ESC Heart Failure最新文献

{"title":"Poor cardiovascular outcomes of underweight abdominal obesity in the entire population of newly diagnosed heart failure.","authors":"Joongmin Kim, Sungyoun Chun, Jong-Kwan Park, Hancheol Lee, Ji-Yong Jang, Hyeongsoo Kim, Geunhee Park, Seung-Jin Oh, Se-Jung Yoon","doi":"10.1002/ehf2.15413","DOIUrl":"https://doi.org/10.1002/ehf2.15413","url":null,"abstract":"<p><strong>Aims: </strong>Body mass index (BMI) has been widely used as a simple tool for predicting cardiovascular risk. Here we aimed to analyse the distribution and cardiovascular outcomes according to BMI and waist circumference (WC) of the newly diagnosed heart failure (HF) patients in the entire population of the Republic of Korea for 10 years.</p><p><strong>Methods: </strong>A total of 999 127 patients newly diagnosed with HF between 2012 and 2021 among the entire population were included. The epidemiologic data of each subgroup according to BMI and WC were analysed, and cardiovascular outcomes were evaluated.</p><p><strong>Results: </strong>Over the decade from 2012 to 2021, the obese group accounted for 47.1% of the newly diagnosed HF population. Kaplan-Meier curve and hazard ratio of cardiovascular events in each subgroup revealed significantly increased rates of hospitalization, death from all causes, cardiovascular death, acute myocardial infarction, atrial fibrillation and composite cardiac events in the underweight group compared with other groups (P value < 0.05). The subgroups of abdominal obesity in normal, overweight and obese patients revealed significantly high hazard ratio in almost all cardiovascular events (P value < 0.05). Conversely, the overweight and obese groups without abdominal obesity showed the best cardiovascular outcomes. Increased cardiovascular risk was shown in groups with abdominal obesity even at the same BMI.</p><p><strong>Conclusion: </strong>The cardiovascular prognosis was significantly worse in the underweight group than in the obese group, especially in the underweight abdominal obesity group. Even in the same BMI group, the prognosis is worse in the group with abdominal obesity. For a more accurate cardiovascular prognosis analysis, it is necessary to use WC along with BMI.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of epicardial adipose tissue on myocardial function and structure in patients with severe aortic valve stenosis.","authors":"Judith Gronwald, Torben Lange, Sören J Backhaus, Bo E Beuthner, Ruben Evertz, Miriam Puls, Johannes T Kowallick, Karl Toischer, Gerd Hasenfuß, Andreas Schuster, Alexander Schulz","doi":"10.1002/ehf2.15422","DOIUrl":"https://doi.org/10.1002/ehf2.15422","url":null,"abstract":"<p><strong>Aims: </strong>Epicardial adipose tissue (EAT) is closely associated with the development of heart failure and adverse myocardial remodelling. In patients with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), increased EAT has been identified as a predictor of adverse outcomes; however, the underlying pathophysiological mechanisms remain unclear. This study aims to explore the effects of increased EAT volumes on myocardial remodelling and dysfunction in patients with severe AS.</p><p><strong>Methods and results: </strong>One hundred thirty-seven patients with severe AS (median age 80 years, 62% male) underwent cardiac magnetic resonance imaging (CMR) prior to TAVR. Myocardial volumes and function as well as EAT volumes were quantified from CMR acquisitions. The cohort was dichotomised at the median EAT volume. Patients with increased EAT volumes above the median (≥46.5 mL/m²) showed impaired left atrial (LA) reservoir strain (Es) as a distinct functional feature compared with patients with lower EAT volumes (11.8% [7.6-16.7] vs. 15.0% [10.9-19.1], P = 0.011), while left ventricular (LV) morphology and function (all P ≥ 0.216), right atrial and ventricular morphology and function (all P ≥ 0.090), as well as tissue characteristics (all ≥ 0.229) were similar between both groups. In a subgroup analysis of the four types of severe AS, the difference was most prominent in patients with low ejection fraction high-gradient AS. In multivariable regression analyses, EAT was independently associated with impaired LA Es, irrespective of co-morbidities, ventricular function, tissue characteristics and functional characteristics of AS.