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

BackgroundDiagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, particularly in older adults. While the Heart Failure Association (HFA)-PEFF and H2FPEF Scores offer structured diagnostic approaches, their clinical utility is still debated. This study aims to compare the diagnostic accuracy of HFpEF Scores versus inclusion criteria used in sodium-glucose cotransporter-2 inhibitors (SGLT2i) trials, age-adjusted N-terminal pro B-type natriuretic peptide (NT-proBNP) thresholds and the universal definition of heart failure (HF).MethodsDiagnostic tools were assessed using sex-weighted and age-weighted propensity score adjustment in individuals aged 60–80 years from two established HFpEF cohorts (MEtabolic Road to DIAstolic Heart Failure (MEDIA), n=297; Karolinska-Rennes (KaRen), n=174) and two community-based cohorts without HF (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS), n=461; Malmö, n=1030).ResultsHFA-PEFF and H2FPEF Scores classified a large proportion of participants in both community-based cohorts (up to 81% in Malmö) and HFpEF cohorts (up to 75% in MEDIA) in the intermediate-likelihood category, requiring further diagnostic evaluation. Their diagnostic discrimination ranged from moderate to good. The universal definition of HF, SGLT2i trial criteria and NT-proBNP age-adjusted thresholds showed diagnostic performance comparable to HFA-PEFF Scores in the HFpEF cohorts and correctly excluded almost all individuals in the community cohorts. The universal definition of HF demonstrated a diagnostic discrimination higher than H2FPEF and comparable to HFA-PEFF, with the most balanced performance in terms of sensitivity and specificity.ConclusionsUsing scores, a substantial proportion of HFpEF individuals fall into the intermediate likelihood category, highlighting diagnostic uncertainty. Simpler tools, such as the universal definition of HF, demonstrate comparable or even superior diagnostic and rule-out performances for HFpEF, emphasising the need for more practical and reliable approaches to HFpEF diagnosis.

Abstract Background The use of intravenous (IV) diuretics in an outpatient setting may represent an alternative to conventional hospitalization. Our objective was to identify factors associated with diuretic response during ambulatory IV diuretic sessions in a population of advanced heart failure with no therapeutic project and a frequent flyer profile. Method All patients with 4-h IV diuretic sessions were analysed. An initial bolus followed a tailored protocol for continuous infusion based on the patient's baseline diuretic dose. Variables associated with diuresis and natriuresis following furosemide infusion were evaluated using mixed linear models. Results Seventy-six patients (mean age 75.4 years; LVEF 42.7%; eGFR 40.7 mL/min/1.73 m2) totalling 175 IV diuretic sessions were included. Mean diuresis was 1.0 L, natriuresis 92.6 mmol/L, and weight loss 610 grams. Baseline use of ACE inhibitors (+302 mL, P = 0.0005), eGFR (+160 mL per 10 mL/min/1.73 m2 increase, P < 0.0001), and addition of thiazide during the diuretic session (+238 mL, P = 0.0001) were associated with higher diuresis. Prior percutaneous mitral valve repair or chronic thiazide treatment was associated with lower diuresis. Baseline use of ACE inhibitors (+10.83 mmol/L, P = 0.018) was associated with higher natriuresis. Worsening renal function (>3 mg/L increase from baseline) and dyskalaemia 48 h after these sessions were uncommon (respectively 11% and 15%). Conclusions Ambulatory 4-h IV loop diuretic sessions induced a diuresis of approximately 1000 mL with a substantial sodium content, without causing significant complications. Addition of thiazide during the session increased diuresis and/or natriuresis, and could potentially be implemented to maximize the efficacy of ambulatory IV diuretic therapy.

Aims The prognostic value of ‘high dose’ loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). Methods and results All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into ‘low dose’, ‘intermediate dose’, and ‘high dose’ loop diuretics corresponding to furosemide equivalent doses of ≤40, 40–250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N‐terminal pro‐B‐type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for ‘low dose’, ‘intermediate dose’, and ‘high dose’ patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the ‘high dose’ group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six‐fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the ‘low dose’ group. ‘Intermediate doses’ were not significantly associated with these two outcomes in adjusted models (P > 0.05). Conclusions A ‘high dose’ of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre‐HT patients.

Aims The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non‐inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist. Methods and results All non‐inotrope patients (n = 837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The ‘warm‐dry’, ‘cold‐dry’, ‘warm‐wet’, and ‘cold‐wet’ profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12 months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P = 0.008). Taking the ‘warm‐dry’ category as reference, a significant increase in the risk of primary outcome was observed only in the ‘wet’ categories, irrespectively of ‘warm/cold’ status: hazard ratios, 1.50; 1.06–2.13; P = 0.024 in ‘warm‐wet’ and 1.77; 1. 25–2.49; P = 0.001 in ‘cold‐wet’. Conclusions Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. ‘Wet’ patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.

