European Heart Journal

Ferrari, Roberto; Guardigli, Gabriele

doi: 10.1093/eurheartj/ehx675pmid: 29206967

This second article in the Ferrara prevention series discusses how history has shaped the city to focus on the prevention of cardiovascular disease  In the previous article in CardioPulse,1 we examined the reasons why cardiologists, who have been so successful in treating cardiovascular (CV) diseases, should also be active in CV prevention by providing models on how prevention programmes could be implemented. Atherosclerotic CV diseases will continue to be the major epidemic in the future and, in the past, epidemics were cured not by drugs alone but also by lifestyle modifications.2 So, it is time to take the lead in prevention! This is what we are doing in Ferrara with a university-based programme entitled ‘Ferrara, City of Prevention’. The specific aim is to provide an example of how to make a population healthier over a 6-year period. Let’s try to explain the programme, starting from the obvious questions: why Ferrara? Ferrara has a population of 135 000 and is situated in northern Italy in the county of Emilia Romagna which borders Veneto. The city itself is located between Bologna, home of the oldest university in the world, founded in 1088, and Padova which is known for being home to the first Faculty of Medicine, founded in 1399. It is probably because of its geographical position that the University of Ferrara also has a long history, founded in 1391 by Marquis Alberto V D'Este with the approval of Pope Boniface IX. The University itself is known to have hosted many illustrious professors and scholars such as Ludovico Ariosto, Nicolaus Copernicus, Paracelsus, and Girolamo Savonarola to mention but a few. However, it is the ducal architect Biagio Rossetti (1447–1516) who is relevant to ‘Ferrara, City of Prevention’. Rossetti was asked by Duke Ercole 1 D’Este (Figure 1A—picture of Duke) to expand the medieval part of the city (Figure 1B—map of city). Between 1492–1505, he designed and created a totally new section which still exists today. It is called the ‘Ercolean Addition’ and is considered the first urban project in the world, a sort of ‘ideal city’ for which Ferrara at the time was named ‘the first modern European city’. Rossetti must have had some idea of prevention, or simply just good common sense. His design featured wide pavements, streets and palaces (Figure 2 Via Ercole D’Este) with interiors that are a far cry from the modern blocks of apartments that we have become accustomed to today. His careful attention to the proportionate balance between buildings and green spaces was also very important. Even today, this part of the city is called ‘aria nuova’ which translates to ‘new air’, emphasising the role of gardens and orchards that purify and clean the air, (Figure 3) which was putrid at times during the medieval era. Figure 1 Open in new tabDownload slide (B) Medieval Ferrara, with Rossetti addition. Figure 1 Open in new tabDownload slide (B) Medieval Ferrara, with Rossetti addition. Figure 1 Open in new tabDownload slide (A) Duke Ercole I D’Este. Figure 1 Open in new tabDownload slide (A) Duke Ercole I D’Este. Figure 2 Open in new tabDownload slide Via Ercole D’Este, designed by Biagio Rossetti. Figure 2 Open in new tabDownload slide Via Ercole D’Este, designed by Biagio Rossetti. Figure 3 Open in new tabDownload slide Piazza Ariosta, area Nuova. Figure 3 Open in new tabDownload slide Piazza Ariosta, area Nuova. Apart from this historical involvement in prevention, Ferrara today offers other important opportunities: together with the University, agriculture is the major industry with a significant production of fruits and vegetables which are, of course, the keys factors for a healthy diet. The local population has an opportunity to purchase these ingredients directly from the farmers at local markets rather than from the supermarket shelf (Figure 4). Still on the subject of healthy food, Ferrara is situated at the delta of the River Po, the largest river in Italy, on the coast of the Adriatic Sea with a vast and spectacular group of lagoons (Figure 5) of both salt and freshwater which is a paradise for birds, fish, clams and eels, etc. Figure 4 Open in new tabDownload slide A typical market stall. Figure 4 Open in new tabDownload slide A typical market stall. Figure 5 Open in new tabDownload slide Lagoons of the River Po Delta. Figure 5 Open in new tabDownload slide Lagoons of the River Po Delta. The Faculty of Science created a florid university-driven fishing industry, including the so-called ‘pesce azzurro’ or ‘blue fish’ such as anchovies, sardines, and mackerel. These fish have two advantages (i) they are economical and therefore affordable to all and (ii) they contain a high quantity of Omega 3 polyunsaturated fatty acids which are a proven ingredient for secondary CV prevention.3,4 So, it would appear, that if the inhabitants of Ferrara wish, they have the opportunity to purchase this wonderful fresh produce at a reasonable price. But, are they doing so or do they still crave junk food? Unfortunately, the second option is still more popular and advertising the benefits of healthy food is one of the objectives of our programme. Regular exercise is another cornerstone of prevention. Ferrara is recognized by The United Nations Educational, Scientific and Cultural Organisation (UNESCO) for its beauty and also for being the city of bicycles: almost everyone uses a bicycle to move in and around the city, including the elderly population. The town is still surrounded by more than six miles of ancient walls, mainly built in the 15th and 16th centuries for military purposes or rather for the prevention from outsiders. Today, the spaces below and above the wall have become a ‘downtown’ area where people meet to talk, cycle, walk, exercise, and run in the shade of the enormous lime trees (Figure 6) and away from the modern-day traffic and pollution. It follows that the actual design of Ferrara encourages the population to move about. Consequently, the University of Ferrara has developed a special interest in sports medicine and created the ‘Centro Universitario Sportivo’ which has run several programmes to encourage locals to any age group to exercise. Figure 6 Open in new tabDownload slide Medieval walls of Ferrara. Figure 6 Open in new tabDownload slide Medieval walls of Ferrara. The size of the city and the number of inhabitants is also relevant. Ferrara is not the size of London or Peking, nor does it have a network with millions of inhabitants. A significant proportion of the residents can be reached by a single programme if it is conducted well. Last but not least, Ferrara only has one cardiovascular centre for both the university and the local hospital. This means there are less bureaucratic hurdles to overcome when designing and running a major project[WorldCat]. In conclusion, it seems that Ferrara could be the ideal city for prevention. It has the right number of inhabitants, a long-lasting history of prevention and a university which, in one way or another, has always been involved in the key elements of prevention, food, and exercise. This is important because prevention is knowledge, awareness, and information. In one word, it is a ‘culture’ and the university is the one institution that must provide culture. The fundamental role of the university in ‘Ferrara, the City of Prevention’ will be explained in the next issue of CardioPulse. Stay with us! Gabriele Guardigli Cardiovascular Centre, University of Ferrara, Italy [email protected] Acknowledgement The project ‘Ferrara, city of Prevention’ is supported by a generous bequest on behalf of Antonio Filippini. Conflict of interest: none declared. References References are available as supplementary material at European Heart Journal online. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Vranckx, Pascal; Windecker, Stephan; Welsh, Robert C; Valgimigli, Marco; Mehran, Roxana; Dangas, George

doi: 10.1093/eurheartj/ehx390pmid: 29020333

Transcatheter aortic valve implantation (TAVI) has emerged as a valuable treatment alternative to surgical aortic valve replacement among patients with symptomatic aortic stenosis at increased surgical risk. The rapid technological evolution from early to current-generation TAVI systems with low-profile delivery catheters, bioprosthetic valves with proven midterm durability, and improved positioning and retrieval features have made important contributions to the widespread clinical use of this minimal invasive therapy. Although peri-procedural and long-term thrombotic and bleeding events after TAVI remain a relevant concern, the optimal antithrombotic strategy and duration to mitigate these risks remain unclear. This review provides an overview of recent insights in this field, and highlights current and future antithrombotic trials focusing on optimizing outcomes in patients undergoing TAVI.

