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Document Reviewers: Rudolf A. de Boer (CPG Review Co‐ordinator) (Netherlands), P. Christian Schulze (CPG Review Co‐ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands) All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelines See the European Heart Journal online for supplementary documents that include evidence tables. [ABSTRACT FROM AUTHOR]

Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post‐discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre‐discharge and titration to target doses in the early post‐discharge period, of guideline‐directed medical therapy may improve both short‐ and long‐term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre‐discharge and the early post‐discharge phase after a hospitalization for acute heart failure. [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) is associated with a poor prognosis regardless of left ventricular ejection fraction (LVEF). STRONG-HF showed the efficacy and safety of a strategy of rapid uptitration of oral treatment for heart failure (HF) and close follow-up (high-intensity care), compared with usual care, in patients recently hospitalized for AHF and enrolled independently from their LVEF. In this study, we sought to assess the impact of baseline LVEF on the effects of high-intensity care vs usual care in STRONG-HF. The STRONG-HF trial enrolled patients hospitalized for AHF with any LVEF and not treated with full doses of renin-angiotensin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. High-intensity care with uptitration of oral medications was performed independently from LVEF. The primary endpoint was the composite of HF rehospitalization or all-cause death at day 180. Among the 1,078 patients randomized, 731 (68%) had LVEF ≤40% and 347 (32%) had LVEF >40%. The treatment benefit of high-intensity care vs usual care on the primary endpoint was consistent across the whole LVEF spectrum (interaction P with LVEF as a continuous variable = 0.372). Mean difference in the EQ-5D visual analog scale change from baseline to day 90 between treatment arms was slightly greater at higher LVEF values, but with no interaction between LVEF as a continuous variable and the treatment strategy (interaction P = 0.358). Serious adverse events were also independent from LVEF. Rapid uptitration of oral medications for HF and close follow-up reduce 180-day death and HF rehospitalization after AHF hospitalization independently from LVEF. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-ProBNP Testing, of Heart Failure Therapies [STRONG-HF]; NCT03412201) [Display omitted] [ABSTRACT FROM AUTHOR]

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline‐recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: In AFFIRM‐AHF, intravenous ferric carboxymaltose (FCM) reduced heart failure (HF) hospitalisations and improved quality of life versus placebo in iron‐deficient patients stabilised after an acute HF episode. This analysis explored the effects of FCM versus placebo in patients with ischaemic and non‐ischaemic HF aetiology. Methods and results: We included 1082 patients from AFFIRM‐AHF: 590 with ischaemic HF (defined as investigator‐reported ischaemic HF aetiology and/or prior acute myocardial infarction and/or prior coronary revascularisation) and 492 with non‐ischaemic HF. The prevalences of male sex, comorbidities, and history of HF were higher in the ischaemic versus non‐ischaemic HF subgroup. Annualised event rates for the primary composite outcome of total HF hospitalisations and cardiovascular death with FCM versus placebo were 65.3 versus 100.6 per 100 patient‐years in the ischaemic HF subgroup (rate ratio [RR] 0.65, 95% confidence interval [CI] 0.47–0.89, p = 0.007) and 58.3 versus 52.5 in the non‐ischaemic HF subgroup (RR 1.11, 95% CI 0.75–1.66, p = 0.60) (pinteraction = 0.039). An interaction between HF aetiology and treatment effect was also observed for the secondary outcome of total HF hospitalisations (pinteraction = 0.038). A nominal increase in quality of life, assessed using the 12‐item Kansas City Cardiomyopathy Questionnaire, was observed with FCM versus placebo, within each subgroup. Conclusions: Heart failure hospitalisations and cardiovascular deaths occurred at a higher rate in patients with ishaemic versus those with non‐ischaemic HF and were reduced by FCM versus placebo only in ischaemic patients. Further studies are needed to assess the role of aetiology in FCM efficacy. [ABSTRACT FROM AUTHOR]

Aims: We examined the effects of istaroxime in patients hospitalized for acute heart failure (AHF) related Society for Cardiovascular Angiography and Interventions (SCAI) stage B pre‐cardiogenic shock (CS). Methods and results: Sixty patients with AHF without acute myocardial infarction with pre‐CS, defined as systolic blood pressure (SBP) <90 mmHg without hypoperfusion, venous lactate ≥2 mmol/L and/or mechanical or inotropic support, were randomized to istaroxime 1.0–1.5 μg/kg/min or placebo for 24 h. The primary endpoint, the adjusted area under the curve (AUC) change in SBP from time of treatment to 6 h, was 53.1 (standard error [SE] 6.88) mmHg × hour versus 30.9 (SE 6.76) mmHg × hour with istaroxime versus placebo (p = 0.017). Adjusted SBP AUC at 24 h was 291.2 (SE 27.5) versus 208.7 (SE 27.0) mmHg × hour (p = 0.025). At 24 h, some echocardiographic measurements improved with istaroxime versus placebo including cardiac index (+0.21 L/min/m2; p = 0.016), left atrial area (−1.8 cm2; p = 0.008), and left ventricular end‐systolic volume (−12.0 ml; p = 0.034). There were no significant differences in pulse pressure, laboratory measurements, serious adverse events or adverse events between the treatment groups except for more nausea, vomiting and infusion site pain in the istaroxime‐treated patients. In a post‐hoc analysis, patients receiving ≤1.0 μg/kg/min versus 1.5 μg/kg/min had similar increase in blood pressure, but a trend towards less adverse events. Conclusion: In a phase 2a study of patients with AHF related pre‐CS, istaroxime improved blood pressure and some echocardiography measures related to heart failure and was well tolerated. [ABSTRACT FROM AUTHOR]

Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online. [ABSTRACT FROM AUTHOR]

GLO:P3O/01nov21:ejhf2320-fig-0001.jpg PHOTO (COLOR): 1 Network of regionalized cardiogenic shock (CS) care system and characteristics of the hub CS centre. B This article refers to 'Impact of hospital transfer to hubs on outcomes of cardiogenic shock in the real world' by D.Y. Lu I et al i ., published in this issue on pages 1927-1937. b Cardiogenic shock (CS) is a complex multifactorial clinical syndrome, developing as a continuum, and progressing from the initial insult to the subsequent occurrence of organ failure and death.1 Despite advanced management, including aetiological treatment and mechanical circulatory support (MCS), CS represents the most severe manifestation of acute heart failure2 with in-hospital mortality varying between 30-50%, depending on the underlying aetiology.1,3-5 CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested. Recently, new approaches to care of CS patients have focused on mechanisms beyond medical therapies I per se i , implying that CS management should consider appropriate organization of the health care services in order to facilitate optimal care coordination and to minimize time delay.6 There is growing interest for developing CS centres and CS teams using a standardized multidisciplinary team-based approach in the management of CS. [Extracted from the article]

Aims: We assessed eligibility for omecamtiv mecarbil (OM) in a real-world cohort with heart failure with reduced ejection fraction (HFrEF) according to the selection criteria of the GALACTIC-HF trial (trial scenario) and selected trial´s criteria more likely to impact real-world use (pragmatic scenario). Methods and results: We included 31,015 patients with HFrEF lasting ≥3 months and registered in the Swedish HF registry between 2000–2021. Trial eligibility was calculated by applying all the GALACTIC-HF selection criteria. The pragmatic scenario considered only the New York Heart Association class, history of worsening HF, N-terminal pro-B-type natriuretic peptides (NT-proBNP), blood pressure and renal failure criteria defined as in the trial. Eligibility for OM in chronic HFrEF was 21% and 36% in the trial and pragmatic scenarios, respectively. Eligibility was higher in those with EF<30% (trial: 27%, pragmatic: 44%), in-patients (trial:30%, pragmatic:57%), severe HF (trial: 35%, pragmatic: 60%), NYHA class III-IV (trial: 26%, pragmatic: 45%), and NT-proBNP≥5,000pg/mL (trial: 30%, pragmatic: 51%). The criteria that most limited eligibility were history of a recent worsening HF event (60% eligible in chronic HFrEF), elevated NT-proBNP (82% eligible), and deviating blood pressure (82% eligible). Overall, eligible patients were characterized by more severe HF and higher CV event-rates in both scenarios, and higher comorbidity burden in the pragmatic scenario. Conclusion: Approximately 21% of real-world chronic HFrEF patients would be eligible for OM according to the GALACTIC-HF selection criteria, and 36% according to the criteria more likely to affect OM use in clinical practice. Criteria in both scenarios identified a patient-group with severe HF and high CV event-rates. [ABSTRACT FROM AUTHOR]

Numerous guideline documents have issued recommendations to clinicians concerning the treatment of chronic heart failure and a reduced ejection fraction. However, guidelines do not describe what constitutes an acceptable standard of care, and thus, practitioners who adhere to only a small fraction of the recommendations might claim that they are treating patients 'in accordance with the guidelines'. As a result, <1% of patients with heart failure are receiving all life-prolonging treatments at trial-proven doses. A major impediment to the widespread adoption of trial-based treatments is a lack of any existing framework that would allow physicians to describe the adequacy of care. To address this deficiency, we propose a novel simple approach that would ask practitioners if a patient had been treated using the dosing algorithm that had been shown to be effective for each drug class. The proposed framework recognizes that all landmark survival trials in heart failure were 'strategy trials', i.e. the studies mandated a standardized forced-titration treatment plan that required timely uptitration to specified target dose unless patients experienced clinically meaningful, intolerable or serious adverse events, which persisted or recurred despite adjustment of other medications. Adherence to trial-proven regimens might be improved if physicians were asked to describe the degree to which a patient's treatment adhered to or deviated from the strategies that had been used to demonstrate the survival benefits of neurohormonal antagonists. The proposed framework should also promote practitioner self-awareness about the lack of evidence supporting the current widespread use of subtarget doses that are non-adherent with trial-proven forced-titration strategies. [ABSTRACT FROM AUTHOR]

An editorial is presented that 5-year follow-up of the COAPT trial, which demonstrated that transcatheter repair of the mitral valve in patients with heart failure and secondary mitral regurgitation led to significant reductions in hospitalization rates and mortality. Topics include the importance of functional mitral regurgitation in heart failure progression, the need for guideline-recommended therapies and the potential benefits of transcatheter intervention in reducing mitral regurgitation.

