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CardioPulse ArticlesImportant news from the European Heart Journal for 2013A short portrait of Prof. Alberto ZanchettiThird universal definition of myocardial infarctionBratislava Medical JournalEconomic evaluation in cardiology

DOI: http://dx.doi.org/10.1093/eurheartj/ehs296 2503-2509 First published online: 14 October 2012

Important news from the European Heart Journal for 2013

Into the future on the shoulder of past achievements

The European Heart Journal has developed beyond expectations:1 It has become a global journal receiving an increasing number of manuscripts every year (this year 3800 papers are expected to be submitted), and its articles are increasingly cited,2 leading to a steadily growing impact factor, which reached 10.5 this year. The feedback from our readers in surveys is excellent and an impressive number of articles are downloaded every day. This could be achieved only on the basis of the work of the previous editors3 and a highly devoted editorial team.

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Onward to new heights. An ebullient Thomas F. Lüscher, Editor-in-Chief, celebrating the Journal's new Impact Factor of 10.478 with Deputy Editors Ulf Landmesser (L), Frank Ruschitzka, and Associate Editor Christophe Wyss

Furthermore, a large number of competent and highly motivated reviewers have helped in selecting the right manuscripts. Last but not least, strict adherence to rules on good publishing practice has been essential.4

The ESC Journal Family is growing

Many new features have helped as well: The ESC Journal Family now works closely together and shares an increasing number of manuscripts, ideas, and strategies. This is important for submitting authors, readers, and for the ESC journals alike. Indeed, with the current acceptance rate of only 10% at the European Heart Journal, many papers that cannot be accepted by the main journal may be suitable for the specialty journals. If considered by the specialty editor, the paper can be resubmitted on the basis of the reviews obtained in the first round by reviewers of the European Heart Journal, thereby saving time and effort for the authors. This system has worked very well and will continue with an ESC Journal Family now encompassing a total of 9 products covering all areas of cardiovascular medicine.

The EHJ platform

The platform of the European Heart Journal has also been improved and has been made more user-friendly with novel features such as:

Interactive Cardiovascular Flashlights,

The EHJ Cardio Image Bank


My Cardio Interview series


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My Cardio Interview. T. Lüscher, M. Brignole, R. Sutton on ISSUE 3 Trial. T. Lüscher in an incisive video interview on the ISSUE 3 Trial with M. Brignole and R. Sutton

The image bank contains all the figures and schematics published in the European Heart Journal, which are available in PowerPoint format for the use of our readers. The slides are listed according to the topic and can be accessed easily. Interactive case reports are a new initiative together with the ESC educations committee allowing for more in-depth training of visitors. Finally, through our My Cardio Video interview series, which is produced by Managing Editor Sam Rogers, the editors of the European Heart Journal have conducted nearly 100 video interviews with key opinion leaders and the presenters of hotline and late breaking clinical trial sessions at the Annual Congresses of the European Society of Cardiology, the American Heart Association Scientific Session, and the American College of Cardiology. These interviews are aired on the EHJ website within 2 weeks of the congresses and have proved to be extremely popular as evidenced by the nearly 60 000 visits since this new feature was introduced.

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Furthermore, on the web platform, the CardioNewsWire feature has been implemented presenting current news from the ESC and its journals, as well as cardiovascular medicine at large for our readers:


Importantly, the European Heart Journal App is now available on the iPad and iPhone together with some of its specialty journals for direct use.

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EHJ iPhone App

The next steps: going weekly

The European Heart Journal has to evolve further. To this end, we will begin publishing weekly as of January 2013. Thus, as with all other premier journals, the European Heart Journal will be available every week and enjoy an increased visibility and shorter time to print. In particular, the number of educational products such as editorials, review articles, and current opinions will increase, while the number of original research papers will remain the same. The increased space may also be used for novel features to be developed in the future.

We are proud to run the flagship of the European Society of Cardiology together with the editors of our sister journals and look forward to further improving the quality and international standing of the European Heart Journal with the help of the entire editorial team, our submitting authors, and reviewers.

Thomas F. Lüscher, MD, FESC

Editor-in-Chief European Heart Journal


A short portrait of Prof. Alberto Zanchetti

Diana Berry MA describes a world leader in the war against hypertension

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Alberto Zanchetti

A European cardiologist, Prof. Alberto Zanchetti has, since he first qualified in 1950, been fighting to find a perfect solution to one of our increasing modern day scourges, hypertension. Prof. Zanchetti studied medicine at the University of Parma, Italy, which was his home city. After graduation, he went on to train in neurophysiology at the University of Pisa, where he worked with Prof. Giuseppe Moruzzi, the renowned neurophysiologist whom Zanchetti recognizes as one of the most influential people in developing his career and by whom he was inspired to undertake further research into the neural control of circulation and the resulting derangement seen in both hypertension and cardiovascular diseases. Prof. Moruzzi was also instrumental in teaching research methodology and the important ethical factors involved.

