ESC Heart Failure最新文献

Aims: Endogenous catecholamine release-inhibitory peptide catestatin has been associated with heart failure (HF). This subgroup analysis of our cohort of HF compared the different effects of catestatin as a predictor for cardiac outcomes in patients with HF with reduced (HFrEF), mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction.

Methods: Plasma catestatin was measured in the HF patient cohort of 228 cases with a whole spectrum of ejection fraction. The cardiac deaths were analysed according to prespecified subgroups.

Results: Over a median follow-up of 52.5 months, the association between plasma catestatin and cardiac death was different in patients with HFrEF, HFmrEF or HFpEF [hazard ratio (HR) 1.53, 95% confidence interval (CI) 0.99-2.37 and HR 2.73, 95% CI 1.56-4.75, respectively; interaction P = 0.022]. Patients with HFmrEF/HFpEF were older and more likely to be female, with non-ischaemic cardiomyopathy and atrial fibrillation but lower levels of plasma B-type natriuretic peptide (BNP). Similar adverse cardiac events occurred in patients with HFmrEF/HFpEF as in HFrEF. Plasma catestatin was a better predictor for cardiovascular death in the HFmrEF/HFpEF patients [area under the receiver operating characteristic curve (AUC) = 0.72, 95% CI 0.45-0.74] than in the HFrEF patients (AUC = 0.59, 95% CI 0.587-0.849). The optimal cut point of plasma catestatin level of 0.86 ng/mL predicted a 2.80-fold elevated risk for cardiac death in HFmrEF/HFpEF.

Conclusions: Elevated plasma catestatin might be a more sensitive predictor for cardiac outcome in patients with HFmrEF/HFpEF than in HFrEF.

Aims: Dynamic alterations in cardiac DNA methylation have been implicated in the development of heart failure (HF) with evidence of ischaemic heart disease (IHD); however, there is limited research into cell specific, DNA methylation sensitive genes that are affected by dysregulated DNA methylation patterns. In this study, we aimed to identify DNA methylation sensitive genes in the ischaemic heart and elucidate their role in cardiac fibrosis.

Methods: A multi-omics integrative analysis was carried out on RNA sequencing and methylation sequencing on HF with IHD (n = 9) versus non-failing (n = 9) left ventricular tissue, which identified Integrin beta-like 1 (ITGBL1) as a gene of interest. Expression of Itgbl1 was assessed in three animal models of HF; an ischaemia-reperfusion pig model, a myocardial infarction mouse model and an angiotensin-II infused mouse model. Single nuclei RNA sequencing was carried out on heart tissue from angiotensin-II infused mice to establish the expression profile of Itgbl1 across cardiac cell populations. Subsequent in vitro analyses were conducted to elucidate a role for ITGBL1 in human cardiac fibroblasts. DNA pyrosequencing was applied to assess ITGBL1 CpG methylation status in genomic DNA from human cardiac tissue and stimulated cardiac fibroblasts.

Results: ITGBL1 was >2-fold up-regulated (FDR adj P = 0.03) and >10-fold hypomethylated (FDR adj P = 0.01) in human HF with IHD left ventricular tissue compared with non-failing controls. Expression of Itgbl1 was up-regulated in three isolated animal models of HF and showed conserved correlation between increased Itgbl1 and diastolic dysfunction. Single nuclei RNA sequencing highlighted that Itgbl1 is primarily expressed in cardiac fibroblasts, while functional studies elucidated a role for ITGBL1 in cardiac fibroblast migration, evident in 50% reduced 24 h fibroblast wound closure occurring subsequent to siRNA-targeted ITGBL1 knockdown. Lastly, evidence provided from DNA pyrosequencing supports the theory that differential expression of ITGBL1 is caused by DNA hypomethylation.

Conclusions: ITGBL1 is a gene that is mainly expressed in fibroblasts, plays an important role in cardiac fibroblast migration, and whose expression is significantly increased in the failing heart. The mechanism by which increased ITGBL1 occurs is through DNA hypomethylation.

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been widely demonstrated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization, regardless of left ventricular ejection fraction (LVEF). However, data on the extent to which rehospitalization is suppressed following HF hospitalization are limited. This study investigated the effects of SGLT2i on rehospitalization and cardiovascular death.

