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Abstract Aims Recognizing the rising concern of environmental impacts on health, the study aims to explore how specific environmental factors such as air pollution, humidity, and temperature variations contribute to the prevalence of cardiovascular disease (CVD) mortality, emphasizing the role of air quality, climate variables, and lifestyle factors in the disease mortality specifically. Methods and results Analysis of province‐level data on CVD mortality in Turkey from 2010 to 2019, assessing the correlations with environmental and lifestyle factors like particulate matter, sulfur dioxide, meteorological variables, and smoking and alcohol consumption. The study employs the SAS TRAJ procedure and Ordinal Logistic Regression for statistical analysis. The multiplicity correction was done through Benjamini–Hoechberg false discovery rate (FDR) approach. As expected, both smoking and alcohol consumption were found to be significantly associated with CVD mortality (odds ratio (OR): 1.10, 95% CI: 1.08, 1.11, P‐value

Abstract Aims We aimed to determine the use of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and to identify clinical factors associated with their use in patients with heart failure (HF) in a real‐life setting. Methods Real‐world data on Empagliflozin and Dapagliflozin use in patients with HEART failure: The RED–HEART study is a multicentre, cross‐sectional and observational study that included HF patients in the outpatient setting regardless of ejection fraction from 19 cardiology centres between August 2023 and December 2023. Results The study population consisted of 1923 patients with HF, predominantly men (61.2%), with a median age of 66 (range: 19–101) years. Overall, 925 patients (48.1%) were receiving SGLT2is. Among the study population, 22.1% had HF with preserved ejection fraction, 21.5% had HF with mildly reduced ejection fraction, 56.4% had HF with reduced ejection fraction and the use of SGLT2is was 42.0%, 47.9% and 50.6% in each group, respectively (P = 0.012). The use of SGLT2is was 76.6% in patients with HF and diabetes, 19.8% in patients with HF and chronic kidney disease and 26.8% in patients without diabetes and chronic kidney disease (P

Abstract Aims Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre‐CS patients. Methods and Results The SEISMiC study is a multinational, multicentre, randomized, double‐blind, placebo‐controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre‐CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70–100 mmHg for at least 2 h] and clinically confirmed congestion, NT‐proBNP ≥1400 pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6 h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60 h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24 h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies. Conclusions The study results will contribute to our understanding of the role of istaroxime in pre‐CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) requires an efficient screening method. We developed a deep learning model (DLM) to screen HFpEF risk using electrocardiograms (ECGs). Methods and results A cohort study was conducted utilising data from Cohorts A and B. A convolutional neural network‐long short‐term memory (CNN‐LSTM) DLM was employed. HFpEF risk was determined by left ventricular end‐diastolic pressure (LVEDP) and clinical symptoms. The DLM was trained by ECGs. LVEDP for each patient was collected through invasive left ventricular catheterisation. Cohort A and B comprised data from individuals at high risk for HFpEF (LVEDP > 12 mmHg) and low risk for HFpEF (LVEDP ≤ 12 mmHg). The model was trained on Cohort A and prospectively validated on Cohort B. Results A total of 238 patients underwent ECG and left ventricular catheterisation for model training in Cohort A, and 117 patients for validation in Cohort B. The DLM achieved 78% accuracy in assessing HFpEF risk in Cohort A, while in Cohort B, it demonstrated 78% accuracy, 71.9% specificity, and 71.7% sensitivity. In the validation Cohort B, the DLM‐identified high‐risk HFpEF group exhibited significantly higher prevalence of diabetes (22.03%–11.86%, P

Abstract In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium–glucose co‐transporter‐2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up‐titration along with a close follow‐up with frequent clinical and laboratory re‐assessment after an episode of acute HF (the so‐called ‘high‐intensity care’ strategy) was associated with better outcomes in the STRONG‐HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP‐HFpEF‐DM and STEP‐HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH‐AHF supported the use of natriuresis‐guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.

Abstract Aims Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) have been widely demonstrated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization, regardless of left ventricular ejection fraction (LVEF). However, data on the extent to which rehospitalization is suppressed following HF hospitalization are limited. This study investigated the effects of SGLT2i on rehospitalization and cardiovascular death. Methods and results The OASIS‐HF study, a multicentre, prospective observational cohort study, enrolled 361 patients aged ≥75 years hospitalized for acute decompensated HF. The impact on composite events of HF rehospitalization or cardiovascular death and the number of annual rehospitalizations were evaluated between the conventional medical therapy and SGLT2i groups. The change in eGFR slope at the 1‐year mark after the initiation of treatment in both groups was also assessed. Over an average follow‐up period of 24.9 months, composite events occurred in 70 (35.4%) of the conventional therapy group and 36 (22.1%) of the SGLT2i group (log‐rank: P = 0.016). The average number of rehospitalizations for HF per year was 0.22 ± 0.13 vs. 0.14 ± 0.08, respectively (P = 0.019). The change in eGFR over 1 year was significantly slower in the SGLT2i group compared with the conventional group (−3.55 ± 8.46 vs. −1.42 ± 7.28 mL/min/1.73 m2, P = 0.025). Conclusions The SGLT2i are not only associated with the reduction of the composite events of HF rehospitalization or cardiovascular death and protect against worsening renal function but also with a decrease in long‐term repeated HF rehospitalizations.

Abstract Aims This study aims to develop and validate an optimal model for predicting worsening heart failure (WHF). Multiple machine learning (ML) algorithms were compared, and the results were interpreted using SHapley Additive exPlanations (SHAP). A clinical risk calculation tool was subsequently developed based on these findings. Methods and results This nested case–control study included 200 patients with chronic heart failure (CHF) from the China‐Japan Friendship Hospital (September 2019 to December 2022). Sixty‐five variables were collected, including basic information, physical and chemical examinations, and quality of life assessments. WHF occurrence within a 3‐month follow‐up was the outcome event. Variables were screened using LASSO regression, univariate analysis, and comparison of key variables in multiple ML models. Eighty per cent of the data was used for training and 20% for testing. The best models were identified by integrating nine ML algorithms and interpreted using SHAP, and to develop a final risk calculation tool. Among participants, 68 (34.0%) were female, with a mean age (standard deviation, SD) of 68.57 (12.80) years. During the follow‐up, 60 participants (30%) developed WHF. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), creatinine (Cr), uric acid (UA), haemoglobin (Hb), and emotional area score on the Minnesota Heart Failure Quality of Life Questionnaire were critical predictors of WHF occurrence. The random forest (RF) model was the best model to predict WHF with an area under the curve (AUC) (95% confidence interval, CI) of 0.842 (0.675–1.000), accuracy of 0.775, sensitivity of 0.900, specificity of 0.833, negative predictive value of 0.800, and positive predictive value of 0.600 for the test set. SHAP analysis highlighted NT‐proBNP, UA, and Cr as significant predictors. An online risk predictor based on the RF model was developed for personalized WHF risk assessment. Conclusions This study identifies NT‐proBNP, Cr, UA, Hb, and emotional area scores as crucial predictors of WHF in CHF patients. Among the nine ML algorithms assessed, the RF model showed the highest predictive accuracy. SHAP analysis further emphasized NT‐proBNP, UA, and Cr as the most significant predictors. An online risk prediction tool based on the RF model was subsequently developed to enhance early and personalized WHF risk assessment in clinical settings.

