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STUDY OBJECTIVE: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied. DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS/OUTCOME MEASURES: Using the American Heart Associations Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19. RESULTS: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20-3/24/21) and 26,459 patients were admitted in the year prior (2/16/19-2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p

BACKGROUND: Despite evidence that guideline-directed medical therapies (GDMTs) improve outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF), implementation remains suboptimal. OBJECTIVES: The purpose of this study was to measure GDMT implementation during acute HFrEF hospitalization, evaluate the association between socioeconomic factors and GDMT implementation, and assess the association of GDMT utilization with subsequent clinical events. METHODS: Retrospective determination of GDMT utilization using a modified optimal medical therapy (mOMT) score (which accounts for specific contraindications to drugs) during unplanned HF hospitalization of consecutive adult patients with new-onset or previously diagnosed HFrEF from 2017 to 2018. Outcomes included discharge mOMT score, association between socioeconomic factors and GDMT implementation (assessed using both the Mann-Whitney U test for binary variables and the Kruskall-Wallace for nonbinary variables), composite outcome 1-year all-cause mortality and 1-year HF readmission, and each component as a function of discharge mOMT score (assessed using univariate and multivariable Cox proportional hazards regression models). RESULTS: Of 391 patients fulfilling entry criteria (of which 152 [38.9%] had new-onset HFrEF), only 49 (12.5%) had a perfect or near-perfect discharge mOMT score. Black patients and those experiencing homelessness had significantly lower discharge mOMT scores. Higher discharge mOMT score is associated with a lower rate of composite endpoint events, particularly in patients with new-onset HFrEF. Overall, a 0.1-increase in the mOMT score resulted in a 9.2% reduction in the composite endpoint. CONCLUSIONS: Suboptimal implementation of GDMT during HF hospitalization is widespread and is associated with a worse outcome. Black patients and patients experiencing homelessness were less likely to have GDMT optimized.

Background: New type of arrhythmia called atrial high-rate episodes (AHREs) has been discovered thanks to the ability of cardiac electronic implantable devices to track, record, and analyze complex arrhythmias. The aim is to determine factors associated with AHRE in HFrEF/CRT patients and the effect of AHRE on functional capacity and quality of life (QoL). Results: We interrogated 100 patients' devices to gauge the incidence and burden of AHRE, then assessed their functional capacity using the standard 6-min walk test (6MWT), and evaluated their QoL using the Minnesota Living with HF questionnaire (MLHFQ) score. 34% of patients had AHRE, and 91.2% of them had AF. By multivariate logistic regression analysis, smoking (OR 9.426, 95% CI [1.33, 66.65], P 0.025), higher BMI (OR 1.336, 95% CI [1.09, 1.635], P 0.005), and increased LAVI (OR 1.16, 95% CI [1.063, 1.262], P < 0.001) are independent predictors for AHRE. There was a significant correlation between AHRE and the distance walked during 6MWT when compared to the distance expected for an equivalent healthy individual (82.02 ± 17.22% in the non-AHRE group vs. 75.15 ± 15.78% in the AHRE group, P < 0.001). It was found that AHRE was statistically linked to a higher total MLHFQ score (46.76 ± 9.82 in the AHRE group vs. 36.97 ± 7.76 in the non-AHRE group, P 0.032), with higher physical scores in the AHRE group. Conclusion: AHRE significantly reduces functional status and perceived quality of life in HFrEF patients receiving CRT. Longer than five minutes of AHRE was associated with a higher MLHFQ score and worse performance on the 6MWT. In that patient population, smoking, obesity, and elevated LAVI were independent predictors of AHRE. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the therapeutic effect of Vericiguat through cardiopulmonary exercise testing (CPET) in patients with chronic heart failure and reduced ejection fraction (HFrEF). Methods: A prospective observational study was conducted from May 2022 to May 2023, focusing on patients with HFrEF admitted to our hospital. Eligible patients were sequentially numbered and enrolled based on specific inclusion and exclusion criteria. They were divided into two groups: one receiving standard heart failure therapy and the other receiving standard therapy plus Vericiguat. Data were collected at baseline and at 1, 3, and 6 months post-discharge, including NT-proBNP, sST2, and echocardiographic assessments. All patients underwent CPET before discharge and again six months post-discharge for within-subject comparisons. Results: The study enrolled 158 patients, with 79 in each treatment arm. No significant baseline differences were observed in the Weber Functional Classification or CPET parameters. At six months, the Vericiguat group exhibited a significant reduction in patients classified as C (from 31.6 to 7.5%) and D (from 31.6 to 3.7%), with P values less than 0.05. Additionally, Vericiguat significantly improved Peak Oxygen Consumption (from 14.24 ± 6.21 to 19.03 ± 4.87 ml/kg/min) and Anaerobic Threshold (from 10.48 ± 3.82 to 13.48 ± 3.31 ml/kg/min). Compared to the standard treatment group, the Vericiguat group demonstrated significantly higher Peak Oxygen Consumption, Anaerobic Threshold, and a lower Carbon Dioxide Equivalent Slope, with P values all below 0.05. Conclusions: Vericiguat safely enhances exercise tolerance, as evaluated by CPET, in high-risk patients with HFrEF. [ABSTRACT FROM AUTHOR]

