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Aims The association between the dissemination of scientific articles on Twitter and online visibility (including Altmetric score) is still controversial and the impact on citation rates has never been addressed for cardiovascular medicine journals. Methods and Results The ESC Journals Study randomized 696 papers published in the ESC Journals family (March 2018–May 2019) for promotion on Twitter or to a control arm (with no active tweeting from ESC channels) and aimed to assess if Twitter promotion was associated with an increase in citation rate (primary endpoint) and Altmetric score. This is a preliminary analysis of 536 articles (77% of total) published until December 2018 (therefore, papers published at least 6 months before collecting citation and Altmetrics data). In the analysis of the primary endpoint, Twitter promotion of articles was associated with a 1.43 (95% confidence interval 1.29–1.58) higher rate of citations, and this effect was independent of the type of article. Both Altmetric score and number of users tweeting were positively associated with the number of citations in both arms, with evidence of a stronger association (interaction) in the Twitter arm. Conclusion Therefore, a social media strategy of Twitter promotion for cardiovascular medicine papers seems to be associated with increased online visibility and higher number of citations. The final analysis will include 696 papers and 2-year scientific citation rate and is estimated to be concluded in March 2021.

The association between the dissemination of scientific articles on Twitter and online visibility (as assessed by the Altmetric Score) is still controversial, and the impact on citation rates has never been rigorously addressed for cardiovascular medicine journals using a randomized design. The ESC Journals Study randomized 695 papers published in the ESC Journal Family (March 2018–May 2019) for promotion on Twitter or to a control arm (with no active tweeting from ESC channels) and aimed to assess whether Twitter promotion was associated with an increase in citation rates (primary endpoint) and of the Altmetric Score. This is the final analysis including 694 articles (one paper excluded due to retraction). After a median follow-up of 994 days (interquartile range: 936–1063 days), Twitter promotion of articles was associated with a 1.12 (95% confidence interval: 1.08–1.15) higher rate of citations, and this effect was independent of the type of article. Altmetric Attention Score and number of users tweeting were positive predictors for the number of citations. A social media strategy of Twitter promotion for cardiovascular medicine papers seems to be associated with increased online visibility and higher numbers of citations.

Background The P wave dispersion concept was created to describe the non-uniform atrial conduction as a separate AF factor. However the major assumptions of the theory are inconsistent with the main principle of electrocardiography, which assumes that 12 leads of ECG, recorded simultaneously, register the same events at the same time. The presence of dispersion suggests the presence of a P wave in one lead, while in the other one it has ended and no longer exists. This observation per se could be considered as a methodological artifact. Objective The major objective is to present that the P wave dispersion descends from imprecise measurements in various ECG leads. We intend to demonstrate that more accurate measurements make this parameter disappear. Methods Our study included 150 patients (89F, 61M) assessed using the electrophysiological system, which allowed to assess the sinus P waves. The P wave duration was measured by 3 independent researchers in all leads twice: 1. paper speed=50 mm/s, enhancement 16x (basic measurement) 2. paper speed=200 mm/s, enhancement 128–256x, simultaneously measuring the P wave dispersion. All measurements were repeated 3 times. Results The results are presented in Table 1 Conclusion 1. The P wave dispersion is the artifact of measurement. It is clear that after using much more accurate tools, the parameter disappears. 2. The P-wave dispersion is connected with Pmax, therefore may be apparently clinically useful but as a matter of fact, doesn't carry any meaning itself. 3.The significant P wave duration parameter should be a total atrial activation time, from the beginning of the earliest recorded P wave, till the end of the last Pwave recorded in any lead. Funding Acknowledgement Type of funding source: None

Background Review of scientific literature is a time consuming but fundamental step in any kind of scientific research. A consistent manual filtering of papers is always necessary in order to evaluate their relevance with respect to the topic of interest, as the sorting provided by most common research engines is rarely efficient in terms of matching with the desired contents. Purpose The aim of this study was to develop, and validate versus manual analysis, an automated tool for performing an efficient search through medical scientific literature, according to keywords relevant to the application of specific technologies in the field of cardiology. Methods Using this multiplatform tool implemented in Python, PyQt5 library, the user is required to insert a list of keywords, from which all the possible search strings were built by connecting them with logical operators. The algorithm automatically queries the on-line database PubMed (NCBI) and downloads all the resulting abstracts, with titles and keywords. Results related to the field of cardiology are identified counting the occurrences of “marker” words collected in a dedicated dictionary, developed on the base of the Unified Medical Language System (U.S. NLM). Then, a search-specific dictionary is automatically developed according to the statistical distribution of words in the texts of abstracts, titles and keywords and weighting them according to their relative frequency (ratio between occurrences and number of considered papers). Finally, for each paper the occurrences of these “marker” words are counted and a matching-probability score is assigned, providing a sorting of the results according to expected matching with the topic of interest, together with a threshold-based binary classification. In order to validate the algorithm, three different technologies with potential applications in cardiology were considered: smartphone applications (App), machine learning (ML) and virtual reality (VR). The related dictionaries were developed with the dedicated function embedded in the tool, while, for the validation of the results, a dataset of 461 manually-classified abstracts was considered, and algorithm thresholds were iteratively adjusted on the base of validation results. Results The algorithm applied to the validation dataset showed an overall accuracy (acc) of 88.5% (sensitivity (se) 85.78%, specificity (sp) 91.27%) in the identification of cardiology papers, while the results for the three inspected technologies were: App: acc 90.89% (se 92.16%, sp 90.53%) ML: acc 82.65% (se 94.06%, sp 79.44%) VR: acc 91.54% (se 96%, sp 90.3%) The algorithm can process 5000 abstracts in around 2 hours. Conclusions Results of the validation revealed that the proposed approach is highly valuable in speeding-up any search of medical literature focused on a specific technology or application, enabling a quick overview regarding its diffusion and maturity in a specific scientific domain. Algorithm schema Funding Acknowledgement Type of funding source: None

Background Peripartum cardiomyopathy (PPCM) is a rare but serious condition that affects childbearing women. Dopamine agonists (DAs) may represent a specific therapy, potentially facilitating left ventricular recovery, through inhibition of prolactin secretion. However, their therapeutic value in this setting has not been fully demonstrated. Purpose To perform a meta-analysis aimed at evaluating the extent to which DAs are able to interfere with the natural history of PPCM. Methods We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library, Google Scholar, Scopus and DARE for both randomized controlled trials (RCTs) and observational studies addressing the impact of DAs on main outcomes of PPCM patients, published up until February 1, 2020. Endpoints were those of mortality, recovery from heart failure and, likewise, the degree to which left ventricular ejection fraction (LVEF) was restored. All analyses were conducted under a DA plus optimized medical therapy (OMT) vs. OMT alone design, while results were pooled using traditional meta-analytic techniques, under a random-effects model. Odds ratios (ORs) were computed for the first two outcomes, whereas mean difference (MD) was calculated to quantify LVEF restoration. Results 2 RCTs, 2 prospective cohort, 1 prospective case-control and 2 retrospective cohort studies, encompassing 452 patients, were regarded as eligible for quantitative evaluation. 180 patients were allocated to the DA arm, which was mostly represented by bromocriptine; in fact, only 1 study, including 24 patients, specified cabergolin utilization. Overall, 5 papers including 295 patients reported 42 deaths, whereas 5 papers comprising 305 patients detailed 220 heart failure recoveries, thus unveiling that LVEF restoration was the norm. The addition of a DA to OMT provided no signal of a survival benefit (OR 0.71, 95% CI 0.27–1.87, p=0.49, i2=27%). On the other hand, the incorporation of a DA into the therapeutic regimen narrowly missed significance for the heart failure recovery endpoint (OR 2.68, 95% CI 0.98–7.31, p=0.05, i2=56%). Furthermore, DAs were demonstrated to incrementally improve LVEF by 15% (MD 15.00, 95% CI 10.24–19.76, p Conclusion In PPCM patients, the addition of a DA to OMT seems to be both effective at incrementally improving LVEF and safe, even though not reaching survival benefit status. These findings appear to corroborate the so-called prolactin hypothesis for PPCM pathophysiology. Funding Acknowledgement Type of funding source: None