</p><p><strong>Conclusions: </strong>In patients with severe AS, increased EAT volume is independently associated with impaired LA function but not with other features of biventricular morphology, function or tissue composition. The incremental deterioration of LA function, in addition to the afterload imposed by AS in these patients, could increase vulnerability to heart failure and may require consideration as a therapeutic target beyond TAVR.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous vaccination against influenza and respiratory syncytial virus in high-risk heart failure patients.","authors":"Jan Biegus, Leszek Szenborn, Michał Tkaczyszyn, Robert Zymlinski, Gad Cotter, Michał Zakliczynski, Krzysztof Reczuch, Mateusz Guzik, Szymon Urban, Marta Rosiek-Biegus, Berenika Jankowiak, Gracjan Iwanek, Marta Wleklik, Marat Fudim, Piotr Ponikowski","doi":"10.1002/ehf2.15432","DOIUrl":"https://doi.org/10.1002/ehf2.15432","url":null,"abstract":"<p><strong>Background: </strong>There is a scarcity of prospective data on the impact of available vaccinations against respiratory viruses on hard clinical endpoints in patients with heart failure (HF).</p><p><strong>Aims: </strong>We investigated whether, in the population of high-risk HF patients, simultaneous vaccination against influenza and respiratory syncytial virus (RSV) improves outcomes during the subsequent infection season.</p><p><strong>Methods: </strong>We conducted a prospective, randomized, single-centre, open-label study in which patients with high-risk HF were randomized 1:1 to simultaneous influenza and RSV vaccination or standard of care (SOC). The primary composite endpoint comprised all-cause death, HF hospitalization (HFH) or clinical signs/symptoms of infection within a 6 month follow-up period (regular structured telephone interview). Secondary endpoints were components of the composite primary endpoint.</p><p><strong>Results: </strong>Two hundred twenty patients were randomized. During the follow-up period, the primary endpoint occurred in 59% of patients in the vaccination group versus 75% in the SOC group [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.48-0.92, P = 0.01]. Regarding the secondary endpoint analyses, during 6 month follow-up, 3% in the vaccination group died compared with 5% of patients in the SOC arm (HR 0.50, 95% CI 0.12 1.99, P = 0.32), and 18% versus 16% of study participants were hospitalized for HF in the two study arms, respectively (HR 0.86, 95% CI 0.45-1.62, P = 0.64). Infection occurred in 53% of vaccinated patients compared with 68% in SOC (HR 0.68, 95% CI 0.48-0.96, P = 0.03).</p><p><strong>Conclusions: </strong>In the population of high-risk HF, simultaneous vaccination against influenza and RSV reduced the incidence of the primary outcome. The effect was driven by a significant reduction in infections.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological issues in outpatient worsening heart failure research.","authors":"Karim Hnid","doi":"10.1002/ehf2.15438","DOIUrl":"https://doi.org/10.1002/ehf2.15438","url":null,"abstract":"","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'Letter to the editor: Epicardial, visceral and subcutaneous adipose tissue in heart failure with preserved ejection fraction'.","authors":"Ahmed Raza, Ahmad Furqan Anjum","doi":"10.1002/ehf2.15433","DOIUrl":"https://doi.org/10.1002/ehf2.15433","url":null,"abstract":"","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finerenone in diabetic chronic kidney disease-Real-world insights including patients with HFpEF or HFmrEF.","authors":"Kristian Hellenkamp, Sophia Kaebe, Miroslava Valentova, Stephan von Haehling, Fani Delistefani, Katja Gollisch, Dirk Raddatz, Ann-Kathrin Schäfer, Michael J Koziolek, Manuel Wallbach","doi":"10.1002/ehf2.15424","DOIUrl":"https://doi.org/10.1002/ehf2.15424","url":null,"abstract":"<p><strong>Purpose: </strong>Finerenone, a highly selective non-steroidal mineralocorticoid receptor antagonist, was approved for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (diabetic kidney disease, DKD). Finerenone reduced the composite endpoint of heart failure events and cardiovascular death in patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). This study aimed to investigate the safety and cardiac effects of finerenone in patients with DKD with or without HFpEF/HFmrEF in a real-world setting.