Aims Iron deficiency (ID) occurs in about 50% of patients with heart failure (HF). The European Society of Cardiology (ESC) recommends ID diagnostic testing in newly diagnosed patients with HF and during follow‐up, with intravenous iron supplementation (IS) only recommended in patients with HF with reduced ejection fraction (HFrEF). This study aimed to assess prevalence, clinical characteristics, and application of ESC guidelines for ID and IS in patients with HF in the real‐life clinical setting. Methods and results The French transversal multicentre OFICSel registry (300 cardiologists) conducted in 2017 included patients hospitalized for HF at least once in the previous 5 years. Diverse adult patients were eligible including inpatients and outpatients and those with acute and chronic HF. Data were collected from cardiologists and patients using study‐specific surveys. Data included demographic and clinical data, as well as HF and ID management data. Overall, 2822 patients, mainly male (69.3%) with a median age of 69 years (interquartile range 58–78), were included. A total of 1075 patients (38.1%) were tested for ID, with 364 (33.9%) diagnosed. Of these, 168 (46.2%) received IS: 128 (76.2%) intravenous IS and 40 (23.8%) oral. Among the 201 patients with HFrEF diagnosed with ID, 99 (49.3%) received IS: 79 (79.8%) intravenous IS and 20 (20.2%) oral. Conclusions In clinical practice, only one‐third of patients with HF had a diagnostic test for ID. In patients with ID with HFrEF, only 39.3% received intravenous IS as recommended. Thus, in general, cardiologists should be encouraged to follow the ESC guidelines to ensure optimal treatment for patients with HF.

Aims Despite regularly updated guidelines, there is still a delay in referral of advanced heart failure patients to mechanical circulatory support and transplant centres. We aimed to analyse characteristics and outcome of non‐inotrope‐dependent patients implanted with a left ventricular assist device (LVAD). Methods and results The ASSIST‐ICD registry collected LVAD data in 19 centres in France between February 2006 and December 2016. We used data of patients in Interagency Registry for Mechanically Assisted Circulatory Support Classes 4–7. The primary endpoint was survival analysis. Predictors of mortality were searched with multivariable analyses. A total of 303 patients (mean age 61.0 ± 9.9 years, male sex 86.8%) were included in the present analysis. Ischaemic cardiomyopathy was the leading heart failure aetiology (64%), and bridge to transplantation was the main implantation strategy (56.1%). The overall likelihood of being alive while on LVAD support or having a transplant at 1, 2, 3, and 5 years was 66%, 61.7%, 58.7%, and 55.1%, respectively. Age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.00–1.05; P = 0.02], a concomitant procedure (HR 2.32, 95% CI 1.52–3.53; P < 0.0001), and temporary mechanical right ventricular support during LVAD implantation (HR 2.94, 95% CI 1.49–5.77; P = 0.002) were the only independent variables associated with mortality. Heart failure medications before or after LVAD implantation were not associated with survival. Conclusion Ambulatory heart failure patients displayed unsatisfactory survival rates after LVAD implantation. A better selection of patients who can benefit from LVAD may help improving outcomes.