Abstract Aims This study aims to develop explainable machine learning models and clinical tools for predicting mortality in patients in the intensive care unit (ICU) with heart failure (HF). Methods Patients diagnosed with HF who experienced their first ICU stay lasting between 24 h and 28 days were selected from the Medical Information Mart for Intensive Care IV (MIMIC‐IV) database. The primary outcome was all‐cause mortality within 28 days. Data analysis was performed using Python and R, with feature selection conducted via least absolute shrinkage and selection operator (LASSO) regression. Fifteen models were evaluated, and the most effective model was rendered explainable through the Shapley additive explanations (SHAP) approach. A nomogram was developed based on logistic regression to facilitate interpretation. For external validation, the eICU database was utilized. Results After selection, the study included 2343 records, with 1808 surviving and 535 deceased patients. The median age of the study population was 70.00, with ~3/5 males (60.31%). The median length of stay in the ICU was 6.00 days. The median age of the survival group was younger than the non‐survival group (69.00 vs. 73.00), and non‐survival patients spent longer time in the ICU. Seventy‐five features were initially selected, including basic information, vital signs, laboratory tests, haemodynamics and oxygen status. LASSO regression determined the shrinkage parameter α = 0.020, and 44 features were chosen for model construction. The linear discriminant analysis (LDA) model showed the best performance, and the accuracy reached 0.8354 in the training cohort and 0.8563 in the testing cohort. It showed satisfying area under the curve (AUC), recall, precision, F1 score, Cohen's kappa score and Matthew's correlation coefficient. The concordance index (c‐index) reached 0.7972 in the training cohort and 0.8125 in the testing cohort. In external validation, the LDA model achieved approximately 0.9 in accuracy, precision, recall and F1 score, with an AUC of 0.79. Univariable analysis was performed in the training cohort. Features that differed significantly between the survival and non‐survival groups were subjected to multiple logistic regression. The nomogram built on multiple logistic regression included 14 features and demonstrated excellent performance. The AUC of the nomogram is 0.852 in the training cohort, 0.855 in the internal validation cohort and 0.770 in the external validation cohort. The calibration curve showed good consistency. Conclusions The study developed an LDA and a nomogram model for predicting mortality in HF patients in the ICU. The SHAP approach was employed to elucidate the LDA model, enhancing its utility for clinicians. These models were made accessible online for clinical application.

Abstract Aims Wild‐type transthyretin cardiac amyloidosis (ATTRwt CA) is a common, underdiagnosed cause of heart failure (HF) in the elderly. Concurrent extracardiac amyloid infiltration might be responsible for a specific frailty phenotype. This study aims to compare the prevalence and characteristics of frailty parameters in HF patients, with or without ATTRwt CA. Methods In a comparative cross‐sectional study, we prospectively included consecutive HF patients with or without ATTRwt CA (the HF + ATTRwt+ and HF + ATTRwt− groups, respectively) between April 2018 and April 2021. Logistic regression models were used to compare the groups with regard to frailty as assessed using multidimensional geriatric tools. Results We included 123 patients (68 HF + ATTRwt+ and 55 HF + ATTRwt−). The mean age was 80.9 (standard deviation 6.3) years, 87% were male, 34% had left ventricular systolic dysfunction and 34% were New York Heart Association (NYHA) III. Relative to the HF + ATTRwt− group, patients in the HF + ATTRwt+ group were more likely to have shrinking [odds ratios = 2.9 (95% confidence interval, 1.1 to 1.7), P = 0.03], balance disorders [1.8 (1.1 to 2.8), P = 0.02], memory complaints [2.5, (1.0 to 5.9), P = 0.05] and overactive bladder [1.5 (1.1 to 2.2), P = 0.03], independently of age, sex, NYHA class and diabetes status. The proportion of very frail patients was higher (albeit not significantly) in the HF + ATTRwt+ group than in the HF + ATTRwt− group [2.4 (0.9 to 6.9), P = 0.10]. Conclusions ATTRwt CA is associated with a specific frailty phenotype. Patients with ATTRwt CA should be screened for frailty and managed collaboratively by cardiologists and geriatricians, with a view to improving quality of life.

Abstract Aims Intra‐aortic balloon pump (IABP) devices are commonly used in patients with heart failure related cardiogenic shock (HF‐CS), including those with out‐of‐proportion right ventricular (RV) dysfunction. Pulmonary artery pulsatility index (PAPi) is a haemodynamic surrogate for RV performance. We aimed to assess short‐term haemodynamic changes in patients with HF‐CS following IABP support stratified by baseline PAPi. Methods and results This is a single‐centre study of 67 consecutive patients with HF‐CS who underwent IABP placement between 2020 and 2022. The primary aim was haemodynamic changes of specific variables on pulmonary artery catheter monitoring over 72 h following IABP placement. Secondary aims were clinically significant changes in diuretic regimens, changes in inotropes or vasopressors at 72 h following IABP, along with clinical outcomes. Prior to IABP placement, 57% of the total cohort (median age 59 years [48, 69], 31% female) had Society of Cardiovascular Angiography and Interventions Stage C HF‐CS. Thirty‐eight (56%) patients had a PAPi

Abstract Background There is conflicting evidence regarding whether heart failure (HF) increases the risk of developing cancer. Objective This study aimed to assess the association between HF and incident cancer, considering gender differences and HF phenotypes. Methods This retrospective study was conducted on data of adult individuals, free of cancer at baseline, from the First Affiliated Hospital of Wenzhou Medical University between January 2009 and February 2023. The patients with HF were categorized as HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). The primary outcome was incident cancer, including obesity‐related, tobacco‐related, lung, colorectal and breast cancers. Results Of 33 033 individuals enrolled, 16 722 were diagnosed with HF, including 10 086 (60.3%) with HFpEF and 6636 (39.7%) with HFrEF. During a median follow‐up period of 4.6 years (inter‐quartile range: 2.6–7.3), incident cancer was diagnosed in 10.5% (1707 patients) of the non‐HF group and 15.1% (2533 individuals) of the HF group. After adjusting for potential confounding factors, patients with HF had a 58% increased risk of cancer than those without HF [adjusted hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.48–1.69, P

Abstract Aims Incomplete decongestion due to lack of titration of diuretics to effective doses is a common reason for readmission in patients with acute decompensated heart failure (ADHF). The natriuretic response prediction equation (NRPE) is a novel tool that proved to be rapid and accurate to predict natriuretic response and does not need urine collection. However, the NRPE has not been externally validated. The goal of this study was to externally validate the discrimination capacity of the NRPE in patients with ADHF and fluid overload. Methods and results Patients admitted with ADHF who required intravenous loop diuretics were included. A spot urine sample was obtained ~2 h following diuretic administration, and a timed 6‐h urine collection by study staff was carried out. Urine sodium and urine creatinine from the spot urine sample were used to predict the 6‐h natriuretic response using the NRPE. The primary goal was to validate the NRPE to discriminate poor loop diuretic natriuretic response (sodium output

Abstract Aims Intravenous (IV) therapies have transformed the management of various cardiovascular conditions in ambulatory patients. However, uptake of these therapies in ambulatory care settings has several barriers. In this systematic scoping review, we aimed to identify the barriers and facilitators that influence the implementation of current IV therapies in ambulatory settings. Methods We searched MEDLINE, Embase and CINAHL databases from inception to September 2023 for studies on barriers and facilitators of IV therapy uptake in ambulatory patients. We classified the identified factors and performed a thematic analysis. Results Fifteen studies, primarily conducted in North America and Europe, were included. Methodologies varied, precluding quantitative synthesis. Key barriers were identified across several levels. At the medication level, barriers included the need for multiple vials and lengthy preparation. Patient‐level barriers included adverse effects, infections, painful venous access and non‐adherence. Clinician‐level barriers included understaffing, time constraints and safety concerns. Institutional barriers ranged from staff or equipment shortages to liability concerns and complex logistics. Healthcare system barriers included financial constraints and limited care delivery services. Facilitators included evidence‐based indications, patient education and comfort, staff experience, guidance documents, safe settings, favourable insurance policies and supportive guidelines. Conclusions As novel IV treatments emerge, addressing barriers and leveraging facilitators preemptively can enhance the successful implementation of IV therapies and improve clinical outcomes in ambulatory settings.