Background: The 6-minute walk test (6MWT) is a simple and inexpensive way of measuring exercise capacity in patients with heart failure (HF) that predicts morbidity and mortality. However, there are few reports from large multicentre cohorts assessing the predictive value of baseline and changing walk distance.Methods and Results: In BIOSTAT-CHF, a 6MWT was performed at baseline (n = 1714) and 9 months (n = 1520). Cox proportional hazards models were used to assess the associations between 6MWT distance and the composite of HF hospitalization and/or death. Median follow-up was 21 months. The median (pct25-75 ) of the 6MWT distance at baseline was 300 m (200-388 m). Independent predictors of a shorter 6MWT distance included older age, female sex, higher heart rate, New York Heart Association class III/IV, orthopnoea, ischaemic heart disease, a previous stroke, current malignancy, and higher N-terminal pro-B-type natriuretic peptide (all P < 0.05). Patients in the lowest baseline 6MWT tertile (≤ 240 m) were less likely to receive guideline-recommended doses of disease-modifying therapies (P < 0.05). Compared to patients in the highest baseline 6MWT tertile (> 360 m), those in the lowest and middle tertiles had a worse prognosis [adjusted hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.38-2.18]. Patients with a decrease in the distance walked had a worse prognosis (adjusted HR for each 50 m decrease 1.09, 95% CI 1.06-1.12). 6MWT distance was not modified by treatment up-titration nor the 6MWT improved the BIOSTAT-CHF prognostic models.Conclusions: The 6-minute walk test distance at baseline and a decline in walking distance were both associated with worse prognosis but did not improve the prognostic models. 6MWT distance was not modified by treatment up-titration and its use for assessing the benefits of pharmacologic treatment up-titration may be limited. [ABSTRACT FROM AUTHOR]

Introduction: Patients with symptomatic heart failure (HF) require additive therapies and have a poor prognosis. However, patient characteristics and clinical outcome between HF patients treated in the outpatient setting vs. those who are hospitalized remain scarce.Methods and Results: The BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) included 2516 patients with symptoms and/or signs of HF: 1694 as inpatients and 822 as outpatients. Compared to ambulatory HF patients, inpatients had higher heart rate, urea, N-terminal pro-brain natriuretic peptide, lower blood pressure, lower estimated glomerular filtration rate, sodium, potassium, high-density lipoprotein cholesterol, had more often peripheral oedema, diabetes, anaemia, and were less often treated with beta-blockers and angiotensin-converting enzyme inhibitors (ACEi). Outpatients had a more frequent history of HF hospitalization and received more frequently beta-blockers and/or ACEi/angiotensin receptor blockers up-titrated to target doses (P < 0.001). Inpatients had higher rates of the primary outcome of death or HF hospitalization: incidence rate per 100 person-years of 33.4 [95% confidence interval (CI) 31.1-35.9] for inpatients vs. 18.5 (95% CI 16.4-21.0) for outpatients; adjusted hazard ratio 1.24 (95% CI 1.07-1.43). Subdividing patients into low, intermediate and high-risk categories, the primary outcome event rates were 14.3 (95% CI 12.3-16.7), 36.6 (95% CI 32.2-41.5), and 71.3 (95% CI 64.4-79.0) for inpatients vs. 8.4 (95% CI 6.6-10.6), 29.8 (95% CI 24.5-36.2), and 43.3 (95% CI 34.7-54.0) for outpatients, respectively. These findings were externally replicated.Conclusions: Marked differences were observed between inpatients and outpatients with HF. Overall, inpatients were sicker and had higher event rates. However, a substantial proportion of outpatients had similar or higher event rates compared to inpatients. These findings suggest that HF outpatients also have poor prognosis and may be the focus of future trials. [ABSTRACT FROM AUTHOR]

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population. [ABSTRACT FROM AUTHOR]

The November 2023 issue of the European Journal of Heart Failure covers various topics related to heart failure. The use of biomarkers, specifically natriuretic peptides, in the diagnosis and management of heart failure is discussed. Advances in the treatment of different types of cardiomyopathies are summarized. The association between neutrophil-related proteins and adverse cardiac remodeling is explored. The article also examines the role of obesity in heart failure and the impact of degenerative aortic valve stenosis on heart failure with preserved ejection fraction. Prognostic variables, such as the LIFE-HF model and the presence of multiple comorbidities, are discussed. The article also delves into the management of acute heart failure and post-discharge care. The use of intermittent inotropic therapy and the treatment of cardiogenic shock are explored. Additionally, the article covers the phenotypes and clinical outcomes of patients with non-ischemic cardiomyopathy and the prevalence of transthyretin amyloid cardiomyopathy. The importance of screening for and treating iron deficiency and the impact of chronic obstructive pulmonary disease on heart failure are also discussed. [Extracted from the article]

