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Background: Anemia is one of the most frequent comorbidities in patients with heart failure (HF), which potentially can interfere with the effect of guideline-recommended HF medical therapy and can be associated with the use of neurohormonal blockers., Aim: The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment., Methods: The design and main results of the study have been previously described. Patients were randomized within 2 days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90 days were investigated., Results: The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90 days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90-1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference -2.34 (-4.37, -0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon-recovery of anemia-occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90 days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90 days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin., Conclusion: Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Rapid uptitration of guideline-directed medical therapy (GDMT) before and after discharge in hospitalized heart failure (HF) patients is feasible, is safe, and improves outcomes; whether this is also true in patients with coexistent atrial fibrillation/flutter (AF/AFL) is not known., Objectives: This study sought to investigate whether rapid GDMT uptitration before and after discharge for HF is feasible, safe and beneficial in patients with and without AF/AFL., Methods: In this secondary analysis of the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) trial, GDMT uptitration and patient outcomes were analyzed by AF/AFL status and type (permanent, persistent, paroxysmal)., Results: Among 1,078 patients enrolled in STRONG-HF, 496 (46%) had a history of AF, including 238 assigned to high-intensity care (HIC) and 258 to usual care (UC), and 581 did not have a history of AF/AFL, including 304 assigned to HIC and 277 to UC. By day 90, the average percent optimal dose of neurohormonal inhibitors achieved in the HIC arm was similar in patients with and without AF/AFL, reaching approximately 80% of the optimal dose (average absolute difference between AF/AFL and non-AF/AFL groups: -0.81%; 95% CI: -3.51 to 1.89). All-cause death or HF readmission by day 180 occurred less frequently in the HIC than the UC arm, both in patients with and without AF (adjusted HR: 0.75 [95% CI: 0.48-1.19] in AF vs adjusted HR: 0.50 [95% CI: 0.31-0.79] in non-AF/AFL patients; P for interaction = 0.2107). Adverse event rates were similar in patients with and without AF/AFL. AF/AFL type did not affect either uptitration or patient outcomes., Conclusions: Nearly half of acute HF patients have AF/AFL history. Rapid GDMT uptitration before and early after discharge is feasible, is safe, and may improve outcomes regardless of AF presence or type. (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies [STRONG-HF]; NCT03412201)., Competing Interests: Funding Support and Author Disclosures Dr Farmakis has received lecture honoraria or consulting or Advisory Board fees and/or grants from AstraZeneca, Bayer, Boehringer Ingelheim, Leo, Myocardial Solutions, Novartis, Remedica, Roche Diagnostics, and Viatris, all outside the present work. Dr Davison is an employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics and is the director of Heart Initiative, a nonprofit organization. Dr Fountoulaki has received honoraria for lectures from Boehringer Ingelheim and AstraZeneca. Dr Chioncel has received support from Servier for the European Society of Cardiology Congress. Dr Metra has received personal fees from Actelion, Amgen, Livanova, and Vifor Pharma as a member of Executive or Data Monitoring Committees of sponsored clinical trials and from AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics for participation to Advisory Boards or for speaking at sponsored meetings. Dr Celutkiene has received support from Novartis for New York Cardiovascular Seminars and speaker fees from AstraZeneca, Boehringer Ingelheim, Bayer, and Grindex. Dr Cohen-Solal has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. Dr Damasceno is an employee of the Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique, which has received research grants from the Heart Initiative for its participation in this study. Dr Diaz has received supporting fees for the coordination of STRONG-HF trial activities. Dr Edwards is an employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Dr Novosadova is an employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Dr Bistola has received honoraria for lectures or Advisory Boards from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Roche Diagnostics. Dr Pang has served as a consultant for Heart Initiative (Data and Safety Monitorin Board), Roche Diagnostics, Eagle Pharmaceuticals, and Kowa Pharmaceuticals; has served as a former or current investigator for industry studies funded by Abbott, Beckman Coulter, OrthoDiagnostics, and Siemens; and is a 5% owner in the HeartCourse, a Continuing Medical Education course. Dr Saidu has received grants from Medtronic, Servier, and Amylam and honoraria from Merck Sharp & Dohme, Novartis, and Sanofi. Dr Takagi is an employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Dr Voors has received consultancy fees and or research support paid to his employer from AstraZeneca, Anacardio, BMS, Bayer, Boehringer Ingelheim, Corteria, Cytokinetics, Eli Lilly, Merck, Moderna, Novartis, Novo Nordisk, and Roche Diagnostics. Dr Mebazaa has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics and honoraria for lectures from Roche Diagnostics, Bayer, and Merck Sharp & Dohme; has served as a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is the coinventor of a patent on combination therapy for patients having acute or persistent dyspnea. Dr Cotter is an employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics, and is director of Heart Initiative, a nonprofit organization. Dr Filippatos has received research support from the European Union and has received lecture fees from, served on the Advisory Board of, and/or made committee member contributions in clinical trials sponsored by Bayer, Medtronic, Vifor, Servier, Novartis, Impulse Dynamics, Novo Nordisk, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Burst steroid therapy, effective in acute respiratory diseases, may benefit patients with acute heart failure (AHF) in whom inflammatory activation is associated with adverse outcomes., Methods and Results: CORTAHF assessed whether burst steroid therapy reduces inflammation and results in better quality of life and clinical outcomes in AHF. Patients with AHF, N-terminal pro-B-type natriuretic peptide >1500 pg/ml, and high-sensitivity C-reactive protein (hsCRP) >20 mg/L were randomized 1:1 to oral, once daily 40 mg prednisone for 7 days or usual care, without blinding. Patients were followed for 90 days. A total of 101 patients were randomized. At day 7 the primary endpoint, hsCRP decreased in both arms - adjusted geometric mean ratios (GMRs) were 0.30 and 0.40 in the prednisone and usual care arms (ratio of GMRs 0.75, 95% confidence interval [CI] 0.56-1.00, p = 0.0498). The 90-day risk of worsening heart failure (HF), HF readmission or death as reported by the unblinded investigators was significantly lower in the prednisone group (10.4%) than in usual care (30.8%) (hazard ratio 0.31, 95% CI 0.11-0.86, p = 0.016). The EQ-5D visual analogue scale score as reported by the unblinded patients increased more in the prednisone group on day 7 (least squares mean difference 2.57, 95% CI 0.12-5.01 points, p = 0.040). All effects were statistically significant in the pre-specified subgroup with centrally-measured interleukin-6 >13 pg/ml. Adverse events, particularly hyperglycaemia, occurred more in the prednisone group with no difference in infection rate., Conclusion: In this small open-label study of patients with AHF, burst steroid therapy was associated with reduced inflammation as measured by hsCRP levels at day 7 (primary endpoint). Secondary endpoints showed improved quality of life at day 7 and reduced 90-day risk of death or worsening HF. Large prospective studies are needed to evaluate these findings., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

This statement focuses on the fact that women with peripartum cardiomyopathy (PPCM) have a substantial mortality and morbidity rate. Less than 50% of patients have full recovery of their cardiac function within 6 months of diagnosis. Also, patients with recovered cardiac function often suffer from comorbidities, such as hypertension or arrhythmias, which require long-term treatment. This has major implications which extend beyond the life of the patient, as it may also substantially impact her family. Women with a new diagnosis of PPCM should be involved in the decision-making processes regarding therapies, e.g. the recommendation to abstain from breastfeeding, or the use of cardiac implantable electronic devices. Women living with PPCM face the uncertainty of not knowing for some time whether their cardiac function will recover to allow them a near-to-normal life expectancy. This not only impacts their ability to work, which may have financial implications, but may also affect mental health and quality of life for the extended family. Women living with PPCM must be informed that a future pregnancy always carries a substantial risk and, in case of poor cardiac recovery, is associated with a high morbidity and mortality. Patients with PPCM are best managed by an interdisciplinary and multiprofessional approach including e.g. a cardiologist, a gynaecologist, nurses, a psychologist, and social workers. The scope of this document encompasses contemporary challenges and approaches for the management of women diagnosed with PPCM., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality of life and a reduced risk of worsening HF (WHF) events., Methods and Results: The study, which is currently ongoing, will include 100 patients with AHF ages 18-85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT-proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow-up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ-5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed., Conclusions: The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti-inflammatory therapies in AHF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Chloride plays a crucial role in renal salt sensing. This study investigates whether serum chloride is associated with clinical outcomes and decongestive response to acetazolamide in patients with acute decompensated heart failure., Methods: This post hoc analysis includes all 519 patients from the ADVOR trial (Acetazolamide in Decompensated Heart Failure With Volume Overload), randomized to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The impact of baseline serum chloride on the main trial end points and the treatment effect of acetazolamide was assessed, as was the evolution of serum chloride under decongestive treatment., Results: Hypochloremia (<96 mmol/L) and hyperchloremia (>106 mmol/L) were present in 80 (15%) and 53 (10%), respectively, at baseline. Hypochloremia was associated with significantly slower decongestion, a longer length of hospital stay, and increased risk of all-cause mortality and heart failure readmissions. Acetazolamide increased the odds of successful decongestion and reduced length of stay irrespectively of baseline serum chloride levels. No statistically significant interaction between serum chloride levels and the effect of acetazolamide on death or heart failure readmissions was observed. The placebo group exhibited a progressive decline in serum chloride, which was effectively prevented by acetazolamide ( P <0.001)., Conclusions: Hypochloremia is associated with diuretic resistance and worse clinical outcomes. Add-on acetazolamide therapy improves decongestion across the entire range of serum chloride and prevents the drop in chloride levels caused by loop diuretic monotherapy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03505788., Competing Interests: Dr Damman reports speaker/consultancy and research fees to his institution from Astra Zeneca, Abbott, Novartis, FIRE1, and Boehringer Ingelheim. Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the past 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research, educational, and travel grants from Abbott, Amgen, Astra Zeneca, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Corteria, Daiichi, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, Kaneka Corporation, Kantar, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Roche Diagnostics, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, and Zoll Medical UK. The research and educational grants do not impact on Dr Ruschitzka’s personal remuneration. Dr Verbrugge reports a consulting relationship with Abbott Laboratories, Abiomed, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb Belgium, Daiichi-Sankyo, Menarini Benelux, MSD, Novartis Pharma, Novo Nordisk Pharma, Pfizer, Roche Diagnostics, and Qompium.

