Maik J. Grundeken

A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial

BACKGROUND Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent. Here we report secondary clinical and procedural outcomes after 1 year of follow-up. METHODS In a single-blind, multicentre, randomised trial, we enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb, Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience, Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. The co-primary endpoints of this study are vasomotion (change in mean lumen diameter before and after nitrate administration at 3 years) and difference between minimum lumen diameter (after nitrate administration) after the index procedure and at 3 years. Secondary endpoints were procedural performance assessed by quantitative angiography and intravascular ultrasound; composite clinical endpoints based on death, myocardial infarction, and coronary revascularisation; device and procedural success; and angina status assessed by the Seattle Angina Questionnaire and exercise testing at 6 and 12 months. Cumulative angina rate based on adverse event reporting was analysed post hoc. This trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the bioresorbable scaffold group (335 patients, 364 lesions) or the metallic stent group (166 patients, 182 lesions). Dilatation pressure and balloon diameter at the highest pressure during implantation or postdilatation were higher and larger in the metallic stent group, whereas the acute recoil post implantation was similar (0.19 mm for both, p=0.85). Acute lumen gain was lower for the bioresorbable scaffold by quantitative coronary angiography (1.15 mm vs 1.46 mm, p<0.0001) and quantitative intravascular ultrasound (2.85 mm(2)vs 3.60 mm(2), p<0.0001), resulting in a smaller lumen diameter or area post procedure. At 1 year, however, cumulative rates of first new or worsening angina from adverse event reporting were lower (72 patients [22%] in the bioresorbable scaffold group vs 50 [30%] in the metallic stent group, p=0.04), whereas performance during maximum exercise and angina status by SAQ were similar. The 1-year composite device orientated endpoint was similar between the bioresorbable scaffold and metallic stent groups (16 patients [5%] vs five patients [3%], p=0.35). Three patients in the bioresorbable scaffold group had definite or probable scaffold thromboses (one definite acute, one definite sub-acute, and one probable late), compared with no patients in the metallic stent group. There were 17 (5%) major cardiac adverse events in the bioresorbable scaffold group compared with five (3%) events in the metallic stent group, with the most common adverse events being myocardial infarction (15 cases [4%] vs two cases [1%], respectively) and clinically indicated target-lesion revascularisation (four cases [1%] vs three cases [2%], respectively). INTERPRETATION The everolimus-eluting bioresorbable scaffold showed similar 1-year composite secondary clinical outcomes to the everolimus-eluting metallic stent. FUNDING Abbott Vascular.

Initial experience and clinical evaluation of the Absorb bioresorbable vascular scaffold (BVS) in real-world practice: the AMC Single Centre Real World PCI Registry.

AIMS To report procedural and midterm clinical outcomes after the use of the second-generation Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) in a real-world percutaneous coronary intervention (PCI) registry. METHODS AND RESULTS All patients assigned to treatment with the Absorb BVS in the Academic Medical Center, Amsterdam, between August 2012 and August 2013 were included in a prospective registry. A total of 135 patients were included in the study, including 53 (39%) acute coronary syndrome (ACS) patients (13% ST-segment elevation myocardial infarction [STEMI]). In total 159 lesions were treated, including 102 (62%) with a type B2 or C classification. Pre- and post-procedural quantitative coronary angiography (QCA) analyses showed an acute gain of 1.37±0.53 mm. An angiographic success rate was achieved in 152 (96%) of the lesions. Six-month follow-up was available in 97% of the patients. Six-month cumulative target vessel failure (composite of all-cause mortality, any myocardial infarction [MI] and target vessel revascularisation [TVR]) rate was 8.5%, including a 3.0% MI, 3.0% definite scaffold thrombosis, 6.3% target lesion revascularisation, and an 8.5% TVR rate. CONCLUSIONS The use of the Absorb BVS in a cohort reflecting daily clinical practice is feasible and associated with good procedural safety and angiographic success rate. In addition, six-month follow-up is associated with acceptable clinical outcomes.

