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BACKGROUND: Steroidal mineralocorticoid receptor antagonists reduce morbidity and mortality among patients with heart failure and reduced ejection fraction, but their efficacy in those with heart failure and mildly reduced or preserved ejection fraction has not been established. Data regarding the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with heart failure and mildly reduced or preserved ejection fraction are needed. METHODS: In this international, double-blind trial, we randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes. The components of the primary outcome and safety were also assessed. RESULTS: Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007). The total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P = 0.006). The percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia. CONCLUSIONS: In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo. (Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.).

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AIMS: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry. METHODS AND RESULTS: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in the emergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most by a general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized for HF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation of GDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. After the AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85% in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF. CONCLUSION: Use and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohorts and registries including more primary care and general medicine and regions more local or outside of Europe and ESC-affiliated countries.

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INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals. METHODS: The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials. RESULTS: Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1612851.54 up to EUR 6587360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data. CONCLUSIONS: In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals.

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AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

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INTRODUCTION AND OBJECTIVES: Current epidemiological data on heart failure (HF) in Portugal derives from studies conducted two decades ago. The main aim of this study is to determine HF prevalence in the Portuguese population. Using current standards, this manuscript aims to describe the methodology and research protocol applied. METHODS: The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) is a large, three-stage, population-based, nationwide, cross-sectional study. Community-dwelling citizens aged 50 years and older will be randomly selected via stratified multistage sampling. Eligible participants will be invited to attend a screening visit at a mobile clinic for HF symptom assessment, anthropomorphic assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, one-lead electrocardiogram (ECG) and a sociodemographic and health-related quality of life questionnaire (EQ-5D). All subjects with NT-proBNP ≥125 pg/mL or with a prior history of HF will undergo a diagnostic confirmatory assessment at the mobile clinic composed of a 12-lead ECG, comprehensive echocardiography, HF questionnaire (KCCQ) and blood sampling. To validate the screening procedure, a control group will undergo the same diagnostic assessment. Echocardiography results will be centrally validated, and HF diagnosis will be established according to the European Society of Cardiology HF guidelines. A random subsample of patients with an equivocal HF with preserved ejection fraction diagnosis based on the application of the Heart Failure Association preserved ejection fraction diagnostic algorithm will be invited to undergo an exercise echocardiography. CONCLUSIONS: Through the application of current standards, appropriate methodologies, and a strong research protocol, the PORTHOS study will determine the prevalence of HF in mainland Portugal and enable a comprehensive characterization of HF patients, leading to a better understanding of their clinical profile and health-related quality of life.

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Primary hepatic lymphoma (PHL) is extremely rare, accounting for less than 1% of all lymphomas, and is limited to the liver without extrahepatic involvement. A 30-year-old male was admitted in the Emergency Department complaining of weakness, fever, night sweats, significant weight loss, discrete ring alopecia, hepatomegaly, right axillary adenopathy and oedema of both legs. Laboratory evaluation showed normocytic normochromic anaemia, thrombocytosis, hyperbilirubinemia, cholestasis and increased international normalised ratio (INR). A computed tomography (CT) scan found an enlarged liver with a heterogeneous structure and moderate ascites. After admission in our ward further investigation revealed increased sedimentation velocity, ferritin and serum lactate dehydrogenase. A hepatic biopsy was performed which confirmed the diagnosis as a nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The patient was transferred to a haematological ward and underwent chemotherapy with six cycles of R-CHOP. He is in complete remission after a year and half since the beginning of treatment. NLPHL, a very rare lymphoma, is more common in men between the third and fifth decades of life. Usually, the symptoms are very unspecific; a few patients have B symptoms at admission. This kind of presentation is also common in infectious, metabolic and autoimmune diseases, which were excluded in this case. Due to technical issues the final diagnosis was only possible due to the liver biopsy. Treatment with standard Hodgkin lymphoma protocols leads to complete remission in more that 95% of patients with NLPHL. LEARNING POINTS: Differential diagnosis of fever, especially in young patients, is very complex and complete investigation takes time, which can delay the diagnosis of malignancies such as primary hepatic lymphoma (PHL).PHL is very rare, and overlapping symptoms with other liver diseases can make the diagnosis very challenging.When the suspicion of PHL is very high, only the hepatic biopsy can lead to the correct diagnosis because the disease has no extrahepatic involvement.

