Impact of sacubitril/valsartan on cardiac and systemic hypoxia in chronic heart failure.
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SUBMITTER: Nougue H
PROVIDER: S-EPMC10755360 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Impact of sacubitril/valsartan on cardiac and systemic hypoxia in chronic heart failure.
Nougué Hélène H Picard François F Cohen-Solal Alain A Logeart Damien D Launay Jean-Marie JM Vodovar Nicolas N
iScience 20231123 1
In heart failure patients with reduced ejection fraction, Sacubitril/valsartan (S/V) increased proBNP T71 glycosylation, which is regulated negatively by hypoxia via miR-30a <i>in vitro</i>. Using a cohort of 73 HFrEF patients who were transitioned from standard HF medication to S/V, we found that the increase in proBNP T71 glycosylation after S/V was associated with a decrease in cardiac hypoxia. We further found that plasma levels of K709-acteylated HIF1α, HIF-regulated and HIF-independent bio ...[more]
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Project description:BackgroundSacubitril/valsartan (S/V) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Data about the immediate, short-, and intermediate-term hemodynamic effects of S/V are limited.MethodsIn this prospective observational study, 37 outpatients with chronic HFrEF were treated with S/V according to current guideline recommendations. Next to clinical, laboratory and echocardiographic parameters, haemodynamic variables were assessed non-invasively by use of inert gas rebreathing and bioimpedance cardiography at baseline and at 2-week, 3-month and 6-month follow-up. The course of variables throughout the study and the relationship between variables were analysed using fractional polynomials.ResultsS/V treatment resulted in short- and intermediate-term improvements in NYHA functional class (2.3 ± 0.6 at baseline vs. 1.9 ± 0.5 at 6-month follow-up, p = 0.14), 6-min walk test (453 ± 110 vs. 528 ± 98 m, p = 0.02), ejection fraction (31 ± 9 vs. 36 ± 12%, p = 0.13), pulmonary artery pressure (39 ± 10 vs. 31 ± 10 mmHg, p = 0.02), and NT-proBNP values (1702 (782-2897 vs. 1004 (599-1627) ng/L, p = 0.03). In addition, S/V caused immediate decreases in systemic vascular resistance index (SVRI) and systolic blood pressure (SBP), which were associated with a simultaneous drop in stroke volume (SV) and cardiac index (CI). However, while SVRI and SBP remained at low levels during further treatment, SV and CI restored rapidly and increased to slightly higher levels thereafter.ConclusionThe vasodilative effects of S/V result in immediate reductions in SVRI, SBP, SV and CI. However, S/V induces reverse cardiac remodelling, which is apparent shortly after treatment initiation and leads to improvements of clinical, functional, echocardiographic, laboratory and haemodynamic variables.
| S-EPMC9493168 | biostudies-literature
Project description:Sacubitril/Valsartan, used for the treatment of heart failure (HF), is a combination of two drugs, an angiotensin receptor inhibitor, and a neprilysin inhibitor, which activates vasoactive peptides. Even though its beneficial effects on cardiac functions have been demonstrated, the mechanisms underpinning these effects remain poorly understood. To achieve more mechanistic insights, we analyzed the profiles of circulating miRNAs in plasma from patients with stable HF with reduced ejection function (HFrEF) and treated with Sacubitril/Valsartan for six months. miRNAs are short (22-24 nt) non-coding RNAs, which are not only emerging as sensitive and stable biomarkers for various diseases but also participate in the regulation of several biological processes. We found that in patients with high levels of miRNAs, specifically miR-29b-3p, miR-221-3p, and miR-503-5p, Sacubitril/Valsartan significantly reduced their levels at follow-up. We also found a significant negative correlation of miR-29b-3p, miR-221-3p, and miR-503-5p with VO2 at peak exercise, whose levels decrease with HF severity. Furthermore, from a functional point of view, miR-29b-3p, miR-221-3p, and miR-503-5p all target Phosphoinositide-3-Kinase Regulatory Subunit 1, which encodes regulatory subunit 1 of phosphoinositide-3-kinase. Our findings support that an additional mechanism through which Sacubitril/Valsartan exerts its functions is the modulation of miRNAs with potentially relevant roles in HFrEF pathophysiology.
