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. 2015 Jul 20;36(29):1843–1848. doi: 10.1093/eurheartj/ehv249

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PMCID: PMC4571178  PMID: 26240029
Eur Heart J. 2015 Jul 20;36(29):1843–1848.

Editors' network of the European Society of Cardiology National Cardiovascular Journals: scientific input from the National Societies

Scientific relevance and current activities are discussed by Fernando Alfonso, MD, FESC, Chairman of the Editors' Network

National Society Cardiovascular Journals (NSCJs) are the official journals from the corresponding national societies of the European Society of Cardiology (ESC). NSCJs have major scientific value as they publish original high-quality scientific research, but they also play a unique role in education by publishing state-of-the-art review papers, viewpoints, and related materials. However, NSCJs are quite heterogeneous in size and scope and most of them publish in the local languages. In addition, NSCJs remain completely independent as they belong to the corresponding ESC national societies (http://www.escardio.org/membership/national-societies/Pages/journals.aspx#nat-journals).

In this regard, NSCJs provide a unique tool to further disseminate scientific content and educational material with the attractive feature of being able to reach the level of the practicing physician working in the different countries. However, over the years many of these journals have also gained international prestige and scientific recognition and include English editions. Overall, up to 23 NSCJs are currently listed in PubMed and 12 of them have obtained an impact factor on the Thomson Reuters ISI Web of Science database.

Therefore, NSCJs clearly complement the ESC official journals by disseminating novel cardiovascular research and by helping to harmonize education and clinical practice across Europe. Accordingly, they should indeed be considered as part of the ESC journals ‘family’.

Currently, expansive editorial initiatives followed by most major cardiac societies involve creating ‘offspring’ journals from leading cardiovascular journals.1 This policy enables the use of the ‘brand name’ of the mother journal to ensure international prestige and recognition facilitating the launching of brand-new sub-speciality journals. These journals refer papers to one another to prevent loosing manuscripts of considerable merit and to ensure the publication of manuscripts in the most appropriate venue.1

A similar policy has also been successfully followed by the ESC, where the major official journals are now surrounded by a wide array of highly attractive sub-speciality journals.2 In this scenario, NSCJs offer a unique means of further enriching the scientific and educational content provided by the ESC.3,4 Yes, NSCJs are indeed very proud of belonging to the ESC Journals ‘family’.

Just a decade ago the first meeting of the Editors of the NSCJs was organized under the auspices of the ESC. Since then, annual formal meetings of NSCJs Editors have been held during the ESC Annual Congress and, more recently, during the ‘Spring Days' at the Heart House in Nice. The initiative—formerly called ‘Editors' Club’—evolved into the current ‘Editors' Network’ official ESC Task Force.3,4 During these years, this novel editorial initiative has matured, paving the way for a more formal and fruitful editorial collaboration (Table 1).3,4 Editors of NSCJs seek to increase the scientific quality, diffusion, and recognition of their respective journals. Likewise, they are faced with the challenges of a globalized academic world. In this regard, a close collaboration among NSCJs Editors seems essential.

Table 1.

Main editorial initiatives from the editors' network

  1. Database development and yearly update

  2. Website development and dedicated mailbox implementation

  3. Mission statement document (joint publication)

  4. Multidirectional links and efficient networking tools

  5. Education document (joint publication)

  6. Almanac series (yearly)

  7. Clinical practice guidelines: expedited translation and dissemination initiative

  8. ESC late breaking clinical trials: expedited abstract translation and dissemination

  9. ‘Meet the Editors’ session (ESC meetings)

  10. Conflict of interest document (joint publication)

  11. Search engine document (joint publication)
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Initially, detailed editorial data were systematically gathered from all NSCJs. Subsequently, this information was made available from a dedicated site at the ESC website that was produced to increase the visibility of NSCJs. Likewise, bidirectional links between the ESC and the NSCJs were established to provide efficient networking tools.3–5 The Editors' Network eventually proved to be a dynamic platform where multiple joint editorial initiatives flourished (Table 1).

Firstly, a ‘Mission Statement’ document was issued to set common editorial principles and to foster collaboration among NSCJs.3,4 Technical and ethical issues were discussed as a means to gain editorial excellence. Indeed, even today, formal requirements and the technical issues of the submission process for PubMed listing and ISI approval are jointly discussed. Efforts are made to help new or small journals in this regard. In particular, the ‘peer review’ process was considered a critical step in the scientific process and major emphasis was made to adhere to the International Committee of Medical Journals Editors (ICMJE) recommendations. Very recently, the updated ICMJE criteria for authorship have been discussed among NSCJs Editors. Collaboration among NSCJs seems crucial to facilitate an efficient dissemination of novel scientific information across Europe.