Généreux, Philippe; Pibarot, Philippe; Redfors, Björn; Mack, Michael J; Makkar, Raj R; Jaber, Wael A; Svensson, Lars G; Kapadia, Samir; Tuzcu, E Murat; Thourani, Vinod H; Babaliaros, Vasilis; Herrmann, Howard C; Szeto, Wilson Y; Cohen, David J; Lindman, Brian R; McAndrew, Thomas; Alu, Maria C; Douglas, Pamela S; Hahn, Rebecca T;

Naci, Huseyin; Vardas, Panos; Vahanian, Alec; Kirchhof, Paulus; Bardinet, Isabel; Mossialos, Elias

doi: 10.1093/eurheartj/ehx673pmid: 29206965

The recent history of cardiovascular medicine is a remarkable success story. Since the early 1970 s, total cardiovascular mortality in Europe and the USA declined on average 50% for both men and women.1 In the UK alone, approximately 70 000 deaths were prevented or postponed between 1980 and 2000.2 Although this decline started approximately 25 years later in Eastern European countries, cardiovascular mortality in Eastern Europe has also been steadily decreasing since the 1990 s.3 A little more than half of the observed decline in cardiovascular mortality has been attributed to public health approaches and prevention of cardiovascular events. Improvements in population level risk factors such as smoking cessation, and blood pressure and cholesterol control have been shown to be responsible for more than half of the reductions in cardiovascular mortality over the past two decades.4 Significant advances in medical and surgical treatment of patients have accounted for the remaining 40–45% of the total mortality decrease.5,6 In particular, secondary preventive therapies after myocardial infarction or revascularization, initial treatments for acute myocardial infarction or unstable angina, treatments for heart failure, and revascularization for chronic angina have contributed to major improvements in mortality. Despite these major successes, the burden of cardiovascular disease remains significant. According to the most recent Global Burden of Disease study, ischaemic heart disease and stroke account for the majority of deaths around the world.7 In 2013, approximately one-third of all deaths (∼17 million) were attributable to cardiovascular disease—a 35% increase since 1990.8 This trend is likely to continue as more human beings are shielded from the early deaths due to infectious diseases and extreme poverty. Globally, cardiovascular diseases are afflicting ever-increasing numbers of young- and middle-aged adults. This is especially so in low- and middle-income countries that are faced with the double burden of communicable and non-communicable diseases to which cardiovascular illnesses contribute significantly.9 Nearly 80% of the world’s more than 1 billion smokers live in low- and middle-income countries.10 Respectively, ischaemic heart disease and stroke are responsible for the 1st and 3rd highest numbers of years of life lost and disability-adjusted life years worldwide, replacing childhood conditions from 1990 to 2010.11 In addition to such a significant burden of mortality and morbidity, cardiovascular diseases face important quality challenges that extend beyond the traditional boundaries of medical science and practice. For example, there are substantial and quantifiable equity issues: cardiovascular mortality is higher in people with low education, income, social class or those in marginalized ethnic groups, and those living in poor and deprived communities.9 There are also complex behavioural issues: patients rarely adhere to their medications, and there is a significant decline in the use of medications after treatment initiation.12 Finally, access to best care often requires complex infrastructures—including interventional and surgical services, for which best care models need to be constantly refined. As a result, a large proportion of individuals have cardiovascular risk factors that remain uncontrolled despite the availability of proven, effective, and often inexpensive therapies, and large patient populations are deprived of evidence-based care.13 Economic, workforce-related, and political challenges around the world are straining government budgets, and putting unprecedented pressure on health care delivery systems. Currently, the quality of cardiovascular care delivery remains sub-optimal even in some of the richest parts of the world.14 There is now a chasm between what should happen versus what does happen in health care systems. Despite the recent emergence of health technology assessment and clinical practice guideline development efforts over the past decades, observed differences between evidence-based recommendations and their implementation—the so-called evidence-practice gaps—are widespread.15 While health care systems heavily invest in efforts to ensure appropriate provision and use of technologies and services, under-use and over-use problems continue to co-exist side-by-side.16 There is both a lack of implementation of some proven effective strategies, and also inappropriate use of strategies with strong evidence against, or insufficient evidence for their effectiveness and safety. A new future in cardiovascular medicine Tackling these challenges is not straightforward and warrants innovative policy and management responses. A new generation of leaders from within the profession can devise creative solutions and transform the future of cardiovascular medicine. Key insights from social and behavioural sciences can help towards this goal. Over the past decades, cardiovascular medicine has served as an incubator for developing and testing innovative policy mechanisms in health care such as pay-for-performance.17 This is perhaps unsurprising as several cardiovascular outcomes are relatively easy to capture in routinely collected administrative databases and thus amenable to monitoring, measurement, and accountability. In fact, many quality improvement interventions that are commonplace today (e.g. public reporting of outcome data) were first developed, tested, and subsequently rolled out in cardiovascular medicine.18 The reach of policy and economics in cardiovascular medicine is far and wide.19 As new innovative medical and surgical interventions are approved or adopted, their affordability is almost as widely discussed and debated as their health benefits and safety. Questions to which the fields of health policy and economics can help answer are several and include: How are funds collected, pooled, and allocated in health care systems? What are the implications of different health financing mechanisms? What are the advantages and disadvantages of the current processes for medical technology approval and reimbursement? Which population sub-groups are eligible to receive care and at what cost? What type of evidence is used to inform practice guidelines and quality indicators that increasingly form the basis of physician compensation? As an increasing number of countries experiment with new policy mechanisms aimed at improving quality and access, and containing costs, cardiovascular experts are best suited to join forces with health services researchers, managers, economists, and policymakers to inform the design, implementation, and evaluation of future interventions. An interdisciplinary training program can help ensure that stakeholders from different perspectives and backgrounds adopt a common language when discussing current issues and considering alternative solutions. An innovative program for future leaders in cardiovascular medicine The European Heart Academy (EHA) of the European Society of Cardiology has joined forces with the London School of Economics and Political Science (LSE), a global leader in social sciences research and teaching, to develop and deliver a unique Master’s degree program on health economics, policy, and outcomes research aimed at health care professionals in cardiovascular sciences with full-time employment (Box 1). Box 1  Origin and evolution of the program The idea for the Executive MSc in Health Economics, Outcomes, and Management in Cardiovascular Sciences was conceived jointly by Professors Elias Mossialos and Panos Vardas in 2014. The vision behind the program was to equip cardiovascular specialists with essential research and policy skills to make active contributors to health policy discussions. To implement this vision, a working group was immediately formed and included Huseyin Naci and Paulus Kirchhof in addition to Panos Vardas and Elias Mossialos. The working group collaborated on designing a curriculum and establishing an innovative set of modules and assessments. Following the program’s successful launch in December 2015 with its first intake of 39 students, a Steering Committee was formed to monitor the program’s implementation and identify opportunities for participants. The current Steering Committee includes Panos Vardas (Past President of ESC and Chief Strategy Officer of EHA), Alec Vahanian (Chair of EHA), Isabel Bardinet (Executive Director of ESC), Huseyin Naci (MSc Program Co-Director, LSE), Mark Maloney (Head of Academic Partnerships, LSE), and Elias Mossialos (MSc Program Co-Director, LSE). In its first 2 years, the program has attracted high-profile speakers including Jeroen Bax (President of ESC), Professor Sir Julian LeGrand (Former Senior Advisor to Tony Blair), Leeza Osipenko (Director of Scientific Advice, National Institute for Health and Care Excellence), Dr Matt Kearney (National Clinical Director for Cardiovascular Disease Prevention, NHS England), and Professor Tony Rudd (National Clinical Director for Stroke, NHS England). Currently in its 3rd year, the master’s level program has already trained ∼80 cardiovascular specialists from over 20 countries. The program has a carefully crafted curriculum to ensure that health care professionals in the cardiovascular medicine field gain a complementary set of skills to their specialized training in clinical medicine. In addition to compulsory courses focused on quality, economics, and policy, a range of optional modules tackle not only today’s challenges like management and health technology assessment but also tomorrow’s opportunities such as behavioural science and performance measurement in a fast-changing health care environment (Table 1). Table 1 Program structure and overview of modules Compulsory modules . Optional modules (required to take 3 of 6) . Quality and outcomes in cardiovascular sciences Provides an overview of the concept of quality, its key components, and its measurement in different health care systems. Offers a critical perspective on the literature evaluating quality improvement interventions focused on the cardiovascular disease field. Measuring health system performance Presents a framework to discuss the opportunities and challenges with performance measurement in health care. Focuses on the measurement instruments and analytic tools needed for performance measurement. Economic analysis for health policy Serves as an introduction to major developments in the economics of health and health care. Provides health care professionals with a strong understanding of the role economics can play in health policy and health system administration Financing health care Gives a thorough grounding in health financing policy. Focuses on the health financing functions of collecting revenue, pooling funds and purchasing services, as well as on policy choices concerning coverage, resource allocation and provider payment mechanisms. Systematic review and meta-analysis Covers the principles of reviewing and synthesizing the existing body of literature. Provides an overview of methods for quantitatively synthesizing multiple randomized controlled trials in meta-analysis. Research design for evaluating health programs and policies Provides a practical overview of the principles and models of evaluation, and the role of theories, concepts, and hypotheses. Covers study design choices in light of bias, validity and other design trade-offs. Economic evaluation in health care Focuses on analytic methods in the economic evaluation of health interventions. Provides a strong foundation in cost-effectiveness analysis of interventions used in long-term chronic illnesses. Behavioural science for health Introduces the main tools and principles of behavioural sciences and the key state-of-the-art applications to health economics, policy, and management. Applies behavioural science tools to concrete challenges in the health area. Using health economics to analyse and inform policy and practice Gives an overview on how health systems are constructed, and how the various parts of the system interact. Focuses on the role of regulation, resource allocation, payment arrangements, and the complexities of evaluating policy and