BACKGROUND:Effective decongestion is a key therapeutic goal during hospitalisation for acute heart failure (HF), but the clinical significance of intravenous loop diuretic-induced weight loss and its relationship with biomarker changes remain uncertain. METHODS:We included patients hospitalised for HF in the nationwide Swedish Heart Failure Registry (2017-2021) who received intravenous loop diuretics, survived to discharge and had body weight recorded at admission and discharge. Weight loss was defined as ≥2 kg between admission and discharge. Associations between weight loss, changes in biomarkers (estimated glomerular filtration rate (eGFR), N-terminal pro-B-type natriuretic peptides (NT-proBNP), haemoglobin, sodium and potassium) and outcomes were evaluated. The primary outcome was rehospitalisation for HF (re-HHF); the secondary outcome was the composite of cardiovascular death or re-HHF at 30 days and 1 year. RESULTS:Among 4979 patients (median age 80 years; 57% male), median weight change during hospitalisation was -2.5 kg and 2949 (59%) achieved weight loss ≥2 kg. Male sex, atrial fibrillation, obesity, higher admission NT-proBNP and mineralocorticoid receptor antagonist use were independently associated with weight loss. Weight change showed no meaningful association with change in eGFR. Weight loss was independently associated with a lower risk of re-HHF (HR 0.59, 95% CI 0.53 to 0.67) and the composite of cardiovascular death or re-HHF (HR 0.76, 95% CI 0.69 to 0.84) within 30 days but not thereafter. These associations were consistent irrespective of biomarker changes, including worsening renal function. CONCLUSIONS:In this nationwide cohort of patients hospitalised for HF and treated with intravenous loop diuretics, diuretic-induced weight loss, a pragmatic marker of decongestion, was associated with improved short-term clinical outcomes without an accompanying decline in renal function and irrespective of biomarker changes, including worsening renal function.

BACKGROUND:Myeloperoxidase (MPO), a neutrophil-derived enzyme, is associated with oxidative stress and inflammation, which contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Bioactive MPO causes vascular dysfunction and accumulation of serum uric acid (SUA). We investigated the association of plasma MPO and SUA with echocardiographic variables in a populational setting. METHODS:This was a cross-sectional analysis of the fourth visit of the STANISLAS cohort (N=1677 participants, age 49±14 years, 48% male), a population of initially healthy individuals. Participants were divided into four groups according to median plasma MPO and SUA levels. Adjusted linear regression models were used to assess the relationship of plasma MPO and SUA with echocardiographic markers. RESULTS:Participants with high MPO and high SUA were older, had more diabetes, a higher body mass index, lower estimated glomerular filtration rate and higher systolic blood pressure. In multivariable regression analyses, compared with patients with low MPO and low SUA, they had decreased left atrial reservoir strain (mean±SE=-1.43±0.62, p=0.022), decreased mitral annular e' velocity (mean±SE=-0.60±0.16, p<0.001) and more impaired left ventricular systolic global longitudinal strain (mean±SE=0.50±0.23, p=0.029). In contrast, high MPO with low SUA was not associated with impaired diastolic function. CONCLUSIONS:In a population setting, high MPO and SUA, indicative of high bioactive MPO, were associated with early markers of diastolic dysfunction, suggesting a potential role of the MPO pathway in the early development of HFpEF.

Aims We investigated the prevalence of coronary microvascular dysfunction (CMD) and its association with severity of heart failure in patients with reduced or mildly reduced ejection fraction (HFrEF and HFmrEF).Method Patients with stable, symptomatic heart failure with left ventricular ejection fraction (LVEF) <50% were enrolled. Data collection included physical examination, blood samples, Kansas City Cardiomyopathy Questionnaire (KCCQ), carotid to femoral pulse wave velocity, echocardiography and adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR). A CFR <2.5 was used to diagnose CMD. Adjusted multivariable linear regression analysis with CFR as the dependent variable and adjusted multivariate logistic regression with CMD as the dependent variable were performed.Results A total of 125 patients were included, of whom 99 (79%) were men. The overall mean age is 73.4 (±7.5) years. In patients eligible for CFR (n=68, 54%), CMD was present in 45 (66%). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP), hsTroponin-T, lower KCCQ score, lower left and right ventricular and left atrial global longitudinal strain (GLS) (p<0.05). In multivariable linear regression, lower CFR was independently associated with reduced GLS, higher NTproBNP and hsTroponin-T. Furthermore, in adjusted logistic regression analysis, lower LVEF, reduced right ventricular GLS and higher biomarkers were independently associated with an increased risk of CMD.Conclusion CMD was present in 66% of patients with chronic heart failure and HFrEF or HFmrEF. Markers of more severe heart failure, including reduced GLS and higher NTproBNP and hsTroponin-T, were independently associated with lower CFR. Reduced right ventricular GLS and higher levels of the biomarkers were also independently associated with CMD.

