European Journal of Heart Failure最新文献

Heart failure (HF) remains a major global health challenge, characterized by high morbidity, mortality, and healthcare costs despite substantial advances in pharmacological, device-based, and structural therapies. Its increasing prevalence reflects population ageing, improved survival after myocardial infarction, and the rising burden of cardiometabolic disease, while growing clinical heterogeneity across the ejection fraction spectrum demands more precise diagnostic and therapeutic strategies. This state-of-the-art review summarizes contemporary HF evidence published in the European Journal of Heart Failure and ESC Heart Failure Journal, integrating recent advances in epidemiology, aetiology, diagnostics, and treatment. Emerging data underscore the role of multi-parametric biomarkers, advanced imaging, and artificial intelligence-based tools in enabling earlier diagnosis, refined risk stratification, and personalized management. Aetiology-specific insights-including hypertensive and ischaemic heart disease, cardiomyopathies, amyloidosis, and pregnancy-related HF-are reshaping clinical pathways and therapeutic decision-making. Major developments in guideline-directed medical therapy are reviewed, including early and intensive initiation strategies, expanding evidence for sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists across the spectrum of ejection fraction, and persistent gaps between trial evidence and real-world implementation. Advances in decongestion, cardio-renal interactions, structural valve interventions, and device-based monitoring further illustrate the evolving complexity of HF care. Despite an expanding therapeutic armamentarium, delayed diagnosis, underuse of evidence-based therapies, and organizational barriers continue to limit clinical impact. Bridging this implementation gap through earlier prevention, precision phenotyping, and integrated multidisciplinary care is essential to improving outcomes for HF patients.

Aims: The association between heart rate (HR) and clinical outcomes is well understood in patients with heart failure with reduced ejection fraction (HFrEF) but less clear in those with HFmrEF/HFpEF, especially among individuals with atrial fibrillation (AF). In a prespecified analysis of the FINEARTS-HF trial, we examined the association between baseline HR and clinical outcomes by heart rhythm and evaluated finerenone's effect across the spectrum of HR.

Methods: The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events. Heart rhythm (sinus rhythm or AF) was determined from the baseline ECG. Patients with pacemaker rhythm or missing HR/rhythm data were excluded.

Results: Among patients with sinus rhythm (SR n = 3497; 62%), higher baseline HR was associated with a higher incidence rate for the primary outcome. In patients with AF (n = 2190; 38%), no association between HR and outcomes was observed. The effect of finerenone on the primary outcome was consistent across the HR spectrum, regardless of rhythm (P for interaction = 0.96 in SR; 0.49 in AF). In patients with SR, there was no significant HR change with finerenone versus placebo. In AF patients, finerenone led to a small but statistically significant HR reduction: a placebo-corrected decrease of 1.35 bpm (95% CI: 0.41-2.29) from baseline to 12 months.

Conclusions: Among patients with HFpEF/HFmrEF in FINEARTS-HF, higher baseline HR was associated with a higher risk of the primary outcome in patients with SR but not in those with AF. Finerenone's effect on the primary outcome was consistent across the HR spectrum, irrespective of rhythm.

Trial registration: ClinicalTrials.gov NCT04435626.

Aims: Patients with heart failure and reduced ejection fraction (HFrEF) are frequently exposed to polypharmacy, placing them at risk of potentially inappropriate prescribing (PIP)-defined as use of drugs that may worsen HF prognosis, counteract guideline-directed medical therapies (GDMTs), or increase harmful interactions. The prevalence, predictors, and prognostic impact of PIP in HFrEF remain unclear. Therefore, the aim was to investigate the prevalence, predictors, and outcomes of PIP in a large, real-world HFrEF population.

Methods: Patients with HFrEF enrolled in the Swedish HF Registry (2005-20) were included. The European Society of Cardiology position statement of PIP-HFrEF was used to retrieve PIP from the National Prescribed Drugs Register. Associations between PIP and outcomes were assessed using Cox proportional hazards and negative binomial regression for recurrent events.

Results: Among 50 348 patients (median age 75 years, 29% female), 23 583 (47%) were prescribed ≥1 PIP. The most frequent agents were neuroleptics (29%), systemic steroids (10%), and NSAIDs (6%). Independent predictors included rheumatoid arthritis [odds ratio (OR) 3.39; 95% CI, 2.92-3.94], depression (OR 3.06; 95% CI, 2.74-3.42), chronic obstructive pulmonary disease (OR 1.86; 95% CI, 1.76-1.98), and gout (OR 1.48; 95% CI, 1.35-1.62). Patients on PIP were less likely to receive GDMT. Presence of ≥1 PIP was independently associated with increased 3-year risk of HF death (HR, 1.13; 95% CI, 1.04-1.23), all-cause and cardiovascular death, first and recurrent HF hospitalizations.

Conclusion: Nearly half of HFrEF patients received PIP medications, particularly those with multimorbidity, which was independently associated with worse outcomes and less GDMT use. Our data underscore the need for targeted strategies to reduce inappropriate prescribing in HFrEF.

Aims: Cardiogenic shock (CS) is often treated with catecholamines titrated to an adequate target mean arterial pressure (MAP) while minimizing adverse effects. We aim to assess the optimal catecholamine dose/MAP balance in heart failure-associated CS (HF-CS).

