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Author(s): Anker, Stefan D; Butler, Javed; Khan, Muhammad Shahzeb; Abraham, William T; Bauersachs, Johann; Bocchi, Edimar; Bozkurt, Biykem; Braunwald, Eugene; Chopra, Vijay K; Cleland, John G; Ezekowitz, Justin; Filippatos, Gerasimos; Friede, Tim; Hernandez, Adrian F; Lam, Carolyn SP; Lindenfeld, JoAnn; McMurray, John JV; Mehra, Mandeep; Metra, Marco; Packer, Milton; Pieske, Burkert; Pocock, Stuart J; Ponikowski, Piotr; Rosano, Giuseppe MC; Teerlink, John R; Tsutsui, Hiroyuki; Van Veldhuisen, Dirk J; Verma, Subodh; Voors, Adriaan A; Wittes, Janet; Zannad, Faiez; Zhang, Jian; Seferovic, Petar; Coats, Andrew JS | Abstract: 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.

Background Statin intolerance is a clinical syndrome whereby adverse effects associated with statin therapy (most commonly muscle symptoms) result in the discontinuation of therapy. Statin discontinuation is associated with increased risk of adverse cardiac outcomes. Many patients who initially experience adverse effects are able to tolerate statin therapy to some extent. Careful stepwise diagnosis and management of individuals who experience adverse effects is essential to enable optimal reduction of cardiovascular risk. Purpose In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step by step approach to the diagnosis and practical management of statin intolerance resulting from muscle symptoms, and other adverse effects with demonstrated statin causality. Methods Relevant clinical evidence and international clinical guidelines were discussed and assimilated by ILEP members. Consensus was used to formulate recommendations for the diagnosis and management of statin intolerance. Results Consensus resulted in the adoption of three parts to the recommendation. 1) diagnosis of Statin Intolerance; 2) advice for management of all patients with statin intolerance; 3) specific advice for patients who have partial (rather than complete) statin intolerance. Patients with partial statin intolerance are likely to make up the vast majority (even 95%) of statin-intolerant individuals. Each part of the recommendation consists of a four-step process and has an associated acronym to aid memory (see attached recommendations). We adopted the Banach and Mikhailidis four-step approach to diagnosis and we developed novel recommendations for management. Summary of the ILEP SI recommendations. Conclusions We present recommendations, which will enable clinicians to distinguish between rare, severe adverse effects; true statin intolerance, and symptoms incorrectly attributed to statin therapy. In each case we summarize guidelines, clinical evidence and expert opinion pertaining to the optimal management of cardiovascular disease in these patients. Acknowledgement/Funding None

Introduction MINOCA (myocardial infarction with non-obstructive coronary arteries) has been recently redefined by the last ESC guidelines. The aim of this study is to analyze clinical profile and long-term prognosis of these patients. Methods Retrospectively, between 1/2010 and 12/2016 all consecutive patients with the definitive diagnosis of MI in tertiary center were included in this observational study. Patients with unstable angina with non-obstructive coronary artery disease and those who died in-hospital were excluded. Patients were stratified according to the number of significant coronary vessel disease seen by coronary angiography into: 0 (MINOCA); 1; 2; ≥3 vessels. The definition of MINOCA was based on dedicated the 2016 ESC Working Group position paper. Patients with MINOCA were compared to their counterpounds (MIOCA; MI with obstructive CAD) regarding baseline clinical characteristics, on-admission and laboratory data and treatment at hospital discharge. The prognostic meaning of MINOCA vs MIOCA was ascertained by comparing the composite endpoint (re-ACS, stroke and death) rate among groups, using Kaplan-Meier and multivariate Cox regression analyses. Results 13.8% (n=597) pts were classified as MINOCA. They were older and more frequently women than the obstructive group. MINOCA group also had a worse cardiovascular risk profile than pts with obstructive coronary lesions. They were associated more frequently with atrial fibrillation during hospitalization (11.2% vs. 6.8%, p During 15 months (IQR: 12,3–25,5), 613 (14.2) pts had a new ACS, stroke or died (251 pts developed a new ACS, 81 had stroke, and 281 died). The incidence of the composite endpoint was 4.2% in the MINOCA pts, 4.1% in pts with 1-significant coronary vessel disease, 6.3% in the 2-significant coronary vessel disease, and 9.5% in the ≥3-significant coronary vessel disease (p Figure 1. Composite endpoint Conclusions In the present cohort MINOCA was approximately found in one of each 14 patients admitted with MI. These patients had worse CV risk profile and more history of depression. MINOCA pts have similar prognostic impact in terms of hospitalization for a new ACS, stroke and death than the obstructive group.

