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Background Aim Method Results Conclusion Sacubitril/valsartan (an angiotensin receptor‐neprilysin inhibitors [ARNI]) might improve atrial fibrillation (AF) condition, but its added value remains controversial.We aimed to analyse the effect of ARNI on AF burden.We conducted a single‐centre, retrospective self‐controlled study in a tertiary centre. Data were retrieved from January 2019–January 2023. All cardiac resynchronisation therapy‐implantable cardioverter defibrillator (CRT‐D) carriers on ARNI were included if implantation had been at least 3 months before drug initiation. Proarrhythmic events, equal time length control (before ARNI initiation), and exposure (after ARNI initiation) periods were defined. Echocardiographic data were retrieved if they were up to 1 year old before ARNI initiation and if they were available 3 months to 1 year after initiation. AF burden was defined by frequency and median value of paroxysmal events and the overall variation in AF status was determined. Ethical approval was granted by the Ethics Committee of the Centro Hospitalar e Universitário de Coimbra (Reference no: PI OBS.SF.174‐2022) and the study conforms with the Declaration of Helsinki.Seventy‐two patients were included in the study (73.3% men). After ARNI, there was a reduction in New York Heart Association functional class ± standard deviation (2.00 ± 0.75 to 1.85 ± 0.61, p = 0.043) and an increase in left ventricular ejection fraction ± standard deviation (from 31.67% ± 9.28% vs 37.33% ± 14.49%, p = 0.027). Before ARNI initiation, 34 patients did not have AF, 19 had paroxysmal AF, 15 had permanent AF, and 2 had persistent AF. The total amount of AF episodes (91 vs 44, p = 0.808) and median paroxysmal episodes (among those with paroxysmal AF or no AF) (5 vs 3, p = 0.121) were numerically reduced after ARNI initiation, though variation was not statistically significant. No differences were found as well regarding ventricular arrhythmias or device therapies.ARNI did not significantly decrease the number of AF paroxysmal episodes or median number of paroxysmal events per patient. Even though ARNI may have a positive impact on AF burden of heart failure patients, larger studies are needed to provide unequivocal evidence. [ABSTRACT FROM AUTHOR]

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<0.05), had a higher body mass index (30.3 ± 5.0 vs 28.1 ± 5.5, P<0.05) and higher serum creatinine level (101.9 ± 36.0 vs 99.9 ± 26.5 µmol/L, P<0.05). MMR patients had lower left ventricular ejection fraction (27.8 ± 6.9 vs 29.6 ± 6.1%, P<0.05). The serum N-terminal pro-B-type natriuretic peptide, [2563.5 (377–3536) vs 1631 (885–3154), was non significantly higher P=0.07]. Pharmacotherapy use differed for mineralocorticoid antagonist (91.4% in MMR vs 54.2% in Paradigm-HF), and digoxin (13.5% vs 29.2%). Beta-blocker use was similar (96.2% vs 93.1%) as was angiotensin-converting enzyme (ACE) inhibitors – (71.2% vs 78.0%) and angiotensin-receptor blockers – ARB (27.9% vs 22.2%). Dosages of the commonly used ACE inhibitors at the screening visit (Paradigm-HF) / before angiotensin receptor-neprilysin inhibitor administration (MMR) differed significantly only for ramipril (7.0 ± 3.1 mg vs 4.8 ± 2.9 mg, P<0.05), dosages of ARB were – losartan (67.1 ± 30.2 vs 39.6 ± 32.0 mg, P=0.09) and valsartan (181.5 ± 71.1 vs 130.9 ± 82.2 mg, P=0.07). There was a substantial difference in device-based therapy (ICD in 60.6%, CRT 25.9% in MMR vs 14.9% and 7.0% in Paradigm-HF). Conclusion. The differences between the groups for the majority of clinical parameters compared were minimal, except for younger age, higher body mass index and serum creatinine level and lower left ventricular ejection fraction and substantially lower dosage of administered ramipril prior to commencing sacubitril/valsartan therapy. There was a higher prevalence of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) in the MMR group. [ABSTRACT FROM AUTHOR]

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

Background: Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril-valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril-valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI). Materials and methods: Two researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed. Results: In total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) -3.11, 95%CI: -4.05~-2.16, p < 0.001), left ventricular end-diastolic volume (LVEDV) (WMD -7.76, 95%CI: -12.24~-3.27, p = 0.001), left ventricular end-systolic volume (LVESV) (WMD -6.80, 95%CI: -9.45~-4.15, p < 0.001) and left ventricular end-systolic dimension (LVESD) (WMD -2.53, 95%CI: -5.30-0.24, p < 0.001). Subgroup analysis according to the dose of sacubitril-valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril-valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28-0.46, p < 0.001), myocardial reinfarction (OR = 0.54, 95% CI: 0.30-0.98, p = 0.041) and HF (OR = 0.35, 95%CI: 0.26-0.47, p < 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41-4.41, p < 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37-57.76, p < 0.001) and NT-proBNP level (WMD -130.27, 95%CI: -159.14~-101.40, p < 0.001) were statistically significant. Conclusion: In conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril-valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension. [ABSTRACT FROM AUTHOR]

Abstract Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril–valsartan, beta‐blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.

The first angiotensin receptor/neprilysin inhibitor on the market, sacubitril-valsartan, has shown marked improvements in death and hospitalization for heart failure among adults, and is now approved for use in pediatric heart failure. While the ongoing PANORAMA-HF trial is evaluating the effectiveness of sacubitril-valsartan for pediatric patients with a failing systemic left ventricle, the enrollment criteria do not include the majority of pediatric heart failure patients. Additional studies are needed. Using the TriNetX database, we performed a propensity score matched, retrospective cohort study to assess the incidence of a composite of all-cause mortality or heart transplant within 1 year. The 519 patients who received sacubitril-valsartan were compared to 519 matched controls who received an angiotensin converting enzyme inhibitor (ACE) or angiotensin II receptor blocker (ARB). There was no significant difference in the incidence of the composite outcome with sacubitril-valsartan over an ACE/ARB (13.3% vs 13.2%, p = 0.95), or among the components of mortality (5.0% vs 5.8%, p = 0.58) or heart transplantation (8.7% vs 7.5%, p = 0.50). Patients who were receiving full goal-directed medical therapy (14.4% vs 16.0%, p = 0.55) also showed no difference in the composite outcome. We observed a significantly increased incidence of hypotension (10% vs 5.2%, p = 0.006) and a trend toward reduced number of hospitalizations per year (mean (SD) 1.3 (4.4) vs 2.0 (9.1), p = 0.09). Sacubitril-valsartan is not associated with a decrease in the composite of all-cause mortality or heart transplantation within 1 year. Future studies should evaluate the possible reduction in hospitalizations and optimal dosing to minimize hypotension. [ABSTRACT FROM AUTHOR]