Methods and results: The OASIS-HF study, a multicentre, prospective observational cohort study, enrolled 361 patients aged ≥75 years hospitalized for acute decompensated HF. The impact on composite events of HF rehospitalization or cardiovascular death and the number of annual rehospitalizations were evaluated between the conventional medical therapy and SGLT2i groups. The change in eGFR slope at the 1-year mark after the initiation of treatment in both groups was also assessed. Over an average follow-up period of 24.9 months, composite events occurred in 70 (35.4%) of the conventional therapy group and 36 (22.1%) of the SGLT2i group (log-rank: P = 0.016). The average number of rehospitalizations for HF per year was 0.22 ± 0.13 vs. 0.14 ± 0.08, respectively (P = 0.019). The change in eGFR over 1 year was significantly slower in the SGLT2i group compared with the conventional group (-3.55 ± 8.46 vs. -1.42 ± 7.28 mL/min/1.73 m², P = 0.025).

Conclusions: The SGLT2i are not only associated with the reduction of the composite events of HF rehospitalization or cardiovascular death and protect against worsening renal function but also with a decrease in long-term repeated HF rehospitalizations.

Aims: Whether medication adherence to angiotensin receptor-neprilysin inhibitor (ARNI) in real-world practice is associated with the reduced risk of all-cause mortality or hospitalization relative to that with traditional renin-angiotensin system (RAS) blockade remains unclear. This study investigated the influence of medication adherence of ARNI and traditional RAS blockade in heart failure with reduced ejection fraction (HFrEF).

Method: We conducted a nationwide longitudinal cohort study with patients with HFrEF using data from the Korean National Health Insurance Service data (2017-2021) covering the entire population. A total of 13 483 patients with HFrEF who received ARNI were matched 1:1 with 13 483 patients who received traditional RAS blockade using propensity score matching. The primary outcome was a composite of all-cause mortality or any hospitalization within one year. Medication adherence was assessed by calculating the proportion of days covered (PDC) relative to total medication prescribed. ARNI and traditional RAS blockade adherence rates were directly compared to analyse their respective associations with the primary outcome.

Results: Patients in the ARNI group had a lower rate of the primary outcome than those in the traditional RAS blockade group [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.75-0.81; P < 0.001]. Mean PDC values spanning 1 year were 92.6 ± 14.5% and 90.9 ± 17.7% in the ARNI and RAS blockade groups, respectively (P < 0.001). Among patients with PDC ≥ 80%, the risk of primary outcome was significantly lower in the ARNI group than in the RAS blockade group (HR 0.75; 95% CI 0.72-0.78; P < 0.001) while a risk reduction with ARNI was not observed among patients with PDC < 80% (HR 0.95; 95% CI 0.85-1.05; P = 0.313). The beneficial effect was more pronounced among patients with PDC ≥ 80% than that among patients with PDC < 80% (P for interaction <0.001).

Conclusions: In a real-world cohort with HFrEF, ARNI was superior to traditional RAS blockade in reducing the risk of all-cause mortality and hospitalization. The benefit of ARNI was pronounced among patients with high medication adherence but not among those with low medication adherence, highlighting the importance of adherence to ARNI treatment for HFrEF.

Trial registration: PARADE-HF ClinicalTrials.gov number, NCT05329727.

Aims: Central sleep apnoea (CSA) is present in 20-40% of heart failure (HF) patients and is associated with poor clinical outcomes and health status. Transvenous phrenic nerve stimulation (TPNS) is an available treatment for CSA in HF patients. The impact on HF outcomes is incompletely understood. The win ratio (WR) allows inclusion of multiple endpoint components, considers the relative severity of each component, and permits assessment of recurrent events in evaluation of clinical benefit.