| S-EPMC10136141 | biostudies-literature
Project description:Sacubitril/valsartan decreased the risk of sudden cardiac death (SCD) in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, long-term data are sparse. The aim of the present study was to compare the incidence of life-threatening arrhythmias consisting of ventricular tachycardia and/or ventricular fibrillation before and after initiation of sacubitril/valsartan treatment. Out of 12,000 patients with HFrEF from 2016-2018, 148 patients were newly prescribed sacubitril/valsartan, but the long-term data of only 127 patients were available and included in this study. Patients with an average age of 66.8 ± 12.1 had a median left ventricular ejection fraction (LVEF) of 25% (interquartile range (IQR) 5.00-45.00) and 30% (IQR 10.00-55.00, p < 0.0005) before and after sacubitril/valsartan treatment, respectively. Systolic blood pressure decreased from 127.93 ± 22.01 to 118.36 ± 20.55 mmHg (p = 0.0035) at 6 months of follow-up. However, in 59 patients with a long-term outcome of 12 months, ventricular arrhythmias persistently increased (ventricular fibrillation from 27.6 to 29.3%, ventricular tachycardia (VT) from 12% to 13.8%, and nonsustained VT from 26.6 to 33.3%). Sacubitril/valsartan does not reduce the risk of ventricular tachyarrhythmias in chronic HFrEF patients over 12 months of follow-up.
| S-EPMC6832713 | biostudies-literature
Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess benefits and harms of first‐in‐class angiotensin receptor‐neprilysin inhibitor sacubitril/valsartan (LCZ696) as compared to angiotensin‐converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in chronic heart failure (HF) patients with either reduced, mid‐range, or preserved ejection fraction.
| S-EPMC6984414 | biostudies-literature
Project description:Background Sacubitril/valsartan improves health outcomes for heart failure with reduced ejection fraction relative to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, but it carries higher out-of-pocket costs. Neither the impact of cost nor how to integrate cost into medical decisions is well studied. Methods and Results To evaluate the impact of out-of-pocket costs and a novel cost-priming intervention on willingness to take sacubitril/valsartan for heart failure with reduced ejection fraction, participants with self-reported heart disease were surveyed using the online Ipsos Knowledge Panel. Participants were presented with a modified decision aid for sacubitril/valsartan and then, in a 3×2 factorial design, randomly assigned to 1 of 3 cost conditions ($10, $50, or $100/month) and to a control group or cost-priming intervention, defined by being asked questions about their financial situation before learning about the benefits of sacubitril/valsartan. Of the 1013 participants included in the analysis, 85% of respondents were willing to take sacubitril/valsartan at $10, 62% at $50, and 33% at $100 (P<0.0001). In a multivariable logistic regression model, participants were more likely to take sacubitril/valsartan at $10 versus $100 (odds ratio [OR], 14.3 [95% CI, 9.4-21.8]) and $50 compared with $100 (OR, 3.6 [95% CI, 2.5-5.1]). Overall, participants in the cost-primed group were more willing to take sacubitril/valsartan than those not primed to consider their financial situation (63% versus 56%, P=0.04). There was no statistically significant interaction between cost conditions and cost priming. Perceived benefit of sacubitril/valsartan over angiotensin-converting enzyme inhibitors or angiotensin receptor blockers decreased as cost increased but did not vary by cost priming. Conclusions Commonly encountered out-of-pocket costs of sacubitril/valsartan may impact individuals' willingness to take the medication even when recommended by their physicians. Priming individuals to consider personal finances before learning about the drug increased willingness to take sacubitril/valsartan.
| S-EPMC9238635 | biostudies-literature
Project description:(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR-). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (-9.7 ± 5.2% vs. -7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined.
| S-EPMC9917469 | biostudies-literature
Project description:BackgroundThe impact of sacubitril-valsartan on heart failure (HF) patients with preserved ejection fractions (HFpEF) is uncertain. The purpose of this meta-analysis was to explore the clinical advantages and safety of sacubitril-valsartan in patients with HFpEF.MethodsPubMed and Web of Science were searched without any restrictions from inception to 8 May 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed.ResultsFour trials, with a total of 7008 patients were included. Compared with valsartan, sacubitril-valsartan significantly reduced the rate of HF decompensation and of the combined end point of HF decompensation and all-cause mortality. All-cause mortality, New York Heart Association class improvement and rate of hyperkalemia were not significantly different between the two groups. Regarding safety, sacubitril-valsartan was more likely to increase the risk of hypotension.ConclusionThis meta-analysis suggests that sacubitril-valsartan may be an effective strategy to reduce HF decompensation events in patients with HFpEF.Systematic Review registration: CRD42022336077.
| S-EPMC9794138 | biostudies-literature
Project description:AimsSacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration.Methods and resultsPatients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [= LV end-systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow-up] at 6 month follow-up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N-terminal pro-brain natriuretic peptide (NT-proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65 ± 10 years; 18% female, median LVEF 30% [inter-quartile range: 25-34]). At 6 month follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF < 35%), and 204 (60%) no response (no LVRR and LVEF < 35%). Non-ischaemic aetiology, a lower left atrial volume index, and a higher GLS were all independent predictors of LVRR at multivariable logistic analysis (all P < 0.01). A baseline GLS < -9.3% was significantly associated with early response (area under the curve 0.75, P < 0.0001). Left atrial strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P < 0.05).ConclusionsSpeckle tracking echocardiography parameters at baseline could be useful to predict LVRR and clinical response to sacubitril-valsartan and could be used as a guide for treatment in patients with HFrEF.