Background Electrocardiographs (ECG) are obtained by a digital signal. However, they are still printed out of paper to read by physicians. Digitizing the analog ECG from the paper to digital signal make us much easier to access of bid data pool form the daily clinical practice and previous resources. Objective The goal of this study is to digitize paper ECG to detect premature ventricular contraction (PVC). Methods This system consists of 2 steps; digitization and PVC detection. Results First, for digitization, ECG are filtered by the specific cut-off value of red, green and blue, then the filtered ECG image is changed into gray scale. In order to extract ECG signal, the algorithm fine the only one of the biggest white body throughout the X-axis. The X and Y axis is matched with distance and amplitude, depending on dots per inch (DPI). Second, to detect PVC, ECG signal is filtered to eliminate baseline wandering. The characteristics of PVC is higher amplitude and longer duration than normal sinus rhythm, we set two criteria to detect the PVC: 1.5 times the duration, 1.2 points out of the amplitude. For the synchronization of timing, lead II rhythm strip was used by PVC detection and then the rest of 12-lead ECG is matched based on lead II synchronization (Figure 1). We applied this algorithm to the 300 real patient's ECG. 290 of 300 (96.7%) ECG are successfully digitized signal and PVC detection. Conclusion We successfully developed the algorithm analog ECG signal into digital signal to detect PVC. In the future, this method helps to gather big data from ECG papers to develop a new algorithm to localization of PVC. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Korean Heart Rhythm Society 2019 Research Fund

Background Cholesterol crystals (CCs) have been recognized as only ghost images. Recently, free monolayer and multilayer CCs besides atheromatous materials from aortic ruptured plaque, obtained using nonobstructive angioscopy, were demonstrated using polarized light microscopy. Purpose The aim of the study was to detect free CCs from coronary slow flow. Methods A total of 86 patients with coronary artery disease underwent angioscopy with coronary artery sampling. Blood in the coronary artery with and without temporary slow flow was sampled. The blood sample was spread onto a filter paper, and the filter paper was rinsed with distilled water (filter paper-rinse method). The rinse water was scanned using polarized light microscopy, and CCs were detected. The dimensions of CCs from the coronary artery and aortic ruptured plaques were measured for 100 randomly selected samples. The lengths and widths of the CCs were measured. Results CCs were obtained in 31 of 86 patients (36.0%). CCs were detected in 38.4% of patients with acute coronary syndrome and in 31.9% of patients with stable angina. CCs were detected 47.1% with slow flow and in 25% without slow flow. Cholesterol Crystals in Coronary Artery Conclusions CCs from the coronary artery can be successfully obtained by using our original method. CCs were detected in patients with clinically stable angina and in those without coronary artery slow flow.

Over the past 20 years, there has been a shift from vitamin K antagonists to direct oral anticoagulants (DOACs), which include the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban. Although DOACs are associated with less serious bleeding than vitamin K antagonists, bleeding still occurs with DOACs, particularly in the elderly and in those with comorbidities. Reversal of the anticoagulant effects of the DOACs may be needed in patients with serious bleeding and in those requiring urgent surgery or intervention. Reversal can be effected with specific agents, such as idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, or with non-specific agents, such as prothrombin complex concentrates, activated prothrombin complex concentrate, and recombinant activated factor VII. This paper (i) provides an update on when and how to reverse the DOACs, (ii) describes new reversal agents under development, and (iii) provides a strategic framework for the reversal of the factor XI inhibitors currently under investigation in phase three clinical trials.

The author reviews statistical methods commonly applied in economic evaluations that rely on individual patient-level data. The paper includes a review of foundational concepts, unique characteristics of health economic data, and methods developed to address them. The paper then highlights issues that should be considered in the interpretation of findings from economic evaluations.

Every activity needs a strategy—and publishing is no exception to the rule. When the current editorial team had the privilege to manage the flagship of the European Society of Cardiology (ESC), the European Heart Journal , in 2009, an initial and ambitious strategy was implemented.1 The strategy included (i) the nomination of deputy and associate editors from around the world (‘going global’); (ii) the creation of the ESC Journal Family with manuscript transfer (‘l'union fait la force’); (iii) improved readability of the journal with the introduction of CardioPulse, invited reviews, and editorials with high quality illustrations (‘reading must be fun’); (iv) shorter turnaround time for manuscripts of first decision (currently 22 days) and expansion of the FAST TRACK expedited review process to both the ESC Hotline Sessions and basic science papers (‘fast and innovative’); and (v) introduction of novel electronic features (i.e. iPad and iPhone versions, and new media features, i.e. My Cardio Interview of hotline presenters, among others; ‘modern and young’ ( Table 1 ). View this table: Table 1 New features introduced in the European Heart Journal 2009–2011 and as of 2012 Thanks to the help of our editors, editorial board members, and numerous reviewers, as well as the continued support of the board of the ESC, the major aims of the initial strategy were accomplished. Indeed, the journal has received an increasing number of manuscripts (with 3800 submissions expected this year), transferred a growing number of suitable papers to the specialty journals (currently ∼500 per year), published a large number of Hotline papers presented at the ESC Annual Congress, the American Heart Association Scientific Sessions, or the American College of Cardiology, and is present at national and specialty congresses with its ‘Best of the EHJ Sessions’. Furthermore, its revamped homepage is widely visited, papers and guidelines are downloaded in large numbers, and …

Can we improve our understanding of cardiovascular disease (CVD) causality and prediction? Intuitively, we can. Recent publications, however, could be misinterpreted as suggesting the opposite. First, the Interheart study, which concluded that nine conventional risk factors explain >90% of premature myocardial infarction, is at risk for being interpreted as saying that other, 'new' cardiovascular risk factors can only cause a small remaining fraction of disease of at most 10%. Secondly, papers addressing the predictive value of new risk factors or markers of early CVD risk have concluded that risk prediction does not improve by adding these variables to risk models. In this paper, we will explain that searching for 'new causes' of CVD is still highly relevant, and that improvement of risk prediction is often assessed using inappropriate statistical methodology. © The Author 2008.

Aim To describe and evaluate the methods currently used to summarize, depict, and analyse hospitalization data in clinical studies of patients with heart failure. Methods and Results Studies published during 1999 and 2000 were reviewed if they reported hospitalization data collected during the follow-up of a defined group of adults who had been diagnosed as having heart failure. Of 130 studies identified, the majority considered only the first of any hospital admissions for each individual. When presented, statistical analyses in 70% of papers, and graphics in 75% of papers, were based purely on the first hospitalization. A minority of papers based analyses on the number of admissions (23%), or the amount of time spent in hospital by patients (14%) during the follow-up period. Conclusions Data on the hospitalizations undergone by patients with heart failure are potentially informative about the disease burden to individuals and health services. The widespread practice of focussing a statistical analysis on the first admission a patient undergoes discards those aspects of hospitalization that are informative about disease burden: multiple admissions and length of stay. Statistical methods that incorporate these aspects appeared in a handful of papers, and the more widespread adoption of these is desirable.

Aims To systematically review the management of atrial fibrillation (AF) in patients with heart failure. Methods Studies investigating the management of AF in patients with heart failure published between 1967 to 1998 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. Results Eight studies pertaining to acute and twenty-four pertaining to chronic AF were identified. For patients with acute AF ventricular rate control, anticoagulation and treatment of heart failure should be pursued simultaneously before cardioversion is attempted. Digoxin is relatively ineffective at controlling ventricular response and for cardioversion. Intravenous diltiazem is rapidly effective in controlling ventricular rate and limited evidence suggests it is safe. Amiodarone controls ventricular rate rapidly and increases the rate of cardioversion. There are insufficient data to conclude that immediate anti-coagulation, trans-oesophageal echocardiography to exclude atrial thrombi followed by immediate cardioversion is an appropriate strategy. Patients with chronic AF should be anti-coagulated unless contra-indications exist. It is not clear whether the preferred strategy should be cardioversion and maintenance of sinus rhythm with amiodarone or ventricular rate control of AF combined with anticoagulation to improve outcome including symptoms, morbidity and survival. Electrical cardioversion has a high initial success rate but there is also a high risk of early relapse. Amiodarone currently appears the most effective and safest therapy for maintaining sinus rhythm post-cardioversion. Digoxin is fairly ineffective at controlling ventricular rate during exercise. Addition of a β-blocker reduces ventricular rate and improves symptoms. Whether digoxin is required in addition to β-blockade for the control of AF in this setting is currently under investigation. If pharmacological therapy is ineffective or not tolerated then atrio-ventricular node ablation and permanent pacemaker implantation should be considered. Conclusion There is a paucity of controlled clinical trial data for the management of AF among patients with heart failure. The interaction between AF and heart failure means that neither can be treated optimally without treating both. Presently treatment should be on a case by case basis.