Adult congenital heart disease (ACHD) patients represent a growing population with increasing use of acute emergency department (ED) care. Providing comprehensive ED care necessitates an understanding of the most common clinical scenarios to improve morbidity and mortality in this population. The aim of this position document is to provide a consensus regarding the management of the most common clinical scenarios of ACHD patients presenting to the ED.

Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel formation and/or muscle regeneration. Here, we discuss the use of cells in the context of heart repair, and the most relevant results and current limitations from clinical trials using cell-based therapies to treat IHD and HF. We identify and discuss promising potential new therapeutic strategies that include ex vivo cell-mediated gene therapy, the use of biomaterials and cell-free therapies aimed at increasing the success rates of therapy for IHD and HF. The overall aim of this Position Paper of the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to improve the therapeutic application of cell-based therapies for cardiac regeneration and repair.

Increasing prevalence of cardiovascular disease and new evidence on the effects of antithrombotic therapies have expanded the use of antiplatelet and anticoagulant drugs. In addition, extremely low and high body weights have become more common due to frailty associated with ageing and to the global epidemic of obesity, ‘globesity’, respectively. These extreme body weights affect cardiovascular risk, including mortality, as well as the pharmacokinetics and safety profiles of antithrombotic drugs, some of which have a relatively narrow therapeutic window. The ESC Working Group on Thrombosis therefore assembled a task group to examine the key issues related to this topic and to address the question of whether modified antithrombotic management strategies are required for patients at the extremes of body weight. Greater focus is directed toward to obesity, given its higher prevalence among patients with cardiovascular disease and its associated complexities in terms of pharmacology and pathophysiology. Further research is warranted to optimize antithrombotic therapy in underweight as well as in different classes of obese patients, to guide dosing, dose-adjustment and/or reference intervals, and to establish whether the balance of benefits and risks of antithrombotic drugs can be improved.

The European Society of Cardiology (ESC) has recently published practice guidelines for the management of grown-up congenital heart disease (GUCH).1 For the sake of space, this document did not include recommendations for the organization of care for adults with congenital heart disease (CHD) nor for training in the subspecialty of adult CHD, although emphasis was given to their importance and the need for a separate recommendations paper in the future.1 This publication is a position paper from the ESC Working Group on Grown-up Congenital Heart Disease, which makes recommendations for the standards and organization of care for adults with CHD, as well as for training in GUCH within Europe. Obviously, there is a lack of solid scientific data to support such recommendations and the majority of them must remain based on expert consensus. The remarkable improvement in survival of surgically and interventionally treated patients with CHD has led to an increasing number of GUCH patients, in particular those with more complex disease. There are also patients with newly diagnosed CHD lesions in adulthood such as atrial septal defect, coarctation of the aorta, Ebstein's anomaly and congenitally corrected transposition of the great arteries. The 32nd Bethesda Conference report in 20012 estimated that there were ∼2800 adults with CHD/million population, with more than half having moderate or highly complex disease. More recently, Marelli et al .3 reported a prevalence of 4090/million adults in Quebec for the year 2000 with 380 having severe disease. In Europe, we are currently faced with an estimated GUCH patient population of ∼2.3 million, which significantly outnumbers the paediatric CHD population of ∼1.9 million patients.4 There is general agreement that GUCH patients have very special needs and therefore physicians responsible of their care need specific expertise and training.1–11 It is …