AIMS:The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), together with the National Heart Failure Societies (NHFS), designed the European Heart Failure (HF) Survey with an aim of assessing contemporary HF epidemiology, management resources, availability and reimbursement of guideline-directed medications and devices, and structure of professional and patient organizations. This document presents data on HF epidemiology. METHODS AND RESULTS:The European HF Survey was conducted in 43 ESC member countries. Epidemiology data were exclusively collected from national health statistics from 2019, and standardized according to the European Standard Population, with variable response rates and data completeness among the countries. Median annual HF incidence was 3.9 patients per 1000 person-years (interquartile range [IQR] 3.1-6.5), and median HF prevalence was 1937 patients (IQR 1463-3416) per 100 000 population. Median in-hospital mortality of patients admitted for HF was 8.0% (IQR 4.9-9.6%), and median 1-year all-cause mortality of patients with HF was 14.5% (IQR 8.2-21.6%). Median number of HF-related hospitalizations was 333 (IQR 230-469) per 100 000 population, and median length of stay for HF-related hospitalizations was 8.5 (IQR 7.2-9.2) days. A heterogeneity in HF epidemiology statistics was observed across different countries. CONCLUSIONS:The European HF Survey provides a contemporary insight into HF epidemiology and outcomes across the ESC member countries. These data are valuable to inform strategies to improve prevention, diagnosis, and management of HF. The persisting gaps and considerable heterogeneity in epidemiology statistics highlight the need to further unify data collection and reporting practices across European countries.

Heart failure (HF) is characterized by increasing prevalence, high morbidity and mortality, poor quality of life, and substantial healthcare costs. Despite advancements in pharmacologic and device-based therapies, translating evidence from randomized controlled trials into clinical practice remains suboptimal. The Global Registries and Surveys Programme–Heart Failure (GRASP-HF) is a pan-European, snapshot, observational study, aiming at assessing the real-world implementation of evidence-based HF management. GRASP-HF captures both acute and chronic HF presentations to assess the adherence to the 2021 and 2023 European Society of Cardiology (ESC) HF Guidelines. It also serves as a platform for the accreditation of HF centres for the Improving Care through Accreditation and Recognition in Heart Failure (ICARe-HF) programme. This manuscript outlines the rationale, methodology, and design of GRASP-HF. Unlike previous registries, GRASP-HF ensures that all patients are consecutively enrolled over a pre-defined 2-month period, minimizing selection bias. GRASP-HF offers a real-time perspective on diagnostic strategies, use of guideline-recommended medical therapy and implementation of quality-of-care indicators. In addition, GRASP-HF addresses less explored domains by other registries, such as frailty, rare aetiologies (e.g. amyloidosis, genetic cardiomyopathies, Takotsubo syndrome), as well as non-fatal events during hospitalization and follow-up. GRASP-HF is also designed to inform ESC educational strategies and to benchmark progresses in HF care across European and non-European centres. In conjunction with ICARe-HF, annual repetition of GRASP-HF aims to facilitate continuous feedback between evidence, practice, and quality improvement. GRASP-HF will assist National Cardiac Societies in shaping national and institutional policies and will contribute with data-driven insights to future guideline development.

