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Little is known about the management and disease trajectories of heart failure (HF) patients in the pre-hospital setting when experiencing exacerbating symptoms. Shortness of breath (SOB) is a main reason for contacting out-of-hours primary care (OHS-PC). We aim to describe the care trajectories of these patients with heart failure at the OHS-PC with exacerbating symptom SOB, and to assess 6-months outcomes regarding mortality and hospital admissions. We included patients who contacted Dutch OHS-PC for SOB between September 2020 and August 2021. We selected those in whom HF was considered to be the cause for consultation and further clinical evaluation. We applied descriptive analyses to characterize these patients and their disease trajectories following this OHS-PC contact, and compared patients referred to the Emergency Department (ED) to those who remained in primary care. Of 1,833 calls for SOB, 102 (5.1%) concerned patients with HF, who had a mean age of 79.6 &#xb1; 11.1 years, and 53% were women. Ten (9.8%) patients were directly referred to the ED. The remaining 92 (90.2%) were first assessed by a general practitioner (GP): 62 (60.8%) received a home visit, 15 (14.7%) were seen at the OHS-PC clinic, and 15 (14.7%) received a telephone advice only. Of these 92 patients, 41 (44.6%) patients were subsequently referred to the ED, and 39 (42.4%) were kept at home and received loop diuretics (newly initiated or increased dose). Of the 51 patients referred to the ED (directly or after assessment with the GP), 42 patients (82.4%, p-value < 0.001) were admitted. Six-month all-cause mortality of the 102 patients was 32.3%. At the OHS-PC, one in every 20 contacts for SOB is a HF patient who has a high six-month mortality risk. Patients were directly referred to the hospital, or received initiation or up-titration of loop diuretics.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is widely used as an enrichment criterion in heart failure (HF) randomized controlled trials (RCTs), yet cut-offs vary. This study aims to provide evidence-based guidance on selecting NT-proBNP cut-offs to optimize the balance between event enrichment and screening failure across HF subgroups. Using the Swedish HF Registry (SwedeHF), we applied NT-proBNP cut-offs from prior RCTs (200-5000 pg/mL) and calculated 1-year incidence proportions of a composite CV outcome (CV death or first HF hospitalisation) across subgroups by ejection fraction (EF), care setting (inpatient/outpatient), atrial fibrillation (AF), chronic kidney disease (CKD), and obesity. We quantified point and relative increases in event proportions and potential screening failure at each cut-off and identified optimal prognostic thresholds by maximizing Youden's index. Among 43,750 HF patients, median NT-proBNP was lower in HFpEF/HFmrEF vs HFrEF, outpatients vs inpatients, sinus rhythm vs AF, obese vs not obese, and patients without CKD vs with CKD (all p < 0.001). Higher NT-proBNP cut-offs increased 1-year composite CV proportions but excluded more patients. For example, In HFrEF outpatients, the 1-year proportion rose from 22.0% (no cut-off) to 24.3% at &#x2265;600 pg/mL and 26.2% at &#x2265;1,200 pg/mL, a 19% (95% CI:14.0-24.4) relative increase. Screening failure rose from 16.0% to 26.4% at these respective cut-offs. Optimal prognostic thresholds aligned with or exceeded subgroup median NT-proBNP values. Higher NT-proBNP cut-offs were associated with increased event enrichment but also higher screening failure. These findings support the use of higher cut-offs currently used in HF RCTs and suggest that future trials should tailor NT-proBNP cut-offs to trial aims, balancing enrichment with enrolment feasibility and considering obesity and CKD in addition to EF and AF.

To evaluate the impact of a gamified engagement toolkit on registration rates and data completeness in a real-world registry. Engage-HF is a prospective, observational pre-test:post-test exploratory concept study involving 31 hospitals participating in the Netherlands Heart Registration Heart Failure registry (NHR-HF): 12 that were technically ready and willing to participate formed the intervention group, while the remaining 19 NHR-HF hospitals served as controls. In the intervention group, 28 HF-nurse specialists participated in a 24-week educational program using the Engage-HF toolkit. The primary endpoint was participation, measured by a performance index (average number of patients registered per hospital per month) at the end of the intervention and at 3- and 6-month post-test. Secondary endpoint was data completeness, and an exploratory analysis evaluated participants' experiences with the toolkit and its impact on their HF-registries and 2021 ESC HF-guidelines knowledge. The intervention group showed a numerically higher performance index at the end of the intervention (5.2 vs. 2.1 patients/hospital/month, p=0.41) and at 3-month (4.4 vs. 2.9 patients/hospital/month, p=0.45) post-test. However, at 6-month post-test, the performance index was higher in the control group (3.3 vs. 4.0 patients/hospital/month, p=0.98). Data completeness was high in both groups, with variable-specific differences without a clear pattern. Participants rated the toolkit positively as an educational toolkit but reported neutral impacts on HF-registries or 2021 ESC HF-guidelines knowledge. The Engage-HF toolkit was well-received and may boost short-term participation but did not improve long-term participation or the already high data completeness.