Background Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response. Methods and results A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included. Annualized enrollment rate was calculated as the total number of patients enrolled at each site divided by time that the site was open (patients per year). Sites were classified in low (< 10), medium (10–20) and high enrolling sites (> 20 patients per site/year) and were compared for prognosis and serelaxin effect. High enrolling sites were more prevalent in Eastern Europe and Israel. Time from hospital admission to randomization was shorter in high enrolling sites (6.3 ± 4.4 h > 20 patients sites versus 8.7 ± 4.5 h for < 10 patients sites; p < 0.0001). Patients had slightly fewer comorbidities, lower levels of natriuretic peptides and creatinine and more severe pulmonary congestion in high enrolling sites. Use of evidence-based therapies was higher in high enrolling sites. The rates of worsening heart failure to day 5, 180-day cardiovascular and all-cause mortality and 60-day heart failure/renal failure rehospitalization or cardiovascular death, were similar across study groups even after adjustment for covariates. The effects of serelaxin on these outcomes did not differ by enrollment rate. Conclusions Characteristics of RELAX-AHF study patients enrolled in high versus low enrolling sites differed only slightly and there were no differences in outcomes. Differences in serelaxin effects by enrollment rate were not discernible. [ABSTRACT FROM AUTHOR]

Aims: Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes.Methods and Results: We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00-1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180-day all-cause mortality was 1.01 (95% CI 1.00-1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h.Conclusions: In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients. [ABSTRACT FROM AUTHOR]

Aims Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00-1.02; P =0.021]. Similarly, the HR for each 1mmHg decrease in SBP at 24h for 180-day all-cause mortality was 1.01 (95% CI 1.00-1.03; P =0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h. Conclusions In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients. [ABSTRACT FROM AUTHOR]

Aims: Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous cardiopoietic mesenchymal stem cells (C3BS-CQR-1) on LV remodelling in patients with advanced HF enrolled in the CHART-1 study.Methods and Results: Patients (n=351) with symptomatic advanced HF secondary to ischaemic heart disease, and reduced LV ejection fraction (LVEF <35%) were randomized to receive C3BS-CQR-1 or a sham procedure. In a post hoc analysis we examined the effect of C3BS-CQR-1 on LV reverse remodelling within 1 year of the procedure and the influence of C3BS-CQR-1 dosing in the 271 patients treated as randomized. Delivery of C3BS-CQR-1 was associated with a progressive decrease in both LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) within 52 weeks after treatment. At 1 year, the LVEDV and LVESV of treated patients decreased by 17.0 mL and 12.8 mL greater than controls (P=0.006 and P=0.017, respectively). The effect on LVEDV was maintained after multivariable adjustment for baseline age, systolic blood pressure, LVEDV, LVEF and history of myocardial infarction. The largest reverse remodelling was evident in the patients receiving a moderate number of injections (<20).Conclusion: In CHART-1, intramyocardial administration of cardiopoietic stem cells led to reverse remodelling as evidenced by significant progressive decreases in LVEDV and LVESV through the 52 weeks of follow-up. Further studies are needed to explore the dose response with regard to cell number and injected volume, and reverse remodelling. [ABSTRACT FROM AUTHOR]

Aims Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous cardiopoietic mesenchymal stem cells (C3BS-CQR-1) on LV remodelling in patients with advanced HF enrolled in the CHART-1 study. Methods and results Patients (n=351) with symptomatic advanced HF secondary to ischaemic heart disease, and reduced LV ejection fraction (LVEF <35%) were randomized to receive C3BS-CQR-1 or a sham procedure. In a post hoc analysis we examined the effect of C3BS-CQR-1 on LV reverse remodelling within 1 year of the procedure and the influence of C3BS-CQR-1 dosing in the 271 patients treated as randomized. Delivery of C3BS-CQR-1 was associated with a progressive decrease in both LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) within 52 weeks after treatment. At 1 year, the LVEDV and LVESV of treated patients decreased by 17.0 mL and 12.8 mL greater than controls (P=0.006 and P=0.017, respectively). The effect on LVEDV was maintained after multivariable adjustment for baseline age, systolic blood pressure, LVEDV, LVEF and history of myocardial infarction. The largest reverse remodelling was evident in the patients receiving a moderate number of injections (<20). Conclusion In CHART-1, intramyocardial administration of cardiopoietic stem cells led to reverse remodelling as evidenced by significant progressive decreases in LVEDV and LVESV through the 52 weeks of follow-up. Further studies are needed to explore the dose response with regard to cell number and injected volume, and reverse remodelling. [ABSTRACT FROM AUTHOR]

Adapted from reference[26] gl Of 8298 acute HF patients enrolled in the ESC HF Long-Term Registry, 20% presented hyponatraemia (serum sodium <135 mmol/L) at admission. The benefits of dapagliflozin remained consistent, regardless of background therapy, in 1151 patients with HF and improved ejection fraction from the DELIVER trial with a possible greater reduction in HF events in patients on 0-1 HF medications. Advanced heart failure (HF) is burdened by an extremely poor prognosis.[[1]] Culture, ethnicity, and socio-economic differences should be considered by the health care professionals in the management of patients with advanced HF needing palliative care. 2022; 24: 1493 - 1503. https://doi.org/10.1002/ejhf.2561 2 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). [Extracted from the article]