Another important ‘mentor’ in Zanchetti's career development was Cesare Bartorelli, Professor of Internal Medicine at Siena University and then at the University of Milan. He was instrumental in awakening in Zanchetti a true understanding of what medicine is all about—that is, caring for patients as suffering individuals, not simply as carriers of disease. He also introduced the Prof. to the study of hypertension, which has remained his main medical interest: Zanchetti succeeded him when he retired from his chair at Milan University. Other influential people in the early days of Zanchetti's career included Sir George Pickering, Regius Professor of Medicine at Oxford University, and Franz Gross, Professor of Pharmacology at Heidelberg University, who did pioneering work on the development of antihypertensive drugs.

It was in the 1950s when hypertension first became a treatable disease that further study became both fascinating and demanding. In 1967 Zanchetti moved to the University of Milan and also became chief of a clinical unit devoted to internal medicine at the affiliated hospital ‘Ospedale Maggiore Policlinico’. Through the 1960s, 1970s, and the 1980s, the Prof. became even more interested and involved in studying the pathophysiology of hypertension, looking into baroreflexes involved and the interaction between neural and renal factors in the control of blood pressure. During that period he gave two lectures that covered this subject area: the first was in1977 to the American Heart Association (AHA) looking at the neural regulation of renin release, and in 1986, the Volhard Award lecture at the International Society of Hypertension meeting looked at the interactions between neural and renal mechanisms in hypertension.

In a paper published in 1978 by the AHA,1 Zanchetti and co-authors presented a study of the baroreceptor reflexes in 35 hypertensive humans employing a ‘variable pressure neck chamber to alter carotid sinus transmural pressure in a graded fashion’. A comparison of results was made with those obtained from the 11 ‘normotensives’ also taking part in the study. In both hypertensives and normotensives the reduction of carotid transmural pressure resulted in a linear-related pressor response and vice versa. The study did show that although in normotensives the pressor response was greater than the depressor, in hypertensives the reverse was the case. Ultimately, the study showed that while in normotensives the carotid baroreflex was more effective in guarding against hypotension, in hypertensives the effect was the opposite, i.e. more protective against the dreaded hypertension. The results were similar in comparisons made in respect of carotid baroreceptor control of heart rate.

In 2010, the Prof. again with co-authors wrote an updating editorial in ‘Hypertension’, a journal of the AHA.2 Looking at the problems inherent in resistant hypertension, they summarized the three approaches used to increase the extent of blood pressure reduction and the possibility of achieving blood pressure control. The first possibility was that of improving the drug therapy employed by adding an anti-aldosterone agent to block the sodium-retaining properties of this hormone whose release significantly escaped the effect of blockers of the renin–angiotensin system then available. The second approach would be to add to the usual multi-pharmacological treatment the vasodilator influence of endothelial receptor antagonists, this being found more effective than previous therapeutic attempts. The third possible approach to the tackling of resistant hypertension was a much more invasive procedure to either reduce the pressor or increase the depressor influences that are physiological blood pressure modulators. The reduction of pressor influences is achieved by denervating the kidneys using a radiofrequency generator positioned in the renal arteries inserted by means of a percutaneous catheter.

Given his extremely demanding and indeed successful life in medical research, one may well wonder whether the Prof. can find time for interests and hobbies outside medicine: fortunately, the answer is a positive one! Zanchetti kindly gave me an insight into his world outside medicine. Having been born and brought up in the city of Parma, he is extremely fond of opera and a keen and regular attendant at the La Scala seasons and although unable to sing himself, he pretends to be a connoisseur of voices and the art of singing. He is also very interested in history and art, describing himself as ‘a passionate though impecunious collector of old prints, from Dürer to Rembrandt, from Lucas van Leiden to Goya’.


Third universal definition of myocardial infarction

This landmark definition has been determined by international associations for the global medical community

The third universal definition of myocardial infarction is a truly global document. Developed jointly by the European Society of Cardiology (ESC), the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the World Heart Federation (WHF), it will also be referred to by the US Food and Drug Administration (FDA) as the basis for clinical trial protocols.

