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Aim: There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF.Methods and results: Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible. Patients were classified according to glycated haemoglobin (HbA1c): (i) normal HbA1c, Conclusion: Pre-diabetes is common in patients with HFpEF and is associated with worse clinical status and greater risk of HFH. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT01920711.

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients. The authors acknowledge the Heart Failure Association of the European Society of Cardiology for organizing the meeting during which this topic was discussed. The authors acknowledge T.J. for her expert review of the manuscript, and W.G. S., PharmD (Campbell University College of Pharmacy and Health Sciences), supported by the Heart Failure Association of the European Society of Cardiology for contributions to content development, writing, and editing the manuscript. J.M., C.M. and F.P. performed their expert review of the paper on behalf of Acute Cardiovascular Care Association of the European Society of Cardiology. J.B. and T.T. were supported by the Deutsche Forschungsgemeinschaft, Clinical Research Group 311 (KFO 311) '(Pre-)terminal heart and lung failure: unloading and repair' (DFG; TP1 and TP11). Harjola, VP (corresponding author), Helsinki Univ Hosp, Dept Emergency Med & Serv, Div Emergency Med, PL 340, Helsinki 00029, Finland. veli-pekka.harjola@hus.fi

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes (T2D). Historical concerns about cardiovascular (CV) risks associated with certain glucose-lowering medications gave rise to the introduction of cardiovascular outcomes trials (CVOTs). Initially implemented to help monitor the CV safety of glucose-lowering drugs in patients with T2D, who either had established CVD or were at high risk of CVD, data that emerged from some of these trials started to show benefits. Alongside the anticipated CV safety of many of these agents, evidence for certain sodium–glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revealed potential cardioprotective effects in patients with T2D who are at high risk of CVD events. Reductions in 3-point major adverse CV events (3P-MACE) and CV death have been noted in some of these CVOTs, with additional benefits including reduced risks of hospitalisation for heart failure, progression of renal disease, and all-cause mortality. These new data are leading to a paradigm shift in the current management of T2D, with international guidelines now prioritising SGLT2 inhibitors and/or GLP-1 RAs in certain patient populations. However, clinicians are faced with a large volume of CVOT data when seeking to use this evidence base to bring opportunities to improve CV, heart failure and renal outcomes, and even reduce mortality, in their patients with T2D. The aim of this review is to provide an in-depth summary of CVOT data—crystallising the key findings, from safety to efficacy—and to offer a practical perspective for physicians. Finally, we discuss the next steps for the post-CVOT era, with ongoing studies that may further transform clinical practice and improve outcomes for people with T2D, heart failure or renal disease.

Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils. Cardiac involvement in TTR-related amyloidosis (ATTR) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction. ATTR is an underdiagnosed disorder as well as a crucial determinant of morbidity and mortality, thus justifying the current quest for a safe and effective treatment. Therapies targeting cardiac damage and its direct consequences may yield limited benefit, mostly related to dyspnoea relief through diuretics. For many years, liver or combined heart and liver transplantation have been the only available treatments for patients with mutations causing ATTR, including those with cardiac involvement. The therapeutic options now include several pharmacological agents that inhibit hepatic synthesis of TTR, stabilize the tetramer, or disrupt fibrils. Following the positive results of a phase 3 trial on tafamidis, and preliminary findings on patisiran and inotersen in patients with ATTR-related neuropathy and cardiac involvement, we provide an update on this rapidly evolving field, together with practical recommendations on the management of cardiac involvement.

Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as ‘HFrEF’ (HF with reduced LVEF), ‘HFpEF’ (HF with preserved LVEF), and more recently ‘HFmrEF’ (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone.

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of40%.

Repeated physiological monitoring of comorbidities in heart failure (HF) is pivotal. This document introduces the main challenges related to physiological monitoring in the complex multimorbid HF patient, arising during an ESC consensus meeting on this topic.

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a good death. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure. Funding Agencies|Patient Forum of the European Society of Cardiology

[Abstract] Aim. To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.