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BACKGROUND: Women with heart failure with reduced ejection fraction (HFrEF) receive less guideline-recommended therapy and experience worse quality of life than men. OBJECTIVES: The authors sought to assess differences in baseline characteristics, outcomes, efficacy, and safety of omecamtiv mecarbil between men and women enrolled in the GALACTIC-HF (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction) study. METHODS: In GALACTIC-HF, patients with symptomatic heart failure with EF of 35% or less, recent heart failure event, and elevated natriuretic peptides were randomized to omecamtiv mecarbil or placebo. The current analysis investigated differences in baseline characteristics, clinical outcomes, and efficacy and safety of omecamtiv mecarbil between men and women. RESULTS: Of 8,232 patients analyzed, 21.2% were women. Women more likely self-identified as being Black, had worse symptoms (lower Kansas City Cardiomyopathy Questionnaire Total Symptom Score [KCCQ-TSS]), and were less likely to be treated with angiotensin receptor/neprilysin inhibitor and devices at baseline. Compared with men, women had lower rates of the primary endpoint (adjusted HR: 0.80, 95% CI: 0.73-0.88). Sex did not significantly modify omecamtiv mecarbil's treatment effect (P interaction = 0.68). Women also had 20% less risk of cardiovascular death, heart failure event, and all-cause death. Women participants had lower rates of serious adverse events. CONCLUSIONS: Women participants of the GALACTIC-HF trial had worse quality of life and were less likely to be treated with guideline-based therapies at baseline. Despite KCCQ-TSS being predictive of poor outcomes in this population, women had a 20% lower risk of an HF event or cardiovascular death compared with men. The beneficial effect of omecamtiv mecarbil did not significantly differ by sex. (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).

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INTRODUCTION AND OBJECTIVES: Heart failure (HF) has significant morbidity and mortality, and its prevalence will continue to increase in the future. This unfavorable evolution requires reflection as well as recommendations and decisions based on expert critical and strategic appraisal. METHODS: In the Acceleration on Heart Failure Empowerment and Awareness - the Portuguese Challenge (ATHENA-PT) study, a range of strategic factors that represent the strengths, weaknesses, threats, and opportunities (SWOT) of HF in Portugal were established. These factors were assessed quantitatively by experts, to create a final SWOT matrix for the management and prevention of HF in Portugal and to outline recommendations. RESULTS: For HF management, the panel emphasized the following strategic recommendations: (i) reimbursement of natriuretic peptides testing in primary healthcare; (ii) reimbursement of Doppler assessment in echocardiographic studies and promotion of detailed information in reports; (iii) intervention to improve the prognosis of patients with HF with preserved ejection fraction; (iv) ensuring effective healthcare transition between hospital and ambulatory units, using checklists/protocols; and (v) reinforcement and commitment to the training of primary health physicians and to the cardiac rehabilitation of patients. For the prevention of HF, the following recommendations/proposals were proposed: (i) campaigns to raise awareness of cardiovascular disease risk factors; (ii) promotion of physical exercise and healthy eating; and (iii) avoidance of therapeutic inertia in the management of risk factors. CONCLUSIONS: The acknowledgment of various strategic factors and their prioritization by experts made it possible to create and reinforce a range of new strategic recommendations for the management and prevention of HF.

