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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.

Major depression is a highly prevalent condition, affecting approximately 10% of the population. It is also a growing global problem, and has been consistently associated with increased risk of coronary heart disease (CHD). It is therefore not surprising that depression is highly comorbid with CHD, being two to three times more common among patients with CHD than in the general population. The prevalence of depression is 15–30% in patients with CHD, and is approximately twice as high in women than men, especially affecting young women in the aftermath of acute myocardial infarction (MI). Depression as a risk factor for CHD has been characterized from mild depressive symptoms to a clinical diagnosis of major depression. As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), clinical depression, or major depression, is characterized by depressed mood or anhedonia (loss of interest or pleasure) for at least 2 weeks accompanied by significant functional impairment and additional somatic or cognitive symptoms. Most epidemiological studies of depression and incidence of CHD have used depressive symptom scales, and have frequently demonstrated a dose–response pattern, with higher levels of depressive symptoms being associated with higher risk. The exact mechanisms linking depression to increased CHD risk are complex and multifactorial, and still incompletely understood. Although adverse lifestyle behaviours and traditional CHD risk factors, such as smoking and sedentary lifestyle, largely contribute to the risk, they do not explain it entirely. In CHD patients, depression is also associated with severity of functional impairment, lower adherence to therapy and lower participation in cardiac rehabilitation. Whether and to what extent these factors explain the relationship between depression and CHD deserves future study. The present paper summarizes key aspects in our current knowledge linking depression and CHD within the intersecting fields of neuroscience, cardiovascular physiology, and behavioural medicine, with the objective of bringing attention to this area and stimulating interdisciplinary research, clinical awareness, and improved care.

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.

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.

There is strong need to develop the current stratified practice of CVD management into a better personalized cardiovascular medicine, within a broad framework of global patient care. Clinical information obtained from history and physical examination, functional and imaging studies, biochemical biomarkers, genetic/epigenetic data, and pathophysiological insights into disease-driving processes need to be integrated into a new taxonomy of CVDs to allow personalized disease management. This has the potential for major health benefits for the population suffering from cardiovascular diseases.

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.

Aims Cardiovascular disease is the most common cause of mortality and morbidity in the world, but the pharmaceutical industry's willingness to invest in this field has declined because of the many challenges involved with bringing new cardiovascular drugs to market, including late-stage failures, escalating regulatory requirements, bureaucracy of the clinical trial business enterprise, and limited patient access after approval. This contrasts with the remaining burden of cardiovascular disease in Europe and in the world. Thus, clinical cardiovascular research needs to adapt to address the impact of these challenges in order to ensure development of new cardiovascular medicines.Methods and results The present paper is the outcome of a two-day workshop held by the Cardiovascular Round Table of the European Society of Cardiology. We propose strategies to improve development of effective new cardiovascular therapies. These can include (i) the use of biomarkers to describe patients who will benefit from new therapies more precisely, achieving better human target validation; (ii) targeted, mechanism-based approaches to drug development for defined populations; (iii) the use of information technology to simplify data collection and follow-up in clinical trials; (iv) streamlining adverse event collection and reducing monitoring; (v) extended patent protection or limited rapid approval of new agents to motivate investment in early phase development; and (vi) collecting data needed for health technology assessment continuously throughout the drug development process (before and after approval) to minimize delays in patient access. Collaboration across industry, academia, regulators, and payers will be necessary to enact change and to unlock the existing potential for cardiovascular clinical drug development.Conclusions A coordinated effort involving academia, regulators, industry, and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier availability of innovative therapies and better management of cardiovascular diseases.

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 …

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

Previous work from the European Society of Cardiology (ESC), the European Atherosclerosis Society (EAS) and from other groups has addressed the benefits of statin treatment in different patient populations.1–4 Unfortunately, adherence to guideline-recommended statin therapy is suboptimal: Statins are underused and LDL cholesterol targets are not met in up to 80% of high-risk patients.5–7 Excellent reviews have recently been published on the issue of statin intolerance and some lay media as well strongly emphasize this issue.8 True and verified statin intolerance, however, is uncommon and is not the main reason for poor adherence to statin treatment. Because poor adherence to statin treatment in turn is extremely common, it appears necessary to discuss the problem of statin adherence in a broader context and to develop strategies to overcome it. This clinically important task has not yet been the focus of a review or practice recommendation and therefore is the aim of the present position paper from the ESC working group on Cardiovascular Pharmacotherapy. This work takes the position that statin therapy is underutilized because of non-adherence not solely related to statin side effects and proposes steps to be taken in cardiovascular practice to improve statin adherence and thus cardiovascular outcomes. Our article aims to highlight the scientific background that helps to (i) overcome statin non-adherence by definition and description of true adverse statin effects, (ii) increase statin adherence by changing reservation against lipid lowering in media and the public, and (iii) guide efforts in the scientific community to close the gap between knowledge and practice of lipid management. Although statins are generally well-tolerated, statin adherence is poor in clinical practice: A survey of statin prescription claims showed a 30% discontinuation rate within the first year following initial prescription for primary prevention in USA.9 Data from the Danish …

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 …

Considered one of the pre-eminent cardiologists of our time, Dr Eugene Braunwald, MD, has extended knowledge of congestive heart failure, coronary artery disease, and valvular heart disease. Having published hundreds of papers and medical articles, with his textbook Braunwald’s Heart Disease cited worldwide, Dr Braunwald has received numerous honours and awards. Born in Austria in 1929, his family emigrated to the USA during World War II and after his studies he began a long, successful and hugely-influential career as a cardiologist. Now well into his 80s, he still practices medicine and continues to contribute to the field of cardiology.