Clinical practices and attitudes regarding the diagnosis and management of heart failure: findings from the CORE Needs Assessment Survey

Epidemiological studies on heart failure (HF) using large health care databases are becoming increasingly frequent, as they represent an invaluable opportunity to characterize the importance and risk factors of HF from a population perspective. Nevertheless, because of its complex diagnosis and natural history, the heterogeneous use of the relevant terminology in routine clinical practice, and the limitations of some disease coding systems, HF can be a challenging condition to assess using large health care databases as the main source of information. In this narrative review, we discuss some of the challenges that researchers may face, with a special focus on the identification and validation of chronic HF cases and acute HF decompensations. For each of these challenges, we present some potential solutions inspired by the literature and/or based on our research experience, aimed at increasing the internal validity of research and at informing its interpretation. We also discuss future directions on the field, presenting constructive recommendations aimed at facilitating the conduct of valid epidemiological studies on HF in the coming years

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period

Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time-averaged proportional change in N-terminal pro-brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks

Levosimendan in Acute and Advanced Heart Failure : An Appraisal of the Clinical Database and Evaluation of Its Therapeutic Applications

The use of inotropes for correcting hemodynamic dysfunction in patients with congestive heart failure has been described over many decades. However, negative or insufficient data have been collected regarding the effects of cardiac glycosides, catecholamines, and phosphodiesterase inhibitors on quality of life and survival. More recently, the calcium sensitizer and potassium channel-opener levosimendan has been proposed as a safer inodilator than traditional agents in some heart failure settings, such as advanced heart failure. At the 2017 annual congress of the Heart Failure Association of the European Society of Cardiology (Paris, April 30-May 2), a series of tutorials delivered by lecturers from 8 European countries examined how to use levosimendan safely and effectively in acute and advanced heart failure. The proceedings of those tutorials have been collated in this review to provide an expert perspective on the optimized use of levosimendan in those settings.Peer reviewe

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure—Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents

Haemodynamic Balance in Acute and Advanced Heart Failure: An Expert Perspective on the Role of Levosimendan

Acute and advanced heart failure are associated with substantial adverse short- and longer-term prognosis. Both conditions necessitate complex treatment choices to restore haemodynamic stability and organ perfusion, relieve congestion, improve symptoms and allow the patient to leave the hospital and achieve an adequate quality of life. Among the available intravenous vasoactive therapies, inotropes constitute an option when an increase in cardiac contractility is needed to reverse a low output state. Within the inotrope category, levosimendan is well suited to the needs of both sets of patients since, in contrast to conventional adrenergic inotropes, it has not been linked in clinical trials or wider clinical usage with increased mortality risk and retains its efficacy in the presence of beta-adrenergic receptor blockade; it is further believed to possess beneficial renal effects. The overall haemodynamic profile and clinical tolerability of levosimendan, combined with its extended duration of action, have encouraged its intermittent use in patients with advanced heart failure. This paper summarises the key messages derived from a series of 12 tutorials held at the Heart Failure 2019 congress organised in Athens, Greece, by the Heart Failure Association of the European Society of Cardiology

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure—Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. (C) 2019 The Authors. Published by Elsevier B.V.Peer reviewe

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years

Clinical practices and attitudes regarding the diagnosis and management of heart failure: findings from the CORE Needs Assessment Survey

Aims CORE is a continuing medical education initiative designed to support the evidence-based management of heart failure (HF) in the primary and secondary care settings. The goal of the CORE Needs Assessment Survey is to describe current clinical practice patterns and attitudes among global stakeholders in HF care. Methods and results The CORE Steering Committee guided the development of survey questions to assess clinical practice, confidence, and attitudes/perceptions among cardiologists, primary care physicians, and nurses involved in HF management. In total, 346 healthcare professionals from Australia (n = 59), Austria (n = 59), Canada (n = 60), Spain (n = 58), Sweden (n = 52), and the UK (n = 58) contributed survey data. Results revealed multiple gaps over the spectrum of HF care, including diagnosis (low recognition of the signs and symptoms of HF and limited use of diagnostic tests), treatment planning (underuse of recommended agents and subtherapeutic dosing), treatment monitoring and adjustment (lack of adherence to recommendations), and long-term management (low confidence in providing patient education). Although primary care and specialist physicians and nurses shared common unmet needs, healthcare professional-specific clinical gaps were also identified. Conclusions The CORE Needs Assessment Survey provides timely data describing current clinical practices and attitudes among physicians and nurses regarding key aspects of HF care. These findings will be useful for guiding the development of interventions tailored to the specific educational needs of different provider types and designed to support the evidence-based care of patients with HF