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Introduction Recurrent hospitalizations for worsening heart failure (WHF) represent a major global public health concern, resulting in significant individual morbimortality and socioeconomic costs. This real-life study aimed to determine the rate and predictors of readmission for WHF in a cohort of outpatients with chronic heart failure (CHF) followed in a heart failure clinic (HFC) at a university hospital. Methods We conducted a longitudinal, observational, and retrospective study of all consecutive CHF patients seen at the HFC of the São Francisco Xavier Hospital, Lisbon, by a multidisciplinary team in 2019. The patients were followed for one year and were on optimized therapy. The inclusion criteria for the study were patients who had been hospitalized and subsequently discharged at least three months prior to their enrollment. Patient demographics, heart failure (HF) characterization, comorbidities, pharmacological treatment, treatments of decompensated HF in the day hospital (DH), hospitalizations for WHF, and death were recorded. We applied logistic regression analysis to assess predictors of hospital readmission for HF. Results A total of 351 patients were included: 90 patients (26%) had WHF requiring treatment with intravenous diuretics in the DH; 45 patients (mean age: 79.1 ± 9.0 years) were readmitted for decompensated HF within one year (12.8%) with no gender difference, while 87.2% of the patients (mean age: 74.9 ± 12.1 years) were never readmitted. Readmitted patients were significantly older than those who were not (p=0.031). Additionally, they had a higher New York Heart Association (NYHA) functional classification (p<.001), were on a higher daily dose of furosemide (p=0.008) at the time of the inclusion visit, were more frequently affected by the chronic obstructive pulmonary disease (COPD) (p=0.004); had been treated more often in the DH for WHF (p<.001) and had a higher mortality rate (p<.001) at one year. Conclusions This study aimed to determine WHF patient readmission rates and predictors. According to our results, a higher NYHA class, the need for treatment in the DH for WHF, a daily dose of furosemide equal to or greater than 80 mg, and COPD were predictors of readmission for WHF. CHF patients continue to experience WHF and recurrent hospitalizations despite therapeutic advances and close follow-up in the HFC with the multidisciplinary team. Besides COPD, the HF readmission risk factors found were mainly related to advanced disease. Furthermore, the structured and multidisciplinary approach of our disease management program likely contributed to our relatively low rate of readmissions.

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Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7-12.8; 14.9-17.1; p = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients.

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Acute heart failure (HF) decompensation generally manifests with signs and symptoms of congestion that strongly predict poor poor patient outcome. Loop diuretics are the cornerstone of therapy to counteract fluid overload and are widely used for acute management and chronic stabilization of HF. However, a diminished response to loop diuretics is a common problem, affecting the patient's clinical course and potentially prolonging hospitalization. Diuretic resistance is defined as failure to decongest despite appropriate and escalating loop diuretic therapy. We propose a protocol for the management of diuretic resistance. The initial approach should include an assessment of causes of pseudo-diuretic resistance. Adjustments to loop diuretic therapy, such as increasing doses and frequency of administration and sequential nephron blockade, may be successful. For hospitalized patients with progressive disease there are more invasive methods for fluid removal. Switching from oral to intravenous loop diuretics is essential to avoid variable absorption and for symptomatic relief. Extracorporeal ultrafiltration is also an option since this technique is highly effective at removing plasma fluid from blood. While extracorporeal ultrafiltration is an invasive solution, peritoneal dialysis is a home-based, intermittent therapeutic option that can enable efficient management of fluid overload, preventing HF-related hospital admission, and improving quality of life. As a last resort for fluid removal, a peritoneal dialysis regimen should fully exploit its decongestive properties and should be tailored to the patient's characteristics and clinical needs.

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INTRODUCTION: Acute decompensated heart failure (ADHF) admissions are frequently complicated by different patterns of serum creatinine (SCr) elevation. We aimed to assess the prognostic impact of worsening renal function (WRF) based on the timing of its occurrence. METHODS: This was a retrospective cohort of patients admitted for ADHF. Standard WRF was defined as an increase in SCr of ≥0.3 mg/dl during hospitalization. WRF timing was classified as early (within 48 hours of admission) or late (>48 hours). Acute kidney injury (AKI) at admission was defined as a rise in SCr of ≥0.3 mg/dl from outpatient baseline measurement to first measurement at admission. The primary endpoint was a composite of all-cause mortality or hospitalization for cardiovascular events at one-year follow-up. RESULTS: Overall, 249 patients were included (mean age 77±11 years, 62% with preserved left ventricular ejection fraction). Early WRF occurred in 49 patients (19.7%) and was associated with a higher risk of the primary outcome (HR 2.49; 95% CI 1.66-3.73), whereas late WRF was not (p=0.411). After stratification for the presence of early WRF and/or AKI at admission, only patients with early WRF but no AKI at admission and patients with both AKI at admission and early WRF showed a higher risk of the primary outcome after multivariate Cox regression. CONCLUSION: Early WRF was associated with a higher risk of the primary outcome. The timing of WRF seems to be an important factor to take into account when considering the prognostic impact of creatinine variations during hospitalization for ADHF.

