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Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). The present meta-analysis evaluates the effect of intravenous (IV) iron-carbohydrate complex supplementation in patients with HF with reduced ejection fraction (HFrEF) and ID/iron deficiency anaemia (IDA). Randomized controlled trials (RCTs) comparing IV iron-carbohydrate complexes with placebo/standard of care in patients with HFrEF with ID/IDA were identified using Embase (from 1957) and PubMed (from 1989) databases through 25 May 2021. Twelve RCTs including 2381 patients were included in this analysis. The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65); P 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms. These findings align with the European Society of Cardiology's 2021 HF guidelines, which recommend the consideration of FCM in symptomatic patients with a left ventricular ejection fraction45% and ID.

General practitioners (GPs) play a central role in healthcare, serving as the first point of contact, making appropriate referrals and coordinating care for chronic conditions such as heart failure (HF). We sought to determine healthcare use by people with HF in primary care.In this Study of Heart failure in the Australian Primary carE setting (SHAPE), we analysed records of 1.93 million adult patients who attended a total of 43 practices between 1 July 2013 and 30 June 2018. We identified and examined the data of 20,219 patients with HF to describe the frequency of visits and use of Medicare Benefits Schedule items.Patients with HF saw GPs 14.4 times per annum on average; 59.5% had a General Practice Management Plan (GPMP), 2.9% of GPMPs were reviewed annually or more frequently, and 46.8% of patients had been referred to a cardiologist. A total of 3761 had coexisting anxiety or depression, and of these 37.1% had a mental health plan.Patients with HF visit their GP frequently, with many not reaching guideline therapy nor referred to cardiologists. Low use of care planning and reviews presents an opportunity for GPs to improve care.

In the Asia-Pacific region, heart failure (HF) is associated with significant health and socioeconomic burden. Given the differences in the epidemiology of HF, as well as the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of chronic HF in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were either ‘agree’ or ‘neutral’. The resulting statements provide guidance on the diagnosis, assessment and treatment of patients with HF with reduced, mildly reduced or preserved ejection fraction in the Asia-Pacific region.

Background Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.Methods In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged >= 40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033.Findings Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1.0 [95% CI 0.8-1.2]; p=0.85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (p(interaction)=0.002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (p(interaction)=0.012 [>= 29.7 mL/m(2), worse outcomes]), and sex (p(interaction=)0.02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0.11).Interpretation Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Aims Heart failure (HF) causes significant morbidity and mortality, but the rates and characteristics of people with HF in Australia are not well studied. SHAPE set out to describe the characteristics of HF patients seen in the real‐world setting. Methods We analysed anonymized patient data extracted from the clinical software of 43 participating GP clinics for the 5 year period from 1 July 2013 to 30 June 2018. Patients were stratified into ‘definite’ and ‘probable’ HF based on a hierarchy of selection criteria and analysed for their clinical characteristics. Symptoms and signs of HF and ejection fraction data were searched for within the free text of the medical notes. Results Of the 1.12 million adults seen regularly, 20 219 were classified as having definite or probable HF. The mean age of the population was 69.8 years, 50.6% were female, and mean body mass index was 31.2 kg/m2. Fewer than 1 in 6 had the HF diagnosis optimally recorded. Only 3.2% (650 patients) had their left ventricular ejection fraction (EF) quantified: 40.9% had an EF ≥50% and 59.1% had an EF

Aims: To systematically review randomized controlled trials assessing effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)-derived evidence for SGLT2i efficacy mechanisms in heart failure (HF). Methods and results: Systematic searches of Medline and Embase were performed. In seven trials [3730–17 160 patients; low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27–39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type-2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects. Five trials (56–105 patients; low RoB) assessed the effects of 6–12 months of SGLT2i treatment on left ventricular structure/function; four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N-terminal pro B-type natriuretic peptide levels; significant reductions vs. placebo were reported after 8–12 months (two studies; 3730–4744 patients) but not ≤12 weeks (three studies; 80–263 patients). Limited available RCT-derived evidence suggests various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics (natriuresis and reduced interstitial fluid without blood volume contraction/neurohormonal activation) and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics. Conclusions: Sodium–glucose cotransporter 2 inhibitors reduce HHF regardless of T2DM status, and reversal of adverse left ventricular remodelling likely contributes to this efficacy. Hypothesis-driven mechanistic trials remain sparse, although numerous trials are planned or ongoing.

