Interatrial shunt devices for heart failure with normal ejection fraction: a technology update

Heart failure with normal ejection fraction (HeFNEF) accounts for ~50% of heart failure admissions. Its pathophysiology and diagnostic criteria are yet to be defined clearly which may hinder the search for effective treatments. The clinical hallmark of HeFNEF is exertional breathlessness, often due to an abnormal increase in left atrial pressure during exercise. Creation of an interatrial communication to offload the left atrium is a possible therapeutic approach. There are two percutaneously delivered devices currently under investigation which are discussed in this review

Diuretic Treatment in Patients with Heart Failure: Current Evidence and Future Directions – Part I: Loop Diuretics

Purpose of Review: Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion—loop diuretics—has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and the current trial evidence for different diuretic strategies and explore potential future directions of research. Recent Findings: We will assess recent trials including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF amongst others, and assess how these may influence current practice and future research. Summary: There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF

Diuretic Treatment in Patients with Heart Failure: Current Evidence and Future Directions-Part II: Combination Therapy

Purpose of Review Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion loop diuretics-has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and current trial evidence for different diuretic strategies and explore potential future directions of research. Recent Findings We will assess recent trials, including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF, and assess how these may influence current practice and future research. Summary There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high-dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF

Synthetic protein scaffold-mediated manipulation of LOX-1 scavenger receptor in cell function, vascular physiology and disease

Binding and internalization of oxidized low-density lipoprotein (oxLDL) by immune cells within the arterial sub-intimal layer is a key step in the initiation and progression of atherosclerosis. Scavenger receptors (SRs) are a “super-family” of cell surface receptors expressed by immune cells which promote the removal of harmful non-self or altered-self targets, including oxidatively modified ligands such as oxLDL. Lectin-like oxidized LDL receptor-1 (LOX-1) is a member of the SR-E family of scavenger receptors. LOX-1 – oxLDL binding has been shown to exert significant pro-atherogenic effects. In this study, we used in vitro and in vivo models of atherosclerosis to explore the effectiveness of LOX-1 targeting in the inhibition of oxLDL binding and the amelioration of atherosclerosis and neointimal hyperplasia. LOX-1 was targeted using novel non-antibody artificial binding proteins, known as Affimers. Immunofluorescence studies using a tetracycline- inducible cell line expressing LOX-1 demonstrate the binding efficiency of fluorescent-labelled LOX-1 Affimers to LOX-1 in live cells. In same cell line, we co-incubated fluorescent-labelled oxLDL with increasing concentrations of LOX- 1 Affimers. The findings show that LOX-1 Affimers inhibit LOX-1 – oxLDL binding. ELISA studies were carried out to identify LOX-1 affimers with comparable affinity for both human and murine LOX-1. The most cross-reactive LOX-1 Affimer was taken forward in to a transgenic mouse model of diet-induced atherosclerosis. This model used APO-E null and APO-E/LOX-1 null mice to compare the effects of LOX-1 knockout with LOX-1 targeting using LOX-1 affimers. LOX-1 knockout resulted in a reduction in aortic and peripheral arterial atherosclerosis, and neointimal hyperplasia. LOX-1 targeting with affimers produced promising results. Treatment with LOX-1 affimers reduced atherosclerosis and NIH, but to a lesser extent compared with LOX-1 knockout. Treatment with LOX-1 affimer exerted additional metabolic benefits including protective effects against diet- induced obesity and insulin resistance. The results from these studies suggest that LOX-1 is an attractive target in the development of novel therapeutics in atherosclerosis. Targeted LOX-1 inhibition potentially offers protective benefits in associated metabolic disorders such as obesity and insulin resistance

Pharmacological and non-pharmacological treatment for decompensated heart failure: what is new?

Purpose of the Review: Acute heart failure (AHF) is a life-threatening clinical condition that requires prompt medical attention. The aim of the current review is to summarise the results of recent clinical trials conducted in patients with AHF. Recent Findings: Several novel compounds have apparently beneficial acute effects on cardiovascular haemodynamics and patients’ symptoms, but their administration has not yet translated into improved survival and has been deleterious in some cases. Summary: The management of patients with AHF is challenging and reflects the heterogeneity of patient’s presentation, the complexity and severity of a multi-organ syndrome, and the limited therapeutic options, usually restricted to a combination of diuretics and vasodilators. Ongoing trials of novel treatments may provide evidence of an effect on outcomes

