Percutaneous mitral valve interventions in the real world: Early and 1-year results from the ACCESS-EU, A prospective, multicenter, nonrandomized post-approval study of the Mitraclip therapy in Europe
Maisano F.,San Raffaele Scientific Institute |
Franzen O.,Rigshospitalet |
Baldus S.,University of Hamburg |
Hausleiter J.,Deutsches Herzzentrum Munich |
And 8 more authors.
Journal of the American College of Cardiology | Year: 2013
Objectives The purpose of this article is to report early and mid-term outcomes of the ACCESS-EU study (ACCESS-Europe A Two-Phase Observational Study of the MitraClip System in Europe), a European prospective, multicenter, nonrandomized post-approval study of MitraClip therapy (Abbott Vascular, Inc., Santa Clara, California). Background MitraClip has been increasingly performed in Europe after approval; the ACCESS-EU registry provides a snapshot of the real-world clinical demographic data and outcomes. Methods A total of 567 patients with significant mitral valve regurgitation (MR) underwent MitraClip therapy at 14 European sites. Mean logistic European System for Cardiac Operative Risk Evaluation at baseline was 23.0 ± 18.3; 84.9% patients were in New York Heart Association functional class III or IV, and 52.7% of patients had an ejection fraction ≤40%. Results The MitraClip implant rate was 99.6%. A total of 19 patients (3.4%) died within 30 days after the MitraClip procedure. The Kaplan-Meier survival at 1 year was 81.8%. Intensive care unit and hospital length of stay was 2.5 ± 6.5 days and 7.7 ± 8.2 days, respectively. Single leaflet device attachment was reported in 27 patients (4.8%). There were no MitraClip device embolizations. Thirty-six subjects (6.3%) required mitral valve surgery within 12 months after the MitraClip implant procedure. There was improvement in the severity of MR at 12 months, compared with baseline (p < 0.0001), with 78.9% of patients free from MR, severity of >2+ at 12 months. At 12 months, 71.4% of patients had New York Heart Association functional class II or class I. Six-min-walk-test improved 59.5 ± 112.4 m, and Minnesota-living-with-heart-failure score improved 13.5 ± 20.5 points. Conclusions In the real-world, post-approval experience in Europe, patients undergoing the MitraClip therapy are high-risk, elderly patients, mainly affected by functional MR. In this patient population, the MitraClip procedure is effective with low rates of hospital mortality and adverse events. © 2013 by the American College of Cardiology Foundation Published by Elsevier Inc.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.4.1-12 | Award Amount: 16.04M | Year: 2009
Recent research suggests that the hypoxic micro-environment of tumours is one of the major drivers of metastatic spread of cancer. Furthermore, hypoxic tumour micro-environments may result in treatment resistance of cancer cells, therefore causing a double effect of reducing the potential of a successful treatment of the cancer patient. This project seeks to clarify the roles and functions of the hypoxic tumour micro-environment in relation to the survival of solid tumours likely to metastasise. We will gain new knowledge about molecular mechanisms behind hypoxia-driven metastasis, like the epithelial-mesenchymal transition (EMT) by several routes: (a): mechanisms related to cell growth- and cell proliferation (UPR, mTOR, CA9, HIF, Notch, and VHL), (b): angiogenesis and lymphangiogenesis, (c): metabolism and pH-regulation (d): the handling of reactive oxygen species (ROS). We will generate animal models for the study of the role of hypoxia in metastases and develop a bio-bank of tumour and blood samples for molecular diagnostic studies. We will identify and develop advanced imaging techniques and biomarkers and identify micro-metastases in bone marrow of patients to assist in the selection of appropriate stratification of the actual primary tumours and metastases micro-environmental conditions. We will also create a machine-learning based classifier of tumour hypoxia. The consortium has the necessary expertise to perform proof-of-principle clinical testing of new treatment strategies. We will thus perform clinical tests of new drugs developed to attack the regulatory mechanisms selected from the pre-clinical work and possible synergisms of combined treatments. We will also test new radiotherapy strategies for treatment of primary as well as metastatic tumours. Cancer types chosen for clinical studies are non-small-cell lung carcinoma, squamous cell carcinoma of the larynx, prostate cancer, primary breast cancer and rectal cancer.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.2-1 | Award Amount: 7.98M | Year: 2010