Abstract Aims Although left ventricular assist device (LVAD) implantation improves prognosis of advanced heart failure patients still suffer from impaired exercise capacity and quality of life (QoL). Exercise training may improve both; however, the available evidence about exercise training effects in LVAD patients remains inconclusive due to small and monocentric randomized controlled trials. This study aims to aggregate the individual participant data (IPD) to perform meta‐analysis on the safety and efficacy of exercise training on exercise capacity and QoL over standard care in LVAD patients. Methods Randomized controlled trials comparing exercise training and standard care (no supervised training) will be identified through database searching. Corresponding authors of eligible randomized controlled trials will be invited to share IPD. All IPD will be checked, recalculated to validate findings in initial reports, merged in a single dataset and stored in a secured encrypted database server. The merged IPD will be screened for quality, risk of bias, and heterogeneity of the included trials. Random effects meta‐analyses will be conducted using one‐stage and two‐stage approaches, in particular with a view to subgroup analyses. Results Based on findings of the individual randomized trials, we expected to obtain superior effects of exercise training on submaximal exercise capacity and QoL and similar effects on maximal aerobic capacity when compared with standard care. Conclusions Our study will be the first to harmonize IPD in meta‐analysis to demonstrate the effects of exercise training on exercise performance and QoL over standard care in LVAD patients. PROSPERO registration number CRD42023480119

Abstract Aims Baroreceptor activation therapy (BAT) is a promising new treatment strategy for patients with heart failure with reduced ejection fraction (HFrEF). It provides symptomatic relief, improvement in left ventricular function and reduction of cardiac biomarkers. Data regarding the long‐term effect of BAT on HFrEF are scarce. This retrospective, monocentric study aimed to assess long‐term outcome in patients who underwent BAT. Methods Patients with HFrEF who received BAT at Hannover Medical School between 2014 and 2023 were followed until the latest available follow‐up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow‐ups. Results Twenty‐three patients (mean age 66 ± 10 years, 83% male) with HFrEF were included in the study. Aetiology of heart failure was ischaemic in 70%. The majority of patients (96%) suffered from New York Heart Association (NYHA) III with a mean left ventricular ejection fraction (LVEF) of 23 ± 8% and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) of 2463 ± 2922 pg/mL. A complication occurred in one patient during BAT implantation (4%). The mean follow‐up was 3 ± 2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1 year, of which one patient remained in ameliorated NYHA for 7.5 years. Echocardiographic evaluation revealed significant improvement in LVEF by 9 ± 9% after 1 year (P

Abstract Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random‐effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1‐year all‐cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: −0.13 to 9.21). Meta‐regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1‐year all‐cause mortality, first HHF, and improved LVEF with IV iron therapy.

Abstract Aims Nutrition and inflammation status play a vital role in the prognosis of patients with heart failure (HF). This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a novel composite indicator of inflammation and nutrition, and short‐term mortality among critically ill patients with HF. Methods This retrospective study included 548 critically ill patients with HF from the MIMIC‐IV database. ALI was computed using body mass index, serum albumin and neutrophil–lymphocyte ratio. The primary endpoint was all‐cause in‐hospital mortality, and the secondary endpoint was 90 day mortality. Kaplan–Meier survival curve analysis with long‐rank test and Cox proportional hazards regression models were employed to assess the relationship between baseline ALI and short‐term mortality risk. The incremental predictive ability of ALI was evaluated by C‐statistic, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results The average age of 548 patients was 72.2 (61.9, 82.1) years, with 60% being male. Sixty‐three patients (11.5%) died in the hospital, and 114 patients (20.8%) died within 90 days of intensive care unit admission. The Kaplan–Meier analysis revealed that the cumulative incidences of both in‐hospital and 90 day mortality were significantly higher in patients with lower ALI (log‐rank test, in‐hospital mortality: P

Abstract Aims Cardiac implantable electrical devices such as cardiac resynchronization therapy with defibrillator (CRT‐Ds) or cardiac contractility modulation (CCMs) are therapy options for patients with symptomatic heart failure (HF) and reduced left ventricular ejection fraction (LVEF) despite optimal medical treatment. As yet, a comparison between both devices has not been performed. Methods and results The Mannheim Cardiac Resynchronization Therapy Registry (MARACANA) and the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) included all patients who received CRTs or CCMs in our medical centre between 2012 and 2021. For the present analysis, we retrospectively compared patients provided with either CRT‐Ds (n = 220) or CCMs with additional defibrillators (n = 105) regarding New York Heart Association classification (NYHA), LVEF, tricuspid annular plane systolic excursion (TAPSE), QRS‐width and other HF modification aspects after 12 months. Before implantation, CCM patients presented with lower LVEF (23.6 ± 6.2 vs. 26.3 ± 6.5%) and worse NYHA (3.03 ± 0.47 vs. 2.81 ± 0.48, both P 0.05), while the paced QRS‐width with CRT‐D after 12 months was lower than intrinsic values at baseline (157.5 ± 16.5 vs. 139.2 ± 16 ms, P

Abstract Aims Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. Methods and results From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2‐year follow‐up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow‐up paths, as well as specific end‐stages conditions of the disease. Finally, we conducted a 5‐year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n = 527) and external (n = 777) populations. We analyzed 4876 patients (age = 63 [53–71], male gender n = 3973 (81.5%), NYHA class I–II n = 3576 (73.3%), III–IV n = 1300 (26.7%), LVEF = 33 [25.5–39.9], atrial fibrillation n = 791 (16.2%), peak VO2% pred = 54.8 [43.8–67.2]), with a minimum 2‐year follow‐up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end‐stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5‐year follow‐up for each study cohort cluster was successfully compared with those in the validation cohorts (R = 0.94 and R = 0.84, P

Abstract Aims Few studies have focused on the effect of torsemide versus furosemide after discharge on prognosis in patients with heart failure with preserved ejection fraction (HFpEF). This single‐centre retrospective real‐world study was conducted to evaluate the effect of torsemide versus furosemide after discharge on all‐cause mortality and rehospitalization for heart failure in patients with HFpEF. Methods Consecutive patients who were diagnosis with HFpEF after discharge between January 2015 and April 2018 at the First Affiliated Hospital of Dalian Medical University and who had been treated with torsemide or furosemide were included in this study. The primary outcome was all‐cause mortality. The second outcome was rehospitalization for heart failure. Results A total of 445 patients (mean age 68.56 ± 8.07, female 55%) were divided into the torsemide group (N = 258) or furosemide group (N = 187) based on the treatment course at discharge from the hospital. During a mean follow‐up of 87.67 ± 11.15 months, death occurred in 68 of 258 patients (26.36%) in the torsemide group and 60 of 187 patients (30.09%) in the furosemide group [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.57–1.15, P = 0.239]. Rehospitalization for heart failure occurred in 111 of 258 patients (43.02%) in the torsemide groups and 110 of 187 patients (58.82%) in the furosemide group (HR 0.64, 95% CI 0.49–0.85, P = 0.002). Conclusions Compared with furosemide, torsemide did not significantly reduce all‐cause mortality, but there was association between torsemide and reduced rehospitalization for heart failure in patients with HFpEF.