| S-EPMC10053272 | biostudies-literature
Project description:AimsOptimizing medical cardiac treatment for sleep apnoea (SA) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is an expert Grade C recommendation based on six studies encompassing a total of 67 patients only. Whether sacubitril-valsartan (SV), a cornerstone of HFrEF medical treatment, impacts SA is unknown and requires evaluation.Methods and resultsThe ENTRESTO-SAS trial is a six-centre, prospective, open-label real-life cohort study (NCT02916160). Ambulatory patients eligible for SV (i.e. HFrEF adults who remain symptomatic despite optimal treatment) were evaluated before and after 3 months of SV (including nocturnal ventilatory polygraphy); 118 patients were final analysed [median age was 66 (IQ25-75 : 56-73) years, 81.4% male, 36.5% New York Heart Association III-IV, N-terminal pro-B-type natriuretic peptide level of 1564 (701-3376) ng/L, left ventricular ejection fraction of 30 (25-34)%, 60.7% ischaemic HFrEF, 97.5% initially treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, 83.9% with beta-blockers, 64.4% with mineralocorticoid receptor antagonists, and 74.6% with diuretics]. Three groups were defined according to initial central/obstructive apnoea-hypopnoea indices (AHIs): G1 (n = 49, AHIcentral ≥ 5/h and AHIobstructive < 15/h); G2 (n = 27, AHIobstructive ≥ 15/h); and G3 (n = 42, AHIcentral < 5/h and AHIobstructive < 15/h). At 3 months, the AHI (main predefined outcome) decreased significantly by -7.10/h (IQ25-75 : -16.10 to 0.40; P < 0.001) in G1 + G2 without positive airway pressure treatment (45 patients, median initial AHI of 24.20 (IQ25-75 : 16.40-43.50)/h). Of these, 24.4% presented an AHI decrease ≥50% and 37.78% had a final AHI < 15/h (tendency for improvement from an initial value of 20%: P = 0.0574). For G1 patients (n = 37), AHI significantly decreased from a median of 22.90 (16.00-43.50)/h to 19.20 (12.70-31.10)/h (P = 0.002). For G2 patients (n = 8), AHI decreased from a median of 30.10 (26.40-47.60)/h to 22.75 (14.60-36.90)/h (statistically non-significant, P = 0.059).ConclusionsIn this real-life population, SV treatment for 3 months in SA patients is associated with a significant decrease in AHI. These results support the current guidelines that recommend first an optimization of the HFrEF treatment in patients with HFrEF and central SA. A potential positive airway pressure sparing effect merits further investigation.
| S-EPMC8318447 | biostudies-literature
Project description:AimsSleep-disordered breathing (SDB) is a highly prevalent co-morbidity in patients with chronic heart failure (CHF) and can play a detrimental role in the pathophysiology course of CHF. However, the best way to manage SDB in CHF remains a matter of debate. Sacubitril-valsartan has been included in the 2016 European Society of Cardiology guidelines as an alternative to angiotensin-converting enzyme inhibitors to further reduce the risk of progression of CHF, CHF hospitalization, and death in ambulatory patients. Sacubitril and valsartan are good candidates for correcting SDB of CHF patients because their known mechanisms of action are likely to counteract the pathophysiology of SDB in CHF.Methods and resultsThe ENTRESTO-SAS trial is a 3-month, multicentric, prospective, open-label real-life cohort study. Patients eligible for sacubitril-valsartan treatment (i.e. adults with left ventricular ejection fraction ≤35%, who remain symptomatic despite optimal treatment with an angiotensin-converting enzyme inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist) will be evaluated before and after 3 months of treatment (nocturnal ventilatory polygraphy, echocardiography, laboratory testing, and quality-of-life and SDB questionnaires). The primary outcome is the change in the Apnoea-Hypopnoea Index, before and after 3 months of treatment. One hundred twenty patients are required to detect a significant 20% improvement of the Apnoea-Hypopnoea Index with a power of 90% at an alpha risk of 5%.ConclusionsIn the context of the SERVE-HF study, physicians are waiting for new trials and alternative therapies. We sought to assess in the ENTRESTO-SAS trial whether sacubitril-valsartan could improve the outcome of SDB in CHF patients.
| S-EPMC5933955 | biostudies-literature