According to the European Society of Cardiology there has been an increase in the life expectancy at the age of 65 of the European population from 15.0 to 17.0 years in the years since 1980. In the elderly, up to 50% of deaths are caused by cardiovascular diseases, the majority accounted for by coronary artery disease. The most effective treatment for obstructive coronary disease is percutaneous intervention with coronary stenting and fuelled by the increasing disease burden there has been a rapid increase in the number of percutaneous coronary intervention procedures in Europe from 184,000 in 1992 to 885,000 in 2004. If the rate of progression remains constant, the projected number of coronary intervention procedures per annum will be about 1.5 million by 2010, with a stenting rate of close to 100%. The principal safety issue with current coronary stenting procedures is late stent thrombosis which, with a case mortality rate approaching 50%, makes this problem a very significant European health issue. The PRESTIGE project will result in significant improvement in prediction and prevention of late stent thrombosis by providing novel strategies that causally impede incident events without increasing the overall risk of bleeding. These goals will be achieved by a multidisciplinary consortium formed by world-leading EU-based specialists covering the requisite scientific skills and experience. Since the first drug-eluting stent was introduced in 2002 the growth of this sector has been explosive. Forecasts predicted the potential for this market segment to exceed 4.6 billion by 2009. The economic impact of this very ambitious project will be to provide the European health industries with novel stent products and new imaging technologies to identify patients at-risk, as well as amended European treatment guidelines. The social impact will be, amongst others, a tremendous cost reduction for the public and private health insurance systems all over Europe.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-1 | Award Amount: 7.88M | Year: 2013
Atherosclerosis and its most disabling sequelae, coronary artery disease (CAD) and stroke, are leading causes of death in Europe. Until now, preventive and therapeutic interventions for these diseases aim at ameliorating the effects of established cardiovascular risk factors. More recently, results of genome-wide association (GWA) studies added to our perception of mechanisms leading to atherosclerosis. At present, over 40 CAD and several genomic risk loci have been identified, the majority through efforts led by the applicants. Some genes at these loci work through known risk factors such as lipids and, in fact, are already established or evolving treatment targets. However, this is not true for the majority of risk variants, which implies that key pathways leading to atherosclerosis are yet to be exploited for therapeutic intervention. This EU network (CVgenes@target), which brings together an equal number of SME- and academic partners, will utilize genomic variants affecting atherosclerosis risk for identification of both underlying genes and affected pathways in order to identify, characterize, and validate novel therapeutically relevant targets for prevention and treatment of CAD and stroke. In programme 1 we will investigate molecular mechanisms at the genomic loci in order to further unravel causal genes, in programme 2 we will explore in vitro and in vivo whether the pathways disturbed by causal genes are suitable for therapeutic intervention, and in programme 3 we will establish assays and initiate high throughput screens to tackle therapeutically attractive targets. Our resources including large OMICs and state-of-the-art bioinformatics platforms as well as multiple, already established in vitro and in vivo models support the feasibility of the approach. In fact, two genomic risk loci (ADAMTS7 (CAD); HDAC9 (stroke and CAD)), both identified in GWA studies under direction of the applicants, already revealed attractive targets for therapeutic intervention.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.4.2-2 | Award Amount: 3.93M | Year: 2011
EpoCan aims to develop and implement a comprehensive interdisciplinary strategy to assess the long-term risks of erythropoietin (EPO) and its derivatives (epoetins) on tumour growth progression and thromboembolic events in cancer patients, cardiovascular events, and the development of cancer in chronic kidney disease. Approximately 400,000 patients across Europe receive epoetins treatment each year. Recent meta-analysis data have raised concerns over increased mortality in some patient groups. Hence the urgent need to evaluate the risk-benefit ratio of epoetin treatment and its potential long-term effects. EpoCan brings together a multidisciplinary consortium of 12 world leading academic, industrial and medical partners, with long-standing, complementary expertise in haemostasis, oncology and EPO biology. EpoCan aims to (1) Identify, detect and measure possible long-term hazards of epoetin treatment; (2) Develop novel prognostic tools and new complementary therapeutic reagents: (3) Evaluate the risk-benefit ratio to pave the way for new safety and efficacy criteria. EpoCan will: (a) Utilize a wide array of cellular models to thoroughly analyze EPO/EPO receptor(EPO-R)interaction and signalling, to define the relationship between EPO-R expression in tumour samples and the clinical outcome in cancer patients; (b) Establish and test new, personalized, predictive tools (EPO-R peptide antagonists, novel specific anti-EPO-R monoclonal antibodies, thromboembolic tests); (c) Create new murine models as hosts for tumour implantation subjected to EPO and derivatives established above; (d) Screen and analyze clinical databases; (e) Define models to predict hazardous versus safe/beneficial roles of epoetins in the treatment of cancer and kidney failure associated anaemia. Data obtained will be integrated into coherent models using novel computational algorithms developed for EpoCan. Results are expected to have broad ramifications, with special relevance for clinical oncology.
Meredith Am I.T.,Monash University |
Walters D.L.,University of Queensland |
Dumonteil N.,Toulouse University Hospital Center |
Worthley S.G.,Royal Adelaide Hospital |
And 12 more authors.