AIMS: The aim of this study was to assess long-term safety of intravenous cardiovascular agents-vasodilators, inotropes and/or vasopressors-in acute heart failure (AHF). METHODS AND RESULTS: The European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long-term all-cause mortality. Main secondary endpoints were in-hospital and post-discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long-term mortality [HR 0.784, 95% confidence interval (CI) 0.596-1.032] nor in-hospital mortality (HR 1.049, 95% CI 0.592-1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long-term all-cause mortality (HR 1.434, 95% CI 1.128-1.823), as well as in-hospital mortality (HR 1.873, 95% CI 1.151-3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long-term mortality in patients discharged alive (HR 1.078, 95% CI 0.769-1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031-2.572 vs. no inotropes). CONCLUSIONS: Vasodilators did not demonstrate any association with long-term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all-cause death, mostly related to excess of in-hospital mortality in AHF.

Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future?

Aims In 2007, the Heart Failure Association of the European Society of Cardiology (ESC) launched the information website heartfailurematters.org (HFM site) with the aim of creating a practical tool through which to provide advice and guidelines for living with heart failure to patients, their carers, health care professionals and the general public worldwide. The website is managed by the ESC at the European Heart House and is currently available in nine languages. The aim of this study is to describe the background, objectives, use, lessons learned and future directions of the HFM site. Methods and results Data on the number of visitor sessions on the site as measured by Google Analytics were used to explore use of the HFM site from 2010 to 2015. Worldwide, the annual number of sessions increased from 416 345 in 2010 to 1 636 368 in 2015. Most users (72–75%) found the site by using a search engine. Desktops and, more recently, smartphones were used to visit the website, accounting for 50% and 38%, respectively, of visits to the site in 2015. Conclusions Although its use has increased, the HFM site has not yet reached its full potential: fewer than 2 million users have visited the website, whereas the number of people living with heart failure worldwide is estimated to be 23 million. Uptake and use could be further improved by a continuous process of qualitative assessment of users' preferences, and the provision of professional helpdesk facilities, comprehensive information technology, and promotional support.

Aims The objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure (HF) patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group. Methods and results The European Society of Cardiology Heart Failure Long-Term Registry is a prospective, observational study collecting epidemiological information and 1-year follow-up data in 9134 HF patients. Patients were classified according to baseline LVEF into HF with reduced EF [EF 50% (HFpEF)]. In comparison with HFpEF subjects, patients with HFrEF were younger (64 years vs. 69 years), more commonly male (78% vs. 52%), more likely to have an ischaemic aetiology (49% vs. 24%) and left bundle branch block (24% vs. 9%), but less likely to have hypertension (56% vs. 67%) or atrial fibrillation (18% vs. 32%). The HFmrEF group resembled the HFrEF group in some features, including age, gender and ischaemic aetiology, but had less left ventricular and atrial dilation. Mortality at 1 year differed significantly between HFrEF and HFpEF (8.8% vs. 6.3%); HFmrEF patients experienced intermediate rates (7.6%). Age, New York Heart Association (NYHA) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups. Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF. A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients. Atrial fibrillation predicted mortality in HFpEF patients. Conclusions Heart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography, clinical presentation, aetiology and outcomes at 1 year. Differences in predictors for mortality might improve risk stratification and management goals.

Heart failure (HF) and frailty are two distinct yet commonly associated conditions. The interplay between the two conditions is complex, due to overlaps in underlying mechanisms, symptoms and prognosis. The assessment of frailty in patients with HF is crucial, as it is associated with both unfavourable outcomes and reduced access and tolerance to treatments. However, to date a consensus definition of frailty in patients with HF remains lacking and the need for a validated assessment score, for identifying those HF patients with frailty, is high and timely. This position paper proposes a new definition of frailty for use by healthcare professionals in the setting of HF and creates a foundation for the design of a tailored and validated score for this common condition.

Pharmacotherapy in chronic heart failure (HF) is challenging, due to the diverse neuroendocrine, inflammatory, metabolic and immunological mechanisms involved in its pathogenesis, the presence of co-morbidities and use of multiple therapies. Further, physiological parameters influencing drug pharmacokinetics (PKs) and pharmacodynamics (PDs) may be altered in patients with HF. There is growing evidence that the disease-induced physiological changes may influence the PKs and PDs of all drugs used in patients with HF. Therapeutic approaches should consider all factors that might influence the response to treatment and dosage should be tailored to individual patients. Hence, further studies are required to understand the PK and PD differences between chronic HF patients and healthy subjects. Because PK is difficult to be assessed in the individual patient with HF, PD effects should be used to tailor therapy in patients with HF.

Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches.