Heart failure is a major burden in Australia in terms of morbidity, mortality and healthcare expenditure. Multiple evidence-based therapies are recommended for heart failure with reduced ejection fraction (HFrEF), but data on physician adherence to therapy guidelines are limited.To compare use of HFrEF therapies against current evidence-based guidelines in an Australian hospital inpatient population.A retrospective review of patients admitted with a principal diagnosis of HFrEF across six metropolitan hospitals in Sydney, Australia, between January 2015 and June 2016. Use of medical and device therapies was compared with guideline recommendations using individual patient indications/contraindications. Readmission and mortality data were collected for a 1-year period following the admission.Of the 1028 HFrEF patients identified, 39 were being managed with palliative intent, leaving 989 patients for the primary analysis. Use of beta-blockers (87.7% actual use/93.6% recommended use) and diuretics (88.4%/99.3%) was high among eligible patients. There were large evidence-practice gaps for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB; 66.4%/89.0%) and aldosterone antagonists (41.0%/77.1%). In absolute terms, use of these therapies each increased by over 11% from admission. Ivabradine (11.5%/21.2%), automated internal cardiac defibrillators (29.5%/66.1%) and cardiac resynchronisation therapy (13.1%/28.7%) were used in a minority of eligible patients. Over the 1-year follow-up period, the mortality rate was 14.8%, and 44.2% of patients were readmitted to hospital at least once.Hospitalisation is a key mechanism for initiation of HFrEF therapies. The large evidence-practice gaps for ACEI/ARB and aldosterone antagonists represent potential avenues for improved HFrEF management.

Women have been historically underrepresented in clinical trials of heart failure (HF). We aimed to assess for sex differences in patient characteristics and the efficacy of guideline-directed medical therapy (GDMT) in HF. Systematic literature search for randomized controlled trials (RCTs) of GDMT reporting cardiovascular outcomes by sex in patients with HF. The primary outcome was the composite of cardiovascular death and hospitalization for HF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using inverse variance weighting and random effects meta-analysis. Twenty-six RCTs totaling 84,818 participants (27% women) were included. Women with HF were older, had higher New York Heart Association (NYHA) class, more hypertension and obesity, and higher mean left ventricular ejection fraction compared to men. There was evidence for most GDMT in reducing the primary outcome in women with HF with reduced ejection fraction (HFrEF) (angiotensin-converting enzyme inhibitors/angiotensin-receptor blocker [RR 0.86, 95% CI 0.75-0.97], angiotensin-receptor blocker/neprilysin inhibitor (ARNI) [RR 0.77, 95% CI 0.62-0.94], beta-blocker [RR 0.67, 95% CI 0.51-0.89], ivabradine [RR 0.74, 95% CI 0.60-0.91], and sodium-glucose cotransporter-2 (SGLT2) inhibitors [RR 0.66, 95% CI 0.54-0.81]) and a non-significant trend for benefit with mineralocorticoid-receptor-antagonist (MRA) [RR 0.77, 95% CI 0.52-1.16]). Compared to men with HFrEF, GDMT reduced the primary outcome in women to a similar degree across all drug classes (ratio of RR 1.05, 95% CI 0.96-1.14). Despite differences in baseline characteristics and an underrepresentation of women in HF clinical trials, GDMT are as efficacious in women as compared to men in reducing cardiovascular events in HF.