Journal of the American College of Cardiology | Year: 2014
Results Mean age was 84.4 years, 57% of the patients were female, and 76% were New York Heart Association functional class III/IV. Mean aortic valve area was 0.7 ± 0.2 cm2. The valve was successfully implanted in all patients, with no cases of valve embolization, ectopic valve deployment, or additional valve implantation. All repositioning (n = 26) and retrieval (n = 6) attempts were successful; 34 patients (28.6%) received a permanent pacemaker. The primary device performance endpoint was met, because the mean gradient improved from 46.4 ± 15.0 mm Hg to 11.5 ± 5.2 mm Hg. At 30 days, the mortality rate was 4.2%, and the rate of disabling stroke was 1.7%; 1 (1.0%) patient had moderate PVR, whereas none had severe PVR.Conclusions REPRISE II demonstrates the safety and effectiveness of the Lotus valve in patients with severe aortic stenosis who are at high surgical risk. The valve could be positioned successfully with minimal PVR. (REPRISE II: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Evaluation of Safety and Performance; NCT01627691).Background Transcatheter aortic valve replacement provides results comparable to those of surgery in patients at high surgical risk, but complications can impact long-term outcomes. The Lotus valve, designed to improve upon earlier devices, is fully repositionable and retrievable, with a unique seal to minimize paravalvular regurgitation (PVR).Objectives The prospective, single-arm, multicenter REPRISE II study (REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System: Evaluation of Safety and Performance) evaluated the transcatheter valve system for treatment of severe symptomatic calcific aortic valve stenosis.Methods Patients (n = 120; aortic annulus 19 to 27 mm) considered by a multidisciplinary heart team to be at high surgical risk received the valve transfemorally. The primary device performance endpoint, 30-day mean pressure gradient, was assessed by an independent echocardiographic core laboratory and compared with a pre-specified performance goal. The primary safety endpoint was 30-day mortality. Secondary endpoints included safety/effectiveness metrics per Valve Academic Research Consortium criteria. © 2014 American College of Cardiology Foundation.
Walther T.,Kerckhoff Herzzentrum |
Hamm C.W.,Abteilung Radiologie |
Schuler G.,Abteilung Radiologie |
Berkowitsch A.,Abteilung Radiologie |
And 10 more authors.
Journal of the American College of Cardiology | Year: 2015
Background Transcatheter aortic valve replacement (TAVR) has evolved into a routine procedure with good outcomes in high-risk patients. Objectives TAVR complication rates were evaluated based on prospective data from the German Aortic Valve Registry (GARY). Methods From 2011 to 2013, a total of 15,964 TAVR procedures were registered. We evaluated the total cohort for severe vital complications (SVCs), including the following: death on the day of intervention, conversion to sternotomy, low cardiac output that required mechanical support, aortic dissection, and annular rupture; technical complications of the procedures (TCOs), such as repositioning or retrieval of the valve prosthesis and embolization of the prosthesis; and other complications. Results Mean patient age was 81 ± 6 years, 54% of the patients were women, the median logistic Euroscore I was 18.3, the German aortic valve score was 5.6, and the Society of Thoracic Surgeons score was 5.0. Overall in-hospital mortality was 5.2%, whereas SVCs occurred in 5.0% of the population. Independent predictors for SVCs were female sex, pre-operative New York Heart Association functional class IV, ejection fraction <30%, pre-operative intravenous inotropes, arterial vascular disease, and higher degree of calcifications. TCOs occurred in 4.7% of patients and decreased significantly from 2011 to 2013. An emergency sternotomy was performed in 1.3% of the patients; however, multivariate analysis did not identify any predictors for conversion to sternotomy. Conclusions The all-comers GARY registry revealed good outcomes after TAVR and a regression in complications. Survival of approximately 60% of patients who experienced SVCs or who required sternotomy underlines the need for heart team-led indication, intervention, and follow-up care of TAVR patients. © 2015 American College of Cardiology Foundation.
Sibbing D.,Deutsches Herzzentrum Munich |
Koch W.,Deutsches Herzzentrum Munich |
Gebhard D.,Deutsches Herzzentrum Munich |
Schuster T.,TU Munich |
And 6 more authors.