Background and aim: Heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of heart failure (HF) hospitalizations and cardiovascular death (CVD). Both dapagliflozin and sacubitril-valsartan have recently shown convincing reductions in the combined risk of CVD and HF hospitalizations in patients with HF and mildly reduced ejection fraction (HFmrEF) or HFpEF. We aimed to investigate the cost-per-outcome implications of dapagliflozin vs sacubitril-valsartan in the treatment of HFmrEF or HFpEF patients. Methods: We compared the annualized cost needed to treat (CNT) to prevent the composite outcome of total HF hospitalizations and CVD with dapagliflozin or sacubitril-valsartan. The CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNT was calculated based on data collected from the DELIVER trial for dapagliflozin and a pooled analysis of the PARAGLIDE-HF and PARAGON-HF trials for sacubitril-valsartan. Costs were based on 2022 US prices. Scenario analyses were performed to attenuate the differences in the studies' populations. s Results: The aNNT with dapagliflozin in DELIVER was 30 (95% confidence interval [CI]: 21-62) versus 44 (95% CI: 25-311) with sacubitril-valsartan in a pooled analysis of PARAGLIDE-HF and PARAGON-HF, with an annual cost of $4,951 and $5,576, respectively. The corresponding CNTs were $148,547.13 (95% CI: $103,982.99-$306,997.39) for dapagliflozin and $245,346.77 (95% CI: $139,401.58-1,734,155.60) for sacubitril-valsartan for preventing the composite outcome of CVD and HF hospitalizations. The CNT for preventing all-cause mortality was lower for dapagliflozin than sacubitril-valsartan $1,128,958.15 [CI: $401,077.24-8] vs $2,185,816.71 [CI: $607,790.87-8]. Conclusion: Dapagliflozin provides a better monetary value than sacubitril-valsartan in preventing the composite outcome of total HF hospitalizations and CVD among patients with HFmrEF or HFpEF. [ABSTRACT FROM AUTHOR]

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril–valsartan, beta‐blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat. [ABSTRACT FROM AUTHOR]

Abstract Aims Red cell distribution width (RDW) is a strong prognostic marker in patients with heart failure (HF) and reduced ejection fraction and other conditions. However, very little is known about its prognostic significance in HF with preserved ejection fraction. We examined the relationship between RDW and outcomes and the effect of sacubitril/valsartan, compared with valsartan, on RDW and clinical outcomes in PARAGON‐HF. Methods and results PARAGON‐HF enrolled patients with a left ventricular ejection fraction of ≥45%, structural heart disease, and elevated N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). The primary endpoint was a composite of total HF hospitalizations and cardiovascular deaths. Median RDW at randomization was 14.1% (interquartile range 13.5–15.0%). Patients with higher RDW levels were more often men and had more comorbidity, a higher heart rate and NT‐proBNP concentration, more advanced New York Heart Association class, and worse Kansas City Cardiomyopathy Questionnaire scores. There was a graded relationship between quartiles of RDW at randomization and the primary endpoint, with a significantly higher risk associated with increasing RDW, even after adjustment for NT‐proBNP and other prognostic variables {Quartile 1, reference; Quartile 2, rate ratio 1.03 [95% confidence interval (CI) 0.83 to 1.28]; Quartile 3, 1.25 [1.01 to 1.54]; Quartile 4, 1.70 [1.39 to 2.08]}. This association was seen for each of the secondary outcomes, including cardiovascular and all‐cause death. Compared with valsartan, sacubitril/valsartan reduced RDW at 48 weeks [mean change −0.09 (95% CI −0.15 to −0.02)]. The effect of sacubitril/valsartan vs. valsartan was not significantly modified by RDW levels at randomization. Conclusions RDW, a routinely available and inexpensive biomarker, provides incremental prognostic information when added to established predictors. Compared with valsartan, sacubitril/valsartan led to a small reduction in RDW.

Background: Sacubitril‐valsartan, an inhibitor of the angiotensin receptor neprilysin (ARNi), has been purported to exhibit superiority over angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in individuals diagnosed with heart failure. Hypothesis: This paper gives an updated meta‐analysis comparing the efficacy and safety of sacubitril‐valsartan to that of standard treatment for different types of heart failure. Results: The meta‐analysis comprised a total of nine randomized controlled trials (RCTs), incorporating data from a substantial sample size of 15 939 patients. The study observed a decrease in overall mortality and mortality related to cardiovascular causes among patients in the heart failure with reduced ejection fraction (HFrEF) category who were treated with sacubitril‐valsartan. However, no statistically significant variation in this outcome was seen among patients with heart failure with preserved ejection fraction and HFmrEF. Patients who were administered sacubitril‐valsartan had a notably elevated likelihood of experiencing hypotension. Nevertheless, no significant disparities were observed in terms of other adverse events among the various treatment groups. Conclusion: Current meta‐analysis provide support for use of sacubitril‐valsartan in decreasing mortality in patients with HFrEF. However, more numbers of studies are required to draw a definite conclusion on other benefits associated with sacubitril‐valsartan use over standard treatment of ACE inhibitors and ARBs. [ABSTRACT FROM AUTHOR]

Aims: Red cell distribution width (RDW) is a strong prognostic marker in patients with heart failure (HF) and reduced ejection fraction and other conditions. However, very little is known about its prognostic significance in HF with preserved ejection fraction. We examined the relationship between RDW and outcomes and the effect of sacubitril/valsartan, compared with valsartan, on RDW and clinical outcomes in PARAGON‐HF. Methods and results: PARAGON‐HF enrolled patients with a left ventricular ejection fraction of ≥45%, structural heart disease, and elevated N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). The primary endpoint was a composite of total HF hospitalizations and cardiovascular deaths. Median RDW at randomization was 14.1% (interquartile range 13.5–15.0%). Patients with higher RDW levels were more often men and had more comorbidity, a higher heart rate and NT‐proBNP concentration, more advanced New York Heart Association class, and worse Kansas City Cardiomyopathy Questionnaire scores. There was a graded relationship between quartiles of RDW at randomization and the primary endpoint, with a significantly higher risk associated with increasing RDW, even after adjustment for NT‐proBNP and other prognostic variables {Quartile 1, reference; Quartile 2, rate ratio 1.03 [95% confidence interval (CI) 0.83 to 1.28]; Quartile 3, 1.25 [1.01 to 1.54]; Quartile 4, 1.70 [1.39 to 2.08]}. This association was seen for each of the secondary outcomes, including cardiovascular and all‐cause death. Compared with valsartan, sacubitril/valsartan reduced RDW at 48 weeks [mean change −0.09 (95% CI −0.15 to −0.02)]. The effect of sacubitril/valsartan vs. valsartan was not significantly modified by RDW levels at randomization. Conclusions: RDW, a routinely available and inexpensive biomarker, provides incremental prognostic information when added to established predictors. Compared with valsartan, sacubitril/valsartan led to a small reduction in RDW. [ABSTRACT FROM AUTHOR]

Data on angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (SV) in patients undergoing maintenance dialysis is scarce. Our study aimed to investigate the effect of SV on patients undergoing dialysis. We retrospectively reviewed the data of end-stage kidney disease (ESRD) patients undergoing either peritoneal dialysis (PD) or hemodialysis (HD) in our center. A total of 51 patients receiving SV treatment were enrolled in the SV group. Another 51 age and sex-matched patients on dialysis without SV treatment were selected as the control group. All the patients were regularly followed up in the dialysis clinic. Their clinical, biochemical, and echocardiographic parameters were all recorded at baseline and during follow-up. The effect and safety of SV were further analyzed. A total of 102 ESRD patients on dialysis (51 patients in the SV group and 51 patients in the control group) were finally enrolled. The median follow-up time was 349 days (interquartile range [IQR]: 217–535 days). The level of B-type natriuretic peptide (BNP) (median [IQR] before and after SV treatment: 596.35 pg/ml [190.6–1714.85] vs. 188.7 pg/ml [83.34–600.35], p < 0.001) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (median [IQR]: 6316.00 pg/ml [4552.00–28598.00] vs. 5074.00 pg/ml [2229.00–9851.00], p = 0.022) were significantly decreased after treatment with SV. The variant rate of left ventricular ejection fraction (LVEF) was significantly higher in the SV group compared to the control group, especially in the PD subgroup. No significant difference was found in other echocardiographic parameters between SV and control group. Subgroup analysis of the PD group showed an increase in daily PD ultrafiltration (median [IQR]: 400 ml/d [200-500] vs. 500 ml/d [200–850], p = 0.114) after SV treatment. Variant rate of overhydration (OH) measured by the body composition monitor (BCM) of the SV group were significantly different from the control group (median [IQR]: −13.13% [−42.85%–27.84%] vs. 0% [−17.95%–53.85%], p = 0.049). The rate of hyperkalemia was slightly higher but without significant difference before and after the introduction of SV (19.6% vs. 27.5%, p = 0.350). No event of hypotension and angioedema were observed. SV might have a cardio-protective role in ESRD patients undergoing dialysis, especially in PD patients. Serum potassium should be monitored during the treatment. [ABSTRACT FROM AUTHOR]