Abstract Aims Mitral transcatheter edge‐to‐edge repair (M‐TEER) is a valid treatment option for severe mitral regurgitation (MR), necessitating accurate risk stratification of M‐TEER candidates for effective patient selection, optimal periprocedural care and improved long‐term outcomes. The body mass index (BMI) is a simple and practical prognostic index, and the obesity paradox has been widely reported. Methods and Results Between April 2018 and June 2021, 2149 patients undergoing M‐TEER were registered in the prospective multicentre registry and classified into three groups: underweight (BMI

Abstract Aims Nocturnal hypoxaemic burden, quantified as time spent with oxygen saturation below 90% (T90), is an established independent predictor of mortality in heart failure (HF) with reduced ejection fraction. The prognostic value of T90 in HF with preserved ejection fraction (HFpEF) is unknown. This study aims to determine the association of T90 with adverse outcomes in HFpEF. Methods and results One hundred twenty‐six patients prospectively included from our specialised HFpEF outpatient clinic underwent ambulatory home sleep monitoring to obtain oximetry data, including T90. We investigated the association between T90 and a composite endpoint of HF hospitalisations or all‐cause mortality. Nocturnal hypoxaemic burden in this HFpEF population was high, with a median T90 of 13.7 min. In only 10 patients (7.9%), oxygen saturation was at no time point below 90%. After median 34 months [IQR 18.4–52.0] of follow‐up, 32 patients (25%) reached the composite endpoint. T90 was significantly associated with the composite endpoint, also after adjusting for potential confounders (HR 1.004 (95% CI 1.001–1.007, P = 0.019) per 1 min T90 increase or HR 1.265 (95% CI 1.061–1.488) per 1 h T90 increase). Patients with HFpEF in the highest T90 tertile (T90 ≥ 31.4 min) had a significantly higher event rate compared to patients in the lowest two T90 tertiles, with 19 (45%) versus 13 (15%) events, respectively (P

Abstract Aims In cardiac sarcoidosis (CS) patients, the benefit of cardiac resynchronization therapy (CRT) remains unclear. We sought to assess the short‐term and long‐term effects of CRT in CS patients with a range of left ventricular (LV) ejection fractions (LVEFs). Methods Consecutive CS patients with heart failure with reduced ejection fraction (HFrEF; LVEF ≤ 40%), mildly reduced ejection fraction (HFmrEF; LVEF 41%–49%) and preserved ejection fraction (HFpEF; LVEF ≥ 50) treated with CRT under the care of a tertiary UK centre between 2008 and 2023 were reviewed. CRT response was defined by >5% improvement in serial LVEF. The primary endpoint was a composite of all‐cause mortality, cardiac transplantation or unplanned hospitalization for decompensated heart failure. The secondary endpoint included ventricular arrhythmic events. Results Of the 100 patients enrolled (age 58 ± 10 years; 71% male), 63 had HFrEF, 17 had HFmrEF and 20 had HFpEF. After short‐term follow‐up (9.8 ± 5.4 months), HFrEF patients demonstrated significant LVEF response (P

Abstract Aims Limited evidence exists regarding the outcomes of cancer patients hospitalized with new onset acute heart failure (AHF). We assessed the in‐hospital mortality and 1 year outcomes of cancer patients admitted for new onset AHF, taking into account both past and active cancer status as well as cancer site. Methods We examined administrative data of adult patients hospitalized with a first episode of AHF from 2003 to 2018 in Lombardy, Italy. Patients were categorized based on their cancer history. The primary endpoint was in‐hospital mortality with secondary endpoints including 1 year all‐cause mortality and 1 year re‐hospitalization for AHF. Results Among 283 144 patients AHF hospitalizations, 55 145 (19%) involved patients with a history of cancer (60% past cancer, 40% active cancer). Both in‐hospital and 1 year mortality rates were higher among cancer patients compared with those without (9.3% vs. 6.4% and 34.9% vs. 22.3%, respectively; P

Abstract Aims This survey investigates natriuretic peptide (NP) testing in community and hospital settings, assessing awareness, accessibility, and utilization. Methods and results This investigator‐initiated survey, conceived within the HFA of the European Society of Cardiology, comprised 14 questions. It underwent validation and pilot testing to ensure question readability and online system functionality. The survey was accessible for 87 days, from 5 April 2023 to 1 July 2023 via a web platform. There were 751 healthcare professionals across 99 countries who responded. Of them, 92.5% had access to NPs testing in hospital whereas 34.3% had no access to NTproBNP in community settings. Access to point of care NP testing was uncommon (9.6%). Public insurance fully covered NPs testing in 31.0% of cases, with private insurance providing coverage in 37.9%. The majority (84.0%) of participants believed that the medical evidence supporting NPs testing was strong, and 54.7% considered it cost‐effective. Also, 35.8% found access, awareness, and adoption to be in favour of NPs testing both in hospital and community settings. Strategies to optimize NP testing involved regular guideline updates (57.9%), prioritizing NPs testing for dyspnoea assessment (36.4%), and introducing clinician feedback mechanisms (21.2%). Notably, 40% lacked a community‐based HF diagnostic pathway for referring high‐NP patients for echocardiography and cardiology evaluation. Conclusions This survey reveals NP awareness, access, and adoption across several countries. Highlighting the importance of community‐based early heart failure diagnosis and optimizing HF diagnostic pathways remains a crucial, unmet opportunity to improve patient outcomes.

Abstract Aims Dynamic alterations in cardiac DNA methylation have been implicated in the development of heart failure (HF) with evidence of ischaemic heart disease (IHD); however, there is limited research into cell specific, DNA methylation sensitive genes that are affected by dysregulated DNA methylation patterns. In this study, we aimed to identify DNA methylation sensitive genes in the ischaemic heart and elucidate their role in cardiac fibrosis. Methods A multi‐omics integrative analysis was carried out on RNA sequencing and methylation sequencing on HF with IHD (n = 9) versus non‐failing (n = 9) left ventricular tissue, which identified Integrin beta‐like 1 (ITGBL1) as a gene of interest. Expression of Itgbl1 was assessed in three animal models of HF; an ischaemia‐reperfusion pig model, a myocardial infarction mouse model and an angiotensin‐II infused mouse model. Single nuclei RNA sequencing was carried out on heart tissue from angiotensin‐II infused mice to establish the expression profile of Itgbl1 across cardiac cell populations. Subsequent in vitro analyses were conducted to elucidate a role for ITGBL1 in human cardiac fibroblasts. DNA pyrosequencing was applied to assess ITGBL1 CpG methylation status in genomic DNA from human cardiac tissue and stimulated cardiac fibroblasts. Results ITGBL1 was >2‐fold up‐regulated (FDR adj P = 0.03) and >10‐fold hypomethylated (FDR adj P = 0.01) in human HF with IHD left ventricular tissue compared with non‐failing controls. Expression of Itgbl1 was up‐regulated in three isolated animal models of HF and showed conserved correlation between increased Itgbl1 and diastolic dysfunction. Single nuclei RNA sequencing highlighted that Itgbl1 is primarily expressed in cardiac fibroblasts, while functional studies elucidated a role for ITGBL1 in cardiac fibroblast migration, evident in 50% reduced 24 h fibroblast wound closure occurring subsequent to siRNA‐targeted ITGBL1 knockdown. Lastly, evidence provided from DNA pyrosequencing supports the theory that differential expression of ITGBL1 is caused by DNA hypomethylation. Conclusions ITGBL1 is a gene that is mainly expressed in fibroblasts, plays an important role in cardiac fibroblast migration, and whose expression is significantly increased in the failing heart. The mechanism by which increased ITGBL1 occurs is through DNA hypomethylation.