A randomized trial of a dedicated bifurcation stent versus provisional stenting in the treatment of coronary bifurcation lesions

BACKGROUND Bifurcation lesions are frequent among patients with symptomatic coronary disease treated by percutaneous coronary intervention. Current evidence recommends a conservative (provisional) approach when treating the side branch (SB). OBJECTIVES The TRYTON (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries) bifurcation trial sought to compare treatment of de novo true bifurcation lesions using a dedicated bifurcation stent or SB balloon angioplasty. METHODS We randomly assigned patients with true bifurcation lesions to a main vessel stent plus provisional stenting or the bifurcation stent. The primary endpoint (powered for noninferiority) was target vessel failure (TVF) (cardiac death, target vessel myocardial infarction, and target vessel revascularization). The secondary angiographic endpoint (powered for superiority) was in-segment percent diameter stenosis of the SB at 9 months. RESULTS We randomized 704 patients with bifurcation coronary lesions at 58 centers (30 from Europe and 28 from the United States). At 9 months, TVF was 17.4% in the bifurcation stent group compared with 12.8% in the provisional group (p=0.11), mainly because of a higher periprocedural myocardial infarction rate (13.6% vs. 10.1%, p=0.19). The TVF difference of +4.6% (2-sided 95% confidence interval: -1.0 to 10.3; upper limit of the 1-sided 95% confidence interval: 10.3) was not within the pre-specified noninferiority margin of 5.5% (p=0.42 for noninferiority). The SB in-segment diameter stenosis among the angiographic cohort was lower in the bifurcation stent group compared with the provisional group (31.6% vs. 38.6%, p=0.002 for superiority), with no difference in binary restenosis rates (diameter stenosis≥50%) at 9 months follow-up (22.6% vs. 26.8%, p=0.44). CONCLUSIONS Provisional stenting should remain the preferred strategy for treatment of non-left main true coronary bifurcation lesions. (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [TRYTON]; NCT01258972).

Six-month and one-year clinical outcomes after placement of a dedicated coronary bifurcation stent: A patient-level pooled analysis of eight registry studies

AIMS Smaller studies have previously shown promising results after Tryton Side Branch Stent™ (Tryton Medical, Durham, NC, USA) placement. However, these previous studies were limited by their small sample size and relatively short follow-up. We performed a patient-level pooled analysis to evaluate six-month and one year clinical outcomes of more than 900 patients who were enrolled in eight registries with the Tryton stent. METHODS AND RESULTS Data from eight Tryton registries, including 905 patients with 929 bifurcation lesions, were pooled on a patient level to form one dataset. The primary outcome was six-month target vessel failure (TVF), defined as the composite of cardiac death, any myocardial infarction, and clinically indicated target vessel revascularisation. Procedural success was defined as successful stent placement and no in-hospital major adverse cardiac events. Multivariable analysis was performed to determine independent predictors for one-year TVF. Follow-up data were available in 97%. Procedural success was 95% and TVF rate was 6.5% at six months and 8.5% at one year. Stent thrombosis occurred in 0.5% of patients. Left main coronary artery bifurcation lesion (HR 6.46) and main branch reference vessel diameter <3.0 mm (HR 2.62) were independent predictors for TVF. CONCLUSIONS In the real world setting of registries including more than 900 patients, the use of the Tryton stent is associated with procedural and mid-term clinical results that compare very favourably with historical studies. The primary endpoint of TVF was primarily determined by reference vessel diameter of the main branch and left main bifurcation lesion location.

In vitro validation and comparison of different software packages or algorithms for coronary bifurcation analysis using calibrated phantoms: Implications for clinical practice and research of bifurcation stenting

The accuracy and precision of quantitative coronary angiography (QCA) software dedicated for bifurcation lesions compared with conventional single‐vessel analysis remains unknown. Furthermore, comparison of different bifurcation analysis algorithms has not been performed.