</p><p><strong>Methods: </strong>Patients with DKD were prospectively enrolled and were treated with finerenone according to best clinical practice. Clinical, laboratory and echocardiographic assessments were performed before, 4 weeks and 6 months after starting finerenone.</p><p><strong>Results: </strong>Thirty-one patients with DKD were included. At baseline, patients had a typical risk profile with arterial hypertension (90.3%) and hyperlipoproteinemia (87.1%). Most patients were treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (93.5%). Treatment with finerenone was safe and well tolerated: after 4 weeks, the glomerular filtration rate decreased slightly from 52 (43-78) mL/min/1.73 m² to 48.0 (39.0-71.0) mL/min/1.73 m² (P = 0.002 vs. baseline), but stabilized thereafter. Similarly, the median potassium value increased from 4.2 (3.8-4.5) mmol/L to 4.4 (4.2-4.8) mmol/L (P = 0.017) after 4 weeks, but remained stable thereafter [4.4 (4.1-4.6) mmol/L (P = 0.079)]. Only one patient (3.2%) had an unplanned hospitalization and concomitant hyperkalaemia up to 6.0 mmol/L. HFpEF/HFmrEF was frequently found in patients with DKD (71.0%), although most patients had a rather early stage with only mild symptoms and a median N-terminal pro B-type natriuretic peptide (NT-proBNP) value of 150.8 (54.5-325.7) ng/L. During treatment with finerenone, NT-proBNP and left ventricular mass index (LVMI) remained stable. In contrast, left atrial volume index (LAVI) decreased from baseline [31.2 (26.8-39.7) mL/m²] to 4 weeks follow-up [29.7 (20.8-33.6) mL/m², P = 0.027] and decreased further after 6 months [26.6 (20.8-34.9) mL/m², P = 0.029]. In the subgroup of patients with HFpEF/HFmrEF, E/e' decreased from 11.9 (8.7-14.5) at baseline to 9.9 (8.0-12.4) after 6 months (P = 0.043).</p><p><strong>Conclusions: </strong>In a real-world setting, treatment with finerenone is safe and well-tolerated in patients with DKD and may improve functional and structural cardiac parameters. Further investigation is warranted.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographic region variation in patient characteristics, clinical outcomes and treatment of HFrEF in the VICTORIA trial.","authors":"Cynthia M Westerhout, Wendimagegn Alemayehu, Alain Cohen-Solal, Carolyn S P Lam, Justin A Ezekowitz, Stefano Corda, Ciaran J McMullan, Christopher M O'Connor, Paul W Armstrong","doi":"10.1002/ehf2.15416","DOIUrl":"https://doi.org/10.1002/ehf2.15416","url":null,"abstract":"<p><strong>Aims: </strong>Heterogeneity in demographics, aetiology, healthcare access and guideline-directed medical therapy (GDMT), and survival bias of patients with heart failure with reduced ejection fraction (HFrEF) is evident from international trials and registries. The current study examines conventional geographic variation in participants' phenotypes, standard of care, clinical outcomes and treatment effects of vericiguat versus placebo within the VICTORIA trial. We then evaluate an alternative approach to assessing the relationship between geographic variation in the efficacy of new therapeutics.</p><p><strong>Methods and results: </strong>Characteristics, standard of care and outcomes (time to first HF hospitalization (HFH) or cardiovascular death (CVD), time to first HFH and to CVD) of the 5050 participants from 42 countries and the effect of vericiguat versus placebo were analysed according to five prespecified geographic regions. Further examination of the study treatment effect according to country-level human development index (HDI) was undertaken to evaluate intra-regional variation. Notable inter-region differences existed in participant characteristics, standard of care at randomization and clinical outcomes. There was no modification of vericiguat's treatment benefit across geographic regions for the primary composite endpoint or its components. When examined by HDI, vericiguat's benefit on HFH and the primary composite was retained overall but attenuated as HDI rose (P_interaction = 0.009, 0.088, respectively). There was no apparent treatment effect modification due to HDI on cardiovascular death (P_interaction = 0.623).