SGLT2-inhibitors: Should they be considered anti-remodeling drugs?

Heart failure (HF) is a complex syndrome characterized by multiple aetiologies and a progressive clinical course with a strong impact in terms of morbidity, mortality and public health costs. According to the neurohormonal hypothesis, HF with reduced ejection fraction (HFrEF) is considered a neurohormonal disease and HF patients benefit from the use of medications that interfere with and modulate the negative effects of neurohormonal systems (i.e. permanent renin–angiotensin–aldosterone system activation). The foundation of HF treatment includes the combination of well-known neurohormonal antagonists such as angiotensin receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. However, recently, Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-i) have emerged as a new additional cornerstone of HF treatment – they are now regarded as one of the four keystone drugs to be introduced as first line therapy in HFrEF (class I recommended drug). Moreover, SGLT2-i have been shown to decrease combined endpoints of cardiovascular mortality and worsening HF regardless of ejection fraction (EF), and also to prevent the onset of HF in patients who are at high cardiovascular risk. The pathophysiologic mechanisms that may explain the benefit in clinical outcomes of the SGLT2-i in patients with HF are still incompletely understood. Therefore, it is of great interest to analyze the biological changes, which may occur in patients taking SGLT2-i because this may be helpful to elucidate how SGLT2-i may lead to improved cardiovascular outcomes. In this context, the metanalysis published in the European Journal of Internal Medicine by Fan et al. is timely and relevant because it evaluates the potential structural and functional impact of SGLT2-i in human heart giving possible translational understandings of the biologic consequences caused by SGLT2-i

Heart failure outcomes in patients with type 2 diabetes mellitus: findings from the cardiovascular outcome trials of antidiabetes agents

Type 2 diabetes mellitus (T2DM) is a recognised risk factor for several cardiovascular (CV) conditions including heart failure (HF). Findings that reflect CV risk associated with T2DM medications have led to regulatory requirement of conducting CV outcome trials (CVOTs) for new antidiabetes drugs. Over the years, several CVOTs using different glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors have reported neutral or improved CV risks or hospitalisation for HF. However, these studies included only a small proportion of the patients with baseline HF thus limiting the available evidence. Ongoing trials such as EMPEROR programme and DAPA-HF in large patient populations with chronic HF could potentially broaden the use of these drugs beyond their conventional therapeutic indication

Vorhofflimmerndiagnostik mittels EKG-fähiger Smartwatches

Background!#!The fiberoptic endoscopic evaluation of swallowing (FEES) is considered to be an indispensable instrumental procedure in the management of patients with dysphagia. The aim of the implemented training curriculum is to raise the quality standards and to contribute to an upgrading of the procedure.!##!Objective!#!The study evaluated to what extent a standardized implementation, evaluation and documentation of FEES takes place in Germany after the introduction of the curriculum.!##!Material and methods!#!In this study 603 neurological and geriatric hospitals in Germany were interviewed by the use of an online questionnaire regarding structural features and the course of the investigation.!##!Results!#!A total of 190 institutions completed the survey. Of the institutions 43.31% had only implemented FEES since the publication of the curriculum. The practical application is increasingly carried out by physicians (59%), the clinical reports and cost recommendations are carried out by speech therapists (62% and 83%, respectively). The practical application by speech therapists increases with increasing level of training. Despite orientation towards the standard protocol according to Langmore, there are differences in the implementation of the anatomical physiological examination, the consistencies and foods administered and the scoring of swallowing-relevant parameters.!##!Discussion!#!The introduction of the curriculum has led to an upgrading of the FEES and to a strengthening of speech therapy as the implementing professional group. At the current state of the art there is a homogeneous course of the examination in essential aspects but it shows a need for further uniformity. The FEES curriculum could be used as a guiding instrument for further standardization

Effects of hormonal changes on sarcopenia in chronic kidney disease: where are we now and what can we do?

Sarcopenia or muscle wasting is a progressive and generalized skeletal muscle disorder involving the accelerated loss of muscle mass and function, often associated with muscle weakness (dynapenia) and frailty. Whereas primary sarcopenia is related to ageing, secondary sarcopenia happens independent of age in the context of chronic disease states such as chronic kidney disease (CKD). Sarcopenia has become a major focus of research and public policy debate due to its impact on patient's health-related quality of life, health-care expenditure, morbidity, and mortality. The development of sarcopenia in patients with CKD is multifactorial and it may occur independently of weight loss or cachexia including under obese sarcopenia. Hormonal imbalances can facilitate the development of sarcopenia in the general population and is a common finding in CKD. Hormones that may influence the development of sarcopenia are testosterone, growth hormone, insulin, thyroid hormones, and vitamin D. Although the relationship between free testosterone level that is low in uraemic patients and sarcopenia in CKD is not well-defined, functional improvement may be seen. Unlike testosterone, it is known that vitamin D is associated with muscle strength, muscle size, and physical performance in patients with CKD. Outcomes after vitamin D replacement therapy are still controversial. The half-life of growth hormone (GH) is prolonged in patients with CKD. Besides, IGF-1 levels are normal in patients with Stage 4 CKD-a minimal reduction is seen in the end-stage renal disease. Unresponsiveness or resistance of IGF-1 and changes in the GH/IGF-1 axis are the main causes of sarcopenia in CKD. Low serum T3 level is frequent in CKD, but the net effect on sarcopenia is not well-studied. CKD patients develop insulin resistance (IR) from the earliest period even before GFR decline begins. IR reduces glucose utilization as an energy source by hepatic gluconeogenesis, decreasing muscle glucose uptake, impairing intracellular glucose metabolism. This cascade results in muscle protein breakdown. IR and sarcopenia might also be a new pathway for targeting. Ghrelin, oestrogen, cortisol, and dehydroepiandrosterone may be other players in the setting of sarcopenia. In this review, we mainly examine the effects of hormonal changes on the occurrence of sarcopenia in patients with CKD via the available data

Advanced cancer is also a heart failure syndrome: a hypothesis

We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti-cancer therapies. This includes an increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilatation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways. We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti-cancer therapies. The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients. We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio-oncology

Natura 2000 and the regulation of agricultural ammonia emissions

This article provides a comparative analysis of the regulation of ammonia emissions, primarily from livestock installations, in Denmark, Germany and the Netherlands. It discusses the challenges of regulating agricultural ammonia emissions in view of the rulings of the Court of Justice of the European Union (cjeu) on Art. 6(3) of the Habitats Directive. It is argued that the need to ensure certainty concerning the absence of significant effects on Natura 2000 sites is challenged by the uncertainties regarding both the state of individual habitat types and the potential impact of individual projects. A more integrated or programmatic approach may provide an alternative approach to individual assessments, but it is necessary to ensure that additional loads from new or enlarged livestock installations are permitted in areas with high ammonia loads only where it is certain that a programmatic approach will ensure that there are no harmful effects. This might be an almost impossible task