Patients are ultimately the end-users of medical therapies and need to be actively integrated as contributors and decision-makers in the process of product development throughout product lifecycles. This is increasingly being recognized by patients, investigators, regulators, payers, sponsors, and medical journals. However, cardiovascular research remains behind other fields in terms of the extent of patient involvement and awareness of clinical trials in cardiovascular research. True patient partnerships in cardiovascular therapeutic development may permit more rapid recognition of unmet needs, ensure alignment of product development priorities with patient priorities, improve efficiency of trials (e.g. recruitment), and ensure outcomes of value to patients are being measured in trials (e.g. quality of life). This paper reviews ongoing initiatives and remaining opportunities to accomplish contributive patient involvement in cardiovascular clinical research.

With the increasing incidence of heart failure due mainly to diastolic dysfunction, a consensus statement on how to diagnose diastolic heart failure is clearly important. The paper by Paulus and co-authors represents a significant effort.1 It contains a detailed discussion on whether diastolic heart failure represents a separate entity, or whether it is an early stage where systolic function is only mildly impaired, but with later progression to more severe dysfunction. Newer information on possible mechanisms for the diastolic dysfunction is discussed, and there is clearly more to be learned in this area. However, it is not easy to see diastolic heart failure as a separate single entity when several different diseases can result in cardiac involvement with predominantly diastolic dysfunction. In the paper, the authors have chosen to replace the term diastolic heart failure with the term HFNEF [heart failure with normal left ventricular (LV) ejection fraction (EF)], citing clarity, even if evidence of diastolic dysfunction is included for the diagnosis of HFNEF. However, heart failure with normal EF can also occur in other conditions and without the presence of diastolic dysfunction.2 The flowcharts for diagnosing or excluding diastolic heart failure are useful, presenting simple and easy pathways and clear cut-off levels. While this can be an advantage, it may also raise questions about excluding data that might improve sensitivity and/or specificity. The choice of LV EF > 50% has been customary to equate with normal systolic function—or, as here, normal or mildly reduced systolic function. It is mentioned that longitudinal shortening may be reduced, but compensated for by increased radial shortening. A decrease in longitudinal shortening is an early sign of LV systolic dysfunction in both non-dilated and dilated ventricles.3–6 However, since the majority of studies as well as laboratories and cardiologists still … *Corresponding author. Tel: +34 972 660871. E-mail address : livhatle{at}eresmas.net

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Janssen Australia and New Zealand (Janssen-Cilag Pty Ltd) Pulmonary Arterial Hypertension (PAH) management strategies focus on lowering mortality risk, extending the patient’s life span through the control and alleviation of disease symptoms, improving Quality of Life (QoL) and decreasing the burden of illness. This paper describes preliminary results of an Investigator Initiated pilot study exploring the relationship between PRO measures (PAH-SYMPACT, EQ5D5L); Burden of Illness assessment; and the ESC/ERS Risk Stratification. Findings Measures of PAH risk and QoL were assessed in 42 patients presenting to the IPAH clinic for management; mean age 69.2 [range 39, 84]; females 35 (83.3%), males 7 (16.7%). Tools analysed and compared included: PAH-SYMPACT and EQ-5D-5L as PRO and QoL measures; and ESC-ERS PAH risk stratification criteria to assess mortality risk. Health utility scores were derived from existing value sets: there was a 20% median reduction in QALYs for our patient population, with detrimental effects being more marked in those patients with greater impairment of EQ-5D-5L physical and cognitive-emotional domains (respectively: r = -0.92, p Conclusions The fact that PRO indices showed little correlation with established risk stratification markers implies that the information provided by PROs is not redundant, and it is yet be assessed whether the incorporation of PRO’s may add further to the precision of risk assessment, a little-studied area which this group is further exploring. There should be more widespread and uniform use of PRO measures as part of standard PAH management.

Funding Acknowledgements Type of funding sources: None. Background Diabetes is a well-known risk factor for cardiovascular diseases and continues to be a global public health challenge. In Australia, prevalence rates of diabetes increase with age with almost 1 in 5 older people reported being diagnosed with diabetes. Older persons with diabetes are also more likely to have multiple comorbidities adding to their complexity. A better understanding of comorbidity patterns and their associated factors in older people with diabetes is instrumental to identify groups of individuals that differ in healthcare needs, resources utilized, and health trajectories. Purpose To identify comorbidity patterns in community-dwelling older adults with type 2 diabetes attending general practice settings in Australia. Methods This is a cross-sectional study based on the Bettering the Evaluation And Care of Health (BEACH) data. The BEACH program was a continuous, national study of the state of general practice clinical activity in Australia from 1998 to 2016. As part of the program, General Practitioners (GPs) would collect additional patient information during patient visits through structured paper-based recording sheets. For the purposes of this sub-study, a random sample of 1800 participating GPs were invited to record all diagnosed chronic conditions for 30 consecutive patients over twelve five-weeks recording periods between November 2012 and March 2016. The dataset was analyzed with descriptive analysis and exploratory factor analyses were applied to examine comorbidity patterns. Result From the dataset, there were 14 042 patients aged ≥65 with recorded chronic conditions. Of these, 2688 reported to have other comorbidities in addition to the diagnosis of diabetes. Hypertension was present in 67.33% (95% CI: 64.62 – 70.04) of these participants, followed by hyperlipidemia, 44.85% (95% CI: 41.80 –47.90), ischemic heart disease, 22.81% (95% CI: 20.74 – 24.87), atrial fibrillation, 10.25% (95% CI: 8.86 – 11.63), congestive heart failure, 7.03% (95% CI: 5.99 – 8.09), stroke/cerebrovascular accident, 6.76% (95% CI:5.36 -8.16) and peripheral vascular disease 5.26% (4.36 – 6.15). Top non-cardiovascular co-morbidities included arthritis, 51.78% (95% CI: 48.80–54.77) and depression, 15.52% (95% CI 13.78 –17.27). We identified two comorbidity patterns among older people with diabetes. The first were primarily psychological and musculoskeletal (Depression, Anxiety, Insomnia, Chronic Back Pain, Arthritis, Gastroesophageal Reflux Disease, Osteoporosis) and the second were cardiovascular conditions (Congestive Heart Failure, Ischaemic Heart Disease, Atrial Fibrillation, Peripheral Vascular Disease) and Chronic Renal Failure. Conclusion The prevalence of cardiovascular and non-cardiovascular comorbidities in older patients with diabetes was high. These findings highlight the need for elaborating primary care strategies to reduce cardiovascular risk and improve long-term care for this population.

Сърдечно-съдовата медицина през 2022 г: 10-те най-добри статии за клапни сърдечни заболявания The year in cardiovascular medicine 2022: the top 10 papers in valvular heart disease

Atrial fibrillation, a commonly encountered arrhythmia, has in recent years, been the subject of increased interest and intensive clinical research. There is also increasing awareness that atrial fibrillation is a major cause of embolic events which in 75% of cases are complicated by cerebrovascular accidents[1,2]. Atrial fibrillation is often associated with heart disease but a significant proportion of patients (about 30%) have no detectable heart disease[3]. Symptoms, occasionally disabling, haemo-dynamic impairment and a decrease in life expectancy are among the untoward effects of atrial fibrillation, resulting in an important morbidity, mortality and an increased cost for the health care provider[4]. The Working Group of Arrhythmias of the European Society of Cardiology created a Study Group on Atrial Fibrillation in order to establish recommen-dations for the better management of this arrhythmia and to promote multicentre studies. The purpose of this paper is to briefly outline the state of our knowledge on the clinical presentation, the causes, the mechanisms and therapeutic approaches currently available and to propose recommendations for management. Although atrial flutter can coexist with atrial fibrillation, it is considered a different arrhythmia and will not be covered in the present paper.

Aim This study reports on the results and safety of a simplified method of trans-septal catheterization for radiofrequency catheter ablation of cardiac arrhythmias. Method and Results Over 5 years, 411 patients underwent trans-septal catheterization for radio frequency catheter ablation: 388 patients had a left-sided accessory pathway, 19 a left-sided focal atrial tachycardia, two atrial fibrillation and two post-infarction ventricular tachycardia. All but one patient with ventricular tachycardia underwent elective trans-septal catheterization. In the absence of a patent foramen ovale, puncture of the atrial septum was performed by using an 8F Mullins sheath and a Brockenbrough needle, according to the simplified method described in this paper. Trans-septal catheterization was accomplished in 383/388 patients (98.7%); in 41 patients a second trans-septal catheterization and radio frequency catheter ablation was performed for initial failure or recurrence. Radiofrequency catheter ablation was successful in 96% of accessory pathway patients, 90% of atrial tachycardia patients, in both patients with atrial fibrillation and in both patients with ventricular tachycardia. No complication related to trans-septal catheterization was observed. Conclusion In experienced hands and according to the method described in this paper, the elective use of transseptal catheterization for radiofrequency catheter ablation in a large cohort of patients with cardiac arrhythmias is feasible, safe and allows successful ablation in the vast majority of the patients.

