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CardioPulse Articles‘Meet the Legends’ programme at European Society of Cardiology Congress 2013Archives des Maladies du Cœur et des Vaisseaux-PratiqueCardioPulse Survey series: UkraineThe strengths and limitations of the Ukrainian Healthcare systemBook ReviewFast Facts: ObesityNeurological complications in infective endocarditis

DOI: http://dx.doi.org/10.1093/eurheartj/eht446 3461-3468 First published online: 1 December 2013

‘Meet the Legends’ programme at European Society of Cardiology Congress 2013

This innovative session of the European Society of Cardiology was designed for young cardiologists and the general audience to interact with key figures who have shaped present-day cardiology

A new session was presented at the ESC Congress 2013, Amsterdam: ‘A day with the Legends’. Four renowned cardiologists were chosen as speakers to give insights into their own clinical and research contributions. Keith Fox, the ESC's Congress programme chairperson, said of the programme, ‘the whole idea of this new session is to give trainees a feel for the pathways these eminent cardiologists have taken. Hearing these legends will hopefully encourage young cardiologists to take control of their own future. The aim is to inspire them when starting their careers, to be proactive and believe that they too can shape the future of cardiology’. Each of the presentations was followed by an open forum where delegates quizzed these heroes.

The ESC ‘Legends’ chosen for 2013 were:

  • A. John Camm: spoke on ‘The rise and fall of antiarrhythmic drugs’.

  • Bernard Gersh: presented ‘Evidence and Uncertainties in the Management of Symptomatic Hypertrophic Cardiomyopathy’.

  • Frans Van de Werf: discussed ‘The history of coronary reperfusion in STEMI’.

  • Lars Wallentin: considered ‘The evolution in knowledge of the pathogenesis and treatment of ACS’.

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Alan John Camm, MD PhD FESC

During the European Society of Cardiology Congress 2013 in Amsterdam, we were honoured to listen to Prof. A. John Camm from University of London, who gave an extraordinary lecture entitled ‘The rise and fall of antiarrhythmic drugs’ during one of the ‘Meet the Legends’ sessions.

Prof. Camm is a worldwide renowned expert in arrhythmias, atrial fibrillation, ventricular tachycardia, ablation, devices, antiarrhythmic drugs, and anticoagulation, to name but a few of his areas of expertise.

Prof. Camm holds the European Society of Cardiology Gold Medal (awarded 2005), given to ‘exceptional cardiologists for their contribution to medicine’ and the British Cardiovascular Society Mackenzie Medal (awarded 2008), given annually for ‘outstanding service to British cardiology’.

Among his numerous activities, he is also an editor-in-chief of Clinical Cardiology and EP-EuroPace, and an editor of the European Heart Journal and the European Society of Cardiology Textbook of Cardiovascular Medicine.

During his lecture, Prof. Camm recapitulated the fascinating journey that cardiology went through searching for the Holy Grail for the treatment of supraventricular and ventricular arrhythmias. Although several antiarrhythmic drugs have been developed, only a few of them exhibited the acceptable safety and efficacy to be implemented in clinical practice. Some, which were introduced with the great hope that they would revolutionize the modern treatment of arrhythmias, disappointingly resulted in increased cardiovascular mortality.

The challenging area is the treatment of arrhythmias in a growing population of patients with heart failure as well as those with atrial fibrillation. In the contemporary era, the position of antiarrhythmic drugs has to be confronted with the rapidly developing invasive procedures aimed to ablate the substrate of arrhythmias and other implanted devices.

As depicted during the discussion, there is also progress occurring in imaging techniques, e.g. assessing the magnitude of myocardial fibrosis, which, in the future, may help cardiologists to identify patients who could most benefit from invasive procedures.

During recent decades, the role of antiarrhythmic drugs has markedly changed but should not be underestimated as, in particular, there are novel molecules appearing on the horizon. Both pharmacological and non-pharmacological developments in arrhythmology, along with numerous important questions which remain to be answered, make this field extremely exciting, particularly for young cardiologists.

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Bernard Gersh, MD PhD FESC

Prof. Bernard Gersh, the first ‘Cardiology Legend’ speaker of the ESC Congress 2013 has a life-long career that spans three continents: from Zambia and South Africa, to Oxford University as a Rhode Scholar, and then in the USA, mostly at the Mayo Clinic.

