http://repub.eur.nl/res/aut/5657/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39926/ 2013-05-01T00:00:00Z Background: Overlapping first generation sirolimus-and paclitaxel-eluting stents are associated with persistent inflammation, fibrin deposition and delayed endothelialisation in preclinical models, and adverse angiographic and clinical outcomes-including death and myocardial infarction (MI)-in clinical studies. Objectives: To establish as to whether there are any safety concerns with newer generation drug-eluting stents (DES). Design: Propensity score adjustment of baseline anatomical and clinical characteristics were used to compare clinical outcomes (Kaplan-Meier estimates) between patients implanted with overlapping DES (Resolute zotarolimus-eluting stent (R-ZES) or R-ZES/other DES) against no overlapping DES. Additionally, angiographic outcomes for overlapping R-ZES and everolimus-eluting stents were evaluated in the randomised RESOLUTE All-Comers Trial. Setting: Patient level data from five controlled studies of the RESOLUTE Global Clinical Program evaluating the R-ZES were pooled. Enrolment criteria were generally unrestrictive. Patients:5130 patients. Main outcome measures:2-year clinical outcomes and 13-month angiographic outcomes. Results:644 of 5130 patients (12.6%) in the RESOLUTE Global Clinical Program underwent overlapping DES implantation. Implantation of overlapping DES was associated with an increased frequency of MI and more complex/calcified lesion types at baseline. Adjusted in-hospital, 30-day and 2-year clinical outcomes indicated comparable cardiac death (2-year overlap vs non-overlap:3.0% vs 2.1%, p=0.36), major adverse cardiac events (13.3% vs 10.7%, p=0.19), target-vessel MI (3.9% vs 3.4%, p=0.40), clinically driven target vessel revascularisation (7.7% vs 6.5%, p=0.32), and definite/probable stent thrombosis (1.4% vs 0.9%, p=0.28). 13-month adjusted angiographic outcomes were comparable between overlapping and non-overlapping DES. Conclusions: Overlapping newer generation DES are safe and effective, with comparable angiographic and clinical outcomes-including repeat revascularisation-to non-overlapping DES. http://repub.eur.nl/res/pub/38093/ 2012-12-11T00:00:00Z The concern about how the effects of pharmacologic as well as device therapies are understood in clinical practice requires attention to the methods of randomized clinical trials, including the selection of meaningful clinical endpoints. http://repub.eur.nl/res/pub/39328/ 2012-11-01T00:00:00Z Objectives: The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. BACKGROUND: A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. METHODS AND Results: Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints. Conclusions: This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavours of applying definitions to other transcatheter valve therapies (for example, mitral valve repair). Published on behalf of the European Association for Cardio-Thoracic Surgery. The article has been co-published in the European Heart Journal, EuroIntervention, Journal of the American College of Cardiology, and Journal of Thoracic and Cardiovascular Surgery. All rights reserved. © The Author 2012. http://repub.eur.nl/res/pub/37632/ 2012-10-01T00:00:00Z Objective: To assess the differential implications of cardiac biomarker type on peri-procedural myocardial infarction (PMI) reporting. Setting: The Resolute 'All-Comers' stent trial. Interventions: Blood samples for creatine kinase (CK), CK-myoband (CK-MB) mass or cardiac troponin (cTn) (optional) were collected before and at 6, 12 and 18 h after the assigned percutaneous coronary intervention or at discharge. PMIs were adjudicated using either the 2007 universal definition of MI (type-4a) or the extended historical definition of MI. Patients: 2121/2292 patients (92.5%) had an analysable dataset for either biomarker. 890/2121 patients (42%) presented with an acute coronary syndrome (ACS). 267/890 patients (30%) were within 24 h of an ST-segment elevation MI. Main outcome measures: Type-4a MI was diagnosed in 208/2121 patients (9.8%) when cTn was used (CKMB mass if cTn not available), and in 93/2121 of patients (4.4%) when CK-MB mass was used (cTn if CK-MB mass not available). With the extended historical CK-based definition of MI, PMI was diagnosed in 65/2121 patients (3.1%). Adjudication of type-4a MI in patients with an ACS was problematic with <10% of the potential type-4a MI being confirmed as an event, as compared with approximately 95% in stable patients undergoing elective PCI. Type-4a MI was not associated with the subsequent hazard for cardiac mortality (p=0.6). Conclusions: The percentage of adjudicated PMI events is driven by the MI-definition criteria and biomarker type. Type-4a MI may not be a reliable component of the primary composite end point in coronary stent investigations which recruit patients with ACS. Trial registration number: http://www.ClinicalTrials. gov; Unique identifier: NCT00617084. http://repub.eur.nl/res/pub/34636/ 2011-06-01T00:00:00Z Objectives: This study sought to assess the impact of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SXscore) on clinical outcomes in patients undergoing percutaneous coronary intervention. Background: The