Abstract Background The diagnosis of pulmonary hypertension (PH) relies on measuring pulmonary artery pressures at right heart catheterization (RHC). Echocardiographic tricuspid regurgitation velocity (TRV) is a screening tool to define PH probability. While latest guidelines reduced RHC threshold for PH diagnosis, TRV thresholds were not. We aimed to update TRV thresholds for PH probability according to the novel RHC criteria. Methods Patients undergoing RHC for suspected PH were prospectively enrolled. A retrospective cohort was used for external validation. All patients underwent echocardiography and RHC within 6-hours under stable conditions. Results In the derivation cohort (n=400), 85% of patients had PH at RHC. However, only 68% had intermediate or high PH probability with the conventional 280 cm/s TRV threshold (76% sensitivity, 24% false-negative rate). The optimal threshold for low probability was 250 cm/s, with higher sensitivity (90%, 10% false-negative rate). In the validation cohort (n=1,348), 76% of patients had PH. In this cohort, the proposed 250 cm/s low probability threshold was confirmed to hold high sensitivity (97%, 3% false-negative rate). Conclusions This large multicenter derivation-validation study supports lowering the TRV threshold from ≤280 to ≤250 cm/s to decrease false-negative rate and missing referral to RHC in patients with suspected PH. Graphical abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition with high morbidity and mortality. Risk stratification of patients with HFpEF is important for advancing therapeutic development and improving clinical care. Research Question: Predicting overall mortality and heart failure (HF) Hospitalization in real world HFpEF population Aims : to leverage machine learning model to develop prognostic models based on real-world data, with the potential to support risk stratification in routine clinical practice Methods: CONFIDENT is an observational, multi-cohort study across three centers in Europe and the US. Patients with HFpEF, according to the HFA-PEFF criteria with ≥ 2 years of follow-up, were included from 2013 to 2022. The dataset included multimodal data from electronic health records, lab tests, echocardiography, and electrocardiography, with 82 baseline candidate variables. We developed machine learning-based prognostic models to predict all-cause mortality and HF hospitalization. Model performance was compared to conventional risk score in an external validation cohort. Results: A total of 1208 patients were included in the study. The mean age was 72±12. The 2-year risk of HF hospitalization and all-cause mortality ranged from 13 to 44% and 9 to 19% respectively. The all-cause mortality prognostic model achieved good discrimination with a C-index of 0.67 [95%CI, 0.66-0.68], and 0.68 [95%CI 0.66-0.69] in the training cohorts, and 0.72 [95%CI 0.65-0.78] in the validation cohort, and performed better than the PREDICT-HFpEF score (C-index: 0.66 [95%CI 0.65-0.68], p-value =0.012; 0.60, [95%CI 0.59-0.62],p-value < 0.01 and 0.67 [95%CI 0.58-0.73], p-value =0.013 respectively. Similar results were observed when compared to the Meta-Analysis Global Group In Chronic Heart Failure Risk Score (MAGGIC). Similarly, the model derived for HF hospitalization outperformed PREDICT-HFpEF and MAGGIC + natriuretic peptide. Conclusion: CONFIDENT prognostic models for all-cause mortality and HF hospitalization using routinely collected variables can reliably predict outcomes and facilitate personalized care and trial recruitment strategies in HFpEF.

Clinical endpoint classification (CEC)-that is, evaluation of clinical events using pre-defined criteria-is commonly conducted in clinical trial operations to ensure systematic and consistent assessment of endpoints needed to assess the intervention's safety and efficacy. This is particularly relevant for heart failure (HF) trials given the subjective decision-making around hospitalizations and variation in how worsening HF events are managed (both in hospital and in ambulatory settings). Several CEC strategies have been adopted to address the growing need for pragmatic clinical trials that enhance generalizability and minimize research burden on trial sites and patients. This review summarizes common CEC strategies including the traditional approach, investigator-reported endpoints, CEC using real-world data and CEC utilizing large language models. We summarize CEC strategies used in recent HF pragmatic trials and present challenges and considerations for CEC in HF pragmatic trials from the selection of clinical endpoints and data collection to CEC.

Background: New-onset postoperative atrial fibrillation or flutter (POAF) is a known complication following mitral valve surgery in patients with mitral valve prolapse (MVP) and mitral regurgitation (MR). Aim: To characterize the types, clinical correlates, and long-term outcomes of POAF in patients undergoing mitral valve surgery for degenerative MR. Methods: Patients with MVP and moderate or severe degenerative MR who underwent mitral valve surgery between 2010-2024 at Karolinska University Hospital were included. Data were extracted from electronic medical records, ECGs, and echocardiograms. Comprehensive outcome tracking was performed with no patients lost to follow-up. Patients were excluded if they had prior atrial fibrillation/flutter, mitral stenosis, rheumatic mitral valve disease, endocarditis, or prior mitral valve surgery. Cox regression was adjusted for age, sex, BMI, hypertension, hypercholesterolemia, diabetes, hemoglobin, prior PCI or CABG, eGFR, NYHA class, pulmonary hypertension, LVEF, and mitral valve repair vs replacement. Results: Among 786 patients, 49.7% developed POAF, 82.4% during the index hospitalization. Most events were paroxysmal 89.5%, persistent 6.1%, and permanent 4.3%. Patients with POAF were older, more often in NYHA class III-IV, had lower LVEF and elevated pulmonary artery systolic pressures compared to those without POAF. No differences were observed in preoperative left atrial volume index, MR severity, MVP etiology or anticoagulation use between the groups. Patients with POAF were less likely to have undergone mitral valve repair, had longer cardiopulmonary bypass and cross-clamp time, and more frequently underwent concomitant CABG or tricuspid valve intervention. During a median follow-up time of 4.4 years, POAF was independently associated with increased risk of heart failure hospitalization, permanent pacemaker implantation and mitral valve reoperation, Figure. There were no significant associations with endocarditis, stroke or all-cause mortality. Conclusions: POAF occurred in nearly half of all patients undergoing mitral valve surgery for degenerative MR, most commonly in paroxysmal form during the index hospitalization. POAF was associated with worse preoperative status, more complex surgical procedures, and significantly increased long-term risk of heart failure, pacemaker implantation and reoperation. These findings highlight the need for strategies to prevent and manage POAF in this high-risk population.