‘This is very important because steering committees setting up protocols for clinical trials, and especially companies supporting the big trials, will follow requirements from the FDA’, says Prof. Kristian Thygesen (Denmark), co-chair of the document Task Force.

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Kristian Thygesen

It will be published in five journals simultaneously, giving broad coverage. These are European Heart Journal on behalf of the ESC, the Journal of the American College of Cardiology for the ACCF, and Circulation for the AHA. For the first time, it will also be published in the World Heart Federation's Global Heart and Nature Reviews Cardiology.

The first joint document, published in 2000, was not called a universal definition of myocardial infarction but so-called ESC/ACC criteria for redefinition of myocardial infarction. It was a consensus document between the ESC and ACC. Myocardial infarction had previously been defined primarily on the basis of electrocardiography (ECG). The 2000 document shifted the definition towards a biochemical and clinical approach.

In 2007 the ESC and ACC were joined by the AHA and WHF for a second document defining myocardial infarction. The phrase ‘universal definition’ was adopted to signify that it had been developed by a global group of organizations and that the definition was broader than it had been in the past. The 2007 document was more widely accepted by clinicians.

‘After the 2000 document there was still some hesitancy among clinicians to use the new cardiac biomarkers, the new troponins’, says Thygesen. ‘But in 2007 it was really accepted that you use troponins as the primary biomarker and in addition, there would be clinical signs as well’.

In 2011, the World Health Organization (WHO) accepted the universal definition. It had hesitated in 2007, claiming that the new universal definition for myocardial infarction was only for Europe and North America and did not apply to poor countries. Together with Prof. Philip Poole-Wilson, Thygesen worked with the WHO to create its own version of the universal definition,1 which will be referred to when preparing the next update of the international classification of diseases.

New issues and questions began to emerge after the 2007 universal definition and the presidents of the ESC, ACCF, AHA, and WHF agreed that a new Global Task Force should be established to develop what would be called the third universal definition of myocardial infarction. The Global Task Force for the 2012 update has 52 members and includes members from countries that had not been represented in the previous Task Force such as China and Russia.

In 2007, the Task Force suggested for the first time that myocardial infarction should be classified into five different types. The 2012 update further develops these five types. Other aspects of the 2007 document are fine-tuned, including the sections on detecting myocardial infarction using ECG and imaging techniques.

Situations can arise in which the new troponins are released in the absence of myocardial infarction. These include myocardial injury and cell death. A new figure is included to help clinicians and scientists understand how these situations are different from myocardial infarction. This will help with diagnosis.

A controversial area that is given more space in 2012 is the issue of troponin elevations after percutaneous coronary intervention (PCI) or coronary bypass (CABG). After much discussion, a consensus decision was reached on the levels of troponin required for a diagnosis of procedure-related myocardial infarction. The levels of troponin required for diagnosing a heart attack or myocardial infarction due to non-cardiac procedures and cardiac procedures other than PCI and CABG are also clearly set out.

A consensus was difficult to reach because it is' an area in which clinical trials cannot be done to compile evidence. In addition, interventionalists and surgeons are not keen to have myocardial infarction as a complication and want to set the bar high.

An effort was made to distinguish between diagnosis and prognosis, which are two different things but can become confused. Myocardial infarction is frequently used as an endpoint in clinical trials and biomarkers are often used to set the diagnosis. This gave further impetus for the need to differentiate between diagnosis and prognosis.

The third universal definition of myocardial infarction was presented and discussed at the ESC Congress in Munich in August 2012 and its pocket guidelines were distributed. Thygesen believes that the national cardiac societies will incorporate the third universal definition of myocardial infarction into their national guidelines. ‘There is no other universal definition and so they will refer to this one’, he says. ‘The 2007 document has very high citation impacts’.

He adds: ‘It will be used worldwide. I'm sure it will be used in developed countries, but we have to help in the poor countries – that is more a political matter'.

He is also confident that the WHO will give its backing to the 2012 definition, particularly given that one of its key figures is a member of the Task Force. Thygesen is still a member of the WHO myocardial infarction committee and believes it will produce a WHO communication based on the 2012 global task force document.

It was a WHO working group that came up with the first definition of myocardial infarction in the 1950s. Working groups two, three, four, and five came up with subsequent definitions and until the beginning of the 1970s and even later on, it was the leading force in this field.

Thygesen believes that the current Global Task Force should continue running. ‘I don't know of any other task force that has been set up in such a way’, he says. ‘It's really unique to have so many societies working together’.