SXscore has been demonstrated to have an ability to predict clinical outcomes in patients undergoing percutaneous revascularization. Current studies are limited by the relatively small number of patients in each SXscore group. Methods: Patient-level data from 7 contemporary coronary stent trials were pooled by an independent academic research organization (Cardialysis, Rotterdam, the Netherlands). Analysis was performed on a cohort of 6,508 patients treated with drug-eluting stents and who had calculated SXscores. Clinical outcomes in terms of death, myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE, a composite of death, MI, and repeat revascularization) were subsequently stratified according to SXscore quartiles: SXscoreQ1≤8 (n = 1,702); 8 < SXscoreQ2<15 (n = 1,528); 15 ≤ SXscoreQ3≥23 (n = 1,620); and SXscoreQ4<23 (n = 1,658). Results: One-year outcomes were available in 6,496 patients (99.8%). At 1-year follow-up, all clinical outcomes including mortality, MI, repeat revascularization, MACE, and definite and any stent thrombosis were all significantly higher in patients in the highest SXscore quartile. Similar trends were observed in a subgroup of 2,093 patients (32.2%) who presented with an ST- or nonST-segment elevation MI. The rate of MACE among patients with an SXscore >32 and ≤32 was 24.9% and 14.0%, respectively (p < 0.001). The SXscore was identified as an independent predictor of all clinical outcomes including mortality, MACE, and stent thrombosis (p < 0.001 for all). Conclusions: This study confirms the consistent ability of the SXscore to identify patients who are at highest risk of adverse events. http://repub.eur.nl/res/pub/25978/ 2011-04-09T00:00:00Z In the RESOLUTE All Comers trial, the Resolute zotarolimus-eluting stent was non-inferior to the Xience V everolimus-eluting stent for the primary stent-related endpoint of target lesion failure (cardiac death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation) at 1 year. However, data for long-term safety and efficacy from randomised studies of new generation drug-eluting coronary stents in patients treated in routine clinical practice are scarce. We report the prespecified 2-year clinical outcomes from the RESOLUTE All Comers trial. In 2008, patients with at least one coronary lesion 2·25-4·0 mm in diameter, with greater than 50 stenosis, were randomly assigned to a Resolute zotarolimus-eluting stent or a Xience V everolimus-eluting stent at 17 centres in Europe and Israel. Randomisation was by an interactive voice response system stratified by centre. Study investigators were not masked to treatment allocation; but those who did data management and analysis, and patients were masked. There were no restrictions as to the number of vessels or lesions treated, or the number of stents implanted. We assessed prespecified safety and efficacy outcomes at 2 years with specific focus on patient-related composite (all death, all myocardial infarction, all revascularisation) and stent-related composite outcomes. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00617084. 1140 patients were assigned to the zotarolimus-eluting stent and 1152 to the everolimus-eluting stent; 1121 and 1128 patients, respectively, completed 2-year follow-up. The patient-related outcome (231 [20·6] zotarolimus vs 231 [20·5] everolimus; difference 0·1, 95 CI -3·2 to 3·5; p=0·958) and stent-related outcome (126 [11·2] vs 121 [10·7]; difference 0·5, -2·1 to 3·1; p=0·736) did not differ between groups, although rates of the stent-related outcome were substantially lower than were those for the patient-related outcome. Three patients in each group (0·3) had very late (after 1 year) stent thrombosis. Similar safety and efficacy outcomes were sustained between two new generation drug-eluting stents at 2-year follow-up. The greater number of patient-related than stent-related events in patients with complex clinical and lesion characteristics emphasises that during long-term follow-up, the optimisation of secondary prevention is at least as important as the selection of which new generation drug-eluting stent to implant in a specific lesion. Medtronic (USA). http://repub.eur.nl/res/pub/28035/ 2010-03-16T00:00:00Z Objectives: The purpose of this study is to compare the 5-year clinical outcomes, safety, and efficacy of sirolimus-eluting stents (SES) in the ARTS II (Arterial Revascularization Therapies Study II) with the outcomes of coronary artery bypass graft (CABG) and bare-metal stenting (BMS) from the ARTS I. Background: The long-term outcomes after SES implantation in patients with multivessel disease remains to be established. Methods: The ARTS I was a randomized trial of 1,205 patients with multivessel disease comparing CABG and BMS. The ARTS II study was a nonrandomized trial with the Cypher sirolimus-eluting stent (Cordis, a Johnson & Johnson Company, Warren, New Jersey), applying the same inclusion and exclusion criteria, end points, and protocol definitions. The ARTS II trial enrolled 607 patients, with an attempt to enroll at least one-third of patients with 3-vessel disease. Results: At 5-year, the death/stroke/myocardial infarction event-free survival rate was 87.1% in ARTS II SES, versus 86.0% (p = 0.1) and 81.9% (p = 0.007) in ARTS I