Searching in PubMed for the string ‘tool or toy’ in the title of medical papers, we found that over the past three decades about 50 papers brought up the dilemma concerning whether a novel technology is a useful tool, or merely an expensive toy. The papers are from 15 different medical disciplines spanning from radiology, neurology, anaesthesia, and surgery. Surprisingly, in almost half of these papers the ‘tool or toy’ dilemma is posed for new technologies introduced in the cardiovascular field. Several of them, such as stress echocardiography and transoesophageal echocardiography, have become widely diffused and have definitely become routine practice. Although this analysis of the medical literature is gross, the result underlines that this dilemma is not so rare. In fact, new technologies are periodically proposed and the reaction of the medical community is usually quite ambiguous, varying from the hardest scepticism to the warmest enthusiasm. Actually, far from being an expression of physicians' uncertainty, the dilemma is justified by the fact that on one hand new technologies, especially in their early phases, are associated with high costs for equipment acquisition and their disposable parts, that the field of application is not well defined, and that the initial version is usually not completely developed because the engineer's work requires physician's feedback to ameliorate and render user friendly, brand new technologies. On the other hand, the introduction of new technologies may be the first step in a revolution which advances the frontiers of medical science and therapeutic approaches by providing more effective treatments in an always increasing cohort of patients. In 1996, the in vivo use of a non-fluoroscopic magnetic technology for endocardial navigation and mapping of the heart was reported.1 Although initially the focus was on the fact that the position of the catheter could be … *Corresponding author. Tel: +39 0332 278934; fax: +39 0332 393309. E-mail address : rdeponti{at}alice.it

Under the editorial directives of Prof Kim Fox, the European Heart Journal has become one of the most important international journals in clinical cardiovascular (CV) medicine. This has paralleled the growing influence and importance of the European Society of Cardiology (ESC), of which the European Heart Journal is the principal journal, in global CV medicine today. Besides high-level, peer-reviewed research papers, the Journal is the forum where the ESC publishes its much used and cited guidelines aimed at promoting the immediate use of the latest research findings for patient treatment, positioning the Journal at the forefront of the trend towards an evidence-based clinical CV medicine. As of 1st October 2002, the Editorial Office left London, England, and came to Leuven in Belgium. This change of address and leadership has led to a significant number of changes within the journal itself including a broadening of the scope of the articles published and the introduction of a fully electronic and online system, which facilitates the submission of manuscripts from authors and streamlines the reviewing and publication processes. In order to manage the amount of papers and the broad and numerous scope of subspecialities, a local team of 22 Associate Editors, each with a specialty in a sub-discipline of CV medicine, has been established offering immediate expertise in the evaluation of each manuscript submitted to the European Heart Journal . The evaluation system (Fig. 1) has become highly comprehensive with each published paper now receiving a minimum of seven reviewers: three Editors, two or three expert reviewers, a detailed statistical review by our in-house bio-statisticians and final editing of the manuscript to ensure the accuracy of the … *Correspondence to: Dr. Neil Goodman, PhD, Department of Cardiology, Gasthuisberg University Hospital, Herestraat 49, B3000 Leuven, Belgium. Tel.: +32-16-342-118; fax: +32-16-342-138 neil.goodman{at}uz.kuleuven.ac.be

Arrhythmias remain a frequent cause of morbidity and mortality in cardiovascular (CV) patients, and thus an important issue for practising cardiologists. Therefore, the European Society of Cardiology has published guidelines on cardiac pacing and resynchronization therapy1 and on atrial fibrillation,2 syncope,3 and ventricular arrhythmias,4 and, together with our US sister societies, on supraventricular arrhythmias,5 to help physicians in their daily work. Nevertheless, many unsolved issues remain. In this issue of the European Heart Journal , the editors selected four papers dealing with pacing and arrhythmias. The first paper, entitled ‘Long-term clinical effects of ventricular pacing reduction with a changeover mode to minimize ventricular pacing in a general pacemaker population’, by Martin Stockburger et al .6 reports the results of the ANSWER study which evaluated whether an AAI–DDD changeover mode to minimize ventricular pacing (SafeR) improves outcome compared with DDD in a general dual-chamber pacemaker population. Indeed, it has been suggested that right ventricular pacing would increase the risk in heart failure and atrial fibrillation. ANSWER was a randomized controlled multicentre trial assessing SafeR vs. standard DDD in sinus node disease or atrioventricular block patients. After a 1-month run-in period, 650 patients were …

The current issue of the European Heart Journal focuses on a novel area of research, i.e. the function of microribonucloidacids (miRNAs). miRNAs are short, usually around 22-nucleotide-long non-coding RNAs involved in the regulation of gene expression ( Figure 1 ).1 They guide ribonucleoprotein complexes that induce translational repression or messenger RNA degradation to targeted messenger RNAs. miRNAs were first described the development of nematode worms in 1993, but are now recognized to play an important role in human health and disease as well. Since their discovery, an increasing number of miRNAs with a whole array of biological effects have been found. Interestingly, overexpression or underexpression of specific single miRNAs or signatures of several nucleotides has been implicated in the development of several diseases, including those affecting the heart and the circulation. Indeed, the European Heart Journal has published a series of papers suggesting the involvement of microRNAs in resistant hypertension, the progression of vascular disease, neovascularization, aspirin resistance, myocardial fibrosis, myocarditis, myocardial infarction, and heart failure.2–5 Figure 1 Schematic of microRNA biogenesis and action. The mature microRNA sequence is given in red. TF, transcription factor; Pol, RNA polymerase II or III; Exp5, exportin 5. (From Condorelli et al. 1). In this issue of the European Heart Journal, four papers report new findings on the potential …

Background Numerous online journals are referred to as predatory journals because their efforts are focused primarily on collecting publication fees rather than on content, peer review, or manuscript presentation. Many of these journals send Academic Spam Mails (ASM), requesting manuscript submissions. Purpose/Methods Over a 3-month period, all ASMs addressed to the author were collected and analyzed. A fake publication was created with a commonly used structure (Introduction, Methods, Results and Discussion). The article just repeated the phrase “Please get me off your mailing list” over and over again. This publication was submitted in response to each request to test the control mechanisms of the respective journals. Results During the study period, excluding duplicate requests, 125 ASMs (average 2.1 per business day) were received from a wide variety of journals spanning 38 different subject areas, of which 29/38 (76.4%) were from the medical field. 16/125 (16%) were related to a previously published article but not among the author's most important publications (median h-index rank 22; range 10–138). The majority (73.6%) of journals were listed in Beall's predatory journal list, only an absolute minority (0.8%) were listed in the Directory of Open Access Journals, and 96% were not listed in PubMed. Original papers (94.4%), reviews (88.0%), and case reports (87.2%) were most frequently requested; the publication charge (APC) was a median of $1,199 (range $50–3,586); in about 22% of cases, it was not apparent whether APCs were charged and, if so, how much. For the 125 nonsense publications sent out, there was a response in 16/125 (13%) (6 acknowledgements of receipt, 3 apologies, 2 the journal comments that the publication consisted of only one sentence, and 5 other responses). Interestingly, in one case editorial board members had also created a nonsense publication titled: “Ok we not send mail to you” and sent it to the author. 21.6% of the journals had sent ASM to the author again during the next months. Conclusions Academic spam mails from “predatory” online journals are a common problem. They are recognizable by their appearance in warning lists or non-appearance in directories of reputable open access journals. A placement of a nonsense publication in such a “predatory journal” was not successful. Funding Acknowledgement Type of funding sources: None.