International audience; BACKGROUND: With an increasing prevalence of patients with valvular heart disease (VHD), a dedicated management approach is needed. The challenges encountered are manifold and include appropriate diagnosis and quantification of valve lesion, organization of adequate follow-up, and making the right management decisions, in particular with regard to the timing and choice of interventions. Data from the Euro Heart Survey have shown a substantial discrepancy between guidelines and clinical practice in the field of VHD and many patients are denied surgery despite having clear indications. The concept of heart valve clinics (HVCs) is increasingly recognized as the way to proceed. At the same time, very few centres have developed such expertise, indicating that specific recommendations for the initial development and subsequent operating requirements of an HVC are needed. AIMS: The aim of this position paper is to provide insights into the rationale, organization, structure, and expertise needed to establish and operate an HVC. Although the main goal is to improve the clinical management of patients with VHD, the impact of HVCs on education is of particular importance: larger patient volumes foster the required expertise among more senior physicians but are also fundamental for training new cardiologists, medical students, and nurses. Additional benefits arise from research opportunities resulting from such an organized structure and the delivery of standardized care protocols. CONCLUSION: The growing volume of patients with VHD, their changing characteristics, and the growing technological opportunities of refined diagnosis and treatment in addition to the potential dismal prognosis if overlooked mandate specialized evaluation and care by dedicated physicians working in a specialized environment that is called the HVC.

Udgivelsesdato: 2009-Jan-27 Oral antiplatelet drugs are a cornerstone of modern pharmacotherapy in cardiovascular atherothrombotic diseases. The efficacy of acetylsalicylic acid (ASA, aspirin) and clopidogrel in decreasing the risk of adverse events in coronary heart disease patients has been well established in the past 20 years. Despite chronic oral antiplatelet therapy, a number of atherothombotic events continue to occur. In recent years, a number of reports in the literature have shown possible relationships between residual platelet activity, as measured with a variety of laboratory tests, and clinical outcome, raising the possibility that 'resistance' to oral antiplatelet drugs may underlie many such clinical adverse events. The present position paper, conveyed within a group of clinical cardiologists with expertise in thrombosis appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, has been further elaborated and endorsed by the Working Group on Thrombosis of the European Society of Cardiology. It aims at summarizing the main findings in this complex area, issuing opinions in cases of high controversy, and fostering future research in this area to obtain reliable laboratory and clinical data for the resolution of the many problems still open.

The epidemic of obesity is recognized as one of the most important public health problems facing the world today. According to 2014 World Health Organization (WHO) data,1 39% of adults worldwide are overweight (body mass index, BMI ≥ 25 kg/m2) and 13% of adults are obese (BMI ≥ 30 kg/m2). Thus, more than half a billion adults worldwide are classified as obese. The prevalence of obesity varies by geographical region, gender and income level. The highest prevalence is found in the USA (61% overweight, 27% obese), closely followed by Europe (59% overweight, 23% obese), with the lowest prevalence in South–East Asia (22% overweight, and 5% obese). In Europe, the vast majority of countries have an overweight prevalence of more than 60%.1 Asians generally have a higher percentage of body fat than Caucasians of the same age, sex and BMI. Even below the usual cut-off of BMI = 25 kg/m2 Asian people seem to be at increased risk for type 2 diabetes.2 This may have implications for obesity diagnostic criteria. Indeed, the proposed optimal BMI cut-off values by WHO in Asian populations seems to vary from 22 to 25 kg/m2 based on the ethnic background. A Consensus Statement for Diagnosis of Obesity, Abdominal Obesity and the Metabolic Syndrome for Asian Indians has suggested the following BMI cut-off values: normal BMI = 18.0–22.9 kg/m2; overweight = 23.0–24.9 kg/m2; and obesity > 25 kg/m2.3 Thus it is indeed debatable whether uniform BMI cut-off values to diagnose obesity and/or for cardiovascular risk stratification purposes can be use worldwide. The use of additional anthropometric measurements e.g. waist-circumference or CT based quantification of abdominal/subcutaneous fat volume could help to better delineate obesity and risk parameters and to implement preventive strategies against obesity in each specific ethnic scenario.