This study aimed to determine whether the prognostic implications of body mass index (BMI) differ according to heart failure (HF) phenotype and sex. From the Korean HF III registry (n = 7,351), we analyzed 5,271 patients hospitalized for acute heart failure (AHF) with available data. BMI was categorized as low (<18.5&#x202f;kg/m&#xb2;), normal (18.5-24.9), or high (&#x2265;25.0) using cut-off values consistent with Asia-Pacific criteria. The primary outcome was a composite of 2-year all-cause mortality or heart transplantation. Kaplan-Meier analyses and multivariable Cox proportional hazards models, including interaction terms for BMI, sex, and HF phenotype, were performed. In HF with reduced ejection fraction (HFrEF), lower BMI was consistently associated with worse outcomes in both men and women. In contrast, in HF with preserved ejection fraction (HFpEF), BMI was prognostic in women but not in men: survival differed by BMI category in Kaplan-Meier analyses for all subgroups except men with HFpEF. In multivariable analyses, higher BMI was independently associated with lower risk in women with HFrEF (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.45-0.96, p&#x202f;=&#x202f;0.032), whereas lower BMI in women with HFpEF showed a borderline association with higher risk (HR 1.56, 95% CI 0.99-2.47, p&#x202f;=&#x202f;0.057). The prognostic implications of BMI in AHF differ according to HF phenotype and sex. Lower BMI is a consistent adverse marker in HFrEF in both sexes and shows a borderline adverse association in women with HFpEF, whereas BMI is not prognostic in men with HFpEF. These findings highlight the importance of sex- and phenotype-specific interpretation of BMI in risk assessment.

Heart failure (HF) is a disease often preceded by other cardiac disorders, such as myocardial infarction (MI) and atrial fibrillation (AF). We aimed to evaluate whether the plasma protein profiles of three groups of patients with incident HF-HF with preceding MI, HF with preceding AF, and HF with no preceding MI or HF-would be similar, and whether a common protein profile across all three HF groups could be detected. We analysed data from 50 765 UK Biobank (UKB) participants with measurements on 2922 plasma proteins. Participants who developed HF after enrolment (12,6 years, median follow-up) were divided in those who, between enrolment and HF diagnosis, experienced a MI (MI-HF group, n = 269), developed AF (AF-HF, n = 519), or were not diagnosed with MI or AF (noMInoAF-HF, n = 1059). We estimate hazard ratios (HR) with 95% confidence interval (CI) for the associations between protein measurements and incident HF using multivariable adjusted Cox models. Proteins associated with the outcome across all three HF groups where further evaluated in relation to magnetic resonance-measured left ventricular ejection fraction (LV-EF) in 5097 UKB participants, and to echocardiography-measured diastolic E/A-ratio in 502 POEM study participants. After correction for multiple testing, 110 proteins were uniquely associated with HF in the noMInoAF-HF group, 21 proteins in the AF-HF group, and only one protein (ADGRG2) in the MI-HF group. Across all three HF groups, the same 60 proteins were significantly associated with HF, 13 of which were related to LV-EF and another 7 were associated with the E/A-ratio. LRRN1 was inversely associated with incident HF in the MI-HF group [HR 0.49 (95% CI, 0.36, 0.67)], the AF-HF group [0.51 (0.41, 0.63)], and in the noMInoAF-HF group [0.58 (0.50, 0.68)]; all remaining proteins were positively associated with HF. ADM was the top association in the MI-HF group [HR 5.19 (3.06, 8.78)] and the AF-HF group [7.78 (5.31, 11.41)]. The most significant enriched pathways for the 60 shared proteins were interleukin-10 signalling, transcription of death receptors, and TNF receptor binding. A plasma protein profile associated with heart failure independently of prior MI or AF was identified. This protein profile represents several pathophysiological pathways of interest, and some of these proteins were also related to either LV-EF or the E/A ratio. In addition, a number of proteins were found to be uniquely associated with only one of the three HF traits.