Introduction Continuity equation is the cornerstone of aortic valve area (AVA) calculation in patients with aortic stenosis (AS). In patients with irregular rhythms (IR) - especially atrial fibrillation (AF)-, values of velocity-time integral (VTI) at left ventricular outflow tract (LVOT) and aortic valve (AV) vary between heart beats. The usual recommendation is to average the measurements of 5 or 10 beats in both locations. However, original papers describing continuity equation, from which that recommendation arises (refs 1 & 2), only included 3 and 2 AF patients, respectively. To our knowledge, there are not clinical studies to support this procedure and its accuracy has not been established. In contrast, in a previous study our team had evaluated the accuracy of the double envelope technique to assess both LVOT and AV VTI in the same beat, with a 7.8% (CI 95%: 5.8–10.3) difference (error) in the estimation of AVA when compared to pulsed wave of LVOT in patients with stable sinus rhythm. Purpose To evaluate how dispersion in VTIs due to IR impacts on variability of AVA calculations. Methods For each patient, we recorded multiple measurements of VTI in both LVOT and AV (mean 36.8 beats, range 29–47) per patient and location). Reference AVA was estimated using the average of all these measurements. To estimate the accuracy of averaging 5 or 10 heart beats, we created a computer code which simulated the AVA calculation using random samples of these measurements, and calculated the difference between true AVA and that obtained in the simulation (expressed as percentage of the true value). The process was iterated 10,000 times to obtain the distribution of differences and to estimate its mean value. Data handling and graphic representation was performed with Python 3.9.6 and Pyodbc, Pandas, NumPy, Matplotlib and Seaborn libraries. Results We included data from 8 patients with AS and IR (Age: 71 to 89, mean 82.5 years; Aetiology: degenerative (100%); Sex: 3 males / 5 females; Rhythm: AF [7], atrial flutter [1]; Severity: severe [3], moderate [4], mild [1]). Mean difference in AVA calculations was 8.2% (range: 5.1–13.5%). With 10 beats, mean difference was 5.7% (range: 3.6–9.5%). Figute 1 shows violin plot with distribution in each patient of recorded VTIs at both AV (left) and LVOT (right). To ease visualization, data are expressed as percentage of mean values. Fig 2 shows how that variability results in inaccuracy of AVA calculations with 5 (left) or 10 beats (right). Note that in many cases, possible results are located on both sides of the severity threshold of 1 cm2 (red line). Conclusion AVA assessment using 5 beats average results in a mean difference (error) of 8.2%, which can be reduced to a mean of 5.7% using 10 beats. These differences are comparable with the previously observed with the double envelope technique (7.8%). Funding Acknowledgement Type of funding sources: None.

Background Immediate diagnosis of acute decompensated heart failure (ADHF) is essential in patients with dyspnoea. Remote Dielectric Sensing (ReDS), an electromagnetic non-invasive technology, estimates lung fluid content fast and observer-independently. In previous studies, ReDS discriminated congested heart failure patients from normal subjects with high accuracy. But not all ADHF patients have pulmonary interstitial congestion in the real world, and it is unknown if ReDS detects ADHF in consecutive patients with acute dyspnoea. Purpose To examine if ReDS can detect ADHF in consecutive dyspnoeic emergency patients and to compare ReDS with other diagnostic methods. Method This prospective observational study included consecutive patients with dyspnoea from the emergency departments. The exclusion criteria were age below 50 years, acute coronary syndrome, conditions prohibiting a supine CT scan, and no informed consent. We examined all patients immediately with ReDS, low-dose chest CT, echocardiogram, lung ultrasound (LUS), NT-proBNP, and Boston score. The Boston score used chest X-ray and clinical signs such as orthopnoea, jugular venous elevation, lung crackles and pedal oedema, and a score ≥8 equalled definite ADHF. A “LUS-score” ≥3 with at least 3 B-lines in one zone bilaterally equalled ADHF. ReDS values >35% lung fluid content were positive for pulmonary congestion, according to previous studies. According to ESC guidelines, an expert panel adjudicated the ADHF diagnosis based on clinical signs, chest X-ray image, NT-proBNP, echocardiographic cardiac dysfunction (HFvhd, HFrEF, HFmrEF, HFpEF), and elevated LV filling pressure. Importantly, the panel was blinded to the ReDS values. For sub-analyses, we divided ADHF patients into a “CT-congested” ADHF subgroup if an independent chest CT showed interstitial congestion. We classified ADHF patients without congestion on CT, as the “mildly-congested” subgroup. Results 97 included patients were examined within a median of 4.8 hours from admittance: 39 (40%) had ADHF, and 25 (26%) were ReDS-positive. ADHF patients had median LVEF 48%, NT-proBNP 347 pmol/l, and 85% had echocardiographic elevated LV filling pressure. ReDS detected ADHF with 46% sensitivity, 88% specificity, and 71% accuracy. The AUC for ReDS to detect ADHF (Figure 1), on a continuous scale, was similar to the Boston score (p=0.88) and the LUS score (p=0.74), but lower than NT-proBNP (p=0.02). The 21 (22%) CT-congested ADHF patients had higher ReDS values than the 18 (19%) mildly-congested ADHF patients (Figure 2, median 38% vs 30%, p Conclusion ReDS detects ADHF similarly to the Boston score and lung ultrasound but is inferior to NT-proBNP. This study suggests that ReDS primarily identifies CT-congested ADHF patients, but not the ADHF patients without interstitial congestion. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by the research fund of Bispebjerg University Hospital and Holger & Ruth Hesse's Mindefond. Sensible Medical Ltd made the ReDS device available for free and provided an unrestricted grant to specifically collect the ReDS measurements. The sponsors did not affect the statistical analyses, study design, data collection, or writing of the paper.

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with high cardiovascular morbidity and mortality. However, cardiac involvement, especially at an early stages of the disease is largely underdiagnosed due to non-specific nature of the symptoms and low sensitivity of current diagnostic tools such as 2D conventional echocardiography derived left ventricular ejection fraction (LVEF), on the other hand, speckle tracking echocardiography (STE) derived left ventricular global longitudinal strain (LV GLS) has shown to be a reliable and sensitive tool for the diagnosis of subtle myocardial changes in various entities. Purpose The present study aimed to perform an extensive systemic review and meta-analysis of the current case-control studies based on the assessment of the left ventricular systolic function with standard and advanced echocardiographic methods. Methods The objectives, literature search strategies, inclusion and exclusion criteria, outcome measurements, and methods of statistical analysis were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE). Results A total of 825 papers were collected according to our searching criteria, of those 20 studies including 1121 SLE patients and 1010 controls with evaluated LVEF and 8 studies including 387 patients and 283 controls with evaluated LV GLS were selected. We found, that overall patients with SLE exhibited lower levels of LVEF [weighted mean difference -WMD (95%CI) 0.336 (−0.423 to −0.248); p Conclusions LV systolic function as measured by LVEF and LV GLS is significantly affected in SLE patients. Data from meta-analysis suggest that STE derived LV GLS assessment potentially represents a new tool to improve precise and early assessment of LV function and may improve risk-stratification in patients with SLE. Funding Acknowledgement Type of funding sources: None.

Background A Perugini Grade 1 myocardial uptake on amyloid cardiac scintigraphy does not establish the diagnosis of amyloid transthyretin cardiomyopathy (ATTR-CA), and according to current position papers mandates an endomyocardial biopsy to rule in or rule out ATTR-CA. We aimed to investigate whether Perugini Grade 1 reflects an early stage of ATTR-CA or a false positive result thus obliviating the need for further evaluation. Methods Study population was comprised of consecutive ≥70 years old patients who underwent a baseline cardiac scintigraphy scan for the presumed diagnosis of ATTR-CA at our institution between the years 2017–2020 and had a Perugini Grade 1 score. Patients with Perugini Grade 2 or 3 comprised our control group. At the beginning of 2022, Perugini Grade 1 patients prospectively underwent a repeat follow-up evaluation which included clinical examination, echocardiography with strain parameters, cardiac biomarkers measurement and cardiac scintigraphy. Cardiac magnetic resonance (CMR) and genetic testing for ATTR-CA mutations were analyzed as well. Preliminary results Fifty patients were included in the baseline study cohort, of whom 44% (n=22) were females. A carpal tunnel syndrome history was present in 10 patients (20%). Baseline troponin T and NT pro-BNP levels were 23 (IQR 14,39) and 1557 (IQR 237, 5746) ng/L, respectively. Wall thickness by echocardiography was 12 (11, 15) mm and 8 patients (16%) had severe mitral annulus calcification. Left ventricular ejection fraction (LVEF) was 60 (IQR 50, 60)%. At a median follow-up of 31 (20, 35) months, 7 patients (14%) were diagnosed with plasma-cell dyscrasias and 6 patients (12%) were hospitalized for heart failure exacerbations. Follow-up troponin T and NT pro-BNP levels were 27 (IQR 21,46) pg/ml and 1158 (IQR 434, 7249) ng/L, respectively (p=NS compared to baseline). Wall thickness by echocardiography was 12 (12, 15) mm and LVEF was 60 (IQR 50, 60)% (p=NS compared to baseline). Follow-up cardiac scintigraphy demonstrated Perugini Grade 1 in all re-tested patients. Two patients and 14 patients (32% total) underwent an endomyocardial biopsy or CMR, respectively, for a definitive diagnosis. All 16 tests were incompatible with amyloid cardiomyopathy. Genetic data results will be added. All-cause survival was similar between patients with Perugini Grade 1 versus Grades 2 and 3 (log rank p=0.103). Conclusion At long-term follow-up, Perugini Grade 1 patients do not demonstrate progression of laboratory or imaging amyloid characteristics. This suggests that Perugini grade 1 reflects a false positive result for ATTR-CA rather than an early stage in the disease. Larger-scale data should further question the need for an endomyocardial biopsy in these patients. Funding Acknowledgement Type of funding sources: None.

