ESC 2017

www.healthcare-in-europe.com CARDIOLOGY 7 1 0 2 N E W S A N D T E C H N O L O G Y U P D A T E S F O R C A R D I A C C A R E B A R C E L O N A S PA I N 2 6 A U G – 3 0 A U G 2 0 1 7 The ESC Congress 2017 With 4,500 accepted abstracts, 600 sessions and 30,000 expected attendees, ESC Congress 2017 is undoubtedly the world’s largest cardiovascular event. European Hospital correspondent Mélisande Rouger asked Dr Stephan Achenbach, Congress Program Committee Chairperson, for an overview of issues and events unfolding in Barcelona from August 26-30 the Congress, explained During Stephan Achenbach, the ESC issues guidelines on how to manage patients with cardiovascular disease. ‘In 2017 the guidelines focus on how to treat ST myocardial infarc- tion, valve disease, peripheral artery disease and dual antiplatelet thera- py, which is very important in coro- nary intervention. ‘The Hot Lines presentations are late clinical trials; we have very promising publications, especially in the field of prevention – both primary and secondary. ‘We also commemorate the anniversary of percutaneous coronary intervention. Forty years ago, Andreas Grüntzig performed the first balloon angio- plasty of coronary artery stenosis. ‘This year, we’ll learn a lot that’s new about the connection between heart disease and inflammation, considering the huge amount of abstracts received on the topic. ‘Many of our sessions are joint sessions with partners, for instance sister associations such as the American College of Cardiology, the American Heart Association, the Japanese circulatory society, and the Indian and Chinese cardiac societies. ‘We will also have sessions with subspecialty societies, including European Society of Hypertension and the European Society of CardioVascular Surgery, but also with genetics cardiology, pediatric cardiology, etc. ‘Last, but not least, we will have very interesting sessions with the New England Journal of Medicine, JAG and the Lancet. ‘This is a new addition because digital health is really becoming important in cardiology. We’re coop- erating with Mobile World Capital Barcelona, a tremendously large congress on mobile technologies. We will have interactive lecturers sharing their experience of mobile technology in cardiology.’ ‘Our challenges arise from the opportunities. Today we have many more options to treat and pre- vent cardiovascular disease, but they are expensive and we need to find resources and to direct those resources to patients who really need it. I think that’s the challenge. As our opportunities become more complex we have to ensure that they remain economically viable. European research focuses on many aspects, but mainly on the develop- ment of percutaneous valve disease treatment, really advancing percuta- neous catheter-based treatment of aortic stenosis and percutaneous treatment of other valve disease. Europe really has a leading role there. ‘Personally I am also involved with imaging, in the context of these new valve treatments, to pre- pare and guide the procedure and to decide which strategy to use in which patient. ‘Imaging is tremendously impor- tant to fix heart disease. There’s a growing interest among cardiolo- gists to use imaging and high-end imaging using computed tomogra- phy or magnetic resonance.’’ ‘Europe has this very wide spectrum of high and low- income countries, so the field is very heterogeneous. The ESC has to cater to all these countries. ‘In terms of trends, Europeans are traditionally early adopters of new technologies, treatments and diag- nostic methods. They need to make these strategies economically viable.’ ‘Issues of data sharing and pri- vacy, and selecting meaningful data are very important in cardiology as in any other field. ‘The ESC has a working group on e-cardiology and the congress will feature sessions on e-cardiology and big data. Data is both a major opportunity and a problem.’ ‘The most important and promis- ing indication for wearable devices use is screening for atrial fibrillation because it predisposes to stroke. Some research at the ESC will focus on that aspect. ‘If you can find fibrillation early, you can prevent stroke, so this is a major opportunity for wearable technology, and it has not been looked at extensively yet. In the Stephan Achenbach MD graduated from the University of Erlangen Medical School in Germany in 1993. Today he is still there, as Professor of Medicine and chairman of its cardiology department. He has not only held posts in Erlangen, but also in Boston, Maryland, USA, and Giessen, Germany. With main clinical interests in interventional cardiology, general cardiology as well as cardiac imaging and intensive care medicine, Achenbach has authored around 550 publications listed in Medline. Between 2014-2016 he served as Vice President of the European Society of Cardiology (ESC) and is currently a Board Member and Chairperson of the ESC Congress Program Committee. future there will be other indica- tions, and there will be indications for cardiovascular risk factors such as diabetes and hypertension. ‘There’s also a new generation of devices that are implanted in patients to monitor physiologi- cal parameters. CardioMEMS, for instance, is implanted in one of the lungs of a patient to measure blood pressure inside the organ. It has been shown that patients with heart failure benefit from having such devices implanted.’ ‘We don’t know how to control the monster we created’ Will software steal the heart of cardiology? Celebrating 40 years of PCI, car- diologists fret over their future with big data, machine learning and robots, John Brosky reports Software may replace cardiologists one day, but never the hands-on work of interventional cardiologists and their armatorium of hardware. That was the curious consensus at the start of the 2017 EuroPCR congress, which saw the arrival of a robot performing catheter-based procedures and advances in com- puter-assisted diagnostic tools to aid guidewire operators with clinical decisions, such as whether to stent or not to stent. This confident view among panel- lists at the conference came during a session dedicated to teasing out the ‘Next Big Thing in Cardio-Vascular Medicine’ at the largest European gathering of interventional cardiolo- gists. As with this year’s congress of the European Society of Cardiology (ESC), the EuroPCR meeting cel- ebrated the 40th anniversary of the first angioplasty procedure, which opened a new specialisation for interventional cardiology. Many of the leading members of ESC are contemporaries of the pioneer for percutaneous coronary interventions (PCI), the German radiologist Andreas Grüntzig who re-opened a clogged artery using a hard wire catheter in 1977 at the University Hospital of Zurich. Today there are almost 8,000 mem- bers of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), making this the second largest of the asso- ciations within the legal structure of the ESC, surpassed only by the Heart Failure Association. By 2015 the worldwide market for PCI had grown to $6.3 billion according to the Dublin-based firm Research and Markets. Grüntzig’s primitive tool opened what EuroPCR keynote speaker Stephen Oesterle called the vascular highway that enables interventional cardiologists, ‘to go anywhere you need to go in the body.’ The field today covers 30 proce- dures that can be performed over- the-wire to place stents or treat vessels with drug-eluting balloons. And this does not take into account the growing practice of structural valve repair that is also performed over-the-wire. www.healthcare-in-europe.com k c o t s r e t t u h S / g n i r p s t h g i L : e c r u o S ‘Heart failure and mitral repair are two areas where developers are currently working to create catheter- based treatments,’ he said. Yet, we are still treating end-stage disease, he told colleagues, suggest- ing new catheter-based procedures could be developed for preventive strategies, such as implanting sen- sors to monitor blood pressure or glucose levels. A practicing cardiologist for 25 years, Oesterle worked for 15 years Continued on page 2