Heart failure (HF) affects 64 million people worldwide, yet updated global estimates of its incidence are lacking. Conduct a systematic review (SR) and meta-analysis to estimate the global incidence of heart failure and analyze its variations according to geographic region, sex, age, and clinical characteristics. A SR was performed in MEDLINE (PubMed), Scopus, EMBASE, and Web of Science (including SciELO) for observational studies published between 2000 and 2025 reporting HF incidence rates in the general population. Studies with recognized diagnostic criteria (Framingham, ESC, ACC/AHA) or standardized codifications (ICD) were included. The meta-analysis employed a random-effects model with the REML method. Subgroup analyses (sex, age, region, phenotypes) and meta-regression were conducted to explore temporal trends. Forty-two studies (2001-2025) from 18 countries were included, with 57% categorized as low risk of bias. The combined global incidence was 2.72 cases per 1,000 person-years (95% CI: 1.95-3.81), being higher in North America (6.06) than in Europe (2.65) and Asia (4.08). Incidence was higher in men (1.93) than in women (1.62), and substantially higher in the population >50 years (12.38). Meta-regression by publication year showed no significant temporal trend (p&#x2009;=&#x2009;0.255); however, when the midpoint of the data collection period was used, a significant declining trend was identified (p&#x2009;=&#x2009;0.009, R 2&#x2009;=&#x2009;23.75%). This meta-analysis provides updated global HF incidence estimates, revealing significant regional disparities and rates quadrupling in the population over 50 years. However, the pooled estimate is predominantly derived from high-income countries, limiting generalizability to low- and middle-income settings.

Natriuresis-guided diuresis has been investigated in prospective trials for acute heart failure (HF), but its impact on diuretic prescribing in clinical practice is uncertain. From September 2021, routine urine sodium measurement was implemented for all patients admitted with acute HF to our intensive cardiac care unit. We compared diuretic prescribing in 160 prospective post-implementation patients (up to April 2023) with 206 historical controls (from January 2020). Multivariable logistic regression evaluated the odds of aggressive diuretic use, defined as the upper tertile of total furosemide dose administered within the first 72 hours (&#x2265;340 mg). Propensity score matching on prespecified covariates created a balanced cohort for sensitivity analysis. The median age was 71 (IQR 60-80), with 252 (69%) men. Post-implementation, patients received higher median total furosemide dose at 72 hours (340 [180-525] mg vs. 220 [120-320] mg; p&#x202f;<&#x202f;0.001), and were more likely to receive aggressive diuresis (adjusted OR 4.8, 95% CI 2.86-8.25; p<0.001). Propensity score matching of 264 patients yielded consistent results (adjusted OR 5.2, 95% CI 3.004-9.46; p<0.001). At 72 hours, the post-implementation group had higher cumulative urine output (6,250 mL vs. 4,873 mL; p<0.001) and more frequent resolution of jugular venous distension (25% vs. 5%; p<0.001) and peripheral edema (14% vs. 5%; p=0.009), with no difference in pleural effusion (7% vs. 5%; p=0.550). Routine urine sodium measurement in acute HF patients in intensive care settings was associated with more aggressive diuretic use, increased diuresis, and more rapid improvement in congestion markers.

