European Journal of Heart Failure最新文献

Aims: Older adults with atrial fibrillation (AFib) face a high risk of heart failure (HF). We investigated whether the coexistence of AFib and metabolic dysfunction-associated steatotic liver disease (MASLD) and its subtypes, including MASLD with increased alcohol intake (MetALD) and alcoholic liver disease (ALD), further increases the risk of HF.

Methods and results: Patients (aged ≥60 years) with AFib diagnosed between 2002 and 2010 were collected from the Korean National Health Insurance Service database. MASLD status was determined during 2009-2010 [fatty liver index (FLI) ≥30]. The association between MASLD and incident HF was assessed using Fine-Gray subdistribution hazard models. Participants were followed from 1 January 2011, until the occurrence of HF, death, or 31 December 2019, whichever came first. Among 7543 older adults with AFib, 3168 had MASLD, 259 had MetALD, and 159 had ALD. The presence of MASLD (subdistribution hazard ratio, 1.22; 95% CI, 1.10-1.35, P < .001), MetALD (1.36; 1.05-1.76, P = .019), and ALD (1.42; 1.03-1.97, P = .034) was associated with a higher risk of incident HF. In restricted cubic spline analyses, significant dose-response relationships were observed for both the FLI and daily alcohol consumption, each of which was associated with increased HF risk among patients with AFib.

Conclusion: Coexistence of AFib and MASLD identifies a high-risk overlap state for incident HF in older adults. These findings highlight the importance of recognizing inflammatory liver dysfunction driven by metabolic and alcohol-related factors as a potential amplifier of HF risk in older adults with AFib.

Background and aims: We aimed to determine whether treatment-related changes in surrogate markers predict longer-term therapeutic effects on all-cause mortality and heart failure (HF) hospitalization in randomized trials of HF.

Method: Systematic literature search included randomized trials of interventions in patients with HF until October 2024. Random-effects meta-regression models with inverse variance weighting were calculated between fifteen surrogate markers and the clinical endpoints of 1) all-cause mortality and 2) HF hospitalisation. The degree of heterogeneity of each model explained by the surrogate marker was determined with R2. Surrogate threshold effects (STEs) were also calculated.

Results: Ninety-six randomized trials with median follow-up 12 months were included, enrolling a total of 120,304 patients with HF. Treatment related changes in natriuretic peptides (NPs) were weakly correlated with all-cause mortality (64 comparisons, p=0.002, R2=12%, STE=-34%) and HF hospitalization (41 comparisons, p<0.001, R2=34%, STE=-30%). Changes in LVEF were moderately correlated with mortality (69 comparisons, p<0.001, R2=59%, STE=+6%) and strongly correlated with HF hospitalization (45 comparisons, p<0.001, R2=90%, STE=+2%), although this finding was only observed in trials of HFrEF. LV end-diastolic diameter was correlated with HF hospitalization but not mortality. Other echocardiographic markers were not predictive of clinical endpoints. Treatment related changes in patient reported outcomes and exercise capacity were either weakly correlated with clinical outcomes or derived from small clinical trials.

Conclusion: In HF trials, most surrogate markers, including NPs and echocardiographic measures were only weakly or moderately correlated with treatment effects on all-cause mortality. There is insufficient evidence to support the use of a single biomarker or echocardiographic measure in regulatory trials of HF.

Obesity is prevalent among patients with heart failure (HF), especially in those with preserved ejection fraction (HFpEF), and complicates diagnosis, therapy, and monitoring. It alters haemodynamics, biomarker interpretation, and drug pharmacokinetics, potentially influencing treatment response. Evidence from subgroup analyses of major HF trials suggests that renin-angiotensin system inhibitors (mainly sacubitril-valsartan), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors provide consistent benefits across body mass index (BMI) categories, with no major obesity-specific safety concerns. In contrast, data on beta-blockers in obese HF patients remains limited, largely reflecting the older design of pivotal trials. Management should include careful assessment of congestion, acknowledging the limitations of physical examination, and integrate natriuretic peptides measurement and imaging evaluation to guide individualised diuretic strategies. This expert consensus provides a comprehensive and pragmatic framework for the use of guideline-directed medical therapy in patients with HF and obesity, exploring the available evidence for each drug class and addressing efficacy, patient selection, safety, and monitoring.