2 CA R D I O LO G Y The simple, efficacious technique that revolutionised cardiology Coronary angioplasty is 40 years old Report: Mark Nicholls Coronary angioplasty is arguably the most revolutionary breakthrough in the history of cardiology. While the technique is today performed on millions of patients worldwide, its origins can be traced back to the work of Dr Andreas Grüntzig in Zurich, Switzerland, in the late 1970s. Tragically, Grüntzig never lived to see the impact of his research, hav- ing died in a plane crash in 1985. Yet, across the world, his work has an enduring legacy and changed the face of cardiology forever. Later this summer – on 16 September - the world of medicine will be marking the 40th anniversary of the first coronary angioplasty. Before Grüntzig embraced the concept, others had experiment- ed in the field. The technique of angiography was first developed in 1927 by the Portuguese physi- cian Egas Moniz at the University of Lisbon for cerebral angiography while, in the 1960s, American inter- ventional radiologist Charles Dotter pioneered angioplasty and the cath- eter-delivered stent, which were first used to dilate peripheral arteries by inserting sequential catheters with increasing diameters through the narrowing artery. In 1958, Dr Mason Sones per- formed the first selective coronary angiogram and a few years later, Melvin Judkins introduced catheters shaped to reach the coronary arter- ies to perform selective coronary angiography. It was this work that Grüntzig built on to perform the first success- ful percutaneous transluminal coro- nary angioplasty (PTCA) – or percu- taneous coronary intervention (PCI) – on a human on 16 September 1977 at University Hospital, Zurich. Born in 1939 in Dresden, Germany, Grüntzig studied medicine at Heidelberg University, graduating in 1964. He rotated through a series of internships in Mannheim, Hanover, Bad Harzburg, and Ludwigshafen, before moving to the department of Angiology at the University Hospital of Zurich in 1969. His initial procedure used an k c o t s r e t t u h S / s d r a w y h : e c r u o S expandable balloon based on bal- loons for use in peripheral arteries, created on a kitchen table in his apartment, helped by his assistant Maria Schlumpf. This was used on 38-year-old severe angina patient Adolph Bachman – the same age as Grüntzig. He successfully dilated a stenosed short non-branching sec- tion of the Left Anterior Descending (LAD) artery and presented the Stent angioplasty procedure with placing a balloon results of the procedure at the American Heart Association meet- ing two months later to widespread acknowledgement. Grüntzig per- formed coronary angioplasties on further patients in Zurich and taught the technique to other cardiologists, as the field evolved. Contribution through example Professor Tony Gershlick, consultant cardiologist at Leicester’s Hospitals and Honorary Professor of Interventional Cardiology at the University of Leicester, reflects on Andreas Grüntzig’s legacy… ‘Whilst not part of the original cohort who visited Grüntzig at the very beginning, my recollections of the procedure go back to an impressionable and formative age for me as a junior doctor at the National Heart Hospital in 1980, when Tony Rickards undertook what I believe to be the first UK balloon angioplasty patient. ‘There was clearly a lot of excitement and undoubtedly something going on, so I decided I’d make a rare trip to the catheter laboratory. It was not possible… there were crowds of people.’ Inspired, Professor Gershlick became closely linked to the evolution of interventional cardiology, through the ’90s – the decade of invention – and later was the first UK cardiologist to implant a drug eluting stent (DES) and first to implant a bio-absorbable stent. Awarded the inaugural British Cardiovascular Intervention Society (BCIS) Lifetime Achievement Career Award in January, recognising his ‘outstanding contribution to the speciality of coronary intervention’, he reflects on the door that Grüntzig opened. ‘All of what we do now – radial day case intervention with great outcomes, especially in STEMI and even in complex surgical cases – would not be possible without Gruntzig’s far-reaching insights. More important is the capturing of great minds and innovators by his original work. That legacy continues unabated today. ‘He was a clinical scientist and his original studies taught us careful clinical studies, meticulous honest observations and robust reporting and interpretation of outcomes. Most importantly he never oversold the procedure. ‘His contribution through example was and remains immense. Now, if by chance the first five patients had died - which was clearly a possibility considering the kit and lack of understanding regarding risk – then that would have been a completely different story. Maybe his real contribution was that in his hands, despite all, they didn’t.’ Tony Gershlick is a consultant cardiologist at Leicester’s Hospitals and Honorary Professor of Interventional Cardiology at the University of Leicester. For more than two decades he has been at the forefront of developments in interventional cardiology in the UK and was the first cardiologist in the UK to implant a drug eluting stent (DES) and a bio-absorbable stent. In January 2017 he was awarded the inaugural British Cardiovascular Intervention Society (BCIS) Lifetime Achievement Career Award in recognition of his outstanding contribution to the speciality of coronary intervention. Naturally, there were complica- tions, such as abrupt vessel closure after balloon angioplasty and reste- nosis but from the initial percuta- neous balloon angioplasty; intrac- oronary stents were deployed in the mid-1980s. Through the ’90s and beyond, various incremental improvements in balloon and stent technology arrived, along with newer devices and medicine regimens resulting in the drug eluting stent, designed to help reduce in-stent restenosis. These also reduced the risk of stent thrombosis. former Chairman Coronary angioplasty is now the mainstay of cardiac care those recalls One man who is Bernhard early procedures Meier, and Professor of Cardiology and cur- rent Senior Consultant at the Swiss Cardiovascular Centre at Bern University Hospital. He worked with Grüntzig during the early develop- ment of the technique, and also ‘found’ the first patient to undergo the procedure. Meier has been involved in cor- onary angioplasty as a specialist in interventional cardiology since the first case Grüntzig performed in Zurich 1977, having joined the team in 1976. ‘I watched him doing peripheral angioplasty and helped him accumulate the respective data. The former Chairman and Professor of Cardiology at the Swiss Cardiovascular Centre in Bern University Hospital, Bernhard Meier is currently Senior Consultant developing the centre into the most active for interventional cardiology in Switzerland. A close associate of Dr Andreas Grüntzig, Meier has been involved in coronary angioplasty as an interventional cardiology specialist since the first case in 1977. He was involved in the development of structural interventions such as closure of the patent foramen ovale (PFO) and the left atrial appendage (LAA), and in the introduction of transarterial aortic valve implantation (TAVI) in Switzerland. I also suffered with him through more than a year of the desper- ate search for a patient suitable to become the first-in-man PCI recipi- ent,’ Meier recalled. ‘Serendipity led me to find the first patient and assist Dr Grüntzig. Finding this patient when he was away and presenting the case to him upon his return was certainly one of my career high- lights. ‘I’ve been able to take care of this patient up to now. He’s still doing extremely well, 40 years after his historical intervention, without ever needing coronary artery bypass surgery.’ When, in 1980, Grüntzig left Switzerland for the USA, Meier fol- lowed and spent three years with him in Atlanta, undergoing his cardi- ology training at Emory University. Back in Switzerland, Meier fur- ther developed the technique as head of invasive cardiology at University Hospital, Geneva (1983- 92). In 1992, he became chairman of the Cardiology Department at Bern University Hospital, turning it into the most active interventional cardi- ology centre in Switzerland. Meier recalls Grüntzig (11 years his senior) as a role model: ‘He was good looking, a sociable person, and full of great ideas with the nec- essary energy to pursue them even against a headwind from sceptics and envious – and sometime mis- chievous – colleagues and superiors. ‘He also liked and lived simplic- ity as the basis of successful medi- cine. The balloon catheter to treat coronary artery stenosis is about as simple and as efficacious as it gets. Will software steal the heart of cardiology? Continued from page 1 with the medical device manu- facturer Medtronic before joining the venture fund New Enterprise Associates, where he partnered Dr Scott Gottlieb who, in May 2017, was appointed new Commissioner of the USA’s Food & Drug Administration. Confounding the audience When Oesterle shifted his talk from hardware to software he began to confound the audience. The next big thing in the cardio- vascular space, he said, is not in the room today – unless you count the smart phones in everyone’s pocket. The research and development budget at Apple is $17 billion annu- ally, and what they are working on will make the future iPhone a healthcare companion, he said. Google Life Sciences, now called Verily, has invested $4 billion over the past two years to create part- nerships with Johnson & Johnson’s surgical division and glucose moni- toring specialist Dexcom, as well as several major pharmaceutical com- panies. IBM has declared that healthcare is the future of the company, he said, and the Watson super-comput- er is not meant to play games, hav- ing already shown it can outperform radiologists. Data analytics coupled with cog- nitive computing will take over healthcare, Oesterle predicted. ‘We have come to a point where com- puting power is massive, it is fast and it is incredibly cheap. Your next-generation competitor will come from software.’ As a venture capitalist, he noted that less than 10 percent of pri- vate equity funding goes to medical technologies, that 20 percent goes to biotechnologies and ‘70 percent goes into the software that is going to disrupt our practice, just as it has disrupted other industries.’ ‘No one wants to back a new stent, distributed healthcare is where the money is going,’ he said, adding that consumer-oriented medical technol- ogies aim to pass up the clinician in order to go directly to the patient. Vice President for Medical Affairs at Medtronic Vascular, Martin Rothman spoke up to say: ‘I just can’t see these next big things.’ And he agreed the next big cardiovas- cular enterprise based on software would not be Medtronic. ‘It’s not our core skill. We do some software engineering but what we really do is micro-engineering and that is our skill.’ Then he added: ‘When we talk about what will be the next big application in data handling, we quickly come to the important ques- tion: Where is the revenue? When we sell a stent or a TAVR [transcathe- ter aortic valve replacement], we get revenue. How do you get revenue when you sell a software click? How do you make that work? We don’t understand it,’ he said. With the authority of his white- haired seniority, Eberhard Grube, the Chief of the Department of Cardiology and Angiology at the Heart Centre in Siegburg, Germany, followed up on these comments: ‘We are speaking of things that may come in 20 years. It makes me dizzy talking about five billion here and 50 billion there. ‘Perhaps,’ he suggested, ‘we are more down-to-earth.’ Then he cau- tioned colleagues, ‘We hear about an unlimited imagination in what software can do, and then we look at what happened with a hospital in the United Kingdom when it no longer had access to its data. We have created a monster we do not know how to control.’ EUROPEAN HOSPITAL Vol 26 Issue 4/17

CA R D I O LO G Y 3 Improved monitoring and raised quality of life Intelligent shirts ‘watch’ cardiac patients to follow up patients more closely and anticipate the disease progres- sion. Cardiologist David Del Val MD is currently completing his fellowship in haemodynamics and interventional cardiology at Ramón y Cajal University Hospital in Madrid, Spain. Having gained his medical degree from Madrid Autonomous University his residency in cardiology was at Ramón y Cajal Hospital. Later, at Alcalá University, he specialised in scientific investigation methodology. worsening of a given pathology. Therefore, we can anticipate and plan our actions to fight the disease, initiate early treatment, avoid hos- pitalisation and reduce healthcare costs. ‘For the moment, I’m not involved in other projects validating wearable technology, but I consider this to be a field with major projection for patients suffering chronic diseases. ‘Our cardiology department is currently working on a cutaneous patch that enables continuous medi- cation of different haemodynamic parameters, a system that can help ‘The department also leads anoth- er project in which a toothbrush enables us, daily, to measure vital signs and various biomarkers in the saliva.’ ‘Wearable technology enables us to remotely follow up different key parameters early, to detect any With hearts so strongly connected, shouldn‘t cardiac solutions be, too? Visit us at booth # F400 Perfectly attuned: our state-of-the-art cardiac solutions. From diagnosis to therapy and follow-up, all medical technologies along the clinical pathway are connected to build a smart network. Improve the outcome for the most important person in the room: the patient. Explore the heart of healthcare: siemens.com/cardiology A pioneering study has certi- fied that wearable technol- ogy produced better results in monitoring cardiac patients and improving their quality of life compared to conventional systems. European Hospital cor- respondent Mélisande Rouger spoke with Spanish cardiologist David Del Val MD, who led the study, before he presented his results at the European Congress of Cardiology held in Barcelona. David Del Val: ‘Medicine, and more particularly cardiology, is experienc- ing a real technological revolution. Many devices have been developed to improve diagnostic therapy effi- ciency and patients’ quality of life. However, very few studies have actually measured the pertinence of these devices in real life. This study is a pioneering work because it compares efficiency in a new wearable device and conventional systems in clinical practice. ‘The study was designed to com- pare monitoring efficiency in terms of perceived life quality benefits in patients using a wearable system developed by a company called Nuubo and conventional electrocar- diographic monitoring systems. ‘150 patients alternatively used intelligent shirts and a conventional ambulatory monitoring system to monitor their cardiac rhythm during 24 hours. ‘Results showed that the effective monitoring time was higher with the new system using wearable technol- ogy compared to the conventional system. Questionnaires answered by patients also revealed that quality of life indices were higher in those who used a wearable device. ‘Our cardiology department start- ed work with Nuubo’s technology five years ago. We have worked with the same company on other projects to evaluate prolonged electrocardio- graphic monitoring over a week and a month, and electrocardiographic monitoring on sportsmen during competitions. We obtained very pos- itive results in both projects. ‘Personally I have always been very interested in medical technol- ogy advances, especially for car- diology; that’s why I seized the opportunity to lead the first clinical experiments with Nuubo’s monitor- ing system.’ Are collected data then stored in the patient’s electronic health record? ‘The data generated by these devic- es is stored on a memory card and can be downloaded and analysed thanks to dedicated software. We write a report based on this data, which is kept in the patient’s health record. Unfortunately, in our hospi- tal, there isn’t any system enabling connection and incorporation of this data directly into the electronic clinical history, which doubtlessly would be a great advance.’ Are you or your colleagues work- ing on other wearable technology projects? www.healthcare-in-europe.com

4 CA R D I O LO G Y We must protect cardiologists from cancer risk CorPath enters the vascular highway stand of Robocath, in his role as a key opinion leader for the company, which is also based in Rouen. He discloses that he has no finan- cial interest in the company but an enthusiasm for a system that can put a shielding wall between him and the irradiating X-ray projector that, as he points out, hovers just inches from his head during some time- long procedures. The R-One system from Robocath is not the first remote stenting robot for cardiology. Two systems approved by the USA’s Food & Drug Administration are commercialised by Corindus, based in Waltham, Massachusetts, which during EuroPCR 2017 cel- ebrated what it called a milestone for the 100th percutaneous coronary intervention (PCI) performed using the second generation CorPath GRX System. Although Corindus systems hold a CE Mark, the company has yet to sell a CorPath robot in Europe. Robocath is currently complet- ing pre-clinical trials as part of its submission for a CE Mark approval that it hopes to receive in 2018. A submission of the device to the FDA is expected in 2019. The results of a single-centre REMOTE-PCI [percutaneous coro- nary intervention] study spon- sored by Corindus were pub- lished in the January 2017 edi- tion of EuroIntervention, the jour- nal of the European Association of Percutaneous Cardiovascular Interventions the European Society of Cardiology (ESC). (EAPCI) and PCI was successfully performed on 19 of 22 target lesions using radial access, the first demonstration of the ability to perform PCI from outside the confines of the cath lab by using a combination of robotics and telecommunications. The CorPath 200 cockpit to con- trol the robot was installed in a separate room, roughly 17 meters from the patient table, isolating the operator but maintaining continu- ous video and audio contact with both the patient and any personnel in the lab. Principal investigator Ryan Madder MD, a cardiologist and researcher Neuroradiologist Philippe Bencteux, is the founder of Robocath, based in Rouen, France. with the Spectrum Medical Group based in Grand Rapids, Michigan, told European Hospital that, in addi- tion to the stenting procedures, he has successfully utilised the CorPath robot to perform the diagnostic procedure of fraction flow reserve (FFR) to assess lesion severity. Potentially, Madder said the remote robotic system can be installed anywhere there is a fluor- oscopy suite, and that it suggests a potential for tele-stenting, an ability to perform procedures in regions where PCI is currently unavailable by utilising a robotic cockpit located in a distant expert centre. ‘We are still very early in this study; there’s a lot of work to be done,’ he noted. ‘We are ways off from deploying a system to commu- nity hospitals.’ Shielding cardiologists from harmful radiation is the goal for two systems capable of navigat- ing the vascular highway, John Brosky reports ‘We cannot continue to accept work- ing in conditions that put our lives in danger,’ says Alain Cribier, the pioneering cardiologist from the University Hospital of Rouen, who first implanted an aortic heart valve via a catheter in 2002. ‘You don’t feel anything; radiation is not pain- ful, but there is an accumulation of dose when you do this for decades, day-in and day-out,’ he explained. A study, published by the American Heart Association in August 2016, demonstrated a direct relation between working in a cath- eterisation lab and developing radi- ation-induced cancer, cataracts and skin lesions. According to the study, interven- tional cardiologists accumulate sig- nificant lifetime radiation exposure in the range of 50 milliseverts to 200 mSv, which corresponds to a whole body dose equivalent to 10,000 chest X-rays. ‘I have lost several col- leagues to brain can- cer,’ Alain Cribier told European Hospital. ‘We all have mus- culoskeletal prob- lems,’ he said, bringing out of a closet the 12-kilo lead apron he wears during 12-hour work shifts that can result in aggra- vated orthopaedic maladies. At EuroPCR in May 2017 in Paris, Cribier met with fellow cardiologists on the Cardiologists must keep up We must embrace the potential of digital data Report: Mark Nicholls Leading cardiologist and healthcare researcher Professor Harlan Krumholz has warned that medical practitioners must embrace the potential of digital data generated by patients if they are to avoid being left behind as the digital revolution moves forward at an ever-advancing pace. As Professor of Medicine (Cardiology) at Yale School of Medicine, he delivered the prestig- ious Paul Wood Lecture at the June conference in Manchester, UK, of the British Cardiovascular Society on a theme of ‘Personalised medicine and computational cardiology – enhanc- ing cardiovascular care and health in the next era’. Tex vector / Shutterstock ‘Data generated every day for a variety of practical purposes can serve as an inexhaustible source of knowl- edge to fuel learning in a healthcare system,’ he said, but warned that if medicine wants to take advantage of technology, it has to catch up with the digital revolution. He pointed to statis- tics that show the average American Prof. Alain Cribier, MD, is head of Cardiology at the Charles Nicolle Hospital , in Rouen University, France. Back at the R-One robotic system from Robocath, Cribier provided a demonstration. ‘This is not a totally new idea,’ he said. ‘There are sur- gical robots, orthopaedic robots, robots for brain surgery. But it was not considered possible for cardi- ology. I was sceptical myself but, over 10 years, I have followed the progress step-by-step as they solved technical problems.’ At the patient table, Cribier feeds the catheter into a single-use car- tridge, an integral part of the robotic mechanism that contains the grasp- ers that advance and turn the guide- wire. Walking from the patient table to the control panel behind a radiation shield, he said, ‘The robot does not perform anything itself, everything is controlled by the operator’s hand,’ he pointed out. ‘I can do exactly the same things using the robot that I would do with my hands, advance the wire, retreat, rotate and push.’ At the controls he advances and rotates the guidewire simultaneous- ly, pushing and turning, something the CorPath robot cannot do. Cribier expects in a next step the robot can be applied to periph- eral artery procedures as it uses the same sized wire. Corindus has already been granted an extended indication by the FDA to apply the CorPath for peripheral procedures. As for the transcatheter aortic valve replacement procedures that he pioneered, Cribier said, ‘There is no question the system can be adapted to accept these larger cath- eters. This system will allow physi- cians to go anywhere on the vascu- lar highway.’ spend 5.6 hours on digital devices every day, including those in older age groups, and that medicine has to recognise the power of this trend. Krumholz also suggested that medi- cine has not learned to communicate as rapidly, effectively and simply with its audience in the way that other sectors, such as weather forecasters, retailers, and traffic bulletins, have. Medicine, he said, had been slow to find ways of integrating digital data into practice, pointing to the tran- sition to electronic health records, where he feels health professionals in the USA were slow to get involved as hospitals made the transition - eased with $50bn of funding. In 2008, 9.4% of records were electronic health records (HER) but, by 2015, it was 83.8%. He also felt patients should have access to their own record to share it in ways that can improve their care and augment research, being partners as ‘citizen scientists’. The most important element about precision medicine, Krumholz con- tinued, is that it can be driven with patients as partners and that the doc- tors and researchers should recognise the value of patient reported outcome data that are generated from wearable EUROPEAN HOSPITAL Vol 26 Issue 4/17

CA R D I O LO G Y 5 An exciting new approach for heart bypass surgery Transforming veins into arteries Raimondo Ascione is Professor of Cardiac Surgery and Translational Research at the University of Bristol, UK. He is also Academic Director of the pre-clinical Translational Biomedical Research Centre (TBRC), which bridges the gap between basic science research and the NHS to boost the translation of fundamental discoveries and emerging biomedical technologies to the bedside. Ascione is also Chief Investigator of clinical trials and experimental work aimed to protect adult high-risk patients from complications during cardiac surgery. surgery is performed. In future, the vision is that patients would be admitted to hospital a few weeks before their operation for veins to be taken from their leg and engi- neered in a laboratory into arteries. The patient would return to hos- pital a few weeks later for bypass surgery operation with surgeons using the vein material that has been transformed into arterial-qual- ity conduits. ‘In terms of surgical technique, it would be pretty much the same,’ Ascione added. ‘Stitching and sutur- ing these arterial-like grafts will be similar to those grafts surgeons are already used to, so no further train- ing would be necessary.’ The technique could also benefit vascular surgeons who, for periph- eral vascular grafting in patients with blocked arteries in their legs, can only use vein or synthetic mate- rial with poor mid-term outcome. Around 17,000 coronary artery bypass operations are carried out in the United Kingdom each year, with many thousands more conducted internationally. This approach could improve longer-term outcomes for heart by- pass patients. ‘Ultimately,’ Ascione concluded, ‘this research could mean that peo- ple receive longer-lasting grafts, improving their life expectancy while reducing their need for future surgery and use of hospital resourc- es.’ Report: Mark Nicholls Scientists in the United Kingdom are investigating the potential of a new regenerative and tissue engineer- ing technique that could transform veins into arteries to improve the outcomes for patients undergoing heart bypass surgery. The research, at Bristol University, led by cardiac surgeon Professor Raimondo Ascione, alongside Professor Sarah George and Dr Jason Johnson, could revolution- ise the approach to cardiac artery bypass surgery. Presently, replacement arteries for bypass operations are limited, so surgeons use veins taken from the patient’s leg to replace the blocked vessels of the heart. Populating veins with artery-like cells However, while arterial grafts can continue to work well for up to 20 years, up to half of vein grafts can become blocked within 5-10 years as the greater blood pressure of the artery environment dam- ages the graft after implant. ‘With the bypass surgery we are taking a piece of vein from the leg which has a thin wall with blood flowing at a very low pressure,’ explained Professor Ascione, Chair of Cardiac Surgery and Translational Research at Bristol. ‘But when put into the heart it has to support and sustain a much higher pressure because it is being put into an arterial system, a high pressure system, so this is what leads to problems with the vein. ‘Currently, veins are used for approximately 80% of all grafts made during heart bypass surgery. They work well in the short-term, devices and data collection mobile technologies. Suggesting that data acquisition is an important new dimension to the way doctors approach medicine, Krumholz said: ‘Medicine now is more than ever an information science and increas- ingly a digital information science.’ Yet he harbours concerns about whether physicians are truly making the best use of available data unless they ‘learn to use and develop new knowledge iteratively’ and acquire ‘smart enough’ systems to process the data and utilise it. Among his key concerns is that current medical research enterprises cannot keep pace with the infor- mation needs of patients, clinicians, administrators and policymakers. The digital revolution, tools and approach- es, he pointed out, could augment and accelerate knowledge – produc- ing a new paradigm of a learning healthcare system. ‘Medicine needs to realise that we are in a new era,’ he said. Health professionals, not the technicians, have to be the key, as they understand what patients need and the complexity of the problems that our patients face. ‘The next generation must be deployed in a way that preserves the www.healthcare-in-europe.com but they are not designed for the demands of working as an artery.’ This may result in the grafted vein thickening its wall and becoming blocked and, when this happens, the heart bypass operation may have to be repeated, or the patient may even suffer a heart attack. The Bristol team aim to achieve the vein-to-artery transformation by ‘washing’ cells from the vein, strip- ping it back to leave a tube-like scaf- fold made from extracellular matrix. An artery can then be built on this framework by populating it with arterial-like cells. This will be done either before surgery, in a dynamic bioreactor that mimics the arterial environment, or after the surgical implant by the host’s natural healing processes. ‘With the old cells stripped out of the vein we are only left with the vascular skeleton, the actual framework of the vein,’ Ascione explained. ‘The vein goes from being “pinky” to like a white ghost colour. Then we can use this acellu- lar skeleton of just vascular extracel- lular matrix and transform it into a high-pressure system and seed the arterial cells on this. Tissue-engineered arterial grafts improve long-term outcomes ‘By stripping back a vein and using it as the framework on which to build an artery, we hope to create in the lab tissue-engineered arterial grafts that are better able to cope with the demands of carrying blood from the heart.’ The professor has already dem- onstrated the feasibility of these approaches in pilot studies and is now leading a new project to find the best method to re-populate the tube-like scaffolds derived from veins with cells. Plain and pre-populated scaf- folds will be implanted into pigs at the new Translational Biomedical Research Centre (TBRC) co-funded by the British Heart Foundation (BHF) and the Medical research Council (MRC) to establish if they give a better result than the grafts that are currently used. If this proves successful, it could see a new approach to the way heart bypass Cardiologist Professor Harlan Krumholz is a healthcare researcher at Yale University and Yale-New Haven Hospital, and the Harold H Hines, Jr. Professor of Medicine and Director of the Yale Center for Outcomes Research and Evaluation (CORE) – one of the America’s most productive research units dedicated to producing innovations to improve patient outcomes and promote better population health. He is also a Director of the Robert Wood Johnson Foundation Clinical Scholars Program, which prepares especially talented physicians to become future healthcare leaders. special nature of our profession but the advances in technology should help us be better, not replace the human touch. We should not be afraid of technology when it comes to health. It is better to embrace it - it can make us smarter than ever in looking after large populations.’ XENIOS CONSOLE - ONE INTEGRATED LUNG & HEART THERAPY PLATFORM • • Next-generation therapies for lung and heart failure on one single platform Full spectrum of extracorporeal support • Wide range of applications - from highly effective removal of carbon dioxide to complete oxygenation From customized ECMO sets up to longterm approved patient kits High safety features • • L U N G A N D H E A R T T H S E I P A R E www.xenios-ag.com

6 CA R D I O LO G Y New scan detects inflammation after heart attack Exciting hyperpolarised MRI Report: Mark Nicholls A new type of scan that can detect cardiac inflammation may help tai- lor treatment for patients who have suffered a heart attack, according to research findings presented at the British Cardiovascular Society (BCS) conference in June. Developed in the UK, hyperpolarised MRI (h-MRI) enables cardiologists to see more detail of healthy and diseased hearts than conventional scans, including the level of inflammation post-myo- cardial infarction. Detecting inflammation in the heart the British Heart Funded by Foundation (BHF) the University of Oxford researchers now believe h-MRI could help scientists develop and monitor the effects of new, inflammation-targeting treatments that may improve the heart’s heal- ing process in heart attack patients. The discovery could have signifi- cant benefits because the hearts of patients who have suffered a myo- cardial infarction (MI) can undergo continued inflammation even during the healing process, and despite receiving emergency treatment. Yet research into why this may happen remains limited as con- ventional scans cannot detect or measure inflammation in the heart, whereas h-MRI can. Conventional MRI measures how protons change position when exposed to a magnetic field, but h-MRI works by producing images from carbon molecules, which make up the energy sources needed to help the heart pump and can offer doctors a clearer picture of inflam- mation in the heart. h-MRI as biomarker and pharmacological target For the study, the team measured production of lactate in the dam- aged heart tissue of rats and found that after a heart attack immune cells within the injured heart mus- cle become active and are repro- grammed to make lactate, leading to inflammation in the heart. By monitoring how much lactate is pro- duced in the damaged tissue, they were able to identify and measure the level of inflammation in the heart. Following on from that, the team administered the experimental drug 2-deoxyglucose (2-DG) to the rats after the heart attack, to try and combat the inflammation. to monitor Using h-MRI the heart’s response, they found that 2-DG reduced lactate production and inflammation, and improved the heart’s function. The cutting edge scanning system They showed that high hyperpolar- ised lactate signal in the days after myocardial infarction is caused by macrophage-driven inflammation, and reflects not just the number of inflammatory cells infiltrating the myocardium but also the inflamma- tory phenotype of those cells. The Oxford scientists – one of the first groups to use h-MRI to study the human heart – believe that h-MRI will not only detect inflammation in damaged heart tis- sue but also could provide a novel method for the detection of myocar- dial inflammation with high transla- tional potential as both a biomarker and novel potential pharmacological target. ‘H-MRI is a cutting-edge scanning system which allows doctors to bet- ter understand the innermost work- ings of the heart non-invasively, and how they become abnormal in heart The Oxford University team used the hyper- polariser laboratory to investigate how the experimental drug 2-deoxyglucose (2-DG) may improve heart function after a heart attack Andrew Lewis MD is a Specialist Registrar in Cardiology at the Great Western Hospital in Swindon, UK, and won the Young Investigator’s Prize Competition at the British Cardiovascular Society conference in Manchester for his research into myocardial inflammation imaging. disease,’ Dr Andrew Lewis, Specialist Registrar in Cardiology at the Great Western Hospital in Swindon, summed up. ‘In this research, we used h-MRI imaging to capture the healing processes in experimental models after a heart attack, and also tested new treatments to improve the heart’s recovery. More studies needed ‘Our work has identified several forms of heart disease where this technique could be used to improve diagnosis and treatment,’ Lewis added. This is incredibly exciting, and we intend to move forward with patient studies as quickly as possible.’ Lessons gained from an EHRA 2017 Symposium Cardiac resynchronisation therapy improvements Which CRT patients can be ‘downgraded’ from a CRT-D device with defibrillator function to a CRT-P with just a pacemaker function? This, with two further current CRT issues – chronotropic incompe- tence and telemonitoring of CRT patients – featured prominently at the Europace-Cardiostim Congress in Vienna. For more than 20 years, cardiac resyn- chronisation therapy (CRT) has been a pillar in the treatment of chronic heart failure (CHF). CRT devices are either pacemakers (CRT-Ps) or implantable defibrillators (CRT-Ds), which are implanted in the patient’s chest. These are connected to the heart with three leads, the third one linking to the left ventricle which pumps blood through the body. While both types of devices synchronise the heartbeat, CRT-Ps prevent the heart from beating too slowly and CRT-Ds prevent it from beating too quickly. At a satellite symposium at the Europace-Cardiostim Congress (EHRA 2017) experts debated whether patients who respond well to a CRT-D and show improved heart function should receive a CRT-P in the next scheduled device replacement. The background: Many patients respond so well to CRT that their heart function markedly improves and a CRT-D might not be needed; indeed between 10-25% are so-called super-responders, i.e. their cardiac device restores a normal ejection fraction in the left ventricle, lowering the risk of sudden cardiac arrest to that of a healthy person. At EHRA 2017, Dr. Jacques Mansourati from Brest University Hospital in France, presented a study investigating this very issue: The BioContinue study is observing 277 CRT patients in eight countries to determine which patients need a defibrillator. According to pre- liminary study data, 39% of patients who receive a CRT replacement do not need a defibrillator because the therapy increased the ejection frac- tion of the left ventricle by at least 40% and no ventricular tachycardia was reported. ‘During a scheduled replacement of the device, respond- ers and super-responders can be downgraded from a CRT device with defibrillator to one without this function,’ Mansourati explained. The second controversial issue in CRT is chronotropic incompetence: In 20-40% of all CRT patients, heart rate does not increase commensu- rate with increased physical activity. ‘Chronotropic incompetence could be a major factor in patients who do not respond to CRT,’ said Dr. Mattias Roser from Charité Berlin. In these cases, Roser points out, rate- adaptive pacing might provide a solution, as indicated by BioCreate, a pilot study conducted at Charité to investigate whether Closed Loop Stimulation in heart failure patients with chronotropic incompetence can improve clinical outcomes. This technology, developed by Biotronik, responds naturally to patients’ phys- ical and mental activity or stress, adapting heart rates physiologically. Roser is optimistic: ‘We consider this a highly potential approach to significantly improve the treatment of CRT patients,’ he said. The third, but by no means least, important issue is remote monitor- ing of ICD patients. Ever since the IN-TIME study showed Biotronik Home Monitoring reduced mortal- ity in heart failure patients, the use of this technology has been included in the clinical guidelines. However, data presented at EHRA 2017 indicate that not all tele-mon- itoring systems are created equal: they do offer different clinical out- comes. TRUECOIN, a meta-analysis, showed Biotronik Home Monitoring to reduce mortality in all types of ICD patients. EUROPEAN HOSPITAL Vol 26 Issue 4/17

CA R D I O LO G Y 7 Where will material come from as demand grows? Renewing the promise of bioabsorbable implants Columbia University Medical Center and New York-Presbyterian Hospital. Elazer Edelman, who directs the Harvard-MIT Biomedical Engineering Center and is a member of the U.S. FDA’s Science Board, chaired the ses- sion. The Chief Technology Officer and co-founder of Xeltis, Martijn Cox, explained the principle of what his company calls endogenous tissue res- toration using electrospun fabrics. Electrospun materials bring a spark of hope to a cardiovascular landscape darkened by setbacks for reabsorbable stents, John Brosky reports It was famously said that implanting a device in a person to cure a disease is to implant a new disease. Simply put, the human body will continually fight against foreign materials, leading to chronic inflammations or repeat- ed interventions. Which explains the recent excitement among cardiologists for a new generation of materials that can repair a diseased condition, and then disappear as the body absorbs the foreign material. The earliest advances in this field were made with bio-reabsorbable stents (BRS), which have also deliv- ered the greatest setbacks. Two- and three-year results for the leading stent, the Absorb BRS from Abbott Vascular, not only failed to demonstrate the promised benefits, but also in some trials showed a dangerous tendency for in-stent thrombosis. In the August 2017 issue of EuroIntervention, Editor- in-Chief Patrick Serruys noted the long-term follow-up data from ran- domised trials ‘sometimes contradict themselves’, and show that, ‘we went from the best result to the worst result.’ With improved technology, he con- cluded, ‘We will reach the promised land, which is not for tomorrow but for the day after.’ Beyond stents, which utilise a hard- ened bioabsorbable polymer, other cardiovascular applications for bioab- sorbable materials have shown more promising long-term results with the first in-human trials. The technology that may open a new path to the Promised Land is electrospinning, where an electro- spray technique combined with the spinning of fibres creates a highly 6 months transapical aortic valve versatile soft fabric for implantation devices that the body can absorb over time. tor,’ he said, adding that there are mul- tiple projects moving in the cardiology pipeline. While this technology has been known for 100 years, and for decades has been used to produce absorbable sutures for surgical closings, it is only recently that new devices using the materials have emerged. According to Benoit Studlé, the CEO of Statice, which designs and manufactures these next-generation cardiac implants, the rediscovery of this technology is due to a pro- gressive evolution in the savoir-faire for engineering unique chemical and mechanical properties. ‘The medical need has been better defined, which has created a greater demand, and as a result, there is a market today. This is a great motiva- As a contract manufacturer, Studlé can not speak about projects being developed by innovative physicians and start-up entrepreneurs at Statice – except to say the company is a partner in a pan-European program TEH-TUBE, [tissue engineering of the right heart outflow tract by a biofunc- tionalised bioresorbable polymeric valved tube] and REVAMED, a €4 mil- lion program to develop implantable biosynthetic patches for drug delivery to aid with surgical closings, wound dressings and pain management. Statice engineers are also creating electrospun fabrics for an aortic valve, but this is still in an early stage of development. Supporting women in electrophysiology and cardiology The EPIC Alliance ‘We are now in an era where patients with implantable devices – not just pacemakers, but also cardioverter defibrillators – can undergo MRI scanning. Although there are still open questions, we no longer have to exclude these patients from this very important imaging technol- ogy,’ said Seattle-based cardiologist Professor Jeanne E Poole, during the Europace-Cardiostim Congress (EHRA 2017) in Vienna. While dis- cussing implantable devices and MRI is not unusual at a scien- tific congress, the satellite sym- posium ‘Clinical Decision Making in Electrophysiology/Arrhythmias’, chaired by Professor Poole, differed from other such events