Objective: Impaired right ventricular (RV)-pulmonary arterial (PA) coupling, calculated by measuring the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), can be used as an early indicator of right ventricular dysfunction (RVD) in patients with heart failure with a reduced ejection fraction (HFrEF). Patients suffering from HFrEF experience improvements in left ventricular (LV) function through the administration of sacubitril/valsartan therapy. In addition, the albumin-bilirubin (ALBI) score was associated with the fluid overload status and adverse clinical outcomes in patients with heart failure. This study aimed to assess whether angiotensin receptor-neprilysin inhibitor (ARNI) affects the TAPSE /PASP in patients with HFrEF, and whether there is a correlation between changes in the ALBI score and ARNI treatment. Methods: A retrospective observational study was conducted on 305 patients with HFrEF and RVD who were hospitalized between June 2020 and December 2021. One year after treatment, laboratory test results, ALBI score, transthoracic echocardiography (TTE), New York Heart Association classification, Minnesota Living with Heart Failure Questionnaire scores and changes in relevant variables were reevaluated. Results: Compared to before sacubitril/valsartan treatment, the ALBI was found to be significantly reduced after one year of follow-up (-2.42 ± 0.37 vs. -2.51 ± 0.32, p < 0.001). Additionally, A significant improvement was demonstrated in the following echocardiography parameters assessing RV function after 1 year of treatment with sacubitril/valsartan: TAPSE (15 ± 1 vs. 18 ± 2 mm, p < 0.001), PASP (45 ± 8 vs. 40 ± 9 mmHg, p < 0.001), pulmonary artery diastolic pressure (PADP) (22 ± 4 vs. 19 ± 4 mmHg, p < 0.001), RV-PA coupling (0.35 ± 0.08 vs. 0.48 ± 0.12, p < 0.001), and RV s'(8.7 ± 2.2 vs. 9.5 ± 2.6 cm/s, p < 0.001). Multivariate analysis showed that the improvement of RV-PA coupling was associated with baseline PASP (r: -0.45, p < 0.001) and PADP (r: -0.45, p < 0.001). Conclusions: Sacubitril/valsartan improves RV-PA conjugation in patients with RVD and HFrEF, and has a positive impact on the ALBI score by improving liver function in patients with HFrEF. [ABSTRACT FROM AUTHOR]

• Depressive symptoms (DS) and physical inactivity (PIA) predict event-free survival in patients with heart failure (HF). • In patients with HF and reduced ejection fraction, DS and PIA interact to predict the combined endpoint of rehospitalization or mortality. • In patients with HF and preserved ejection fraction, DS alone predict the combined endpoint of rehospitalization or mortality. Heart failure (HF) subtype, depressive symptoms, and physical inactivity independently contribute to survival outcomes, but the effect of the interaction of these variables on survival outcomes remains unknown. We aimed to determine whether depressive symptoms and engagement in physical activity differentially interact to predict the combined endpoint of all-cause death or rehospitalization among patients with HF and reduced (HFrEF) or preserved ejection fraction (HFpEF). This study was a secondary analysis. The sample was categorized by the presence or absence of depressive symptoms, and engagement or non-engagement in physical activity. Cox proportional hazard modeling was used to predict the combined endpoint of all-cause death or rehospitalization. A total of 1002 patients with HF were included (mean age 64.3 ± 12.7 years; 637 males [64 %]; 844 White [84 %]). Among them, 35.3 % did not engage in physical activity, while 64.7 % engaged in any level of physical activity, and 29.7 % had depressive symptoms. In both subtypes, depressive symptoms were associated with the highest risk of all-cause death or rehospitalization. Among patients with HFrEF, those with depressive symptoms who did not engage in physical activity were associated with a 136 % higher risk of the combined endpoint, while among those with HFpEF, depressive symptoms and engagement in physical activity were associated with a 78 % higher risk. Depressive symptoms and lack of physical activity predicted the combined endpoint of all-cause death or rehospitalization among patients with HFrEF, while depressive symptoms alone were the strongest predictor among patients with HFpEF. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heart failure (HF) constitutes a complex clinical syndrome that is highly prevalent worldwide, comprises a serious prognosis, and results in a reduced quality of life. Exercise capacity is one of the most significant parameters involved in the prognosis in HF patients. Our objective was to evaluate the relationship between the selected cardiopulmonary exercise testing (CPET) parameters and the concentration of novel biomarker sST2 in a group of patients with heart failure with reduced ejection fraction (HFrEF). Methods: A group of 135 patients with HFrEF was enrolled in this prospective cohort study. Patients were in the stable phase of the disease in the prior 4 weeks and received optimal medical treatment. Clinical and biochemical parameters were investigated. All patients performed maximal CPET. Results: The mean (SD) concentration of sST2 was 45.5 ± 39.2 ng/mL. Based on the CPET results, the cut-off value (52.377 ng/mL) was established, optimal for the discrimination of relative peakVO2 < 12 mL/kg/min. Patients were divided into two groups according to sST2 cut-off values determined with an ROC curve (AUC 0.692, 95% CI: 0.567–0.816). The mean relative peakVO2 in patients with higher sST2 was 14.5 ± 4.6 mL/kg/min, while in the second group, it was 17.6 ± 5.2 (p = 0.002). In the sST2 ≥ 52.377 ng/mL group, 55.6% of patients achieved VO2 < 50%. Subjects with lower sST2 values obtained higher values of PETCO2 (p < 0.001) and higher values of pulse O2 (p = 0.01). VE/VCO2slope (p = 0.002) was higher in patients with increased sST2 concentration. Conclusions: The concentration of sST2 protein is substantially associated with the clinical severity of heart failure with reduced left ventricular ejection fraction assessed by functional capacity through CPET. [ABSTRACT FROM AUTHOR]