Aims: Many European healthcare providers struggle to adopt multidisciplinary, integrated care pathways for people with heart failure (HF) as recommended by the European Society of Cardiology. PRO-HF (Program to Optimize Heart Failure Patient Pathways) was developed to help clinicians identify strengths, gaps, and shortcomings in their HF pathways and support tailored interventions to optimize pathways and enhance patient care. We report initial findings from baseline assessments of HF pathway characteristics and challenges from 10 hospitals in six European countries (France, Ireland, Portugal, Spain, The Netherlands, and United Kingdom)., Methods and Results: Baseline assessments were holistic appraisals of full HF services to calibrate current status and development needs and assist management teams in prioritizing improvement projects. Assessments were performed using a comprehensive checklist of measures covering the HF patient journey from diagnosis to ongoing follow-up. These included a digital survey sent to full HF care teams and one-to-one interviews. The digital survey focused on four key areas (HF outpatient clinic; remote patient management; efficient device implantation and inpatient pathways; and network maximization) and 16 dimensions of excellence. Priority areas and themes for action identified in baseline assessments were (i) provision of HF specialist care; (ii) data capture and analysis; (iii) institutional care protocols; (iv) hospital-wide strategies; and (v) multidisciplinary teams (MDTs). Suboptimal specialist care of emergency inpatients was an issue at all hospitals and prioritized at 8/10. Availability and accessibility of data on patients, activities, and outcomes was an issue at all hospitals and prioritized by 4/10. A lack of clear protocols, templates, and tools for some HF activities created variability in patient care (e.g., HF specialist consultations, diagnostic testing, follow-up appointments, medications, and device eligibility) and inefficient use of clinician time. This made it difficult to initiate new technologies (e.g., remote patient monitoring) due to the risk of overburdening staff. MDTs were frequently understaffed. Multiple interventions were identified to address gaps and shortcomings that could be tailored to specific needs of individual hospitals (e.g., inpatient pathway optimization, creation/optimization of HF outpatient clinics, development of an HF performance dashboard, enhancement of protocol adherence, streamlining cardiac resynchronisation therapy pathways, and MDT coordination)., Conclusions: PRO-HF provides a valuable opportunity to identify gaps and significant shortcomings in HF pathways in European hospitals. Preliminary findings from hospitals that have initiated suggested changes to address these challenges are encouraging, though longer-term follow-up from more hospitals is needed to confirm the impact of PRO-HF on HF pathway optimization and patient care., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Guideline-directed medical therapy (GDMT) decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF (Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure), high-intensity care (HIC) in the form of rapid uptitration of heart failure (HF) GDMT was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses., Objectives: The authors sought to assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable MAGGIC (Meta-Analysis Global Group in Chronic) HF risk score., Methods: In STRONG-HF, 1,078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) vs usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable., Results: Among 1,062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC vs UC group and did not differ by MAGGIC risk score tertiles (interaction nonsignificant). The incidence of all-cause death or HF readmission at day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1, 2, and 3. The HIC arm was at lower risk of all-cause death or HF readmission at day 180 (HR: 0.66; 95% CI: 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR: 0.51; 95% CI: 0.62-0.68 in tertiles 1, 2, and 3; interaction nonsignificant) for all comparisons and continuous (interaction nonsignificant) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction nonsignificant)., Conclusions: HIC led to better use of GDMT and lower HF-related morbidity and mortality compared with UC, regardless of the underlying HF risk profile. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies [STRONG-HF]; NCT03412201)., Competing Interests: Funding Support and Author Disclosures Funding for the STRONG-HF study was through an unrestricted grant provided to the Heart Initiative by Roche Diagnostics International (Rotkreuz, Switzerland). The funder had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit the manuscript for publication. Dr Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (K23HL150159), the American Heart Association (2nd Century Early Faculty Independence Award), The Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Inc, Edwards Lifesciences LLC, Esperion Therapeutics, Inc, and Novartis. Dr Mebazaa has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and Merck Sharp & Dohme; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. Drs Cotter, Davison, Edwards, Mebazaa, Novosadova, and Takagi are employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Drs Cotter and Davison are directors of Heart Initiative, a nonprofit organization. Dr Adamo has received speaker fees from Abbott Vascular and Medtronic. Dr Celutkiene has received personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche Diagnostics, and Pfizer. Dr Chioncel has received grants from Servier. Dr Cohen-Solal has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. Dr Damasceno works for the Faculty of Medicine, Eduardo Mondlane University (Maputo, Mozambique), which received research grants from the Heart Initiative for their participation in this study. Dr Diaz has received supporting fees for coordination of STRONG-HF trial activities. Dr Filippatos has received lecture fees or was a committee member for trials and registries sponsored by Bayer, Vifor, Boehringer Ingelheim, Medtronic, Servier, and Amgen. Dr Sliwa has received grants from Medtronic, Servier, and Amylam and honoraria from Merck Sharp & Dohme, Novartis, and Sanofi. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/ Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Redcardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder and nonexecutive director of Us2.ai. Dr Metra has received personal fees from Amgen, Livanova, and Vifor Pharma as a member of executive committees of sponsored clinical trials and from AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics for participation to advisory boards or for speaking at sponsored meetings. Dr Pagnesi has received personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, and Vifor Pharma. Dr Pang has received grants or research contracts from American Heart Association, Roche, Siemens, Ortho Diagnostics, Abbott, Beckman Coulter, and Siemens; consulting fees from Roche; honoraria from WebMD; and he has financial interest in The Heart Course. Dr Voors has received consultancy fees or research support from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Myocardia, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. Dr Filippatos has received lecture fees and/or advisory and/or trial committee membership by Bayer, Boehringer Ingelheim, Servier, Novartis, Impulse Dynamics, Vifor, Medtronic, Cardior, Novo Nordisc and Research Grants from the European Union. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) is a systemic disease associated with a high risk of morbidity, mortality, increased risk of hospitalizations, and low quality of life. Therefore, effective, systemic treatment strategies are necessary to mitigate these risks. In this manuscript, we emphasize the concept of high-intensity care to optimize guideline-directed medical therapy (GDMT) in HF patients. The document highlights the importance of achieving optimal recommended doses of GDMT medications, including beta-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter inhibitors to improve patient outcomes, achieve effective, sustainable decongestion, and improve patient quality of life. The document also discusses potential obstacles to GDMT optimization, such as clinical inertia, physiological limitations, comorbidities, non-adherence, and frailty. Lastly, it also attempts to provide possible future scenarios of high-intensive care that could improve patient outcomes., (© 2024. The Author(s).)