Incidence and Potential Mechanism(s) of Post-Procedural Rise of Cardiac Biomarker in Patients With Coronary Artery Narrowing After Implantation of an Everolimus-Eluting Bioresorbable Vascular Scaffold or Everolimus-Eluting Metallic Stent.

OBJECTIVES This study sought to evaluate the mechanism of post-procedural cardiac biomarker (CB) rise following device implantation. BACKGROUND A fully bioresorbable Absorb scaffold, compared with everolimus-eluting metallic stents (EES), might be associated with a higher incidence of periprocedural myocardial injury. METHODS In 501 patients with stable or unstable angina randomized to either Absorb (335 patients) or EES (n = 166) in the ABSORB II trial, 3 types of CB (creatine kinase, creatine kinase-myocardial band, and troponin) were obtained before and after procedure. Per protocol, periprocedural myocardial infarction (PMI) was defined as creatine kinase rise >2× the upper limit of normal with creatine kinase-myocardial band rise. RESULTS Incidence of side branch occlusion and any anatomic complications assessed by angiography was similar between the 2 treatment arms (side branch occlusion: Absorb: 5.3% vs. Xience: 7.6%, p = 0.07; any anatomic complication: Absorb: 16.4% vs. EES: 19.9%, p = 0.39). Fourteen patients who presented with recent myocardial infarction at entry with normalized creatine kinase-myocardial band according to the protocol were excluded for post-CB analysis. The overall compliance for CB was 97.8%. The CB rise subcategorized in 7 different ranges was comparable between the 2 treatment arms. PMI rate was numerically higher in the Absorb arm according to the per-protocol definitions, and treatment with overlapping devices was the only independent determinant of per-protocol PMI (odds ratio: 5.07, 95% confidence interval: 1.78 to 14.41, p = 0.002). CONCLUSIONS There were no differences in the incidence of CB rise and PMI between Absorb and EES. Device overlap might be a precipitating factor of myocardial injury. (ABSORB II Randomized Clinical Trial: A Clinical Evaluation to Compare the Safety, Efficacy, and Performance of Absorb Everolimus Eluting Bioresorbable Vascular Scaffold System Against Xience Everolimus Eluting Coronary Stent System in the Treatment of Subjects With Ischemic Heart Disease Caused by De Novo Native Coronary Artery Lesions [ABSORB II]; NCT01425281).

Inter–Core Lab Variability in Analyzing Quantitative Coronary Angiography for Bifurcation Lesions: A Post-Hoc Analysis of a Randomized Trial

OBJECTIVES This study sought to evaluate inter-core lab variability in quantitative coronary angiography (QCA) analysis of bifurcation lesions. BACKGROUND QCA of bifurcation lesions is challenging. To date there are no data available on the inter-core lab variability of bifurcation QCA analysis. METHODS The randomized Tryton IDE (Tryton Pivotal IDE Coronary Bifurcation Trial) compared the Tryton Side Branch Stent (Tryton Medical, Durham, North Carolina) with balloon angioplasty as side branch treatment. QCA was performed in an angiographic subcohort (n = 326) at 9-month follow-up. Inter-core lab variability of QCA analysis between the Cardiovascular Research Foundation and the Cardialysis core labs was evaluated before and after alignment of the used QCA methodology using angiographic data derived from this angiographic follow-up cohort. RESULTS In the original analysis, before alignment of QCA methodology, the mean difference between the core labs (bias) was large for all QCA parameters with wide 95% limits of agreement (1.96 × SD of the bias), indicating marked variability. The bias of the key angiographic endpoint of the Tryton trial, in-segment percentage diameter stenosis (%DS) of the side branch, was 5.5% (95% limits of agreement: -26.7% to 37.8%). After reanalysis, the bias of the in-segment %DS of the side branch reduced to 1.8% (95% limits of agreement: -16.7% to 20.4%). Importantly, after alignment of the 2 core labs, there was no longer a difference between both treatment groups (%DS of the side branch: treatment group A vs. group B: 34.4 ± 19.4% vs. 32.4 ± 16.1%, p = 0.340). CONCLUSIONS Originally, a marked inter-core lab variability of bifurcation QCA analysis was found. After alignment of methodology, inter-core lab variability decreased considerably and impacted angiographic trial results. This latter finding emphasizes the importance of using the same methodology among different core labs worldwide. (Tryton Pivotal Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [TRYTON]; NCT01258972).

