European Journal of Heart Failure最新文献

Aims: Omecamtiv mecarbil (OM) has been shown to benefit individuals with heart failure and reduced ejection fraction but the clinical experience of cardiac myosin activators and risk of life-threatening ventricular arrhythmias (VA) is limited. We investigated the effects of OM on incidence of VA, cardiac arrest, and sudden death (SD) in the GALACTIC-HF trial.

Methods: GALACTIC-HF was a placebo-controlled randomized trial testing the efficacy and safety of OM in participants with symptomatic chronic HF and LVEF ≤35%. Ventricular arrhythmias and cardiac arrest were investigator-reported adverse events while SD was centrally adjudicated. Severe HF was defined according to the ESC-HFA criteria. The effect of OM on the composite of the first occurrence of serious VA, cardiac arrest, or SD was examined using Cox proportional hazards models.

Results: Over a median follow-up of 21.8 months, 706 out of the 8232 participants randomized in the GALACTIC-HF trial experienced serious VA, cardiac arrest, or SD. Randomization to OM led to a trend towards reduced risk for the composite arrhythmic outcome (377 events in the placebo group vs. 329 in the OM study arm; HR 0.86; 95% CI 0.75-1.00; P = .054). The strength of the association between OM and lower risk of composite events was stronger in participants with an LVEF ≤the median level of 28% (HR 0.77; 95% CI 0.63-0.94; P = .009) and appeared consistent in participants with severe HF.

Conclusion: In this post hoc analysis of the GALACTIC-HF trial, we observed a potential reduction in life-threatening arrhythmia, cardiac arrest, and SD with OM treatment, especially in patients with severely reduced LVEF. These findings require prospective validation in the ongoing COMET-HF trial.

Renal artery stenosis due to atherosclerotic renovascular disease (ARVD) is common but under-recognized amongst patients with heart failure and chronic kidney disease (CKD). Whether renal artery stenosis is just a manifestation of widespread atherosclerotic disease or a driver of heart failure symptoms, disease progression, and prognosis is controversial and may depend on distinguishing anatomic from functional renal artery stenosis. Anatomical renal artery stenosis can cause nephron damage due to micro-embolization/infarction or activation of inflammatory pathway, leading to a decline in estimated glomerular filtration rate (eGFR) and albuminuria. Functionally significant renal artery stenosis will, in addition, alter renal haemodynamics, favouring water and salt retention, and may cause nephron ischaemia. Clinical manifestations of renal artery stenosis include hypertension, a progressive decline in renal function, worsening heart failure, and 'flash pulmonary oedema'. Anatomical renal artery stenosis can be identified non-invasively using various methods but confirming functional significance may be difficult, creating uncertainty about which patients are likely to benefit from revascularization. If there is a large decline in eGFR after initiating renin-angiotensin-aldosterone system inhibitors (RAASi), this should raise the suspicion of functionally important renal artery stenosis. However, RAASi are an important first line therapy for both ARVD and heart failure. For patients with ARVD and heart failure, RAASi and other guideline-recommended therapies should be initiated with appropriate monitoring of renal function. Further randomized trials investigating the effects of renal revascularization of functionally significant renal artery stenosis on symptoms, renal function, diuretic efficacy, and prognosis in patients with heart failure are required.

Aims: Patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) have a high comorbidity burden, which may necessitate numerous medications. Patients and clinicians may be hesitant about initiating another medication, especially among those already experiencing polypharmacy. This pre-specified analysis sought to examine the efficacy and safety of adding finerenone based on the concomitant medication number.

Methods: In the FINEARTS-HF trial, baseline medication use was collected in all 6001 participants with HFmrEF/HFpEF. Clinical outcomes and treatment effects were assessed by the categories of total medication count ('non-polypharmacy': ≤4 medications; 'polypharmacy': 5-9 medications; and 'hyper-polypharmacy': ≥10 medications) and as continuous variables. The primary outcome was a composite of cardiovascular death and total HF events.

Results: Overall (age: 72 ± 10 years; 46% women), the total number of medications at baseline ranged from 0 to 29 (mean: 8.4 ± 3.6), with 3588 (60%) meeting polypharmacy and 1878 (31%) meeting hyper-polypharmacy. Incidence rates for the primary outcome increased across medication categories: non-polypharmacy, 10.2; polypharmacy, 12.3; and hyper-polypharmacy, 26.1 per 100 person-years. The treatment benefits of finerenone in reducing the primary outcome were consistent across the spectrum of total medication count (Pinteraction = 0.94). Any serious adverse events and study drug discontinuation were not more frequent with finerenone vs placebo, regardless of polypharmacy categories.

Conclusion: In FINEARTS-HF, >90% of patients with HFmrEF/HFpEF met the criteria for polypharmacy or hyper-polypharmacy, and these patients faced excess risks of cardiovascular events. Finerenone safely reduced cardiovascular death and total HF events across a broad range of baseline medication use.