performance. Principles of health technology assessment Introduces the role of Health Technology Assessment in health care reimbursement and coverage decision making. Covers the key operational modalities of health technology assessment, the different models of value assessment and how they link to decision-making. Dissertation Offers an opportunity to carry out independent study. Integrates approaches and knowledge learned across courses and present results to address a health/clinical policy. Introduction to management in health care Introduces the main principles of management and strategy and related issues that impact on organisational change, group decision making, innovation and leadership. Applies academic management knowledge to health care practice. Compulsory modules . Optional modules (required to take 3 of 6) . Quality and outcomes in cardiovascular sciences Provides an overview of the concept of quality, its key components, and its measurement in different health care systems. Offers a critical perspective on the literature evaluating quality improvement interventions focused on the cardiovascular disease field. Measuring health system performance Presents a framework to discuss the opportunities and challenges with performance measurement in health care. Focuses on the measurement instruments and analytic tools needed for performance measurement. Economic analysis for health policy Serves as an introduction to major developments in the economics of health and health care. Provides health care professionals with a strong understanding of the role economics can play in health policy and health system administration Financing health care Gives a thorough grounding in health financing policy. Focuses on the health financing functions of collecting revenue, pooling funds and purchasing services, as well as on policy choices concerning coverage, resource allocation and provider payment mechanisms. Systematic review and meta-analysis Covers the principles of reviewing and synthesizing the existing body of literature. Provides an overview of methods for quantitatively synthesizing multiple randomized controlled trials in meta-analysis. Research design for evaluating health programs and policies Provides a practical overview of the principles and models of evaluation, and the role of theories, concepts, and hypotheses. Covers study design choices in light of bias, validity and other design trade-offs. Economic evaluation in health care Focuses on analytic methods in the economic evaluation of health interventions. Provides a strong foundation in cost-effectiveness analysis of interventions used in long-term chronic illnesses. Behavioural science for health Introduces the main tools and principles of behavioural sciences and the key state-of-the-art applications to health economics, policy, and management. Applies behavioural science tools to concrete challenges in the health area. Using health economics to analyse and inform policy and practice Gives an overview on how health systems are constructed, and how the various parts of the system interact. Focuses on the role of regulation, resource allocation, payment arrangements, and the complexities of evaluating policy and performance. Principles of health technology assessment Introduces the role of Health Technology Assessment in health care reimbursement and coverage decision making. Covers the key operational modalities of health technology assessment, the different models of value assessment and how they link to decision-making. Dissertation Offers an opportunity to carry out independent study. Integrates approaches and knowledge learned across courses and present results to address a health/clinical policy. Introduction to management in health care Introduces the main principles of management and strategy and related issues that impact on organisational change, group decision making, innovation and leadership. Applies academic management knowledge to health care practice. Table 1 Program structure and overview of modules Compulsory modules . Optional modules (required to take 3 of 6) . Quality and outcomes in cardiovascular sciences Provides an overview of the concept of quality, its key components, and its measurement in different health care systems. Offers a critical perspective on the literature evaluating quality improvement interventions focused on the cardiovascular disease field. Measuring health system performance Presents a framework to discuss the opportunities and challenges with performance measurement in health care. Focuses on the measurement instruments and analytic tools needed for performance measurement. Economic analysis for health policy Serves as an introduction to major developments in the economics of health and health care. Provides health care professionals with a strong understanding of the role economics can play in health policy and health system administration Financing health care Gives a thorough grounding in health financing policy. Focuses on the health financing functions of collecting revenue, pooling funds and purchasing services, as well as on policy choices concerning coverage, resource allocation and provider payment mechanisms. Systematic review and meta-analysis Covers the principles of reviewing and synthesizing the existing body of literature. Provides an overview of methods for quantitatively synthesizing multiple randomized controlled trials in meta-analysis. Research design for evaluating health programs and policies Provides a practical overview of the principles and models of evaluation, and the role of theories, concepts, and hypotheses. Covers study design choices in light of bias, validity and other design trade-offs. Economic evaluation in health care Focuses on analytic methods in the economic evaluation of health interventions. Provides a strong foundation in cost-effectiveness analysis of interventions used in long-term chronic illnesses. Behavioural science for health Introduces the main tools and principles of behavioural sciences and the key state-of-the-art applications to health economics, policy, and management. Applies behavioural science tools to concrete challenges in the health area. Using health economics to analyse and inform policy and practice Gives an overview on how health systems are constructed, and how the various parts of the system interact. Focuses on the role of regulation, resource allocation, payment arrangements, and the complexities of evaluating policy and performance. Principles of health technology assessment Introduces the role of Health Technology Assessment in health care reimbursement and coverage decision making. Covers the key operational modalities of health technology assessment, the different models of value assessment and how they link to decision-making. Dissertation Offers an opportunity to carry out independent study. Integrates approaches and knowledge learned across courses and present results to address a health/clinical policy. Introduction to management in health care Introduces the main principles of management and strategy and related issues that impact on organisational change, group decision making, innovation and leadership. Applies academic management knowledge to health care practice. Compulsory modules . Optional modules (required to take 3 of 6) . Quality and outcomes in cardiovascular sciences Provides an overview of the concept of quality, its key components, and its measurement in different health care systems. Offers a critical perspective on the literature evaluating quality improvement interventions focused on the cardiovascular disease field. Measuring health system performance Presents a framework to discuss the opportunities and challenges with performance measurement in health care. Focuses on the measurement instruments and analytic tools needed for performance measurement. Economic analysis for health policy Serves as an introduction to major developments in the economics of health and health care. Provides health care professionals with a strong understanding of the role economics can play in health policy and health system administration Financing health care Gives a thorough grounding in health financing policy. Focuses on the health financing functions of collecting revenue, pooling funds and purchasing services, as well as on policy choices concerning coverage, resource allocation and provider payment mechanisms. Systematic review and meta-analysis Covers the principles of reviewing and synthesizing the existing body of literature. Provides an overview of methods for quantitatively synthesizing multiple randomized controlled trials in meta-analysis. Research design for evaluating health programs and policies Provides a practical overview of the principles and models of evaluation, and the role of theories, concepts, and hypotheses. Covers study design choices in light of bias, validity and other design trade-offs. Economic evaluation in health care Focuses on analytic methods in the economic evaluation of health interventions. Provides a strong foundation in cost-effectiveness analysis of interventions used in long-term chronic illnesses. Behavioural science for health Introduces the main tools and principles of behavioural sciences and the key state-of-the-art applications to health economics, policy, and management. Applies behavioural science tools to concrete challenges in the health area. Using health economics to analyse and inform policy and practice Gives an overview on how health systems are constructed, and how the various parts of the system interact. Focuses on the role of regulation, resource allocation, payment arrangements, and the complexities of evaluating policy and performance. Principles of health technology assessment Introduces the role of Health Technology Assessment in health care reimbursement and coverage decision making. Covers the key operational modalities of health technology assessment, the different models of value assessment and how they link to decision-making. Dissertation Offers an opportunity to carry out independent study. Integrates approaches and knowledge learned across courses and present results to address a health/clinical policy. Introduction to management in health care Introduces the main principles of management and strategy and related issues that impact on organisational change, group decision making, innovation and leadership. Applies academic management knowledge to health care practice. With advanced training in outcomes research, policy, and health economics, course participants leave the program equipped with key skills to become the future champions of policy and management change in their clinics, hospitals, national and regional health systems, regulatory authorities, and even at the world stage. An expanding network of graduates are expected to take on roles in guideline development panels, health technology assessment committees, public-private research initiatives, consulting companies, and pharmaceutical, medical device, biotech, and big data and data analytics industries.20,21 Conclusion As health care costs continue to rise, cardiovascular medicine will undisputedly come under greater scrutiny over the next decade. London School of Economics and Political Science’s inter-disciplinary post-graduate training program developed in collaboration with the ESC is aimed at equipping health care professionals within cardiovascular medicine with a highly relevant skillset in social sciences. With such training, researchers, and practitioners from within the profession have an opportunity to become active voices and role models in discussions that affect every corner of medicine and its practice. Huseyin Naci PhD MHS Corresponding author Assistant Professor of Health Policy LSE Health, Department of Health Policy, London School of Economics and Political Science Tel: +44 207 955 6874 Email: [email protected] Paulus Kirchhof MD University of Birmingham Institute of Cardiovascular Sciences, SWBH and UHB NHS Trusts, Birmingham, UK Panos Vardas MD PhD Professor of Cardiology University of Crete Past President ESC Chief Strategy Advisor European Heart Agency Alec Vahanian University Paris VII Paris, France Jan Steffel MD Department of Cardiology University of Zurich, Switzerland Isabel Bardinet Executive Director of ESC Elias Mossialos MD PhD FRCP FFPH Department of Health Policy London School of Economics and Political Science. London, UK Conflict of interest: none declared. References References are available as supplementary material at European Heart Journal online. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Franciosi, Giorgio; Trunfio, Rafael; Ferrari, Enrico; Demertzis, Stefanos