Known as one of the world's premier academic cardiologists, he has combined superior teaching skills with important clinical research. Bernard Gersh is a worldwide expert in several fields from coronary artery disease to clinical electrophysiology and cardiomyopathies.

For this ‘Meet the Legends’ session he chose to speak about the ‘Evidence and Uncertainties in the Management of Symptomatic Hypertrophic Cardiomyopathy (HCM)’. In this exciting and vivid lecture, he began by focusing on the three key elements of HCM management: (i) avoiding competitive sports, volume depletion, and isometric exercise; (ii) screening first-degree relatives; (iii) assessing the risk for and preventing sudden cardiac death. The control of symptoms should also be a mainstay, first with medical therapy (using ‘drugs that are almost 50 years old’) and, when this fails, with interventions such as surgical myectomy or alcohol septal ablation (ASA).

According to B. Gersh it is curious that we practically have no randomized trials in HCM. Nevertheless, the observational data suggest that, in experienced centres, myectomy is a very safe procedure, can improve symptoms, and probably can alter the long-term natural history of obstructive HCM. Interestingly, the history of surgical myectomy is also one of the greatest ironies in CV disease, because its inventor, Dr Andrew G. Morrow, probably, died of HCM.

Alcohol septal ablation is performed mainly in Europe but there are some concerns. The rate of procedural complications exceeds that of myectomy (due to the risk of pacemaker placement) and the long-term outcome remains unknown. Registry data suggest that the risk of arrhythmias after ASA may not be negligible (4–5%/year), but more studies are needed. Nevertheless, in elderly patients with comorbidities ASA can be a better alternative.

Answering questions from the audience, Prof. Gersh addressed the genotype-phenotype interaction as one of the greatest challenges and unknowns in HCM.

Looking into the future of Cardiology and Cardiovascular Research, he concluded by reinforcing the need for more investment to diminish the inequalities of access to cardiovascular care worldwide, with a special focus on fighting the CV epidemic that is rising in underdeveloped countries.

Dr Gersh's interests in cardiology are many, as are his publications. He has written 708 articles and 133 book chapters, and is the editor of 13 books and on the editorial board of 25 journals including the EHJ. He is a member of many Boards and has served on many Steering Committees. Currently, he is Chairman of the WHO Cardiovascular Working Group on ICD 11 Reclassification.

Among the honours Dr Gersh has received are the 2004 Distinguished Achievement Award of the AHA Council of Clinical Cardiology and the 2007 ACC Distinguished Service Award. He received a PhD (Honorius causa) from The University of Coimbra, Portugal in 2005. Dr Gersh is also the recipient of the 2012 James B. Herrick award.

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Lars Wallentin, MD PhD FESC

Lars Wallentin is one of the most outstanding figures of cardiology. He was appointed as Head of the Department of Cardiology and first Professor of Cardiology at University Hospital, Uppsala, Sweden, in 1991. He founded the Cardiothoracic Centre at Uppsala in 1994. Since then, the impact of his work on Swedish and European cardiology has grown without interruption, and he is, now, one of the most respected personalities in the world of cardiology.

He is a member of numerous research councils, medical societies, task forces, and editorial boards, and is an expert for the Swedish Board of Health and Welfare. From 1998 to 1999, Prof. Wallentin was President of the Swedish Cardiac Society, and from 2000 to 2002, he founded and served as President of the Swedish Heart Association. He founded and became the first Director of Uppsala Clinical Research Centre (UCR) in 2001 and also the first Leader of the UCR Competence Centre for National Quality Registers in 2002. He has received several prestigious research awards and was honoured with the European Society of Cardiology Gold Medal in 2010.

Lars Wallentin is best known for his multiple contributions to cardiovascular research. His work has been particularly relevant in the development of new antithrombotics for the prevention or treatment of cardiovascular diseases, such as low-dose aspirin, low molecular weight heparin, and ticagrelor for the treatment of ACS, and dabigatran and apixaban for the prevention of embolic events in patients with atrial fibrillation. His research also played a pivotal role in improving risk stratification in ACS and determining the role of an early invasive strategy as the preferred approach for patients with NSTEACS. He and his team also made important contributions in other research fields, such as new biomarkers and genetics. Furthermore, his group has pioneered the development and implementation of continuous Internet-based national quality registers for monitoring and improvement of the quality of cardiac care and also for use as research tools.