2-D : two-dimensional 3-D : three-dimensional 5-FU : 5-fluorouracil ACE : angiotensin-converting enzyme ARB : angiotensin II receptor blocker ASE : American Society of Echocardiography BNP : B-type natriuretic peptide CABG : coronary artery bypass graft CAD : coronary artery

Jose Zamorano discusses the need for and what cardiology can expect in the ESC position paper One of the changes that we have recently seen in the European Society of Cardiology (ESC) Core Curriculum, is the presence of a chapter entitled Cardio Oncology. Such topic has also been considered for an ESC Committee of Practice Guidelines position paper. We may wonder about the need for such a new topic. There is no doubt however that malignancy is a worldwide health and social problem. Advances in treatment have led to improved survival of cancer patients, but morbidity and mortality has also increased due to the side effects of treatment. This means that as survival rates in cancer patients improve, there is an increased interest in preventing or treating potential complications related to cancer therapies. If we look to the major potential side effects of anticancer drugs, cardiovascular diseases (CVD) are one of the most frequent complications that may lead to abandoning of the treatment. We need to differentiate cardiotoxicity (direct effects of the cancer treatment) to the new appearance of CVD due to accelerated development of CVD in …

Optimizing outcomes after percutaneous coronary intervention (PCI) requires balancing between the risks of thrombotic and bleeding events in individual patients.1–3 However, finding the optimal balance is not always straightforward since the risks of thrombotic and bleeding complications may differ extremely between individuals. In addition, the individual effects of anticoagulant and antiplatelet drugs are not uniform in patients.4 Recent European guidelines1,3 recommend the use of prasugrel or ticagrelor instead of clopidogrel in all PCI-treated acute coronary syndrome (ACS) patients without contraindication, acknowledging that laboratory assessment of P2Y12-receptor inhibition may be considered only in selected cases when clopidogrel is used.1 However, there is no guidance with respect to the appropriate methodology and the suggested interpretation of results. The Working Group on Thrombosis of the European Society of Cardiology aimed to review the available evidence and the clinical relevance of platelet function testing in order to reach a consensus regarding the methodology, evaluation, and clinical interpretation of platelet function in patients undergoing PCI. Regarding the choice between available P2Y12-inhibitors, the 2011 ESC guidelines on non-ST segment elevation acute coronary syndromes (NSTE-ACS)1 and the 2012 guidelines on ST-segment elevation myocardial infarction3 recommend prasugrel and ticagrelor for all ACS patients without contraindication, and clopidogrel is only recommended if these agents are not available. Despite the restrictive recommendations for clopidogrel, it still holds a class I indication in ACS due to the large differences in the availability of the new-generation P2Y12-inhibitors among European countries. According to the 2011 ACCF/AHA/SCAI guidelines for PCI,5 a P2Y12-inhibitor should be given for ACS patients without preferring novel P2Y12-inhibitors over clopidogrel. Similarly, the 2012 ACCF/AHA unstable angina/non-ST-segment elevation myocardial infarction guidelines6 and the 2013 ACCF/AHA ST-elevation myocardial infarction guidelines …

The management of acute myocardial infarction (AMI)1 has evolved over the past century and particularly in the past 50 years. Important milestones include the development of the electrocardiogram, coronary care units, coronary angiography, reperfusion therapies, and troponin assays. These innovations are the foundation of contemporary AMI management strategies that include a diagnosis centred on elevated troponin values associated with corroborative clinical evidence,1 early use of coronary angiography, and reperfusion therapies.2–4 Pivotal in the evolution of these contemporary strategies were the early AMI coronary angiography studies undertaken by DeWood et al. These pioneering studies demonstrated that, in patients presenting with ST elevation myocardial infarction (STEMI), almost 90% had an occluded coronary artery provided that angiography was undertaken within 4 h of chest pain onset.5 In contrast, in AMI patients who did not present with ST elevation (non-ST elevation myocardial infarction or NSTEMI), only 26% had an occluded coronary artery when angiography was performed within 24 h of symptom onset.6 In both of these landmark studies,5,6 >90% of the acute MI patients had angiographic evidence of obstructive coronary artery disease (CAD), underscoring the importance of the atherosclerotic process in the pathogenesis of AMI. Although DeWood's studies underscore the importance of obstructive CAD in AMI, it is fascinating that ∼10% had no significant CAD on coronary angiography. This is confirmed in several large AMI registries7–9 where 1–13% of AMI's occurred in the absence of obstructive CAD thereby eliciting an important set of questions—what is the mechanism of the myocardial damage in these patients? Do these patients differ from those with obstructive CAD? Should they be …