Secondly, promoting diffusion of high-quality ‘educative content’ was also identified as a major mission of NSCJs, and another consensus document entitled: ‘Role of Journals in Education’ was issued.5 The ‘Almanac’ series represents yet another proposal for selected educational material to be made available to all interested NSCJs. Along the same lines, the possibility of obtaining high-quality educational content directly from the European Heart Journal has also recently been discussed. The ‘Year in Cardiology’ series may represent highly attractive pieces in this regard. More recently, the important role of NSCJs Editors to harmonize education across European countries has been emphasized. Joint policies to implement the Core Curriculum in cardiology and to address accreditation issues are considered of paramount importance.

Thirdly, the Editors' Network discussed and supported the new ICMJE proposal on conflicts of interests (COIs) including an electronic ‘uniform’ format for disclosure.6–8 Importantly, all these three major joint editorial initiatives (Mission statement, Education, and COIs) were nicely complemented by new data obtained by comprehensive structured questionnaires that were specifically designed and sent to the NSCJs Editors in order to obtain an accurate picture of the actual editorial situation across Europe.4,5,8

Collaboration among NSCJs was essential to disseminate and promote the clinical application of ESC Clinical Practice Guidelines.3,4 Translation and expedited publications of these Guidelines into national local languages facilitates their implementation into clinical practice. Likewise, during the ESC Congress, specific editorial sessions (Meet the Editors) highlighting burning editorial issues together with a strategy for an early translation and publication of late breaking clinical trials was organized by the NSCJs. More recently, the Editors' Network developed another joint editorial initiative that enabled the inclusion of many NSCJs in the powerful Search Engine currently available from the ESC Web page.9,10 From an editorial standpoint, this represents another effective tool to increase the visibility of NSCJs.

This ongoing joint editorial effort provides a solid foundation for the future. NSCJs clearly provide a unique scientific input to the ESC. The Editors' Network is currently actively working to:

  1. Stimulate collaboration among NSCJs Editors

  2. Improve scientific collaboration between NSCJs and the official Journals of the ESC

  3. Enhance editorial standards

  4. Improve the scientific quality of contents and, last but not least

  5. Foster dissemination of scientific knowledge

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Eur Heart J. 2015 Jul 20;36(29):1843–1848.

Hand grip strength predicts myocardial infarction and stroke

Weak hand grip strength is linked with shorter survival and a greater risk of myocardial infarction or stroke, according to the PURE study.

The study of nearly 140 000 adults from 17 countries also found that grip strength was a stronger predictor of death than systolic blood pressure.

Reduced muscular strength, which can be measured by grip strength, has been consistently linked with early death, disability, and illness. But until now, information on the prognostic value of grip strength was limited, and mainly obtained from select high-income countries.

The Prospective Urban-Rural Epidemiology (PURE) study was conducted in countries of varying incomes and sociocultural settings. Grip strength was assessed using a handgrip dynamometer and subjects were followed for a median of 4 years.

The researchers found that every 5 kg decline in grip strength was associated with a 16% increased risk of death from any cause, a 17% greater risk of cardiovascular death, a 17% higher risk of non-cardiovascular mortality, a 7% increased risk of heart attack, and a 9% higher risk of stroke.

The associations persisted even after adjusting for age, education level, employment status, physical activity level, and tobacco and alcohol use.

Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure.

A low grip strength was linked with higher death rates in people who develop cardiovascular and non-cardiovascular diseases, suggesting that muscle strength can predict the risk of death in people who develop a major illness.

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Lead author Dr Darryl Leong said: ‘Grip strength could be an easy and inexpensive test to assess an individual's risk of death and cardiovascular disease. Further research is needed to establish whether efforts to improve muscle strength are likely to reduce an individual's risk of death and cardiovascular disease’.

The full Lancet paper is here: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62000-6/abstract.

Jennifer Taylor MPhil

jen.taylor2@btinternet.com

Eur Heart J. 2015 Jul 20;36(29):1843–1848.

Effect of remote ischaemic conditioning on clinical outcomes in patients presenting with an ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

The rationale and study design for the multicentre, randomized, controlled CONDI2/ERIC-PPCI study are discussed

Introduction

Ischaemic heart disease (IHD) is the leading cause of death and disability in Europe and worldwide. In patients presenting with an acute ST-elevation myocardial infarction (STEMI), early myocardial reperfusion using primary percutaneous coronary intervention (PPCI) is the most effective treatment for limiting myocardial infarct (MI) size and improving clinical outcomes. However, despite timely PPCI, the morbidity and mortality of STEMI patients remain significant—as such novel therapeutic strategies are required to reduce MI size in order to preserve left ventricular (LV) ejection fraction, prevent the onset of heart failure, and improve patient survival.