in one par- ticular way: the panel was all-female. This symposium was organised by the Electrophysiologist International Community Alliance (EPIC Alliance). the EPIC Alliance aims to advance career opportunities for women in electro- physiology and cardiology. The net- work currently includes 250 women in 2010, Founded www.healthcare-in-europe.com electrophysiologists and cardiac device specialists internationally. ‘It is focused on helping women achieve a pathway in electrophysi- ology equally as successful as men,’ Poole pointed out. First and foremost, the founders of the EPIC Alliance wanted to cre- ate a network for women working in electrophysiology and cardiology. ‘Globally, we did not know each other; many of the female elec- trophysiologists and cardiac device specialists had not met women from other countries working in this field,’ Poole explained during our interview. Today, EPIC Alliance activities have moved far beyond the ini- tial networking aspect to provide members with an array of profes- sional development opportunities. Members are supported in submit- ting abstracts and organising sym- posia at conferences; experienced mentors share their knowledge and support young and upcoming phy- sicians; the alliance also organises meetings and networking events for members to gather at global and local levels. ‘The EPIC Alliance is the most successful organisation supporting women in our field, in which very few women work,’ said Poole, estimating that only about 10 percent of all electrophysiologists and cardiac device specialists are female. Women, she surmises, may be put off by the two to three years of additional training and by extremely long working hours, two factors that appear to be irreconcilable with motherhood and family. However, Poole herself provides a convincing example that a satisfactory work/life balance can be achieved. ‘But,’ she underlines, ‘we do need role models and we must ensure women are vis- ible at scientific congresses.’ Male colleagues, she added, would also benefit from a sustain- able work/life balance: ‘We are all just human beings working in a very exciting speciality.’ The human body colonises implant- ed scaffolding by creating proteins and collagen to build new tissue, while macrophages also attach to the structure and simultaneously dissolve the foreign material. Serruys suggested the dynamic ten- sion between the rate of destruction and the rate of construction would be the subject of debate for a long time. ‘How sharp, how long, how fast? There may yet be surprises, we may discover new enemies,’ he said. Virmani showed that among the children implanted with the Xeltis valved conduit, the diameter of the valve is not only well-maintained after two years, it is enlarging, ‘so that as the child will grow, this conduit will allow enlargement of the pulmonary trunk as well as the valve’. Yet, a conduit is not an aortic valve, she said, showing histological evidence to demonstrate a critical inconsistency in the creation of new tissue at the hinge point of the aortic valve. ‘We need to think completely differently about how colonisation and tissue formation is achieved,’ she said. ‘Unfortunately, we cannot learn this on the bench top The promised land of synthetic implants that can heal is clearly not for tomorrow. Yet, as Edelman noted, there is urgency in cardiovascular interven- tions. ‘Today heart valves are made from the hide of a very small herd of animals in a very small part of the world. This forces us to consider where these materials are going to come from, as the demand grows greater,’ Edelman pointed out. According to Leon, in a summary statement: ‘This innovative treatment approach has the potential to reduce complications, re-interventions and healthcare costs, while improving quality of life for patients with heart valve disease. This would represent a major leap forward in heart valve therapy.’ Printed by: WVD, Möhrfelden, Germany Publication frequency: bi-monthly Representatives China & Hongkong: Gavin Hua, Sun China Media Co, Ltd. 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A Swiss firm that can speak pub- licly about its work in cardiovascular applications is Xeltis, which, during EuroPCR 2017, renewed the hopes for bioabsorbable implants in a crowded scientific session. Xeltis presented the 24-month results for a pulmonary heart valve to correct or reconstruct right ventricular outflow tract in 10 children, as well as the first study results from the compa- ny’s preclinical aortic valve program. The prestigious panel of key opin- ion leaders would have been enough to pack the room, as it included presentations by Serruys, who is a professor of Cardiology Imperial College London; Thierry Carrel, from the University Hospital Bern Clinic, who also serves on the editorial board of several international journals; the internationally renowned cardiovas- cular pathologist Renu Virmani; and, Martin Leon, the director at the Center for Interventional Vascular Therapy at Editor-in-Chief: Brenda Marsh Art Director: Olaf Skrober Editorial team: Wolfgang Behrends, Lena Petzold, Marcel Rasch Senior Writer: John Brosky Executive Director: Daniela Zimmermann Founded by Heinz-Jürgen Witzke ISSN 0942-9085 Correspondents Austria: Michael Kraßnitzer, Christian Pruszinsky. China: Nat Whitney France: Jane MacDougall. Germany: Anja Behringer, Annette Bus, Walter Depner, Cornelia Wels-Maug, Holger Zorn. Great Britain: Brenda Marsh, Mark Nicholls. Malta: Moira Mizzi. Spain: Mélisande Rouger, Eduardo de la Sota. The Netherlands: Madeleine van de Wouw. USA: Cynthia E. Keen, i.t. Communications, Lisa Chamoff. Subscriptions Liane Kaiser, Theodor-Althoff-Str. 45, 45133 Essen, Germany Subscription rate 6 issues: 42 Euro, Single copy: 7 Euro. Send order and cheque to: European Hospital Subscription Dept XeltisAortic Valve Project6 months Transapical aortic valve Leaflet #32mm2mm2mmGross imageX-ray imagePre-implantCoaptationHingeFree marginLeaflet #2Leaflet #1

13 –16 NOVEMBER 2017 DÜSSELDORF GERMANY www.medica.de/MLF2 NEW at MEDICA THE INTERNATIONAL FORUM FOR LABORATORY MEDICINE Organization Prof. Dr. med. Georg Hoffmann Trillium GmbH Medical Publishing House and Deutsches Herz- zentrum München Doctors and patients, health policymakers and healthcare providers, media representatives and all other visitors of the world’s largest medical trade fair are invited to four exciting focal days with top-class lectures and panel discussions. The event takes place each day from 11 a.m. to 4 p.m. in the new hall 18 and is free of charge for trade fair visitors. The conference language is English. Early detection of cancer and cardiovascular diseases Monday, 13 November 2017: Oncology – Can cancer be detected by a blood test? Tuesday, 14 November 2017: Cardiology – More diagnostic conﬁ dence with myocardial infarction and heart insufﬁ ciency Prof. Dr. med. Stefan Holdenrieder, Deutsches Herzzentrum München The laboratory comes to the patient Wednesday, 15 November 2017: Diabetology – From self-test to continuous glucose measurement Prof. Dr. med. Peter Luppa, Klinikum rechts der Isar der TU München Dangerous travel companions Thursday, 16 November 2017: Infectiology – New multi-resistance in the age of migration Priv.-Doz. Dr. med. Beniam Ghebremedhin, Universität Witten/Herdecke, HELIOS Universitätsklinikum Wuppertal Messe Düsseldorf GmbH Postfach 10 10 06 _ 40001 Düsseldorf _ Germany Tel. + 49(0)2 11/ 45 60-01 _ Fax + 49(0)2 11/ 45 60-6 68 www.messe-duesseldorf.de