Background Rapid reperfusion of the epicardial coronary artery by primary percutaneous coronary intervention (PCI) is the guideline-recommended treatment for ST-segment elevation myocardial infarction (STEMI). However, in a substantial proportion of patients, despite restored patency of the epicardial coronary artery, perfusion to the distal coronary microvasculature is not fully achieved. The principal cause of this phenomenon is severe microvascular dysfunction or loss of integrity leading to microvascular obstruction (MVO). Objectives Aim of the research was to understand the relationship between microvascular obstruction (MVO) and/or infarct size (IS) and/or left ventricular ejection fraction (LVEF) assessed early after PCI in STEMI patients and subsequent all-cause mortality, reinfarction, and hospitalization for heart failure (HF). Methods A literature review was performed with no restrictions in terms of geography or design of study. Publications related to the validation and/or comparison of methods to quantify microvascular obstruction or infarct size were discarded. Results Search criteria yielded 23 references. After exclusion of validation studies, 13 publications were retained. Most of these papers were authored by the same group of investigators. A pooled patient-level analysis from 10 randomized primary PCI trials (total 2,632 patients) established that IS was strongly associated with all-cause mortality and hospitalization for HF but not significantly related to subsequent infarction. Pooled analysis of patient data from 7 of these 10 randomized primary PCI studies showed that MVO was also significantly associated with all-cause mortality and hospitalization for HF but not related to subsequent infarction. 5 of these 10 randomized primary PCI trials allowed categorization of patients by time of the day of the primary PCI intervention. No association was found between the time of day and IS, MVO, or prognosis after STEMI. A similar analysis concluded that recent smoking was unrelated to IS or MVO but was associated with a worse prognosis after primary PCI in STEMI. No correlation was established between body mass index and IS, MVO or LVEF, or one-year rates of death or HF hospitalization. A sub-study of a nationwide randomized investigation in Denmark assessed the impact of age of STEMI on IS and LVEF and the composite endpoint of death and re-hospitalization for HF. Patients Conclusions MVO and IS assessed early after primary PCI in STEMI are strongly associated with death and hospitalization for HF within one year. Innovative technologies that limit IS by improving microcirculation function during STEMI are of great individual and socioeconomic value. Funding Acknowledgement Type of funding sources: Private company.

Introduction and aims The transition towards adult-focused healthcare comprises a complex process through which adolescents with congenital heart disease (CHD) should be carefully guided. Various task forces encourage implementing person-tailored transition programs, but detailed data on adolescents' preferences regarding disease-related information and acquirable transitional skills are mostly lacking. This study examined these preferences towards adolescents with moderately and severely complex CHD. Material and methods A cross-sectional descriptive study including logistic regression analysis was performed in a Belgian tertiary CHD center with adolescents recruited from “Transition With a Heart” (TWAH). For this 4-year transition program, adolescents were invited to complete a communication paper (focused on the need for information) and an individualized transition plan (focused on the evaluation of transitional skills) prior to an outpatient visit. Only questionnaires completed in the early transition stage, from January 2016 to August 2021, were used for data analysis. Results Forty-nine adolescents completed both questionnaires at an average age of 15.9±1.2 years. Of all adolescents, 59% indicated the need for information about the heart defect and surgical treatment, followed by 45% that expressed the need for information about sports and medication; and ≤27% regarding psychosocially-related topics. The proportion of girls needing information was larger than boys. Significantly more girls than boys requested information about surgeries (76% versus 46%; p=0.04). Younger adolescents were more likely to express a need for information about most topics and significantly more likely regarding surgeries (odds ratio=0.53; 95% CI [0.26 to 0.88]; p=0.03). A maximum of 14% of adolescents were interested in acquiring transitional skills. Larger proportions of adolescents perceived the relevant transitional skills as insufficient, from 21% to 83%. Conclusion The preferences for disease-related information of adolescents with CHD are mainly related to medical topics and tend to decrease with increasing age. This motivates timely gauging of individual information needs and delivering disease-related information, ideally in the early teens. Furthermore, preferences varied according to gender, with more information requested by girls. Adolescents expressed minimal needs to acquire transitional skills despite the low self-perceived skills levels. This paradox requires further research to enable the adaptation of transition interventions. Funding Acknowledgement Type of funding sources: None.

In this issue there are two papers that concern brachytherapy and at variance with the European Heart Journal’s policy, one paper deals with experimental results

Globally, there has been little change in mortality rates from cardiovascular (CV) diseases or cancers over the past two decades (1997–2018). This is especially true for heart failure (HF) where 5-year mortality rates remain as high as 45–55%. In the same timeframe, the proportion of drug revenue, and regulatory drug approvals for cancer drugs, far out paces those for CV drugs. In 2018, while cancer drugs made 27% of Food and Drug Administration drug approvals, only 1% of drug approvals was for a CV drug, and over this entire 20 year span, only four drugs were approved for HF in the USA. Cardiovascular trialists need to reassess the design, execution, and purpose of CV clinical trials. In the area of oncology research, trials are much smaller, follow-up is shorter, and targeted therapies are common. Cardiovascular diseases and cancer are the two most common causes of death globally, and although they differ substantially, this review evaluates whether some elements of oncology research may be applicable in the CV arena. As one of the most underserved CV diseases, the review focuses on aspects of cancer research that may be applicable to HF research with the aim of streamlining the clinical trial process and decreasing the time and cost required to bring safe, effective, treatments to patients who need them. The paper is based on discussions among clinical trialists, industry representatives, regulatory authorities, and patients, which took place at the Cardiovascular Clinical Trialists Workshop in Washington, DC, on 8 December 2019 (https://www.globalcvctforum.com/2019 (14 September 2020)).

The Copenhagen City Heart Study is a prospective cardiovascular population study designed to evaluate incidence of, and risk factors for, cardiovascular disease. A random sample, comprising approximately 20 000 people, were invited to participate. Initial information about potential risk factors was collected during 1976–78 (attendance rate 74%); data about 389 new cases of first acute myocardial infarction (AMI) was obtained from a second survey in 1981–83, as well as from hospital and death registers up to 31 December 1983. The average observation period was 6.5 years. Cox's regression model was used for data analysis. Some ‘basic’ factors, namely age, sex, family history of AMI, early parental death, height, earlobe crease, length of school education, income and living alone or with a partner were dealt with in a previous paper and are among the potential risk factors for A MI included in the Copenhagen City Heart Study. In this analysis we also include life-style characteristics, some biological traits and disease conditions. An increased risk for first AMI among smokers was graded; the estimated relative risk (ERR) for heavy smokers consuming more than 29 g tobacco per day was 2.8 relative to non-smokers. Alcohol intake of five or more drinks per day was associated with a decreased risk, an ERR of 0.6 relative to those who did not drink alcohol daily. Physical inactivity during work but not at leisure was associated with increased risk (ERR 1.4) as was body mass index where the risk was mediated mainly through blood pressure and plasma triglycerides. Oral contraception was not associated with an increased risk, whereas with diabetes the risk increased (the ERR for diabetes being 1.8). Plasma cholesterol above the level of approximately 7mmol 1−1 proportionally increased risk; the ERR in the 1.5% with the highest level was 3.7. A low triglyceride level was associated with low risk; the ERR in the fifth of the study population with the lowest level was 0.6. Elevated blood pressure also proportionally increased risk. Subjects on antihypertensive drug treatment had higher risk than non-treated subjects with similar blood pressure. The effect of socioeconomic factors described in the previous paper was not mediated through their influence on the risk factors included in the present analysis.

When I took over the editorial office of the European Heart Journal in the autumn of 2002 the flow of papers was mainly handled manually, and online submission did not even exist. Today more papers are read on the website of the journal than on paper, and an efficient electronic platform distributes manuscripts for review around the world in a few seconds. The use of the internet had a tremendous impact on the review process and the speed of publication. This is not the end of the electronic revolution. Let me give you one example. Even today, most papers are published several months (and, in the case of a cumbersome review, sometimes a year) after submission, thus hampering progress especially in rapidly evolving fields. Furthermore, debates on important published study results usually take place at meetings or webcasts organized several months after publication. Writing a letter to the editor is another possible way of commenting on published results, …

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas.