In this respect, the heart can be protected against acute lethal ischaemia/reperfusion injury (IRI) by applying cycles of brief non-lethal ischaemia/reperfusion to an organ or tissue remote from the heart—a phenomenon called remote ischaemic conditioning (RIC).1–3 Interestingly, RIC can be induced non-invasively by simply inflating and deflating a blood pressure cuff placed on the upper arm, an intervention that has been reported to reduce MI size in several proof-of-concept clinical studies.4–10 Whether RIC can improve long-term clinical outcomes in this patient group is unknown and is the objective of the CONDI2/ERIC-PPCI study.

Methods

Study design

The CONDI2/ERIC-PPCI study is a European (Denmark, Serbia, Spain, and UK) prospective, randomized, controlled, clinical trial of 4300 STEMI patients undergoing PPCI. The study will be conducted in accordance with the Declaration of Helsinki and has been approved by the Ethics committees of the respective countries. All patients will provide informed written consent.

Study population

Inclusion criteria

  1. Onset of symptoms within 12 h

  2. Age ≥ 18 years

  3. Suspected STEMI (ST-elevation at the J-point in two contiguous leads with the cut-off points: ≥0.2 mV in men or ≥0.15 mV in women in leads V2–V3 and/or ≥0.1 mV in other leads)

Exclusion criteria

  1. Known ineligibility for PPCI

  2. Previous coronary artery bypass graft surgery

  3. Myocardial infarction (MI) within the previous 30 days

  4. Treatment with thrombolysis within the previous 30 days

  5. Left bundle branch block (LBBB)

  6. Patients treated with therapeutic hypothermia

  7. Conditions precluding use of RIC (paresis of upper limb, use of an arterio-venous shunt)

  8. Life expectancy of less than 1 year due to non-cardiac pathology

Randomization

Patients will be randomized to either RIC or control. Randomization will be coordinated centrally via a secure website and will be stratified by centre using random permuted blocks. The PPCI operator, medical staff, and the research investigator collecting and analysing the data will be blinded to the treatment allocation.

Trial interventions

An automated CellAegis AutoRIC™ cuff device (www.cellaegisdevices.com) will be used to deliver the RIC protocol. The RIC and sham RIC intervention will be delivered prior to PPCI and according to local conditions—where ambulance transit times allow, the trial intervention will be delivered in the ambulance (Denmark and Spain), but where ambulance transit times are short the trial intervention will be delivered on immediate arrival at the PPCI centre (Serbia and UK).

Remote ischaemic conditioning intervention

An automated autoRIC™ cuff will be placed on the upper arm and inflated to 200 mmHg for 5 min and then deflated for 5 min, a cycle which will be undertaken four times in total. For patients presenting with a systolic blood pressure (SBP) ≥175 mmHg, a manual blood pressure cuff will be used and inflated to 25 mmHg above systolic blood pressure.

Sham remote ischaemic conditioning intervention

In sites where the trial intervention is applied on arrival at the PPCI centre (Serbia and UK), an AutoRIC™ cuff visually identical to that used in the RIC protocol will be placed on the upper arm and a simulated RIC protocol applied. Inflation will be simulated and held for 5 min, deflation will then be simulated and held for 5 min, a cycle which will be undertaken four times in total. For feasibility and logistical reasons, in those patients recruited and randomized in the ambulance no sham RIC control will be delivered (Denmark and Spain).

As the RIC/sham RIC protocol lasts 35 min, in cases where the door-PPCI time is less than 35 min, the RIC/sham RIC protocol may overlap with the beginning of the PPCI procedure. Under no circumstances will the RIC protocol delay the onset of PPCI.

Study endpoints

Primary endpoint

The primary endpoint will be cardiac death and heart failure hospitalization at 12 months. These events will be validated by an independent event validation committee (EVC). Heart failure hospitalization will be defined as an event that meets the following criteria (in brief)11: (i) the patient is admitted to the hospital with a primary diagnosis of heart failure (HF); (ii) the patient exhibits documented new or worsening symptoms due to HF on presentation; (iii) the patient has objective evidence of new or worsening HF; and (iv) the patient receives initiation or intensification of treatment specifically for HF.