Aims Evidence suggests an excess risk of non-thromboembolic major adverse cardiac events (MACE) associated with atrial fibrillation (AF), particularly in individuals free of overt coronary artery disease (CAD). Metabolic syndrome (MetS) increases cardiovascular risk in the general population, but less is known how it influences outcomes in AF patients. We aimed to assess whether MetS affects the risk of MACE in AF patients without overt CAD. Methods and results This prospective, observational study enrolled 843 AF patients (mean-age, 62.5 ± 12.1 years, 38.6% female) without overt CAD. Metabolic syndrome was defined according to the National Cholesterol Education Program. The 5-year composite MACE included myocardial infarction (MI), coronary revascularization, and cardiac death. Metabolic syndrome was present in 302 (35.8%) patients. At 5-year follow-up, 118 (14.0%) patients experienced MACE (2.80%/year). Metabolic syndrome conferred a multivariable adjusted hazard ratio (aHR) of 1.98 for MACE [95% confidence interval (CI), 1.23-3.16; P = 0.004], and for individual outcomes: MI (aHR, 2.00; 95% CI, 1.69-5.11; P

The left atrium (LA) plays an important role in cardiovascular homeostasis through the modulation of cardiac filling and output, as well as the regulation of circulatory volume and tone. LA remodelling is characterised by dynamic alterations in atrial structure, function and electrophysiology. Most frequently, it occurs in association with ageing, hypertension, ischaemia, metabolic and pulmonary disorders (central illustration, figure 1). LA dilatation, the hallmark of atrial remodelling, has been increasingly recognised as a prognostic biomarker of thromboembolic and cardiovascular events, in particular in patients with atrial fibrillation (AF). However, cardiovascular risk attributable to atrial dilatation also appears to be increased in individuals without AF and is incompletely explained by the associated comorbidities and risk factors. The clarification of this issue was attempted by putting forward the concept of atrial cardiomyopathy , as a primary form of atrial abnormality, in which atrial fibrosis, hypercoagulability, contractile and endothelial dysfunction may lead to incident AF, heart failure (HF) and thromboembolism, independent of other causes (central illustration, figure 1).1 However, evidence from human studies supporting this concept is inconclusive. Also, a comparison of cardiovascular risk associated with LA dilatation in patients with and without AF has not been systematically conducted. Figure 1 Central illustration: Risk factors and clinical consequences of left atrial dilatation The study by Froehlich et al ,2 published in Heart , provides a new insight into this important subject. This study presents a systematic review and a meta-analysis of 91 observational studies exploring the association between several indices of LA dilatation and outcomes in patients with AF (23 studies with a total of 14 936 participants) and those without AF (68 studies with a total of 50 720 patients). The studies included in the meta-analysis integrated data on a wide array of background cardiovascular pathology, including hypertension, ischaemic …

Aim & Methods One critical factor enhancing the implementation of successful diagnostic and therapeutic strategies into clinical practice is awareness among the lay public. We describe awareness in a contemporary, multinational convenience sample of subjects attending the Heart Failure Awareness (HFA) Day Initiatives in 2013. Results We analysed 2,438 subjects (Germany 33%, Lithuania 42%, Romania 8%, Slovenia 17%) : 53% were female, 58% were aged >60 years, 11% (had) worked in the medical sector, 82% heard about HF before. Shortness of breath and tiredness were correctly identified as symptoms of heart failure in 71% and 61%, but only 52% recognized swelling of feet and legs as a clinical sign; 31% considered heart failure a normal symptom of old age, and only 38% realized the particularly poor prognosis after a heart failure related hospitalization. Subjects who had heard about heart failure before had a lower prevalence of common misbeliefs about HF. Conclusion In subjects participating in the HFA Day initiative 2013, the level of awareness was unsatisfactory, and important misconceptions remain. The educational and awareness activities for both the population at large and also for decision makers should be broadened and intensified.