Background: The STRONG-HF trial showed that high-intensity care (HIC) consisting of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up reduced all-cause death or heart failure (HF) readmission at 180 days compared to usual care (UC). We hypothesized that significant differences in patient characteristics, management, and outcomes over the enrolment period may exist., Methods: Two groups of the 1,078 patients enrolled in STRONG-HF were created according to the order of enrolment within center. The early group consisted of the first 10 patients enrolled at each center (N = 342) and the late group consisted of the following patients (N = 736)., Results: Late enrollees were younger, had more frequently reduced ejection fraction, slightly lower NT-proBNP and creatinine levels compared with early enrollees. The primary outcome occurred less frequently in early compared to late enrollees (15% vs. 21%, aHR 0.65, 95% CI 0.42-0.99, P = .044). No treatment-by-enrolment interaction was seen in respect to the average percentage of optimal dose of GDMT after randomization, which was consistently higher in early and late patients randomized to HIC compared to UC. The higher use of renin-angiotensin-inhibitors in the HIC arm was more pronounced in the late enrollees both after randomization (interaction-P = .013) and at 90 days (interaction-P < .001). No interaction was observed for safety events. Patients randomized late to UC displayed a trend toward more severe outcomes (26% vs. 16%, P = .10), but the efficacy of HIC showed no interaction with the enrolment group (aHR 0.77, 95% CI 0.35-1.67 in early and 0.58, 95% CI 0.40-0.83 in late enrollees, adjusted interaction-P = .51) with similar outcomes in the HIC arm in late and early enrollees (16% vs. 13%, P = .73)., Conclusions: Late enrollees have different clinical characteristics and higher event rates compared to early enrollees. GDMT implementation in the HIC arm robustly achieved similar doses with consistent efficacy in early and late enrollees, mitigating the higher risk of adverse outcome in late enrollees., Trial Registration: ClinicalTrials.gov Identifier: NCT03412201., Competing Interests: Conflict of interest AM has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. BD, MB, CE, MN, KT, GC are employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. BD and GC are directors of Heart Initiative, a non-profit organisation. MAd has received speaker fees from Abbott Vascular and Medtronic. JC has received personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche Diagnostics, and Pfizer. AC-S has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. OC received grants from Servier. AD works for the Faculty of Medicine, Eduardo Mondlane University (Maputo, Mozambique), which received research grants from the Heart Initiative for their participation in this study. RD has received supporting fees for coordination of STRONG-HF trial activities. GF has received lecture fees or was a committee member for trials and registries sponsored by Bayer, Vifor, Boehringer Ingelheim, Medtronic, Servier and Amgen. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd., Redcardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder & non-executive director of Us2.ai. MP has received personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics and Vifor Pharma. PSP has received grants or research contracts from American Heart Association, Roche, Siemens, Ortho Diagnostics, Abbott, Beckman Coulter, and Siemens; consulting fees from Roche; honoraria from WebMD; and he has financial interest in The Heart Course. KS has received grants from Medtronic, Servier, and Amylam and honoraria from MSD, Novartis, and Sanofi. AAV has received consultancy fees or research support from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Myocardia, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Comprehensive uptitration of neurohormonal blockade targets fundamental mechanisms underlying development of congestion and may be an additional approach for decongestion after acute heart failure (AHF)., Objectives: This hypothesis was tested in the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies) trial., Methods: In STRONG-HF, patients with AHF were randomized to the high-intensity care (HIC) arm with fast up-titration of neurohormonal blockade or to usual care (UC). Successful decongestion was defined as an absence of peripheral edema, pulmonary rales, and jugular venous pressure <6 cm., Results: At baseline, the same proportion of patients in both arms had successful decongestion (HIC 48% vs UC 46%; P = 0.52). At day 90, higher proportion of patients in the HIC arm (75%) experienced successful decongestion vs the UC arm (68%) (P = 0.0001). Each separate component of the congestion score was significantly better in the HIC arm (all, P < 0.05). Additional markers of decongestion also favored the HIC: weight reduction (adjusted mean difference: -1.36 kg; 95% CI: -1.92 to -0.79 kg), N-terminal pro-B-type natriuretic peptide level, and lower orthopnea severity (all, P < 0.001). More effective decongestion was achieved despite a lower mean daily dose of loop diuretics at day 90 in the HIC arm. Among patients with successful decongestion at baseline, those in the HIC arm had a significantly better chance of sustaining decongestion at day 90. Successful decongestion in all subjects was associated with a lower risk of 180-day HF readmission or all-cause death (HR: 0.40; 95% CI: 0.27-0.59; P < 0.0001)., Conclusions: In STRONG-HF, intensive uptitration of neurohormonal blockade was associated with more efficient and sustained decongestion at day 90 and a lower risk of the primary endpoint., Competing Interests: Funding Support and Author Disclosures The study was funded through a grant provided to Heart Initiative by Roche Diagnostics International. Dr Mebazaa has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; has received honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnea. Drs Cotter and Davison are directors of Heart Initiative, a nonprofit organization, and employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Dr Cohen-Solal has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. Dr Metra has received personal fees from Amgen, LivaNova, and Vifor Pharma as a member of executive committees of sponsored clinical trials; and from AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics for participation to advisory boards or for speaking at sponsored meetings. Mr Edwards, Drs Barros, Novosadova, and Takagi are employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Dr Chioncel has received grants from Servier. Dr Diaz has received supporting fees for coordination of STRONG-HF trial activities. Dr Filippatos has received lecture fees or was a committee member for trials and registries sponsored by Bayer, Vifor, Boehringer Ingelheim, Medtronic, Servier, and Amgen. Dr Sliwa has received grants from Medtronic and Servier; and has received honoraria from MSD, Novartis, and Sanofi. Dr Voors has received consultancy fees or research support from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Myocardia, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. Dr Damasceno works for the Faculty of Medicine, Eduardo Mondlane University (Maputo, Mozambique), which received research grants from the Heart Initiative for their participation in this study. Dr Pang has received grants or research contracts from the American Heart Association, Roche, Siemens, Ortho Diagnostics, Abbott, Beckman Coulter, and Siemens; has received consulting fees from Roche; has received honoraria from WebMD; and has financial interest in The Heart Course. Dr Čelutkienė has received personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche Diagnostics, and Pfizer. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as a consultant for or on the Advisory Board/Steering Committee/Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd., Redcardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as co-founder and nonexecutive director of Us2.ai. Dr Pagnesi has received personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, and Vifor Pharma. Dr Arrigo has received speaker fees from Abbott Vascular and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The benefits of rapidly up-titrating evidence-based treatments following heart failure (HF) hospitalizations were demonstrated in the The Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) trial and emphasized in contemporary HF guidelines. We aimed to assess up-titration patterns of guideline-directed medical treatments in the Taiwanese HF population. Combining data from the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry and the Treatment with Angiotensin Receptor neprilysin inhibitor for Taiwan Acute Heart Failure (TAROT-AHF) study cohort, we formed the "Taiwan real-world cohort". We compared these data with subgroups of patients with left ventricular ejection fraction ≤40% in the STRONG-HF trial. Patients in the Taiwan cohort exhibited similar blood pressure, heart rate and N-terminal pro B-type natriuretic peptide levels at discharge compared with those in the STRONG-HF trial. A higher proportion of patients in the STRONG-HF high-intensity care group received up-titrations compared with those in the usual care group and the Taiwan cohort. Composite all-cause mortality or HF hospitalization at 180 days for patients in the high-intensity care group, usual care group, and Taiwan cohort were 17.4%, 23.7%, and 31.9%, respectively, with differences largely contributed by HF hospitalization (10.1%, 17.9%, and 27.6%, respectively), whereas all-cause mortality rates were similar (11.0%, 9.6%, and 9.3%, respectively). Gender did not affect this trend. In conclusion, our data highlights a treatment gap between the STRONG-HF trial and real-world practices in Taiwan, urging prompt optimization of HF therapy., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Biologically active adrenomedullin (bio-ADM) is a promising marker of residual congestion. The STRONG-HF trial showed that high-intensity care (HIC) of guideline-directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio-ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated., Methods and Results: We measured plasma bio-ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio-ADM correlated with most signs of congestion, with the exception of rales. Changes in bio-ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma -0.24; p = 0.0001). Patients in the highest tertile of baseline bio-ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180-day all-cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42-3.22) and 180-day HF rehospitalization (HR 2.33, 95% CI 1.38-3.94). Areas under the receiver-operating characteristic curves were 0.5977 (95% CI 0.5561-0.6393), 0.5800 (95% CI 0.5356-0.6243), and 0.6159 (95% CI 0.5711-0.6607) for bio-ADM, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their combination, respectively, suggesting that both bio-ADM and NT-proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio-ADM and NT-proBNP than NT-proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio-ADM concentration (interaction p = 0.37). In contrast to NT-proBNP, the 90-day change in bio-ADM did not differ significantly between HIC and usual care., Conclusions: Bio-ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio-ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT-proBNP., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The effects of initiating sacubitril/valsartan in patients with stable heart failure with reduced ejection fraction (HFrEF) on response to fluid and sodium expansion are unknown., Methods and Results: We have explored changes in natriuresis, diuresis, and congestion in response to the administration of intravenous fluid/sodium load in patients with HFrEF before as compared to after the initiation of sacubitril/valsartan. At baseline (before sacubitril/valsartan initiation) and 2 and 3 months after the initiation, patients underwent an evaluation that consisted of three phases of 3 h: the rest phase (0-3 h), the load phase (3-6 h) in which 1 L of intravenous Ringer solution was administered, and the diuretic phase (6-9 h) at the beginning of which furosemide was administered. Overall, 216 patients completed the study. In comparison to baseline values, at 2 and 3 months after sacubitril/valsartan initiation, patients' diuresis and natriuresis in response to Ringer administration significantly increased (mean difference: 38.8 [17.38] ml, p = 0.0040, and 9.6 [2.02] mmol, p < 0.0001, respectively). Symptoms and signs of congestion after the fluid/sodium challenge were significantly decreased at months 2 and 3 compared to baseline. Compared to baseline, there was also an increment of natriuresis after furosemide administration on sacubitril/valsartan (9.8 [5.13] mmol, p = 0.0167). There was a significant decrease in body weight in subsequent visits when compared to baseline values (-0.50 [-12.7, 7.4] kg at 2 months, and -0.75 [-15.9, 7.5] kg at 3 months; both p < 0.0001)., Conclusions: The initiation of sacubitril/valsartan in HFrEF patients was associated with improvements in natriuresis, diuresis, and weight loss and better clinical adaptation to potentially decongestive stressors., (© 2024 European Society of Cardiology.)