Abstract Aims We aimed to create a predictive model utilizing machine learning (ML) to identify new cases of congestive heart failure (CHF) in individuals with diabetes in primary health care (PHC) through the analysis of diagnostic data. Methods We used a sex‐ and age‐matched case–control design. Cases of new CHF were identified across all outpatient care settings 2015–2022 (n = 9098). We included individuals 30 years and above, by sex and age groups of 30–65 years and >65 years. The controls (five per case) were sampled from the individuals in 2015–2022 without CHF at any time between 2010 and 2022, in total 45 490. From the stochastic gradient boosting (SGB) technique model, we obtained a rank of the 10 most important factors related to newly diagnosed CHF in individuals with diabetes, with the normalized relative influence (NRI) score and a corresponding odds ratio of marginal effects (ORME). Area under curve (AUC) was calculated. Results For women 30–65 years and >65 years, we identified 488 and 3240 new cases of CHF, respectively, and men 30–65 years and >65 years 1196 and 4174 new cases. Among the 10 most important factors in the four groups (divided by sex and lower and higher age) for newly diagnosed CHF, we found the number of visits 12 months before diagnosis (NRI 44.3%–55.9%), coronary artery disease (NRI 2.9%–7.8%), atrial fibrillation and flutter (NRI 6.6%–12.2%) and ‘abnormalities of breathing’ (ICD‐10 code R06) (NRI 2.6%–4.4%) were predictive in all groups. For younger women, a diagnosis of COPD (NRI 2.7%) contributed to the predictive effect, while for older women, oedema (NRI 3.1%) and number of years with diabetes (NRI 3.5%) contributed to the predictive effect. For men in both age groups, chronic renal disease had predictive effect (NRI 3.9%–5.1%) The model prediction of CHF among patients with diabetes was high, AUC around 0.85 for the four groups, and with sensitivity over 0.783 and specificity over 0.708 for all four groups. Conclusions An SGB model using routinely collected data about diagnoses and number of visits in primary care, can accurately predict risk for diagnosis of heart failure in individuals with diabetes. Age and sex difference in predictive factors warrant further examination.

Abstract Objective Heart failure with preserved ejection fraction (HFpEF) is a growing concern among the elderly population, significantly impacting morbidity and mortality rates. This study aimed to screen and investigate the characteristics and prognosis of early‐stage HFpEF in the elderly. Methods A total of 1789 community‐dwelling individuals aged over 65 from northern Shanghai were enrolled. According to American Heart Association (AHA) guidelines, participants were classified into four groups: HFpEF stage 0, HFpEF stage A, HFpEF stage B and HFpEF stage C. Major endpoints included major adverse cardiovascular events (MACEs), all‐cause death and cardiovascular death. Results After a mean follow‐up period of 7.10 ± 1.27 years, 1623 elderly subjects were included [HFpEF stage 0 (10.3%), HFpEF stage A (16.3%), HFpEF stage B (60.6%) and HFpEF stage C (12.8%)]. Patients with HFpEF stage A, HFpEF stage B and HFpEF stage C exhibited more MACEs than those in HFpEF stage 0 (P

Abstract Aims In clinical trials, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). We aimed to share our real‐world experience with the efficacy and safety of mavacamten in this patient population. Methods and results This retrospective, single‐centre study included patients with symptomatic oHCM from March 2023 to November 2023. Inclusion criteria were oHCM, age >18 years, significant LVOTO (gradient >50 mmHg at rest or with Valsalva), New York Heart Association (NYHA) class ≥II despite maximally tolerated medical therapy, and left ventricular ejection fraction (LVEF) >55%. Patients were evaluated by echocardiography, NYHA class, electrocardiography and Holter monitor on each monthly visit for 3 months. A total of 31 patients were included in this study. The mean (SD) age was 58 (16.5) years, and 14 (45%) were female. Mean provoked left ventricular outflow tract gradient (LVOTG) reduced by −49.4 mmHg (P

Abstract Aims Heart failure with reduced ejection fraction (HFrEF) is a leading cause of death worldwide; thus, therapeutic improvements are needed. In vivo preclinical models are essential to identify molecular drug targets for future therapies. Transverse aortic constriction (TAC) is a well‐established model of HFrEF; however, highly experienced personnel are needed for the surgery, and several weeks of follow‐up are necessary to develop HFrEF. To this end, we aimed (i) to develop an easy‐to‐perform mouse model of HFrEF by treating Balb/c mice with angiotensin‐II (Ang‐II) for 2 weeks by minipump and (ii) to compare its cardiac phenotype and transcriptome to the well‐established TAC model of HFrEF in C57BL/6J mice. Methods Mortality and gross pathological data, cardiac structural and functional characteristics assessed by echocardiography and immunohistochemistry and differential gene expression obtained by RNA‐sequencing and gene‐ontology analyses were used to characterize and compare the two models. To achieve statistical comparability between the two models, changes in treatment groups related to the corresponding control were compared (ΔTAC vs. ΔAng‐II). Results Compared with the well‐established TAC model, chronic Ang‐II treatment of Balb/c mice shares similarities in cardiac systolic functional decline (left ventricular ejection fraction: −57.25 ± 7.17% vs. −43.68 ± 5.31% in ΔTAC vs. ΔAng‐II; P = 0.1794) but shows a lesser degree of left ventricular dilation (left ventricular end‐systolic volume: 190.81 ± 44.13 vs. 57.37 ± 10.18 mL in ΔTAC vs. ΔAng‐II; P = 0.0252) and hypertrophy (cell surface area: 58.44 ± 6.1 vs. 10.24 ± 2.87 μm2 in ΔTAC vs. ΔAng‐II; P

Abstract Aims The left bundle branch block (LBBB) is a strong predictor of response to cardiac resynchronization therapy (CRT). However, a significant number of patients do not respond to the treatment. The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St‐LBBB) on CRT response, hospitalizations, ventricular arrhythmia (VA) events and mortality. Methods This study is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided into two groups according to the fulfilment or not of St‐LBBB criteria. Results The study included 82 patients with ischaemic (ICM) and non‐ischaemic (NICM) cardiomyopathy [46 (56%) with St‐LBBB and 36 (44%) with non‐St‐LBBB]. Patients with St‐LBBB showed higher CRT response rates compared with those with non‐St‐LBBB (P

Abstract Background Heart failure (HF) is the leading cause of morbidity and mortality worldwide. Stemness refers to the self‐renewal and differentiation ability of cells. However, little is known about the heart's stemness properties. Thus, the current study aims to identify putative stemness‐related biomarkers to construct a viable prediction model of HF and characterize the immune infiltration features of HF. Methods HF datasets from the Gene Expression Omnibus (GEO) database were adopted as the training and validation cohorts while stemness‐related genes were obtained from GeneCards and previously published papers. Feature selection was performed using two machine learning algorithms. Nomogram models were then constructed to predict HF risk based on the selected key genes. Moreover, the biological functions of the key genes were evaluated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) pathway analyses, and gene set variation analysis (GSVA) and enrichment analysis (GSEA) were performed between the high‐ and low‐risk groups. The immune infiltration landscape in HF was investigated, and the interaction network of key genes was analysed to predict potential targets and molecular mechanisms. Results Seven key genes, namely SMOC2, LUM, FNDC1, SCUBE2, CD163, BLM and S1PR3, were included in the proposed nomogram. This nomogram showed good predictive performance for HF diagnosis in the training and validation sets. GO and KEGG analyses revealed that the key genes were primarily associated with ageing, inflammatory processes and DNA oxidation. GSEA and GSVA identified various inflammatory and immune signalling pathways that were enriched between the high‐ and low‐risk groups. The infiltration of 15 immune cell subsets suggests that adaptive immunity has an important role in HF. Conclusions Our study identified a clinically significant stemness‐related signature for predicting HF risk, with the potential to improve early disease diagnosis, optimize risk stratification and provide new strategies for treating patients with HF.