Background and aim:Heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of heart failure (HF) hospitalizations and cardiovascular death (CVD). Both dapagliflozin and sacubitril–valsartan have recently shown convincing reductions in the combined risk of CVD and HF hospitalizations in patients with HF and mildly reduced ejection fraction (HFmrEF) or HFpEF. We aimed to investigate the cost-per-outcome implications of dapagliflozin vs sacubitril–valsartan in the treatment of HFmrEF or HFpEF patients.Methods:We compared the annualized cost needed to treat (CNT) to prevent the composite outcome of total HF hospitalizations and CVD with dapagliflozin or sacubitril–valsartan. The CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNT was calculated based on data collected from the DELIVER trial for dapagliflozin and a pooled analysis of the PARAGLIDE-HF and PARAGON-HF trials for sacubitril–valsartan. Costs were based on 2022 US prices. Scenario analyses were performed to attenuate the differences in the studies’ populations.Results:The aNNT with dapagliflozin in DELIVER was 30 (95% confidence interval [CI]: 21-62) versus 44 (95% CI: 25-311) with sacubitril–valsartan in a pooled analysis of PARAGLIDE-HF and PARAGON-HF, with an annual cost of $4,951 and $5,576, respectively. The corresponding CNTs were $148,547.13 (95% CI: $103,982.99–$306,997.39) for dapagliflozin and $245,346.77 (95% CI: $139,401.58–1,734,155.60) for sacubitril–valsartan for preventing the composite outcome of CVD and HF hospitalizations. The CNT for preventing all-cause mortality was lower for dapagliflozin than sacubitril–valsartan $1,128,958.15 [CI: $401,077.24–∞] vs $2,185,816.71 [CI: $607,790.87–∞].Conclusion:Dapagliflozin provides a better monetary value than sacubitril–valsartan in preventing the composite outcome of total HF hospitalizations and CVD among patients with HFmrEF or HFpEF.

AbstractObjectives Data on angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (SV) in patients undergoing maintenance dialysis is scarce. Our study aimed to investigate the effect of SV on patients undergoing dialysis.Methods We retrospectively reviewed the data of end-stage kidney disease (ESRD) patients undergoing either peritoneal dialysis (PD) or hemodialysis (HD) in our center. A total of 51 patients receiving SV treatment were enrolled in the SV group. Another 51 age and sex-matched patients on dialysis without SV treatment were selected as the control group. All the patients were regularly followed up in the dialysis clinic. Their clinical, biochemical, and echocardiographic parameters were all recorded at baseline and during follow-up. The effect and safety of SV were further analyzed.Results A total of 102 ESRD patients on dialysis (51 patients in the SV group and 51 patients in the control group) were finally enrolled. The median follow-up time was 349 days (interquartile range [IQR]: 217–535 days). The level of B-type natriuretic peptide (BNP) (median [IQR] before and after SV treatment: 596.35 pg/ml [190.6–1714.85] vs. 188.7 pg/ml [83.34–600.35], p

Heart failure (HF) is a significant event for public health. It has a prevalence between 1-2%, mortality rate between 7-17%, and hospitalization between 32-44%. This implies a risk to health and quality of life, but also great financial efforts for health systems. Sacubitril/valsartan is a medication recognized for its efficacy, and this consensus seeks to synthesize the available information regarding its use for the benefit of patients. This document consists of a description of the epidemiology of HF, pharmacology of the drug, clinical trials, use of the drug in cases with reduced ejection fraction, mildly reduced ejection frac- tion and preserved ejection fraction, available literature on HF guidelines, recommendations and conclusions. [ABSTRACT FROM AUTHOR]

Abstract Background Although the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has demonstrated a valuable effect on cardiac function in patients with heart failure with a reduced ejection fraction, the effect of this agent in hemodialysis patients is not well known. Case presentation Sacubitril-valsartan was administered to two anuric hemodialysis patients, an 81-year-old woman and a 79-year-old man, after aortic valve replacement for aortic stenosis. Following sacubitril-valsartan administration, the two patients’ N-terminal pro-brain natriuretic peptide levels decreased from 110,373 to 47,742 and 22,723 to 7692 pg/mL within one month, respectively, and were sustained within the lower levels thereafter. Although the patients’ left ventricular ejection fractions were 40.0% and 28.4%, respectively, these values did not change at seven and four months after sacubitril-valsartan administration (41.0% and 30.0%, respectively) but increased gradually to 56.6% and 54.9% at 11 and 13 months, respectively, and were sustained at the same levels thereafter. Conclusions Long-term sacubitril-valsartan administration can improve cardiac function in hemodialysis patients with a reduced ejection fraction.

Purpose: To systematically assess the efficacy and safety of sacubitril/valsartan (SV) by comparison with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for the treatment of heart failure caused by acute myocardial infarction (HF-AMI) based on current randomized controlled trials (RCTs). Methods: Several electronic databases were searched up to 27 May 2023. Primary endpoints were the efficacy including the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), N-terminal pro-B type natriuretic peptide (NT-proBNP) and 6-min walk test (6MWT) and secondary endpoints were the safety including the major adverse cardiovascular event (MACE) and adverse reaction (AE). Results: A total of 14 RCTs were included and all patients were from China. Among included 1,991 patients, 997 patients received SVs and 994 patients received ACEIs/ARBs. The pooled results demonstrated that patients in the SV group showed significantly better efficacy representing as increased LVEF [weighted mean difference (WMD): 4.43%, 95% confidence interval (CI): 2.84%-6.02%, p < 0.001] and 6MWT (WMD: 30.84 m, 95% CI: 25.65 m-36.03 m, p < 0.001) and decreased LVEDD (WMD: -3.24 mm, 95% CI: -4.96 mm ~ -1.52 mm, p < 0.001) and NT-proBNP (WMD: -188.12 pg/mL, 95% CI: -246.75 pg/mL ~ 129.49 pg/mL, p < 0.001), which was also verified by subgroup analysis based on the history of percutaneous coronary intervention (PCI). Besides, the SV group showed significantly lower incidence rate of MACE [relative risk (RR): 0.60, 95% CI: 0.47-0.75, p < 0.001] and patients receiving SVs in the non-PCI group also showed lower incidence of AE (RR: 0.38, 95% CI: 0.20-0.71, p = 0.002). Conclusion: For the treatment of HF-AMI, SV is more effective and safer than ACEI/ARB based on current evidence, but more high-quality RCTs are still needed to verify above findings. [ABSTRACT FROM AUTHOR]

Background: The 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. Hypothesis: LCZ696 treatment can reduce rehospitalization rate for HF, delay the occurrence of rehospitalization for HF, and prolong the survival time. Methods: We 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. Results: Sixty‐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). Conclusions: Our 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. [ABSTRACT FROM AUTHOR]