Heart failure is the most common cardiovascular complication during pregnancy and the postpartum period. It is associated with increased risk of maternal morbidity and mortality as well as potentially life-threatening foetal pathology. Management of heart failure in pregnancy requires expert knowledge of cardiovascular disease as well as obstetrics which underscores the importance of multidisciplinary cardio-obstetrics teams in order to optimize diagnosis, treatment and outcome. This includes counselling of women at risk before and during the course of pregnancy in order to strengthen the relationship between medical specialists and patients, as well as to allow patient-centred delivery of care and improve quality of life., (© 2024 European Society of Cardiology.)

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion., (© 2024 European Society of Cardiology.)

Background: Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) demonstrated the safety and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) with high-intensity care (HIC) compared with usual care in patients hospitalized for acute heart failure (HF). In the HIC group, the following safety indicators were used to guide up-titration: estimated glomerular filtration rate of <30 mL/min/1.73 m 2 , serum potassium of >5.0 mmol/L, systolic blood pressure (SBP) of <95 mmHg, heart rate of <55 bpm, and N-terminal pro-B-type natriuretic peptide concentration of >10% higher than predischarge values., Methods and Results: We examined the impact of protocol-specified safety indicators on achieved dose of GDMT and clinical outcomes. Three hundred thirteen of the 542 patients in the HIC arm (57.7%) met ≥1 safety indicator at any follow-up visit 1-6 weeks after discharge. As compared with those without, patients meeting ≥1 safety indicator had more severe HF symptoms, lower SBP, and higher heart rate at baseline and achieved a lower average percentage of GDMT optimal doses (mean difference vs the HIC arm patients not reaching any safety indicator, -11.0% [95% confidence interval [CI] -13.6 to -8.4%], P < .001). The primary end point of 180-day all-cause death or HF readmission occurred in 15.0% of patients with any safety indicator vs 14.2% of those without (adjusted hazard ratio 0.84, 95% CI 0.48-1.46, P = .540). None of each of the safety indicators, considered alone, was significantly associated with the primary end point, but an SBP of <95 mm Hg was associated with a trend toward increased 180-day all-cause mortality (adjusted hazard ratio 2.68, 95% CI 0.94-7.64, P = .065) and estimated glomerular filtration rate decreased to <30 mL/min/1.73 m 2 with more HF readmissions (adjusted hazard ratio 3.60, 95% CI 1.22-10.60, P = .0203). The occurrence of a safety indicator was associated with a smaller 90-day improvement in the EURO-QoL 5-Dimension visual analog scale (adjusted mean difference -3.32 points, 95% CI -5.97 to -0.66, P = .015)., Conclusions: Among patients with acute HF enrolled in STRONG-HF in the HIC arm, the occurrence of any safety indicator was associated with the administration of slightly lower GDMT doses and less improvement in quality of life, but with no significant increase in the primary outcome of 180-day HF readmission or death when appropriately addressed according to the study protocol., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This analysis provides details on baseline and changes in quality of life (QoL) and its components as measured by EQ-5D-5L questionnaire, as well as association with objective outcomes, applying high-intensity heart failure (HF) care in patients with acute HF., Methods: In STRONG-HF trial (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) patients with acute HF were randomized just before discharge to either usual care or a high-intensity care strategy of guideline-directed medical therapy up-titration. Patients ranked their state of health on the EQ-5D visual analog scale score ranging from 0 (the worst imaginable health) to 100 (the best imaginable health) at baseline and at 90 days follow-up., Results: In 1072 patients with acute HF with available assessment of QoL (539/533 patients assigned high-intensity care/usual care) the mean baseline EQ-visual analog scale score was 59.2 (SD, 15.1) with no difference between the treatment groups. Patients with lower baseline EQ-visual analog scale (meaning worse QoL) were more likely to be women, self-reported Black and non-European ( P <0.001). The strongest independent predictors of a greater improvement in QoL were younger age ( P <0.001), no HF hospitalization in the previous year ( P <0.001), lower NYHA class before hospital admission ( P <0.001) and high-intensity care treatment (mean difference, 4.2 [95% CI, 2.5-5.8]; P <0.001). No statistically significant heterogeneity in the benefits of high-intensity care was seen across patient subgroups of different ages, with left ventricular ejection fraction above or below 40%, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and systolic blood pressure above or below the median value. The treatment effect on the primary end point did not vary significantly across baseline EQ-visual analog scale ( P interaction =0.87)., Conclusions: Early up-titration of guideline-directed medical therapy significantly improves all dimensions of QoL in patients with HF and improves prognosis regardless of baseline self-assessed health status. The likelihood of achieving optimal doses of HF medications does not depend on baseline QoL., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03412201., Competing Interests: Disclosures Dr Mebazaa has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. Drs Davison, Barros, Novosadova, Takagi, Cotter, and C. Edwards are employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Drs Davison and Cotter are directors of Heart Initiative a nonprofit organization. Dr Adamo has received speaker fees from Abbott Vascular and Medtronic. Dr Čelutkienė has received personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche Diagnostics, and Pfizer. Dr Cohen-Solal has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. Dr Chioncel received grants from Servier. Dr Damasceno works for the Faculty of Medicine, Eduardo Mondlane University (Maputo, Mozambique), which received research grants from the Heart Initiative for their participation in this study. Dr Diaz has received supporting fees for coordination of STRONG-HF trial activities. Dr Filippatos has received lecture fees or was a committee member for trials and registries sponsored by Bayer, Vifor, Boehringer Ingelheim, Medtronic, Servier and Amgen. Dr Pagnesi has received personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim and Vifor Pharma. Dr Pang has received grants or research contracts from American Heart Association, Roche, Siemens, Ortho Diagnostics, Abbott, Beckman Coulter, and Siemens; consulting fees from Roche; honoraria from WebMD; and he has financial interest in The Heart Course. Dr Sliwa has received grants from Medtronic, Servier, and Amylam and honoraria from MSD, Novartis, and Sanofi. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Novo Nordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and nonexecutive director of Us2.ai. Dr Voors has received consultancy fees or research support from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Myocardia, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. All other authors declare no conflicts.

