ESC Heart Failure最新文献

Introduction: Natriuresis-guided diuresis has been investigated in prospective trials for acute heart failure (HF), but its impact on diuretic prescribing in clinical practice is uncertain.

Methods: From September 2021, routine urine sodium measurement was implemented for all patients admitted with acute HF to our intensive cardiac care unit. We compared diuretic prescribing in 160 prospective post-implementation patients (up to April 2023) with 206 historical controls (from January 2020). Multivariable logistic regression evaluated the odds of aggressive diuretic use, defined as the upper tertile of total furosemide dose administered within the first 72 h (≥340 mg). Propensity score matching on prespecified covariates created a balanced cohort for sensitivity analysis.

Results: The median age was 71 (interquartile range 60-80), with 252 (69%) men. Post-implementation, patients received higher median total furosemide dose at 72 h (340 [180-525] mg vs. 220 [120-320] mg; P < .001), and were more likely to receive aggressive diuresis (adjusted OR 4.8, 95% CI 2.86-8.25; P < .001). Propensity score matching of 264 patients yielded consistent results (adjusted OR 5.2, 95% CI 3.004-9.46; P < .001). At 72 h, the post-implementation group had higher cumulative urine output (6250 mL vs. 4873 mL; P < .001) and more frequent resolution of jugular venous distension (25% vs. 5%; P < .001) and peripheral oedema (14% vs. 5%; P = .009), with no difference in pleural effusion (7% vs. 5%; P = .550).

Conclusion: Routine urine sodium measurement in acute HF patients in intensive care settings was associated with more aggressive diuretic use, increased diuresis, and more rapid improvement in congestion markers.

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

Aims: Normothermic ex vivo heart perfusion (NEVHP) allows functional assessment and preservation of donor hearts, but the biological responses occurring during perfusion are not well characterized. This pilot study evaluated the feasibility of sequential biomarker monitoring during human cardiac NEVHP and described inflammatory, endothelial, and hemostatic responses over time.

Methods: This single-center, prospective, observational pilot study included five consecutive donor hearts preserved with the TransMedics Organ Care System (OCS) at the University Hospital of Rennes between March 2021 and January 2023. OCS use was indicated for expected cold ischemia >4 hours or surgical complexity. Perfusate samples were collected after priming (T0), at 10 minutes (T1), 60 minutes (T2), and before cooling (T3). Cytokines, chemokines, endothelial markers, and hemostatic factors were quantified by multiplex immunoassay and ELISA. Data were analyzed using linear mixed-effects models and expressed as fold-change versus T0.

Results: Donor median age was 44 years (IQR 36-50) and 60% male. All grafts were transplanted. Recipient mean age was 53±9 years and 20% female. Two of five (40%) developed severe primary graft dysfunction. Sequential sampling was successful in all perfusions. Inflammatory mediators rose during perfusion: at T3 versus T0, IL-8 increased 11.5-fold (95% CI 6.5-20.1), bFGF 8.4-fold (6.7-10.5), IL-6 4.5-fold (2.4-8.2), and MCP-1/CCL2 4.1-fold (2.6-6.6). IL-10 and TNF-α showed smaller increases (2.0- and 1.6-fold). Leukocyte counts remained stable (0.57×109/L at T0; fold-change 0.9). Endothelial markers showed activation without evidence of injury. Angiopoietin-2 increased 1.6-fold (1.2-2.1) and VEGF 2.0-fold (1.2-3.5), while angiopoietin-1, syndecan-1, soluble E-selectin, thrombomodulin, VEGFR2, PlGF, and vWF:Ag showed minimal or inconsistent changes. These trajectories are consistent with endothelial activation in the absence of glycocalyx shedding or structural disruption. Despite high heparin levels (median 6.9 IU/mL), low-grade hemostatic activation occurred. D-dimer increased 1.9-fold (1.3-2.7), fibrin monomer 2.2-fold (1.2-3.9), and soluble P-selectin 1.5-fold (1.1-2.0). Platelet counts declined to 0.8 (0.7-0.9) relative to baseline. Hematocrit decreased slightly (15.5% to 14.6%, fold-change 0.94), consistent with mild hemodilution.

Conclusions: Sequential biomarker monitoring during NEVHP was feasible and demonstrated inflammatory, endothelial, and hemostatic changes. These biological patterns require confirmation in larger cohorts, as potential tools for graft assessment and optimization of perfusion circuits and perfusate composition.

Aims: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition with high morbidity and mortality. Accurate risk stratification is important for advancing drug development and improving clinical care.