It is accepted that the ESC is the driving force behind the Task Force, with support from the Committee for Clinical Practice Guidelines and the Practice Guidelines Department. It' is a good example of Europe leading the way in an important field in cardiology.

‘My personal feeling is that we should, in one way or another, continue to have this Global Task Force because there will be new biomarkers, new drugs and new interventions’, says Thygesen. ‘If you change the management or the treatment of disease and thereby the outcome, then after a while you also have to modify the diagnosis’.

Jennifer Taylor


Bratislava Medical Journal

Founded after the First World War, the journal has published continuously since 1921

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After World War I, the Czechs and Slovaks created a common state, Czechoslovakia, which was established on 28 October 1918. The following year (1919) the Czech professors established a Slovak university in Bratislava, which was given the name of Comenius University. The first rector (chancellor) was Prof. Kristian Hynek. In the academic year 1921–1922, he founded the medical journal Bratislavské lekárske listy (Bratislava Medical Letters). The journal was published during the academic year.

The first volume was issued in 1921 and another was published in 1922. At that time, the journal was published in the Slovak and Czech languages. The abstracts were in German, English, French, and in Russian. The journal has been published continuously, without interruption, even during World War II. ‘This is a piece of our journal history of which we are very proud’, says Editor-in-chief Prof. Ivan Hulin (Bratislava, Slovakia).

Today the journal, now called Bratislava Medical Journal—Bratislavské lekárske listy, brands itself as an international journal for biomedical sciences and clinical medicine. It is published monthly in English. Over the last 5 years, manuscripts have been published from nearly 100 countries. The bulk of manuscripts come from Slovakia (38–40%), with the USA in fourth position.

The journal's abbreviated title is Bratisl Med J (Bratisl Lek Listy). It continues to be published by Comenius University, School of Medicine, in Bratislava, Slovakia.

Bratislava Medical Journal publishes peer-reviewed articles on all aspects of biomedical sciences, including original clinical studies, review articles, and experimental investigations with clear clinical relevance. During the period 1921–1970, ∼30% of the manuscripts focussed on topics in cardiology. Today the journal is dominated by papers in the fields of general medicine, oncology, and cardiology. It is read by clinicians and scientists.

Cardiology-related papers already published in 2012 include: ‘Low density lipoprotein size in relation to carotid intima-media thickness in coronary artery disease’; ‘Impaired endothelium-dependent and -independent relaxation of aorta from diabetic rats’; and ‘Association of angiotensin converting enzyme gene (I/D) polymorphism with hypertension and type 2 diabetes’.

The editorial team receives >1000 manuscripts every year but accepts and publishes between 120 and 140 papers. The impact factor is 0.345.

The journal's website, www.elis.sk, gives detailed instructions for authors on the requirements for manuscripts. For example it says, ‘we are not interested in manuscripts with the conclusion ‘the authors confirmed the results of other authors'. Neither are we interested in manuscripts which conclude that ‘the findings need a further study on the issue’.

The editors say that they will consider both invited and uninvited review articles but that authors should describe in a covering letter how their work differs from existing reviews on the subject. The aim is to publish review articles that are not just a review of the existing literature but that bring a new perspective to the issue.

While it is acknowledged that case reports ‘are often interesting as a rarity or structural or functional variability’, they too should take a new look at the problem.

Hulin has an editorial staff office composed of three members and is supported by a team of scientific editors and an international editorial board. The scientific editors are primarily from Slovakia (Bratislava, Kosice, Martin), with others from Belgium (Aalst), USA (St Louis, Boston), and Germany (Hannover). Members of the editorial board are based in Slovakia, the Czech Republic, Hungary, Russia, France, Italy, UK, Germany, Austria, USA, Canada, and Japan.

Asked what his vision is for the future of the journal, Hulin says: ‘My desire is to publish in our journal manuscripts by Nobel Prize laureates’.

Jennifer Taylor, MPhil

Economic evaluation in cardiology

Dr Luís F. Azevedo discusses critical tools in the quest for more rational, efficient, and equitable decisions… if and when properly used!