doi: 10.1093/eurheartj/ehw395pmid: 27694192

The Jacoub technique for surgical management of a giant pulmonary artery (PA) aneurysm, has never been reported before. A 73-years-old hypertensive lady, with an abdominal aortic aneurysm of 45mm, underwent computed tomography scan (CAT scan), that revealed a concomitant main PA aneurysm of 65 mm diameter. Transthoracic echocardiogram (TTE) showed: normal biventricular function, pulmonary artery pressure, and a competent pulmonary valve. Conservative management was decided, with follow up every 6 months. Three years later, the patient was dyspneic on exercise. The abdominal aneurysm had progressed to 49mm. A repeat CAT scan confirmed PA trunk of 68×64 mm, right PA of 28.4 mm diameter, left PA of 30.5 mm (Panel 1). TTE showed an incompetent pulmonary valve, dilated right ventricle with reduced function (EF 45%), PA pressure 48 mm Hg. A preoperative coronary angiogram revealed three-vessels coronary disease. Open in new tabDownload slide Panel 1, Computed tomography scan showing the giant pulmonary aneurysm in coronal (A and B) and sagittal (C) planes. Panel 2, Intra-operative image showing the giant pulmonary aneurysm. Panel 3, Surgical technique representation. Panel 4, The final surgical result after pulmonary artery replacement, following the Yacoub s technique, and external stenting of vein grafts. Panel 5, Arterial wall staining with Alcian blue, showing degenerative myxoid alterations. Panel 6, Magnetic resonance video showing a competent pulmonary valve. Open in new tabDownload slide Panel 1, Computed tomography scan showing the giant pulmonary aneurysm in coronal (A and B) and sagittal (C) planes. Panel 2, Intra-operative image showing the giant pulmonary aneurysm. Panel 3, Surgical technique representation. Panel 4, The final surgical result after pulmonary artery replacement, following the Yacoub s technique, and external stenting of vein grafts. Panel 5, Arterial wall staining with Alcian blue, showing degenerative myxoid alterations. Panel 6, Magnetic resonance video showing a competent pulmonary valve. At sternotomy, the PA appeared dilated up to the bifurcation, with a transparent wall (Panel 2). Coronary grafts were performed first. Then, on bypass with a beating heart, the pulmonary artery was opened longitudinally. The leaflets were morphologically intact and symmetrical; a Yacoub procedure was deemed ideal, in order to preserve the native valve and fully exclude the diseased arterial tissue up to the main bifurcation (Panels 3–4). At post-operative TE eco, the pulmonary valve regurgitation was trivial. Home discharge was 7 days later. Histological examination showed a mixoid degenerated media, with sub-intimal fibrosis (Panel 5). At 2 months follow-up, the patient reported a significant improvement of symptoms, with absence of dyspnea. Magnetic Resonance Imaging (MRI) confirmed the absence of pulmonary regurgitation (Panel 6). Supplementary material is available at European Heart Journal online. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: [email protected].