Bleeding is the main adverse effect when using oral anticoagulants (OACs). The risk of major bleeding with vitamin K antagonists (VKAs) is dependent on the quality of anticoagulation control and estimated to be ∼1.3/100 patients/year in patients with INR 2.0–3.0.1,2 Multiple limitations of VKAs stimulated the development of non-vitamin K antagonist oral anticoagulants (NOACs) acting directly on coagulation factors, including factor FIIa (thrombin) and FXa. Pharmacological properties of the NOACs relevant for bleeding are summarized in the supplement including Supplementary material online, Table S1 and their main effects are summarized in Supplementary material online, Table S2 . The risk of bleeding in patients managed with NOACs was properly assessed in the four landmark Phase III trials in patients with atrial fibrillation (AF; Table 1 ). Major bleeding was the principal safety outcome in RE-LY,3,4 ARISTOTLE,5 and ENGAGE AF.6 In ROCKET-AF, the primary safety endpoint was the composite of major and non-major clinically relevant bleeding.7 The risk of major bleeding was significantly reduced with dabigatran 110 mg b.i.d., apixaban and both doses of edoxaban3–6 while the bleeding rates for dabigatran 150 mg b.i.d. and rivaroxaban were similar to those with warfarin ( Table 1 ). View this table: Table 1 Risk of bleeding with non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation (rates per 100 patients-years) Gastrointestinal (GI) bleeding accounts for ∼90% of major extracranial haemorrhages in patients with AF receiving VKAs.8 With the NOACs, dabigatran 150 mg b.i.d., rivaroxaban, and edoxaban 60 mg o.d. significantly increased rates of GI bleeding (∼1.5-fold) compared with warfarin.3,6,7 While rivaroxaban increases upper and lower GI bleeding …

Contains fulltext : 233788.pdf (Publisher’s version ) (Open Access) Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

Background Observational studies evaluating the link between sleep duration and kidney function reported controversial results. In the present study, Mendelian Randomization (MR) analysis was applied to obtain unconfounded estimates of the casual association of genetically determined sleep duration with estimated glomerular filtration rate (eGFR) and the risk of chronic kidney disease (CKD). Methods Data from the largest genome-wide association studies (GWAS) on self-reported and accelerometer derived sleep duration, eGFR and CKD were analysed in total, as well as separately in diabetic and non-diabetic individuals. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, as well as MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. To rule out the impact of single single-nucleotide polymorphism (SNP), the leave-one-out method was used. Results Overall, individuals with genetically longer self-reported sleep duration had a higher CKD risk (IVW: beta=0.358, p=0.047). Furthermore, in non-diabetics, longer self-reported sleep duration was negatively associated eGFR (IVW: beta=−0.024, p=0.020). Similarly, accelerometer derived sleep duration was negatively related to eGFR in the total population (IVW: beta=−0.019, p=0.047) and the non-diabetic individuals (IVW: beta=−0.025, p=0.014) (Table). No significant association was found between self-reported sleep duration and eGFR in the whole population (IVW: beta=−0.019, p=0.072) and T2DM patients (IVW: beta=0.028, p=0.484). None of the estimated associations was subjected to a significant level of heterogeneity. Furthermore, MR-PRESSO analysis did not show any chance of outliers for all estimates. The pleiotropy test, with very negligible intercept and insignificant p value. The results of the MR-RAPS were identical with the IVW estimates, highlighting again no possibility of pleiotropy. The leave-one-out method demonstrated that the links were not driven by single SNPs. Conclusions For the first time, the present study shed a light on the potential harmful effects of longer sleep duration (measured both objectively and subjectively) on kidney function. This finding was observed in the total population and in non-diabetic individuals, but not in those with diabetes. Further research is needed to elucidate the links between sleep duration, eGFR and CKD. Funding Acknowledgement Type of funding source: None