Aims: Intensive follow-up post-hospitalization for heart failure (HHF) is recommended, but difficult to pursue. Risk stratification of HHF with preserved ejection fraction (HFpEF) might help to improve resource allocation. However, it remains elusive and no study has applied cluster analysis in the acute setting.

Methods: Consecutive patients with HHF and left ventricular EF >40% were enrolled and evaluated at discharge. A composite endpoint of all-cause death, urgent heart transplant, HF hospitalization, or emergency department visit for decompensated HF was assessed at 12 months. Cluster analysis was performed using prespecified variables, while Cox regression and classification and regression tree analysis identified predictors of adverse outcomes.

Results: A total of 1052 HF patients were screened. After excluding HF with EF below 40%, 471 patients (median age 78 years, 44% women) were included. Among them, three clusters were identified.Cluster 1 comprised younger patients with de novo HF, fewer comorbidities, preserved renal function, and lower B-type natriuretic peptides (BNP) and neutrophil-lymphocyte ratio (NLR) levels. Cluster 2 consisted mainly of elderly women with hypertension and atrial fibrillation. Cluster 3 included older patients with worsening HF, higher NYHA class, renal dysfunction, anaemia, and elevated BNP and NLR. Compared with Cluster 1, risk was nearly threefold higher in Cluster 2 [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7-5.2, P < .001] and fivefold higher in Cluster 3 (HR 4.8, 95% CI 2.7-8.4, P < .001). Outcome results were consistent in the vulnerable period (3 months). NYHA class and NLR emerged as key prognostic nodes.

Conclusion: Cluster analysis identified low-, intermediate-, and high-risk acute HFpEF phenotypes. These data might support personalized management strategies in hospitalized HFpEF.

Aims: Patients with heart failure (HF) are at increased risk of developing dementia, an outcome that substantially worsens clinical prognosis and quality of life. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are well-established in cardiovascular protection, but their association with incident dementia remains poorly documented, particularly in non-diabetic populations.

Methods: We conducted a retrospective cohort study using the TriNetX Research Network (2016-2025), including adults with HF and no prior history of dementia or diabetes. Patients initiating SGLT2i (n = 46 049) were compared with non-users (n = 205 010). After 1:1 propensity score matching, 39 979 pairs were analysed. The primary outcome was new-onset dementia. Secondary outcomes were Alzheimer's disease, vascular dementia, and all-cause mortality. Additional cardiovascular outcomes included ischaemic stroke, myocardial infarction, and end-stage kidney disease (ESKD). Outcomes were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models.

Results: Over a relatively short median follow-up of 1.2 years in a population with a mean age of 64 years, SGLT2i use was associated with a significantly lower risk of new-onset dementia [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.68-0.87; P < .001]. Risks were also reduced for Alzheimer's disease (HR 0.58, 95% CI 0.45-0.74; P < .001), vascular dementia (HR 0.41, 95% CI 0.27-0.62; P < .001), and all-cause mortality (HR 0.63, 95% CI 0.61-0.66; P < .001). SGLT2i therapy was further associated with lower risks of ischaemic stroke (HR 0.67, 95% CI 0.60-0.75; P < .001) and ESKD (HR 0.75, 95% CI 0.63-0.89; P = .001).

Conclusion: In this large, real-world patient with HF without diabetes, SGLT2i therapy was associated with a significantly lower risk of new-onset dementia and all-cause mortality.

Aims: Myocardial inflammation has been proposed as a central mechanism in heart failure with preserved ejection fraction (HFpEF), supported by experimental work suggesting immune cell-mediated activation of pro-fibrotic signalling. However, bulk transcriptomic analyses of human HFpEF myocardium did not demonstrate an activation of pro-inflammatory mediators or pathways. Here we investigated whether immune cell enrichment is present in human HFpEF myocardium.

Methods: We analysed left ventricular (LV) epicardial biopsies from 28 adults undergoing elective coronary artery bypass grafting with preserved LV ejection fraction (≥50%). Participants were classified as referent controls (n = 10), preclinical HFpEF Stage B (n = 10), or overt HFpEF Stage C (n = 8). High-resolution spatial transcriptomics and quantitative immunofluorescence for CD45, CD68, and CD3G were used to determine the abundance and phenotypic composition of immune lineage cells.

Results: Heart failure with preserved ejection fraction patients were older and more obese when compared to control subjects. Spatial transcriptomic profiling revealed normal immune cell abundances across all groups (mean 0.68 ± 0.52% in controls, 0.90 ± 0.49% in HFpEF Stage B, and 0.78 ± 0.29% in HFpEF Stage C; P = NS), without differences in immune cell subsets or adaptive immune cell signatures. Immunofluorescence confirmed the absence of differences.

Conclusions: Spatially resolved human myocardial profiling did not demonstrate an increase in immune lineage cells in preclinical or overt HFpEF, challenging the concept that myocardial immune cell infiltration is a major driver of HFpEF. These findings support a model in which haemodynamic load and systemic factors, rather than local immune cell expansion, drive myocardial hypertrophy and fibrosis in HFpEF.