Carlos Collet

Clinical outcomes of state-of-the-art percutaneous coronary revascularization in patients with de novo three vessel disease: 1-year results of the SYNTAX II study.

Abstract Aims To investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease. Methods and results The SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39–0.85, P = 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11–0.70, P = 0.007) and revascularisation (HR 0.57, 95% CI 0.37–0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27–1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10–4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07–0.97, P = 0.045). Conclusion At one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted. ClinicalTrials.gov Identifier NCT02015832

Bioresorbable Scaffold: The Emerging Reality and Future Directions

In the era of drug-eluting stents, large-scale randomized trials and all-comer registries have shown excellent clinical results. However, even the latest-generation drug-eluting stent has not managed to address all the limitations of permanent metallic coronary stents, such as the risks of target lesion revascularization, neoatherosclerosis, preclusion of late lumen enlargement, and the lack of reactive vasomotion. Furthermore, the risk of very late stent, although substantially reduced with newer-generation drug-eluting stent, still remains. These problems were anticipated to be solved with the advent of fully biodegradable devices. Fully bioresorbable coronary scaffolds have been designed to function transiently to prevent acute recoil, but have retained the capability to inhibit neointimal proliferation by eluting immunosuppressive drugs. Nevertheless, long-term follow-up data of the leading bioresorbable scaffold (Absorb) are becoming available and have raised a concern about the relatively higher incidence of scaffold thrombosis. To reduce the rate of clinical events, improvements in the device, as well as implantation procedure, are being evaluated. This review will focus on the current CE-mark approved bioresorbable scaffolds, their basic characteristics, and clinical results. In addition, we summarize the current limitations of bioresorbable scaffold and their possible solutions.

Late thrombotic events after bioresorbable scaffold implantation: a systematic review and meta-analysis of randomized clinical trials

Aims To compare the long-term safety and efficacy of bioresorbable vascular scaffold (BVS) with everolimus-eluting stent (EES) after percutaneous coronary interventions. Methods and results A systematic review and meta-analysis of randomized clinical trials comparing clinical outcomes of patients treated with BVS and EES with at least 24 months follow-up was performed. Adjusted random-effect model by the Knapp-Hartung method was used to compute odds ratios (OR) and 95% confidence intervals (CI). The primary safety outcome of interest was the risk of definite/probable device thrombosis (DT). The primary efficacy outcome of interest was the risk of target lesion failure (TLF). Five randomized clinical trials (n = 1730) were included. Patients treated with Absorb BVS had a higher risk of definite/probable DT compared with patients treated with EES (OR 2.93, 95%CI 1.37-6.26, P = 0.01). Very late DT (VLDT) occurred in 13 patients [12/996 (1.4%, 95%CI: 0.08-2.5) Absorb BVS vs. 1/701 (0.5%, 95%CI: 0.2-1.6) EES; OR 3.04; 95%CI 1.2-7.68, P = 0.03], 92% of the VLDT in the BVS group occurred in the absence of dual antiplatelet therapy (DAPT). Patients treated with Absorb BVS had a trend towards higher risk of TLF (OR 1.48, 95%CI 0.90-2.42, P = 0.09), driven by a higher risk of target vessel myocardial infarction and ischaemia-driven target lesion revascularization. No difference was found in the risk of cardiac death. Conclusion Compared with EES, the use of Absorb BVS was associated with a higher rate of DT and a trend towards higher risk of TLF. VLDT occurred in 1.4% of the patients, the majority of these events occurred in the absence of DAPT.

Single or dual antiplatelet therapy after PCI

The optimal duration and type of antiplatelet therapy after implantation of a drug-eluting stent (DES) remains uncertain. At the time of the first-in-man implantation of the sirolimus DES in 1999, the protocol-defined dual antiplatelet therapy (DAPT) duration was only 2 months. Subsequently, DAPT duration was extended to 1 year on the basis of anecdotal historical data, and this practice was then incorporated into clinical guidelines. For >1 decade, trialists have sought to compare the safety and efficacy of abbreviated (<6 months) and prolonged (>12 months) DAPT regimens. However, the body of evidence is limited by the heterogeneity of end points, time of randomization, and bleeding criteria used in each trial. Pharmaceutical advances led to the introduction of new ADP-receptor antagonists, which are thought to be more effective than clopidogrel. The ADP-receptor antagonists moved the focus from the optimal duration of DAPT to the potential efficacy of single antiplatelet therapy after DES implantation. In this Review, we summarize the current evidence on the duration of DAPT and the risk of bleeding and adverse cardiac events after DES implantation, and describe the pitfalls of trial interpretation. The ongoing, prospective trials to test single antiplatelet therapy after DES implantation are also discussed.