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Worsening heart failure (HF) is associated with a high risk of death and rehospitalization. Despite that, real world evidence about the impact of worsening HF on clinical practice is scarce. A narrative review about registries addressing recent worsening HF events in Spain, with special emphasis on patients recently hospitalized for HF was performed. Worsening HF can be defined as situations where the patient's HF deteriorates to the extent that it necessitates initiation or intensification of diuretic treatment (mainly intravenous). The events can occur at the outpatient level, generally in the day hospital, in the emergency department or even hospitalization. Early identification of worsening HF events is essential to establish appropriate treatment as soon as possible. In this context, robust clinical benefits have been reported for renin-angiotensin system inhibitors, sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors, and vericiguat. In Spain, several registries of patients with HF have been developed, some of them including patients recently hospitalized for HF, but not with recent worsening HF events. Therefore, registries addressing recent worsening events would be desirable. Using a practical approach, this review analyzes the importance of worsening HF events, with special emphasis on Spanish data. [ABSTRACT FROM AUTHOR]

Several guidelines have recommended the use of angiotensin receptor neprilysin inhibitors (ARNIs) as replacement for angiotensin-converting enzyme inhibitors in the management of heart failure. Till date, there are no reviews done that comprehensively cover different aspects of efficacy and safety parameters. Hence, we have performed a comprehensive systematic review and meta-analysis on role of ARNIs for the management of heart failure patients. Searches were done in Embase, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, PubMed Central, Cochrane Library, MEDLINE, Google Scholar, ScienceDirect and Clinicaltrials.gov until June 2022. Risk of bias assessment was done with Cochrane's risk of bias tool. Meta-analysis was carried out using random-effects model. Pooled standardized mean difference (SMD)/mean difference (MD) and/or risk ratio (RR) with 95% confidence intervals (CIs) was reported. In total, we analysed 34 studies, with almost all of them had a high risk of bias. Pooled RR was 0.88 (95% CI: 0.82–0.95) for all-cause mortality, 0.84 (95% CI: 0.77–0.92) for cardiovascular mortality and 0.78 (95% CI: 0.70–0.87) for hospitalization. Pooled MD was 3.74 (95% CI: 1.93–5.55) for left ventricular ejection fraction, −2.16 (95% CI: −3.58 to −0.74) for left atrial volume index, −3.80 (95% CI: −6.60 to −1.00) for left ventricular end-diastolic dimension and −1.16 (95% CI: −1.98 to −0.35) for E/E′ ratio. Regarding adverse events, pooled RR was 1.55 (95% CI: 1.31–1.85) for symptomatic hypotension, 0.93 (95% CI: 0.78–1.11) for worsening renal function, 1.09 (95% CI: 0.94–1.26) for hyperkalaemia and 1.29 (95% CI: 0.67–2.50) for angioedema. ARNIs had beneficial efficacy and safety profile on the management of heart failure especially patients with reduced ejection fraction. [ABSTRACT FROM AUTHOR]

Objectives: Sacubitril-valsartan, a recently approved treatment for heart failure, has shown some promise as a possible therapeutic option for diabetes mellitus. It is still not clear whether those beneficial effects are comparable to valsartan effects. In this work, we aimed at investigating Sacubitril-valsartan effect on metabolic changes in a model of high-fat high fructose diet-induced diabetes mellitus, in comparison to the metabolic changes induced by valsartan only. Methods: Rats were ad libitum fed with either standard chow plus tap water for drinking (controls) or 60% beef tallow and 10% fructose drinking water (diseased) for 11 weeks. Starting in week 9, each group was subdivided into four, namely vehicle, pioglitazone, Sacubitril-valsartan and valsartan. Treatments were administered from weeks 9 to 11, while rats were maintained in their respective diet groups. Key findings: Sacubitril-valsartan treatment significantly decreased daily food intake, body weight and epididymal white adipose weight, and normalized insulin and glycosylated haemoglobin in high-fat high fructose. Both valsartan and Sacubitril-valsartan only attenuated the elevated fasting blood glucose levels, glucose, insulin and pyruvate tolerance and increased protein kinase B phosphorylation in diseased rats. Conclusions: Sacubitril-valsartan may be an effective modulator of diabetes mellitus-associated metabolic aberration, superiorly compared to valsartan only. [ABSTRACT FROM AUTHOR]

Hai Fan,1 Yuesong Wang,1 Xuezhong Wang,1 Xuebin Dong,1 Xuwu Shao,1 Fei Yang2 1Department of Cardiovascular Medicine, People’s Hospital of Maanshan, Maanshan, Anhui, People’s Republic of China; 2Department of Laboratory, People’s Hospital of Maanshan, Maanshan, Anhui, People’s Republic of ChinaCorrespondence: Hai Fan, Tel +86-18255552083, Email 491640302@qq.comPurpose: This study aimed to investigate the effect of emergency percutaneous coronary intervention (PCI) combined with sacubitril-valsartan (Entresto) on the cardiac prognosis in patients with acute myocardial infarction (AMI).Patients and Methods: A total of 78 AMI patients who were treated in our hospital between January 2020 and September 2021 were included and randomly divided into treatment group and control group (n=39 per group). In the control group, patients were treated with primary PCI combined with irbesartan; in the treatment group, patients were treated with primary PCI combined with Entresto; pharmacotherapy lasted for 3 months. The left ventricular remodeling indexes, serum N-terminal B-type natriuretic peptide precursor (NT-proBNP), serum homocysteine (HCY), cystatin C (CysC) and results of 6-minute walk test (6MWT) before and after treatment were compared between two groups. The incidence of major adverse cardiovascular events (MACE) was determined and compared between them.Results: (1) Before treatment, there were no marked differences in the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), NT-proBNP, left ventricular ejection fraction (LVEF), HCY, CysC, and results of 6MWT between two groups (P> 0.05). After treatment, the LVEDS, LVEDD, NT-proBNP, HCY and CysC in the control group were significantly higher than in the treatment group (P< 0.05). The recovery of LVEF and 6MWT in the treatment group was significantly better than in the control group (P< 0.05). After treatment, there was no significant difference in the IVST between two groups (P> 0.05). (2) The incidence of MACE in the control group was significantly higher than in the treatment group (P< 0.05).Conclusion: Compared with irbesartan, Entresto can further improve the cardiac function, prevent ventricular remodeling, and further optimize the clinical efficacy of PCI in AMI patients.Keywords: percutaneous coronary intervention, sacubitril-valsartan, acute myocardial infarction, ventricular remodeling

Abstract Aims Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF). Methods and results Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM–1 μM) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound‐healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers [fold‐change (Log2): COL1A1–1.3; IL‐1b–1.9; IL‐6–1.7; FN1–2.9 (P

Worsening heart failure (HF) is associated with a high risk of death and HF hospitalization. A systematic search was conducted on PubMed (MEDLINE), using the MeSH terms [Heart failure] + [Worsening] + [Treatment] + [Vulnerable period] up to February 2023. Original data from clinical trials, and observational studies were critically analyzed. Although the vulnerable period has been traditionally limited to the first 6 months after HF hospitalization, the fact is that there are other clinical scenarios in which the patient is particularly vulnerable. These vulnerable patients may also include those that require parenteral administration of diuretics in the day hospital or emergency department, those in which the increase of oral diuretic dose in an outpatient setting is needed to relief congestive symptoms, as well as those that remain symptomatic despite treatment. On the other hand, HF is a complex disease in which different neurohormonal systems are involved. Therefore, to actually reduce the HF burden, a comprehensive management, targeting all the neurohormonal systems that are involved in the pathogenesis of HF, through the use of those drugs that have demonstrated to positively modify the clinical course of HF, is needed. [ABSTRACT FROM AUTHOR]