CABG and BMS cohorts, respectively. The 5-year major adverse cardiac and cerebrovascular event (MACCE) rate in ARTS II (27.5%) was significantly higher than ARTS I CABG (21.1%, p = 0.02), and lower than in ARTS I BMS (41.5%, p < 0.001). The cumulative incidence of definite stent thrombosis was 3.8%. Thirty-two percent (56 of 176) of major adverse cardiac events (MACE) at 5 years were related to possible, probable, or definite stent thrombosis. Conclusions: At 5 years, SES had a safety record comparable to CABG and superior to BMS, and a MACCE rate that was higher than in patients treated with CABG, and lower than in those treated with BMS. Approximately one-third of the events seen with SES could be prevented through the elimination of early, late, and very late stent thrombosis. http://repub.eur.nl/res/pub/27932/ 2010-03-01T00:00:00Z Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18° C or 37° C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 ± 1% at baseline vs. -3 ± 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 ± 5%) and stroke volume (12 ± 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 ± 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 ± 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine ± inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37° C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis. Copyright http://repub.eur.nl/res/pub/24078/ 2009-08-01T00:00:00Z Objectives: In a single center experience, we retrospectively evaluated the short-term safety and efficacy of the TandemHeart® percutaneous transseptal left ventricular assist (PTVA®) system to deliver extracorporeal circulatory support during catheter based treatment of the unprotected left main coronary artery (ULMCA). Background: Percutaneous Coronary Intervention (PCI) of the ULMCA usually has been restricted to patients who are hemodynamically unstable or ineligible for coronary artery bypass grafting (CABG). High-risk patients for CABG should be considered at increased risk for PCI as well. In these patients the TandemHeart PTVA System (p-LVAD) may provide a valuable safeguard to reduce procedural risks. Methods and Results: Between July 2002 and May 2008 the TandemHeart was used in 9 very high risk patients (Logistic Euro score: 13.64 (7.46-29.67); Syntax score:43 (41-50); Mayo Clinic Risk score (MCRS) 7 (6-8); age: median 65 (range 55-71) undergoing elective PCI for the novo lesions on the ULMCA. All patients were declined for CABG by a heart team. A "true" percutaneous insertion technique was used in all patients, technical success rate was 100%. The median (range) time for implementation of circulatory support was 27 min (24-30). A median (range) pump flow up to 4.36 (3.40-5.54) L/min was achieved with significant reduction of left ventricular filling pressures, pulmonary capillary wedge pressure and a small increase of systemic arterial pressures. Median (range) duration of support was 93 min (50.4-102). Successful weaning was achieved in all patients. There was no in hospital death, survival at 6 months was (89%), whereas vascular access site complications were seen in 4 patients (44.4%). Conclusions: In very high risk PCI, assisted circulation using the TandemHeart-PTVA provides effective, total left ventricular support and may contribute to a reduced procedural risk and improved survival. The rate of device related cardiac and vascular complications was acceptable. http://repub.eur.nl/res/pub/29780/ 2008-12-09T00:00:00Z Objectives: The purpose of this study was to assess the 3-year outcome of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES) in patients who had multivessel coronary artery disease with and without diabetes mellitus. Background: The optimal method of revascularization in diabetic patients remains in dispute. Methods: The ARTS-II (Arterial Revascularization Therapies Study-Part II) trial is a single-arm study (n = 607) that included 159 diabetic patients treated with SES whose 3-year clinical outcome was compared with that of the historical diabetic and nondiabetic arms of the randomized ARTS-I trial (n = 1,205, including 96 diabetic patients in the CABG arm and 112 in the PCI arm). Results: At 3 years, among nondiabetic patients, the incidence of the primary composite of death, CVA, myocardial infarction (MI), and repeat revascularization (major adverse cardiac and cerebrovascular events [MACCE]), was significantly lower in ARTS-II than in ARTS-I PCI (adjusted odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.26 to 0.64) and similar to ARTS-I CABG. The ARTS-II patients were at significantly lower risk for death, CVA, and MI as compared with both the ARTS-I PCI (adjusted OR: 0.55; 95% CI: 0.34 to 0.91) and ARTS-I CABG patients (adjusted OR: 0.56; 95% CI: 0.35 to 0.92). Among diabetic patients, the incidence of MACCE in ARTS-II was similar to that of both PCI and CABG in ARTS-I. Conversely, the incidence of death, CVA, and MI was significantly lower in ARTS-II than in ARTS-I PCI (adjusted OR: 0.67; 95% CI: 0.27 to 1.65) and was similar to that of ARTS-I CABG. Conclusions: At 3 years, PCI using SES for patients with multivessel coronary artery disease seems to be safer and more efficacious than PCI using bare-metal stents, irrespective of the diabetic