Aim To investigate the association of sinus heart rate pre- and post-ablation and recurrence rates in patients undergoing catheter ablation for atrial fibrillation. Methods Between January 2012 and December 2017, data of 482 patients undergoing their first pulmonary vein isolation (PVI) were included. All patients were followed-up for 12 months and were screened for any atrial tachyarrhythmia. Sinus heart rate measurements were recorded before (PRE), directly post ablation (POST) and 3 months post ablation (3M). Results In the total study population, the mean resting sinus heart rate at PRE (mean 57.9 bpm (95% CI, 57.1–58.7 bpm)) increased by over 10 bpm to POST (mean 69.4 bpm (95% CI, 68.5–70.3 bpm); p Conclusion Our study confirms the impact of PVI on cardiac autonomic function with a significant heart increase post-ablation. A heart rate ≥60bpm at 3M and a heart rate change ≥11 bpm (PRE to 3M) are associated with a favorable outcome in terms of recurrences. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Research Foundation

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy. ispartof: EUROPEAN HEART JOURNAL vol:39 issue:22 pages:2032-2046 ispartof: location:England status: published

Tumours and heart disease remain the most important causes of morbidity and mortality worldwide. Interestingly, in some countries—thanks to the enormous progress made in cardiology over the last decades—cancer has surpassed heart disease as the major cause of mortality.1 However, oncology has also seen an impressive expansion of its therapeutic options with the development of more effective chemotherapeutic drugs. Unfortunately, some chemotherapeutics, in particular anthracyclins, actually have toxic cardiovascular effects. Most commonly, they interfere with the myocardium, reduce cardiac pump function, and eventually induce heart failure, cause arrhythmias, or promote coronary lesion formation. As a result, many heart centres have established specialized units in cardio-oncology in order to improve the management of such patients. Thus, the Position Paper on Cardio-Oncology entitled ‘ 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity ’ by Zamorano et al. on behalf of the ESC Committee for Practice Guidelines and the Task Force for Cancer Treatments and Cardiovascular Toxicity of the European Society of Cardiology is a timely document.2 The …

Contains fulltext : 89482.pdf (Publisher’s version ) (Closed access) Cardiovascular remodelling in the conditioned athlete is frequently associated with physiological ECG changes. Abnormalities, however, may be detected which represent expression of an underlying heart disease that puts the athlete at risk of arrhythmic cardiac arrest during sports. It is mandatory that ECG changes resulting from intensive physical training are distinguished from abnormalities which reflect a potential cardiac pathology. The present article represents the consensus statement of an international panel of cardiologists and sports medical physicians with expertise in the fields of electrocardiography, imaging, inherited cardiovascular disease, cardiovascular pathology, and management of young competitive athletes. The document provides cardiologists and sports medical physicians with a modern approach to correct interpretation of 12-lead ECG in the athlete and emerging understanding of incomplete penetrance of inherited cardiovascular disease. When the ECG of an athlete is examined, the main objective is to distinguish between physiological patterns that should cause no alarm and those that require action and/or additional testing to exclude (or confirm) the suspicion of an underlying cardiovascular condition carrying the risk of sudden death during sports. The aim of the present position paper is to provide a framework for this distinction. For every ECG abnormality, the document focuses on the ensuing clinical work-up required for differential diagnosis and clinical assessment. When appropriate the referral options for risk stratification and cardiovascular management of the athlete are briefly addressed. 01 januari 2010

Aims To compare the efficacy [low-density lipoprotein cholesterol (LDL-C) lowering] and safety of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9, compared with ezetimibe, as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia. Methods and results COMBO II is a double-blind, double-dummy, active-controlled, parallel-group, 104-week study of alirocumab vs. ezetimibe. Patients ( n = 720) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled (August 2012–May 2013). This pre-specified analysis was conducted after the last patient completed 52 weeks. Patients were randomized to subcutaneous alirocumab 75 mg every 2 weeks (plus oral placebo) or oral ezetimibe 10 mg daily (plus subcutaneous placebo) on a background of statin therapy. At Week 24, mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4% for alirocumab vs. 20.7 ± 1.9% for ezetimibe (difference 29.8 ± 2.3%; P < 0.0001); 77.0% of alirocumab and 45.6% of ezetimibe patients achieved LDL-C

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.

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.

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.

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

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 …

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.