Funding Acknowledgements Type of funding sources: None. Background Recent recommendations suggest a combination of Angiotensin receptor neprilysin inhibitor (ARNI) and beta blocker with other classes of medications in heart failure with reduced ejection fraction (HFrEF) (1). Despite currently available treatment options, mortality remains high (2). From the recent robust clinical trials, both SGLT2 inhibitor (SGLT2i) and ARNI have been found to decrease HF hospitalizations and CV death (3-5). This paper aims to determine the efficacy of SGLT2i and ARNI combination versus ARNI alone in the management of HFrEF. Methods Randomized controlled, prospective or retrospective cohort trials on ARNI with SGLT2i versus ARNI without SGLT2i in patients with left ventricular ejection fraction of 40% or less were included. A search using Pubmed, CENTRAL, and ScienceDirect was conducted on April 29, 2021. Risk of bias was assessed using Cochrane’s Collaboration tool for RCTs and STROBE checklist for cohort, case-control and cross-sectional studies. Review Manager version 5.4 software was used for data synthesis and analysis. Outcomes were measured as mean differences and risk ratio for continuous data and dichotomous data with 95% confidence interval. Results Three studies were screened with a total of 1,742 patients; 759 received a combination of SGLT2i and ARNI while 983 received standard care plus ARNI. There was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the combination SGLT2i/ARNI group (HR 0.69, 95% CI 0.56-0.85, and p value of 0.0005). There was significant reduction in heart failure hospitalization in the treatment group with SGLT2i (HR of 0.61, a 95% CI 0.49-0.78) compared to the group without treatment of a SGLT2 inhibitor (< 0.0001). Composite renal event favors combination of ARNI and SGLT2i in some studies (HR of 0.73, with a 95% CI 0.39-1.38), however was not statistically significant (p value = 0.34). Conclusion Addition of SGLT2i with ARNI provides significant decrease in mortality and hospitalization among patients with HFrEF compared to control as well as improvement in renal function.

In the current paper, we review recently published studies that are helping us to understand how the treatment landscape for glucagon-like peptiide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors is moving forward. We have also included relevant articles related to cardiovascular disease prevention in the setting of obesity, atherogenic dyslipidaemia and chronic kidney disease.

Myocardial infarction (MI) is associated with the increase in plasma levels of inflammatory and haematopoietic cytokines and mobilization of a heterogenous population of cells which consists predominantly of committed lineages (monocytes, polymorphonuclear granulocytes, and lymphocytes), as well as numerous types of stem/progenitor cells [endothelial progenitor cells (EPCs), haematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs)]. The number of circulating EPCs may have a prognostic value; however, this concept remains to be proved in large prospective studies.1,2 The number of circulating EPCs and mature endothelial cells (ECs) supposedly reflects the vascular endothelial injury and the repair mechanisms activated to restore the endothelial integrity. The article by Ferrario et al. 3 investigates the haemoglobin-independent increase of the plasma levels of erythropoietin (Epo) in patients with acute MI and seeks to confirm the hypothesis that changes of Epo levels are associated with the mobilization of EPCs and ECs from the bone marrow. The paper by Ferrario et al. confirms previous work by the same group, published in 2005, describing the mobilization of heterogenous population of progenitor cells in patients with acute MI.4 In the present paper the authors identify two populations of immature EPCs (CD34+CD133+VEGFR2+ and CD34+CD117+VEGFR2+), more mature EPCs, and mature ECs (CD34+VEGFR2+). This study continues the search for humoral factors involved in EPC mobilization following acute myocardial ischaemia and vascular injury. One of the important issues … *Corresponding author. Tel: +48 604188669; fax: +48 32 2523930. E-mail address: wojwoj{at}mp.pl

This paper will critically review the main features of the various techniques (plasma noradrenaline assay, noradrenaline spillover technique, microneurographic recording of postganglionic muscle sympathetic nerve and power spectral analysis of blood pressure and heart rate signals in specific bands) currently employed to assess sympathetic cardiovascular control in humans. After highlighting the advantages and limitations of each approach, the paper will describe some of the results obtained by employing the above mentioned techniques to detect abnormalities in sympathetic cardiovascular tone in physiological and pathological conditions.

Research findings presented in scientific conferences have a considerable direct and indirect impact on decision-making of clinicians. Investigators in various fields of research have examined the possible differences in aims, results, and conclusions between conference abstracts and subsequent corresponding published papers. They documented that differences between data presented in conference abstracts and published papers are frequent and occasionally major. These findings strongly support the position that we should not hurry to incorporate in clinical decision-making data presented at international or national scientific conferences. Instead, we believe that we better serve our patients by waiting at least for the evaluation of potential scientific advances by rigorous peer review.

Graham and colleagues report health-related quality of life (HRQoL) in a cohort of patients 1 and 3 years after undergoing cardiac catheterization.1 The paper focuses on differences in HRQoL between groups of elderly patients (all >70 years of age) who were subsequently revascularized and those who received medication only. The former had consistently better HRQoL at both times, with a tendency for patients who had bypass surgery to report better health than those who had percutaneous intervention. The paper contributes to the growing literature suggesting that coronary revascularization is under-used,2–4 although it remains uncertain whether under-use arises because revascularization is withheld or refused. Increasing priority is being placed on estimating the effectiveness of interventions using outcomes that directly reflect patients' perceptions of the value of treatment (i.e. the extent to which benefits exceed harms), especially for interventions designed primarily to reduce the symptoms and physical impairments associated with chronic disease. Physicians are often suspicious about HRQoL, which they may perceive to be ‘soft’ or subjective. This suspicion is not warranted when properly validated instruments such as the Seattle Angina Questionnaire (and, more recently, the Coronary Revascularization Outcome Questionnaire),5 are used in participant-blinded randomized controlled trials (RCTs), where the interpretation of differences between groups is straightforward. Rather, physicians should see these instruments as measuring directly aspects of patients' lives, which they aim to influence by their clinical management. Interpretation of differences in HRQoL is more complex in observational studies, such as Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH).1 The authors analysed … *Corresponding author. Tel: +44 117 928 3143; fax: +44 117 929 9737. E-mail address : barney.reeves{at}bristol.ac.uk

We read the paper by Mukherjee et al .1 on similar efficacy outcomes with tirofiban and ReoPro with a lot of interest and considerable reservations. The paper was hand-delivered to me by the representative of one of the drugs in the study with the proud claim that both drugs were equivalent. The authors are to be applauded in conducting a very well-designed trial with 100% follow-up in terms of mortality. The outcome reported was pre-specified, in line with modern concepts of trial execution. The authors also do well to point out a significant limitation of their study in …

We have read with great interest the paper which was recently published by Straus et al. 1 on the association between the use of non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death (SCD). On the basis of their findings, which were drawn from a large population-based case-control study, the authors concluded that the use of certain non-cardiac drugs that prolong myocardial repolarization is indeed associated with an increased risk of SCD. This study seems to represent an extension of a methodologically almost identical study published in 2004 by the same group.2 This previous study reviewed all cases of death in the Integrated Primary Care Information study between 1 January 1995 and 1 April 2001 (in the recently published paper, the time of observation was extended to 1 …

This editorial refers to ‘Reasons for terminating an exercise test provide independent prognostic information: 2014 apparently healthy men followed for 26 years’† by J. Bodegard et al., on page 1394 Exercise testing as a screening modality must be considered in a new light given the paper by Bodegard et al. 1 and three other recent screening studies. First, this paper demonstrates the importance of using cardiac endpoints for evaluating cardiac tests. When adjusting for age, men who stopped exercising exclusively because of impaired breathing had a two-fold increased risk of dying from coronary heart disease (CHD) and a 3.5-fold increased risk of dying from pulmonary causes when compared with men who stopped due to volitional fatigue. Although all-cause mortality must be the primary endpoint of intervention studies, this is not the case for cardiac tests, where the goal is to determine which patients should be considered for a cardiac intervention to improve outcome. The authors demonstrated that certain responses predict pulmonary endpoints more so than cardiac. Secondly, this data set of 2014 asymptomatic Norwegians and two studies of asymptomatic Americans have clearly demonstrated the substantial risk ratios generated by the standard exercise test when combined with other risk factors. From the Cooper Clinic comes the largest screening study of the exercise test to predict CHD … *Corresponding author. E-mail address : vicmd{at}pacbell.net