Patient profiles in heart failure with reduced ejection fraction: Prevalence, characteristics, treatments and outcomes in a real-world heart failure population. Electronic nudges to increase influenza vaccination uptake among patients with heart failure: A pre-specified analysis of the NUDGE-FLU trial. An early diagnosis, and hence treatment, of heart failure (HF) may have a major impact on health care resources and patients' longevity and quality of life.[1] The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) provided a clinical consensus statement addressed to general practitioners and to non-cardiology physicians to facilitate the early diagnosis of HF with a major role to screening strategies, including the measurement of brain natriuretic peptides (BNP).[2] Epidemiology Myocardial infarction is one of the most common causes of HF.[[3], [5]] Docherty I et al i .[7] examined changes in the risk of HF hospitalizations (HFH) following a first acute myocardial infarction (AMI) in Scotland in the years 1991 to 2016. Such patients were younger, had a lower left ventricular ejection fraction (LVEF) and were less likely to have an ischaemic aetiology.[12] Iron deficiency (ID) is common in HF patients and should be treated with intravenous iron.[[3], [13]] An analysis from SwedeHF reported an improvement in iron screening since 2016, even if it remained <25% as in 2018. [Extracted from the article]

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome.[[1], [3]] A scientific statement from the Heart Failure Association (HFA) described most common HFpEF phenotypes, related comorbidities and treatment options for each phenotype.[4] Exercise testing has a key role in the diagnosis and prognostic assessment of HFpEF.[[1], [5]] In a study by Alogna I et al i .,[7] 398 patients with HFpEF undergoing comprehensive echocardiography and invasive cardiopulmonary exercise testing were categorized low versus preserved biventricular cardiac power output (BCPO) reserve (< vs >= median of 1.57 W). A secondary analysis of the BLUSHED-AHF trial, designed to investigate the effect of LUS-guided therapy in patients with acute HF, tested the use of artificial intelligence/machine learning (AI/ML)-based automated guidance systems in order to detect lung congestion. Prevalence, clinical characteristics and outcomes of heart failure patients with or without isolated or combined mitral and tricuspid regurgitation: An analysis from the ESC-HFA Heart Failure Long-Term Registry. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure in elderly patients: A sub-analysis of the STRONG-HF randomized clinical trial. [Extracted from the article]

Heart failure has reached epidemic proportions given the ageing of populations and is associated with high mortality and re-hospitalization rates. This article reviews and summarizes recent advances in the diagnosis, assessment and treatment of the patients with heart failure. Data are discussed based also on the most recent guidelines indications. Open issues and unmet needs are highlighted. [ABSTRACT FROM AUTHOR]

Aims: The course of patients following admission for acute heart failure (AHF) is of major importance to patients and healthcare providers. We examined predictors and associations of length of stay (LOS), 30-day post-discharge readmission and 90-day post-discharge mortality in 1990 patients enrolled in the PROTECT study.Methods and Results: PROTECT was a randomized study that examined the effect of the adenosine blocker rolofylline in patients within 24 h of admission for AHF with mild to moderate renal impairment. Geographic-region-adjusted multivariable models showed that LOS was only partly explained by the severity of heart failure (HF), comorbidities (diabetes mellitus, renal impairment, ischaemic heart disease) and degree of metabolic dysfunction (cholesterol and albumin) at baseline (adjusted R(2) 0.27). Addition of in-hospital worsening heart failure (WHF) and changes in metabolic markers contributed significantly to prediction of LOS [R(2) difference 0.050, 95% confidence interval (CI) 0.0282-0.072]. Thirty-day HF readmission was associated with more severe HF and previous HF admission but not with LOS (odds ratios 1.00, 95% CI 0.97-1.04). Death within 90 days after discharge was associated with older age, more severe HF, worse renal function, and lower sodium and bicarbonate at admission; LOS was a strong predictor of 90-day post-discharge mortality.Conclusions: In patients admitted for AHF, LOS is not well-predicted by traditional markers of disease severity, but strongly associated with the occurrence of in-hospital WHF. Longer LOS is a strong predictor of early mortality after discharge but not of readmission. These findings may help focus efforts to reduce LOS and post-discharge outcomes on patients' subgroups at increased risk. [ABSTRACT FROM AUTHOR]

18 Reichart D, Kalbacher D, Rübsamen N, Tigges E, Thomas C, Schirmer J, Reichenspurner H, Blankenberg S, Conradi L, Schäfer U, Lubos E. The impact of residual mitral regurgitation after MitraClip therapy in functional mitral regurgitation. B This article refers to 'Treating symptoms and reversing remodelling: clinical and echocardiographic 1-year outcomes with percutaneous mitral annuloplasty for mild to moderate secondary mitral regurgitation' by K.K. Witte I et al i ., published in this issue on pages 1971-1978. b The prognostic value of secondary mitral regurgitation (SMR) in patients with heart failure (HF) is well known.1-3 It increases with increasing SMR severity and long-term survival can be extremely low (<60% at 8 years) even in patients with moderate SMR.2 The prevalence of moderate SMR in patients with HF with reduced ejection fraction (HFrEF) is relevant (43% in a recent series by Bartko I et al i .). [Extracted from the article]