Introduction: Sacubitril/valsartan reduces all‐cause mortality in heart failure (HF) patients compared to angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). ACEIs/ARBs have been shown to decrease the incidence of atrial fibrillation (AF). We hypothesized sacubitril–valsartan decreases the incidence of AF compared to ACEis/ARBs. Methods: Clinicaltrials.gov was searched for trials by terms sacubitril/valsartan, entresto, sacubitril, valsartan. Randomized controlled human trials of sacubitril/valsartan reporting AF were included. Data were extracted independently by two reviewers. Data was pooled using a random effect model. Publication bias was evaluated by funnel plots. Results: A total of 11 trials including 11,458 patients on sacubitril/valsartan and 10,128 patients on ACEI/ARBs were identified. A total of 284 AF events were reported in the sacubitril/valsartan group compared to 256 AF events in ACEIs/ARBs. Patients on sacubitril/valsartan were as likely as patients on ACEIs/ARBs to develop AF (pooled odds ratio [OR] = 1.091, 95% confidence interval [CI] = 0.917–1.298, p =.324). Six atrial flutter (AFl) events were reported in six trials; 48 out of 9165 patients in the sacubitril/valsartan group developed AFl compared to 46 out of 8759 in ACEi/ARBs group. There was no difference in AFl risk between the two groups (pooled OR = 1.028, 95% CI = 0.681–1.553, p =.894). Finally, sacubitril/valsartan did not reduce the risk of atrial arrhythmias (AF + AFl) compared to ACEi/ARBs (pooled OR = 1.081, 95% CI = 0.922–1.269, p =.337). Conclusion: Although sacubitril/valsartan reduces mortality compared to ACEIs/ARBs in HF patients, they do not reduce AF risk compared to these drugs. [ABSTRACT FROM AUTHOR]

Objective: The current meta-analysis reviews the different randomized controlled trials (RCTs) on the use of sacubitril-valsartan (SV) thoroughly and assesses its effectiveness and safety as a drug for heart failure. Data Sources: Relevant articles for meta-analysis were searched from PubMed, MEDLINE, and Central databases using appropriate keywords. Study Selection and data extraction: Studies were included as per the predefined PICOS criteria. Demographic summary and event data change in heart conditions after drug intake and adverse effects of drugs under both the SV and control arms were determined. The risk of bias and comparative drug efficiency in terms of diagnostic odds ratio (OR) and risk ratio (RR) were determined using RevMan software. Data Synthesis: Ten RCTs with total 18 164 heart failure patients were included according to the inclusion criteria from the year 2015 to 2022. Included studies have patients of different age groups treated with either SV or control. For the change in number of patients with heart conditions after drug intake, we obtained the pooled OR of 0.80 (95% CI, 0.71-0.91) and pooled RR of 0.92 (95% CI, 0.88-0.96). The OR value less than 1 is indicative of high efficiency of SV in lowering the number of heart patients. All these values are statistically significant (P < 0.05) and suggested better recovery of patients with SV as compared with the control drugs with minimal risk and side effects. Conclusions: The present evidence shows that SV is effective in the treatment of heart failure, reducing hospitalization and cardiovascular mortality, and that the adverse effects are comparable or fewer than those associated with other drugs used for this indication. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effect of sacubitril-valsartan (SV) on central apneas (CA) and obstructive apneas (OA) in patients with heart failure with reduced ejection fraction (HFrEF). Methods: In patients with HFrEF, SV initiation was titrated to the highest tolerable dosage. Patients were evaluated with portable apnea monitoring, echocardiography, and cardiopulmonary exercise testing at baseline and 3 months later. Results: Of a total of 18 patients, 9 (50%) had OA, 7 (39%) had CA, and 2 (11%) had normal breathing. SV therapy was related to a reduction in NT-pro BNP and an improvement in LV function after 3 months. Portable apnea monitoring revealed a significant decrease of the respiratory event index (REI) after treatment with SV (20 ± 23 events/h to 7 ± 7 events/h, p = 0.003). When subgrouping according to type of apneas, REI, and time spent below 90% saturation (T90) decreased in patients with CA and OA (all p < 0.05). Conclusion: In this prospective study, SV treatment for 3 months in patients with CA and OA is associated with a significant decrease in REI. [ABSTRACT FROM AUTHOR]

Background: The episode of acute decompensated heart failure (ADHF) is the main cause of hospitalization for heart failure (HF). Sacubitril-valsartan has been proven to be effective in reducing the risks of hospitalization for HF in ADHF. When to initiate sacubitril-valsartan in ADHF to make it the most cost-effective in China remains unclear. Methods: A lifetime Markov model with a 1-month cycle length was developed to evaluate the cost-effectiveness of early or late initiation of sacubitril-valsartan versus enalapril in ADHF. Early initiation of sacubitril-valsartan meant that it was initiated after stabilization from ADHF, and late initiation of sacubitril-valsartan meant that it was initiated after stabilization from HF, which includes no hospitalization for at least three consecutive months. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the ratio of incremental cost to incremental effectiveness. The secondary outcomes were total costs and total effectiveness. Three times of per capita GDP of China in 2021 was set as the willingness-to-pay threshold. One-way sensitivity analysis and probabilistic sensitivity analysis were employed to test the robustness of the results. Results: The early initiation of sacubitril-valsartan treatment resulted in an ICER of 3,662.4 USD per quality-adjusted life year, lower than the willingness-to-pay threshold, and the late initiation of sacubitril-valsartan treatment gained an ICER of 4,444.4 USD/QALY, still lower than the willingness-to-pay threshold. One-way sensitivity analysis showed that our results were robust, and probabilistic sensitivity analysis suggested that early initiation of sacubitril-valsartan in ADHF was costeffective under a 97.4% circumstance. Conclusion: Early initiation of sacubitril-valsartan after stabilization of ADHF is highly cost-effective compared with the use of enalapril; late initiation of sacubitril-valsartan after stabilization of HF is still cost-effective but not as cost-effective as early initiation of sacubitril-valsartan in ADHF. For Chinese ADHF patients, the time to initiate sacubitril-valsartan should be when thepatient is stabilized from ADHF rather than when stabilized from HF, from the perspective of economic evaluation. [ABSTRACT FROM AUTHOR]

Background PARAGON‐HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril–valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril–valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril–valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril–valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril–valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril–valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68–0.80). The protective effect of sacubitril–valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66–0.86]; P

