BACKGROUND: This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF).
METHODS: This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day.
RESULTS: Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e\') improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF.
CONCLUSIONS: SV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.

CRC is a common but serious complication or sequela of tumor treatment, and new coping strategies are urgently needed. SV is a classic clinical cardiovascular protective drug, which has been widely used in the treatment of heart failure, hypertension and other diseases. It has good therapeutic effect in other cardiovascular diseases such as diabetes cardiomyopathy, ischemic cardiomyopathy and vascular disease, but it has not been proved by research that SV can prevent and treat CRC.
In this study, DOX was used to induce a rat CRC model and evaluate the therapeutic effect of SV on it. Subsequently, R software was applied to analyze the control group, SV group, and DOX group in databases GSE207283 and GSE22369, and to screen for common differentially expressed genes. Use the DAVID website for enrichment analysis and visualization. Use STRING website to analyze and visualize protein interaction networks of key genes. Finally, experimental verification was conducted on key genes.
Our research results show that SV has a protective effect on DOX induced myocardial injury by alleviating Weight loss, increasing Ejection fraction, and reducing the level of biomarkers of myocardial injury. Meanwhile, SV can effectively alleviate the above abnormalities. Bioinformatics and KEGG pathway analysis showed significant enrichment of metabolic and MAPK signaling pathways, suggesting that they may be the main regulatory pathway for SV treatment of CRC. Subsequent studies have also confirmed that SV can inhibit DOX induced myocardial injury through the MAPK signaling pathway, and alleviate DOX induced oxidative stress and inflammatory states.
Our research indicates that SV is a potential drug for treating CRC and preliminarily elucidates its molecular mechanism of regulating the MAPK pathway to improve oxidative stress and inflammation.

BACKGROUND: Sacubitril-valsartan (SV) monotherapy has been shown to help patients with Heart failure with reduced ejection fraction (HFrEF), but whether adding a sodium-glucose cotransporter-2 inhibitor (SGLT2i) improves treatment results even more is unknown.
OBJECTIVE: The goal of this study was to look at the efficacy of SV with additional SGLT2i in HFrEF patients.
METHODS: For this study, several databases, such as PubMed, EMBASE, Web of Science, and the Cochrane Library, were searched. A coherent search approach was used for data extraction. Review Manager 5.2 and MedCalc were used for conducting the meta-analysis and bias analysis. A meta-regression study correlates patient mean age with primary and secondary outcomes.
RESULTS: Seven trials totaling 16 100 patients were included in this meta-analysis. All-cause mortality, cardiovascular mortality, and improvement in mean left ventricular ejection fraction (LVEF) were the study\'s major objectives, while hospitalization for heart failure (HF) was calculated to be its secondary outcome. Our analysis showed that HFrEF patients receiving the combination of SV and SGLT2i had better treatment outcomes than the standard SV monotherapy, with risk ratios of 0.76 (0.65-0.88) for all-cause mortality, 0.65 (0.49-0.86) for cardiovascular mortality, 1.41 (-0.59 to 3.42) for change in mean LVEF, and 0.80 (0.64-1.01) for hospitalization for HF. According to the regression analysis, older HFrEF patients have higher rates of hospitalization, cardiovascular disease, and overall death.
CONCLUSIONS: The combination of SV and SGLT2i may have a greater cardiovascular protective effect and minimize the risk of death or hospitalization due to heart failure in HFrEF.

The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all-cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up-titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up-titration success.
From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1-72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P-value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV-FW-LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794-0.954) to predict maximum Sac/Val dose tolerability.
Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE <16 mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses.

The \"2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure\" replaces the \"2013 ACCF/AHA Guideline for the Management of Heart Failure\" and the \"2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.\" The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.
A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients\' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

The \"2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure\" replaces the \"2013 ACCF/AHA Guideline for the Management of Heart Failure\" and the \"2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.\" The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.
A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients\' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