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Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute heart failure are caused by congestive conditions, not all patients have a congestive phenotype, reflecting the complexity of a process with multiple pathophysiological pathways. The use of diuretics, usually loop diuretics, is the mainstay of treatment for congestion. However, many patients develop resistance, thus constituting a challenge with no consensual solution to date, despite extensive debate over the years. Despite its frequent use in clinical practice, the co-administration of albumin and furosemide remains controversial in the management of patients with acute heart failure, hypoalbuminemia, and diuretic resistance. This review addresses the pathophysiological mechanisms of congestion in patients with acute heart failure and explores the theoretical basis that supports the co-administration of albumin and furosemide in this clinical context. It is intended to clarify the potential benefit of the combined approach in this specific population and identify possible gaps in the literature that could be the subject of future studies.

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AIM: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF). METHODS AND RESULTS: The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1-Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80-1.09), > median 0.81 (0.73-0.90) (p-interaction = 0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and > median 0.88 (0.80-0.96) (p-interaction = 0.035). There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (p-interaction = 0.086). CONCLUSIONS: In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016-002299-28.

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AIMS: We tested the hypothesis that initiation versus non-initiation of sacubitril/valsartan is associated with a more favorable subsequent change in left ventricular ejection fraction (LVEF) in a real-world setting. METHODS: A prospective, non-randomized, double-arm, open-label, cohort study had been conducted across 687 centers in 17 European countries enrolling HFrEF patients aged ≥18 years with symptoms of HF (New York Heart Association [NYHA] II-IV) and "reduced LVEF". For the current analysis, 2602 patients with LVEF measured at baseline and follow-up were chosen, of which 860 (33%, mean age 67 years, 26% women) were started on sacubitril/valsartan at baseline and 1742 (67%, 68 years, 23% women) were not. Patients started on sacubitril/valsartan had higher NYHA class and lower LVEF. RESULTS: LVEF increased from mean 32.7% to 38.1% in the sacubitril/valsartan group versus from 35.9% to 38.7% in the non-sacubitril/valsartan group (mean difference in increase 2.6%, p < 0.001). LVEF increased from baseline in 64% versus 53% of patients and increased by ≥5% (absolute %) in 50% versus 35% of patients in the sacubitril/valsartan versus non-sacubitril/valsartan groups, respectively. In the overall cohort, initiation of sacubitril/valsartan was independently associated with any increase in LVEF (adjusted odds ratio [OR] 1.49 [1.26-1.75]) and with increase by ≥5% (OR 1.65 [1.39-1.95]). CONCLUSION: Initiating versus not initiating sacubitril/valsartan was independently associated with a greater subsequent increase in LVEF in this real-world setting. Reverse cardiac remodeling may be one mechanism of benefit of sacubitril/valsartan.

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AIMS: Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity. METHODS: TRANSITION, a randomized, open-label study compared sacubitril/valsartan initiation pre-discharge vs. post-discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10-week and 26-week post-randomization. RESULTS: Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril/valsartan target dose (97/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre-discharge or post-discharge respectively [diabetes subgroup: 47% (n = 105/226) vs. 50% (n = 115/228); relative risk ratio (RRR), 0.923; P = 0.412; non-diabetes subgroup: 45% (n = 119/267) vs. 51% (n = 133/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49/51 mg or 97/103 mg bid [diabetes subgroup: 61.1% (n = 138/226) vs. 67.5% (n = 154/228); RRR, 0.909; P = 0.175; non-diabetes subgroup: 62.9% [n = 168/267] vs 69.3% [n = 181/261]; RRR, 0.906; P = 0.118] or any dose for ≥2 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192/226) vs. 88.2% (n = 201/228); RRR, 0.966; P = 0.356; non-diabetes subgroup: 86.9% (n = 232/267) vs. 90.8% (n = 237/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre-discharge or post-discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non-diabetes subgroups at 10 weeks, respectively: pre-discharge (7.5% vs. 7.1%) or post-discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT-proBNP (P < 0.005) and hs-TnT (P < 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non-diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non-diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks. CONCLUSIONS: Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up-titration and tolerability as in those without diabetes.