Whitlock, Richard P; McClure, Graham R; Eikelboom, John W

doi: 10.1093/eurheartj/ehx367pmid: 29020261

This editorial refers to ‘Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation’†, by N.M. Korteland et al., on page 3370. Aortic stenosis is the most common form of valvular heart disease in the developed world, and valve replacement is still the standard treatment. Mechanical valves are generally preferred over tissue valves for younger patients with aortic stenosis because of their greater durability. Information provided on The American Heart Association website suggests that most manufactured mechanical valves ‘will last throughout the remainder of the patients’ lifetime’,1 but the life expectancy of younger patients with aortic stenosis is almost halved at the time of valve implantation.2 In this issue of the journal, Takkenberg and colleagues explore outcomes after bi-leaflet mechanical aortic valve replacement in younger patients by performing a meta-analysis of 29 observational studies published between 1995 and 2015 that involved 5728 patients aged 18–55 years (mean age 48 years).3 Their pooled results indicate early (<30 days) mortality of 3.15% and late (>30 days) mortality of 1.55%/year (of which 38.7% were valve related); and annual rates of thrombo-embolism of 0.90%, major bleeding of 0.85%, non-structural valve dysfunction of 0.39%, endocarditis of 0.41%, valve thrombosis of 0.14%, and re-intervention of 0.51%. The pooled mean follow-up was only 5.7 years, but using a microsimulation model they estimated age-specific life expectancy and lifetime risk of valve-related morbidity. For example, they estimated that a 45-year-old undergoing mechanical valve replacement has a life expectancy of 19 years (compared with 34 years in the general population), and lifetime risk of thrombo-embolism, bleeding, and re-intervention of 18, 15, and 10%, respectively. The results of Takkenberg and colleagues need to be cautiously interpreted because they are based on observational studies with substantial potential for selection, reporting, and publication bias, and on simulations that require assumptions about event rates beyond the observed follow-up period. Despite these potential limitations, their results are consistent with individual published reports and most probably provide the most reliable estimates of event rates and survival for younger patients undergoing mechanical aortic valve replacement What are the implications of these data for clinical practice? The durability of mechanical valves shown by Takkenberg and colleague supports their preferential use in younger patient, but there is clearly an urgent need to improve anticoagulant therapy because of the very high lifetime rate of thrombo-embolic and bleeding complications. Potential approaches to improving anticoagulant therapy might include increasing the quality of international normalized ratio (INR) control, reducing the intensity of anticoagulation in patients implanted with less thrombogenic valves, or testing of alternative agents that are more effective and safer. Randomized trials have demonstrated that the quality of vitamin K antagonist therapy can be optimized by self-monitoring and management by specialist clinics, but these approaches are resource-intensive, and even in the best of hands rarely achieve a time in therapeutic range >75%. Reducing the intensity of warfarin anticoagulation in patients implanted with less thrombogenic valves has had limited success. The PROACT trial conducted in 375 patients with an On-X mechanical aortic valve replacement showed that on a background of aspirin, lower intensity (INR 1.5–2.0) compared with standard intensity (INR 2.0–3.0) warfarin reduced bleeding without compromising efficacy. Despite this promising result, the annual rate of any bleeding with lower intensity therapy was still 2.74%/year and the composite of bleeding, thrombo-embolism, and thrombosis was 4.57%/year;4 these annual event rates remain a major concern for younger patients facing life-long anticoagulant therapy. Furthermore, targeting a lower INR range does not obviate the need for routine coagulation monitoring and lifestyle restrictions, and the teratogenicity of vitamin K antagonists is highly problematic for women of child-bearing age. Tecarfarin is a highly promising new vitamin K antagonist that is metabolized exclusively by carboxyl esterases, thereby eliminating some of the variability associated with the cytochrome-mediated metabolism of traditional vitamin K antagonists. By producing more stable anticoagulation, tecarfarin has the potential to reduce bleeding and thrombo-embolic complications, but this remains to be demonstrated in outcome studies.5 The attraction of non-vitamin K antagonist oral anticoagulants (NOACs) is that they have been shown in other clinical settings to be at least as effective as warfarin with less bleeding, and are much more convenient because they do not require routine coagulation monitoring. However, in patients with mechanical heart valves, the oral direct thrombin inhibitor, dabigatran etexilate, was less effective than warfarin for prevention of thrombo-embolic complications and produced more bleeding. Apixaban and rivaroxaban, which target coagulation factor Xa, have shown promise in pre-clinical mechanical heart valve studies,6 but human studies are yet to be performed. Based on emerging evidence suggesting that thrombosis in patients with mechanical heart valves results from upstream activation of the contact pathway through factor XII, other experimental drugs currently under development that selectively target factor XI or factor XII may prove successful for this indication. The most common alternative to a mechanical valve is a biological valve. Similar to mechanical valves, biological valve implantation is associated with reduced life expectancy in younger patients with advanced aortic valve disease.2,7,8 Thus, a 40-year-old patient undergoing biological valve implantation today has a 20 year reduction in life expectancy, and, after 20 years, only 38% will be alive and without re-operation for valve deterioration. The major attraction of a biological valve for patients is avoidance of the need for life-long anticoagulation. However, recent data suggest that subclinical biological valve thrombosis is much more common than previously thought, and is an important cause of adverse outcomes.9 Thus four-dimensional computed tomographic imaging has detected small thrombi in 7–10% of patients with a biological aortic valve replacement. These thrombi are believed to be associated with increased risk of both transient ischaemic attack and early valve degeneration. NOACs appear to be effective for the treatment of biological valve thrombi and are currently being tested in the ATLANTIS trial and Envisage-TAVI AF trials in patients undergoing transcatheter aortic valve implantation.10,11 However, even if thrombo-embolism can be prevented by anticoagulation, biological valves cannot be expected to provide life expectancy similar to that of the general population. The landscape of bioprosthetic valve replacement is changing, as techniques for valve-in-valve transcatheter aortic valve implantation (TAVI) evolve. Small studies have shown promising short-term mortality outcomes when compared with conventional re-operation, but further investigation is required to determine long-term outcomes.12 If the risk associated with structural valve dysfunction requiring re-operation is mitigated with low-risk re-intervention options, improvements in survival may be achieved. The only other option for younger patients requiring aortic valve replacement is pulmonary autograft (the Ross procedure). With this approach, the patient’s native pulmonary valve is autografted to the aortic position and a homograft bioprosthesis is implanted to the pulmonary position, where the lower pressures of the pulmonary circulation result in improved durability of the prosthesis. The Ross procedure was developed with the aim of providing a durable aortic valve substitute with optimal haemodynamics while avoiding the need for lifelong anticoagulation.13–15 The main disadvantages of the Ross procedure are its surgical complexity and the iatrogenic creation of pathology in the right ventricular outflow tract (RVOT) with associated risk of pulmonary homograft failure.16,17 Furthermore, TAVI has not been evaluated for re-intervention of the autografted valve. Unfavourable early results have further dampened enthusiasm for the Ross procedure, and very few surgeons have expertise in the technique. Nevertheless, some believe that failure to use the Ross procedure is a lost opportunity for younger patients with aortic valve disease.18 In 2009, Takkenberg and colleagues published a systematic review and meta-analysis of 39 studies involving 1749 patients undergoing the Ross procedure. The results suggested favourable rates of late mortality (0.64%/year), structural and non-structural valve dysfunction [left ventricular outflow tract (LVOT) site 0.78%/year, RVOT site 0.55%/year], and the composite of thrombo-embolism, bleeding, and valve thrombosis (0.36%/year), but high early mortality (3.2%). More recently, an analysis from the STS database involving 2188 patients with a mean age of 42 showed increased operative mortality with the Ross procedure when compared with conventional tissue aortic valve replacement [relative risk (RR) 3.0, 95% confidence interval (CI) 1.5–6.1, absolute risk 2.7%]. These results did not adjust for lack of surgical expertise at low volume Ross centres.19 On the other hand, large propensity-matched cohort analyses have suggested long-term survival with the Ross procedure comparable with that of the general population and lower rates of re-operation than biological and mechanical valve prosthesis.20–22 Similar results have been reported from a single-centre, single-surgeon randomized controlled trial comparing the Ross procedure with homograft surgery (n = 216).13 However, most of the data on the Ross procedure are of low quality, and lack of surgical expertise limits the generalizability of the results. Current ESC/EACTS Guidelines suggest that the main advantage of the Ross procedure is in children.23 Further evaluation of the Ross procedure for younger adults would ideally be performed using an expertise-based randomized controlled trial in which patients randomized to the Ross procedure are treated by surgeons with expertise in the surgical technique. In 2017, the role of valve replacement as the only definitive treatment for advanced aortic valve disease remains unquestioned, but outcomes are suboptimal. The choice of prosthesis is complex and must take into account patient characteristics and preferences as well as surgical expertise (Figure 1). There is, as of yet, no perfect replacement for the native aortic valve, and nowhere is this clearer than in younger adults. The work by Takkenberg and colleagues helps us to better appreciate the challenges and paves the way for intensified efforts to improve outcomes for these patients. Figure 1 Open in new tabDownload slide Factors influencing choice of valve prosthesis in younger patients with severe aortic valve disease. Figure 1 Open in new tabDownload slide Factors influencing choice of valve prosthesis in younger patients with severe aortic valve disease. Conflict of interest: R.P.W. reports personal fees from Armetheon, Boehringer Ingelheim, and Atricure outside the submitted work. G.R.M. has no conflicts to declare. J.E. reports honoraria and grant support from Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb/Pfizer, Daiichi Sankyo, Glaxo Smith Kline, Janssen, Sanofi Aventis, and Eli Lilly, as well as a personnel award from the Heart and Stroke Foundation. References 1 Types of Replacement Heart Valves . http://www.heart.org/HEARTORG/Conditions/More/HeartValveProblemsandDisease/Types-of-Replacement-Heart-Valves_UCM_451175_Article.jsp#.WQsn-bvyujk (4 May 2017). 2 Bourguignon T , Bouquiaux-Stablo A-L, Candolfi P, Mirza A, Loardi C, May M-A, El-Khoury R, Marchand M, Aupart M. Very long-term outcomes of the Carpentier–Edwards Perimount valve in aortic position . Ann Thorac Surg 2015 ; 99 : 831 – 837 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Korteland NM , Etnel JRG, Arabkhani B, Mokhles MM, Mohamad A, Roos-Hesselink JW, Bogers AJJC, Takkenberg JJM. Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation . Eur Heart J 2017 ; 38 : 3370 – 3377 . OpenURL Placeholder Text WorldCat 4 Puskas J , Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A, PROACT Investigators . Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial . J Thorac Cardiovasc Surg 2014 ; 147 : 1202 – 1210 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Whitlock RP , Fordyce CB, Midei MG, Ellis D, Garcia D, Weitz JI, Canafax DM, Albrecht D, Milner PG. A randomised, double blind comparison of tecarfarin, a novel vitamin K antagonist, with warfarin. The EmbraceAC Trial . Thromb Haemost 2016 ; 116 : 241 – 250 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Chan NC , Weitz JI, Eikelboom JW. Anticoagulation for mechanical heart valves: will oral factor Xa inhibitors be effective? Arterioscler Thromb Vasc Biol 2017 ; 37 : 743 – 745 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Bourguignon T , El Khoury R, Candolfi P, Loardi C, Mirza A, Boulanger-Lothion J, Bouquiaux-Stablo-Duncan A-L, Espitalier F, Marchand M, Aupart M. Very long-term outcomes of the carpentier–Edwards Perimount aortic valve in patients aged 60 or younger . Ann Thorac Surg 2015 ; 100 : 853 – 859 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Forcillo J , El Hamamsy I, Stevens L-M, Badrudin D, Pellerin M, Perrault LP, Cartier R, Bouchard D, Carrier M, Demers P. The perimount valve in the aortic position: twenty-year experience with patients under 60 years old . Ann Thorac Surg 2014 ; 97 : 1526 – 1532 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Holmes DR , Mack MJ. Aortic valve bioprostheses: leaflet immobility and valve thrombosis . Circulation 2017 ; 135 : 1749 – 1756 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis . ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02664649 (4 May 2017). 11 Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation (ENVISAGE-TAVI AF) . ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02943785 (5 May 2017). 12 Grubitzsch H , Zobel S, Christ T, Holinski S, Stangl K, Treskatsch S, Falk V, Laule M. Redo procedures for degenerated stentless aortic xenografts and the role of valve-in-valve transcatheter techniques . Eur J Cardiothorac Surg 2017 ; 51 : 653 – 659 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 13 El-Hamamsy I , Eryigit Z, Stevens L-M, Sarang Z, George R, Clark L, Melina G, Takkenberg JJM, Yacoub MH. Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomised controlled trial . Lancet 2010 ; 376 : 524 – 531 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Mazine A , David TE, Rao V, Hickey EJ, Christie S, Manlhiot C, Ouzounian M. Long-term outcomes of the Ross procedure versus mechanical aortic valve replacement: clinical perspective . Circulation 2016 ; 134 : 576 – 585 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Stelzer P. The Ross procedure: state of the art 2011 . Semin Thorac Cardiovasc Surg 2011 ; 23 : 115 – 123 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Stulak JM , Burkhart HM, Sundt TM, Connolly HM, Suri RM, Schaff HV, Dearani JA. Spectrum and outcome of reoperations after the Ross procedure: clinical perspective . Circulation 2010 ; 122 : 1153 – 1158 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Rahimtoola SH. Choice of prosthetic heart valve in adults an update . J Am Coll Cardiol 2010 ; 55 : 2413 – 2426 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Mazine A , Ouzounian M. Aortic valve replacement in young and middle-aged adults: looking beyond the tree that hides the forest . Ann Transl Med 2017 ; 5 : 92 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Reece TB , Welke KF, O’Brien S, Grau-Sepulveda MV, Grover FL, Gammie JS. Rethinking the Ross procedure in adults . Ann Thorac Surg 2014 ; 97 : 175 – 181 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Mazine A , David TE, Rao V, Hickey EJ, Christie S, Manlhiot C, Ouzounian M. Long-term outcomes of the Ross procedure versus mechanical aortic valve replacement: propensity-matched cohort study . Circulation 2016 ; 134 : 576 – 585 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Andreas M , Wiedemann D, Seebacher G, Rath C, Aref T, Rosenhek R, Heinze G, Eigenbauer E, Simon P, Ruetzler K, Hiesmayr J-M, Moritz A, Laufer G, Kocher A. The Ross procedure offers excellent survival compared with mechanical aortic valve replacement in a real-world setting . Eur J Cardiothorac Surg 2014 ; 46 : 409 – 414 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Sharabiani MTA , Dorobantu DM, Mahani AS, Turner M, Peter Tometzki AJ, Angelini GD, Parry AJ, Caputo M, Stoica SC. Aortic valve replacement and the Ross operation in children and young adults . J Am Coll Cardiol 2016 ; 67 : 2858 – 2870 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Vahanian A , Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schafers H-J, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012) . The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) . Eur J Cardiothoracic Surg 2012 ; 42 : S1 – S44 . Google Scholar Crossref Search ADS WorldCat Author notes " The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. " † doi:10.1093/eurheartj/ehx199. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Galassi, Alfredo R