To externally validate an FDA-approved artificial intelligence (AI) tool for detecting heart failure with preserved ejection fraction (HFpEF) using echocardiographic video clips, comparing its performance to invasive haemodynamic criteria in a real-world referral cohort with unexplained dyspnoea. We retrospectively analysed 47 patients who underwent transthoracic echocardiography (TTE) and right heart catheterization (RHC), including 28 with both rest and exercise haemodynamics. The AI model evaluated apical 4-chamber video data and classified outputs as HFpEF, no HFpEF, or non-diagnostic, without any other clinical data. The primary outcome was invasively defined HFpEF: pulmonary capillary wedge pressure (PCWP) &#x2265;15&#x2005;mmHg at rest or &#x2265;25&#x2005;mmHg with exercise. Secondary analysis used a PCWP/cardiac output (CO) slope >2&#x2005;mmHg/L/min. We assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Among patients with exercise RHC (n = 28), 71% met haemodynamic HFpEF criteria. The AI tool demonstrated sensitivity of 30%, specificity of 88%, PPV of 86%, and NPV of 33%. Using the PCWP/CO slope (n = 25), specificity and PPV were 100%, sensitivity 27%, and NPV 16%. AI-positive patients had significantly higher resting PCWP (20 vs 15&#x2005;mmHg, P = .029), mean PA pressure (29 vs 24&#x2005;mmHg, P = .02), and PVR (2.1 vs 1.3 WU, P = .002). In patients with indeterminate H2FPEF scores (n = 25), the AI correctly identified 80% of those with invasively confirmed HFpEF. Model performance was consistent across TTE-RHC intervals <365 and <90 days. This AI model demonstrated high specificity and positive predictive value (PPV) for detecting HFpEF, reliably identifying patients with more advanced haemodynamic abnormalities. Its performance remained robust across variable intervals between transthoracic echocardiography (TTE) and right heart catheterization (RHC), and in patients with indeterminate clinical scores. Due to limited sensitivity, the tool is best utilized to enrich identification of patients with clearly abnormal haemodynamics rather than to exclude HFpEF, particularly in early or borderline cases. While broader use as a screening tool is promising, prospective validation studies are necessary to confirm its utility in general populations.

Metabolic-associated fatty liver disease (MAFLD) and heart failure with preserved ejection fraction (HFpEF) share overlapping metabolic and inflammatory pathways, yet HFpEF is frequently underrecognized due to atypical symptoms and complex etiology. We aimed to evaluate a domain-tuned large language model (MedGuide-14B) for HFpEF detection from electronic health records (EHRs) among patients with MAFLD, and to compare outcomes between model-identified and clinically recognized cases. In this multicenter retrospective cohort, MedGuide-14B was fine-tuned on large-scale clinical encounters and utilized to&#xa0;analyze structured EHR data including demographics, comorbidities, and laboratory tests, together with free-text clinical notes. Patients were classified as clinically diagnosed HFpEF, MedGuide-identified HFpEF (defined as probability &#x2265;0.70 based on ESC criteria), or non-HFpEF. Model performance was benchmarked against clinical diagnoses, and blinded validation was conducted for a prospectively sampled subset of MedGuide-identified cases. Outcomes included rehospitalization and mortality during follow-up. Among 24,011 patients with MAFLD, 3,049 (12.7%) had clinically diagnosed HFpEF, while MedGuide-14B additionally identified 4,226 (17.6%) previously undiagnosed cases, of which 90.4% were confirmed on blinded validation (&#x3ba;&#x2009;=&#x2009;0.85). For clinically diagnosed HFpEF, model performance achieved an AUC of 0.94, with a sensitivity of 95.0% and a specificity of 92.3%. Rehospitalization occurred in 67.2% of clinically diagnosed HFpEF, 55.6% of MedGuide-identified HFpEF, and 38.4% of non-HFpEF patients (P&#x2009;<&#x2009;0.001). At 48 months, cumulative all-cause mortality was 18.9%, 12.3%, and 4.6%, respectively, and cardiovascular mortality was 10.8%, 5.9%, and 1.5% (log-rank P&#x2009;<&#x2009;0.05). Applied to routine EHR data, a domain-tuned large language model substantially increased the detection of HFpEF among patients with MAFLD, identifying a sizeable and previously unrecognized subgroup at intermediate yet clinically meaningful risk. Embedding such a model into EHR workflows may enable earlier evaluation and targeted testing, although prospective validation across diverse settings is warranted.