Background: Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation in patients with HF with reduced ejection fraction (HFrEF)., Methods and Results: Two matched groups of patients with HFrEF and with no peripheral VC vs without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼ 30 mmHg increase in venous pressure (venous stress test [VST]). Blood and ECs were sampled before and after 90 minutes of VST. We studied 44 patients (age 53 ± 12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II (ang-2), angiopoietin-2, vascular cell adhesion molecule-1, and CD146 significantly increased after the VST. Enhanced endothelin-1 and angiopoietin-2 responses to the VST were present in patients with vs without recent hospitalization and were prospectively associated with incident HF-related events; 6698 messenger ribonucleic acid (mRNA probe sets were differentially expressed in ECs after VST., Conclusions: Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation and promotes unfavorable transcriptome remodeling in ECs of patients with HFrEF. A distinct biological sensitivity to VC appears to be associated with high risk for HF progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acute right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale) is a life-threatening condition that may arise in different clinical settings. Patients at risk of developing or with manifest acute cor pulmonale usually present with an acute pulmonary disease (e.g. pulmonary embolism, pneumonia, and acute respiratory distress syndrome) and are managed initially in emergency departments and later in intensive care units. According to the clinical setting, other specialties are involved (cardiology, pneumology, internal medicine). As such, coordinated delivery of care is particularly challenging but, as shown during the COVID-19 pandemic, has a major impact on prognosis. A common framework for the management of acute cor pulmonale with inclusion of the perspectives of all involved disciplines is urgently needed., Competing Interests: Conflict of interest: H.A.I.S. has received honoraria from Abiomed, Boehringer Ingelheim, and AstraZeneca. A.V.-B. participates to a research advisory board from Air Liquide company. A.M. has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics and honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. No other relevant conflict of interest was reported., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Patients are at high risk of death or readmission following hospitalization for heart failure (HF). We tested the effect of a transitional care model that included month-long nurse-led home visits and long-term heart function clinic visits - with services titrated to estimated risk of clinical events - on 3-year outcomes following hospitalization., Methods and Results: In a pragmatic, stepped-wedge cluster randomized trial, 10 hospitals were randomized to the intervention versus usual care. The primary outcome was a composite of all-cause death, readmission, or emergency department (ED) visit. Secondary outcomes included components of the primary composite outcomes, HF readmissions and healthcare resource utilization. There were 2494 patients (50.4% female) with mean age of 77.7 years. The primary outcome was reached in 1040 (94.2%) patients in the intervention and 1314 (94.5%) in the usual care group at 3 years. The intervention did not reduce the risk of the primary composite outcome (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.81-1.05) nor the component outcomes overall, although numerically reduced the risk of ED visits in women but not men (HR 0.79, 95% CI 0.63-1.00 vs. HR 0.98, 95% CI 0.80-1.19; sex-treatment interaction p = 0.23). The uptake of guideline-directed medical therapy was no different with the intervention than with usual care, with the exception of sacubitril/valsartan, which increased with the intervention (3.3% vs 1.5%; relative risk 6.2, 95% CI 1.92-20.06)., Conclusions: More than 9 of 10 patients hospitalized for HF experienced all-cause death, readmission, or ED visit at 3 years. A transitional care model with services titrated to risk did not improve the composite of these endpoints, likely because there were no major differences in uptake of medical therapies between the groups., Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02112227., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Acute heart failure (AHF) is a clinical complex disease and a worldwide issue due to its inconsistent diagnosis and poor prognosis. The cornerstone of pathophysiology of AHF is systemic venous congestion, which is led by the underlying structural and functional cardiac condition. Systemic venous congestion is a major target for AHF management because it causes symptoms and organs dysfunction, and is associated with poor prognosis. The mainstay of decongestive therapy is diuresis with intravenous loop diuretics combined with other diuretics including thiazides when necessary, and non-invasive ventilation. The presence of unresolved congestion at discharge can lead heart failure related rehospitalization, and careful follow-up is required especially during "vulnerable phase", several months after discharge. The updated recommendation for management of AHF has been provided by latest guidelines from European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America. Several large studies have currently demonstrated the benefits of guideline-directed oral medical therapies, and trials are ongoing on medication such as selective sodium-glucose transport proteins 2 inhibitors and protocols for congestive therapy. This review aimed to summarize the latest insights in AHF, based primarily on the most recent guidelines and large randomized controlled trials., Competing Interests: Disclosure of interests A.M. Personal fees from Orion, Roche, Adrenomed and Fire 1 and grants and personal fees from 4TEEN4, Abbott, Roche and Sphyngotec. B.D. Invitation to a meeting in Henningsdorf by 4TEEN4 Pharmaceuticals GmbH., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Aims: A high-intensity care (HIC) strategy with rapid guideline-directed medical therapy (GDMT) up-titration and close follow-up visits improved outcomes, compared to usual care (UC), in patients recently hospitalized for acute heart failure (AHF). Hypotension is a major limitation to GDMT implementation. We aimed to assess the impact of baseline systolic blood pressure (SBP) on the effects of HIC versus UC and the role of early SBP changes in STRONG-HF., Methods and Results: A total of 1075 patients hospitalized for AHF with SBP ≥100 mmHg were included in STRONG-HF. For the purpose of this post-hoc analysis, patients were stratified by tertiles of baseline SBP (<118, 118-128, and ≥129 mmHg) and, in the HIC arm, by tertiles of changes in SBP from the values measured before discharge to those measured at 1 week after discharge (≥2 mmHg increase, ≤7 mmHg decrease to <2 mmHg increase, and ≥8 mmHg decrease). The primary endpoint was 180-day heart failure rehospitalization or death. The effect of HIC versus UC on the primary endpoint was independent of baseline SBP evaluated as tertiles (p interaction  = 0.77) or as a continuous variable (p interaction  = 0.91). In the HIC arm, patients with increased, stable and decreased SBP at 1 week reached 83.5%, 76.2% and 75.3% of target doses of GDMT at day 90. The risk of the primary endpoint was not significantly different between patients with different SBP changes at 1 week (adjusted p = 0.46)., Conclusions: In STRONG-HF, the benefits of HIC versus UC were independent of baseline SBP. Rapid GDMT up-titration was performed also in patients with an early SBP drop, resulting in similar 180-day outcome as compared to patients with stable or increased SBP., (© 2024 European Society of Cardiology.)

Importance: The Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) trial strived for rapid uptitration aiming to reach 100% optimal doses of guideline-directed medical therapy (GDMT) within 2 weeks after discharge from an acute heart failure (AHF) admission., Objective: To assess the association between degree of GDMT doses achieved in high-intensity care and outcomes., Design, Setting, and Participants: This was a post hoc secondary analysis of the STRONG-HF randomized clinical trial, conducted from May 2018 to September 2022. Included in the study were patients with AHF who were not treated with optimal doses of GDMT before and after discharge from an AHF admission. Data were analyzed from January to October 2023., Interventions: The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses was computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%). Dose and dose group were included as a time-dependent covariate in Cox regression models, which were used to test whether outcomes differed by dose., Main Outcome Measures: Post hoc secondary analyses of postdischarge 180-day HF readmission or death and 90-day change in quality of life., Results: A total of 515 patients (mean [SD] age, 62.7 [13.4] years; 311 male [60.4%]) assigned high-intensity care were included in this analysis. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Patients with lower blood pressure and more congestion were less likely to be uptitrated to optimal GDMT doses at week 2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day HF readmission or all-cause death (primary end point: adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P = .01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P = .007). Quality of life at 90 days, measured by the EQ-5D visual analog scale, improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, -4.88 to 5.07 and 3.13; 95% CI, -1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P = .07). Adverse events to day 90 occurred less frequently in participants with HIC who were prescribed higher GDMT doses at week 2., Conclusions and Relevance: Results of this post hoc analysis of the STRONG-HF randomized clinical trial show that, among patients randomly assigned to high-intensity care, achieving higher doses of HF GDMT 2 weeks after discharge was feasible and safe in most patients., Trial Registration: ClinicalTrials.gov Identifier: NCT03412201.

Cardiogenic shock is a primary cardiac disorder that results in both clinical and biochemical evidence of tissue hypoperfusion and can lead to multi-organ failure and death depending on its severity. Inadequate cardiac contractility or cardiac power secondary to acute myocardial infarction remains the most frequent cause of cardiogenic shock, although its contribution has declined over the past two decades, compared with other causes. Despite some advances in cardiogenic shock management, this clinical syndrome is still burdened by an extremely high mortality. Its management is based on immediate stabilization of haemodynamic parameters so that further treatment, including mechanical circulatory support and transfer to specialized tertiary care centres, can be accomplished. With these aims, medical therapy, consisting mainly of inotropic drugs and vasopressors, still has a major role. The purpose of this article is to review current evidence on the use of these medications in patients with cardiogenic shock and discuss specific clinical settings with indications to their use., (© 2024 European Society of Cardiology.)

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care., (© 2024 European Society of Cardiology.)

Aims: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry., Methods and Results: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF., Conclusions: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024 European Society of Cardiology.)