During ESC Congress 2013 in Amsterdam, Prof. Wallentin, in his ‘Meet the Legend’ presentation, talked about the historical evolution in the knowledge of pathogenesis and treatment of ACS. One of the points addressed during the session was the new opportunities for research with the use of national registries (such as the Swedish one that he founded and coordinated), firstly, as a tool of research and, secondly, as a mechanism to encourage hospitals to improve their results. At this year’s' ESC Congress the SwedeHeart registry and UCR presented the first large-scale registry-based, prospective randomized clinical trial—a new ground-breaking concept that will probably evolve to become a widely used complement to the classic randomized clinical trials.

Asked about the burning issues to be resolved in cardiology, he pointed out an absence of people willing to invest time in research and a need to find new enthusiastic leaders. He also pointed out that the current economic situation is hampering the implementation of new, more effective, safer, and convenient medical treatments.

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Frans Van de Werf, MD PhD FESC (credit Sam C. Rogers)

Frans Van de Werf is professor of cardiology at the Department of Cardiovascular Medicine at the University of Leuven, Belgium, where he has worked for almost his entire career, and has become one of the world's leading experts in thrombolytic therapy.

He has served as a visiting professor in a number of institutions, including the Cleveland Clinic Foundation, Massachusetts General Hospital, Harvard Medical School, and the Mayo Clinic.

Dr Van de Werf was the editor-in-chief of the European Heart Journal from 2003 until 2009 and is on the editorial boards of many journals including the New England Journal of Medicine (NEJM), Circulation, Nature Review Cardiology, International Journal of Cardiology, Coronary Artery Disease, Japanese Circulation Journal, Cardiology in Review, and others. He is a past recipient of the International Roche Chair in Cardiology and the 5-yearly Joseph Maisin award of the Fund of Scientific Research of Belgium and a past president of the Belgian Society of Cardiology. He was the chairman of the European Society of Cardiology programme committee for the Annual Congresses of 1996 and 1997. As chairman of the Publications Committee, he served on the Board of the European Society of Cardiology from 2003 to 2009. He was the chairman of the European Society of Cardiology Task Force for updating the guidelines for treatment of ST-elevation acute myocardial infarction.

In November 2006, he gave the Paul Dudley White International Lecture at the Scientific Sessions of the American Heart Association in Chicago. He received the Gold Medal of the European Society of Cardiology in 2009. In September 2010, he again joined the ESC Board as chairman of the ESC Committee for European Affairs.

Dr Van de Werf's research interests include coronary reperfusion, antithrombotic therapies, left ventricular function, and cardiac imaging. He is currently a Fellow of the European Society of Cardiology, the American College of Cardiology, and the American Heart Association. He is the author or co-author of >600 peer-review articles.

During ESC Congress 2013 in Amsterdam, Dr Van de Werf, in his “Meet the Legend” presentation, spoke about the history of coronary reperfusion and STEMI. He pointed out that the in-hospital mortality rate after myocardial infarction has dropped from 15 to 2.5% during the course of his career. He also believes that primary percutaneous coronary intervention (PCI) will remain the key reperfusion therapy in most countries. However, as demonstrated in a recently published paper by Bates1 in the NEJM, we now have to focus on the delay between the onset of symptoms and the arrival at the door of the PCI hospital. In some countries, fibrinolysis with an invasive follow-up, the pharmaco-invasive approach, will play a role (cfr STREAM study).2

Michal Pazdernik, MD

Institute for Clinical and Experimental Medicine, Prague, Czech Republic, pazdernik.michal{at}gmail.com

Steen Dalby Kristensen, MD, FESC

Department of Cardiology, Aarhus University Hospital, Denmark, steendk{at}dadlnet.dk


Archives des Maladies du Cœur et des Vaisseaux-Pratique

A Journal published by the French Society of Cardiology in French, devoted to continuous medical education

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The first cardiovascular journal, Archives des Maladies du Cœur, des Vaisseaux et du Sang, launched in 1908 by Louis-Henri Vaquez consisted of three main sections: original articles, reviews, and comments on other cardiovascular publications and books. It became the official journal of the French Society of Cardiology (SFC) after the Society was formed in 1937 and was subsequently published every month in French until 2008.