BACKGROUND: Despite coronary re-vascularization, the common complications of acute myocardial infarction (AMI), cardiac remodeling, and heart failure (HF), is increasing globally. Sacubitril valsartan (SV), an angiotensin receptor-neprilysin inhibitor (ARNI), has been previously demonstrated to improve HF. We further hypothesize that ultra-early SV treatment is also effective in preventing cardiac remodeling for patients with AMI following primary percutaneous coronary intervention (PCI).
METHODS: The Assessment of ultra-early administration of Sacubitril Valsartan to improve cardiac remodeling in patients with Acute Myocardial Infarction following primary PCI (ASV-AMI) trial is a prospective, multicenter, randomized controlled trial in China planning to enroll at least 1,942 eligible patients from 10 centers. After successful primary PCI of culprit artery within 24 h, AMI patients are randomized to 2 h group or 3-7 days group with SV treatment. The major endpoints are echocardiographic measurement, cardiothoracic ratio, and N-Terminal pro-B-Type Natriuretic Peptide (NT pro-BNP) at baseline, 1, 3, 6, and 12 months. The secondary endpoints included MACE (cardiac arrest, cardiogenic death, myocardial infarction, and target vessel re-vascularization), in-/out-patient HF, EuroQol Five Dimensions Questionnaire (EQ-5D), and Kansas City Cardiomyopathy Questionnaire (KCCQ).
CONCLUSIONS: The ASV-AMI trial is the first clinical trial of ultra-early administration of SV in the treatment of post-PCI AMI, adding more clinical evidence. Early application of SV to prevent cardiac remodeling in AMI patient is a major focus of this trial.
BACKGROUND: Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn; ChiCTR2100051979). Registered on 11 October 2021.

BACKGROUND: Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real-world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging.
METHODS: Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA class II-III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy.
RESULTS: After 6-month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, p < 0.001), TAPSE (19 ± 3 vs. 18 ± 3 mm, p < 0.001), RV FAC (38 ± 7 vs. 34 ± 6 mm, p < 0.001), RV S\' (12 ± 2 vs. 10 ± 2 cm/s, p < 0.001), RV-FW-LS (-20 ± 5 vs. -18 ± 5%, p < 0.001), RV-4Ch-LS (-16 ± 5 vs. -14 ± 5%, p < 0.001). At multivariable analysis improvement in RV-FW-LS was associated to baseline levels of RV S\' (r 0.75, p < 0.01) and RAV (r -0.32, p < 0.05).
CONCLUSIONS: In a real-world scenario, 6-month therapy with S/V was associated with an improved RV function in HFrEF. RV function improvement may be predicted by assessing baseline RV S\' and right atrial volume values.

UNASSIGNED: Left ventricular (LV) remodelling is a major mechanism underlying disease progression in patients with heart failure (HF) with reduced ejection fraction (EF). Previous studies that LVEF improvement and reverse remodelling can be achieved after therapy with Sacubitril/Valsartan in real-world settings. Therefore, we sought to investigate possible predictors of LV remodelling, in particular echocardiographic parameters derived by Tissue Doppler Imaging.
UNASSIGNED: Patients with chronic HF, LV dysfunction (EF < 35%), NYHA class II-III were followed up between September 2016 and January 2019. All patients underwent clinical and echocardiography follow up at baseline and after 12 months of therapy with sacubitril/valsartan.
UNASSIGNED: Fifty-four consecutive outpatients were enrolled in the study. At follow-up visit LVEF (38 ± 9 vs. 30 ± 5%, p < 0.0001), LVEDD (61 ± 8 vs. 62 ± 8 mm, p = 0.0085), LVESV (114 ± 57 vs. 130 ± 56 mm3, p = 0.0001), mitral regurgitation severity (1 ± 1 vs. 2 ± 1, p < 0.0001), and left atrial area (23 ± 6 vs. 24 ± 6 mm2, p = 0.0121) changed compared to the baseline value. Changes in LVEF (follow up vs baseline) correlated with baseline levels of heart rate (r = 0.24, p = 0.048), LVEDD (r= -0.33, p = 0.004), LVEDV (r= -0.39, p = 0.001), LVESV (r = 0.37, p = 0.002), and changes in LVESV (r=-0.34, p = 0.006). Correlations remained significant even after correction at multivariate analysis including age and gender.
UNASSIGNED: Treatment with sacubitril/valsartan in patients with systolic dysfunction is associated with an improvement in LVEF in a real world scenario. Smaller LV volumes are associated with better reverse LV remodelling.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical condition characterized by large pathophysiology heterogeneity with lack of effective therapies as proven by the disappointing results generated by randomized controlled trials. The innovative therapeutic concept provided by sacubitril-valsartan, a molecule combining angiotensin receptor blocking agent and neprilysin inhibitor has suggested the hypothesis it would have led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and preserved ejection fraction. The PARAGON-HF (ClinicalTrials.gov number, NCT01920711) investigated HF subjects class II to IV HF, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The trial missed the primary outcome of cardiovascular death and HF hospitalization (HFH) in the overall study population. A subgroup analysis addressed significant decrease of HFH in subjects with left ventricular ejection fraction below the median 57% value in the study. The data were consistent with previous post hoc analysis performed in studies where candesartan and spironolactone were investigated in HFpEF. Those results open the door to investigate angiotensin aldosterone and peptidases inhibition efficacy in the unexplored HF middle range ejection fraction, currently lacking of valid evidence.