Secondary endpoints

  1. Rates of cardiac death and heart failure hospitalization at 30 days.

  2. Rates of all-cause death, coronary revascularization, re-infarction, stroke at 30 days and 12 months

  3. TIMI flow post-PPCI

  4. ST-segment resolution on 90 min ECG post-PPCI

  5. Enzymatic MI size will be assessed from a 48 h area-under-the-curve (AUC) high-sensitive Troponin-T (hsTrop-T) using blood samples collected at time 0, 6, 12, 24, and 48 h in a 400 patient sub-study.

  6. MI size will be measured by cardiac magnetic resonance (CMR) scan performed at 6 months in a 250 patient sub-study.

Sample size determination

The primary combined endpoint will be cardiac death and heart failure hospitalization at 12 months. According to the UK NIAP 2008 database, cardiac mortality at 12 months ranged from 5.8–16.7% depending on the call to balloon time, with the overall 12 month death rate of 8.7% for all PPCI patients. In a recent Danish clinical study post-PPCI, the 1-year mortality was 9.4% and the cumulative risk of readmission with heart failure was 8%.12 In another, non-UK based, clinical study, the incidence of heart failure hospitalization was 12.7% at 12 months post-PPCI.13 We have based our power calculations on these published studies, accounting for the marked improvements in clinical outcomes in the contemporary era by using much more conservative event rates. As a conservative estimate we will use a combined cardiac death and heart failure hospitalization event rate of 11.0% at 12 months for all-comer STEMI patients. We have estimated the effect size to be a 25% relative reduction in the event rate. The rationale for this is based on proof-of-concept clinical studies in which RIC have reported 30% reductions in MI size.4–10 To demonstrate a 25% reduction in the primary composite endpoint in the RIC-treated group (from 11.0–8.25%), with 80% power and at the 5% significance level, will require 1805 patients per treatment arm which equates to 3610 patients in total. Therefore, we will need to recruit 4300 STEMI patients (conservatively allowing for a 15% drop-out rate at 12 months).

Statistical analysis

A detailed statistical analysis plan will be produced prior to un-blinding of any data. The primary analysis will be a comparison of the cardiac death or heart failure hospitalization event rate 1 year after randomization between the RIC and the control arms of the trial amongst all STEMI patients. Hazard ratios and confidence intervals will be calculated using Cox proportional hazards modelling and Kaplan–Meier curves will be produced. In addition, risk differences at 1 year will also be calculated together with 95% confidence intervals. The results for the individual components of the primary endpoint will also be presented together with other time-to-event secondary endpoints such as cardiac death or heart failure hospitalization at 30 days. Differences in means (continuous variables) together with 95% confidence intervals will be calculated using linear regression models and analysis of covariance techniques where appropriate. The primary analysis will be performed on an intention-to-treat basis, i.e. by including all patients where possible according to the group to which they were randomized irrespective of whether they received the intervention as allocated. A secondary per-protocol analysis will be undertaken including only patients who receive the allocated intervention as intended.

Clinical study monitoring and data management

The Clinical Trials Units at the London School of Hygiene and Tropical Medicine, London, UK and the Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital will oversee the trial. The nominated sponsor of the ERIC-PPCI arm will be University College London, and of the CONDI2 arm will be the University of Aarhus.

Discussion

The phenomenon of RIC was initially described in 1993 by Przyklenk et al.1 in a seminal experimental study, demonstrating that the cardioprotective effect of ischaemic preconditioning could extend from one coronary artery territory to another. The concept of RIC was then extended to organs and tissue remote from the heart (reviewed in Hausenloy and Yellon2).

Its translation into the clinical setting was facilitated by the discovery in 2002 by Kharbanda et al.14 that the RIC stimulus could be induced non-invasively in human volunteers by simply inflating and deflating a blood pressure cuff placed on the upper arm. Since then RIC has been investigated as a cardioprotective strategy in a number of clinical settings including cardiac bypass surgery,15–20 elective PCI,21,22 and stroke23 with mixed results.

Despite intensive investigation, the mechanisms underlying RIC remain unclear but have been attributed to a neuro-hormonal pathway linking the RIC-treated organ or tissue to the target organ.2,3,24

Remote ischaemic conditioning has also been investigated in the setting of STEMI in five small proof-of-concept clinical studies.4,6–9 The first study by Botker et al.4,25 reported that RIC (four-5 min upper arm cuff inflations and deflations) administered in the ambulance by paramedics on route to the PPCI centre, significantly increased mean salvage index from 0.57 in control to 0.69 with RIC at 30 days (as measured by myocardial single-photon emission computerized tomography (SPECT)).