Objective: People living with HIV have an increased risk of heart failure (HF). There are different subtypes of HF. Knowledge about the factors differentiating HF subtypes in people with HIV is limited but necessary to guide preventive measures and treatment. Methods: A retrospective review of medical records was undertaken in people with HIV aged ≥18 years who received care at the University of Miami/Jackson Memorial HIV Clinic between January 2017 and November 2019 (N = 1166). Patients with an echocardiogram available for review (n = 305) were included. HF was defined as a documented diagnosis of any HF subtype (n = 52). We stratified those with HF by their ejection fraction (EF) into HF with preserved EF (HFpEF), HF with borderline EF, or HF with reduced EF (HFrEF). Results: The prevalence of HF was 4.5%. The cohort included 46.2% females and 75% self‐identified African Americans. Those with HF had a higher prevalence of hypertension, prior myocardial infarction, angina, coronary artery disease, percutaneous coronary intervention, coronary artery bypass grafting, diastolic dysfunction, and left ventricle hypertrophy. People with HIV with HF with borderline EF exhibited more coronary artery disease than those with HFpEF. Conclusions: We characterize HF in people with HIV in South Florida and report the prevalence of HF and HF subtypes. Only a small percentage of patients had echocardiograms performed, suggesting an ongoing need for recognition of the increased risk of HF in people living with HIV, and raising the concern about lack of awareness contributing to underdiagnosis and missed treatment opportunities in this population. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heart failure presents a significant public health challenge, affecting millions in the US, with projections of increasing prevalence and economic burdens. Obstructive sleep apnea (OSA) is highly prevalent among HF patients. This study analyzes the impact of OSA on the outcomes in patients admitted with acute decompensated heart failure. Methods: We conducted a retrospective cohort study using the National Inpatient Sample database (NIS) 2020, focusing on patients admitted with acute heart failure. Patient outcomes were compared between those with and without a secondary diagnosis of OSA, identified via validated ICD-10 codes. Subgroup analysis was conducted between heart failure patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Results: Among 65,649 patients with acute heart failure, 4595 (7%) patients were found to have OSA. The patients with OSA were more likely to be male, older in age and had a higher burden of comorbidities. No significant differences were observed in mortality between heart failure patients with and without OSA. In HFrEF patients, OSA was associated with longer hospital stays (6.45 days vs. 5.79 days, p < 0.001), higher rates of acute kidney injury (AKI) (adjusted odds ratio 1.28, 95% CI: 1.07–1.54, p = 0.007), and atrial fibrillation (adjusted odds ratio 1.35, 95% CI: 1.13–1.61, p = 0.001). In HFpEF patients, an association between OSA and AF was observed (adjusted odds ratio 1.20, 95% CI: 1.01–1.42, p = 0.03). Conclusions: OSA is associated with poor in-hospital outcomes in patients admitted with acute heart failure. HFrEF subgroup is especially vulnerable, with OSA leading to a significant increase in healthcare utilization and complication rates in these patients. This nationwide study underscores the importance of timely identification and treatment of OSA in heart failure to alleviate healthcare burdens and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure (HF) with improved ejection fraction (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. The identification of predictors for HFimpEF may play a crucial role in the individual management of HF with reduced ejection fraction (HFrEF). Cell-free nuclear (cf-nDNA) DNA is released from damaged cells and contributes to impaired cardiac structure and function and inflammation. The purpose of the study was to elucidate whether cf-nDNA is associated with HFimpEF. Methods: The study prescreened 1416 patients with HF using a local database. Between October 2021 and August 2022, we included 452 patients with chronic HFrEF after prescription of optimal guideline-based therapy and identified 177 HFimpEF individuals. Circulating biomarkers were measured at baseline and after 6 months. Detection of cf-nDNA was executed with real-time quantitative PCR (qPCR) using NADH dehydrogenase, ND2, and beta-2-microglobulin. Results: We found that HFimpEF was associated with a significant decrease in the levels of cf-nDNA when compared with the patients from persistent HFrEF cohort. The presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; p = 0.044), type 2 diabetes mellitus (OR = 0.77; p = 0.042), and digoxin administration (OR = 0.85; p = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤ 1940 pmol/mL (OR = 1.42, p = 0.001), relative decrease in NT-proBNP levels (>35% vs. ≤35%) from baseline (OR = 1.52; p = 0.001), and cf-nDNA ≤ 7.5 μmol/L (OR = 1.56; p = 0.001) were positive predictors for HFimpEF. Conclusions: We established that the levels of cf-nDNA ≤ 7.5 μmol/L independently predicted HFimpEF and improved the discriminative ability of ischemia-induced cardiomyopathy, IV NYHA class, and single-measured NT-proBNP and led to a relative decrease in NT-proBNP levels ≤35% from baseline in individuals with HFrEF. [ABSTRACT FROM AUTHOR]

Aims: Functional capacity provides important clinical information in patients with heart failure (HF) and reduced ejection fraction (HFrEF). The 6‐min walk test (6MWT) is a simple and inexpensive tool for assessing functional capacity and risk. Although change in 6MWT is frequently used as a surrogate outcome in HF trials, the association with mortality is unclear. We aimed to assess the prognostic importance of changes in 6MWT. Methods and results: Patients with chronic HFrEF referred to HF outpatient clinics in Norway completed a 6MWT at the first visit (baseline) and at a stable follow‐up visit after treatment optimization (follow‐up). Absolute and relative changes in 6MWT were analysed in association with mortality risk using Cox regression models and flexible cubic splines. The study included 3636 HFrEF patients aged 67.3 ± 11.6 years, 23% women, with left ventricular ejection fraction 30 ± 7%. At baseline, mean 6MWT was 438 ± 125 m, median N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) 1574 (732–3093) ng/L, and 27% had New York Heart Association (NYHA) class III/IV. After optimization of guideline‐directed medical therapy (median 147 [86–240] days), 6MWT increased by mean 40 ± 74 m, NT‐proBNP decreased by median 425 (14–1322) ng/L, and NYHA class improved in 38% of patients. Patients with greater improvements in 6MWT were younger, with greater improvements in NYHA class (r = 0.27, p < 0.001) and larger reductions in NT‐proBNP concentrations (r = 0.19, p < 0.001). After mean 845 ± 595 days, 419 (11.5%) patients were dead. Both absolute and relative changes in 6MWT were non‐linearly associated with survival, attenuating as 6MWT increased. A 50 m increase in 6MWT was associated with a 17% lower mortality risk (hazard ratio 0.84, 95% confidence interval 0.77–0.90, p < 0.001) in the fully adjusted model, including changes in NYHA class, NT‐proBNP concentrations, and other established risk factors. The associations were more pronounced in patients with lower baseline 6MWT and higher age. Conclusion: Improvement in 6MWT in patients with HFrEF is associated with increased survival, independent of changes in NT‐proBNP and NYHA class. These findings support 6MWT change as a surrogate outcome in HF trials. [ABSTRACT FROM AUTHOR]