The December 2023 issue of the European Journal of Heart Failure covers a range of topics related to medical therapy in chronic and acute heart failure. Some of the key findings include the benefits of qiliqiangxin, a plant-based formulation, in reducing the risk of cardiovascular death or hospitalization in heart failure patients. The use of mineralocorticoid receptor antagonists (MRAs) in patients with kidney dysfunction was found to be safe and not associated with a higher risk of renal events. The impact of COVID-19 on heart failure patients and the effects of exercise training in heart failure were also discussed. Additionally, the issue includes studies on the percutaneous treatment of tricuspid regurgitation, the association between socio-economic status and prognosis, and the use of machine-learning procedures to predict prognosis. [Extracted from the article]

Prevention of heart failure (HF) has a key role in our health care.[[1]] Multivariable prediction models are frequently used to estimate the risk of incident HF. Comorbidities Cancer is a common comorbidity in HF patients.[[2], [32]] A total of 193 359 Danish patients with new-onset HF from 2000 to 2018 were stratified into three groups according to comorbid breast, gastrointestinal and lung cancer: no cancer, history of cancer and active cancer. Effect of patient-centered transitional care services on patient-reported outcomes in heart failure: Sex-specific analysis of the PACT-HF randomized controlled trial. Palliative care in heart failure guidelines: A comparison of the 2021 ESC and the 2022 AHA/ACC/HFSA guidelines on heart failure. [Extracted from the article]

Background Worsening heart failure (WHF) symptoms despite initial therapy during admission for acute heart failure (AHF) is associated with worse outcomes. The association between the time of the WHF event and the intensity of WHF therapy with outcomes is unknown. Methods and results In the PROTECT trial of 2033 AHF patients, we investigated the association between time of occurrence of WHF and intensity of therapy, with subsequent outcomes. WHF was defined by standardized, physician-determined assessment. Early WHF was defined as occurring on days 2-3 and late on days 4-7. Low intensity included restarting/increasing diuretics or vasodilators and high intensity included initiation of inotropes, vasopressors, inodilators, or mechanical support. Outcomes were death or cardiovascular/renal hospitalization over 60 days and death over 180 days. Of the 1879 patients with complete follow-up after day 7, 12.7% (n=238) experienced WHF: 47.9% early and 52.1% late. Treatment intensity was low in 72.3% and high in 24.8% (2.9% missing). After adjusting for baseline predictors of outcome, WHF was associated with a trend toward increased 60-day death or cardiovascular/renal hospitalization [hazard ratio (HR) 1.26; 95% confidence interval (CI) 0.99-1.60; P =0.063] and increased 180-day death (HR 1.77; 95% CI 1.33-2.34; P <0.001). There was no evidence of a differential association between the time of occurrence of WHF and outcomes. High-intensity therapy was not significantly associated with increased event rates (180-day mortality: HR 1.44; 95% CI 0.80-2.59 vs. low). Conclusions Inhospital WHF was associated with increased 180-day death. The time of occurrence and intensity of WHF therapy may provide less prognostic information than whether or not WHF occurred. [ABSTRACT FROM AUTHOR]

Aims: Previous heart failure (HF) trials suggested that age influences patient characteristics and outcome; however, under-representation of elderly patients has limited characterization of this cohort. Whether standard prognostic variables have differential utility in various age groups is unclear.Methods and Results: The PROTECT trial investigated 2033 patients (median age 72 years) with acute HF randomized to rolofylline or placebo. Patients were divided into five groups based on the quintiles of age: ≤59, 60-68, 69-74, 75-79, and ≥80 years. Baseline characteristics, medications, and outcomes (30-day death or cardiovascular/renal hospitalization, and death at 30 and 180 days) were explored. The prognostic utility of baseline characteristics for outcomes was investigated in the different groups and in those aged <80 years vs. ≥80 years. With increasing age, patients were more likely to be women with hypertension, AF, and higher EF. Increased age was associated with increased risk of 30- and 180-day outcomes, which persisted after multivariable adjustment (hazard ratio for 180-day death = 1.17; 95% confidence interval 1.11-1.24 for each 5-year increase). The prognostic utility of baseline characteristics such as previous HF hospitalization and serum sodium, systolic blood pressure, and NYHA class was attenuated in the elderly for the endpoint of 180-day mortality. An increase in albumin was associated with a greater reduction in risk in patients aged ≥80 years vs. <80 years.Conclusions: In a large trial of acute HF, there were differences in baseline characteristics and outcomes amongst patients of different ages. Standard prognostic variables exhibit different utility in elderly patients. [ABSTRACT FROM AUTHOR]

