Dramatic disease regression in a case of HFrEF with end-stage renal failure treated with sacubitril/valsartan and SGLT2i.
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SUBMITTER: Mapelli M
PROVIDER: S-EPMC10192298 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
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Dramatic disease regression in a case of HFrEF with end-stage renal failure treated with sacubitril/valsartan and SGLT2i.
Mapelli Massimo M Mantegazza Valentina V Ferrari Cristina C Cimino Roberto R Maragna Riccardo R Pontone Gianluca G Pepi Mauro M Agostoni Piergiuseppe P
ESC heart failure 20230312 3
The amount of evidence for guideline-directed new heart failure (HFrEF) disease-modifying drugs in the context of chronic kidney disease (CKD) is relatively modest, especially in end-stage CKD. We report a case of dramatic reverse remodelling and disease regression in a naïve HFrEF young woman on haemodialysis treated with sacubitril/valsartan and SGLT2i. At 10-month follow-up, the patient normalized left ventricle and atrial volumes and improved ejection fraction to the normal range, assessed b ...[more]
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Project description:AimsSacubitril/valsartan (SV) reduced heart failure hospitalization and cardiovascular mortality compared with enalapril in the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure trial. However, this trial excluded patients with end stage of renal disease (ESRD); thus, the efficacy and safety of SV in heart failure with reduced ejection fraction (HFrEF) with ESRD remains uncertain.Methods and resultsWe retrospectively analysed the clinical and laboratory data of 501 HFrEF patients who administered with SV from March 2017 to April 2019 in a single tertiary university hospital. A total of 23 HFrEF patients with ESRD on dialysis [58.3% non-ischaemic heart failure; left ventricular ejection fraction (LVEF): 29.7 ± 4.4%] were included in this study. At baseline and follow-up visit, we evaluated cardiovascular biomarkers such as high-sensitive troponin T (hsTnT), soluble ST2 (sST2), echocardiographic parameters, and clinical and adverse events. The mean dose of SV was 90 ± 43 mg/day at baseline and 123 ± 62 mg/day at last follow-up (follow-up duration: median 132 days). The level of hsTnT was significantly reduced from 236.2 ± 355.3 to 97.0 ± 14.0 pg/mL (P = 0.002), and the sST2 level was significantly reduced from 40.4 ± 44.0 to 19.6 ± 14.1 ng/mL (P = 0.005). LVEF was significantly improved from 29.7 ± 4.4% to 40.8 ± 10.4% (P = 0.002). During the follow-up, up-titration, down-titration, and maintenance of SV dosing were observed in 7 (30%), 5 (21.7%), and 11 patients (47.8%), respectively. SV down-titration group had adverse events including symptomatic hypotension (systolic blood pressure <100 mmHg) (n = 4) and dizziness (n = 1), but they did not discontinue SV therapy.ConclusionsWe found that SV could safely reduce the hsTnT and sST2 levels and improve LVEF in HFrEF patients with ESRD. As far as we know, this is the first study to show the efficacy and safety of SV in HFrEF with ESRD on dialysis. Larger prospective, long-term follow-up study should be warranted.
| S-EPMC7261577 | biostudies-literature
Project description:BackgroundThe data on the effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (LCZ696) in chronic heart failure (CHF) patients with end-stage renal disease (ESRD) requiring dialysis are lacking. This study assessed the efficacy and safety of LCZ696 in CHF patients with ESRD on dialysis.HypothesisLCZ696 treatment can reduce rehospitalization rate for HF, delay the occurrence of rehospitalization for HF, and prolong the survival time.MethodsWe retrospectively analyzed the clinical data of CHF patients with ESRD on dialysis who were admitted to the Second Hospital of Tianjin Medical University from August 2019 to October 2021.ResultsSixty-five patients had primary outcome during the follow-up. The incidence of rehospitalization for HF in the control group was significantly higher than that in the LCZ696 group (73.47% vs. 43.28%, p = .001). There was no significant difference in mortality between the two groups (8.96% vs. 10.20%, p = 1.000). Our study included a time-to-event analysis through 1 year for the primary outcome-Kaplan-Meier curve showed that the LCZ696 group had significantly longer free-event survival time than the control group over 1-year follow-up (median survival time 139.0 days vs. 116.0 days, p = .037).ConclusionsOur study found that LCZ696 treatment was associated with a reduction in HF rehospitalization without significant effects on serum creatinine and serum potassium levels. LCZ696 is effective and safe in CHF patients with ESRD on dialysis.