Abstract Background Sarcopenia is widely recognized as an age‐related syndrome that involves a progressive loss of skeletal muscle mass and muscle strength. Many studies have shown that sarcopenia is associated with disease severity and exercise intolerance, as well as an independent predictor of mortality in patients with chronic heart failure. However, there is little research on the impact of sarcopenia on patients hospitalized with acute decompensated heart failure (ADHF). Methods This is a prospective, multicentre, observational cohort study. Enrolment of at least 500 participants adults aged over 18 years hospitalized for ADHF is planned, with a minimum of 195 cases each for patients with and without sarcopenia. Each patient is followed up for 6 months, 1 year, 2 years or until the occurrence of endpoint. The primary clinical outcome is all‐cause mortality at 6 months. Other clinical outcomes of interest include cardiovascular mortality, all‐cause hospitalization, heart failure hospitalization and survival time from enrolment to event occurrence. The sympathetic nervous activity, psychosocial factors, quality of life, physical function, and physical activity will be assessed and recorded at baseline. This study will examine the correlation between sarcopenia and prognosis in different subgroups of patients, and explore the additive effect of different comorbidities and sarcopenia on prognosis in patients with ADHF. Conclusions This study will provide important information and evidence on the clinical aspects of sarcopenia in patients with ADHF, potentially contributing to accurate risk stratification and optimal clinical management for patients with ADHF. REGISTRATION: (URL: https://www.clinicaltrials.gov); Unique identifier: NCT06298825.

Abstract Aims Endogenous catecholamine release‐inhibitory peptide catestatin has been associated with heart failure (HF). This subgroup analysis of our cohort of HF compared the different effects of catestatin as a predictor for cardiac outcomes in patients with HF with reduced (HFrEF), mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction. Methods Plasma catestatin was measured in the HF patient cohort of 228 cases with a whole spectrum of ejection fraction. The cardiac deaths were analysed according to prespecified subgroups. Results Over a median follow‐up of 52.5 months, the association between plasma catestatin and cardiac death was different in patients with HFrEF, HFmrEF or HFpEF [hazard ratio (HR) 1.53, 95% confidence interval (CI) 0.99–2.37 and HR 2.73, 95% CI 1.56–4.75, respectively; interaction P = 0.022]. Patients with HFmrEF/HFpEF were older and more likely to be female, with non‐ischaemic cardiomyopathy and atrial fibrillation but lower levels of plasma B‐type natriuretic peptide (BNP). Similar adverse cardiac events occurred in patients with HFmrEF/HFpEF as in HFrEF. Plasma catestatin was a better predictor for cardiovascular death in the HFmrEF/HFpEF patients [area under the receiver operating characteristic curve (AUC) = 0.72, 95% CI 0.45–0.74] than in the HFrEF patients (AUC = 0.59, 95% CI 0.587–0.849). The optimal cut point of plasma catestatin level of 0.86 ng/mL predicted a 2.80‐fold elevated risk for cardiac death in HFmrEF/HFpEF. Conclusions Elevated plasma catestatin might be a more sensitive predictor for cardiac outcome in patients with HFmrEF/HFpEF than in HFrEF.

Abstract Aims Peripartum cardiomyopathy (PPCM) may result in a number of detrimental adverse cardiovascular events, notably persistent left ventricular ejection fraction (LVEF) reduction or even mortality. Imaging parameters on cardiac magnetic resonance (CMR) and their prognostic implications have rarely been perused in PPCM. We aimed to describe CMR's prognostic value in predicting poor left ventricular (LV) function recovery using late gadolinium enhancement (LGE) and T2‐weighted or T2 mapping. Methods and results PubMed, Europe PMC, and ScienceDirect were screened for studies on late gadolinium enhancement (LGE) and myocardial oedema using CMR and PPCM. The outcome of interest was poor LV function recovery, with a follow‐up period of at least 6 months. Comparisons between groups with the presence of LGE, myocardial oedema, and recovered against non‐recovered patients were pooled. A random‐effects model was employed to calculate the effect size. All pooled results were expressed as risk ratios (RRs) and 95% confidence intervals (CI). The area under the curve (AUC) was generated to test overall prognostic accuracy. Six cohort studies with 162 patients were included. The mean age of participants in this study was 30.6 years, and the majority of patients were diagnosed with PPCM after delivery. LGE was associated with a higher risk of poor LV function recovery, particularly when conducted at a later stage of disease (≥2.8 months) [RR = 2.83 (95% CI = 1.25–6.40); P = 0.001]. On the contrary, CMR conducted early (

Abstract Aims To investigate the association between the elapsed time to cardiology care following a primary care physician (PCP) referral and 1 year outcomes among patients with heart failure (HF). Methods Data from electronic medical records at our institution encompassing all PCP referrals to cardiology consultation from 2010 to 2021 (N = 68 518) were analysed. Of these, 6379 patients had a prior diagnosis of HF. Using a Cox regression model for hospitalization and mortality outcomes, the association between delay time in cardiology care post‐PCP referral and 1 year outcomes was examined, adjusting for age, gender and comorbidities. Results A significant increase in 1 year mortality rates with delayed cardiology care was observed for each day: all‐cause (0.25%), cardiovascular (CV) (0.13%) and HF (0.11%). In multivariate analysis, continuous delay to consultation was independently associated with higher risk of all‐cause [hazard ratio (HR): 1.02; 95% confidence interval (CI) (1.01–1.02); P 14 days). Conclusions Delay in cardiology assistance following a PCP referral among patients previously diagnosed with HF was associated with increased in all‐cause, CV, and HF mortality at 1 year.

Abstract Aims Prior evidence has shown a significant link between inflammation and the development of myocarditis. This study aimed to investigate the causal relationship between inflammation‐related genes (IRGs) and myocarditis. Methods and results In this study, the causal relationship between 167 IRGs and myocarditis were investigated using datasets from the Gene Set Enrichment Analysis and Integrative Epidemiology Unit open genome‐wide association study (IEU OpenGWAS) databases. The GWAS data (finn‐b‐I9 MYOCARD) contained single nucleotide polymorphisms (SNPs) data from 117 755 myocarditis samples (16 379 455 SNPs, 829 cases vs. 116 926 controls). Five algorithms [MR‐Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode regression] were employed for the MR analysis, with IVW as the primary method, and sensitivity analysis was conducted. Subcellular localization and protein–protein interaction (PPI) network analyses were performed for selected biomarkers. Results were verified in ebi‐a‐GCST90018882 (24 180 570 SNPs, 633 cases vs. 427 278 controls) and finn‐b‐I9 MYOCARD EXNONE (16 380 466 SNPs, 829 cases vs. 217 963 controls) to enhance reliability. Results IRF7 and ADORA2B were shown to be two exposure factors after screening. Univariable MR (UVMR) analysis revealed that IRF7 was a risk factor for myocarditis [IVW: odd ratio (OR) = 1.041, 95% confidence interval (CI) = 1.018–1.955, P = 0.039], while ADORA2B was a protective factors for myocarditis (IVW: OR = 0.799, 95% CI = 0.640–0.997, P = 0.047). Sensitivity analysis confirmed the robustness of these findings. Multivariable MR (MVMR) analysis further demonstrated a direct causal role of ADORA2B in preventing myocarditis. Subcellular localization analysis indicated predominant cytoplasmic expression and limited mitochondrial expression for both genes. The results of PPI analysis showed that 20 genes were predicted to be associated with IRF7 function, such as response to type I interferon, pattern recognition receptor signalling pathway, and toll‐like receptor signalling pathway. The results in finn‐b‐I9 MYOCARD EXNONE were consistent with MR analysis. Conclusions The findings indicated there was a causal connection between IRGs (IRF7 and ADORA2B) and myocarditis, which offered a crucial point of reference and guidance for future studies and myocarditis treatment.