Aims Worsening heart failure ( WHF) in the first 7 days after an admission for acute HF ( AHF) has been proposed as a therapeutic target in several recent AHF studies and was a co-primary endpoint of the VERITAS studies. Methods and results Patients were randomized within 24 h of admission for AHF. WHF was defined as worsening or persistent signs and symptoms of HF requiring additional intravenous or mechanical therapy for HF or death within 7 days of randomization. Multivariable models were developed to predict the time to WHF through day 7. Unadjusted and multivariable-adjusted associations of WHF with the length of stay ( LOS) of the index hospitalization, and 30- and 90-day outcomes were estimated. WHF occurred by day 7 in 27% of the 1347 patients enrolled. Age, co-morbidities, and markers of HF severity were moderately predictive of WHF; the C-index for a multivariable model for WHF was 0.66. After multivariable adjustment for baseline characteristics, WHF was associated with an increase in LOS of 4.33 days [95% confidence interval ( CI) 3.54-5.13 days], a hazard ratio ( HR) for 30-day HF readmission or death of 2.43 (95% CI 1.75-3.40), and a HR for 90-day mortality of 2.57 (95% CI 1.81-3.65), all with P < 0.0001.The associations of WHF with these outcomes remained largely unchanged after adjustment for both baseline characteristics and changes in markers of renal and hepatic dysfunction during the first day of admission. Conclusions In patients admitted for AHF, WHF is a significant clinical event that is associated with delays in discharge and higher rates for readmission and death. [ABSTRACT FROM AUTHOR]

Half of these patients had a diagnosis of acute HF and presented higher levels of interleukin-6 compared to patients with other causes of dyspnoea. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Baroreflex activation therapy with the Barostim device in patients with heart failure with reduced ejection fraction: a patient level meta-analysis of randomized controlled trials. Sympathetic activity Autonomic nervous system is a main target on novel interventions.[[1], [3]] Badrov I et al i .[5] investigated determinants of augmented muscle sympathetic nerve activity (MSNA) in 177 heart failure (HF) patients and 658 healthy volunteers. [Extracted from the article]

Objectives: The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure. Background: Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage. Methods: The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies. Results: Serelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro–brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion. Conclusions: Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission. [ABSTRACT FROM AUTHOR]

Aims We hypothesized that nebivolol, a beta-blocker with nitric oxide-releasing properties, could favourably affect exercise capacity in patients with heart failure and preserved left ventricular ejection fraction (HFPEF). Methods and results A total of 116 subjects with HFPEF, in New York Heart Association (NYHA) functional class II–III, with left ventricular ejection fraction (LVEF) >45%, and with echo-Doppler signs of LV diastolic dysfunction, were randomized to 6 months treatment with nebivolol or placebo, following a double-blind, parallel group design. The primary endpoint of the study was the change in 6 min walk test distance (6MWTD) after 6 months. Nebivolol did not improve 6MWTD (from 420 ±143 to 428 ±141 m with nebivolol vs. from 412 ±123 to 446 ±119 m with placebo, P = 0.004 for interaction) compared with placebo, and the peak oxygen uptake also remained unchanged (peakVO2; from 17.02 ±4.79 to 16.32 ±3.76 mL/kg/min with nebivolol vs. from 17.79 ±5.96 to 18.59 ±5.64 mL/kg/min with placebo, P = 0.63 for interaction). Resting and peak blood pressure and heart rate decreased with nebivolol. A significant correlation was found between the change in peak exercise heart rate and that in peakVO2 (r = 0.391; P = 0.003) for the nebivolol group. Quality of life, assessed using the Minnesota Living with Heart Failure™ Questionnaire, and NYHA classification improved to a similar extent in both groups, whereas N-terminal pro brain natriuretic peptide (NT-pro BNP) plasma levels remained unchanged. Conclusions Compared with placebo, 6 months treatment with nebivolol did not improve exercise capacity in patients with HFPEF. Its negative chronotropic effect may have contributed to this result. [ABSTRACT FROM AUTHOR]

Abnormalities of cardiac function, with high intraventricular filling pressure and low cardiac output, play a central role in patients with heart failure. Agents with inotropic properties are potentially useful to correct these abnormalities. However, with the exception of digoxin, no inotropic agent has been associated with favourable effects on outcomes. This is likely related to the mechanism of action of current agents, which is based on an increase in intracellular cyclic adenosine monophosphate and calcium concentrations. Novel agents acting through different mechanisms, such as sarcoplasmic reticulum calcium uptake, cardiac myosin and myocardial metabolism, have the potential to improve myocardial efficiency and lower myocardial oxygen consumption. These characteristics might allow a haemodynamic improvement in the absence of untoward effects on the clinical course and prognosis of the patients. [ABSTRACT FROM AUTHOR]