Aims: Iron deficiency (ID) is prevalent in heart failure (HF). While the impact of ID is well-documented in those with left ventricular ejection fraction (LVEF) <50 (HFrEF & HFmrEF), its role in those with LVEF>50 (HFpEF) is uncertain. We aimed to elucidate and compare the clinical relevance of ID across the LVEF spectrum using multiple definitions.

Methods: Patients with known LVEF and iron parameters from the index and validation cohort of The BIOSTAT-CHF study were pooled (n=3642). ID was defined using three criteria: 1) IDTSAT: transferrin saturation (TSAT) <20%, 2) IDSI: serum iron ≤13 μmol/L, and 3) IDESC: the ESC guideline definition (ferritin <100 µg/L or 100-299 µg/L with TSAT <20%).

Results: The prevalence of ID ranged from 57-75% depending on definition and LVEF, with the highest rates in HFpEF and in very low LVEF. More than half of patients met all three definitions, but nearly one-third were classified discordantly. ID was consistently associated with lower quality of life and greater physical limitations (both P < .01) across all definitions and LVEF categories. Independent associates of ID included female sex, higher heart rate, proton pump inhibitor use, anemia, hypoalbuminemia, worse renal function, and fluid retention. ID was associated with increased CV and non CV death, all-cause mortality, HF hospitalizations, and their composite in patients with LVEF <50% across all definitions (p<0.05). In HFpEF, no definition showed consistent prognostic significance, though interactions with LVEF group were observed for IDTSAT and IDESC (p_interaction <0.05).

Conclusion: ID is common and clinically relevant across the HF spectrum, irrespective of definition, and is associated with impaired quality of life and adverse outcomes in patients with LVEF <50%. In HFpEF, however, the prognostic impact of ID appears less pronounced and may depend on the definition applied, highlighting the need for refined diagnostic criteria in this group.

Aims: Dilated cardiomyopathy (DCM) encompasses genetic and acquired aetiologies, yet the impact of immune-mediated mechanisms remains unclear. This study investigates the clinical characteristics and outcomes of immune-mediated DCM (ID-CMP).

Methods: From the Maastricht Cardiomyopathy registry, 194 patients with ID-CMP were compared with 678 non-immune DCM controls over a median follow-up of 5.2 (3.7-10.7) years. ID-CMP was categorized into autoimmune-mediated (adaptive immunity dysfunction), autoinflammatory-driven (innate immunity dysfunction), and mixed-pattern (MHC Class I associations and autoinflammatory components). Patients with features of >1 category were classified as overlapping-CMP. Echocardiographic and genetic data were collected. Cox regression assessed major adverse cardiovascular events (MACE: cardiac mortality, heart failure hospitalization, life-threatening arrhythmias). Left ventricular ejection fraction (LVEF) trajectories were analysed using linear mixed-effects models. Findings were validated in an independent cohort of 201 ID-CMP patients.

Results: ID-CMP was associated with a higher risk of MACE [HR: 1.68 (1.1-2.5), P = .012] after adjustment for age, sex, and baseline LVEF, confirmed in an external validation cohort [HR:2.40 (1.6-3.5), P < .001]. LVEF was lower in ID-CMP during the first year but converged with non-immune DCM thereafter (P0-1year = .018; P>1year = ns). Outcomes did not differ among ID-CMP subtypes. Inflammation on EMB was related to worse clinical outcome [HR:2.0 (1.1-3.6), P = .017]. Pathogenic DCM gene variants were equally frequent in ID-CMP and non-ID-CMP patients (22% vs 20%, P = ns).

Conclusion: ID-CMP patients have a higher risk of MACE despite similar LVEF trajectories, as confirmed in a validation cohort. Cardiac immune cell infiltration suggests an inflammatory substrate independent of genetics.