Facing the expanding requirements for postgraduate continuous medical education (CME) of cardiovascular physicians and in consideration of the anticipated limited progression in the impact factor that was expected with a publication exclusively in French, the SFC revisited its editorial policy in 2008. Accordingly, the journal was divided into a new publication in English, Archives of Cardiovascular Diseases, in which original contributions are published and a CME-devoted journal published in French, Archives des Maladies du Coeur et des Vaisseaux-Pratique (AMCVP).

Continuous medical education contents of AMCVP are scheduled in thematic issues focusing on evolving fields of cardiovascular diseases and related management. The Editorial board, which is nominated for 4 years by the board of SFC, includes Jean-Yves Artigou, Directeur du Comité de rédaction, Jean-Jacques Monsuez, Rédacteur en chef, and 12 members, all selected for their highly recognized competence in a specific cardiovascular area: Jean-François Aupetit (heart failure), Richard Brion (exercise, competition, rehabilitation), Didier Carrié (coronary artery disease), Michel Desnos (cardiomyopathies and myocardial diseases), Hervé Douard (prevention and public health education), Albert Hagège (cardiomyopathies, and also current President of SFC), Daniel Herpin (hypertension), Antoine Leenhardt (arrhythmias, pacing, electrophysiology), Jean-Jacques Mercadier (basic cardiology), Alain Pavie (cardiac surgery), Christian Rey (congenital heart diseases), and Raymond Roudaut (valvular heart diseases) (Figure 1).

Figure 1

Rita Salvatore (secretary), and Jean-Yves Artigou (chairman of editorial board).

Each issue is organized as follows:

  • a core seminar consisting of two state of the art reviews, a case-report and a technical check-list for practice, all focusing on the same CME topic;

  • an article on cardiovascular pathophysiology ‘basic science for cardiologists’;

  • comments on relevant papers from other cardiovascular journals ‘revue de presse’;

  • information and comments on recently released guidelines by SFC, ESC, and endorsement of ESC Guidelines by the SFC;

  • news about SFC academic activities;

  • a short article on the history of cardiology.

Archives des Maladies du Coeur et des Vaisseaux-Pratique is widely distributed. The objectives of the Editorial board and of the SFC board are to target a broad readership of French-speaking cardiologists in France as well as throughout the francophone countries, which also includes large cardiology teams in Northern and sub-Saharan Africa. Online access to Archives-Pratique (which is also included with regular individual subscription) has proved very useful in making the contents widely available abroad. An average of 16 000 articles are downloaded annually.

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CardioPulse Survey series: Ukraine
The strengths and limitations of the Ukrainian Healthcare system

Prof. Alexander Parkhomenko FESC, vice-president of the Ukrainian Association of Cardiology, answers a short healthcare questionnaire


Nations around the world struggle to deliver the promises of modern medicine to their populations. No one knows the ‘right’ answer and yet many challenges are remarkably similar across countries. For instance, we live in an era of extraordinary possibility and technological complexity in clinical medicine. This has led to better results for our patients, but also escalating costs and strain on our shared resources.

Although healthcare reform has received greatest attention in the USA, it is no stranger to Europe. Despite sharing fairly consistent goals, Europe's healthcare systems remain varied and distinct. Each country's approach differs as much as their history, culture, and geography. In the UK, global budgets and public providers are distinguishing characteristics. In comparison, the German healthcare system is decentralized with a mixture of public and private funding sources. Each of these reflect widely divergent choices that impact on fundamental issues for their populations, such as access to care and out-of-pocket costs.

We believe lessons can be learned from this ‘natural laboratory’ of Europe, particularly in cardiovascular medicine where there has been simultaneous growth in evidence-based medicine and high-end services. Accordingly, we are asking cardiovascular leaders from several European and non-European countries to briefly describe the greatest strengths and limitations of their healthcare systems, as well as its most important challenges for the next decade.

We think you will find the answers enlightening and agree that such collective experiences have much to teach the world. We also are confident that you will enjoy reading this series as much as we enjoyed working on it.

Brahmajee Nallamothu MD and Thomas F. Lüscher MD

1. What is the greatest strength of the Ukraine's health system in tackling cardiovascular disease (e.g. prevention, acute treatment, long-term treatment)?

During last decade significant progress has been made in targeting prevention and management of cardiovascular disease in the Ukraine.

Recent implementation of state programmes on hypertension and population research improved detection of hypertension and facilitated primary and secondary prevention measures. State programmes on pre-hospital thrombolysis and primary PCI (stent for life initiative) in STEMI patients were started and are currently working successfully.