Acute-on-chronic heart failure (ACHF) currently represents the leading etiology of cardiogenic shock (CS). We aimed to assess the prognostic value of history of heart failure (HF) in patients with refractory CS as well as its effect on the benefit of moderate hypothermia (MH) (33–34 °C). Of the 334 patients included in the HYPO-ECMO trial, 321 (96 %) had available HF history information, among whom 65 (20 %) had prior HF. Inverse probability weighting (IPW) was used to compare ACHF patients and de-novo HF (DNHF) patients. Primary outcome was all-cause mortality at day 30. Main secondary outcomes were mortality and the composite of death, heart transplant, escalation to left ventricular assist device, or stroke up to day 180. At 30 days, 26 patients (40.0 %) died in the ACHF group versus 122 patients (47.7 %) in the DNHF group (crude risk difference (RD), −7.7 % [−21.0 to 5.7] p = 0.26; IPW RD, −11.6 % [−24.8 to 1.6] p = 0.084). Mortality (IPW RD, −13.7 % [−27.1 to −0.2], p = 0.047) and the composite outcome (IPW RD, −19.5 % [−32.9 to −6.1], p = 0.004) were significantly lower at day 180 in the ACHF group. Patients randomized to MH tended to have a lower risk for the primary outcome (RD -10.9 %, [−23.1 to 1.2], p = 0.078) and a significant reduction in composite outcome (p < 0.05 at each timepoint) in the DNHF group but not in the ACHF group, despite the absence of a significant interaction (p > 0.05). In VA-ECMO-treated CS, ACHF was associated with comparable 30-day survival but lower 180-day mortality and morbidity-mortality. In this exploratory post-hoc analysis, MH appeared to be associated with improved outcomes in DNHF patients only. ClinicalTrials.gov Identifier: NCT02754193 [Display omitted] •In refractory cardiogenic shock treated with VA-ECMO, prior heart failure (HF) was not associated to higher 30-day mortality.•Prior HF should not preclude the use of VA-ECMO in refractory cardiogenic shock patients.•Despite the absence of interaction with HF status, moderate hypothermia (MH) appeared to exclusively benefit patients with de-novo HF.•Further research is needed to identify patients who could benefit from MH in CS managed with VA-ECMO.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve outcomes in patients with heart failure (HF), and are recommended to be initiated in the 6 weeks following an HF hospitalization. We aimed to explore prescription rates and clinical benefits of SGLT2is among patients with newly diagnosed HF and reduced ejection fraction (HFrEF) in real-world practice. We conducted a retrospective analysis using the TriNetX Global Collaborative research network. Patients with HFrEF who experienced their first HF hospitalization between September 2021 and December 2023 were identified and were categorized into 2 groups based on the initiation of SGLT2is within 6 weeks following HF hospitalization. After using propensity score matching to baseline characteristics, Cox hazard ratios (HRs) were calculated to compare outcomes over a1-year period. Among the identified 70,042 patients with HFrEF, 21.3% were initiated on SGLT2is within 6 weeks following their first HF hospitalization. SGLT2i users were younger, more likely to be male and had a higher prevalence of diabetes, compared with SGLT2i non-users. After matching, 14,670 matched pairs were created (mean age 64 ± 17 years; 41.6% female; 20% Black). SGLT2i users vs. non-users had a lower risk of 1-year all-cause mortality (HR, 95%CI=0.75, 0.69 to 0.83), all-cause hospitalizations (HR, 95%CI=0.86, 0.83 to 0.91), and emergency department visits (HR, 95%CI=0.91, 0.86 to 0.96). In this large multinational real-world data of patients with HFrEF, the prescription rate for SGLT2is within 6 weeks after the first HF hospitalization remained low. However, SGLT2i initiation was associated with improved outcomes, underscoring the importance of guideline-recommended early use.

Abstract Background and Aims Semaglutide and tirzepatide have been shown to reduce body weight, improve health status, and lower rates of clinical events in patients with obesity and heart failure with preserved ejection fraction (HFpEF). Although recent data suggest that tirzepatide leads to greater weight loss compared to semaglutide in non-HF populations, it remains uncertain whether these different drugs might result in different clinical event rates. This study aims to compare the rates of clinical outcomes for semaglutide vs tirzepatide in patients with obesity and HFpEF. Methods In this non-randomized, observational cohort study, adults with obesity and a concurrent diagnosis of HFpEF who initiated treatment with semaglutide or tirzepatide for the first time between November 2023 and May 2025 were identified using electronic health record data from the TriNetX Global Collaborative Research Network. The primary endpoint was a composite of all-cause mortality and HF hospitalization, evaluated after propensity score matching (PSM). Results Among 3983 patients meeting the study criteria (semaglutide, 2719; tirzepatide, 1264), 1258 remained in each group after PSM (mean age 66 years, 41% male, 77% White, mean body mass index 42 kg/m², 63% with diabetes). Over a median follow-up of 24 weeks, semaglutide and tirzepatide were associated with a similar risk of the primary composite endpoint (HR 1.14 [95% CI, 0.89–1.46]; P = .286), and of its individual components (all-cause death: HR 1.24 [95% CI, 0.63–2.44]; P = .531; HF hospitalization: HR 1.10 [95% CI, 0.85–1.43]; P = .471), irrespective of diabetes status. Conclusions In this real-world analysis, no difference was observed between semaglutide and tirzepatide in terms of clinical outcomes among patients with obesity and HFpEF. Graphical Abstract Graphical Abstract Study design and key findings of the study. Patients were selected from the TriNetX network between 2023 and 2025, including individuals with obesity and HFpEF receiving treatment with either semaglutide or tirzepatide (left). A 1:1 propensity score–matched design was applied to balance demographic characteristics, BMI, laboratory values, comorbidities, and HF medications between treatment groups (middle). Over a median follow-up of 24 weeks, semaglutide and tirzepatide showed similar risks for the composite endpoint of all-cause death and HF hospitalization, with no differences in individual components or by diabetic status (right). Abbreviations: ACD, all-cause death; HFH, heart failure hospitalization; HFpEF, heart failure with preserved ejection fraction; PSM, propensity score matching; T2DM, type 2 diabetes mellitus.