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Luis F. Ribeiro de Azevedo

For many reasons, the medical community is increasingly interested in tools that may help us to systematically analyse and maximize the economic efficiency of health-care delivery and the use of technologies. Economic evaluation is currently the single most important set of tools supporting decision-makers at all levels of health policy and practice, in their quest for more rational, efficient, and equitable decisions.14

Economic evaluation may be defined as a set of methods and tools that explicitly and systematically analyse and compare alternative courses of action in terms of both costs and their consequences.1 Four basic types of economic evaluation studies are used: cost-minimization analysis, cost–benefit analysis, cost-effectiveness analysis (CEA), and cost–utility analysis (CUA). In the fields of health and medicine, CEA and CUA are the main approaches used.2,4

In CEA, the aim is to estimate the comparative cost per unit of effectiveness, measured in natural units of relevant health outcomes of some technology or intervention, relative to a suitable and useful comparator. For example, we may want to determine whether drug-eluting stents (DES) are good value for money in long-term everyday practice compared with bare-metal stents (BMS),5 and for that we could perform a CEA and obtain an incremental cost-effectiveness ratio (ICER) comparing the alternatives regarding major adverse cardiac events (MACEs). The result could be that the ICER was €64 732, meaning that DES has this incremental cost to prevent one additional MACEs compared with BMS.5 Furthermore, in a CUA, the aim is to estimate the comparative cost per unit of effectiveness of some technology, but here the units are adjusted for the quality of life associated with the health states evaluated and the subjects' preferences. Thus, the effectiveness measure in CUA is usually the quality-adjusted life-year (QALY). In our previous example, we may also find that DES costs an additional €40 467 per QALY gained compared with BMS.5 These results compared with the assumed cost-effectiveness thresholds would allow us to conclude that DES is indeed not cost-effective compared with BMS.5

This set of methods, although the best tools currently available are still evolving conceptually and methodologically and have many caveats and problems. Because of the difficulties associated with the studied objects and constructs, they are many times prone to bias and measurement error, sometimes use debatable assumptions and often have limited generalizability.1,69 Thus, it is crucial that decision-makers, at all levels, appreciate the relevance of being able to adequately understand and critically appraise these kinds of studies; and it has to be kept in mind that these are tools available to inform decision-making and not to substitute the decision-makers.

Many issues are indeed crucial when critically appraising economic evaluation studies.1,3,611 Although it is not possible to detail here the criteria and procedures involved in critically appraising these kinds of studies, some particularly important issues deserve a special mention:

  1. To give particular attention to the entities involved in funding and performing the studies and the study perspective they assume.

  2. An adequate choice of the technologies and especially the comparators used.

  3. An adequate measurement of costs. This task is difficult and prone to bias and important measurement errors.

  4. The measurement of effectiveness of alternatives and the measurement of quality of life and utilities. There are still many important conceptual and practical issues involved in the measurement of utilities that are far from consensual.

  5. The adequate interpretation of ICERs. The risks of comparing ICERs coming from different technologies or contexts and the consideration of assumed and eventually arguable, cost-effectiveness thresholds for decision.

  6. The frequent use of extrapolations, modelling, and simulation techniques in these types of studies should be kept in mind and adequately put into perspective. In fact, modelling techniques are by far the best or the only methods available to tackle the complexity of some issues at hand; however, we should be conscious of the many assumptions they entail and be very cautious in the interpretation of their results and conclusions.

  7. The important consideration to the issues of generalizability of results from economic evaluations.

References are available for those interested in further details.1,3,611

In the last decades, because of the high burden of cardiovascular diseases and the rapid development of technologies,1214 cardiology is an area where economic issues have been raised more frequently.2,4 Within the field of cardiology, one might even conclude that this type of research has adequately grown to become an integrated part of the development and analysis of every new technology.2,4

An increasing number of health-care systems worldwide are using economic evaluations to make decisions about which interventions or technologies should be authorized or recommended and how they should be funded or reimbursed.1519 Important cuts in health-care spending are now being put into practice worldwide. If health-care systems cover some technologies, many other, sometimes more basic, are left uncovered or under-covered. Moreover, patients when faced with economic difficulties often stop or postpone the use of important drugs and devices and frequently, the attending physicians will be unaware of this fact. Although governmental approaches are primarily focused on decreasing health-care spending, it is the responsibility of the medical profession to become cost-conscious and maximize the efficiency of interventions (giving good use to resources and cutting unnecessary costs).2024

The crucial role of clinicians as active and knowledgeable partners in the design and conduct of economic evaluations and their ability to critically appraise and adequately apply this type of scientific evidence are becoming more and more important.2,4,2025 Nevertheless, there is still a long road to walk concerning (i) the change in clinicians' attitudes and mind framing regarding these issues and (ii) the improvement of academic and professional curricula. Economic issues and a cost-conscious clinical practice2024 have changed from being an ethical dilemma, once thought as being in the antipodes of the medical mind, to an ethical, humanitarian, and clinical obligation!

Luís Filipe Azevedo

Faculty of Medicine, University of Porto, Porto, Portugal