Circulation: Heart Failure最新文献

Background: Patients with heart failure tend to experience higher rates of hospital readmissions compared with other ambulatory care-sensitive conditions. In Sweden, the nationwide Care Coordination Act (CCA) was introduced in January 2018 with the goal of improving care coordination, resulting in a reduction of readmissions and length of stay. There is insufficient knowledge regarding the effect of this reform on patients with heart failure.

Methods: We studied the association of implementing CCA on all-cause 30-day readmissions and length of stay for patients over 65 years of age with International Classification of Diseases code I50 (Heart Failure). The data set included all admissions with a primary diagnosis of heart failure among elderly, multimorbid patients between 2015 and 2019. An interrupted time series analysis using hierarchical mixed models with random effects clustered at the hospital ward level was conducted.

Results: A total of 111 414 admissions were included. The average readmission rate for patients with heart failure was 26.8% before and 26.7% after the CCA. The average length of stay was 8.4 days before the CCA and 8.1 days after. Mortality within 30 days was 7.3% before the CCA and 7.5% after. There were no significant differences between the periods before and after. In an analysis assessing the overall linear time trend 2 of 21 regions showed a reduction in readmissions and 10 in length of stay.

Conclusions: After introducing the CCA, no detectable impact was found on readmissions or mortality for patients with heart failure, which is in line with previous studies, such as those studying the US Hospital Readmission Reduction Program. Although no overall association with length of stay could be identified, it was reduced in several Swedish regions. The heterogeneity between regions could be used to understand the specific components needed to achieve the reduction of readmissions in future studies.

Background: Although the effects of various combinations of treatments on mortality and morbidity outcomes in heart failure with reduced ejection fraction (HFrEF) have been evaluated, the impact on quality of life is unknown. This study evaluated and compared the composite impact of pharmacological therapies on quality of life in HFrEF using a frequentist network meta-analysis and systematic review methodology.

Methods: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1, 2021 and August 10, 2024. We included all contemporary and efficacious HFrEF therapies used in adults. The primary outcome was change in quality of life measured through the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire, expressed as mean difference (MD).

Results: We identified 41 randomized controlled trials representing 41 145 patients (76.5% male). The trials had a median of 276 participants (105-464), a mean left ventricular ejection fraction of 28%, and a median follow-up time of 5 months (3-8). A combination of angiotensin receptor blocker/neprilysin inhibitors (ARNi)+β-blockers (BB)+sodium-glucose cotransporter 2 inhibitors (SGLT2i; MD, +5.3 [+0.4, +10.3]) was the most effective at improving quality of life followed by ARNi+BB+mineralocorticoid receptor antagonists (MRA)+SGLT2i (MD, +7.1 [-1.0 to +15.2]), ACE inhibitor+BB+MRA+SGLT2i (MD, +5.3 [-2.6, to +13.3]), and ACE inhibitor+BB+MRA+ivabradine (MD, +5.2 [-3.1 to +13.6]), which were not statistically significant. Individually, the most effective treatments for improving quality of life were SGLT2i (MD, +3.4 [+1.4 to +5.30]), ivabradine (MD, +3.3 [+0.1 to +6.4]), ARNi (MD, +2.6 [-3.2 to +8.5]), and MRA (MD, +1.8 [-4.8 to +8.4]).

Conclusions: A composite of ARNi+BB+SGLT2i or ARNi+BB+MRA+SGLT2i was the most effective at improving quality of life in patients with HFrEF.

Background: Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. We aimed to analyze transpulmonary gradients of proteins consumed or elaborated across the lungs to identify mediators of PVD by unbiased proteomics.

Methods: Overall, 21 controls and 160 patients with HF with reduced ejection fraction underwent pulmonary artery catheterization with blood sampling from postcapillary (wedged balloon) and precapillary (unwedged) position to obtain transpulmonary gradients. The samples from controls and HF from the highest (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using the proteomic proximity extension assay (Olink) of 275 proteins. Venous blood concentrations or transpulmonary gradients were analyzed to identify biomarkers or potential mediators of PVD.