Aims: We investigated the prevalence, clinical characteristics, and prognosis of patients with heart failure (HF) with improved ejection fraction (HFimpEF). Methods and results: We used data from BIOSTAT‐CHF including patients with a left ventricular ejection fraction (LVEF) ≤40% at baseline who had LVEF re‐assessed at 9 months. HFimpEF was defined as a LVEF >40% and a LVEF ≥10% increase from baseline at 9 months. We validated findings in the ASIAN‐HF registry. The primary outcome was a composite of time to HF rehospitalization or all‐cause mortality. In BIOSTAT‐CHF, about 20% of patients developed HFimpEF, that was associated with a lower primary event rate of all‐cause mortality (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.28–0.97, p = 0.040) and the composite endpoint (HR 0.46, 95% CI 0.30–0.70, p < 0.001) compared with patients who remained in persistent HF with reduced ejection fraction (HFrEF). The findings were similar in the ASIAN‐HF (HR 0.40, 95% CI 0.18–0.89, p = 0.024, and HR 0.29, 95% CI 0.17–0.48, p < 0.001). Five independently common predictors for HFimpEF in both BIOSTAT‐CHF and ASIAN‐HF were female sex, absence of ischaemic heart disease, higher LVEF, smaller left ventricular end‐diastolic and end‐systolic diameter at baseline. A predictive model combining only five predictors (absence of ischaemic heart disease and left bundle branch block, smaller left ventricular end‐systolic and left atrial diameter, and higher platelet count) for HFimpEF in the BIOSTAT‐CHF achieved an area under the curve of 0.772 and 0.688 in the ASIAN‐HF (due to missing left atrial diameter and platelet count). Conclusions: Approximately 20–30% of patients with HFrEF improved to HFimpEF within 1 year with better clinical outcomes. In addition, the predictive model with clinical predictors could more accurately predict HFimpEF in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Aims: Inflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with HF. Methods: We analysed interleukin‐6 and hsCRP levels by ELISA and immunonephelometry, respectively, in HFpEF and HFrEF patients referred for coronary angiography and assessed the prognostic value in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Results: HF was present in 1086 patients (N = 506 HFpEF; N = 580 HFrEF; mean age 65 ± 10 years; 28% female). Increasing IL‐6 levels were significantly associated with increased CV mortality in HFpEF [1.5 (95% CI: 1.1–2.2), P = 0.018] but not HFrEF [HR 1.3 (95% CI: 1.0–1.7), P = 0.06] patients. High‐sensitive CRP followed a similar pattern but failed to reach statistical significance after full‐adjustment (HFpEF: HR 1.4 95%C I: 1.0–2.0; P = 0.065; HFrEF HR: 1.0 95% CI: 0.7–1.3; P = 0.800). Interaction analysis in patients stratified by IL‐6 and N terminal pro brain natriuretic peptide (NT‐proBNP) above and below the median revealed a stepwise increase in CV‐mortality in HFpEF (P = 0.036) but not HFrEF patients (P = 0.220). To investigate the relationship between IL‐6 and NT‐proBNP, we assessed the genetic IL6‐Receptor variant p.Asp358Ala (rs2228145) which is linked to impaired IL‐6 receptor signalling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT‐pro‐BNP levels compared with wildtype carriers (HFpEF 779 pg/mL ± 787 vs. 1180 pg/ mL ± 1532; P = 0.008; HFrEF 2289 pg/ mL ± 3439 vs. 2326 pg/ mL ± 3386; P = 0.94), raising the hypothesis that IL‐6 signalling may play a pathophysiological role in HFpEF. Conclusions: These data suggest a predictive value of elevated IL‐6 for CV‐mortality in HFpEF but not in HFrEF patients. [ABSTRACT FROM AUTHOR]

Background: Despite atrial fibrillation guideline recommendations, many patients with heart failure with reduced ejection fraction (EF) continue to receive IV diltiazem for acute rate control. Objective: Our institution recently implemented a clinical decision support system (CDSS)-based tool that recommends against the use of diltiazem in patients with an EF ≤ 40%. The objective of this study was to evaluate outcomes of adherence to the aforementioned CDSS-based tool. Methods: This multi-hospital, retrospective study assessed patients who triggered the CDSS alert and compared those who did and did not discontinue diltiazem. The primary outcome was the occurrence of clinical deterioration. The primary endpoint was compared utilizing a Fisher's Exact Test, and a multivariate logistic regression model was developed to confirm the results of the primary analysis. Results: A total of 246 patients were included in this study with 146 patients in the nonadherent group (received diltiazem) and 100 patients in the adherent group (did not receive diltiazem). There was a higher proportion of patients experiencing clinical deterioration in the alert nonadherence group (33% vs 21%, P = 0.044), including increased utilization of inotropes and vasopressors, and higher rate of transfer to ICU. Conclusion and Relevance: In patients with heart failure with reduced EF, diltiazem use after nonadherence to a CDSS alert resulted in an increased risk of clinical deterioration. This study highlights the need for improved provider adherence to diltiazem clinical decision support systems. [ABSTRACT FROM AUTHOR]

Abstract Background There is conflicting evidence regarding whether heart failure (HF) increases the risk of developing cancer. Objective This study aimed to assess the association between HF and incident cancer, considering gender differences and HF phenotypes. Methods This retrospective study was conducted on data of adult individuals, free of cancer at baseline, from the First Affiliated Hospital of Wenzhou Medical University between January 2009 and February 2023. The patients with HF were categorized as HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). The primary outcome was incident cancer, including obesity‐related, tobacco‐related, lung, colorectal and breast cancers. Results Of 33 033 individuals enrolled, 16 722 were diagnosed with HF, including 10 086 (60.3%) with HFpEF and 6636 (39.7%) with HFrEF. During a median follow‐up period of 4.6 years (inter‐quartile range: 2.6–7.3), incident cancer was diagnosed in 10.5% (1707 patients) of the non‐HF group and 15.1% (2533 individuals) of the HF group. After adjusting for potential confounding factors, patients with HF had a 58% increased risk of cancer than those without HF [adjusted hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.48–1.69, P

Abstract 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

Background: The present study aimed to assess the response of sacubitril/valsartan therapy on cardiac reverse remodeling (CRR) by standard and advanced echocardiographic parameters in patients of heart failure with reduced ejection fraction (HFrEF). Methods: One hundred and fifty patients ≥18 years of age with symptomatic heart failure with left ventricular ejection fraction (LVEF)