Aim: In this subgroup analysis of STRONG-HF, we explored the association between changes in renal function and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) according to a high-intensity care (HIC) strategy., Methods and Results: In patients randomized to the HIC arm (n = 542), renal function was assessed at baseline and during follow-up visits. We studied the association with clinical characteristics and outcomes of a decrease in estimated glomerular filtration rate (eGFR) at week 1, defined as ≥15% decrease from baseline. Patients in the usual care group (n = 536) were seen at day 90. The treatment effect of HIC versus usual care was independent of baseline eGFR (p-interaction = 0.4809). A decrease in eGFR within 1 week occurred in 77 (15.5%) patients and was associated with more rales on examination (p = 0.004), and a higher New York Heart Association class at the corresponding visit. Following the decrease in eGFR at 1 week, lower average optimal doses of GDMT were prescribed during follow-up (p = 0.0210) and smaller reductions in N-terminal pro-B-type natriuretic peptide occurred (geometrical mean 0.81 in no eGFR decrease vs 1.12 in GFR decrease, p = 0.0003). The rate of heart failure (HF) readmission or death at 180 days was 12.3% in no eGFR decrease versus 18.5% in eGFR decrease (p = 0.2274) and HF readmissions were 7.8% versus 16.6% (p = 0.0496)., Conclusions: In the STRONG-HF study, HIC reduced 180-day HF readmission or death regardless of baseline eGFR. An early decrease in eGFR during rapid up-titration of GDMT was associated with more evidence of congestion, yet lower doses of GDMT during follow-up., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed., Objectives: This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision., Methods: Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy controls (HCs). Significant changes in protein intensities were determined with nonpaired Student's t-tests and were further classified by using the Boruta algorithm. The proteins' diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation., Results: Patients with PPCM presented with a mean left ventricular ejection fraction of 33.5% ± 9.3% vs 57.0% ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs., Conclusions: Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers., Competing Interests: Funding Support and Author Disclosures Since the start of EORP, the following companies have supported the whole research program: Abbott Vascular International (2011-2021), Amgen Cardiovascular (2009-2018), AstraZeneca (2014-2021), Bayer AG (2009-2018), Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), Bristol-Myers Squibb and Pfizer Alliance (2011-2019), Daiichi Sankyo Europe GmbH (2011-2020), Daiichi Sankyo Europe GmbH and Eli Lilly and Company Alliance (2014-2017), Edwards Lifesciences (2016-2019), Gedeon Richter Plc (2014-2016), Menarini Int Op (2009-2012), Merck Sharp & Dohme–Merck and Co (2011-2014), Novartis Pharma AG (2014-2020), ResMed (2014-2016), Sanofi (2009-2011), Servier (2009-2021), and Vifor (2019-2022). Dr Hoevelmann has received speaker honoraria from Boehringer Ingelheim. Dr Tromp has received support from the National University of Singapore Start-up Grant, the Tier 1 Grant from the Ministry of Education, and the CS-IRG New Investigator Grant from the National Medical Research Council; has received consulting or speaker fees from Daiichi Sankyo, Boehringer Ingelheim, Roche Diagnostics, and Us2.ai; and owns patent US-10702247-B2 unrelated to the present work. Dr Sliwa has funded the proteomic analysis using her unconditional research grants; and has received support from Servier: Institut La Conference Hippocrate for funding of a statistical analysis program. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline-recommended therapy in Europe and other ESC affiliated countries., Methods: Between 1 November 2018 and 31 December 2020, 10 162 patients with chronic or acute/worsening HF with reduced, mildly reduced, or preserved ejection fraction were enrolled from 220 centres in 41 European or ESC affiliated countries. The ESC HF III Registry collected data on baseline characteristics (hospital or clinic presentation), hospital course, diagnostic and therapeutic decisions in hospital and at the clinic visit; and on outcomes at 12-month follow-up. These data include demographics, medical history, physical examination, biomarkers and imaging, quality of life, treatments, and interventions - including drug doses and reasons for non-use, and cause-specific outcomes., Conclusion: The ESC HF III Registry will provide comprehensive and unique insight into contemporary HF characteristics, treatment implementation, and outcomes, and may impact implementation strategies, clinical discovery, trial design, and public policy., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Acute heart failure (AHF) represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Symptoms and clinical signs of AHF (e.g. dyspnoea, orthopnoea, oedema, jugular vein distension, and variation of body weight) are mostly related to systemic venous congestion secondary to various mechanisms including extracellular fluids, increased ventricular filling pressures, and/or auto-transfusion of blood from the splanchnic into the pulmonary circulation. Thus, the initial management of AHF patients should be mostly based on decongestive therapies on admission followed, before discharge, by rapid implementation of guideline-directed oral medical therapies for heart failure. The therapeutic management of AHF requires the identification and rapid diagnosis of the disease, the diagnosis of the cause (or triggering factor), the evaluation of severity, the presence of comorbidities, and, finally, the initiation of a rapid treatment. The most recent guidelines from ESC and ACC/AHA/HFSA have provided updated recommendations on AHF management. Recommended pharmacological treatment for AHF includes diuretic therapy aiming to relieve congestion and achieve optimal fluid status, early and rapid initiation of oral therapies before discharge combined with a close follow-up. Non-pharmacological AHF management requires risk stratification in the emergency department and non-invasive ventilation in case of respiratory failure. Vasodilators should be considered as initial therapy in AHF precipitated by hypertension. On the background of recent large randomized clinical trials and international guidelines, this state-of-the-art review describes current pharmacological treatments and potential directions for future research in AHF., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Acute heart failure is a common and increasingly prevalent condition, affecting >10 million people annually. For those patients who survive to discharge, early readmissions and death rates are >30% everywhere on the planet, making it a malignant condition. Beyond these adverse outcomes, it represents one of the largest drivers of health care costs globally. Studies in the past 2 years have demonstrated that we can induce remissions in this malignant process if therapy is instituted rapidly, at the first acute heart failure episode, using full doses of all available effective medications. Multiple studies have demonstrated that this goal can be achieved safely and effectively. Now the urgent call is for all stakeholders, patients, physicians, payers, politicians, and the public at large to come together to address the gaps in implementation and enable health care providers to induce durable remissions in patients with acute heart failure.

Aims: To assess the potential interaction between non-cardiac comorbidities (NCCs) and the efficacy and safety of high-intensity care (HIC) versus usual care (UC) in the STRONG-HF trial, including stable patients with improved but still elevated natriuretic peptides., Methods and Results: In the trial, eight NCCs were reported: anaemia, diabetes, renal dysfunction, severe liver disease, chronic obstructive pulmonary disease/asthma, stroke/transient ischaemic attack, psychiatric/neurological disorders, and malignancies. Patients were classified by NCC number (0, 1, 2 and ≥3). The treatment effect of HIC versus UC on the primary endpoint, 180-day death or heart failure (HF) rehospitalization, was compared by NCC number and by each individual comorbidity. Among the 1078 patients, the prevalence of 0, 1, 2 and ≥3 NCCs was 24.3%, 39.8%, 24.5% and 11.4%, respectively. Achievement of full doses of HF therapies at 90 and 180 days in the HIC was similar irrespective of NCC number. In HIC, the primary endpoint occurred in 10.0%, 16.6%, 13.6% and 26.2%, in those with 0, 1, 2 and ≥3 NCCs, respectively, as compared to 19.1%, 25.4%, 23.3% and 26.2% in UC (interaction-p = 0.80). The treatment benefit of HIC versus UC on the primary endpoint did not differ significantly by each individual comorbidity. There was no significant treatment interaction by NCC number in quality-of-life improvement (p = 0.98) or the incidence of serious adverse events (p = 0.11)., Conclusions: In the STRONG-HF trial, NCCs neither limited the rapid up-titration of HF therapies, nor attenuated the benefit of HIC on the primary endpoint. In the context of a clinical trial, the benefit-risk ratio favours the rapid up-titration of HF therapies even in patients with multiple NCCs., (© 2023 European Society of Cardiology.)

