically different (1.90 mm [IQR: 1.57 to 2.31 mm] vs. 2.29 mm [IQR: 1.74 to 2.51 mm], d = -0.36). At 12-month follow-up, median in-scaffold late luminal loss with the Mirage and Absorb devices was 0.37 mm (IQR: 0.08 to 0.72 mm) and 0.23 mm (IQR: 0.15 to 0.37 mm), respectively (d = 0.20). On optical coherence tomography, post-procedural diameter stenosis with the Mirage was 11.2 ± 7.1%, which increased to 27.4 ± 12.4% at 6 months and remained stable (31.8 ± 12.9%) at 1 year, whereas the post-procedural optical coherence tomographic diameter stenosis with the Absorb was 8.4 ± 6.6%, which increased to 16.6 ± 8.9% and remained stable (21.2 ± 9.9%) at 1-year follow-up (Mirage vs. Absorb: dpost-procedure = 0.41, d6 months = 1.00, d12 months = 0.92). Angiographic median in-scaffold diameter stenosis was significantly different between study groups at 12 months (28.6% [IQR: 21.0% to 40.7%] for the Mirage, 18.2% [IQR: 13.1% to 31.6%] for the Absorb, d = 0.39). Device- and patient-oriented composite endpoints were comparable between the 2 study groups. CONCLUSIONS: At 12 months, angiographic in-scaffold late loss was not statistically different between the Mirage and Absorb devices, although diameter stenosis on angiography and on optical coherence tomography was significantly higher with the Mirage than with the Absorb. The technique of implantation was suboptimal for both devices, and future trials should incorporate optical coherence tomographic guidance to allow optimal implantation and appropriate assessment of the new technology, considering the novel mechanical properties of the Mirage.

Clinical Outcome of Double Kissing Crush Versus Provisional Stenting of Coronary Artery Bifurcation Lesions: The 5-Year Follow-Up Results From a Randomized and Multicenter DKCRUSH-II Study (Randomized Study on Double Kissing Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions).

BACKGROUND: Provisional stenting is effective for anatomic simple bifurcation lesions. Double kissing crush stenting reduces the 1-year rate of target lesion revascularization. This study aimed to investigate the 5-year clinical results of the DKCRUSH-II study (Randomized Study on Double Kissing Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions). METHODS AND RESULTS: A total of 370 patients with coronary bifurcation lesions who were randomly assigned to either the double kissing crush or provisional stenting group in the DKCRUSH-II study were followed for 5 years. The primary end point was the occurrence of a major adverse cardiac event at 5 years. Patients were classified by simple and complex bifurcation lesions according to the DEFINITION criteria (Definitions and Impact of Complex Bifurcation Lesions on Clinical Outcomes After Percutaneous Coronary Intervention Using Drug-Eluting Stents). At 5 years, the major adverse cardiac event rate (23.8%) in the provisional stenting group was insignificantly different to that of the double kissing group (15.7%; P=0.051). However, the difference in the target lesion revascularization rate between 2 groups was sustained through the 5-year follow-up (16.2% versus 8.6%; P=0.027). The definite and probable stent thrombosis rate was 2.7% in each group (P=1.0). Complex bifurcation was associated with a higher rate of target lesion revascularization (21.6%) at 5 years compared with 11.1% in patients with a simple bifurcation (P=0.037), with an extremely high rate in the provisional stenting group (36.8% versus 12.5%, P=0.005) mainly because of final kissing balloon inflation (19.4% versus 5.2%; P=0.036). CONCLUSIONS: The double kissing crush stenting technique for coronary bifurcation lesions is associated with a lower rate of target lesion revascularization. The optimal stenting approach based on the lesions' complexity may improve the revascularization for patients with complex bifurcations. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org. Unique identifier: ChiCTR-TRC-0000015.