Abstract Aims Inflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with HF. Methods We analysed interleukin‐6 and hsCRP levels by ELISA and immunonephelometry, respectively, in HFpEF and HFrEF patients referred for coronary angiography and assessed the prognostic value in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Results HF was present in 1086 patients (N = 506 HFpEF; N = 580 HFrEF; mean age 65 ± 10 years; 28% female). Increasing IL‐6 levels were significantly associated with increased CV mortality in HFpEF [1.5 (95% CI: 1.1–2.2), P = 0.018] but not HFrEF [HR 1.3 (95% CI: 1.0–1.7), P = 0.06] patients. High‐sensitive CRP followed a similar pattern but failed to reach statistical significance after full‐adjustment (HFpEF: HR 1.4 95%C I: 1.0–2.0; P = 0.065; HFrEF HR: 1.0 95% CI: 0.7–1.3; P = 0.800). Interaction analysis in patients stratified by IL‐6 and N terminal pro brain natriuretic peptide (NT‐proBNP) above and below the median revealed a stepwise increase in CV‐mortality in HFpEF (P = 0.036) but not HFrEF patients (P = 0.220). To investigate the relationship between IL‐6 and NT‐proBNP, we assessed the genetic IL6‐Receptor variant p.Asp358Ala (rs2228145) which is linked to impaired IL‐6 receptor signalling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT‐pro‐BNP levels compared with wildtype carriers (HFpEF 779 pg/mL ± 787 vs. 1180 pg/ mL ± 1532; P = 0.008; HFrEF 2289 pg/ mL ± 3439 vs. 2326 pg/ mL ± 3386; P = 0.94), raising the hypothesis that IL‐6 signalling may play a pathophysiological role in HFpEF. Conclusions These data suggest a predictive value of elevated IL‐6 for CV‐mortality in HFpEF but not in HFrEF patients.

Abstract Background Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles. Methods From January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m2; E/e′

Abstract Background Evidence for the efficacy of pharmacological therapies for heart failure with reduced ejection fraction (HFrEF) is growing. However, there is no consensus on the most effective treatment for HFrEF. This study aimed to evaluate the most effective combination of pharmacological therapy in patients with HFrEF. Methods We systematically searched Medline, Embase, and CENTRAL up to Feb 2022, to include randomized controlled trials (RCTs) that evaluated the efficacy of pharmacological treatment among adults (≥ 18 years) with a diagnosis of HFrEF (defined by a left ventricular ejection fraction ≤ 45%). The outcomes of interest included all-cause death, cardiovascular (CV) death, and hospitalization for heart failure (HHF). A random network meta-analysis using a frequentist framework model was employed to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) and rank the treatments. Results We included 49 RCTs involving 90,529 participants with HFrEF. For reducing all-cause mortality, the combination of angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) was most effective (RR, 0.46; 95% CI, 0.32–0.66). For CV death, the combination of ACEI, BB, MRA, and Vericiguat showed the highest efficacy (RR, 0.34; 95% CI, 0.12–0.90). Regarding reducing HHF, the combination of ACEI, BB, MRA, and SGLT2i as well as the combination of ACEI, BB, MRA, and Ivabradine were equally the most effective (both RR, 0.27; 95% CI, 0.18–0.39). Conclusion This study provides robust evidence supporting the use of combination therapies in HFrEF management, with newer agents offering incremental benefits when added to established guideline-directed medical therapy.

Abstract Background Hypertension (HTN) and diabetes mellitus (DM) are two common comorbidities of heart failure with reduced ejection fraction (HFrEF), each of which can cause right ventricular (RV) dysfunction. The aim of this study was to investigate the impact of DM on RV dysfunction and ventricular interdependence in hypertensive HFrEF patients via cardiac magnetic resonance imaging (MRI) feature tracking. Methods This study included 249 patients with HFrEF: 77 HFrEF controls, 97 with hypertensive HFrEF (HTN-HFrEF [DM-]) and 75 with hypertensive HFrEF and comorbid DM (HTN-HFrEF [DM+]). The cardiac MRI-derived biventricular global radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were obtained and compared among the groups. Multivariable linear regression and mediation analyses were used to evaluate the effects of DM and left ventricular (LV) strain on RV strain. Results The biventricular GLS and GLS of segments 8, 9 and 14 of the interventricular septum (IVS) decreased gradually from the HFrEF control group to the HTN-HFrEF (DM−) group to the HTN-HFrEF (DM+) group (all P

Background and Aims. There are limited data on real clinical practice in heart failure patients in the Czech Republic. We analysed the clinical parameters from the Moravian Midlands Registry (MMR) and compared them to LCZ696 patients in the Paradigm-HF trial. The Moravian Midlands Registry is a retrospective patient database from two outpatient cardiology centres in the Czech Republic. The Paradigm-HF is a large-scale prospective randomized multicentre trial with more than 8000 individuals with stabilized chronic heart failure. Methods. A retrospective analysis of heart failure with reduced ejection fraction patients from two outpatient ­cardiology centres in the Czech Republic from October 2016 to December 2019. Results. Patients in the MMR were younger (60.5 ± 10.7 vs 63.8 ± 11.5 years, P