A Systematic Review and Meta-Analysis on Primary Percutaneous Coronary Intervention of an Unprotected Left Main Coronary Artery Culprit Lesion in the Setting of Acute Myocardial Infarction

OBJECTIVES This study sought to evaluate 30-day all-cause mortality of patients treated with primary percutaneous coronary intervention (PCI) presenting with an acute myocardial infarction (AMI) due to an unprotected left main coronary artery (ULMCA) culprit lesion. In addition, an average estimated mortality rate was extrapolated from the available data. BACKGROUND There are limited data available on clinical outcome after primary PCI in patients presenting with AMI with unprotected left main as the infarct-related coronary artery. METHODS Medical literature databases were searched to identify cohort studies reporting on primary PCI for unprotected left main-related AMI. A total of 13 retrospective studies meeting all pre-specified criteria were included in the meta-analysis. No randomized trials were available. The primary endpoint for the meta-analysis was 30-day all-cause mortality. RESULTS This meta-analysis comprises a total of 977 patients, of which 252 (26%) presented in cardiogenic shock. Thirty-day all-cause mortality was evaluated using a forest plot analysis and showed higher event rates in patients presenting with cardiogenic shock among all subgroups. The average estimated 30-day all-cause mortality was 15% in patients presenting without signs of cardiogenic shock and 55% in patients presenting with cardiogenic shock (relative risk: 3.74, 95% confidence interval [CI]: 2.95 to 4.76, p < 0.001). CONCLUSIONS In this large meta-analysis of patients treated with primary PCI for AMI due to an ULMCA culprit lesion, the 30-day all-cause mortality in patients presenting with shock is much higher than in patients not presenting with shock. The estimated all-cause mortality data may serve as a benchmark for future reference.

Outcomes of a Dedicated Stent in Coronary Bifurcations with Large Side Branches: A Subanalysis of the Randomized TRYTON Bifurcation Study

To examine the benefit of the Tryton dedicated side branch (SB) stent compared with provisional stenting in the treatment of complex bifurcation lesions involving large SBs.

Distal Embolization of Hydrophilic-Coating Material From Coronary Guidewires After Percutaneous Coronary Interventions

Background—Coronary guidewires are indispensable during percutaneous coronary interventions. Nowadays, most guidewires have hydrophilic coatings to improve their trackability, allowing easy lesion passage and facilitating balloon and stent positioning. Recent reports, however, have raised concerns about detachment and subsequent embolization of these hydrophilic coatings. Methods and Results—We have retrospectively reviewed the histological samples of the myocardium, obtained during autopsies in the period 2009 to 2013, from all patients who had a history of percutaneous coronary interventions (n=40). Foreign material was observed in the distal myocardium in 4 patients (10%). Furthermore, we have reviewed 205 thrombus specimens which were obtained during thrombus aspiration in the setting of primary percutaneous coronary interventions in the period 2005 to 2009. In 45% of the cases, foreign material was observed within the thrombus. Finally, we have examined the histopathologic appearance of hydrophilic-guidewire coating material ex vivo by embedding the coating in placenta specimen and cut and stain it in exactly the same manner as the myocardium and thrombus specimen. The histopathologic appearance of the hydrophilic coating ex vivo was identical to the foreign material found in vivo. Conclusions—Distal embolization of hydrophilic-coating material was observed in 10% of the patients who had a history of percutaneous coronary interventions. Hydrophilic-coating material was found in 45% of coronary thrombus specimen obtained during thrombus aspiration. These findings suggest that detachment and distal embolization of hydrophilic-coating material from coronary guidewires occur more often than the sparse literature on this topic suggests.