Background and aims: Mitral transcatheter edge-to-edge repair (M-TEER) is an established therapy for functional mitral regurgitation (FMR) and reduced left ventricular ejection fraction (LVEF). Although guideline-directed medical therapy (GDMT) is ideally optimized before M-TEER, this procedure may facilitate early post-procedural GDMT changes. However, the clinical impact of early in-hospital GDMT modifications remains unclear.

Methods: We analyzed 1,638 patients with FMR and LVEF <50% enrolled in a multicenter Japanese registry. The patients were stratified according to the number of GDMT classes prescribed at discharge (single [n=183]; double [n=505]; triple [n=630]; quadruple [n=320]). Changes from before M-TEER to discharge were categorized as increased (n=271), unchanged (n=1,219), or decreased (n=148). Associations between GDMT patterns and subsequent outcomes were evaluated. The primary endpoint was a composite of all-cause mortality and heart failure rehospitalization at one year.

Results: Primary endpoints were achieved in 357 patients (22%). Event rates decreased across groups (single, 32%; double, 24%; triple, 21%; quadruple, 14%; P<0.001). After adjusting for confounders, a greater number of GDMT classes at discharge independently predicted better prognosis. (hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.73-0.95), whereas pre-M-TEER GDMT was not significant. Compared with decreased GDMT, an unchanged status was not associated with improved outcomes, while an increased status significantly improved prognosis (HR 0.62, 95% CI 0.39-0.99).

Conclusion: In patients with FMR and LVEF <50%, a higher number of GDMT classes at discharge and in-hospital uptitration of the GDMT class were associated with better outcomes, suggesting that early postprocedural GDMT optimization warrants further investigation.

Aims: While elevated heart rate is an established marker of risk in HF, the prognostic relevance of heart rate is less certain in patients with comorbid atrial fibrillation/flutter (AFF). We investigated the associations between heart rate and outcomes according to AFF status in 5 HFmrEF/HFpEF clinical trials.

Methods: In a participant-level pooled analysis of the CHARM-Preserved, I-PRESERVE, TOPCAT-Americas, PARAGON-HF, and DELIVER trials, associations between baseline heart rate and outcomes according to AFF status on ECG at enrolment were assessed with multivariable Cox and Poisson regression models. The primary outcome was CV death or HF hospitalization.

Results: Among 19 975 participants, 5816 (29%) had AFF on baseline ECG. Patients with AFF were older, more frequently male, had a higher baseline heart rate (75 vs 68 bpm, P < .001), and had an increased risk for the primary outcome (adj HR 1.19 [1.10-1.27]). A significant interaction between heart rate, AFF status, and clinical outcomes was observed, such that patients in sinus rhythm had higher event rates with increasing heart rates, while the incident rates for participants in AFF were similar across the range of baseline heart rate (Pinteraction < .001 for the primary outcome). This relationship was not further modified by concomitant β-blocker use.

Conclusions: In this analysis of five HFmrEF/HFpEF trials, baseline heart rate was associated with significantly higher rates of events only in patients in sinus rhythm but not in those with AFF. The optimal management of AFF in the context of HFmrEF/HFpEF requires a dedicated study.

Peripartum cardiomyopathy (PPCM) can be a serious condition, presenting with heart failure with reduced ejection fraction towards the end of pregnancy or in the months following delivery. Less than half of the patients fully recover their cardiac function within 6 months of diagnosis, with substantial regional variation. This clinical consensus statement addresses the global and regional heterogeneity of epidemiological data on PPCM, substantial variation in access to medical care, and the contributing factors to poor adherence, as well as the impact of socioeconomic factors. The scope of this document encompasses contemporary challenges and approaches for the management of women diagnosed with PPCM. We provide a framework of practical aspects of starting disease-specific and guideline-recommended medical therapy, rapid up-titration, and improving adherence. Furthermore, the importance of involving women with a new diagnosis of PPCM in the decision-making processes regarding various therapeutic options is highlighted, as this also affects the mental health and quality of life for the patient, as well as for the extended family.