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INTRODUCTION AND OBJECTIVES: Chronic heart failure (CHF) is a growing public health concern and diagnosis can be challenging, particularly in primary care. This study aims to estimate the budgetary impact of introducing N-terminal pro-B-type natriuretic peptide (NT-proBNP) for CHF diagnosis in a primary care setting from the perspective of the Portuguese health system. METHODS: A budget impact analysis was conducted over one-year from the patients' first presentation. The standard of care (SoC) was compared to NT-proBNP at the point-of-care (PoC) or laboratory (Lab). A decision tree model was used to estimate the downstream costs associated with each of the three pathways. RESULTS: An estimated 81 012 patients were expected to present to primary care with new onset CHF symptoms. The use of NT-proBNP as a primary diagnostic tool is estimated to generate annualized savings of EUR 935 657 and EUR 2 982 443 in the Lab and PoC setting, respectively. Estimated cost savings were due to the need for fewer medical visits, hospitalizations and echocardiograms (ECHO). The Lab and PoC settings led to similar reductions in hospitalizations (14.4%) and ECHO (27%), but the reduction in medical visits was higher in the PoC setting (38% compared to 2.5%), resulting in higher savings compared to Lab. CONCLUSIONS: Using NT-proBNP for CHF diagnosis in primary care could result in considerable costs savings for the public health system in Portugal. This evidence might support health policy makers to reconsider the resource management and define a new strategy to mitigate the impact of CHF.

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AIMS: ARIADNE aimed to assess the association between effects of sacubitril/valsartan and no sacubitril/valsartan treatment and clinical characteristics, functional capacity, and clinical outcomes (cause-specific mortality and hospitalizations) in outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS: ARIADNE was a prospective European registry of 9069 patients with HFrEF treated by office-based cardiologists or selected primary care physicians. Of the 8787 eligible for analysis, 4173 patients were on conventional HF treatment (non-S/V group), whereas 4614 patients were either on sacubitril/valsartan treatment at enrolment or started sacubitril/valsartan within 1 month of enrolment (S/V group). We also generated a restricted analysis set (rS/V) including only those 2108 patients who started sacubitril/valsartan treatment within the month prior to or after enrolment. RESULTS: At the baseline, average age of patients enrolled in the study was 68 years, and 23.9% (2099/8787) were female. At the baseline, the proportions of patients with New York Heart Association (NYHA) Class III symptoms were 30.9 (1288/4173), 42.8 (1974/4614), and 48.2% (1015/2108), in non-S/V, S/V, and rS/V groups, respectively. After 12 months of treatment, the proportion of patients with NYHA Class III at baseline who improved to Class II was 32.0% (290/907) in the non-S/V group vs. 46.3% (648/1399) in S/V group and 48.7% (349/717) in rS/V group. The overall mortality rate was 5.0 per 100 patient-years. Rates of HF hospitalizations were high (20.9, 20.3, and 21.2 per 100 patient-years in the non-S/V, S/V, and rS/V groups, respectively). Emergency room visits without hospitalization occurred in 3.9, 3.2, and 3.9% of patients in the non-S/V, S/V, and rS/V groups, respectively. CONCLUSIONS: This large HFrEF European registry provides a contemporary outcome profile of outpatients with HFrEF treated with or without sacubitril/valsartan. In a real-world setting, sacubitril/valsartan was associated with an improvement of symptoms in patients with HFrEF compared with the conventional HFrEF treatment.

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RESUMEN

The aging of the population has led to an increased prevalence of chronic diseases such as chronic kidney disease. Anemia is one of the most frequent complications of chronic kidney disease, with an impact not only on the quality of life but also on the patient's prognosis and associated costs. Knowledge in this therapeutic area has increased significantly: from the appearance of recombinant erythropoietin in 1989, through the use of increasing doses of parenteral iron and, more recently, to new molecules such as hypoxia-inducible factor inhibitors. The aim of this article is to present a pragmatic review of the state of the art in the epidemiology, pathophysiology, diagnosis and treatment of anemia associated with chronic kidney disease.

O envelhecimento populacional tem-se traduzido no aumento de prevalência de doenças crónicas como a doença renal crónica. A anemia é uma das complicações mais frequentes da doença renal crónica, com impacto não só na qualidade de vida como no prognóstico do doente e nos custos associados. O conhecimento nesta área terapêutica tem aumentado de forma significativa: desde o aparecimento da eritropoietina recombinante em 1989, passando pelo uso de doses crescentes de ferro parentérico e, mais recentemente, a novas moléculas como os inibidores do hypoxia-inducible factor. Os autores pretendem rever, de uma forma pragmática, o estado da arte da anemia associada à doença renal crónica, desde a epidemiologia, à fisiopatologia, ao diagnóstico e ao tratamento.

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