Relationship between changes in cardiac function, functional capacity, and patient-reported health status in heart failure (HF) remains incompletely defined, which may help inform endpoint selection and clarify how distinct clinical domains reflect treatment response. This post hoc analysis of the randomized cardiac microcurrent (C-MIC) II trial, which evaluated the efficacy and safety of C-MIC therapy in patients with chronic HF with reduced ejection fraction on optimal guideline-directed medical therapy, included 65 ambulatory patients with non-ischaemic dilated cardiomyopathy, New York Heart Association (NYHA) Class III-IV symptoms, and baseline left ventricular ejection fraction (LVEF) 25-35%. Correlations between changes in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), 6-minute walk distance (6MWD), core lab-assessed LVEF (primary measure) and site-assessed LVEF, and peak oxygen uptake (peak VO2) were evaluated at 4 weeks, 2 months, 3 months, 4 months, and 6 months using Pearson coefficients with 95% confidence intervals (CI). The mean age was 60.0 &#xb1; 9.7 years and baseline LVEF was 29.8 &#xb1; 3.3%. Baseline 6MWD was 291.4 &#xb1; 61.6&#x2005;m and KCCQ-OSS was 42.6 &#xb1; 22.7. From baseline to 6 months, changes in KCCQ-OSS (n = 63) and 6MWD (n = 61) showed modest correlations with core lab-assessed LVEF (r = 0.39; 95% CI: 0.16-0.58; P = .0015 and r = 0.39; 95% CI: 0.15-0.58; P = .0022, respectively). Changes in KCCQ-OSS and 6MWD correlated strongly (n = 62; r = 0.63; 95% CI: 0.46-0.76; P < .0001). Changes in KCCQ-OSS and 6MWD did not correlate significantly with changes in peak VO2 (P = .06 and P = .30, respectively). Changes in LVEF and peak VO2 (n = 55) demonstrated modest correlation (r = 0.41; 95% CI: 0.16-0.61; P = .002). Baseline correlations with peak VO2 were weak to modest but increased at 6 months for LVEF (n = 59; r = 0.56; 95% CI: 0.35-0.71; P < .0001). In advanced HF, improvements in health status and submaximal functional capacity associate modestly with LVEF, while LVEF correlates more closely with peak VO2. Cardiac function, functional capacity, and health status represent related but distinct domains, supporting multidimensional assessment in HF trials.

Despite recent advances in pharmacological treatment, chronic heart failure (HF) is associated with significant morbidity and mortality, and further treatment options are needed. Intact nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signalling is a prerequisite of cardiovascular health. cGMP produced by NO/NO-sGC acts as a second messenger molecule via various downstream targets, which influence a broad spectrum of critical physiological parameters. Impairment of this cascade in the cardiovascular system is considered an important pathomechanism in HF. This review examines pharmacological therapies that act through the NO-sGC-cGMP signalling pathway. We will focus on the molecular mode(s) of action of NO-independent but haem-dependent sGC stimulators, and will examine evidence from preclinical studies demonstrating cardiovascular benefits of these therapies and their increasing number of effects on other susceptible tissues and organs, which together could contribute to clinical outcomes in HF. The sGC stimulator vericiguat may be considered, in addition to standard therapy, for adults with symptomatic HF with reduced ejection fraction (HFrEF) following a worsening event. The findings from pivotal clinical trials that led to these recommendations will be outlined and classified in terms of their significance for different subpopulations. These include the phase 3 VICTORIA and VICTOR trials. Finally, further research areas and ongoing studies designed to address existing gaps in our knowledge regarding vericiguat and related drugs will be highlighted.