Background and Aims: In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent across the entire range of renal function remains unclear., Methods: This is a pre-specified analysis of the ADVOR trial that randomized 519 patients with ADHF to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The main endpoints of decongestion, diuresis, natriuresis, and clinical outcomes are assessed according to baseline renal function. Changes in renal function are evaluated between treatment arms., Results: On admission, median estimated glomerular filtration rate (eGFR) was 40 (30-52) mL/min/1.73 m². Acetazolamide consistently increased the likelihood of decongestion across the entire spectrum of eGFR (P-interaction = .977). Overall, natriuresis and diuresis were higher with acetazolamide, with a higher treatment effect for patients with low eGFR (both P-interaction < .007). Acetazolamide was associated with a higher incidence of worsening renal function (WRF; rise in creatinine ≥ 0.3 mg/dL) during the treatment period (40.5% vs. 18.9%; P < .001), but there was no difference in creatinine after 3 months (P = .565). This was not associated with a higher incidence of heart failure hospitalizations and mortality (P-interaction = .467). However, decongestion at discharge was associated with a lower incidence of adverse clinical outcomes irrespective of the onset of WRF (P-interaction = .805)., Conclusions: Acetazolamide is associated with a higher rate of successful decongestion across the entire range of renal function with more pronounced effects regarding natriuresis and diuresis in patients with a lower eGFR. While WRF occurred more frequently with acetazolamide, this was not associated with adverse clinical outcomes., Clinicaltrials.gov Identifier: NCT03505788., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Importance: Diagnosing acute heart failure (AHF) is difficult in elderly patients presenting with acute dyspnea to the emergency department., Objectives: To assess the diagnostic accuracy of NT-proBNP, high-sensitivity cardiac troponin-I (Hs-cTnI), soluble ST2 (ST2), galectin-3 and CD146 alone and in combination for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency department., Design, Settings and Participants: This was a prospective, multicenter study performed between September 2016 and January 2020, including elderly patients presenting with acute dyspnea to the emergency department of 6 French hospitals., Intervention: Measurement of NT-proBNP, hs-cTnI, ST2, galectin-3 and CD146., Outcome Measure and Analysis: The reference standard, AHF, was adjudicated by two independent physicians based on ED and hospitalization clinical, biological (excluding biomarkers), radiological and echocardiography data (performed by a cardiologist in the cardiology department specifically for this study). Three exploratory methods (two using a cross-sectional approach with logistic regression and counting all biomarker combinations, and one using a sequential approach with gray zone optimizations) were applied to create comprehensive combinations of the 5 biomarkers for measuring diagnostic accuracy., Main Results: Two hundred thirty-eight patients (median age of 85 years, IQR = 8) were analyzed, and 110 (46%) were diagnosed with AHF. The accuracies of NT-proBNP, CD146, hs-cTnI, galectin-3, and ST2 were 0.72 [95% confidence interval (CI) 0.66-0.77], 0.63 (95% CI 0.57-0.69), 0.59 (95% CI 0.53-0.65), 0.55 (95% CI 0.49-0.61) and 0.51 (95% CI 0.45-0.57), respectively. Regardless of the approach used or how the 5 biomarkers were combined, the best accuracy for diagnosing AHF (0.73, 95% CI 0.67-0.78) did not differ from that of NT-proBNP alone., Conclusion: In this study, NT-proBNP alone exhibited the best diagnostic accuracy for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency departments. None of the other biomarkers alone or combined improved the accuracy compared to NT-proBNP, which is the only biomarker to use in this setting., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: To evaluate the prevalence and associations of non-cardiac comorbidities (NCCs) with in-hospital and post-discharge outcomes in acute heart failure (AHF) across the ejection fraction (EF) spectrum., Methods and Results: The 9326 AHF patients from European Society of Cardiology (ESC)-Heart Failure Association (HFA)-EURObservational Research Programme Heart Failure Long-Term Registry had complete information for the following 12 NCCs: anaemia, chronic obstructive pulmonary disease (COPD), diabetes, depression, hepatic dysfunction, renal dysfunction, malignancy, Parkinson's disease, peripheral vascular disease (PVD), rheumatoid arthritis, sleep apnoea, and stroke/transient ischaemic attack (TIA). Patients were classified by number of NCCs (0, 1, 2, 3, and ≥4). Of the AHF patients, 20.5% had no NCC, 28.5% had 1 NCC, 23.1% had 2 NCC, 15.4% had 3 NCC, and 12.5% had ≥4 NCC. In-hospital and post-discharge mortality increased with number of NCCs from 3.0% and 18.5% for 1 NCC to 12.5% and 36% for ≥4 NCCs.Anaemia, COPD, PVD, sleep apnoea, rheumatoid arthritis, stroke/TIA, Parkinson, and depression were more prevalent in HF with preserved EF (HFpEF). The hazard ratio (95% confidence interval) for post-discharge death for each NCC was for anaemia 1.6 (1.4-1.8), diabetes 1.2 (1.1-1.4), kidney dysfunction 1.7 (1.5-1.9), COPD 1.4 (1.2-1.5), PVD 1.2 (1.1-1.4), stroke/TIA 1.3 (1.1-1.5), depression 1.2 (1.0-1.5), hepatic dysfunction 2.1 (1.8-2.5), malignancy 1.5 (1.2-1.8), sleep apnoea 1.2 (0.9-1.7), rheumatoid arthritis 1.5 (1.1-2.1), and Parkinson 1.4 (0.9-2.1). Anaemia, kidney dysfunction, COPD, and diabetes were associated with post-discharge mortality in all EF categories, PVD, stroke/TIA, and depression only in HF with reduced EF, and sleep apnoea and malignancy only in HFpEF., Conclusion: Multiple NCCs conferred poor in-hospital and post-discharge outcomes. Ejection fraction categories had different prevalence and risk profile associated with individual NCCs., Competing Interests: Conflict of interest: O. Chioncel declare no conflict of interest related to present work; ESC meeting support from Servier. L. Benson declare no conflict of interest. M. Crespo-Leiro reports unrelated to the present work: consultancy or speaker's honoraria from Novartis, AstraZeneca, Boehringer Ingelheim, Abbott, Medtronic, CareDx, Astellas and Vifor Pharma. S.D. Anker reports unrelated to the present work: Grants or contracts: Vifor Int, Abbott Vascular; Consulting fees: CVRx, Amgen, Respicardia, Novo Nordisk, Brahms, Novartis, Sanofi, Cordio; Leadership or fiduciary role in other board: Abbott Vascular, Astra Zeneca, Bayer AG, Bioventrix, Boehringer Ingelheim, Cardiac Dimension, Cardior, Impulse Dynamics, Janssen, Occlutech, Servier, Vifor Int, and V-Wave. A.J.S. Coats reports unrelated to the present work: speaker's honoraria from: Astra Zeneca, Bayer, Boehringer Ingelheim, Edwards, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia, and Viatris. G. Filippatos reports lecture fees and/or committee membership in trials sponsored by Bayer, Vifor, Medtronic, Novartis, Servier, Boehringer Ingelheim, and research support from the European Union. T. McDonagh reports unrelated to the present work: speaker's honoraria from Abbot, Astra Zeneca, Boeringher Ingelheim and Edwards. C. Margineanu none related to the present work. A. Mebazaa reports unrelated to the present work: Grants or contracts from and consulting fees from Roche, 4TEEN4, Corteria; speaker's honoraria from MSD; Patents: S-Form Pharma. M. Metra reports personal fees from Amgen, AstraZeneca, Abbott Vascular, Bayer, Edwards Therapeutics, Livanova, Vifor Pharma, as member of Trials' Committees or advisory boards or for speeches at sponsored meetings in the last 3 years. M. Piepoli reports unrelated to the present work: consultancy, speaker's, institutional fees from Astra-Zeneca, Boehringer- Ingelheim, CHF solution, Menarini, Novartis, Servier M. Adammo reports speaker fees from Abbott Vascular and Medtronic. G.M.C. Rosano declare no conflict of interest. F. Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research-, educational- and/or travel grants from Abbott, Amgen, Astra Zeneca, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Corteria, Daiichi, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, Kaneka Corporation, Kantar, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Roche Diagnostics, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, Trama Solutions, V- Wave, Vascular Medical, Vifor, Wissens Plus, ZOLL. The research and educational grants do not impact on Prof. Ruschitzka`s personal remuneration. G. Savarese reports unrelated to the present work: Grants or contracts: Vifor Pharma, Boehringer Ingelheim, Astra Zeneca, Merck, Cytokinetics; Consulting fees: Societa' Prodotti Antibiotici, Medical Education Global Solutions, Genesis, Agence Recherche (ANR); speaker's honoraria: Servier, Cytokinetics, Medtronic, Dynamicom Education, Vifor Pharma; Support for attending meetings: Boehringer Ingelheim; Data Safety Monitoring Bord or Advisory Board: Astra Zeneca, Uppsala Clinical Research Center, Servier. P. Seferovic reports unrelated to the present work: speaker's honoraria from Servier, Astra Zeneca, Menarini, Boehringer Ingelheim, Novartis and Roche diagnostic. M. Volterrani: none related to the present work. R. Ferrari reports unrelated to the present work: speaker's honoraria and support for attending meetings: Servier International, Merck Serono, Lupin, Sunpharma, Reddys Ltd; leadership or fiduciary role in other board: Scientific Director of Medical Trial Analysis. A. Maggioni: personal fees from AstraZeneca, Bayer, Fresenius, Novartis, outside the submitted work. L.H. Lund is supported by Supported by Karolinska Institutet, the Swedish Research Council [grant 523-2014-2336], the Swedish Heart Lung Foundation [grants 20150557, 20190310], and the Stockholm County Council [grants 20170112, 20190525] and reports unrelated to the present work: Grants: AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, MSD; Consulting: Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Life Sciences, Alleviant; Speaker's honoraria: Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, Bayer; Patent: AnaCardio; Stock ownership: AnaCardio., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To review a contemporary approach to the management of patients with cardiogenic shock (CS)., Data Sources: We reviewed salient medical literature regarding CS., Study Selection: We included professional society scientific statements and clinical studies examining outcomes in patients with CS, with a focus on randomized clinical trials., Data Extraction: We extracted salient study results and scientific statement recommendations regarding the management of CS., Data Synthesis: Professional society recommendations were integrated with evaluated studies., Conclusions: CS results in short-term mortality exceeding 30% despite standard therapy. While acute myocardial infarction (AMI) has been the focus of most CS research, heart failure-related CS now predominates at many centers. CS can present with a wide spectrum of shock severity, including patients who are normotensive despite ongoing hypoperfusion. The Society for Cardiovascular Angiography and Intervention Shock Classification categorizes patients with or at risk of CS according to shock severity, which predicts mortality. The CS population includes a heterogeneous mix of phenotypes defined by ventricular function, hemodynamic profile, biomarkers, and other clinical variables. Integrating the shock severity and CS phenotype with nonmodifiable risk factors for mortality can guide clinical decision-making and prognostication. Identifying and treating the cause of CS is crucial for success, including early culprit vessel revascularization for AMI. Vasopressors and inotropes titrated to restore arterial pressure and perfusion are the cornerstone of initial medical therapy for CS. Temporary mechanical circulatory support (MCS) is indicated for appropriately selected patients as a bridge to recovery, decision, durable MCS, or heart transplant. Randomized controlled trials have not demonstrated better survival with the routine use of temporary MCS in patients with CS. Accordingly, a multidisciplinary team-based approach should be used to tailor the type of hemodynamic support to each individual CS patient's needs based on shock severity, phenotype, and exit strategy., Competing Interests: Dr. Pöss receives research funding from the German Cardiac Society, German Heart Research Foundation, and Dr. Rolf M. Schwiete Foundation. Dr. Schaubroeck has received honoraria from Abiomed. Dr. Morrow’s institution received funding from Abbott, Abiomed, and Amgen; he disclosed that he is a member of the Thrombolysis in Myocardial Infarction Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from: Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Janssen Research and Development, LLC, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, Softcell Medical Limited, and Zora Biosciences. He has received consulting fees from Abbott Laboratories, ARCA Biopharma, InCardia, Inflammatix, Merck & Co, Novartis, and Roche Diagnostics. Dr. Mebazaa received grant from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and WIndtree Therapeutics; he received honoraria for lectures from Roche Diagnostics, Bayer, and MSD; he is a consultant for Corteria Pharmaceuticals, S-Form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; he is coinventor of a patent on combination therapy for patients having acute and/or persistent dyspnea; and he disclosed the off-label product use of Vasopressors and specific mechanical circulatory support devices may not be labeled for use in shock. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Aims: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes., Methods and Results: Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively., Conclusion: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: STRONG-HF showed that rapid up-titration of guideline-recommended medical therapy (GRMT), in a high intensity care (HIC) strategy, was associated with better outcomes compared with usual care. The aim of this study was to assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and its changes early during up-titration., Methods and Results: A total of 1077 patients hospitalized for acute heart failure (HF) and with a >10% NT-proBNP decrease from screening (i.e. admission) to randomization (i.e. pre-discharge), were included. Patients in HIC were stratified by further NT-proBNP changes, from randomization to 1 week later, as decreased (≥30%), stable (<30% decrease to ≤10% increase), or increased (>10%). The primary endpoint was 180-day HF readmission or death. The effect of HIC vs. usual care was independent of baseline NT-proBNP. Patients in the HIC group with stable or increased NT-proBNP were older, with more severe acute HF and worse renal and liver function. Per protocol, patients with increased NT-proBNP received more diuretics and were up-titrated more slowly during the first weeks after discharge. However, by 6 months, they reached 70.4% optimal GRMT doses, compared with 80.3% for those with NT-proBNP decrease. As a result, the primary endpoint at 60 and 90 days occurred in 8.3% and 11.1% of patients with increased NT-proBNP vs. 2.2% and 4.0% in those with decreased NT-proBNP (P = 0.039 and P = 0.045, respectively). However, no difference in outcome was found at 180 days (13.5% vs. 13.2%; P = 0.93)., Conclusion: Among patients with acute HF enrolled in STRONG-HF, HIC reduced 180-day HF readmission or death regardless of baseline NT-proBNP. GRMT up-titration early post-discharge, utilizing increased NT-proBNP as guidance to increase diuretic therapy and reduce the GRMT up-titration rate, resulted in the same 180-day outcomes regardless of early post-discharge NT-proBNP change., Competing Interests: Conflict of interest: A.M. has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. G.C. is employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. .G.C. is director of Heart Initiative, a non-profit organization. B.D. is employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. B.D. is director of Heart Initiative, a non-profit organization. A.C.S. has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. M.M. has received personal fees from Amgen, Livanova, and Vifor Pharma as a member of executive committees of sponsored clinical trials and from AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics for participation to advisory boards or for speaking at sponsored meetings. C.E. is employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. O.C. received grants from Servier. R.D. has received supporting fees for coordination of STRONG-HF trial activities. G.F. has received lecture fees or was a committee member for trials and registries sponsored by Bayer, Vifor, Boehringer Ingelheim, Medtronic, Servier, and Amgen. K.S. has received grants from Medtronic, Servier, and Amylam and honoraria from MSD, Novartis, and Sanofi. A.A.V. has received consultancy fees or research support from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Myocardia, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. MN is employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. KT is employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. A.D. works for the Faculty of Medicine, Eduardo Mondlane University (Maputo, Mozambique), which received research grants from the Heart Initiative for their participation in this study. P.S.P. has received grants or research contracts from American Heart Association, Roche, Siemens, Ortho Diagnostics, Abbott, Beckman Coulter, and Siemens; consulting fees from Roche; honoraria from WebMD; and he has financial interest in The Heart Course. J.C. has received personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche Diagnostics, and Pfizer. C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd., Redcardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder and non-executive director of Us2.ai. M.P. has received personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim and Vifor Pharma. MA has received speaker fees from Abbott Vascular and Medtronic. M.B. is employee of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. The other authors have no conflicts to report., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Acetazolamide, an inhibitor of proximal tubular sodium reabsorption, leads to more effective decongestion in acute heart failure (AHF). It is unknown whether acetazolamide alters serum sodium and potassium levels on top of loop diuretics and if baseline values modify the treatment effect of acetazolamide., Methods and Results: This is a pre-specified sub-analysis of the ADVOR trial that randomized 519 patients with AHF and volume overload in a 1:1 ratio to intravenous acetazolamide or matching placebo on top of standardized intravenous loop diuretics. Mean potassium and sodium levels at randomization were 4.2 ± 0.6 and 139 ± 4 mmol/L in the acetazolamide arm versus 4.2 ± 0.6 and 140 ± 4 mmol/L in the placebo arm. Hypokalaemia (<3.5 mmol/L) on admission was present in 44 (9%) patients and hyponatraemia (≤135 mmol/L) in 82 (16%) patients. After 3 days of treatment, 44 (17%) patients in the acetazolamide arm and 35 (14%) patients in the placebo arm developed hyponatraemia (p = 0.255). Patients randomized to acetazolamide demonstrated a slight decrease in mean potassium levels during decongestion, which was non-significant over time (p = 0.053) and had no significant impact on hypokalaemia incidence (p = 0.061). Severe hypokalaemia (<3.0 mmol/L) occurred in only 7 (1%) patients, similarly distributed between the two treatment arms (p = 0.676). Randomization towards acetazolamide improved decongestive response irrespective of baseline serum sodium and potassium levels., Conclusions: Acetazolamide on top of standardized loop diuretic therapy does not lead to clinically important hypokalaemia or hyponatraemia and improves decongestion over the entire range of baseline serum potassium and sodium levels., (© 2023 European Society of Cardiology.)