Methods and results: CONFIDENT is an observational, multi-cohort study across three centers in Europe and the US. Patients with HFpEF, according to the HFA-PEFF criteria with ≥ 2 years of follow-up, were included from 2013 to 2022. Data include electronic health records, lab tests, echocardiography, and electrocardiography. We developed machine learning-based prognostic models to predict all-cause mortality and heart failure (HF) hospitalization. Model performance was compared to validated risk score and validated in an external cohort.A total of 1208 patients were included in the study. The mean age was 72±12 and the mean BMI 32±9 kg/m2. The 2-year risk of HF hospitalization and all-cause mortality ranged from 13 to 44% and 9 to 19%, respectively. The all-cause mortality prognostic model achieved fair discrimination with a C-index of 0.68 [95% CI 0.62-0.74], and 0.71 [95% CI 0.64-0.78] in the training cohorts, and a good discrimination of 0.72 [95% CI 0.65-0.78] in the validation cohort, but performed better than the PREDICT-HFpEF score (C-index: 0.66 [95% CI 0.54-0.72], p-value = 0.006; 0.65, [95% CI 0.55-0.72], p-value < 0.001 and 0.67 [95% CI 0.59-0.73], p-value = 0.036, respectively). Similar results were observed when compared to the Meta-Analysis Global Group In Chronic Heart Failure Risk Score (MAGGIC). The HF hospitalization model also outperformed both comparators, including MAGGIC + natriuretic peptide.

Conclusion: CONFIDENT prognostic models for all-cause mortality and HF hospitalization using routinely collected variables can reliably predict outcomes and potentially facilitate personalized care and trial recruitment strategies in HFpEF.

Aims: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is widely used as an enrichment criterion in heart failure (HF) randomized controlled trials (RCTs), yet cut-offs vary. This study aims to provide evidence-based guidance on selecting NT-proBNP cut-offs to optimize the balance between event enrichment and screening failure across HF subgroups.

Methods: Using the Swedish HF Registry (SwedeHF), we applied NT-proBNP cut-offs from prior RCTs (200-5000 pg/mL) and calculated 1-year incidence proportions of a composite CV outcome (CV death or first HF hospitalisation) across subgroups by ejection fraction (EF), care setting (inpatient/outpatient), atrial fibrillation (AF), chronic kidney disease (CKD), and obesity. We quantified point and relative increases in event proportions and potential screening failure at each cut-off and identified optimal prognostic thresholds by maximizing Youden's index.

Results: Among 43,750 HF patients, median NT-proBNP was lower in HFpEF/HFmrEF vs HFrEF, outpatients vs inpatients, sinus rhythm vs AF, obese vs not obese, and patients without CKD vs with CKD (all p < 0.001). Higher NT-proBNP cut-offs increased 1-year composite CV proportions but excluded more patients. For example, In HFrEF outpatients, the 1-year proportion rose from 22.0% (no cut-off) to 24.3% at ≥600 pg/mL and 26.2% at ≥1,200 pg/mL, a 19% (95% CI:14.0-24.4) relative increase. Screening failure rose from 16.0% to 26.4% at these respective cut-offs. Optimal prognostic thresholds aligned with or exceeded subgroup median NT-proBNP values.

Conclusion: Higher NT-proBNP cut-offs were associated with increased event enrichment but also higher screening failure. These findings support the use of higher cut-offs currently used in HF RCTs and suggest that future trials should tailor NT-proBNP cut-offs to trial aims, balancing enrichment with enrolment feasibility and considering obesity and CKD in addition to EF and AF.

Background and aims: Peripartum cardiomyopathy (PPCM) is an idiopathic form of heart failure occurring in the peripartum phase. Elevated circulating levels of the senescence-associated-secretory-phenotype (SASP) factor Activin-A have been associated with heart failure severity in acute PPCM patients at baseline diagnosis. Here, we investigated Activin-A serum levels in the German PPCM registry in acute PPCM and during left ventricular (LV) recovery.

Methods and results: Clinical data including LV ejection fraction (LVEF) and Activin-A serum levels were assessed at initial diagnosis (baseline [BL]) and during follow-up (FU) at 3 months (M) and 6M in PPCM patients from the German PPCM Registry (n = 151, mean age 33 ± 5 years) compared to postpartum healthy controls (n = 27, mean age 32 ± 5 years). Activin-A serum levels at BL were elevated (404 pg/ml; interquartile range [IQR]: 197-815, n = 151) compared to healthy postpartum controls (240 pg/ml, IQR:148-446, n = 27; P < .01) and remained persistently elevated above postpartum healthy controls at 3 M (418 pg/ml, IQR: 169-806, n = 100) and 6M-FU (520 pg/ml, IQR: 214-1131, n = 104). Activin-A levels at BL did not correlate with LVEF (Spearman r  = 0.10, P = .2416, n = 139), NT-proBNP (r  = 0.096, P = .2766, n = 131), CRP (r  = -0.0008, P = .9933; n = 110) or PPCM biomarker plasminogen-activator-inhibitor-1 (PAI-1) (r  = 0.095, P = .3273, n = 109). The majority of PPCM patients showed LV recovery 6M after initial diagnosis, indicated by improved LVEF (PPCM BL: 25%, IQR: 20-33, n = 152; 6M-FU: 52% IQR: 45-56, n = 128, P < .0001). Activin-A levels did not differ between full or incomplete LV recovery, or between patients with hypertensive pregnancy disorders.

Conclusions: In PPCM patients from the German PPCM registry Activin-A serum levels were elevated at diagnosis, remained persistently high after 3M- and 6M-FU but were not associated with LV recovery.