BackgroundBased on previous research, both dapagliflozin (DAPA) and sacubitril-valsartan (S/V) improve the prognosis of patients with heart failure (HF). Our study aims to investigate whether the early initiation of DAPA or the combination of DAPA with S/V in different orders would exert a greater protective effect on heart function than that of S/V alone in post-myocardial infarction HF (post-MI HF).MethodsRats were randomized into six groups: (A) Sham; (B) MI; (C) MI + S/V (1st d); (D) MI + DAPA (1st d); (E) MI + S/V (1st d) + DAPA (14th d); (F) MI + DAPA (1st d) + S/V (14th d). The MI model was established in rats via surgical ligation of the left anterior descending coronary artery. Histology, Western blotting, RNA-seq, and other approaches were used to explore the optimal treatment to preserve the heart function in post-MI HF. A daily dose of 1 mg/kg DAPA and 68 mg/kg S/V was administered.ResultsThe results of our study revealed that DAPA or S/V substantially improved the cardiac structure and function. DAPA and S/V monotherapy resulted in comparable reduction in infarct size, fibrosis, myocardium hypertrophy, and apoptosis. The administration of DAPA followed by S/V results in a superior improvement in heart function in rats with post-MI HF than those in other treatment groups. The administration of DAPA following S/V did not result in any additional improvement in heart function as compared to S/V monotherapy in rats with post-MI HF. Our findings further suggest that the combination of DAPA and S/V should not be administered within 3 days after acute myocardial infarction (AMI), as it resulted in a considerable increase in mortality. Our RNA-Seq data revealed that DAPA treatment after AMI altered the expression of genes related to myocardial mitochondrial biogenesis and oxidative phosphorylation.ConclusionsOur study revealed no notable difference in the cardioprotective effects of singular DAPA or S/V in rats with post-MI HF. Based on our preclinical investigation, the most effective treatment strategy for post-MI HF is the administration of DAPA during the 2 weeks, followed by the addition of S/V to DAPA later. Conversely, adopting a therapeutic scheme whereby S/V was administered first, followed by later addition of DAPA, failed to further improve the cardiac function compared to S/V monotherapy.

We aimed to compare therapies of sacubitril/valsartan + spironolactone (S/V + S) with angiotensin-converting enzyme inhibitors + spironolactone (ACEI + S) on the left-sided cardiac reverse remodeling (L-CRR). The second objective was to analyze the usefulness of GLS and LVEF in response to therapy.Methods78 patients (mean age 63.4 years, 20 females) with symptomatic heart failure with reduced ejection fraction were randomized to groups of equal numbers, i.e., 39 patients, and started on therapy of S/V + S or ACEI + S. Second evaluations were made after 6–8 weeks of therapy.ResultsGLS changed from −7.4% to −9.4% (18% improvement) in both arms equally. More than 50% of patients, initially with very severe systolic dysfunction (GLS > −8%), were reclassified to severe (GLS −8% to −12%). LVEF did not improve in any of the groups. The quality of life measured by MLHFQ and walking distance by 6-MWT increased. Positive correlations between GLS and 6MWT (r = 0.41, p = 0.02) and GLS and MHFLQ (r = 0.42, p = 0.03) were found. The S/V + S subgroup demonstrated improvements in LVEDV (Δ16.7 vs. 4.5 ml), E/e ratio (Δ 2.8 vs. 1.4), and LAVI (Δ 9.4 vs. 8.4 ml/m2) as compared to ACEI + S.ConclusionGLS, unlike LVEF, detects early changes in LV systolic function after 6–8 weeks of combined therapy, i.e., SV + S and ACE + S. GLS is more useful than LVEF in assessing early response to treatment. The effect of S/V + S and ACEI + S on LV systolic function was comparable, but the improvement in diastolic function as expressed by E/e’, LAVI, and LVEDV was more pronounced with S/V + S.

Aims: Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF). Methods and results: Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM–1 μM) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound‐healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers [fold‐change (Log2): COL1A1–1.3; IL‐1b–1.9; IL‐6–1.7; FN1–2.9 (P < 0.05)]. Dapagliflozin slowed the migration rate of HFrEF fibroblasts in a dose‐dependent manner and markedly decreased the expression of IL‐1β, IL‐6, MMP3, MMP9, GAL3, and FN1. SGLT2i had no effect on control fibroblasts. These effects were associated with decreased phosphorylation of AKT/GSK3 and PYK2 kinases and the signal transducer and activator of transcription (STAT). A combination of dapagliflozin + LCZ696 further decreased fibroblast migration, although it did not have a significant effect on the regulation of signalling pathways and the expression of biomarkers induced by SGLT2 inhibition alone. In contrast, the combination of dapagliflozin + spironolactone did not change the migration rate of fibroblast but significantly altered SGLT2i responses on MMP9, GAL3, and IL‐1b expression, in association with increased phosphorylation of the kinases AKT/GSK3 and ERK1/2. Conclusions: SGLT2i, LCZ696, and spironolactone modulate the function of isolated myocardial fibroblasts from HFrEF patients through the activation of different signalling pathways. The combination of SGLT2i + LCZ696 shows an additive effect on migration, while spironolactone modifies the signalling pathways activated by SGLT2i and its beneficial effects of biomarkers of heart failure. [ABSTRACT FROM AUTHOR]

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Data on angioedema risk among sacubitril-valsartan (SV) users in real-world settings are limited. We sought to evaluate the risk of angioedema among SV new users compared with angiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor-blocker (ARB) new users separately. We conducted a propensity score–matched cohort study, comparing SV new users (no use of SV, ACE inhibitor, ARB 6 months before) and SV new users with prior use (within 183 or 14 days) of ACE inhibitor or ARB (ACE inhibitor–SV and ARB-SV users; recent ACE inhibitor–SV and recent ARB-SV users, respectively) vs ACE inhibitor and ARB new users separately. Compared with ACE inhibitor, SV new (HR: 0.18; 95% CI: 0.11-0.29) and ACE inhibitor–SV users (HR: 0.31; 95% CI: 0.23-0.43) showed lower risk of angioedema. On the other hand, there was no difference in angioedema risk when SV new users (HR: 0.59; 95% CI: 0.35-1.01) or ARB-SV users (HR: 0.85; 95% CI: 0.58-1.26) were compared with ARB new users. Compared with SV new users, ACE inhibitor–SV users (HR: 1.62; 95% CI: 0.91-2.89) trended toward higher angioedema risk, which intensified when the ACE inhibitor to SV switch occurred within 14 days (recent ACE inhibitor–SV) (HR: 1.98; 95% CI: 1.11-3.53). Similarly, ARB-SV users (HR: 2.03; 95% CI: 1.16-3.54) experienced an increased risk compared with SV new users, which intensified for the more recent switchers (recent ARB-SV) (HR: 2.45; 95% CI: 1.36-4.43). We did not observe an increased risk of angioedema among SV new users compared with ACE inhibitor or ARB users. However, there was an increased risk of angioedema among SV users who recently switched from ACE inhibitor or ARB compared with SV new users. [Display omitted] [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction(HFpEF) is an entity showing an upward trend. The affected population is rising on account of rise in the geriatric population as well as expanding incidence of comorbidities, thus underlining the necessity of greater therapeutic avenues. The underlying disease mechanisms are complicated. Irrespective of EF, HFpEF negatively influences quality of life and hard clinical endpoints. Greater research into HFpEF phenotypes, criteria for definition and improvement in prognosis is the need of the hour. [ABSTRACT FROM AUTHOR]

Background: Angiotensin receptor–neprilysin inhibitor (ARNI) therapy has been associated with improved survival for patients with symptomatic heart failure and reduced ejection fraction (HFrEF). Objectives: We performed a meta-analysis of arrhythmia endpoints from studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with HFrEF to assess for incremental benefit. Methods: We searched PubMed, Embase, and ClinicalTrials.gov. Baseline study characteristics were collected and outcomes were sustained ventricular arrhythmias, atrial arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, sudden cardiac death (SCD), and biventricular (BiV) pacing rate. Results: We included 9 studies, 4 randomized trials, and 5 observational studies (5589 patients on ARNI vs 5615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 ± 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% ± 7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63–0.96; P = .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25–0.79; P = .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21–0.74; P = .004). Higher rates of BiV pacing were seen (mean difference 3.13, 95% CI 2.58–3.68; P < .00001) when compared with ACEIs/ARBs. No difference in atrial arrhythmias was seen. Conclusion: ARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.