Diabetes and heart failure are closely related: patients with diabetes have an increased risk of developing heart failure and those with heart failure are at higher risk of developing diabetes. Furthermore, antidiabetic medications increase the risk of mortality and hospitalisation for heart failure in patients with and without pre-existing heart failure. When the two diseases are considered individually, heart failure has a much poorer prognosis than diabetes mellitus; therefore heart failure has to be a priority for treatment in patients presenting with the two conditions, and the diabetic patient with heart failure should be managed by the heart failure team. No specific randomised clinical trials have been conducted to test the effect of cardiovascular drugs in diabetic patients with heart failure, but a wealth of evidence suggests that all interventions effective at improving prognosis in patients with heart failure are equally beneficial in patients with and without diabetes. The negative effect of glucose-lowering agents in patients with heart failure or at increased risk of heart failure has become evident after the withdrawal of rosiglitazone, a thiazolidinedione, from the EU market due to evidence of increased risk of cardiovascular events and hospitalisations for heart failure. An important issue that remains unresolved is the optimal target level of glycated haemoglobin, as recent studies have demonstrated significant reductions in total mortality, morbidity and risk of heart failure despite achieving HbA1c levels similar to those observed in the UKPDS study conducted some decades ago. Meta-analyses showed that intensive glucose lowering is not associated with any significant reduction in cardiovascular risk but conversely results in a significant increase in heart failure risk. Different medications have different risk: benefit ratios in diabetic patients with heart failure; therefore, the heart failure team must judge the required intensity of glycaemic control, the type and dose of glucose lowering agents and any change in glucose-lowering therapy, according to the clinical conditions present.

[Abstract] AIMS: The aim of this study was to evaluate the in-hospital and 1-year prognostic impact of diabetes and elevated blood glucose levels at hospital admission in patients with acute heart failure (HF). METHODS AND RESULTS: We studied a multinational cohort of 6926 hospitalized patients with acute HF enrolled in the European Society of Cardiology (ESC) and Heart Failure Association (HFA) Long-Term Registry, of whom 49.4% (n = 3422) had known or previously undiagnosed diabetes (defined as self-reported history, or medication use, or fasting glucose levels ≥7.0 mmol/L or haemoglobin A1c ≥6.5%). Compared with those without diabetes, patients with known or previously undiagnosed diabetes had higher cumulative rates of in-hospital mortality, 1-year mortality, and 1-year HF re-hospitalization that occurred independently of multiple clinical risk factors: in-hospital mortality [6.8 vs. 4.4%; adjusted hazard ratio (HR) 1.774; 95% confidence interval (CI) 1.282-2.456, P < 0.001], 1-year all-cause mortality (27.5 vs. 24%; adjusted HR 1.162; 95% CI 1.020-1.325, P = 0.024), and 1-year hospital re-admissions for HF (23.2 vs. 18.5%; adjusted HR 1.320; 95% CI 1.139-1.530, P < 0.001). Moreover, elevated admission blood glucose concentrations were powerfully prognostic for in-hospital mortality, but not for 1-year mortality or re-hospitalizations, in both patients with and without diabetes. CONCLUSIONS: Among patients hospitalized for acute HF, the presence of diabetes is independently associated with an increased risk of in-hospital mortality, 1-year all-cause mortality, and 1-year re-hospitalizations for HF, underscoring the need for more effective and personalized treatments of diabetes in this particularly high-risk patient population.

Background The EURObservational Research Programme is a rolling programme of cardiovascular registries and surveys of the European Society of Cardiology (ESC). These registries will provide information on the nature of cardiovascular disease and its management. This manuscript provides an update on new literature on peripartum cardiomyopathy (PPCM), published since the 2010 Position Statement from the Heart Failure Association of the European Society of Cardiology Working Group on PPCM, and describes a new registry on this under-recognized condition. Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of the pregnancy, or in the months following delivery, where no other cause for heart failure is found. Aims The PPCM Registry aims to describe disease presentation, comorbidities, diagnostic and therapeutic management of patients with PPCM, as well as information on their offspring. Centres not only from ESC and ESC-affiliated countries, but from around the world, are encouraged to participate. Methods A prospective registry on patients presenting with PPCM. At the time of writing, approximately 100 patients have been enrolled from 20 countries. All data entry is online via secure passwords and is supported by well-trained information technology personnel. Conclusion The EURObservational Research Programme will allow a comparison of women from around the world, from different ethnic backgrounds, presenting with PPCM and will report on their 6 month and 12 month outcomes. The study aims to include 1000 patients and follow them for 1 year. New centres volunteering to participate in the study will be welcomed.