doi: 10.1093/eurheartj/ehx674pmid: 29206966

The 10-year Anniversary celebrated at the University of Zurich ‘where it all began’, during the 6th European Live Summit on Retrograde CTO Revascularization  The 10-year anniversary of the EuroCTO Club was celebrated at the University of Zurich (USZ), Switzerland, in the same institution where Andreas Grüntzig performed the first coronary angioplasty 40 years ago. The occasion was the ‘6th European Live Summit on Retrograde CTO Revascularization’, a 2-day meeting held on 28–29 April 2017, directed and co-ordinated for the second time in the last few years by Professors Alfredo R. Galassi, Thomas F. Lüscher, George Sianos, and Oliver Gämperli. The course, approved by the EuroCTO Club and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) was based on 12 live Percutaneous Cardiovascular Interventions performed at the ‘Andreas Grüntzig Catheterization Laboratories’ of the USZ and attended by a large group of international cardiologists. With more than 30 lead operators and key opinion leaders from Europe, South Africa, Taiwan, USA, Canada, the Middle East, Japan, and Asia and 230 participants, the meeting featured a series of lectures and highly appreciated interactive discussions. The past When Andreas Grüntzig performed the first percutaneous coronary angioplasty on 16 September 1977 with his innovative balloon, he only went as far as treating proximal Type A lesions. Following the introduction of guide wires, more distal lesions also became accessible and the use of stents (medicated or plain) has made it possible in recent years to treat even the most complex lesions. However, the chronic total occlusion (CTO) of a coronary artery has remained a challenge for most interventional cardiologists. Andreas Grüntzig, interviewed in 1985 2 weeks before his death in an airplane accident, stated that at that time and for a long time to come, ‘total occlusions were going to be a real problem and until the problem was solved, percutaneous treatment of coronary heart disease would probably never be resolved’. Today, at least one out of every 10 patients undergoing percutaneous coronary intervention (PCI) has one or more CTOs.1 Although the anterograde approach with the new guiding wires developed primarily by Japanese companies or with dedicated systems such as the American dissemination and re-entry systems is successful in most cases, it has been apparent for the last 5 years that operators dedicated to CTOs must be trained in retrograde techniques; considering that a success rate of up to 90% is unattainable without adding that 15–20% success provided by the retrograde approach to lesions untreatable by anterograde techniques. Since its introduction in the 1990s, retrograde revascularization techniques have greatly improved procedural success rates but require considerable operator skills and a profound knowledge of PCI material even amongst experienced operators and therefore International Summits such as this one represent a key to learning new technology and improving clinical outcomes. In 2005, Osamu Katoh promoted the retrograde approach for CTOs by introducing the Controlled Antegrade Retrograde Subintimal Tracking (CART) technique.2 In 2010, the development of dedicated cross-linked microcatheters abolished the need for dilatation of the septal branches and retrograde dilatation of the occlusion by shifting to the reverse CART technique.3 In the following years, the increased varieties of guiding wires, microcatheters, and various techniques with dedicated devices have shifted the attention to an increasingly ‘safe’ retrograde procedure for those with the necessary expertise. It was during this Summit that it was possible to witness both live cases and lectures and how the evolution of these operating techniques have further changed the field of interventional cardiology, in technology as well as in safer and more effective approach methods. The present The congress opened with a new study on the classification of collateral circuits submitted by the Scottish group of James Spratt from NHS Forth Valley, UK, based on eight variables which could demonstrate that a score of >4.5 would be unfavourable to the success of crossing collaterals. Paul Khao of the Taiwan Medical School has shown how the recent introduction of new guides dedicated to the crossing of collateral circuits has changed the way of crossing them by increasing the probability of success and decreasing the risk of perforation of the collateral. Various reports from Japanese Mentors, Masahiko Ochiai, and Masahisa Yamane have shown the evolution of guiding wires up to the so-called ‘next generation’, an unthinkable achievement just a few years ago. Etzuo Tsuchikane from Toyohashi Heart Center, Japan, described the concept of contemporary reverse CART, where the focus of the technique is based on the primary ‘retrograde wiring’, avoiding the ‘kissing wire’ technique, performing anterograde preparation by Balloons of small size, and retrograde crossing through rigid guides directed towards the anterograde ball. Extremely interesting were the two luncheon panels, one on the novelties of retrograde material dedicated to the most powerful microcatheters, double-lumen microcatheters, and balloons for high-pressure dilation, and another on complications which produced a great debate. Another topic of great novelty was the revascularization procedure in patients with low ejection fraction, patients often rejected by surgeons due to a risk of mortality, presented by Alfredo Galassi as a group effort between the University of Catania, Italy, the USZ, Switzerland, and the University of Bad Krozingen, Germany, which showed how angioplasty in this field is safe and effective in improving the degree of ejection fraction and symptoms and ensuring a good prognosis in the medium term.4; The topic has been discussed with Swiss surgeons assisted by Francesco Maisano, Director of Cardiac Surgery at the USZ. Since its foundation in 2006 by European pioneers of the CTOs procedure Alfredo R. Galassi, Carlo DiMario, Gerald S. Werner, Darius Dudek, George Sianos, Nicolaus Reifart, Joachim Büttner, and Hans Bonnier, the EuroCTO Club (www.eurocto.eu) has made it its mission, to teach the most advanced procedural techniques and use the most innovative materials available on the market, to the community of interventionalists interested in these complex procedures. This event, along with the annual EuroCTO Club (ECC) meeting that this year was held in Berlin on 15–16 September, is a crucial meeting point for cardiologists who are dedicated to complex coronary lesions. Conflict of interest: none declared. References References are available as supplementary material at European Heart Journal online. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Ladeiras-Lopes, Ricardo