Among major achievements of the Ukrainian healthcare system is a programme on the diagnosis of and surgical care for prenatal congenital heart, which is organized at a high technical level and is accessible to all paediatric patients.

2. What is its biggest weakness?

Our hospital registry data suggest that, in post-STEMI patients,' adherence to therapy and rates of percutaneous and surgical revascularization after discharge are very low. Only 30–40% of patients receive recommended medical therapy and just 5% of patients underwent CABG during 3 years of follow-up. Hence, not only expensive procedures (coronary stenting, valve replacement procedures, etc.) but also evidence-based long-term treatment remain inaccessible to all patients. Unfortunately, due to financial obstacles and lack of an efficacious insurance system, medical therapy of adults and surgical procedures in non-emergency cases rely solely on patients' ability to cover their own costs.

3. What is being done to measure and improve the quality of care in cardiovascular disease?

In terms of primary prevention Ukrainian Association of Cardiology actively promotes healthy lifestyles and early detection of cardiovascular disease and predisposing risk factors.

Ministry of Health Quality improvement initiatives are also devoted to adherence to CVD management guidelines and implementation of treatment protocols. Quality improvement also targets patient's’ compliance and education.

The quality of cardiovascular disease management is controlled by morbidity and mortality reports via surveys and analysed by local healthcare authorities.

4. What is being done to control costs?

Expenditure for the management of cardiovascular disease is usually controlled at a local level and conforms to a healthcare budget. Medical and surgical care remain underfunded in most regions of the Ukraine.

Partial healthcare expenditure is controlled and covered by private insurance companies.

During the last decade emphasis has been on improving in-hospital care and reducing hospital stay, disability, and related costs.

5. How does the Ukraine address cardiovascular preventive services?

Prevention of CVD is addressed to some extent at the state level. One of the significant recent measures undertaken is a tobacco-cessation programme, which includes providing mandatory information about the harmful effects of smoking on cigarette packs.

Generally, preventive services are not widely available in Ukraine, especially in rural areas. The Ukrainian Association of Cardiology and Department of Population Research of the Ukrainian Institute of Cardiology are leading research and CVD prevention initiatives, such as hypertension detection, weight reduction, smoking cessation, and the promotion of healthy lifestyles. Social advertising of healthy lifestyles on television and by advertizing posters is undertaken partially by non-governmental organizations, but is not yet widespread.

6. How are cardiologists in the Ukraine incorporating innovative drugs and devices (e.g. TAVI) into their practice?

Innovative treatment approaches are implemented by Ukrainian Association of Cardiology via Guidelines and the development of treatment protocols. New drugs and technologies are incorporated into medical practice quite rapidly due to efficient information spread via congresses, meetings, and symposia. However, some devices (e.g. TAVI) are not being used promptly enough in practice due to high costs.

7. What is the greatest challenge facing the Ukraine over the next decade?

One of the challenges is the greater focus on primary and secondary prevention and promotion of healthy lifestyles. Another important challenge is the reorganization of cardiology training programmes and bringing them up to European standards.

Book Review
Fast Facts: Obesity

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David Haslam

Publisher: Health Press, September 2009

ISBN: 978-1-905832-04-0

Paperback: 140 pages

This soft cover booklet is addressed to primary care physicians, junior hospital doctors, and medical students who want rapid access to information. Its small size is convenient to be easily carried in a medical coat pocket.

The two authors D. Haslam and G. Wittert are experienced specialists in obesity and summarize the main topics of the obesity epidemic in a well-structured manner. The booklet is divided into 11 chapters, each dealing with an important topic of obesity, starting with epidemiology, and ending with management tools and programmes available for primary care physicians. Each chapter ends with a highlighted coloured box of: Key Points and Key References.

The chapters covering assessment, causes, consequences, and management issues (physical activity, behavioural therapy, medication, and even surgery) are clearly written, concise, and well arranged. However, there are—as is in the nature of things, especially books—some drawbacks: the rather outdated tables in behavioural advice to patients, the lack of newer techniques in obesity surgery, e.g. sleeve gastrectomy—and the lack of mention of the pitfalls of banding (such as pseudoachalasia), and the rather light chapter on pharmacotherapy.