Methods and results: A WR hierarchy was pre-defined for analysis of the HF subgroup of the remedē® System Pivotal Trial. The analysis used three hierarchical components to compare all treated to all control subjects: longest survival, lowest HF hospitalization rate, and ≥2-category difference in Patient Global Assessment at 6 months. Sensitivity analyses were performed substituting Epworth Sleepiness Scale and 4% oxygen desaturation index for the third component, and a 4-component WR hierarchy was also evaluated. Ninety-one HF subjects, 43 receiving TPNS and 48 in the control group, provided 2064 pairwise comparisons. More patients treated with TPNS experienced clinical benefit compared with control (WR 4.92, 95% confidence interval 2.27-10.63, P < 0.0001). There were 1111 (53.83%) winning pairwise comparisons for the treatment group and 226 (10.95%) for the control group. Similarly, large WRs were observed for all additional WR hierarchies.

Conclusions: This WR analysis of the remedē® System Pivotal Trial suggests that TPNS may be superior to untreated CSA in HF patients with CSA using a hierarchical clinical benefit endpoint composed of mortality, HF hospitalization, and health status.

Formal assessment of myocardial viability (MV) is challenging in acute myocardial infarction-related cardiogenic shock (AMI-CS) patients receiving Impella mechanical circulatory support, as the cardiac magnetic resonance gold standard technique is not feasible due to the metallic components of the device. 18-fluorodesoxyglucose metabolic myocardial positron emission tomography (¹⁸FDG-PET) may represent a valid and feasible alternative to obtain semi-quantitative and objective evidence of MV during Impella support. We hereby report the first series of sequential AMI-CS patients who received ¹⁸FDG-PET scanning to assess MV during Impella support to demonstrate the safety and feasibility of this approach. In this cohort no adverse events occurred during ¹⁸FDG-PET scans, and all images were of excellent quality. This study provides a pragmatic guidance on how to perform this imaging modality during Impella support and finally confirms the safety and feasibility of this advanced imaging method also in this vulnerable cohort of patients.

Aims: Few studies have focused on the effect of torsemide versus furosemide after discharge on prognosis in patients with heart failure with preserved ejection fraction (HFpEF). This single-centre retrospective real-world study was conducted to evaluate the effect of torsemide versus furosemide after discharge on all-cause mortality and rehospitalization for heart failure in patients with HFpEF.

Methods: Consecutive patients who were diagnosis with HFpEF after discharge between January 2015 and April 2018 at the First Affiliated Hospital of Dalian Medical University and who had been treated with torsemide or furosemide were included in this study. The primary outcome was all-cause mortality. The second outcome was rehospitalization for heart failure.

Results: A total of 445 patients (mean age 68.56 ± 8.07, female 55%) were divided into the torsemide group (N = 258) or furosemide group (N = 187) based on the treatment course at discharge from the hospital. During a mean follow-up of 87.67 ± 11.15 months, death occurred in 68 of 258 patients (26.36%) in the torsemide group and 60 of 187 patients (30.09%) in the furosemide group [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.57-1.15, P = 0.239]. Rehospitalization for heart failure occurred in 111 of 258 patients (43.02%) in the torsemide groups and 110 of 187 patients (58.82%) in the furosemide group (HR 0.64, 95% CI 0.49-0.85, P = 0.002).

Conclusions: Compared with furosemide, torsemide did not significantly reduce all-cause mortality, but there was association between torsemide and reduced rehospitalization for heart failure in patients with HFpEF.

Aims: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of death worldwide; thus, therapeutic improvements are needed. In vivo preclinical models are essential to identify molecular drug targets for future therapies. Transverse aortic constriction (TAC) is a well-established model of HFrEF; however, highly experienced personnel are needed for the surgery, and several weeks of follow-up are necessary to develop HFrEF. To this end, we aimed (i) to develop an easy-to-perform mouse model of HFrEF by treating Balb/c mice with angiotensin-II (Ang-II) for 2 weeks by minipump and (ii) to compare its cardiac phenotype and transcriptome to the well-established TAC model of HFrEF in C57BL/6J mice.

Methods: Mortality and gross pathological data, cardiac structural and functional characteristics assessed by echocardiography and immunohistochemistry and differential gene expression obtained by RNA-sequencing and gene-ontology analyses were used to characterize and compare the two models. To achieve statistical comparability between the two models, changes in treatment groups related to the corresponding control were compared (ΔTAC vs. ΔAng-II).