Methods: Patients with HF-CS were retrospectively enrolled from 16 tertiary centres in 5 European countries (2016-2021; NCT03313687). Dosage was quantified by inotropic scores (epinephrine, norepinephrine, and dobutamine). Associations of baseline and seven-day summarized dosage with intensive care unit (ICU) discharge (mixed-effects logistic regression) and 30-day mortality (Cox regression) were analysed. Potential catecholamine/MAP target ratios for optimized outcomes were assessed in models adjusted for age, sex, pH, lactate and prior resuscitation, stratified by centre.

Results: N = 704 patients: median age 63 years, 74% male, 34% post-resuscitation, median lactate 5.2 mmol/l. Of these, 53% were discharged from ICU, 48% died within 30 days. Higher inotropic scores independently predicted a lower probability of ICU discharge (baseline score: OR 0.78 [95%-CI 0.69-0.88]; summarized score: OR 0.46 [0.38-0.56]; both P < .001) and higher risk of 30-day mortality (baseline score: HR 1.27 [1.15-1.40], summarized score HR 1.83 [1.60-2.09]; both P < .001). A score/MAP ratio <0.403 µg/kg/min/mmHg was associated with higher ICU discharge odds (ceiling effect); a < 0.426 µg/kg/min/mmHg with lower 30-day mortality hazards (no ceiling effect). Lowering catecholamine doses by accepting reduced MAP targets was linked to better outcomes.

Conclusion: In HF-CS, higher catecholamine support independently associates with worse outcomes. Accepting lower blood pressure targets to reduce catecholamine dosage may improve outcomes. Validation in randomized controlled trials is urgently needed.

Aims: Given the emerging role of transcatheter valve repair in HFrEF patients with moderate/severe secondary mitral regurgitation (MR), we evaluated the prevalence and outcomes related to MR in the GALACTIC-HF trial.

Methods: The randomized GALACTIC-HF trial compared the efficacy and safety of omecamtiv mecarbil to placebo in 8232 patients with HFrEF, with a primary composite outcome of a first HF event or cardiovascular death.

Results: Of 7998 patients (97.2%) with baseline data on MR, 5782 (72.3%) had no MR, 970 (12.1%) had mild MR, and 1221 (15.3%) had moderate MR (only 25 had severe MR). Patients with moderate MR had a higher risk of the primary outcome than those without MR (adjusted HR 1.11; 95% CI 1.01-1.23); risk was not higher in patients with mild MR. The association between moderate MR and the primary outcome was most prominent in patients with less severe HF (milder NYHA class, higher LVEF, and lower N-terminal pro-B-type natriuretic peptide) compared to more severe HF. In adjusted analyses, MR was not associated with mortality, and the results of all analyses remained consistent after including patients with severe MR. The beneficial treatment effect of omecamtiv mecarbil versus placebo on clinical outcomes was not modified by MR. Over 80% of patients with moderate/severe MR fulfilled the broad inclusion criteria for COAPT and RESHAPE-HF2.

Conclusions: In GALACTIC-HF, almost 15% of patients with heart failure and reduced ejection fraction had moderate MR, which was associated with a higher risk of the primary outcome.

Aims: Left ventricular ejection fraction (LVEF) has been incorporated as an inclusion criterion in HF trials. Patient's characteristics, event risk, and treatment response vary according to LVEF. A better understanding of the biological processes across LVEF is warranted. To study proteomic biomarker expression across LVEF using data from the EMPEROR-Programme.

Methods: Two thousand two hundred and fifty-four patients who had proteomic measurements available using 1134 proteins overlapping between the Explore 1536 and 3072 Olink® platforms were included. Main analyses were performed within the EMPEROR-Preserved dataset due to differences in entry criteria between EMPEROR-Preserved and EMPEROR-Reduced with higher entry N-terminal pro B-type natriuretic peptide (NT-proBNP) levels that varied by LVEF cut-offs in the latter. Protein concentrations were compared using ordinal logistic regression across LVEF categories: 41%-49%, 50%-59%, and ≥60%. The resulting β-coefficient indicates the change in the log-odds for the outcome of being in a lower LVEF category for every NPX unit in log2 scale. Analyses were adjusted for covariates and a false-discovery-rate (FDR) correction was applied.

Results: A total of 297 proteins exhibited a trend of expression across LVEF categories in EMPEROR-Preserved after adjustment for potential confounders and correction for test multiplicity. Of these, the top 10 proteins were: NT-pro BNP (β = 0.18, 95% CI 0.09-0.27), Wnt inhibitory factor-1 (β = 0.40, 95% CI 0.19-0.61), sialomucin core protein 24 (β = 0.48, 95% CI 0.22-0.74), phospholipid transfer protein (β = 0.38, 95% CI 0.17-0.59), natriuretic peptides B (β = 0.13, 95% CI 0.06-0.20), intercellular adhesion molecule 5 (β = 0.31, 95% CI 0.14-0.49), neural cell adhesion molecule 2 (β = 0.45, 95% CI 0.19-0.70), neural cell adhesion molecule L1-like protein (β = 0.45, 95% CI 0.19-0.71), interactor protein for cytohesin exchange factors 1 (β = 0.12, 95% CI 0.05-0.19), and 3-ketoacyl-CoA thiolase, peroxisomal (β = 0.17, 95% CI 0.07-0.26). The correlation between these proteins and LVEF was generally weak (Rho ≤0.2).

Conclusions: Within EMPEROR-Preserved, the top differentially expressed circulating proteins suggest that pathways related to natriuretic peptides, cell-adhesion, and clonal haematopoiesis are overexpressed at mildly-reduced ejection fraction, but none of the proteins passed the 5%FDR cut-off, and the correlation between circulating proteins and LVEF was weak. These findings suggest that circulating proteins may not be a good discriminant of ejection fraction.