</p><p><strong>Conclusions: </strong>Geographic variation in the phenotype of patients with HFrEF, standard of care, and clinical outcomes was observed, while there was no intra-regional heterogeneity in vericiguat's treatment effect. However, when considering contextual/systemic measures via country-level HDI, further insights into treatment effect were revealed. Country-level measures may be helpful in the planning of future trials and in the translation of evidence into practice.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 inhibitors for the prevention and treatment of heart failure: A scientific statement of the HFA and the HFAI.","authors":"Marco Metra, Daniela Tomasoni, Marianna Adamo, Offer Amir, Stefan D Anker, Antoni Bayes-Genis, Michael Boehm, Javed Butler, Ovidiu Chioncel, Gerasimos Filippatos, Finn Gustafsson, Ewa A Jankowska, Juan Carlos Kaski, Brenda Moura, Mark C Petrie, Piotr Ponikowski, Amina Rakisheva, Arsen Ristic, Francois Roubille, Gianluigi Savarese, Petar Seferovic, Peter van der Meer, Maurizio Volterrani, Andrew J Coats, Vijay K Chopra, Giuseppe Rosano","doi":"10.1002/ehf2.15408","DOIUrl":"https://doi.org/10.1002/ehf2.15408","url":null,"abstract":"<p><p>In the 2021 European Society of Cardiology (ESC) heart failure (HF) guidelines, sodium-glucose cotransporter 2 (SGLT2) inhibitors were recommended for the prevention of HF in patients with type 2 diabetes mellitus (T2DM) and for the treatment of HF with reduced ejection fraction (HFrEF). Further trials showed efficacy of empagliflozin and dapagliflozin in patients with HF with preserved ejection fraction (HFpEF). These results prompted a broadened recommendation for the SGLT2 inhibitors dapagliflozin or empagliflozin across the whole left ventricular ejection fraction (LVEF) spectrum in the 2023 Focused Update of the ESC HF guidelines and in other international guidelines. In SOLOIST-WHF and EMPULSE, sotagliflozin (enrolling only patients with T2DM) and empagliflozin, respectively, were beneficial when initiated at the end or soon after an episode of decompensated HF. Based on these results and on the early appearance of their beneficial effects, the administration of SGLT2 inhibitors should start early in patients hospitalized for acute HF. Analyses after study drug withdrawal in randomized clinical trials have shown that their benefits may decline rapidly after discontinuation, and thus, persistence of treatment is advised. In EMPACT-MI, empagliflozin did not reduce the primary outcome of cardiovascular (CV) death/HF hospitalization but reduced first/recurrent HF hospitalizations. Potential benefits of SGLT2 inhibitors in further specific conditions (i.e., cardiac amyloidosis, grown-up congenital heart disease and paediatric patients with HF) have been reported in observational studies but need confirmation from prospective trials. This scientific statement summarizes current evidence regarding the effects of SGLT2 inhibitors for the prevention and treatment of HF.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early diagnostic value of novel biomarkers for breast cancer therapy-related cardiac dysfunction.","authors":"Zhengwei Wang, Yujuan Wu, Jingyi He, Diansa Gao, Zhong Zuo","doi":"10.1002/ehf2.15363","DOIUrl":"https://doi.org/10.1002/ehf2.15363","url":null,"abstract":"<p><strong>Aims: </strong>This study aims to (1) evaluate the diagnostic utility of myeloperoxidase (MPO), growth differentiation factor-15 (GDF-15), C-reactive protein (CRP), placental growth factor (PLGF) and galectin-3 (Gal-3) for cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients through meta-analysis and (2) investigate causal roles using Mendelian randomization (MR).