Aims: Acute heart failure (AHF) has an impact on human health worldwide. Despite guidelines for treatment and management of AHF, mortality rates remain high. The main objective of this study was to compare standard in-hospital treatment and management of AHF against current clinical guidelines and variations across regions., Methods: Between February 2018 and May 2021, investigators were approached to participate in the STRONG-HF study. The lead investigator at 158 sites in 20 countries completed a site feasibility questionnaire. Sites were grouped by country into five different regions: Africa and the Middle East, Eastern Europe, Russia, South America, and Western Europe., Results: According to the questionnaires, there are large differences in how patients present due to AHF and where in the hospital they are treated. There were significant differences in reported percentage of AHF patients receiving angiotensin converting enzymes inhibitors across the regions (P < 0.001), mostly due to prescription of more angiotensin II receptor blockers and angiotensin receptor-neprilysin inhibitors in South America and Western Europe. Reported beta-blocker use was high across all of the regions. Device therapy and percutaneous interventions were more common in Europe. Sites reported a 5 to 8 day length of stay, while in Russia most have a 10 to 12 day length of stay. Regions reported that AHF patients follow up with a community cardiologist or general practitioner post-discharge, although follow-up was commonly more than 1 month post discharge, and not all sites had the capability to measure natriuretic peptides post discharge., Conclusions: In this analysis of feasibility questionnaires, most sites reported general adherence to ESC guidelines for treatment and management of AHF patients although percutaneous and device therapy was less common outside Europe and follow-up after discharge took place late and was not as extensive as recommended. There were wide variations seen within and across regions in some areas., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common in patients with heart failure (HF). The aim of this study was to investigate prevalence, clinical characteristics and outcomes of patients with or without isolated or combined MR and TR across the entire HF spectrum., Methods and Results: The ESC-HFA EORP HF Long-Term Registry is a prospective, multicentre, observational study including patients with HF and 1-year follow-up data. Outpatients without aortic valve disease were included and stratified according to isolated or combined moderate/severe MR and TR. Among 11 298 patients, 7541 (67%) had no MR/TR, 1931 (17%) isolated MR, 616 (5.5%) isolated TR and 1210 (11%) combined MR/TR. Baseline characteristics were differently distributed across MR/TR categories. Compared to HF with reduced ejection fraction, HF with mildly reduced ejection fraction was associated with a lower risk of isolated MR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.60-0.80), and distinctly lower risk of combined MR/TR (OR 0.51; 95% CI 0.41-0.62). HF with preserved ejection fraction (HFpEF) was associated with a distinctly lower risk of isolated MR (OR 0.42; 95% CI 0.36-0.49), and combined MR/TR (OR 0.59; 95% 0.50-0.70), but a distinctly increased risk of isolated TR (OR 1.94; 95% CI 1.61-2.33). All-cause death, cardiovascular death, HF hospitalization and combined outcomes occurred more frequently in combined MR/TR, isolated TR and isolated MR versus no MR/TR. The highest incident rates were observed in isolated TR and combined MR/TR., Conclusion: In a large cohort of outpatients with HF, prevalence of isolated and combined MR and TR was relatively high. Isolated TR was driven by HFpEF and was burdened by an unexpectedly poor outcome., (© 2023 European Society of Cardiology.)

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., (© 2023 European Society of Cardiology.)

Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF., (© 2023 European Society of Cardiology.)