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a management conundrum given the poorly understood pathogenic mechanisms. In recent years, novel echocardiographic measures such as deformation/strain analysis have enabled early identification of left atrial (LA) remodelling and dysfunction which take place prior to structural alterations. LA dysfunction is an important biomarker of cardiovascular disease and an independent predictor of atrial arrhythmias which may play a fundamental role in the pathogenesis of MINOCA. Purpose The goal of our study was to evaluate and characterise LA function by speckle tracking strain echocardiography in patients with MINOCA. Methods Patients admitted to our institution with acute myocardial infarction were assessed and those diagnosed with MINOCA who underwent transthoracic echocardiogram (TTE) within 48-hours of their coronary angiogram were included. Diagnosis of MINOCA was based on the 2017 ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Two-dimensional speckle tracking strain analysis of the LA and left ventricle (LV) was performed offline using vendor independent software (TomTec Arena). Clinical and echocardiographic measures were compared to healthy controls identified from our echocardiography database. We excluded patients with history of atrial fibrillation, heart failure and LV dysfunction (LVEF Results The cohort consisted of 82 patients; 41 patients with MINOCA were compared to 41 age and sex matched controls (61% male, mean age 51±12.8 years). At baseline, patients with MINOCA had a higher prevalence of modifiable vascular risk factors including smoking, hypertension and diabetes (p Conclusion Patients with MINOCA demonstrated lower LASr despite normal LV and LA volumes. This suggests that LA dysfunction may play a role in the pathogenesis of MINOCA. Further studies are required to evaluate the significance of our findings. Funding Acknowledgement Type of funding sources: None.

Background MINOCA's physiopathology, treatment and prognosis are yet to be completely understood. The aim of this study is to compare baseline characteristics and prognosis of MINOCA patients and those of patients with myocardial infarction (MI) and obstructive coronary arteries. Methods We analysed all consecutive patients with MI who underwent coronary angiography admitted in a University Hospital covering a population of 220.000 people during a period of 60 months. The database and the all the patient's angiographies were revised by a group of experts in order to adequate MINOCA to 2020 ESC Guidelines definition and the American Heart Association position paper. Results 680 patients, 68 of whom were MINOCA (10%) with a median of follow up of 31±16 months were analysed (see table 1). We found no differences in both groups' age. Female gender was more prevalent among MINOCA patients. The underlying mechanism in MINOCA was coronary spasm (17.6%), plaque rupture (13.2%), coronary embolism (7.4%), coronary dissection (2.9%), type II infarction (19.1%) or unknown (39.7%). Coronary arteries in MINOCA patients had no obstructions at all in 57.4%, and 30–50% obstruction in 42.6% of the cases. MINOCA patients didn't have higher prevalence of cancer, autoimmune or psychiatric diseases, dyslipidaemia, hypertension or inflammatory analytical parameters. However, we found significant differences in atrial fibrillation, migraine, connective tissue diseases, tobacco use and diabetes. We found no effect of stress in the development of MINOCA (measured with validated STAI and DS-14 scales). Symptoms at admission didn't differ between the two groups, but those with MINOCA had normal ECG more frequently. Prognosis showed relevant differences, as MINOCA patients had less major cardiovascular complications, such as inotropic requirements (0% Vs 4.8%, p=0.04), shock (0% vs 6.6%, p=0.013) and left ventricular dysfunction (11.8 vs 30.2, p=0.015). Furthermore, myocardial injury biomarkers' levels were, significantly lower in MINOCA patients. Death rates tend to be lower both in hospital (0% vs 3.1%, p=0.131) and during follow up (9.1% vs 11.5%, p=0.369). Conclusion Analysing MINOCA patients' clinical profile might help us understanding the underlying physiopathology, prognosis and treatment targets. In these patients, classic cardiovascular risk factors don't appear to be as important as in obstructive patients. At admission, we found no clinical differences that could help making an early diagnosis, even if those with normal ECG and lower levels of myocardial injury biomarkers are more likely to have non-obstructive coronary arteries. These patients seem to have better prognosis and lower myocardial injury than those with obstructive coronary arteries. Further research is needed to provide more evidence on the accurate treatment of these patients. Funding Acknowledgement Type of funding sources: None.

Background Physicians can be reluctant to prescribe antithrombotic agents in frail elderly patients with frequent falls due to the fear for severe bleeding, mainly for intracranial haemorrhage (ICH). Presently, there is only a limited amount of inconclusive data available on the topic. Purpose Identification of risk factors for ICH within a cohort of geriatric patients with repeated falls. Methods All patients of 65 years of age and older with repeated falls at our day clinic were eligible. If an MRI of the brain was performed as part of the assessment, patients were included in this analysis. Baseline characteristics including medical, functional, and cognitive state were collected, a Frailty Index (FI) was calculated [1,2]. Cerebral small vessel disease was described and evaluated as proposed in a position paper in 2013 [3]. Follow-up data concerning major bleeding events were retrieved from the electronic medical files. Odds ratios (OR) with confidence intervals (CI) were calculated. Results 670 patients were eligible; an MRI was performed in 486 patients. The average age was 80 years, 50% was severely frail at the time of inclusion. 83 patients (17%) used OAC (mainly Vitamin K antagonists prescribed for atrial fibrillation), 165 patients (34%) used anti platelet agents (APA), 1 patient used both OAC and APA. In total, 29 major bleeding events (MB) occurred, of which 13 were ICH. Among patients using OAC, 8 MB occurred, of which 2 were ICH. The patient with both OAC and APA did not experience a bleeding event. Well known risk factors for ICH such as hypertension, diabetes mellitus and cognitive impairment were not predictive for ICH in this cohort, nor were the use APA (OR 0.86, 95% CI 0.26–2.84), or vitamin K antagonists (OR 0.88, 95% CI 0.19–4.05). However, a composite factor of using either APA or OAC, heightened the risk for MB (OR 3.24, 95% CI 1.35–7.74), but not for ICH (OR 0.83, 95% 0.27–2.49). Of cerebral small vessel disease, predictive factors for ICH were the presence of lacunes (OR 3.81, 95% CI 1.25–11.56), and relevant white matter hyperintensities (WMH) (defined as a Fazekas score of 2 or more) (OR 11.3, 95% CI 1.45–87.3). Furthermore, cognitive decline defined as an MMSE score of ≤26 heightened the risk of MB (OR 2.28, 95% CI 1.05–4.96). The low number of ICH did not allow for a multivariate analysis. Conclusion This analysis has several important findings. First, despite the long follow up of a cohort of severely frail patients that frequently fall, a low number of MB and ICH was observed. Second, well known risk factors for MB do not seem predictive of ICH in this cohort of very elderly patients. Finally, cognitive decline was predictive for MB, and WMH and lacunes were predictive for ICH. Adding cognitive screening and brain imaging to the diagnostic work up of patients with an indication for OAC could be of value when assessing the future risk for major bleeding events. Funding Acknowledgement Type of funding sources: None.

Background Heart failure (HF) admission is a serious event in the follow up of patients with chronic coronary syndromes (CCS). Stratification schemes have been described for predicting this end-point but none of them has been externally validated. Purpose To develop point-scores for predicting incident HF admission with data from previous studies, to perform an external validation in an independent prospective cohort study, and to compare their discriminative ability for this event. Methods We performed a literature review searching for prospective studies including patients with CCS, excluding patients with HF at baseline, with data on HF admission incidence in follow up and predictive variables. If undescribed previously, scores were developed including those variables independently associated with this outcome, and score points were assigned based in the relative magnitude of the coefficients of Cox regression models. The resulting scores were validated and their discriminative ability compared in a prospective, monocentric, 17-years cohort study, that included consecutive outpatients with CCS. Results Four studies were included: two post-hoc analysis of clinical trials (CARE and PEACE) and two observational registries (CORONOR and CLARIFY). The validation cohort included 1212 patients (mean age 67±11 years, 74% male) followed for up to 17 years (median 12 years, p25–75 5–15 years), with 171 patients suffering at least one HF admission in follow-up. The proportions of the variables needed for scores calculation available in the database of the study were 75% (6/8), 88% (15/17), 100% (8/8) and 85% (17/20) respectively, for each of these study-derived scores. Discriminative ability for predicting HF admission was statistically significant for all (C-statistic 0.72, 95% CI 0.68–0.75, p Conclusions All tested scores showed significant discriminative ability for predicting incident HF admission in this independent validation study. Their discriminative ability was similar, except that CORONOR score performed significantly better than CLARIFY score. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The work for this paper was funded by the Andalusian Society of Cardiology through anunconditional grant from Astra Zeneca. ROC curves for HF predictive scoresHF free survival by CORONOR score