Abstract: Acute heart failure (HF) is the most common diagnosis at discharge in patients aged >65years. It carries a dismal prognosis with a high in-hospital mortality and very high post-discharge mortality and re-hospitalization rates. It is a complex clinical syndrome that cannot be described as a single entity as it varies widely with respect to underlying pathophysiologic mechanisms, clinical presentations and, likely, treatments. It is the aim of this paper to describe some of the main clinical presentations of acute HF. Amongst them, we will consider de novo HF versus acutely decompensated chronic HF, HF caused, and/or worsened, by myocardial ischemia, acute HF with low, normal, or high systolic blood pressure, acute HF caused by lung congestion or fluid retention or fluid redistribution to the lungs, and acute HF with comorbidities (diabetes, anemia, renal insufficiency, etc.). Different pathophysiologic mechanisms and clinical presentations may coexist in the same patient. Identification and, whenever possible, treatment of underlying pathophysiologic mechanisms may become important for acute HF management. [ABSTRACT FROM AUTHOR]

Aims Although dyspnoea is the most common cause of admission for acute heart failure (AHF), more needs to be known about its clinical course and prognostic significance. Methods and results The Pre-RELAX-AHF study randomized 232 subjects with AHF to placebo or four doses of relaxin and evaluated early (6–24 h Likert scale) and persistent [change in visual analogue scale area under the curve (VAS AUC) through Day 5] dyspnoea relief. Worsening heart failure (WHF) was defined as worsening AHF signs and symptoms requiring additional therapy. Patients were followed until Day 180. Early dyspnoea relief was observed in only 25% of all patients, and VAS AUC at 5 days was 45% over baseline values in all patients (32% placebo; 50% all relaxin-treated patients). Worsening heart failure to Day 5 was observed in 16% of all patients (21% placebo; 14% relaxin). Lack of persistent dyspnoea relief and WHF were associated with a longer length of initial hospital stay and worse 60-day outcomes. Conclusion Dyspnoea relief in patients admitted with AHF is often incomplete, and many may show WHF after the initial stabilization. Both lack of persistent dyspnoea relief and in-hospital WHF predict a longer length of stay and worse outcome. [ABSTRACT FROM AUTHOR]

Aims Dyspnoea is the most common symptom leading to hospitalization for acute heart failure (AHF). Its early and persistent relief is an important goal of therapy, but little is known about its course, determinants, and prognostic significance. Methods and results In a post hoc analysis, we studied changes in dyspnoea and in-hospital course in 303 subjects with AHF enrolled in the PROTECT pilot trial. Changes in dyspnoea were assessed by patient self-report using a seven-point Likert scale daily to discharge and at Days 7 and 14. We defined dyspnoea relief as a moderate to marked improvement of dyspnoea at both 24 and 48 h, and treatment success as dyspnoea relief without worsening HF or renal function or death during the first 7 days. Dyspnoea relief occurred in 54% of the patients, while treatment success was achieved in 44% of the patients. By Day 14, only 75% of patients reported a moderate or marked improvement in dyspnoea. Both dyspnoea relief and treatment success were associated with greater improvement in signs of congestion, shorter hospitalization duration, and a lower 60-day mortality rate. Treatment success, but not dyspnoea relief, was also associated with a lower incidence of 60-day death or re-hospitalization for HF or renal failure. Conclusion Half of patients admitted for AHF do not have substantial improvement in dyspnoea at 24 h and 25% do not have substantial improvement at 7 and 14 days from admission. Dyspnoea relief and treatment success are associated with shorter length of stay and lower 60-day mortality. These analyses should be confirmed in larger studies. [ABSTRACT FROM PUBLISHER]

Nebivolol is a third-generation β-adrenergic receptor antagonist (β-blocker) with high selectivity for b1-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional β-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available β-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with β-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional β-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardio protective activity and a good tolerability profile. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate physician-determined worsening heart failure (PD-WHF) in patients admitted with acute heart failure (AHF). Methods: The PROTECT pilot study evaluated rolofylline, an adenosine A1 receptor antagonist, versus placebo in patients with AHF and renal impairment. Signs and symptoms of heart failure (HF) and diuretic administration were prospectively recorded daily for 7 days and patients were followed for 60 days. Patients were categorized into three groups: (A) PD-WHF, based on worsening symptoms and signs of HF and need for additional intravenous (IV) or mechanical therapy (n = 29); (B) increased IV diuretic therapy without PD-WHF (n = 61), and (C) neither PD-WHF nor increase in IV diuretic dose (n = 211). Results: Patients in group A had slower resolution of dyspnea, longer mean (±SD) length of hospitalization (13.8 ± 6.8 vs. 10.5 ± 8.5 and 9.3 ± 5.9 days in groups B and C, respectively; p < 0.05 for both), and higher 60-day death and cardiovascular or renal readmission rates [49.7 (95% confidence interval: 33.1–69.1) vs. 37.3 (26.4–50.9) vs. 19.5% (14.7–25.6) in groups B and C, respectively]. PD-WHF was a strong independent predictor of length of stay and 60-day death and cardiovascular or renal readmission. Conclusions: PD-WHF may be an indicator of short-term risk and treatment efficacy in AHF. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to assess the dose response of the drug relaxin's effect on symptom relief, other clinical outcomes, and safety. Researchers used a placebo-controlled, parallel-group, dose-ranging study to evaluate 234 patients with acute heart failure, dyspnea, or congestive heart disease. They found that the number of serious adverse events was similar between groups and that when given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favorable relief of dyspnoea and other clinical outcomes, with acceptable safety.