Abstract Aims We aim to determine if our previously validated, diagnostic artificial intelligence (AI) electrocardiogram (ECG) model is prognostic for survival among patients with cardiac amyloidosis (CA). Methods A total of 2533 patients with CA (1834 with light chain amyloidosis (AL), 530 with wild‐type transthyretin amyloid protein (ATTRwt) and 169 with hereditary transthyretin amyloid (ATTRv)] were included. An amyloid AI ECG (A2E) score was calculated for each patient reflecting the likelihood of CA. CA stage was calculated using the European modification of the Mayo 2004 criteria for AL and Mayo stage for transthyretin amyloid (ATTR). Risk of death was modelled using Cox proportional hazards, and Kaplan–Meier was used to estimate survival. Results Median age of the cohort was 67 [inter‐quartile ratio (IQR) 59, 74], and 71.6% were male. The median overall survival for the cohort was 35.6 months [95% confidence interval (CI) 32.3, 39.5]. For AL, ATTRwt and ATTRv, respectively, median survival was 22.9 (95% CI 19.2, 28.2), 47.2 (95% CI 43.4, 52.3) and 61.4 (95% CI 48.7, 75.9) months. On univariate analysis, an increasing A2E score was associated with more than a two‐fold risk of all‐cause death. On multivariable analysis, the A2E score retained its importance with a risk ratio of 2.0 (95% CI 1.58, 2.55) in the AL group and 2.7 (95% CI 1.81, 4.24) in the ATTR group. Conclusions Among patients with AL and ATTR amyloidosis, the A2E model helps to stratify risk of CA and adds another dimension of prognostication.

Abstract Background Low muscle mass is associated with high insulin resistance and an increased risk of cardiovascular disease. This study aims to determine whether low muscle mass affects the alterations in myocardial substrate metabolism that are associated with the development of cardiovascular disease. Method The study included 299 individuals (182 men and 117 women) who underwent examination at the Severance Health Check‐up Center between January 2018 and February 2019. Myocardial glucose uptake was assessed using [18F]‐fluorodeoxyglucose‐positron emission tomography (18F‐FDG PET/CT) scanning. Direct segmental bioimpedance analysis was used to measure appendicular skeletal muscle mass (ASM). Results We analysed men and women separately owing to sex‐related body composition differences. ASM/Ht2 was significantly positively correlated with myocardial glucose uptake measured by 18F‐FDG PET/CT [ln (SUVheart/liver)] only in men (r = 0.154, P = 0.038 in men; r = −0.042, P = 0.652 in women, respectively). In men, myocardial glucose uptake was significantly associated with ASM/Ht2 even after adjusting for multiple confounders in a multivariable linear regression model (standardized β = 0.397, P = 0.004, in men; β = − 0.051, P = 0.698, in women). In women, age (β = −0.424 P = 0.029) was independent determinants of myocardial glucose uptake. Conclusions In men, ASM was strongly associated with myocardial glucose uptake as measured by 18F‐FDG PET/CT. In women, age was significantly correlated with myocardial substrate utilization, but not with ASM.

Abstract Aims Racial disparities exist in clinical outcomes for valvular heart disease (VHD). It is unknown whether clinician segregation contributes to these disparities. Among an adequately insured population, we evaluated the relationship between clinician segregation in a hospital and receipt of care by a cardiologist according to patient race. We also evaluated the association between clinician segregation, race and care by a cardiologist on 30‐day readmission and 1‐year survival. Methods and results Using Optum's Clinformatics® Data Mart Database (CDM, US commercial and Medicare beneficiaries) from 2010 to 2018, we identified patients with a primary diagnosis of VHD. Hospitals were categorized into low, medium and high segregation groups (SG), according to clinician segregation index (SI). SI can range from 0–1 (0: the ratio of Black to White patients is the same for all clinicians; 1: each clinician treats only Black or only White patients). Outcomes were analysed using generalized linear mixed effect models. Among 8649 patients [median age 75 (67–82), 45.4% female, 16.1% Black, 83.9% White], odds of care from a cardiologist did not vary across race for all SGs [Low SG adjusted odds ratio (aOR): 0.79 (95% CI: 0.58–1.08), P = 0.14; Medium SG aOR: 0.86 (95% CI: 0.60–1.25), P = 0.43; High SG aOR: 1.07 (95% CI: 0.68–1.69), P = 0.76]. Among those that received care from a cardiologist, there was no difference in the 30‐day readmission between Black and White patients across SGs [Low SG aOR: 1.05 (95% CI: 0.83–1.31), P = 0.70; Medium SG aOR: 1.22 (95% CI: 0.92–1.61), P = 0.17; High SG aOR: 0.81 (95% CI: 0.57–1.17), P = 0.27]. Among patients that did not receive care from a cardiologist, Black patients in low SG had higher odds of 30‐day readmission compared to White patients [aOR: 2.74 (95%CI:1.38–5.43), P

Abstract Aims Heart failure (HF) is a leading cause of mortality in patients with end‐stage renal disease (ESRD) undergoing haemodialysis. Identifying novel predictors of HF is essential for improving diagnostic precision and enhancing patient outcomes. Methods This study included 68 participants from the Haemodialysis Centre at the Second Hospital of Tianjin Medical University. Clinical characteristics and echocardiographic data were collected and analysed. We measured the plasma of 44 cytokines to investigate their correlation with cardiac function and their potential as HF biomarkers. Results In the HF with reduced ejection fraction (HFrEF) group, the levels of several cytokines, including stem cell growth factor‐β (SCGF‐β), C–X–C motif chemokine 10 (CXCL10), interleukin‐1α (IL‐1α), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), interleukin‐16 (IL‐16), interleukin‐1 receptor antagonist protein (IL‐1Ra), interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α), leukaemia inhibitory factor (LIF), C–C motif chemokine 3 (CCL3), interleukin‐10 (IL‐10), interleukin‐2 receptor subunit alpha (IL‐2Rα), tumour necrosis factor ligand superfamily member 10 (TNFSF10), macrophage colony‐stimulating factor (M‐CSF), granulocyte colony‐stimulating factor (G‐CSF) and stem cell factor (SCF), were significantly increased, while C–C motif chemokine 11 (CCL11)/eotaxin levels were decreased compared with those in the control group (P

Abstract Aims Diuretic resistance (i.e., insufficient diuretic and natriuretic response to an appropriate dose of intravenously administered loop diuretic) is a major cause of insufficient decongestion in acute heart failure (AHF). Early assessment of diuretic and natriuretic response already after the first administration of loop diuretic is currently recommended, but few data exist on the prevalence and characteristics of upfront diuretic resistance in AHF. The aim of this sub‐study of the P‐Value‐AHF randomized clinical trial was to investigate the prevalence and characteristics of upfront diuretic resistance in patients presenting with AHF in the emergency department (ED). Methods Consecutive patients presenting with a clinical diagnosis of AHF, ≥1 sign of congestion, and NT‐proBNP >1000 ng/L between February and June 2024 were prospectively screened. Loop diuretics were administered per protocol: 40 mg furosemide i.v. in diuretic‐naïve patients and those on oral torasemide