Circulation | Year: 2010
Background-:The cytochrome P450 (CYP) 2C19 isoenzyme plays an important role in clopidogrel metabolization. A recently explored CYP2C19*17 allelic variant has been linked to increased transcriptional activity, resulting in extensive metabolization of CYP2C19 substrates, which may lead to an enhanced platelet response to clopidogrel treatment. The aim of this study was to assess the impact of CYP2C19*17 on ADP-induced platelet aggregation, the risk of bleeding, and stent thrombosis in clopidogrel-treated patients undergoing percutaneous coronary intervention. Methods and Results-: The study population included 1524 patients undergoing percutaneous coronary intervention after pretreatment with 600 mg clopidogrel. Genotypes were determined with a TaqMan assay. ADP-induced platelet aggregation was assessed on a Multiplate analyzer. The primary clinical safety end point was the 30-day incidence of bleeding defined according to Thrombolysis in Myocardial Infarction criteria, and the primary clinical efficacy end point was the 30-day incidence of stent thrombosis. For both heterozygous (*wt/*17; n=546) and homozygous (*17/*17; n=76) allele carriers, significantly lower ADP-induced platelet aggregation values were found compared with wild-type homozygotes (*wt/*wt; n=902; P=0.039 and P=0.008, respectively). CYP2C19*17 allele carriage was significantly associated with an increased risk of bleeding; the highest risk was observed for CYP2C19*17 homozygous patients (P=0.01, χ2 test for trend). Multivariate analysis confirmed the independent association of CYP2C19*17 allele carriage with platelet aggregation values (P<0.001) and the occurrence of bleeding (P=0.006). No significant influence of CYP2C19*17 on the occurrence of stent thrombosis was found (P=0.79). Conclusions-: CYP2C19*17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding. © 2010 American Heart Association, Inc.
Sonne C.,Deutsches Herzzentrum Munich
GMS Zeitschrift für medizinische Ausbildung | Year: 2013
Regular student evaluations at the Technical University Munich indicate the necessity for improvement of the clinical examination course. The aim of this study was to examine if targeted measures to restructure and improve a clinical examination course session lead to a higher level of student satisfaction as well as better self-assessment of the acquired techniques of clinical examination. At three medical departments of the Technical University Munich during the 2010 summer semester, the quantitative results of 49 student evaluations (ratings 1-6, German scholastic grading system) of the clinical examination course were compared for a course before and a course after structured measures for improvement. These measures included structured teaching instructions, handouts and additional material from the Internet. 47 evaluations were completed before and 34 evaluations after the measures for improvement. The measures named above led to a significant improvement of the evaluative ratings in the following areas: short introduction to the topic of each clinical examination course (from 2.4±1.2 to1.7±1.0; p=0.0020) and to basic measures of hygiene (from 3.8±1.9 to 2.5±1.8; p=0.004), structured demonstration of each clinical examination step (from 2.9±1.5 to 1.8±1.0; p=0.001), sufficient practice of each clinical examination step (from 3.1±1.8 to 2.2±1.4; p=0.030) structured feedback on each clinical examination step (from 3.0±1.4 to 2.3±1.0; p=0.0070), use of handouts (from 5.2±1.4 to 1.8±1.4; p<0.001), advice on additional learning material (from 5.0±1.4 to 3.4±2.0; p<0.001), general learning experience (from 2.4±0.9 to 1.9±0.8; p=0.017), and self-assessment of the acquired techniques of clinical examination (from 3.5±1.3 to 2.5±1.1; p<0.01). Structured changes led to significant improvement in the evaluative ratings of a clinical examination course session concerning preparation of the tutors, structure of the course, and confidence in performing physical examinations.
Agency: European Commission | Branch: FP7 | Program: MC-IOF | Phase: PEOPLE-2007-4-1.IOF | Award Amount: 150.00K | Year: 2008
Atrial fibrillation (AF) is the most important arrhythmia in contemporary cardiology, and despite much progress, remain therapeutic challenges. Invasive electrical studies of the heart are often used in the diagnosis and therapy of arrhythmia. Many forms of arrhythmia can be cured by selective destruction of critical electrical pathways with catheter ablation. A major limitation in studying arrhythmia, however, is the inability to visualize soft tissues, and ablated areas of myocardium during catheter ablation procedures. After performing extensive preliminary work on MRI guided electrophysiology in animal models, the aim of this study is to examine the safety and feasibility of real-time MRI guidance for clinical electrophysiology studies and cardiac ablation procedures using custom made catheters, radiofrequency filters, and a shielded signal acquisition system. The objective is to test the hypothesis that MRI guidance will improve the safety and efficacy of clinical ablation procedures. Specific Aim 1) To study the determinants of successful ablation in patients undergoing standard fluoroscopy guided ablations. Patients with AF will undergo electrophysiology study and ablation using standard fluoroscopy guidance. Completeness of ablation lines will be assessed by MRI, and correlated with acute and chronic recurrence of AF. The effect of ablation lesions on atrial re-modeling will be assessed at 6 months. This aim will provide insight into determinants of success and complications post ablation. Specific Aim 2) To study real-time MRI guidance of electrophysiologic studies and catheter ablation in patients with AF. This portion of the study will be conducted in participants with symptomatic AF. The primary endpoint will be lack of AF documented by Holter monitoring 6 months post ablation. The secondary endpoints will be comparison of inducible arrhythmia at the end of the procedure, procedure time, and complications in each study arm.