doi: 10.1093/eurheartj/ehx676pmid: 29206968

The field of Cardiovascular Medicine is a fast-growing and ever-changing field! We want to help you get all the evidence you need, as well as sharing it with your peers. The European Society of Cardiology (ESC) journals family is now present on Twitter (@ESC_journals). Follow us! Here you’ll find fresh, engaging, and relevant journal content. You already know Twitter (if you don’t, then you definitely should)! Character limits highlight the need for short, concise, relevant, and interesting messages. Using this social media platform is an unbeatable strategy to have access to high-quality scientific updates and lively clinical debates. You can share how you perform an interventional procedure, you can create a poll about a controversial clinical decision, and you can have access to that late-breaking clinical trial just being presented at a cardiology conference. Now, you can get the best from the ESC Journal Family on Twitter as well! Make us your one-stop social media destination for the latest cardiovascular science. Why bother? Here you’ll find a regular flow of the very latest science published in the ESC Journals Family You can engage with the authors, ask questions to the editors, debate with your peers and much more All highlighted articles will be freely accessible for at least 24 h after the tweet is posted! We are here for you! Your peers want to know what you think! Learn from the experts! Follow @ESC_journals and get involved! Conflict of interest: none declared. Cardio Pulse contact: Andros Tofield, Managing Editor. Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Ozkan, Judy

doi: 10.1093/eurheartj/ehx672pmid: 29206964

David Holmes is Professor of Medicine and Consultant Cardiologist at Mayo Clinic in Rochester, MN, USA. His interests include acute coronary syndromes, interventional cardiology, restenosis, and vascular biology. He has been the principal investigator or co-investigator in many significant clinical trials. He has also served in the US Navy at the National Naval Medical Center, MD, USA. In 2011, he was elected President of the American College of Cardiology. Holmes grew up in Chicago and found himself drawn to medicine after his father began to experience heart problems. Talking to, and observing his father’s cardiologist fired an interest and inspired Holmes to enrol at the Medical School of Wisconsin, Milwaukee. As a senior medical student, he secured a 2-month externship at the renowned Mayo Clinic in Rochester, MN, where he was assigned to the electrocardiographic laboratory—a core laboratory—dealing with many hundreds of electrocardiograms every day. He later completed an internship in Seattle, WA at Virginia Mason Hospital and at the end of this period he chose an internal medicine residency at Mayo which turned out to be a formative experience. Onward rounds, he was exposed to expert cardiologists who appeared to possess almost magical abilities to diagnose complex conditions through the laying on of hands and reading of patient history. At Mayo, a ‘cascade of events’ drew him closer to cardiovascular medicine, he says: ‘Initially, I was interested in vascular medicine which was very well-established in Rochester at that time, so I concentrated on that and then moved on to other aspects of cardiovascular disease including interventional cardiology, pacing, and finally electrophysiology’. Between 1976 and 1978 Holmes served with the US Navy as a cardiologist at the National Naval Medical Centre in Bethesda, MD and as an instructor at the newly-formed University of Health Sciences Military Medical School. After the Navy, he returned to Mayo for what he thought would be a short period prior to going into private practice. But the short period grew longer as he became absorbed and involved with pacemakers and electrophysiology. Together with a colleague he was one of the first cardiologists to fully implant a pacemaker in an adult and later in an 18-month-old child. Prior to that time, surgeons always fashioned the pacemaker pockets. He was appointed head of the electrophysiology laboratory and pacing before moving on to interventional cardiology. He headed up both interventional cardiology, the catheterization laboratory and pacing before becoming head of the catheterization laboratory exclusively for almost 20 years. He describes interventional cardiology as a series of wavefronts coming forward and opening up new possibilities. Holmes represented Mayo Clinic at some of the early meetings in Switzerland where Andreas Grüntzig was demonstrating his new interventional techniques. He describes the sessions as dazzling, not just because of the personalities involved, but also because of the possibilities the new techniques offered patients and the futuristic vision that was on the show. For Holmes, the vision continues and the quest goes on. He draws parallels between tuberculosis (TB) and cardiovascular disease and muses that we could someday see the latter broadly eradicated. ‘Early in my career, I saw how we treated TB until there was no need for specialist physicians working in that area. Although this is clearly an unattainable goal, there will be aspects of the cardiovascular disease that we will be able to eliminate’. Although working with new devices and therapies is exciting for a cardiologist, Holmes believes that there is more to clinical medicine than treating disease—it is also about the people. He tells a story about an elderly woman who attended a consultation and how much of the consultation time passed in the discussion of rhubarb. The patient was an expert on, and cultivated a species of giant rhubarb, and had become well-known in her local area as an award-winning grower. The rhubarb was important because, ‘It made the whole consultation a broad event about a human being who happened to have a disease, not just a disease -atrial fibrillation in this case—and from there it was easy to flow into discussing her condition and how we might treat her. It is those sorts of things that make medicine special and make you get up in the morning wondering what is next. For me, medicine is a tremendous platform for making a difference, on an individual, family, societal, and global level’. Holmes believes that an individual’s career is shaped as much by the era in which they operate and the unmet needs of contemporary clinical medicine, as much as it is by personal preference or direction. ‘I started out at the beginning of the era of interventional cardiology and electrophysiology where we were studying basic mechanisms of disease for arrhythmias and basic mechanisms of disease of coronary artery disease and then identifying ways to treat that. It was a matter of focusing on those areas that were growing and where you had a chance to make a difference to try to move, mould, or lead the field in whatever way you could. You obviously select the journey based on your interests, but your interests are often piqued by mentors or specific patients who present with a problem. So, these interactions open up the horizon for growth’. Clinical education, training, and mentorship are facets of the job that Holmes takes seriously. He emphasises the need to pass the torch on to the next generation. ‘When you look back on your own career you can identify those persons who turned on a light which continued to shine on a pathway that you followed. It’s terribly important in all places of learning to turn that light on and expose young kids to intellectual stimulation so that a light comes on in their lives and they become driven to make a difference. For me, the ability to make a difference for patients and for those young people who will grow up to be their physicians is an unbelievably rewarding experience’. His advice to young people is to identify role models, listen to them, interact with them, find out what has made their light go on, and then fashion your own career with bits and pieces borrowed or given by these mentors. He says: ‘There are a handful of people here in Rochester and around the world that I could identify, that exemplify creativity, problem-solving, excitement, passion, integrity, and honesty and these are the qualities that you should identify and then internalise, so that you can then externalise them for the next generation. It is a circle of giving and borrowing and creating and expanding and healing’. For some years Holmes has had his eye on regenerative medicine as an area of huge potential for cardiovascular medicine, but one that was always tantalizingly ‘just around the corner’. He suggests that the dawn of regenerative medicine is now at the corner offering futuristic concepts of ‘spare parts’ and such things as arteries grown to order. His future path is, he says a work in progress and he remains happy to be allowed to follow his interests on the journey. Conflict of interest: none declared. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Lüscher, Thomas F