Abstract Aims We aimed to investigate whether sacubitril–valsartan could further improve the prognosis, cardiac function, and left ventricular (LV) remodelling in patients following acute myocardial infarction (AMI). Methods and results We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) from inception to 10 May 2021 to identify potential articles. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analysed. Thirteen RCTs, covering 1358 patients, were analysed. Compared with angiotensin‐converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril–valsartan did not significantly reduced the cardiovascular mortality [risk ratio (RR) 0.65, 95% confidence interval (CI) 0.22 to 1.93, P = 0.434] and the rate of myocardial reinfarction (RR 0.65, 95% CI 0.29 to 1.46, P = 0.295) of patients following AMI, but the rate of hospitalization for heart failure (HF) (RR 0.48, 95% CI 0.35 to 0.66, P

Background Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits. Methods and Results We conducted a retrospective cohort study within a large, multi‐site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered $100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (P$100 (OR, 2.58 [95% CI, 1.63–4.18], P

BackgroundSeveral studies have investigated the combined use of sacubitril- valsartan after reperfusion in acute ST-segment elevation myocardial infarction (STEMI). However, the sample sizes of these studies were small and their results were somewhat heterogeneous. To determine the effect of sacubitril-valsartan on myocardial ischemia-reperfusion.MethodsSearch PubMed, EMbase, Web of Science and The Cochrane Library, CNKI database, VIP database and Wanfang digital journal full-text database for eligible articles from their date of inception up to April, 2022. All data were meta-analyzed using Review Manager 5.3 and STATA 16.0 software.ResultsA total of 23 studies including 2,326 patients with acute STEMI were included. These results of this meta-analysis indicated that left ventricular ejection fractions (LVEF) value within 6 months after surgery (OR, 4.29; 95% confidence interval, 3.78–4.80; P < 0.00001), left ventricular end-diastolic diameter (LVEDD) value within 6 months after surgery (OR, −3.11; 95% CI, −3.87 to −2.35; P < 0.00001) and left ventricular end-diastolic volume (LVEDV) value 6 months after operation (OR, −6.22; 95% CI, −7.10 to −5.35; P < 0.00001) are better than without sacubitril and valsartan.ConclusionTo sum up the above, the results of this study suggest that sacubitril- valsartan can reduce the reperfusion injury of ischemic myocardium by improving cardiac function within a follow-up period of 6 months.

Objective To investigate the mechanism of cardioprotective effect of sacubitril/valsartan (ARNI) on heart failure rats after myocardial infarction. Methods A total of 60 adult male rats were randomly divided into the control group, the model group and the ARNI group. The model of heart failure was established by the ligation of of anterior descending branch of left coronary artery, while in the control group, threaded was inserted without ligation. The other two groups were given normal saline and ARNI (68 mg/kg) by gavage after ligation. After 3 months, echocardiography was completed to measure left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular end diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF). Hematoxylin and eosin (HE) staining and Masson staining were used to determine the myocardial structure and fibrosis. Enzyme linked immunosorbent assay (ELISA) was used to detect related indicators of inflammation and oxidative stress. Western blot assay was used to detect the expression levels of Bcl-2, Bax, Caspase3, Fas and FasL proteins. Results Compared with the control group, values of LVEDD, LVESD, LVEDV, IL-2, IL-6, TNF-α, Bax, Caspase-3, Fas and FasL were increased, but LVEF, LVFS, SOD, GST, IL-10 and Bcl-2 were decreased in the model group. Myocardial cell necrosis obviously increased, collagen production and fibrosis intensified in the model group. The application of ARNI reduced left ventricular remodeling and increased LVEF and LVFS, decreased inflammation and fibrosis, and decreased expression levels of IL-2, IL-6, TNF-α, Fas and FasL, and increased the expression levels of GST, IL-4, IL-10 and Bcl-2 (P＜0.05). Conclusion Sacubitril/valsartan can reduce myocardial cell apoptosis, reduce oxidative stress, inflammatory response and fibrosis by down-regulating Bax, Fas and FasL proteins, and reducing left ventricular remodeling to preserve LVEF. [ABSTRACT FROM AUTHOR]

Aim: The effect of sacubitril-valsartan (ARNI) in heart failure (HF) patients with mid-range ejection fractions (HFmrEF) remains unclear. This study aimed to investigate the effects of ARNI in HFmrEF patients. Methods: From inception to 15 February 2022, articles were searched via PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Whip, and Wanfang databases. Left ventricular functions, indicators related to HF, quality of life score, 6-Minute Walk Test, total effective rate, mortality, readmission rate, and adverse events were the outcomes. Relative risk (RR), weighted mean difference (WMD), and 95% confidence interval (CI) were used to evaluate the outcomes. The heterogeneity test was conducted for each indicator and measured by I2 statistics. Subgroup analysis was performed regarding the type of study and duration of treatment. Results: Sixteen studies involving 1,937 patients were included in this study. Our results showed ARNI was likely to improve left ventricular function by increasing the left ventricular ejection fraction (LVEF) (WMD: 2.36, 95%CI: 1.09-3.62), stroke volume (WMD: 16.800, 95%CI: 11.385-22.215), and left ventricular shortaxis shortening rate (WMD: 2.05, 95%CI: 0.25-3.86), decreasing left ventricular end-diastolic dimension (WMD: -2.48, 95%CI: -3.83 to -1.13), left atrial diameter (WMD: -2.23, 95%CI: -2.83 to -1.63), C-reactive protein level (WMD: -1.40, 95%CI: -2.62 to -0.18), and N-terminal-pro B-type natriuretic peptide level (WMD: -494.92, 95%CI: -641.34 to -348.50). ARNI has a higher total effective rate (RR: 1.15, 95%CI: 1.08-1.21), Kansas City cardiomyopathy questionnaire (WMD: 4.13, 95%CI: 3.46-4.81), and 6-Minute Walk Test (WMD: 51.35, 95%CI: 26.99-75.71) compared with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). In addition, ARNI decreased the readmission rate (RR: 0.54, 95%CI: 0.43-0.68) (all p < 0.05). Nevertheless, there were no significant differences in the adverse outcomes. Conclusion: This meta-analysis suggests ARNI may be an effective strategy with which to improve the left ventricular function, and quality of life, and reduce the readmission rate in HFmrEF patients. However, long-term clinical studies with large samples are still needed to further explore the efficacy and safety of ARNI compared with ACEI or ARB in the HFmrEF population. [ABSTRACT FROM AUTHOR]

Background: To assess the cost-effectiveness of sacubitril/valsartan compared with enalapril in patients with heart failure with reduced ejection (HFrEF). Methods: A systematic literature search was conducted searching in major electronic databases from inception to January 1, 2021. All relevant full economic evaluation studies of sacubitril/valsartan versus enalapril for the treatment of patients with HFrEF were identified using ad hoc search strategies. Mortality, hospital admissions, quality-adjusted life years (QALYs), lifeyears (LYQs), annual drug costs, total lifetime costs, and incremental cost-effectiveness ratio (ICER) were considered as the outcomes. The quality of the included studies was assessed using the CHEERS checklist. This study was conducted and reported in accordance with the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Results: The initial search yielded a pool of 1026 articles, of which 703 unique articles were screened, 65 full-text articles were assessed for eligibility and 15 studies finally included in the qualitative synthesis. Studies show that sacubitril/valsartan reduces mortality and hospitalization rate. The mean of death risk ratio and hospitalization were computed at 0.843 and 0.844, respectively. Sacubitril/valsartan produced higher annual and total lifetime costs. The lowest and highest lifetime costs for sacubitril/valsartan were found in Thailand ($4,756) and Germany ($118,815), respectively. The lowest ICER was reported in Thailand ($4857/QALY) and the highest in the USA ($143,891/QALY). Conclusion: Sacubitril/valsartan is associated with better outcomes and may be cost-effective compared to enalapril for the management of HFrEF. However, in developing countries such as Thailand, sacubitril-valsartan costs must be reduced to yield an ICER below the threshold. [ABSTRACT FROM AUTHOR]