EARLY PRE-SEASON CHANGES IN THE COUNTERMOVEMENT JUMP OUTCOME AND STRATEGY VARIABLES OF ENGLISH SUPER LEAGUE RUGBY PLAYERS

The aim of this study was to quantify changes in typical (i.e., jump height) and alternative (i.e., jump momentum) countermovement jump (CMJ) outcome and strategy variables, alongside maximal strength, during the early English Super League pre-season period. Twenty professional senior male rugby league players from an English Super League club performed CMJ and isometric mid-thigh pull (IMTP) testing (3 trials of each) on portable dual force plates on the first and last day of pre-season training held prior to a short Christmas break (December 2021). Select CMJ outcome and strategy variables and both absolute and relative (to body mass) peak force for the IMTP trials were automatically calculated via proprietary software. IMTP peak force significantly increased in both absolute and relative terms (moderate effects; g = 0.69) reflecting the aims of the pre-season training programme. Countermovement depth moderately reduced (r = 0.76) but time to take-off and reactive strength index modified remained unchanged. A small but non-significant increase in body mass was noted, which, along with increased jump height (small effect; g = 0.46), contributed to a significant, moderate increase in jump momentum (g = 0.59). Quantifying concomitant changes in CMJ outcome and strategy variables, alongside body mass, during pre-season training may offer richer insight into rugby league players’ future physical development requirements beyond jump height alone

A social return on investment evaluation of the pilot social prescribing EmotionMind Dynamic coaching programme to improve mental wellbeing and self-confidence

The COVID-19 pandemic contributed to longer waiting lists for people seeking to access mental health services. The NHS Five Year Forward View encourages the development of empowerment-based social prescribing interventions to supplement existing mental health programmes. Based in South Wales, EmotionMind Dynamic (EMD) is a lifestyle coaching programme that supports individuals suffering from anxiety or depression. In this evaluation of lifestyle coaching, a mixed-method social return on investment (SROI) methodology was used to value quantitative and qualitative data from face-to-face and online participants. Data collection took place between June 2021 and January 2022. Participants included both self-referred clients and those referred from health services. Mental wellbeing data were collected at baseline and at the end of the programme using the short Warwick−Edinburgh Mental Wellbeing Scale (SWEMWBS) and the General Self-Efficacy Scale (GSES). Baseline and follow-up data were available for 15 face-to-face participants and 17 online clients. Wellbeing valuation quantified and valued outcomes from participants. Results indicated that for every GBP 1 invested, lifestyle coaching generated social values ranging from GBP 4.12−GBP 7.08 for face-to-face clients compared with GBP 2.37−GBP 3.35 for online participants. Overall, lifestyle coaching generated positive social value ratios for both face-to-face and online clients

Highway deicing salt dynamic runoff to surface water and subsequent infiltration to groundwater during severe UK winters

Dynamic impact to the water environment of deicing salt application at a major highway (motorway) interchange in the UK is quantitatively evaluated for two recent severe UK winters. The contaminant transport pathway studied allowed controls on dynamic highway runoff and storm-sewer discharge to a receiving stream and its subsequent leakage to an underlying sandstone aquifer, including possible contribution to long-term chloride increases in supply wells, to be evaluated. Logged stream electrical-conductivity (EC) to estimate chloride concentrations, stream flow, climate and motorway salt application data were used to assess salt fate. Stream loading was responsive to salt applications and climate variability influencing salt release. Chloride (via EC) was predicted to exceed the stream Environmental Quality Standard (250 mg/l) for 33% and 18% of the two winters. Maximum stream concentrations (3500 mg/l, 15% sea water salinity) were ascribed to salt-induced melting and drainage of highway snowfall without dilution from, still frozen, catchment water. Salt persistance on the highway under dry-cold conditions was inferred from stream observations of delayed salt removal. Streambed and stream-loss data demonstrated chloride infiltration could occur to the underlying aquifer with mild and severe winter stream leakage estimated to account for 21 to 54% respectively of the 70 t of increased chloride (over baseline) annually abstracted by supply wells. Deicing salt infiltration lateral to the highway alongside other urban/natural sources were inferred to contribute the shortfall. Challenges in quantifying chloride mass/fluxes (flow gauge accuracy at high flows, salt loading from other roads, weaker chloride-EC correlation at low concentrations), may be largely overcome by modest investment in enhanced data acquisition or minor approach modification. The increased understanding of deicing salt dynamic loading to the water environment obtained is relevant to improved groundwater resource management, highway salt application practice, surface-water - ecosystem management, and decision making on highway drainage to ground