Is quantitative coronary angiography reliable in assessing the lumen gain after treatment with the everolimus-eluting bioresorbable polylactide scaffold?

AIMS The current study aimed to assess the difference in lumen dimension measurements between optical coherence tomography (OCT) and quantitative coronary angiography (QCA) in the polymeric bioresorbable scaffold and metallic stent. METHODS AND RESULTS In the randomised ABSORB Japan trial, 87 lesions in the Absorb arm and 44 lesions in the XIENCE arm were analysed. Post-procedural OCT-QCA lumen dimensions were assessed in matched proximal/distal non-stented/non-scaffolded reference (n=199), scaffolded (n=145) and stented (n=75) cross-sections at the two device edges using the Bland-Altman method. In the non-stented/non-scaffolded reference segments, QCA systematically underestimated lumen diameter (LD) compared with OCT (accuracy, -0.26 mm; precision, 0.47 mm; 95% limits of agreement as a mean bias±1.96 standard deviation, -1.18-0.66 mm). When compared to OCT, QCA of the Absorb led to a more severe underestimation of the LD (-0.30 mm; 0.39 mm; -1.06-0.46 mm) than with the XIENCE (-0.14 mm; 0.31 mm; -0.75-0.46 mm). QCA underestimated LD by 9.1%, 4.9%, and 9.8% in the reference, stented, and scaffolded segments, respectively. The protrusion distance of struts was larger in the Absorb arm than in the XIENCE arm (135±27 µm vs. 18±26 µm, p<0.001), and may have contributed to the observed differences. CONCLUSIONS In-device QCA measurement was differently affected by the presence of a metallic or polymeric scaffold, a fact that had a significant impact on the QCA assessment of acute gain and post-procedural minimum LD.

Long-term serial non-invasive multislice computed tomography angiography with functional evaluation after coronary implantation of a bioresorbable everolimus-eluting scaffold: the ABSORB cohort B MSCT substudy

Aims Multimodality invasive imaging of the first-in-man cohort demonstrated at 5 years stable lumen dimensions and a low rate of major adverse cardiac events (MACE). However, the long-term non-invasive assessment of this device remains to be documented. The objective was to describe the 72-month multislice computed tomography (MSCT) angiographic and functional findings after the implantation of the second iteration of the fully resorbable everolimus-eluting polymeric scaffold. Methods and results In the ABSORB Cohort B trial patients with non-complex de novo lesions were treated with second iteration bioresobable vascular scaffold (BVS). MSCT angiography was performed as an optional investigation at 18 months; patients were reconsented for a second investigation at 72 months. MSCT data were analysed at independent core laboratories for quantitative analysis of lumen dimensions and for calculation of fractional flow reserve derived from computed tomography (FFRCT). From the overall Cohort B (101 patients), 53 patients underwent MSCT imaging at 72 months. The MACE rate was 1.9% (1/53). At 72 months, the median minimal lumen area (MLA) was 4.05 mm2 (interquartile range [IQR]: 3.15-4.90) and the mean percentage area stenosis was 18% (IQR: 4.75-31.25), one scaffold was totally occluded. In 39 patients with paired MSCT analysis, the MLA significantly increased from the first to the second follow-up (Δ = 0.80 mm2, P = 0.002). The change in the median FFRCT scaffold gradient between time points was zero. Conclusion The long-term serial non-invasive MSCT evaluation with FFRCT assessment after bioresorbable scaffold implantation confirmed in-scaffold late lumen enlargement with the persistence of normalization of the FFRCT. Clinical trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856856.