</p><p><strong>Methods: </strong>We conducted a dual-phase analysis. First, a PRISMA-compliant (ID: CRD42023453369) meta-analysis of 12 studies (11 prospective cohorts, 1 RCT; 917 patients; age 50.4 ± 16.0 years; median follow-up 12 months) from five databases (PubMed/Web of Science/Embase/Cochrane/ClinicalTrials.gov) quantified post-treatment biomarker changes using weighted/standardized mean differences (WMD/SMD) and CTRCD risk via hazard ratios (HRs). Second, two-sample MR analysis leveraged MPO-associated single nucleotide polymorphisms (SNPs) to assess causality with heart failure (HF) and cardiomyopathy, employing IVW, MR-Egger, weighted median and simple mode methods with heterogeneity testing.</p><p><strong>Results: </strong>The meta-analysis demonstrated significant post-treatment elevations in: MPO [US patients: SMD = 0.78, 95% confidence interval (CI) 0.45-1.12; I² = 72%; P < 0.00001], GDF-15 (SMD = 0.64, 95% CI 0.24-1.05; I² = 77%; P = 0.002), PLGF (SMD = 0.87, 95% CI 0.10-1.63; I² = 95%; P = 0.03), and CRP (WMD = 0.83, 95% CI 0.46-1.20; I² = 18%; P < 0.0001). Subgroup analyses eliminated heterogeneity for GDF-15 (I² = 0%) and PLGF (I² = 0%), while partially reducing heterogeneity for MPO (I² = 72%). Elevated MPO levels predicted increased CTRCD risk in patients receiving cancer treatment (HR = 1.30, 1.10-1.54; I² = 0%; P = 0.002). MR analysis suggested causal relationships between MPO and both HF [odds ratio (OR) = 1.06, 95% CI 1.02-1.09; P = 0.001] and cardiomyopathy (OR = 1.09, 95% CI 1.02-1.17; P = 0.02), with significant heterogeneity detected in heart failure SNPs (Cochran's Q = 61.63, P = 0.04).</p><p><strong>Conclusions: </strong>Our study suggested that MPO was associated with both diagnostic biomarker profiles and mechanistic pathways in CTRCD pathogenesis. These preliminary findings highlighted MPO as a possible target for further investigation of early CTRCD detection in breast cancer patients.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble urokinase plasminogen activator receptor and outcomes in HFpEF: A TOPCAT ancillary study.","authors":"Christina G Hutten, Annika Tekumulla, Anis Ismail, Alexi Vasbinder, Theresa Farhat, Pennelope Kunkle, Sascha N Goonewardena, Ahmed Abdel-Latif, Bertram Pitt, Salim S Hayek","doi":"10.1002/ehf2.15423","DOIUrl":"https://doi.org/10.1002/ehf2.15423","url":null,"abstract":"<p><strong>Aims: </strong>Inflammation is postulated to be a key pathogenic mechanism in heart failure with preserved ejection fraction (HFpEF). Soluble urokinase plasminogen activator receptor (suPAR), a regulator of innate immune activity, is associated with incident heart failure; however, its role in HFpEF remains unclear. We aimed to elucidate the role of suPAR in HFpEF outcomes.</p><p><strong>Methods: </strong>In this secondary analysis of the TOPCAT trial's North American cohort, suPAR was measured at baseline and 1 year in a subset of patients with HFpEF (n = 406) treated with either spironolactone or placebo. We assessed the association between suPAR levels and adverse outcomes, whether spironolactone influenced suPAR levels and whether the association between spironolactone and outcomes is dependent on suPAR levels. The primary outcome was a composite of cardiovascular death, cardiac arrest or hospitalization for heart failure management.</p><p><strong>Results: </strong>The mean age of participants was 69.5 years, and 46.6% were female. After a median follow-up of 2.9 years, 19.9% experienced the primary outcome event. The 5-year cumulative incidence of the primary outcome in the highest tertile of suPAR (>3.93 ng/mL) was 44%, compared with 14% in the lowest tertile (≤2.94 ng/mL) (P = 0.001). Spironolactone did not significantly change suPAR levels at 1 year, nor was its effect on outcomes modified by baseline suPAR (P for interaction = 0.6). In multivariable analysis, each doubling of baseline suPAR levels was associated with nearly twofold increased risk of the primary outcome, independent of traditional risk factors and natriuretic peptide (NP) levels (HR 1.94 [95% CI 1.33-2.83]). suPAR's risk discrimination ability was superior and additive to that of NP.</p><p><strong>Conclusions: </strong>While suPAR levels independently predict poor outcomes in HFpEF patients, spironolactone does not modulate this inflammatory pathway. The findings suggest that suPAR represents a stable inflammatory biomarker in HFpEF, highlighting the need for further evaluation of targeted anti-inflammatory strategies in this population.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}