Sultan Al Raddadi,1– 3 Majed Almutairi,1,3 Kholoud AlAamer,1,3 Abdulmahsen Alsalman,3,4 Maram Albalawi,5 Meshary Almeshary,1,3 Hisham A Badreldin,1,2,6 Hind Almodaimegh1– 3 1Department of Pharmaceutical Care, King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia; 2Department of Pharmacy Practice, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Department of Research Office, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 4Department of Cardiology Science, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 5Department of Biostatistics and Bioinformatics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 6Department of Saudi Biobank, King Abdullah International Medical Research Center, Riyadh, Saudi ArabiaCorrespondence: Sultan Al Raddadi, Department of Pharmaceutical Care, King Abdulaziz Medical City-Riyadh, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia, Email abuibrahim89@yahoo.comBackground: Sacubitril/valsartan (S/V) is used in managing heart failure with reduced ejection fraction (HFrEF), reducing morbidity and mortality while improving symptoms and prognosis. This study aims to evaluate the effectiveness of S/V in patients with reduced left ventricular ejection fraction (LVEF) and its safety.Methods: This retrospective cohort study included adult patients aged ≥ 18 years diagnosed with HFrEF, receiving S/V, and followed up at a tertiary hospital in Riyadh. Primary outcomes included improvements in LVEF on echocardiography and the number of hospitalizations due to acute decompensated heart failure (ADHF). Secondary outcomes assessed the safety profile of S/V. Multinomial logistic regression analysis was performed with statistical significance set at P < 0.05.&#x202FResults: The study included 107 patients: 80 with LVEF < 30% and 27 with LVEF 30– 40%. Six-month follow-up, LVEF improvement was categorized into three groups: no improvement, LVEF increased by 1 to < 10 points, and LVEF increased by ≥ 10 points. The LVEF was similar across groups (P = 0.59). Although hospitalizations due to ADHF were not significantly different between groups, they numerically decreased after initiating S/V (P = 0.1). S/V was generally well tolerated.Conclusion: This study suggests no significant benefit from S/V regarding LVEF improvement. It is recommended that heart failure clinics assess and titrate S/V to the maximum tolerated dose.Keywords: heart failure with reduced ejection fraction, left ventricular ejection fraction, angiotensin receptor neprilysin inhibitors, sacubitril/valsartan

Aims Methods and results Conclusion Mineralocorticoid receptor antagonists (MRA) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but are underused. Point prevalent use has been described, but the kinetics of discontinuation and the extent of reinitiation have not been studied.Patients with HFrEF enrolled in the Swedish Heart Failure Registry between 2006 and 2021 were linked to the Prescribed Drug Register. The rate of discontinuation during the first year of treatment and reinitiation the year after discontinuation were estimated using the Kaplan–Meier method. Multivariable Cox proportional hazards models were used to assess the predictors of discontinuation. Of 11 474 MRA new users, 71% remained on therapy at 1 year. Baseline characteristics independently associated with discontinuation were: estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.34–2.27), hyperkalaemia (HR 1.73, 95% CI 1.25–2.40), eGFR 30–60 ml/min/1.73 m2 (HR 1.51, 95% CI 1.37–1.66), age ≥80 years (HR 1.26, 95% CI 1.10–1.43), enrolment as inpatient (HR 1.25, 95% CI 1.14–1.38), a diagnosis of atrial fibrillation (HR 1.24, 95% CI 1.10–1.39), living alone (HR 1.23, 95% CI 1.13–1.34), ischaemic heart disease (HR 1.20, 95% CI 1.09–1.31), anaemia (HR 1.17, 95% CI 1.07–1.29), diabetes mellitus (HR 1.15, 95% CI 1.04–1.27) and New York Heart Association class III–IV (HR 1.13, 95% CI 1.02–1.24). Reinitiation within a year occurred in 46% of cases, mostly within 3 months after discontinuation.Among patients with HFrEF initiated on MRA, 71% remained on therapy at 1 year. Discontinuation occurred early and was more common in patients with advanced kidney disease, hyperkalaemia, lack of follow‐up in specialty care, more severe heart failure, comorbidities, and markers of sociodemographic frailty. Among those who discontinued, almost half reinitiated treatment the year following discontinuation. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Progressive heart failure with reduced ejection fraction (HFrEF) is adversely affected by alterations in the myocardial balance between bone marrow‐derived pro‐inflammatory cardiac macrophages and embryo‐derived reparative cardiac resident macrophages. Mesenchymal precursor cells (MPCs) may restore this balance and improve clinical outcomes when inflammation is present. The purpose was to (i) identify risk factors for cardiovascular death (CVD) in control patients with HFrEF in the DREAM‐HF trial, and (ii) determine if MPCs improve major clinical outcomes (CVD, myocardial infarction [MI], stroke) in high‐risk patients with ischaemic HFrEF and inflammation.Cause‐specific regression analyses were used to identify CVD risk factors in DREAM‐HF control patients. Aalen–Johansen cumulative incidence curves were used to examine CVD, 2‐point major adverse cardiovascular events (MACE) (MI or stroke), and 3‐point MACE (CVD or MI or stroke) by treatment group in ischaemic vs non‐ischaemic HFrEF and in patients with or without baseline inflammation. In control DREAM‐HF patients, factors portending the greatest risk for CVD were inflammation (baseline plasma high‐sensitivity C‐reactive protein ≥2 mg/L; p = 0.003) and ischaemic HFrEF aetiology (p = 0.097), with increased CVD risk of 61% and 38%, respectively. Over 30‐month mean follow‐up, MPCs reduced 2‐point and 3‐point MACE by 88% (p = 0.005) and 52% (p = 0.018), respectively, in patients with ischaemic HFrEF and inflammation compared to controls.Ischaemic aetiology and inflammation were identified as major risk factors for MACE in control DREAM‐HF patients. A single intramyocardial MPC administration produced the most significant, sustained reduction in 2‐point and 3‐point MACE in patients with ischaemic HFrEF and inflammation. [ABSTRACT FROM AUTHOR]

Background: Evidence for the efficacy of pharmacological therapies for heart failure with reduced ejection fraction (HFrEF) is growing. However, there is no consensus on the most effective treatment for HFrEF. This study aimed to evaluate the most effective combination of pharmacological therapy in patients with HFrEF. Methods: We systematically searched Medline, Embase, and CENTRAL up to Feb 2022, to include randomized controlled trials (RCTs) that evaluated the efficacy of pharmacological treatment among adults (≥ 18 years) with a diagnosis of HFrEF (defined by a left ventricular ejection fraction ≤ 45%). The outcomes of interest included all-cause death, cardiovascular (CV) death, and hospitalization for heart failure (HHF). A random network meta-analysis using a frequentist framework model was employed to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) and rank the treatments. Results: We included 49 RCTs involving 90,529 participants with HFrEF. For reducing all-cause mortality, the combination of angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) was most effective (RR, 0.46; 95% CI, 0.32–0.66). For CV death, the combination of ACEI, BB, MRA, and Vericiguat showed the highest efficacy (RR, 0.34; 95% CI, 0.12–0.90). Regarding reducing HHF, the combination of ACEI, BB, MRA, and SGLT2i as well as the combination of ACEI, BB, MRA, and Ivabradine were equally the most effective (both RR, 0.27; 95% CI, 0.18–0.39). Conclusion: This study provides robust evidence supporting the use of combination therapies in HFrEF management, with newer agents offering incremental benefits when added to established guideline-directed medical therapy. [ABSTRACT FROM AUTHOR]