This study evaluated the feasibility, acceptability, and clinical effectiveness of a home-based body water monitoring and preemptive management system using bioelectrical impedance analysis (BIA) in patients with heart failure (HF). In this multicenter, open-label, randomized controlled trial, 40 HF patients receiving loop diuretics were assigned to standard care or a home BIA group using a home-based BIA device with a linked application providing weekly feedback and guidance on diuretic management. Feasibility outcomes included study completion, adherence, usability and acceptability scores, and adverse events over 12 weeks. Effectiveness outcomes included changes in NT-proBNP, edema index, New York Heart Association (NYHA) functional class, HF hospitalization, and all-cause mortality. 39 patients were included in the final analysis after exclusion of one patient lost to follow-up in the control group. Patients in the control group were older than those in the home BIA group (70.4&#x2009;&#xb1;&#x2009;8.3 vs. 57.2&#x2009;&#xb1;&#x2009;13.5; P&#x2009;=&#x2009;0.003), and baseline NT-proBNP levels were higher (2737.1&#x2009;&#xb1;&#x2009;3817.1 vs. 1357.7&#x2009;&#xb1;&#x2009;2196.8&#x2005;pg/mL; P&#x2009;=&#x2009;0.013), while other baseline characteristics were comparable. In the home BIA group, the completion rate was 100.0% and adherence to BIA measurements was 82.5%. Acute kidney injury occurred in one patient (5.0%), with no discontinuations due to adverse events. Usability and acceptability were high (4.21&#x2009;&#xb1;&#x2009;0.59; 3.90&#x2009;&#xb1;&#x2009;0.53, respectively) on a 5-point Likert scale. There were no significant differences in changes in NT-proBNP or edema index during follow-up between groups. Worsening NYHA class occurred less frequently in the home BIA group (10.0% vs. 31.6%; P&#x2009;=&#x2009;0.095). Changes in the edema index correlated with changes in NT-proBNP (r&#x2009;=&#x2009;0.544; P&#x2009;=&#x2009;0.002), whereas changes in body weight did not (r&#x2009;=&#x2009;0.237; P&#x2009;=&#x2009;0.147). No HF hospitalizations or deaths occurred. Home-based BIA monitoring with preemptive management is feasible, acceptable, and safe for patients with HF.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiovascular outcomes in obesity and HFpEF; however, their safety and efficacy in heart failure with reduced ejection fraction (HFrEF) remain uncertain. We sought to evaluate the efficacy and safety of GLP-1 RAs in patients with HFrEF. We conducted a multicenter retrospective cohort study of adult patients with HFrEF (LVEF &#x2264;40%) between 2021 and 2024. Patients receiving semaglutide, tirzepatide, or liraglutide were compared with GLP-1RA-na&#xef;ve patients. Propensity score matching (PSM) (1:1; caliper 0.1) was conducted to balance demographics, comorbidities, LVEF, BMI, HbA1c, and guideline-directed medical therapy. Primary outcomes were 1-year all-cause mortality and acute decompensated HF (ADHF) hospitalizations. Secondary outcomes included new ACS, stroke/TIA, AF/flutter, and VT/VF events. A total of 127,021 patients met inclusion criteria. After PSM, 2,550 patients (n=1,275 per group) were analyzed (mean age 61.5 &#xb1;13 years, 33.5% female, 66% White, mean HbA1c 8.1 &#xb1;2.1%, mean LVEF 30 &#xb1;8.7%, mean BMI 34.5 &#xb1;8.4 kg/m2). Patients prescribed GLP-1 RAs had a lower risk of all-cause mortality (7.1% vs 10.2% OR: 0.68, 95% CI: 0.51-0.90; p=0.006). Time-to-event analysis was also consistent (matched HR: 0.54 [95% CI: 0.41-0.7]; p<0.0001). Patients in the GLP-1 RA group also had a lower risk of ADHF (27.7% vs 32.8% OR: 0.79 [95% CI: 0.66-0.93]; p=0.005). New onset ACS, stroke/TIA, AF/flutter, and VT/VF events were similar in both groups. In this real-world cohort, GLP-1RA therapy in HFrEF was associated with reduced mortality and ADHF without an increase in arrhythmic events. Prospective randomized trials are needed to validate these findings.

Inotropic therapy is a cornerstone of medical treatment for patients with low-output heart failure (HF). We aimed to investigate the quantitative effect of specific inotropic drugs on invasive haemodynamics. This meta-analysis assessed the haemodynamic effects of dobutamine, levosimendan, and milrinone in patients with low-output HF. Only studies using invasive haemodynamic assessment were included. The primary outcome was the quantitative change in variables such as cardiac index (CI), pulmonary artery wedge pressure (PAWP), mean pulmonary artery pressure (mPAP), mean arterial pressure (MAP), pulmonary and systemic vascular resistance (PVR and SVR) before and after administration of each drug. Quality was assessed using the National Institutes of Health Quality Assessment Tool (NIH-QAT). A sensitivity analysis compared the effect on acute versus chronic HF populations. Twenty-six studies (n=1,888 patients) were included in the analyses. Based on the NIH-QAT checklist, 11 studies were at low risk of bias, 14 at moderate risk, and 1 at high risk. Meta-analysis showed that all the study drugs improved the haemodynamic variables assessed, without significant differences amongst them, except for MAP (p = 0.0486). Dobutamine and levosimendan caused a non-significant increase in MAP, while milrinone showed a trend toward a reduction in MAP (-3.46 (-7.27 to +0.35)). The heterogeneity across studies was high. In the sensitivity analysis, dobutamine improved CI more than levosimendan in patients with chronic HF. The use of inotropes improves haemodynamic status in patients with low-output HF, with no consistent superiority of one agent over the others. These findings support the current clinical practice of agent selection based on individual patient characteristics. Head-to-head trials in well-phenotyped HF populations are warranted to guide personalised inotrope use.