Aims The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European Society of Cardiology (ESC) vs. non-ESC countries. Methods and results Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with completed case record forms (from 43 countries) entered into this ongoing registry. There were marked differences in socio-demographic parameters such as Human Development Index, GINI index on inequality, and Health Expenditure in PPCM patients from ESC vs. non-ESC countries (P < 0.001 each). Ethnicity was Caucasian (34%), Black African (25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%). Despite the huge disparities in socio-demographic factors and ethnic backgrounds, baseline characteristics are remarkably similar. Drug therapy initiated post-partum included ACE inhibitors/ARBs and mineralocorticoid receptor antagonists with identical frequencies in ESC vs. non-ESC countries. However, in non-ESC countries, there was significantly less use of beta-blockers (70.3% vs. 91.9%) and ivabradine (1.4% vs. 17.1%), but more use of diuretics (91.3% vs. 68.8%), digoxin (37.0% vs. 18.0%), and bromocriptine (32.6% vs. 7.1%) (P < 0.001). More patients in non-ESC vs. ESC countries continued to have symptomatic heart failure after 1 month (92.3% vs. 81.3%, P < 0.001). Venous thrombo-embolic events, arterial embolizations, and cerebrovascular accidents were documented in 28 of 411 patients (6.8%). Neonatal death rate was 3.1%. Conclusion PPCM occurs in women from different ethnic backgrounds globally. Despite marked differences in socio-economic background, mode of presentation was largely similar. Embolic events and persistent heart failure were common within 1 month post-diagnosis and required intensive, multidisciplinary management.

Introduction. Peripartum cardiomyopathy usually presents with systolic heart failure during the last months of pregnancy and up to five months postpartum. The disease is rare and can be fatal. Case Outline. We report a 30-year-old female who was diagnosed with acute myeloid leukemia, with maturation and cytogenetic finding of t(8;21)(q22;q22),del(9)(q22) in January 2004. She was treated with chemotherapy and achieved complete remission that lasts to date. She became pregnant and delivered a healthy newborn with caesarean section in 2009. Seven months later, she again became pregnant and delivered the second child with caesarean section in January 2011. Seven days after delivery she developed symptoms and signs of heart failure. Electrocardiogram showed sinus rhythm, low voltage and negative T-waves in inferior and lateral leads. Echocardiography revealed global left ventricular dysfunction with ejection fraction of 15%, with mobile thrombotic mass of 12 mm attached to the left ventricle wall. She was treated with both unfractionated and low-molecular heparin, diuretics, cardiotonics, and beta-blockers. Within six following weeks left ventricle systolic function improved up to 25-30%. The full clinical recovery was achieved in September 2013, resulting in absence of heart failure and left ventricular ejection fraction of 54%. Conclusion. Peripartum cardiomyopathy is a rare condition. The cause of cardiomyopathy is unknown, but it is believed that it could be triggered by various conditions and risk factors. Although the patient was treated with cardiotoxic drugs (doxorubicin and mitoxantrone) in permitted doses, they could have been contributory factors of myocardial damage. Close monitoring of cardiac function in the peripartal period might be beneficial in patients treated with cardiotoxic drugs. [Projekat Ministarstva nauke Republike Srbije, br. 175080 I br. OI 175034]

Accessibility to the available traditional forms of cardiac rehabilitation programs in heart failure patients is not adequate and adherence to the programs remains unsatisfactory. The home-based telerehabilitation model has been proposed as a promising new option to improve this situation. This papers aims are to discuss the tools available for telemonitoring, and describing their characteristics, applicability, and effectiveness in providing optimal long termmanagement for heart failure patients who are unable to attend traditional cardiac rehabilitation programs. The critical issues of psychological support and adherence to the telerehabilitation programs are outlined. The advantages and limitations of this long term management modality are presented and compared with alternatives. Finally, the importance of further research, multicenter studies of telerehabilitation for heart failure patients and the technological development needs are outlined, in particular interactive remotely controlled intelligent telemedicine systems with increased inter-device compatibility. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Exercise-derived variables have been used in the assessment of functional capacity and prognosis in patients with chronic heart failure. The aim of this study was to assess the relationship between cardiac pumping capability represented by peak cardiac power output and peak oxygen consumption, anaerobic threshold, ventilatory efficiency slope, and peak circulatory power in patients undergoing the 'Harefield Protocol'.Haemodynamic and gas exchange measurements were undertaken during a graded treadmill exercise test. They were performed on 54 patients-18 implanted with left ventricular assist devices (LVADs), 16 explanted (recovered), and 20 moderate-to-severe heart failure patients. Peak oxygen consumption was only highly correlated with peak cardiac power output in explanted LVAD (r = 0.85, P0.01), but not in implanted LVAD and heart failure patients (r = 0.55 and 0.53, P0.05). The anaerobic threshold was only modestly correlated with peak cardiac power output in heart failure and explanted (r = 0.46 and 0.54, P0.05) and weakly in implanted LVAD patients (r = 0.37, P0.05). Peak cardiac power output was well correlated with peak circulatory power in LVAD explanted and implanted (r = 0.82, P0.01; r = 0.63, P0.01) but not in heart failure patients (r = 0.31, P0.05). Ventilatory efficiency slope was only moderately correlated with peak cardiac power output in LVAD-explanted patients (r = -0.52, P0.05).Exercise-derived prognostic indicators demonstrate limited capacity in reflecting cardiac pumping capability in patients treated with LVADs and should therefore be used with caution in interpretation of cardiac organ function.