Nevertheless, the booklet serves what it pledges to be: a fast gap filler for newcomers in a growing world of knowledge for an important disease nowadays: OBESITY!

Andros Tofield

Neurological complications in infective endocarditis

J. Alberto San Román (Valladolid, Spain) and Isidre Vilacosta (Madrid, Spain) discuss the latest data, which they presented at the Acute Cardiac Care Congress in October

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J. Alberto San Román

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Isidre Vilacosta

No other cardiovascular disease has a poorer short-term outcome than left-sided infective endocarditis (LSE). The mortality rate is in the range of 30%. Two steps can be considered crucial in the fight against LSE (Figure 1): first, the inclusion of antibiotics (ABs), which decreased mortality dramatically in a disease considered fatal until then; second, the introduction of surgery in its early management. Despite the design of new, more powerful ABs and advances in surgical methods, mortality rates have remained steady for the last decade. To further reduce mortality, management of neurological complications (NCs), devastating and clinically challenging when they occur, has to be improved.

Figure 1

The crucial steps in the fight against endocarditis. Initially, the use of antibiotics dramatically reduced mortality. Surgery in the active phase of the disease further improved outcome in the early 1960s. No new advances have had any impact on prognosis. Mortality rates have remained steady since then.

To put the problem in perspective, the mortality rate rises up to 50% in patients with NCs, clinical management is difficult, and cardiopulmonary bypass may be deleterious (prohibitive in patients with cerebral haemorrhage); on the other hand, NCs are frequently present when surgery is indicated for other reasons, and even the appearance of NCs may be an indication.

Neurological complications appear in 20–40% of patients with LSE; half of them correspond to ischaemic stroke, 20% to cerebral haemorrhage, and 30% to other complications (transient ischaemic attack, meningitis, infected aneurysm, brain abscess). The best predictor of NCs is delayed initiation of AB therapy;1 thus, the best preventive measure is to initiate an appropriate AB treatment as soon as LSE is suspected, always after blood cultures have been obtained. Other predictors found in the literature include vegetation size, S. aureus infection, mitral position, and treatment with anticoagulants,2,3 the latter only for haemorrhages.

Whether NCs are predictive of poor outcome is an unsolved issue, and studies making a dichotomous classification offer different results.4,5 The key point of this question may be in recognizing, as in every field in medicine, that there are many areas of uncertainty. Poor outcome associated with relevant NCs (complicated,6 moderate-severe,3 or clinical7) when compared with irrelevant (uncomplicated,6 small,3 or subclinical7) has been shown.

The added value of MRI to identify subclinical NCs has been documented.8 Given that these techniques are not readily available in most centres, their use cannot be generalized unless it is demonstrated that new unexpected findings by these techniques effectively change management and, mainly, improve prognosis.

Whether cardiopulmonary bypass is safe in patients with NCs is another controversial topic. Heparinization may convert an ischaemic stroke into a haemorrhage, and hypotension may potentiate oedema and aggravate ischaemia. Several studies, however, suggest that early surgery in patients with ischaemic stroke is safe.6,7 Postponing surgery is recommended in patients with cerebral haemorrhage, a completely different scenario.9

The European Society of Cardiology recognizes the importance of NCs and specifically deals with them in the last guidelines.10 A clear scheme helps to choose the therapeutic strategy in this setting (Figure 2).

Figure 2

Considerations for surgery. The comprehensive clear scheme dealing with neurological complications in patients with endocarditis designed by the European Society of Cardiology can be summarized with two straightforward questions.

The decision-making process can be summarized in two short questions: (i) does the patient have an indication for surgery? (ii) does the patient have a prohibitive surgical risk? If the answer is (i) yes/ (ii) no, surgery should strongly be considered.

All information presented herein is based on small, retrospective studies; therefore, conclusions are far from definitive. More than 15 years ago, David Durack stated that ‘the diagnosis and management of infective endocarditis present an ideal application for the principles of evidence based medicine. Many complex questions and decisions arise, most of which have not been formally asked or answered by means of controlled clinical studies. Current practice is based upon an extensive accumulation of uncontrolled clinical experience, rather than upon proven principles’.11

Unfortunately, researchers on infective endocarditis, including our group, have not followed this recommendation and little evidence is available. Only randomized trials that must be multi-centre in nature, given the low prevalence of this disease, will shed light on this difficult topic. They can be designed12 and done.13 What are we waiting for?

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