In a post hoc subgroup analysis of patients presenting with a left anterior descending coronary artery STEMI, myocardial salvage was increased further, and there was a significant reduction in final MI size and improvement in LV ejection fraction at 30 days.4,25 Interestingly, 4-year follow-up of this patient cohort revealed less all-cause death in those patients given RIC at the time of their PPCI, although this study was not prospectively designed or powered to investigate long-term outcomes.10

Rentoukas et al.6 demonstrated in 96 patients that RIC (three 4-min upper arm cuff inflations and deflations) administered at the PPCI centre improved ST-segment resolution and reduced MI size assessed by biomarker release when compared with control. Crimi et al.7 found that RIC administered after PPCI reduced biochemical infarct size and was also associated with an improvement of T2-weighted oedema volume and >50% ST-segment resolution in STEMI patients undergoing PPCI. White et al.8 found that RIC initiated on arrival at the PPCI centre reduced MI size by 27% (measured by CMR) in STEMI patients. Finally, Prunier et al.9 confirmed the MI-limiting effects of RIC, but failed to demonstrate an additive cardioprotective effect with ischaemic post-conditioning.

Therefore, it is well established that RIC can reduce MI size in STEMI patients treated by PPCI, but whether this beneficial effect translates to improved clinical outcomes is not known and will be investigated in the CONDI2/ERIC-PPCI study.

In conclusion, the CONDI2/ERIC-PPCI study will determine whether limb RIC, a non-invasive low-cost therapeutic intervention can improve long-term clinical outcomes in STEMI patients treated by PPCI and is registered at www.clinicaltrials.gov (identifiers: NCT01857414 and NCT02342522).

Funding

The CONDI2/ERIC-PPCI trial is funded by the Danish Research Council, Trygfonden, the Novo-Nordisk Foundation and British Heart Foundation.

Conflict of interest: H.E.B. and R.K. are shareholders of CellAegis Inc.

Derek J. Hausenloy1,2,3,4*, Rajesh Kharbanda5*, Michael Rahbek Schmidt6, Ulla Kristine Møller6, Jan Ravkilde7, Lisette Okkels Jensen8, Thomas Engstrøm9, José Manuel García Ruiz10, Nebojsa Radovanovic11, Erica F. Christensen12, Henrik Toft Sørensen13, Manish Ramlall1,2, Heerajnarain Bulluck1,2, Richard Evans14, Jennifer Nicholas14, Rosemary Knight14, Tim Clayton14, Derek M. Yellon1,2 and Hans Erik Bøtker6

*These joint first authors contributed equally to this manuscript.

  1. The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK

  2. The National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, UK

  3. National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore

  4. Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore

  5. Oxford National Institute of Health Research Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

  6. University Hospital Skejby, Aarhus, Denmark

  7. Aalborg University Hospital, Aalborg, Denmark

  8. Odense University Hospital, Odense, Denmark

  9. Rigshospitalet, Copenhagen, Denmark

  10. Hospital Universitario Central de Asturias, Oviedo, Spain

  11. Clinical Center of Serbia, Beograd, Serbia

  12. Emergency Medical Service, Central Region, Denmark

  13. Department of Clinical Epidemiology, Aarhus, Denmark

  14. Clinical Trials Unit, London School of Hygiene and Tropical Medicine, London, UK

CONDI2/ERIC-PPCI study investigators

Anthony Mathur (London), Peter O'Kane (Bournemouth), John Greenwood (Leeds), Diana Gorog (Lister), Alisdair Ryding (Norwich), Konrad Grosser (East Kent), Nick Curzen, Andrew Flett (Southampton), Dawn Adamson (Coventry), David Hildick-Smith (Brighton), Julian Gunn (Sheffield), Kai Hogrefe (Kettering), Ian Webb (London), Luciano Candilio (London), James Cotton (New Cross), Kamal Chitkara (Derby), Rob Butler (North Staffordshire), Chiara Bucciarelli-Ducci (Bristol), Stephen Hoole (Cambridge), Reto Gamma (Basildon), Chetan Varma (Birmingham), Vinod Venugopal (Lincoln). Iqbal Malik (London), Kaeng Lee (Birmingham), Ali Dana (Portsmouth).

Corresponding authors. Prof. Derek J. Hausenloy, The Hatter Cardiovascular Institute, University College London, UK. Email: d.hausenloy@ucl.ac.uk; Prof. Hans Erik Bøtker, Department of Cardiology, Aarhus University Hospital, Skejby, Denmark, Email: heb@dadlnet.dk

References

References are available as supplementary material at European Heart Journal online.

Articles from European Heart Journal are provided here courtesy of Oxford University Press

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