Over the last decade, randomized clinical trials of several pharmacologic agents have demonstrated a reduction in cardiovascular mortality and other important secondary outcomes. Angiotensin-Neprilysin Inhibitors and Sodium-Glucose Co-transporter 2 inhibitors have now become pillars in the treatment of heart failure. Ivabradine is a negative chronotropic agent used as an adjunctive therapy in patients with heart failure. Two new hypertension therapies, zilebresiran and aprocitentan, are currently in investigational stages. Finally, mavacamten has emerged as a pharmacologic treatment for hypertrophic obstructive cardiomyopathy. Practitioners must be familiar with the indications and side effects of newer therapies as they are now frequently prescribed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Aims We systematically reviewed the European real‐world evidence (RWE) about sacubitril‐valsartan for heart failure with reduced ejection fraction. Methods and results Twenty‐one articles, including 16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM‐HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random‐effects model meta‐analysis, age was higher (mean difference +3.84, 95% CI 1.92–5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64–0.91), hypertension (OR 0.55, 95% CI 0.37–0.82), and diabetes (OR 0.77, 95% CI 0.64–0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27–5.53) in real‐life than in PARADIGM‐HF. Other clinical and medical features were presented in 19–76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril‐valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23–47) and discontinued in 12.8% (95% CI 7.4–18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all‐cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5–19)/100 person‐year, 8 (95% CI 4–12)/100 person‐year, and 24 (95% CI 5–42)/100 person‐year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and

Abstract Background Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalizations due to heart failure in patients with reduced ejection fraction (HFrEF) when compared to enalapril. Data about sacubitril/valsartan in patients with a history of cancer are scarce, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer. Methods We identified 225 patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan. Out of these, 9.3% (n = 21) had a history of histologically confirmed cancer. Oncologic surgery was performed in 16 (76.2%) patients, 11 (52.4%) patients received previous antineoplastic therapy and 9 patients (42.9%) radiation. Results Sacubitril/valsartan was withdrawn in 3 of 21 patients (14.3%) because of dizziness (n = 2) or pruritus (n = 1). After a median follow-up of 12 months (range 1–34 months), NYHA functional class improved significantly from NYHA 3 to NYHA 2 (mean -0.6, p = 0.006) and left ventricular ejection fraction as assessed by echocardiography increased significantly from 26.8 ± 5.4% to 39.2 ± 10% (mean + 12%, CI 95% [8.4–16.4], p = 0.0004). NT-proBNP was significantly reduced (baseline median 2774 pg/ml, range 1441 – 12,982 vs follow-up 1266 pg/ml, range 199–6324, p = 0.009). There was no significant change in creatinine levels (1.18 ± 0.4 vs 1.22 ± 0.4 mg/dl; mean + 0.005 mg/dl, CI 95% [-0.21- 0.12], p = 0.566). Conclusions In our pilot study we show that sacubitril/valsartan is generally well tolerated in patients with HFrEF and history of cancer. Importantly, even patients with long-standing cardiotoxicity induced heart failure can be treated and up-titrated with sacubitril/valsartan to usual target dosages, leading to improvement in LV function and biomarkers. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.

Background: To assess the cost-effectiveness of sacubitril/valsartan compared with enalapril in patients with heart failure with reduced ejection (HFrEF). Methods: A systematic literature search was conducted searching in major electronic databases from inception to January 1, 2021. All relevant full economic evaluation studies of sacubitril/valsartan versus enalapril for the treatment of patients with HFrEF were identified using ad hoc search strategies. Mortality, hospital admissions, quality-adjusted life years (QALYs), life-years (LYQs), annual drug costs, total lifetime costs, and incremental cost-effectiveness ratio (ICER) were considered as the outcomes. The quality of the included studies was assessed using the CHEERS checklist. This study was conducted and reported in accordance with the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines. Results: The initial search yielded a pool of 1026 articles, of which 703 unique articles were screened, 65 full-text articles were assessed for eligibility and 15 studies finally included in the qualitative synthesis. Studies show that sacubitril/valsartan reduces mortality and hospitalization rate. The mean of death risk ratio and hospitalization were computed at 0.843 and 0.844, respectively. Sacubitril/valsartan produced higher annual and total lifetime costs. The lowest and highest lifetime costs for sacubitril/valsartan were found in Thailand ($4,756) and Germany ($118,815), respectively. The lowest ICER was reported in Thailand ($4857/QALY) and the highest in the USA ($143,891/QALY). Conclusion: Sacubitril/valsartan is associated with better outcomes and may be cost-effective compared to enalapril for the management of HFrEF. However, in developing countries such as Thailand, sacubitril-valsartan costs must be reduced to yield an ICER below the threshold.

ObjectiveTo systematically review the efficacy and safety of sacubitril and valsartan in treating acute myocardial infarction complicated with heart failure and to observe whether it can further improve patients’ cardiac function, delay left ventricular remodeling, and reduce major adverse cardiovascular events (MACEs).MethodsElectronic databases including Pubmed, Embase, the Web of Science, Cochrane Library, Scopus, CNKI, Wanfang Data, and VIP were searched. The search period was from the establishment of the database to March 2022 to search for relevant controlled trials. Two investigators independently screened the literature, extracted data, and assessed the risk of bias. Revman5.3 and Stata14 software were used for statistical analysis.ResultsA total of 13 studies, with 6,968 patients were included. Meta-analysis results showed that sacubitril-valsartan increased left ventricular ejection fraction (LVEF) and decreased NT-proBNP level was better at 6 months and within 3 months of follow-up compared with the control group (P < 0.00001), but there was no significant difference at the 12-month follow-up (P > 0.05). Sacubitril-valsartan reducing LVEDD [MD = −2.55, 95%CI(−3.21, −1.88), P < 0.00001], LVEDVI [MD = −3.61, 95%CI(−6.82, −0.39), P = 0.03], LVESVI [MD = −3.77, 95%CI(−6.05, −1.49), P = 0.001], and increasing the distance of the 6-min walk test [MD = 48.20, 95%CI(40.31, 56.09), P < 0.00001] were more effective. Compared with ACEI/ARB, the use of ARNI can further reduce the total incidence of adverse cardiovascular events [RR = 0.72, 95%CI(0.62, 0.84), P 0.05). In terms of the incidence of adverse reactions, the incidence of cough in ARNI was lower than that in ACEI/ARB group [RR = 0.69, 95%CI(0.60, 0.80), P < 0.00001], but the incidence of hypotension was higher [RR = 1.29, 95%CI(1.18, 1.41), P < 0.00001], and the adverse reactions of hyperkalemia, angioedema and renal insufficiency were not increased (P > 0.05).ConclusionThe use of sacubitril-valsartan sodium in patients with acute myocardial infarction complicated with heart failure can significantly improve cardiac function and reverse ventricular remodeling, reducing the risk of re-hospitalization for heart failure. There is no apparent adverse reaction except easy cause hypotension.Systematic trial registration[www.ClinicalTrials.gov], identifier [CRD42022322901].