Diabetes mellitus-related cardiomyopathy (DMCMP) was originally described as a dilated phenotype with eccentric left ventricular (LV) remodelling and systolic LV dysfunction. Recently however, clinical studies on DMCMP mainly describe a restrictive phenotype with concentric LV remodelling and diastolic LV dysfunction. Both phenotypes are not successive stages of DMCMP but evolve independently to respectively heart failure with preserved left ventricular ejection fraction (HFPEF) or reduced left ventricular ejection fraction (HFREF). Phenotype-specific pathophysiological mechanisms were recently proposed for LV remodelling and dysfunction in HFPEF and HFREF consisting of coronary microvascular endothelial dysfunction in HFPEF and cardiomyocyte cell death in HFREF. A similar preferential involvement of endothelial or cardiomyocyte cell compartments explains DMCMP development into distinct restrictive/HFPEF or dilated/HFREF phenotypes. Diabetes mellitus (DM)-related metabolic derangements such as hyperglycaemia, lipotoxicity, and hyperinsulinaemia favour development of DMCMP with restrictive/HFPEF phenotype, which is more prevalent in obese type 2 DM patients. In contrast, autoimmunity predisposes to a dilated/HFREF phenotype, which manifests itself more in autoimmune-prone type 1 DM patients. Finally, coronary microvascular rarefaction and advanced glycation end-products deposition are relevant to both phenotypes. Diagnosis of DMCMP requires impaired glucose metabolism and exclusion of coronary, valvular, hypertensive, or congenital heart disease and of viral, toxic, familial, or infiltrative cardiomyopathy. In addition, diagnosis of DMCMP with restrictive/HFPEF phenotype requires normal systolic LV function and diastolic LV dysfunction, whereas diagnosis of DMCMP with dilated/HFREF phenotype requires systolic LV dysfunction. Treatment of DMCMP with restrictive/HFPEF phenotype is limited to diuretics and lifestyle modification, whereas DMCMP with dilated/HFREF phenotype is treated in accordance to HF guidelines.

Aims Ularitide is a synthetic form of urodilatin, a natriuretic peptide produced in the kidney with vasodilating, natriuretic, and diuretic effects, that offers promise for the management of decompensated heart failure (DHF). We assessed the efficacy and safety of ularitide in treating patients with DHF. Methods and results In this Phase II randomized, double-blind, placebo-controlled trial, 221 DHF patients received either placebo ( n =53) or ularitide at 7.5 ng/kg/min ( n =60), 15 ng/kg/min ( n =53), or 30 ng/kg/min ( n =55) as a 24-h continuous infusion. At 6 h, ularitide demonstrated a significant decrease in pulmonary capillary wedge pressure ( P =0.052, P =0.000004, P =0.000002, respectively) and improved dyspnoea score in the 7.5, 15, and 30 ng/kg/min ularitide group ( P =0.0026, P =0.0026, P =0.0013, respectively). Ularitide reduced systemic vascular resistance and increased cardiac index for the 15 and 30 ng/kg/min groups ( P =0.017, P =0.00002, respectively). Systolic blood pressure (BP) decreased dose dependency. Heart rate and serum creatinine were unchanged through day 3. Most frequently reported drug-related adverse events through day 3 in all ularitide groups were dose-dependent BP decrease and hypotension. Conclusion Ularitide lowered cardiac filling pressures and improved dyspnoea without apparent early deleterious effects on renal function in DHF patients. These results suggest that ularitide may play a role in the management of DHF.