International audience; Iron deficiency (ID) is a comorbid condition frequently seen in patients with heart failure (HF). Iron has an important role in the transport of oxygen, and is also essential for skeletal and cardiac muscle, which depend on iron for oxygen storage and cellular energy production. Thus, ID per se, even without anaemia, can be harmful. In patients with HF, ID is associated with a poorer quality of life (QoL) and exercise capacity, and a higher risk of hospitalisations and mortality, even in the absence of anaemia. Despite its negative clinical consequences, ID remains under-recognised. However, it is easily diagnosed and managed, and the recently revised 2021 European Society of Cardiology (ESC) guidelines on HF provide specific recommendations for its diagnosis and treatment. Prospective randomised controlled trials in patients with symptomatic HF with reduced ejection fraction (HFrEF) show that correction of ID using intravenous iron (principally ferric carboxymaltose [FCM]) provides improvements in symptoms of HF, exercise capacity and QoL, and a recent trial demonstrated that FCM therapy following hospitalisation due to acute decompensated HF reduced the risk of subsequent HF hospitalisations. This review provides a summary of the epidemiology and pathophysiology of ID in HFrEF, and practical guidance on screening, diagnosing, and treating ID.

This consensus statement of Australian clinicians provides new recommendations for the pharmacological management of heart failure based on studies reported since the publication of the 2018 Australian heart failure guidelines.▪Use of sodium-glucose cotransporter 2 (SGLT2) inhibitors to prevent hospitalisation for heart failure in type 2 diabetes mellitus can be extended to patients with multiple cardiovascular risk factors, albuminuric chronic kidney disease, or atherosclerotic cardiovascular disease. ▪New evidence supports the use of a mineralocorticoid receptor antagonist (finerenone) to prevent heart failure in type 2 diabetes mellitus associated with albuminuric chronic kidney disease. ▪In addition to renin angiotensin system inhibitors (angiotensin receptor neprilysin inhibitor preferred), beta blockers and mineralocorticoid receptor antagonists, an SGLT2 inhibitor (dapagliflozin or empagliflozin) is recommended in all patients with heart failure with reduced left ventricular ejection fraction (LVEF ≤ 40%) (HFrEF). Lower quality evidence supports these therapies in patients with heart failure with mildly reduced LVEF (41-49%) (HFmrEF). ▪A soluble guanylate cyclase stimulator (vericiguat), selective cardiac myosin activator (omecamtiv mecarbil) and, if iron deficient, intravenous iron (ferric carboxymaltose) provide additional benefits in persistent HFrEF. ▪An SGLT2 inhibitor (empagliflozin) should be considered in patients with heart failure with preserved LVEF (≥ 50%) (HFpEF). Key changes in management from this statement: This document broadens the scope of angiotensin receptor neprilysin inhibitor use in patients with HFrEF and HFmrEF. SGLT2 inhibitor use expands to become a cornerstone therapy in HFrEF, with increasing evidence to support its use in HFmrEF and HFpEF.

Aims At present, there is no robust information on the prevalence and incidence of heart failure (HF) in the general Australian community. The present study of primary care data sought to estimate the prevalence and incidence of HF in the community and to describe the demographic and clinical profile of Australians with HF. Methods and results We undertook a retrospective cohort study based on analysis of anonymized medical records of adult patients cared for at 43 Australian general practices between 1 July 2013 and 30 June 2018. Data were extracted from coded and uncoded fields in electronic medical records. The prevalence and annual incidence of HF were calculated, along with 95% confidence intervals, using the ‘active’ population of people who were regular attenders at the practices. Age‐standardized estimates were also derived using the 2017 Australian population as reference. The mean age of the population with HF was 69.8 years, 50.6% were female, and mean body mass index was 31.2 kg/m2. The age‐standardized prevalence was 2.199% [95% confidence interval (CI): 2.168–2.23%], and the age‐standardized annual incidence was 0.348% (95% CI: 0.342–0.354%). These estimates accord with almost 420 000 people living with HF in Australia in 2017, and >66 000 new cases of HF occurring that year. Only 18.9% of patients with definite HF had this formally captured as a ‘diagnosis’ in their medical record. HF was more frequent among those of lower socio‐economic status. Conclusions HF is common in Australia. The majority of HF patients do not have this diagnosis optimally noted in their primary care medical records.