doi: 10.1093/eurheartj/ehx681pmid: 29206969

With the ageing population, the number of patients with aortic stenosis is increasing steadily.1 Many of these elderly patients have co-morbidities and are at increased risk.2,3 Implantation of an artificial valve, with either a transcatheter valve or a mechanical surgical valve or bioprosthesis, improves their symptoms and overall survival; however, certain risks remain such as thrombo-embolism, endocarditis,4 and valvular dysfuncton.5,6 In their review article entitled ‘Thrombo-embolic prevention after transcatheter aortic valve implantation’,7 Pascal Vranckx and colleagues from the Hartcentrum Hasselt in Belgium address one of these issues. They remind us that the rapid technological evolution from early to current-generation transcatheter aortic valve implantation or TAVI systems with low-profile delivery catheters, bioprosthetic valves with proven midterm durability, and improved positioning and retrieval features have facilitated their use and improved outcomes, and further improvements are under way.8 However, peri-procedural and long-term thrombotic and bleeding events after TAVI and surgical aortic valve replacement remain a concern, particularly as the type and duration of the optimal antithrombotic strategy remain unclear. This review provides an overview of recent insights in this field, and highlights current and future antithrombotic trials focusing on optimizing outcomes in patients undergoing TAVI. In patients with aortic stenosis, risk stratification for aortic valve replacement relies mainly on valve-related factors,3,9,10 symptoms, and co-morbidities.11,12 The prognostic impact of extravalvular cardiac damage prior to aortic valve replacement on clinical outcomes is poorly understood. In a FAST TRACK manuscript entitled ‘Staging classification of aortic stenosis based on the extent of cardiac damage’, Philippe Généreux and colleagues from the Cardiovascular Research Foundation in New York, USA sought to define a staging system characterizing the extent of extravalvular cardiac damage and to study its prognostic implication after aortic valve replacement.13 Patients with severe aortic stenosis from the PARTNER 2 trials were pooled and classified according to the presence or absence of cardiac damage as detected by echocardiography prior to aortic valve replacement: no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4; Figure 1). In 1661 patients with sufficient echocardiographic data, 2.8% were classified as Stage 0, 12.8% as Stage 1, 50.8% as Stage 2, 24.9% as Stage 3, and 8.7% as Stage 4. One-year mortality steadily increased from 4.4% in Stage 0, to 9.2% in Stage 1, 14.4% in Stage 2, 21.3% in Stage 3, and 24.5% in Stage 4. The extent of cardiac damage was independently associated with increased mortality after aortic valve replacement, with a hazard ratio of 1.46 for each increment in stage. Thus, this newly described staging classification objectively characterizes the extent of cardiac damage associated with aortic stenosis and has important prognostic implications for clinical outcomes after aortic valve replacement. Figure 1 Open in new tabDownload slide Cardiac stratification of aortic stenosis based on the extent of cardiac damage. LA, left atrial; LV, left ventricular; RV, right ventricular (from Généreux P, Pibarot P, Redfors B, Mack MJ, Makkar RR, Jaber WA, Svensson LG, Kapadia S, Tuzcu EM, Thourani VH, Babaliaros V, Herrmann HC, Szeto WY, Cohen DJ, Lindman BR, McAndrew T, Alu MC, Douglas PS, Hahn RT, Kodali SK, Smith CR, Miller DC, Webb JG, Leon MB. Staging classification of aortic stenosis based on the extent of cardiac damage. See pages 3351–3358). Figure 1 Open in new tabDownload slide Cardiac stratification of aortic stenosis based on the extent of cardiac damage. LA, left atrial; LV, left ventricular; RV, right ventricular (from Généreux P, Pibarot P, Redfors B, Mack MJ, Makkar RR, Jaber WA, Svensson LG, Kapadia S, Tuzcu EM, Thourani VH, Babaliaros V, Herrmann HC, Szeto WY, Cohen DJ, Lindman BR, McAndrew T, Alu MC, Douglas PS, Hahn RT, Kodali SK, Smith CR, Miller DC, Webb JG, Leon MB. Staging classification of aortic stenosis based on the extent of cardiac damage. See pages 3351–3358). Over the last 15 years, many valve models for TAVI have been developed.14 A major step forward to improve acute results was the development of retrievable valves. One of them, the Lotus® Valve by Boston Scientific, has been studied by Volkmar Falk and colleagues from the German Heartcenter Berlin in Germany in their article ‘Safety and efficacy of a repositionable and fully retrievable aortic valve used in routine clinical practice: the RESPOND study’.15 RESPOND was a prospective, open-label, single-arm study evaluating outcomes following TAVI with the repositionable and fully retrievable Lotus Valve in 996 patients with aortic stenosis. Their mean age was 81 years and STS score was 6.0. Repositioning was attempted in 29.2% of patients, with 99% success. The rate of all-cause mortality in the intent-to-treat population at 30 days was 2.6% and the 30-day overall and disabling stroke rates were 3.0% and 2.2%, respectively. However, the 30-day pacemaker implantation rate was 30% in all patients, and 35% in pacemaker-naïve patients. Mean aortic valve gradient declined from 38 mmHg at baseline to 11 mmHg, and aortic valve area increased from 0.7 cm2 at baseline to 1.8 cm2 at discharge. Paravalvular leaks were absent or trace in 92%, with none having had severe leaks and the remainder having mild or moderate leaks. Thus, RESPOND confirms the safety and efficacy of TAVI with the Lotus Valve in routine clinical practice, but documents an unacceptably high pacemaker rate. These aspects are further discussed in an Editorial by Corrado Tamburino from the University of Catania in Italy.16 Younger patients requiring aortic valve replacement are still considered candidates for surgery. Nevertheless, the choice of the valve type remains a challenge and those receiving mechanical valves are prone to anticoagulation-associated bleeding,17,18 while those receiving bioprosthesis may require a second operation after some years due to valve degeneration.19 Thus, the choice of the best valve remains an issue20 which is addressed in a research article entitled ‘Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation’, by Johanna J.M. Takkenberg and colleagues from the Erasmus University Medical Center in Rotterdam, The Netherlands.21 To that end, a systematic review was conducted for papers reporting clinical outcome after aortic valve replacement with bileaflet mechanical valves, with a mean patient age of ≥18 and ≤55 years, published between 1995 and 2015. Twenty-nine publications, encompassing a total of 5728 patients with 32 515 patient-years of follow-up, were included. Mean age at surgery was 48.0 years, early mortality risk was 3.15%, and late mortality risk was 1.55%/year (Figure 2). Of note, only 38.7% of late deaths were valve related. Thrombo-embolism rate was 0.90%/year, major bleeding 0.85%/year, non-structural valve dysfunction 0.39%/year, endocarditis 0.41%/year, and valve thrombosis 0.14%/year; structural valve deterioration did not occur, but the reintervention rate was 0.51%/year, mostly due to non-structural valve dysfunction and endocarditis. Thus, outcome after mechanical aortic valve replacement in non-elderly adults is characterized by suboptimal survival and considerable lifetime risk of anticoagulation-related bleeding, but also reoperation. Hence, the risks and benefits of both mechanical and biological valve options must be discussed with patients in a mutual decision-making process. These surprising findings are put into context in a comprehensive Editorial authored by John W. Eikelboom from McMaster University in Hamilton, Ontario, Canada.22 Figure 2 Open in new tabDownload slide Microsimulation-based age-specific life expectancy and lifetime risk of valve-related morbidity. AVR, aortic valve replacement (from Korteland NM, Etnel JRG, Arabkhani B, Mokhles MM, Mohamad A, Roos-Hesselink JW, Bogers AJJC, Takkenberg JJM. Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation. See pages 3370–3377). Figure 2 Open in new tabDownload slide Microsimulation-based age-specific life expectancy and lifetime risk of valve-related morbidity. AVR, aortic valve replacement (from Korteland NM, Etnel JRG, Arabkhani B, Mokhles MM, Mohamad A, Roos-Hesselink JW, Bogers AJJC, Takkenberg JJM. Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation. See pages 3370–3377). The issue is complemented by a Special Article entitled ‘Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)’ by Davide Capodanno and colleagues from Ferrarotto in Catania, Italy.23 This consensus statement provides a proposal for the standardization of endpoint definitions of future studies on long-term durability of transcatheter and surgical bioprostheses. The document, summarizing the efforts of a task force appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), is endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). The editors hope that readers of this issue of the European Heart Journal will find it of interest. References 1 Baumgartner H , Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, Iung B, Lancellotti P, Lansac E, Munoz DR, Rosenhek R, Sjogren J, Tornos Mas P, Vahanian A, Walther T, Wendler O, Windecker S, Zamorano JL. 2017 ESC/EACTS Guidelines for the management of valvular heart disease . Eur Heart J 2017; 38 : 2739 – 2791 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Wendler O , Schymik G, Treede H, Baumgartner H, Dumonteil N, Neumann FJ, Tarantini G, Zamorano JL, Vahanian A. SOURCE 3: 1-year outcomes post-transcatheter aortic valve implantation using the latest generation of the balloon-expandable transcatheter heart valve . Eur Heart J 2017 ; 38 : 2717 – 2726 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Abramowitz Y , Kazuno Y, Chakravarty T, Kawamori H, Maeno Y, Anderson D, Allison Z, Mangat G, Cheng W, Gopal A, Jilaihawi H, Mack MJ, Makkar RR. 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OpenURL Placeholder Text WorldCat 22 Whitlock RP , McClure GR, Eikelboom JW. Aortic valve replacement in younger patients . Eur Heart J 2017 ; 38 :3378–3381. OpenURL Placeholder Text WorldCat 23 Capodanno D, , Petronio AS,, Prendergast B,, Eltchaninoff H,, Vahanian A,, Modine T,, Lancellotti P, Sondergaard L,, Ludman PF,, Tamburino C,, Piazza N, Hancock J,, Mehilli J,, Byrne RA,, Baumbach A,, Kappetein AP,, Windecker S,, Bax J,, Haude M. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) . Eur Heart J 2017 ; 38 :3382–3390. OpenURL Placeholder Text WorldCat Author notes " With thanks to Amelia Meier-Batschelet for help with compilation of this article. 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