| S-EPMC10436793 | biostudies-literature
Project description:AimsThe 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.Methods and resultsFrom 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.ConclusionsOur 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.
| S-EPMC9715790 | 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:BackgroundGuidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data.ObjectivesThis study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan.MethodsUsing 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects.ResultsAverage age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex.ConclusionsBaseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
| S-EPMC8109279 | biostudies-literature
Project description:IntroductionPatients with end-stage kidney disease (ESKD) frequently develop heart failure, contributing to high mortality. Limited data exist on cardiovascular benefits and safety of sacubitril-valsartan in this population. Our systematic review aims to evaluate the efficacy and safety of sacubitril-valsartan versus standard care in patients with ESKD who are on dialysis.MethodsWe conducted a search in Embase, MEDLINE, and Cochrane databases to identify relevant studies and assessed outcomes using random-effect model and generic inverse variance approach.ResultsAnalysis of 12 studies involving 799 eligible patients with ESKD revealed improvement in left ventricular ejection fraction (LVEF) with sacubitril-valsartan compared to a control group with pooled mean difference (MD) 6.58% (95% confidence interval [CI]: 1.86, 11.29). LVEF significantly improved in patients with LVEF <50% (heart failure with reduced ejection fraction [HFrEF] and heart failure with moderately reduced ejection fraction [HFmrEF]) with MD 12.42% (95% CI: 9.39, 15.45). However, patients with LVEF >50% (heart failure with preserved ejection fraction [HFpEF]) did not exhibit statistically significant effect, MD 2.6% (95% CI: 1.15, 6.35). Sacubitril-valsartan significantly enhanced LVEF in patients with HFrEF, with MD 13.8% (95% CI: 12.04, 15.82). Safety analysis indicated no differences in incidence of hyperkalemia (pooled odds ratio [OR] 0.72; 95% CI: 0.38, 1.36) or hypotension (pooled risk ratio [RR] 1.03; 95% CI: 0.36, 2.98). No cases of angioedema were reported. However, safety analysis relies on evidence of limited robustness due to the observational nature of the studies.ConclusionOur systematic review suggests that sacubitril-valsartan benefits patients with ESKD with HFrEF and HFmrEF by improving LVEF without increasing the risk of hyperkalemia, hypotension, or angioedema compared to standard care. However, safety analysis based on observational studies inherently has limitations for establishing causal relationships.
| S-EPMC10831373 | biostudies-literature
Project description:Background: Heart failure with reduced ejection fraction (HFrEF) is a complex, chronic disease and is among the top causes of morbidity and mortality. Angiotensin receptor-neprilysin inhibitor drugs represented by sacubitril/valsartan are the key drugs for the treatment of HFrEF in western medicine, and Qili Qiangxin Capsule (QQC) is a vital drug for the treatment of HFrEF in Chinese medicine. In recent years, there have been many relevant clinical studies on the combination of the two in the treatment of HFrEF. There are no systematic reviews or meta-analyses specific to sacubitril/valsartan combined with QQC for the treatment of HFrEF, so there is an urgent need to evaluate the effectiveness and safety of these two drugs. Objective: To systematically assess the safety and effectiveness of QQC combined with sacubitril/valsartan in the treatment of HFrEF through a meta-analysis. Methods: Searching studies on the combination of QQC and sacubitril/valsartan in the treatment of HFrEF, from databases such as PubMed, Cochrane Library, Web of Science, Wanfang Databases, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure, prior to 31 October 2021. Two reviewers regulated research selection, data extraction, and risk of bias assessment. Review Manager Software 5.4 was used for meta-analysis. Results: There were 26 studies with 2,427 patients included in total. The meta-analysis showed the combination therapy has significant advantages in improving the clinical efficacy, 6-MWT (RR = 1.18, 95% CI: 1.11-1.26, MD = 70.65, 95% CI: 23.92-117.39), superior in ameliorating LVEF, LVEDD, LVESD, and SV (LVEF: MD = 5.41, 95% CI: 4.74-6.08; LVEDD: MD = -4.41, 95% CI: -6.19 to -2.64; LVESD: MD = -3.56, 95% CI: -4.58 to -2.54; and SV: MD = 5.04, 95% CI: 3.67-6.40), and in improving BNP, NT-proBNP, AngII, and ALD (BNP: MD = -97.55, 95% CI: -112.79 to -82.31; NT-proBNP: MD = -277.22, 95% CI: -348.44 to -206.01; AngII: MD = -11.48, 95% CI: -15.21 to -7.76; and ALD: MD = -26.03, 95% CI: -38.91 to -13.15), and all the differences have statistical advantages (p < 0.05). There are no advantages in improving CO and adverse events (MD = 0.66, 95% CI: -0.12 to 1.43 and RR = 0.62, 95% CI: 0.37-1.04, respectively), and the differences have no statistical advantages. Conclusion: Compared with the control group, QQC combined with sacubitril/valsartan may be effective in the treatment of HFrEF. However, the conclusion of this study must be interpreted carefully due to the high risk and ambiguity of bias in the included trials.