Abstract Aims Heart failure (HF) is characterized by a heightened risk of melanoma, which often metastasizes to the heart. The overlap pathology between HF and melanoma includes chronic low‐grade inflammation and dysregulation of inflammatory cancer‐associated fibroblasts (iCAFs). The impact of HF on iCAF‐driven tumour inflammation remains obscure. Methods and Results To identify critical genes for HF development, transcriptomic data (GSE57338) containing 313 clinical HF samples [136 healthy controls, 95 ischaemia (ISCH) and 82 dilated cardiomyopathy (DCM)] were analysed to screen differentially expressed genes (DEGs) and perform enrichment analysis. Fifty‐one DEGs in ISCH and 62 DEGs in DCM were identified with log2|fold change (FC)| ≥ 1 and P value ≤0.05. All these genes are involved in extracellular matrix organization, immune/inflammatory responses and Wnt signalling pathways. Then, the overall survival curves and prognostic models of DEGs in melanoma were evaluated. The correlation of gene expression with lymphocyte infiltration levels was assessed. Only aldehyde oxidase 1 (AOX1) and amphiregulin (AREG) maintained the same trend in melanoma as in HF, negatively affecting prognosis by regulating lymphocyte infiltration (log‐rank P value = 0.0017 and 0.0019). The potential drug molecules were screened, and the binding energies were calculated via molecular docking. Eniluracil, a known AOX1 targeting drug, was found to stably bind with AREG (hydrogen bond binding energies: −65.633, −63.592 and −62.813 kcal/mol). Conclusions The increased prevalence of melanoma in HF patients and its propensity for cardiac metastasis may be due to AREG‐mediated systemic low‐grade inflammation. Eniluracil holds promise as a therapeutic agent that may block AREG signalling, inhibiting the activation of iCAF mediated by regulatory T cell (Treg) and neutrophil.

Abstract Aims Socioeconomic deprivation is a risk marker for worse prognosis in patients with heart failure (HF), and a potential barrier to referral for advanced HF evaluation. The relationship between socioeconomic status (SES) and invasive haemodynamics in patients undergoing evaluation for advanced HF therapies is unknown. Methods We combined a consecutive clinical registry of patients evaluated for advanced HF with patient‐level data on SES (household income, education, workforce status, cohabitant status and distance from home to tertiary HF centre) derived from nationwide registries. Using this information, the cohort was divided into groups of low‐, medium‐ and high degree of socioeconomic deprivation. The associations between SES and invasive haemodynamics were explored with multiple linear regression adjusted for age and sex. Results A total of 631 patients were included. The median age was 53 years, and 23% were women. Patients in the highest income quartile versus the lowest (Q4 vs. Q1) were older (median age 57 vs. 50 years) and more often male (83% vs. 67%), both P

Abstract Aims Disease staging and prognostic scoring in wild‐type transthyretin‐related cardiac amyloidosis (ATTRwt‐CA) can be captured by two systems (NAC and Columbia scores). However, uncertainty remains as epidemiology of the disease is evolving rapidly. We evaluated features associated with staging systems across ATTRwt‐CA patients from different diagnostic pathways, and their association with prognosis. Methods We performed an analysis on DIAMOND patients with available data to evaluate NAC and Columbia score. DIAMOND was a retrospective study from 17 Italian referral centres for CA, enrolling 1281 patients diagnosed between 2016 and 2021, and aimed at describing characteristics of pathways leading to ATTRwt‐CA diagnosis. Of the original cohort, 811 patients were included in this analysis. Each patient had NAC and Columbia score calculated. Patients were grouped according to NAC and Columbia scoring classes. We described characteristics of patients according to staging classes and diagnostic pathways at diagnosis. Prevalence of early diagnoses, defined as NAC Ia, NYHA class I, no use of diuretics, no history of heart failure (HF) hospitalizations nor of atrial fibrillation prior to diagnosis, was investigated. Finally, prognostic variables were tested alone and grouped as NAC or Columbia scores in Cox univariate and multivariate regression analyses. Prognosis was investigated as all‐cause mortality, in the whole population and dividing patients in HF versus other diagnostic pathways. Results Only 1% of the study population had an early ATTRwt‐CA diagnosis. Distribution of prognostic variables and of NAC and Columbia classes was heterogeneous across diagnostic pathways. The prevalence of NAC III and Columbia III was higher in the HF diagnostic pathway, but all NAC and Columbia classes were present in all pathways. Both NAC and Columbia scores were associated with all‐cause mortality at univariate Cox regression analysis in the whole population, in patients from the HF diagnostic pathway and in those from other pathways. At multivariate analysis, Columbia score remained significantly associated with the outcome, together with age at diagnosis, left ventricular ejection fraction and maximal wall thickness. Conclusions In this contemporary nationwide cohort, an ATTRwt‐CA early diagnosis was very rare. Disease staging with NAC and Columbia scoring systems determined classes of patients with heterogeneous features. Both scores were significantly associated with mortality, but other variables also had prognostic significance.

Abstract Aims Chronic low‐grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM. Methods and results This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9 years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean = 15.2 ± 8.1%, median = 13.0%, IQR = 9.9%–18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)‐2, tumour necrosis factor (TNF)‐α and interferon (IFN)‐α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0 pg/mL, 3.1 vs. 3.9 pg/mL, 4.2 vs.4.7 pg/mL, respectively; all P

Abstract Aims Despite significant morbidity and mortality, recent advances in cardiogenic shock (CS) management have been associated with increased survival. However, little is known regarding the management of patients who survive CS with heart failure (HF) with reduced left ventricular ejection fraction (LVEF, HFrEF), and the utilization of guideline‐directed medical therapy (GDMT) in these patients has not been well described. To fill this gap, we investigated the use of GDMT during an admission for CS and short‐term outcomes using the Inova single‐centre shock registry. Methods We investigated the implementation of GDMT for patients who survived an admission for CS with HFrEF using data from our single‐centre shock registry from January 2017 to December 2019. Baseline characteristics, discharge clinical status, data on GDMT utilization and 30 day, 6 month and 12 month patient outcomes were collected by retrospective chart review. Results Among 520 patients hospitalized for CS during the study period, 185 (35.6%) had HFrEF upon survival to discharge. The median age was 64 years [interquartile range (IQR) 56, 70], 72% (n = 133) were male, 22% (n = 40) were Black and 7% (n = 12) were Hispanic. Forty‐one per cent of patients (n = 76) presented with shock related to acute myocardial infarction (AMI), while 59% (n = 109) had HF‐related CS (HF‐CS). The median length of hospital stay was 12 days (IQR 7, 18). At discharge, the proportions of patients on beta‐blockers, angiotensin‐converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)/angiotensin receptor/neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs) were 78% (n = 144), 58% (n = 107) and 55% (n = 101), respectively. Utilization of three‐drug GDMT was 33.0% (n = 61). Ten per cent of CS survivors with HFrEF (n = 19) were not prescribed any component of GDMT at discharge. Multivariable logistic regression adjusted for baseline GDMT use revealed that patients with lower LVEF and those who transferred to our centre from an outside hospital were more likely to experience GDMT addition (P

Abstract Aims We aim to explore the correlation between coronary artery calcification (CAC) score (CACS) and cardiac structure and function in chronic kidney disease (CKD) patients, create a clinical prediction model for severe CAC associated with cardiac ultrasound indexes. Methods and results The study included 178 non‐dialysis CKD patients who underwent CACS testing and collected general information, serological indices, cardiac ultrasound findings and follow‐up on renal function, heart failure (HF) manifestations and re‐hospitalization. The mean age of participants in the study cohort was 67.4 years; 59% were male, and 66.9% of patients had varying degrees of comorbid CAC. CKD patients with CACS > 100 were older, predominantly male and had a higher proportion of smoking, diabetes and hypertension (P