Background: Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles. Methods: From January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m2; E/e′ < 15; B: SV ≥ 35 ml/m2; E/e′ ≥ 15; C: SV < 35 ml/m2; E/e′ < 15; D: SV < 35 ml/m2; E/e′ ≥ 15). Then, we compared the Dapagliflozin population with two retrospective HF cohorts, hereinafter referred to as Guide Line 2012 (GL 2012) group and Guide Line 2016 (GL 2016) group, in accordance with the HF ESC guidelines in force at the time of patients enrolment. Precisely, we evaluated the changes to baseline in clinical, functional, biochemical, and echocardiographic parameters and compared them to the GL 2012 and GL 2016 groups. Results: Dapagliflozin population (67.18 ± 11.11 years) showed a significant improvement in the echocardiographic and functional parameters (left ventricular ejection fraction [LVEF], LV end-diastolic volume [LVEDV], LVEDV index, stroke volume index [SVi], left atrium volume index [LAVi], filling pressure [E/e′ ratio], tricuspid annular plane systolic excursion [TAPSE], tricuspid annular S′ velocity [RVs'], fractional area change [FAC], inferior vena cava [IVC diameter], pulmonary artery systolic pressure [sPAP], NYHA class, and quality of life) compared to baseline. In particular, TAPSE and right ventricle diameter (RVD1) ameliorate in congestive profiles (B and D); accordingly, the furosemide dose significantly decreased in these profiles. Comparing the three populations, the analysis of echocardiographic parameters (baseline vs follow-up) highlighted a significant decrease of sPAP in the Dapagliflozin population (p < 0.05), while no changes were recorded in the GL 2012 and GL 2016 population. Moreover, at the baseline evaluation, the GL 2012 and 2016 groups needed a higher significant dose of furosemide compared to Dapagliflozin group. Finally, Dapagliflozin patients had significantly fewer rehospitalizations (1.25%) compared with the other two groups (GL 2012 18.89%, p 0.0097; GL 2016 15.32%, p 0.0497). Conclusions: We demonstrate that Dapagliflozin is rapidly effective in an HFrEF real-world population; furthermore, the more significant effect is recorded in HFrEF patients with a congestive profile (B and D), supporting the introduction of Dapagliflozin in patients with a congestive profile and a worse prognosis. In conclusion, our data suggest evaluating the patient's hemodynamic state beyond LVEF in HFrEF. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The prediction of ischaemic stroke in patients with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation (AF) remains challenging. Our aim was to evaluate the performance of machine learning (ML) in identifying the development of ischaemic stroke in this population.We performed a post‐hoc analysis of the WARCEF trial, only including patients without a history of AF. We evaluated the performance of 9 ML models for identifying incident stroke using metrics including area under the curve (AUC) and decision curve analysis. The importance of each feature used in the model was ranked by SAPley Additive exPlanations (SHAP) values.We included 2213 patients with HFrEF but without AF (mean age 58 ± 11 years; 80% male). Of these, 74 (3.3%) had an ischaemic stroke in sinus rhythm during a mean follow‐up of 3.3 ± 1.8 years. Out of the 29 patient‐demographics variables, 12 were selected for the ML training. Almost all ML models demonstrated high AUC values, outperforming the CHA2DS2‐VASc score (AUC: 0.643, 95% confidence interval [CI]: 0.512–0.767). The Support Vector Machine (SVM) and XGBoost models achieved the highest AUCs, with 0.874 (95% CI: 0.769–0.959) and 0.873 (95% CI: 0.783–0.953), respectively. The SVM and LightGBM consistently provided significant net clinical benefits. Key features consistently identified across these models were creatinine clearance (CrCl), blood urea nitrogen (BUN) and warfarin use.Machine‐learning models can be useful in identifying incident ischaemic strokes in patients with HFrEF but without AF. CrCl, BUN and warfarin use were the key features. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Beta‐blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho‐inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta‐blocker compared to those treated with a beta‐blocker.We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta‐blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM‐HF. The primary outcome was time to first heart failure hospitalization or cardiovascular death. Compared to the 7811 patients taking a beta‐blocker, the 588 patients not receiving a beta‐blocker were older, more frequently female, but had a similar mean left ventricular ejection fraction and New York Heart Association class distribution, with little difference in N‐terminal pro‐B‐type natriuretic peptide. Patients not taking beta‐blockers had a higher rate of the primary endpoint than those taking beta‐blockers. The benefit of sacubitril/valsartan on the primary endpoint was evident in both the no beta‐blocker subgroup (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.45–0.82) and the beta‐blocker subgroup (HR 0.82, 95% CI 0.75–0.90; p‐interaction = 0.06). The respective HRs for cardiovascular death were 0.47 (95% CI 0.32–0.69) versus 0.84 (95% CI 0.75–0.95; p‐interaction <0.01) and for HF hospitalization 0.76 (95% CI 0.51–1.12) versus 0.80 (95% CI 0.71–0.90; p‐interaction = 0.73). For all‐cause death, the HR in the no beta‐blocker group was 0.50 (95% CI 0.36–0.71) compared to 0.89 (95% CI 0.80–0.99) in the beta‐blocker group (p‐interaction <0.01). Safety outcomes related to sacubitril/valsartan versus enalapril did not differ according to background beta‐blocker use.Sacubitril/valsartan may be more effective than enalapril in reducing the risk of death in patients not treated with a beta‐blocker compared to those treated with a beta‐blocker, but is effective regardless of beta‐blocker use.Clinical Trial Registration: ClinicalTrials.gov NCT01035255. [ABSTRACT FROM AUTHOR]