Early adjunctive therapy with intravenous acetazolamide in combination with loop diuretics has been shown to enhance decongestion in acute heart failure (AHF). However, patients receiving sodium-glucose cotransporter-2 inhibitors (SGLT2i) were excluded from previous acetazolamide trials, and the efficacy of this combination remains unknown. This study aims to evaluate the natriuretic and diuretic effects of acetazolamide in patients with AHF treated with intravenous furosemide and concomitant SGLT2i therapy. The SANDI study is a prospective, multicentre, observational study enrolling 64 patients hospitalized with AHF and clinical signs of congestion. All participants will receive intravenous loop diuretics and an SGLT2i within the first 24&#x2005;h of admission. If congestion persists 24&#x2005;h after SGLT2i initiation, intravenous acetazolamide will be administered up to 2 consecutive days. The primary endpoint is the change in natriuresis within the first 24&#x2005;h following acetazolamide administration. Secondary endpoints include changes in diuresis, body weight, ADVOR clinical congestion score, and ultrasound-based congestion parameters. The SANDI study will determine whether adding acetazolamide to intravenous furosemide and SGLT2i enhances early natriuresis and diuresis in patients with AHF and persistent congestion.

To build a comprehensive biobank integrated in the Swedish Heart Failure Registry (SwedeHF) comprising comprehensive clinomic data, proteomic, transcriptomic and genomic information in combination with clinical and diagnostic characteristics and additional ICD-code registry data. Blood and urine samples will be biobanked at SwedeHF registration with an optional second sampling after 6 months in patients with HF attending routine clinical visits at nine hospitals with access to healthcare integrated biobanking. Circulating and urine biomarkers will be investigated by proteomic, metabolomic, transcriptomic profiling, explored with genetic data. Sample size assessments were based on the BIOSTAT-CHF cohort and doubled to fulfil all aims targeting 5000 patients. The first 1348 enrolled patients were median 72 years, 30% females, 65% HFrEF and 11% HFpEF. Median NT-proBNP was 1240 (quartile 1-3; 470-2830) pg/mL. This was comparable to the 8506 patients with an index registration in SwedeHF during 2023 with 52% HFrEF and 20% HFpEF, age 75 years, 36% females and NT-proBNP 1560 [629-3617] pg/mL. We are building a high-quality detailed biobank linked to SwedeHF, the world's largest continuous HF registry, consisting of plasma, serum, whole blood and urine samples. The Biobank will enable studies exploring underlying disease mechanisms in HF and response to HF treatment, paving the way for precision medicine and novel drug targets. It will also generate a structure for biobanking in Registry-based Randomized Controlled Trials within the national SwedeHF registry. NCT06435585.

The traditional, hospitalization-centric composite endpoint of cardiovascular (CV) death or time-to-first heart failure (HF) hospitalization is increasingly misaligned with contemporary HF care and, as evidence-based therapies lower event rates over time, requires larger trials with longer follow-up. Improved survival, modern ambulatory pathways mean that a larger share of worsening HF is treated outside the hospital and that patients may experience recurrent worsening HF episodes. Relying on time-to-first hospitalization alone can therefore miss clinically relevant morbidity; recurrent-event approaches can offer additional power mainly when risk heterogeneity is high and treatment discontinuation after a first event is infrequent. To address this gap, we propose a standardized, adjudicated definition of worsening HF events informed by published consensus definitions, expanded to capture ambulatory events across care settings. Building on this definition, we recommend hierarchical primary endpoints that prioritize all-cause death with CV death evaluated as a secondary mortality outcome when prespecified and adjudicated, while robustly measuring morbidity through total adjudicated worsening HF events (first and recurrent), with validated patient-reported outcomes as additional hierarchical levels. We outline operational considerations for event capture and adjudication, including prioritized composite analytic approaches, and highlight safeguards to mitigate ascertainment bias and dilution by more subjectively defined events. Adoption of worsening HF -based hierarchical endpoints can better reflect the total disease burden, improve statistical power, and enhance interpretability across evolving care models.