Results: Compared with the well-established TAC model, chronic Ang-II treatment of Balb/c mice shares similarities in cardiac systolic functional decline (left ventricular ejection fraction: -57.25 ± 7.17% vs. -43.68 ± 5.31% in ΔTAC vs. ΔAng-II; P = 0.1794) but shows a lesser degree of left ventricular dilation (left ventricular end-systolic volume: 190.81 ± 44.13 vs. 57.37 ± 10.18 mL in ΔTAC vs. ΔAng-II; P = 0.0252) and hypertrophy (cell surface area: 58.44 ± 6.1 vs. 10.24 ± 2.87 μm² in ΔTAC vs. ΔAng-II; P < 0.001); nevertheless, transcriptomic changes in the two HFrEF models show strong correlation (Spearman's r = 0.727; P < 0.001). In return, Ang-II treatment in Balb/c mice needs significantly less procedural time [38 min, interquartile range (IQR): 31-46 min in TAC vs. 6 min, IQR: 6-7 min in Ang-II; P < 0.001] and surgical expertise, is less of an object for peri-procedural mortality (15.8% in TAC vs. 0% in Ang-II; P = 0.105) and needs significantly shorter follow-up for developing HFrEF.

Conclusions: Here, we demonstrate for the first time that chronic Ang-II treatment of Balb/c mice is also a relevant, reliable but significantly easier-to-perform preclinical model to identify novel pathomechanisms and targets in future HFrEF research.

Aims: Recognizing the rising concern of environmental impacts on health, the study aims to explore how specific environmental factors such as air pollution, humidity, and temperature variations contribute to the prevalence of cardiovascular disease (CVD) mortality, emphasizing the role of air quality, climate variables, and lifestyle factors in the disease mortality specifically.

Methods and results: Analysis of province-level data on CVD mortality in Turkey from 2010 to 2019, assessing the correlations with environmental and lifestyle factors like particulate matter, sulfur dioxide, meteorological variables, and smoking and alcohol consumption. The study employs the SAS TRAJ procedure and Ordinal Logistic Regression for statistical analysis. The multiplicity correction was done through Benjamini-Hoechberg false discovery rate (FDR) approach. As expected, both smoking and alcohol consumption were found to be significantly associated with CVD mortality (odds ratio (OR): 1.10, 95% CI: 1.08, 1.11, P-value < 0.0001). While median Air Pressure and Humidity were among the most significant markers with OR of 1.10 indicating an increasing CVD mortality, their variability metrics such as coefficient of variation (CV) showed significant protective effects with OR of 0.37 and 0.89, respectively. Temperature and its variability seemed to be protective overall.

Conclusions: Our research highlights the significant influence of environmental factors on cardiovascular health, especially air pressure and humidity, beyond the known factors such as smoking and alcohol consumption. These findings suggest the need for comprehensive public health strategies that address both environmental and lifestyle risk factors to effectively reduce the burden of cardiovascular diseases.

Aims: Intravenous (IV) therapies have transformed the management of various cardiovascular conditions in ambulatory patients. However, uptake of these therapies in ambulatory care settings has several barriers. In this systematic scoping review, we aimed to identify the barriers and facilitators that influence the implementation of current IV therapies in ambulatory settings.

Methods: We searched MEDLINE, Embase and CINAHL databases from inception to September 2023 for studies on barriers and facilitators of IV therapy uptake in ambulatory patients. We classified the identified factors and performed a thematic analysis.

Results: Fifteen studies, primarily conducted in North America and Europe, were included. Methodologies varied, precluding quantitative synthesis. Key barriers were identified across several levels. At the medication level, barriers included the need for multiple vials and lengthy preparation. Patient-level barriers included adverse effects, infections, painful venous access and non-adherence. Clinician-level barriers included understaffing, time constraints and safety concerns. Institutional barriers ranged from staff or equipment shortages to liability concerns and complex logistics. Healthcare system barriers included financial constraints and limited care delivery services. Facilitators included evidence-based indications, patient education and comfort, staff experience, guidance documents, safe settings, favourable insurance policies and supportive guidelines.

Conclusions: As novel IV treatments emerge, addressing barriers and leveraging facilitators preemptively can enhance the successful implementation of IV therapies and improve clinical outcomes in ambulatory settings.