Aims Methods Conclusion In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy.The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all‐cause death. As an event‐driven trial, at least 1080 primary events are expected, but follow‐up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo.VICTOR is the first large event‐driven HFrEF trial performed in the contemporary era of quadruple foundational guideline‐directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF. [ABSTRACT FROM AUTHOR]

Background: Hypertension (HTN) and diabetes mellitus (DM) are two common comorbidities of heart failure with reduced ejection fraction (HFrEF), each of which can cause right ventricular (RV) dysfunction. The aim of this study was to investigate the impact of DM on RV dysfunction and ventricular interdependence in hypertensive HFrEF patients via cardiac magnetic resonance imaging (MRI) feature tracking. Methods: This study included 249 patients with HFrEF: 77 HFrEF controls, 97 with hypertensive HFrEF (HTN-HFrEF [DM-]) and 75 with hypertensive HFrEF and comorbid DM (HTN-HFrEF [DM+]). The cardiac MRI-derived biventricular global radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were obtained and compared among the groups. Multivariable linear regression and mediation analyses were used to evaluate the effects of DM and left ventricular (LV) strain on RV strain. Results: The biventricular GLS and GLS of segments 8, 9 and 14 of the interventricular septum (IVS) decreased gradually from the HFrEF control group to the HTN-HFrEF (DM−) group to the HTN-HFrEF (DM+) group (all P < 0.05). Patients with DM had even lower biventricular GCS and IVS strains in all directions in specific segments than did those without DM and the HFrEF controls (all P < 0.05). DM was independently associated with impaired RVGLS and RVGCS (both P < 0.05) in hypertensive HFrEF patients. The difference in RVGLS between the hypertensive HFrEF subgroups was partly mediated by LVGLS [β = 0.80, 95% CI (0.39–1.31)], and that of RVGCS was partly mediated by LVGCS [β = 0.28, 95% CI (0.01–0.62)]. Conclusions: In hypertensive HFrEF patients, comorbid DM may have aggravated RV dysfunction and was an independent determinant of impaired RV strain. RV dysfunction might be directly affected by DM and partially mediated by LV strain through unfavorable ventricular independence. [ABSTRACT FROM AUTHOR]

Aims: We explored timing, settings and predictors of angiotensin receptor–neprilysin inhibitor (ARNI) initiation in a large, nationwide cohort of patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results: Patients with HFrEF (ejection fraction <40%) registered in the Swedish HF Registry in 2017–2021 and naïve to ARNI were evaluated for timing and location of, and their characteristics at ARNI initiation. ARNI use increased from 8.3% in 2017 to 26.7% in 2021. Among 3892 hospitalized patients, 8% initiated ARNI in‐hospital or ≤14 days after discharge, 4% between 15 and 90 days, and 88% >90 days after discharge or never initiated. Factors associated with earlier initiation included follow‐up in specialized HF care, more severe HF, previous HF treatment use and higher income, whereas older age, higher comorbidity burden and living alone were associated with later/no initiation. Of 16 486 HFrEF patients, 8.1% inpatients and 5.9% outpatients initiated an ARNI at the index date. Factors associated with initiation in outpatients were overall consistent with those linked with an in‐hospital/earlier ARNI initiation; 4.9% of 10 209 with HF duration <6 months and 9.1% of 5877 with HF duration ≥6 months initiated ARNI. Predictors of ARNI initiation in HF duration <6 months were inpatient status, lower ejection fraction, hypertension, whereas previous angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker use was associated with less likely initiation. Discontinuation at 1 year ranged between 13% and 20% across the above‐reported analyses. Conclusions: In‐hospital and early initiation of ARNI are limited in real‐world care but still slightly more likely than in outpatients. ARNI were more likely initiated in patients with more severe HF, which might suggest its use as a second‐line treatment and only following worsening of clinical status. One‐year discontinuation rates were consistent regardless of the timing/setting of ARNI initiation. [ABSTRACT FROM AUTHOR]

Aims: Reverse ventricular remodelling, defined as a decrease in left ventricular end‐systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear. Methods and results: We evaluated paired core‐lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a >5% LVEF increase or >15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57–74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow‐up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77–0.88), growth differentiation factor‐15 (ratio 0.74, 95% CI 0.66–0.84), and insulin‐like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73–0.88). Conclusions: Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to assess the response of sacubitril/valsartan therapy on cardiac reverse remodeling (CRR) by standard and advanced echocardiographic parameters in patients of heart failure with reduced ejection fraction (HFrEF). Methods: One hundred and fifty patients ≥18 years of age with symptomatic heart failure with left ventricular ejection fraction (LVEF) <40.0% were included in this prospective observational study. All patients underwent baseline electrocardiography and standard echocardiographic examination. Patients were given sacubitril/valsartan maximal tolerated dose. Echocardiographic measurements were done after 90 days. The primary outcome measure was a change in LVEF, whereas the secondary outcome measures were changes in left ventricular dimensions and volumes, E/e', pulmonary artery systolic pressure (PASP), and global longitudinal strain (GLS). Comparisons between two discrete variables and medians were performed using the Chi-square test/Fisher's exact test and the Wilcoxon signed–rank test, respectively. Results: The median LVEF (32.5% vs. 30.0%) was significantly higher, whereas left ventricular end-diastolic volume (180 vs. 177.5 mL), left ventricular end-systolic volume (127.5 vs. 122.5 mL), left ventricular end-diastolic diameter (59 vs. 58 mm), left ventricular end-systolic diameter (51 vs. 50 mm), PASP (38 vs. 35), E/e' (15 vs. 14), and GLS (−9.0 vs. −10.0) were significantly lower at 3-month follow-up as compared to baseline levels. Sacubitril/valsartan therapy leads to CRR as early as 90 days in patients with HFrEF. Conclusions: In HFrEF patients, sacubitril/valsartan significantly improved CRR. [ABSTRACT FROM AUTHOR]