| S-EPMC9014182 | biostudies-literature
Project description:AimsA novel tool for the evaluation of left ventricular (LV) systo-diastolic function through echo-derived haemodynamic forces (HDFs) has been recently proposed. The present study aimed to assess the predictive value of HDFs on (i) 6 month treatment response to sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) patients and (ii) cardiovascular events.Methods and resultsEighty-nine consecutive HFrEF patients [70% males, 65 ± 9 years, LV ejection fraction (LVEF) 27 ± 7%] initiating sacubitril/valsartan underwent clinical, laboratory, ultrasound and cardiopulmonary exercise testing evaluations. Patients experiencing no adverse events and showing ≥50% reduction in plasma N-terminal pro-B-type natriuretic peptide and/or ≥10% LVEF increase over 6 months were considered responders. Patients were followed up for the composite endpoint of HF-related hospitalisation, atrial fibrillation and cardiovascular death. Forty-five (51%) patients were responders. Among baseline variables, only HDF-derived whole cardiac cycle LV strength (wLVS) was higher in responders (4.4 ± 1.3 vs. 3.6 ± 1.2; p = 0.01). wLVS was also the only independent predictor of sacubitril/valsartan response at multivariable logistic regression analysis [odds ratio 1.36; 95% confidence interval (CI) 1.10-1.67], with good accuracy at receiver operating characteristic (ROC) analysis [optimal cutpoint: ≥3.7%; area under the curve (AUC) = 0.736]. During a 33 month (23-41) median follow-up, a wLVS increase after 6 months (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≥0.5%; AUC = 0.811), stratified prognosis (log-rank p < 0.0001) and remained an independent predictor for the composite endpoint (hazard ratio 0.76; 95% CI 0.61-0.95; p < 0.01), after adjusting for clinical and instrumental variables.ConclusionsHDF analysis predicts sacubitril/valsartan response and might optimise decision-making in HFrEF patients.
| S-EPMC10567631 | biostudies-literature
Project description:AimEcho-derived haemodynamic classification, based on forward-flow and left ventricular (LV) filling pressure (LVFP) correlates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prognostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan.Methods and resultsIn our multicentre, open-label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m2 ) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e': ≥ or <15): Profile-A: normal-flow, normal-pressure; Profile-B: low-flow, normal-pressure; Profile-C: normal-flow, high-pressure; Profile-D: low-flow, high-pressure. Patients were started on sacubitril/valsartan and followed-up for 12.3 months (median). Rates of the composite of death/HF-hospitalization were assessed by multivariable Cox proportional-hazards models. Twelve sites enrolled 727 patients (64 ± 12 year old; LVEF: 29.8 ± 6.2%). Profile-D had more comorbidities and worse renal and LV function. Target dose of sacubitril/valsartan (97/103 mg BID) was more likely reached in Profile-A (34%) than other profiles (B: 32%, C: 24%, D: 28%, P < 0.001). Event-rate (per 100 patients per year) progressively increased from Profile-A to Profile-D (12.0%, 16.4%, 22.9%, and 35.2%, respectively, P < 0.0001). By covariate-adjusted Cox model, profiles with low forward-flow (B and D) remained associated with poor outcome (P < 0.01). Adding this categorization to MAGGIC-score and natriuretic peptides, provided significant continuous net reclassification improvement (0.329; P < 0.001). Intermediate and high-dose sacubitril/valsartan reduced the event's risk independently of haemodynamic profile.ConclusionsEchocardiographically-derived haemodynamic classification identifies ambulatory HFrEF patients with different risk profiles. In real-world HFrEF outpatients, sacubitril/valsartan is effective in improving outcome across different haemodynamic profiles.
| S-EPMC8934975 | 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.
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