Results: Comparison of Q1 and Q4 of PVR identified PSP-D (pulmonary surfactant-associated protein D) as a marker of PVD. Examination of gradients across the lungs in high PVR HF revealed significant uptake of 18 proteins, mostly associated with inflammation (chemokines, oncostatin-M, MMP9 [matrix metalloproteinase 9]) or with TGF (transforming growth factor)/activin pathway (GDF2 [growth differentiation factor 2]/BMP9 [bone morphogenic protein 9]), and release of 5 proteins, notably IL (interleukin) 6 and IL33. In contrast, these protein gradients were negligible in controls and low PVR patients with HF. Active pulmonary release of IL6 contributed to systemic elevation of IL6 and correlated with right ventricular function.

Conclusions: The lungs of patients with HF with high PVR display abnormal uptake and release of proinflammatory cytokines from IL6/gp130 family (IL6, IL33, oncostatin-M), along with increased transpulmonary uptake of GDF2/BMP9. The study shows that proteins orchestrating inflammation or pulmonary vessel remodeling in group 1 pulmonary hypertension, are also operating in patients with PVD due to HF.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06331208.

Background: Fontan conversion (FC) is associated with a lower risk of atrial arrhythmias and thromboembolism, but it is unknown whether FC improves long-term survival. The purpose of this study was to assess the impact of FC on transplant-free survival.

Method: Adults with Fontan palliation were divided into 3 groups: (1) atriopulmonary Fontan connection; (2) atriopulmonary Fontan and subsequent FC to total cavopulmonary connection (TCPC); (3) TCPC at initial Fontan operation. The risk of death/transplant was compared between the 3 groups using Cox regression analysis.

Results: We studied 534 patients (age 27±9 years; males [N=298; 56%]). Patients were divided into atriopulmonary Fontan group (N=199, 37%); FC-TCPC (N=138, 26%); and TCPC (N=197, 37%). The FC-TCPC and TCPC groups have similar 15-year incidence of death/transplant (42% versus 47%; P=0.8), even after excluding the 8% operative mortality in the FC-TCPC group (38% versus 47%; P=0.3). On multivariable analyses, neither FC nor the type of Fontan connection was associated with death/transplant. Rather, the risk factors for death/transplant were older age, hepatorenal dysfunction, heart failure, and higher Fontan pressures. The prevalence and severity of these comorbidities increased with age, suggesting that these factors reflect the duration of Fontan physiology, rather than the type of Fontan connection.

Conclusions: These findings, in addition to the high operative mortality associated with FC, suggest that this may not be the optimal treatment option for most adults with atriopulmonary Fontan presenting with Fontan failure. Duration of Fontan physiology rather than the type of Fontan connection may be the main determinant of outcomes.

Background: Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI) leading to poor outcomes. Specific biomarkers, with subsequent validation of their prognostic relevance in CS, are urgently needed to improve therapies and outcomes. Accordingly, the present study investigated the plasma proteome using proximity extension assay technology to identify novel specific biomarkers with subsequent validation of their prognostic relevance in CS.

Methods: Using proximity extension assay (Olink Explore, 2942 proteins), the proteomic signature in the plasma of 9 AMI patients without shock and 8 AMI patients with CS (AMICS; exploration cohort) at admission was analyzed. Candidate biomarkers were measured in the plasma of 421 patients with AMICS from the CULPRIT-SHOCK cohort (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock; REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01927549, validation cohort). Their prognostic relevance was assessed for 180-day survival as the primary end point.

Results: Proteome profiling was successful for 2925 proteins and identified VEGFR1 (vascular endothelial growth factor receptor 1, also known as Flt1) as elevated in AMICS compared with nonshock AMI in the exploration cohort (P<0.001). In patients from the independent validation cohort, nonsurvivors had markedly higher VEGFR1 levels (6.8 versus 3.8 ng/L; P<0.001). In Cox regression, VEGFR1 levels were independently associated with a higher 180-day mortality risk even after adjusting for the Simplified Acute Physiology Score II (per ng/L; adjusted hazard ratio, 1.06 [95% CI, 1.03-1.09]; P<0.001) and yielded incremental prognostic information in addition to serum lactate levels (P<0.001). The levels of VEGFR1 in surviving (30 days; n=29) and nonsurviving (n=21) patients with AMICS were determined at different time points (days 0, 1, and 5) in a third cohort, showing continuously higher levels in nonsurvivors.

Conclusions: Plasma proteomic screening identified VEGFR1 as an early biomarker in patients with AMICS that provided independent prognostic information in a large cohort of well-defined patients with AMICS.