status of the patient. Hence, PCI using SES appears to be a valuable alternative to CABG for both diabetic and nondiabetic patients. http://repub.eur.nl/res/pub/15854/ 2008-01-01T00:00:00Z AIMS: To test the hypothesis that intracoronary infusion of pre-oxygenated HBOC-201 during brief, total coronary artery occlusion would preserve left ventricular function. METHODS: Immediately following a successful PCI, the target coronary artery was occluded without ("dry occlusion")--or with--infusion of pre-oxygenated HBOC-201 distal to the stent via the guidewire shaft of an over-the-wire balloon for up to three minutes at an infusion rate of 48 ml/min. A cross-over design was applied. Early signs of myocardial ischaemia were evaluated by left ventricular pressure-volume loops and intracoronary ECG. A 12-lead Holter ECG was activated before the PCI and deactivated four hours after the study period. Primary endpoints were change in left ventricular relaxation indices and in the sum of ST segment deviations. RESULTS: None of the measured parameters differed significantly from their respective baseline values during HBOC-201 infusion. By contrast, ejection fraction (EF), cardiac output (CO) and minimal rate of LV pressure change (dP/dTMIN) decreased significantly and the end diastolic pressure (EDP) and time constant of relaxation increased significantly during dry occlusions (P<0.05). The end diastolic pressure-volume relationship (EDPVR) at the fixed pressure level of 30 mmHg (V30), an index of myocardial compliance, reflected greater myocardial stiffness during dry occlusions compared to occlusions with HBOC-201 infusion. CONCLUSIONS: Intracoronary infusion of oxygenated HBOC-201 is capable of preserving left ventricular function, likely through maintenance of myocardial oxygenation. It is hypothesised, that in an acute setting, HBOC-201 could serve as an oxygen bridge to reperfusion by PCI extending the "golden" time period during which permanent myocardial damage is unlikely. http://repub.eur.nl/res/pub/35429/ 2007-05-01T00:00:00Z BACKGROUND - Although most clinical trials of coronary stents have measured nominally identical safety and effectiveness end points, differences in definitions and timing of assessment have created confusion in interpretation. METHODS AND RESULTS - The Academic Research Consortium is an informal collaboration between academic research organizations in the United States and Europe. Two meetings, in Washington, DC, in January 2006 and in Dublin, Ireland, in June 2006, sponsored by the Academic Research Consortium and including representatives of the US Food and Drug Administration and all device manufacturers who were working with the Food and Drug Administration on drug-eluting stent clinical trial programs, were focused on consensus end point definitions for drug-eluting stent evaluations. The effort was pursued with the objective to establish consistency among end point definitions and provide consensus recommendations. On the basis of considerations from historical legacy to key pathophysiological mechanisms and relevance to clinical interpretability, criteria for assessment of death, myocardial infarction, repeat revascularization, and stent thrombosis were developed. The broadly based consensus end point definitions in this document may be usefully applied or recognized for regulatory and clinical trial purposes. CONCLUSION - Although consensus criteria will inevitably include certain arbitrary features, consensus criteria for clinical end points provide consistency across studies that can facilitate the evaluation of safety and effectiveness of these devices. http://repub.eur.nl/res/pub/4751/ 2003-03-01T00:00:00Z Abstract BACKGROUND: In patients with poor left ventricular function and high-risk coronary lesions, prolonged ischemia during percutaneous coronary intervention (PCI) may have major hemodynamic consequences. The Tandemheart is a percutaneous left ventricular assist device intended for short-term circulatory support. METHODS AND RESULTS: The Tandem-heart incorporates 9-17 F. arterial cannulae and a unique 21 F. transseptal cannula and centrifugal bloodpump. Operating at 7500 rpm, the pump withdraws oxygenated blood from the left atrium and delivers up to 4 liters/min to the arterial circulation. As of May 2001, the Tandem-heart was electively employed in three male patients (ages 52, 54 and 56) scheduled for high-risk PCI. The mean time to initial circulatory support was less than 30 minutes. Systemic hemodynamics significantly improved prior to PCI in two patients. Pump flow after one hour ranged from 2.43 to 3.8 liters/min (mean 3.17 liters/min) and duration of support from 23 to 49 hours (mean 33 hours). Procedural success was 100%, with no significant hemolysis or bleeding. Successful weaning was completed in all patients, who have remained free of major cardiac events up to seven months post-PCI. CONCLUSIONS: In this first clinical experience of elective use of Tandem-heart for circulatory support during high-risk PCI, the device was easily inserted and preserved hemodynamic stability, regardless of the intrinsic cardiac function, creating optimism for more widespread use for this and other indications. http://repub.eur.nl/res/pub/4739/ 2003-02-01T00:00:00Z