Non-invasive Heart Team assessment of multivessel coronary disease with coronary computed tomography angiography based on SYNTAX score II treatment recommendations: design and rationale of the randomised SYNTAX III Revolution trial

AIMS The aim of this study was to investigate whether a Heart Team decision-making process regarding the choice of revascularisation strategy based on non-invasive coronary multislice computed tomography angiography (MSCT) assessment of coronary artery disease (CAD) is equivalent to the standard-of-care invasive angiography-based assessment in patients with multivessel CAD. METHODS AND RESULTS The SYNTAX III Revolution trial is a prospective, multicentre, all-comers randomised trial that will randomise two Heart Teams to select between surgical and percutaneous treatment according to either an invasive conventional angiography or a non-invasive MSCT angiography assessment in patients with multivessel CAD. The treatment selection by each Heart Team will be guided by the SYNTAX score II calculation. The primary endpoint is the level of agreement according to kappa of the initial decision by the Heart Teams on the modality of the revascularisation based on MSCT and angiography assessments. Secondary endpoints include agreement on the number of vessels requiring treatment and the coronary segments in need of revascularisation. CONCLUSIONS The SYNTAX III Revolution trial will provide valuable information regarding the ability of a purely non-invasive coronary anatomy assessment to select accurately the most appropriate revascularisation strategy for patients with multivessel CAD.

The interaction of de-novo and pre-existing aortic regurgitation after TAVI: Insights from a new quantitative aortographic technique.

AIMS The aim of this study was to evaluate the intermediate-term clinical impact of aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) using a novel quantitative angiographic method taking into account the influence of pre-existing AR. METHODS AND RESULTS AR after TAVI was quantified in 338 patients (age 82 [78-86] years; 55% male) and the influence on intermediate-term all-cause mortality was evaluated. In 228 aortograms, AR was quantitated using a dedicated videodensitometric method focused in the left ventricular outflow tract (LVOT-AR). Patients with LVOT-AR >0.17 had a significantly increased all-cause mortality at three years, compared with patients who had LVOT-AR ≤0.17 (adjusted hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.05-2.86, p=0.032). Taking the influence of pre-existing AR into account, patients with post-procedural LVOT-AR >0.17 and ≤mild pre-existing AR had a significantly increased mortality at two years, compared to patients with LVOT-AR >0.17 and >mild pre-existing AR (HR: 2.55, 95% CI: 1.16-5.58, p=0.029). In those with >mild pre-existing AR (n=70), post-TAVI LVOT-AR >0.17 was not associated with increased mortality (HR: 0.77, 95% CI: 0.31-1.91, p=0.578). CONCLUSIONS AR after TAVI could be quantitated utilising LVOT-AR. The cut-point of >0.17 indicates a significant AR pertaining to increased intermediate-term mortality, especially in those with no significant pre-existing AR.

Intracoronary optical coherence tomography: Clinical and research applications and intravascular imaging software overview

By providing valuable information about the coronary artery wall and lumen, intravascular imaging may aid in optimizing interventional procedure results and thereby could improve clinical outcomes following percutaneous coronary intervention (PCI). Intravascular optical coherence tomography (OCT) is a light‐based technology with a tissue penetration of approximately 1 to 3 mm and provides near histological resolution. It has emerged as a technological breakthrough in intravascular imaging with multiple clinical and research applications. OCT provides detailed visualization of the vessel following PCI and provides accurate assessment of post‐procedural stent performance including detection of edge dissection, stent struts apposition, tissue prolapse, and healing parameters. Additionally, it can provide accurate characterization of plaque morphology and provides key information to optimize post‐procedural outcomes. This manuscript aims to review the current clinical and research applications of intracoronary OCT and summarize the analytic OCT imaging software packages currently available.

Tratamento de reestenose intrastent com o novo stent farmacológico FirebirdTM, liberador de sirolimus: resultados angiográficos e ultrassonográficos de um ano de evolução

ABSTRACT Treatment of In-Stent Restenosis with theNew Firebird TM Sirolimus Eluting Stent –One Year Angiographic and IntravascularUltrasound Follow-up Results Background: In-stent restenosis (ISR), resulting from excessiveneointimal hyperplasia, is a major limitation of percutaneouscoronary intervention. Despite the efficacy of first generationdrug-eluting stents (DES) in the treatment of ISR, issues rela-ted to the safety and flexibility/navigability profile haveencouraged the development of new generations of DES.The new Firebird TM DES (Microport Co. Ltd., Shanghai, Chi-na) combines a stainless steel platform (L316) of fine struts(0,0040’), a powerful anti-proliferative agent (sirolimus, ata dose of 9 μg/mm²) and a coating that includes three layersof a durable polymer, which controls drug release. Thoughit is a most used DES in China, little is known about itsperformance, particularly in subgroups of greater complexity. Method: Between February and December 2009, patientswith single bare metal stent restenotic lesions, were sub-mitted to percutaneous coronary intervention with Firebird