Background: Mitral valve prolapse (MVP) is associated with mitral regurgitation (MR), which can lead to adverse cardiac remodelling due to volume overload. In addition, mechanical stress from the prolapsing mitral valve may also induce replacement fibrosis. However, the type and extent of myocardial fibrosis across different MR severities remain poorly defined. Aim: To assess cardiovascular magnetic resonance (CMR) markers of myocardial fibrosis, including late gadolinium enhancement (LGE), indexed extracellular volume fraction (iECV), native T1, and native T2, in MVP patients stratified by MR severity. Methods: Patients with MVP undergoing 1.5T CMR at Karolinska University Hospital between February 2021–April 2025 were included. Imaging was performed to assess mitral annular disjunction, rule out primary cardiomyopathy, or as part of an ongoing CMR study involving MVP patients undergoing mitral valve surgery. Patients were excluded if they had ischemic heart disease, rheumatic mitral valve disease, mitral stenosis, previous mitral valve procedures, endocarditis or signs of primary cardiomyopathy. MR severity was defined by regurgitation fraction (RF) measured by CMR as mild (RF < 20%), moderate (RF 20–39%), and severe (RF ≥ 40%). Native T1 and T2 maps were acquired at rest, and post-contrast T1 maps was used to derive ECV(%) maps. iECV was calculated by multiplying ECV% by left ventricular (LV) end-diastolic myocardial volume indexed to body surface area. Replacement fibrosis was assessed by LGE. Ordinal logistic regression was adjusted for age, sex, hypertension, and diabetes. Results: A total of 127 patients with MVP were included. Of these, 32 (25%) had mild MR, 57 (45%) moderate MR and 38 (30%) severe MR. Characteristics associated with increasing MR were older age, male sex, atrial fibrillation, pulmonary hypertension, higher LVEF, and LV dilatation. iECV, native T1 and LGE increased progressively with MR severity (ORs 1.43, 95% CI: 1.23-1.65; 1.02, 95% CI: 1.01-1.03 and 2.16, 95% CI 1.05-4.39, respectively) (Figures 1, 2 and 3). No significant differences were observed in native T2 between groups. Conclusion: Greater MR severity in patients with MVP was associated with more extensive myocardial abnormalities, including both diffuse and replacement fibrosis. Future studies are needed to determine whether CMR can guide optimal timing of mitral valve surgery to prevent irreversible remodelling and improve clinical outcomes.

Background/Objectives: To assess the association between moderate N-terminal natriuretic peptide (NT-proBNP) and cardiac alterations and prognosis in septuagenarians without heart failure (HF). Methods: From the STROKESTOP II screening study, 230 individuals aged 75/76 years with NT-proBNP < 900 ng/L were randomly selected. Subjects with persistent atrial fibrillation (AF), more than mild valvular disease, or HF were excluded. Echocardiography was performed. NT-proBNP ≥ 125 ng/L and paroxysmal AF (pAF) on thumb ECG were used as grouping variables. Participants were followed up during a median of 5 years for cardiovascular mortality, HF, AF, and cerebrovascular events. Cox regression analysis was employed for prognostic assessment. Results: Three groups were identified: SR ≥ 125 (n = 94, no pAF and NT-proBNP ≥ 125 ng/L), pAF (n = 77, pAF and NT-proBNP ≥ 125 ng/L), and controls (n = 30, no pAF and NT-proBNP < 125 ng/L). NT-proBNP was not associated with structural (left atrial volume and left ventricular (LV) mass) or functional (E/e', LV strain) alterations in any group (p > 0.05). Cardiovascular risk factors (HR: 4.6; CI = 1.7-12.3; p = 0.002), but not NT-proBNP (HR: 1.9; CI = 0.7-5.1; p = 0.2), entailed a prognostic value for the composite endpoint of HF, AF, and cardiovascular death. Conclusions: In septuagenarians without HF, modest NT-proBNP elevation was not associated with echocardiographic changes or prognosis.