P5436Angiotensin receptor-neprilysin inhibitor preserved cardiac function via improving angiogenetic ability in mice model of atherosclerosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y S Suematsu ◽  
A I Ideishi ◽  
K T Tashiro ◽  
T K Kuwano ◽  
S M Miura

Abstract Introduction Angiotensin receptor-neprilysin inhibitor (ARNI) increases natriuretic peptide and improves heart failure. We previously reported that ARNI has the effects of suppression of myocardial hypertrophy and fibrosis in addition to reduction of afterload by natriuretic effect. We investigated the effects of ARNI against mice model of atherosclerosis and heart failure. Method and results Apolipoprotein E knockout mice fed high cholesterol diet for 4 weeks were divided into four groups: no treatment (CTL), valsartan 30 mg/kg (VAL), sacubitril (neprilysin inhibitor) 30 mg/kg (SAC), and ARNI 60mg/kg for additional 13 weeks. Body weight and systolic blood pressure in the VAL, SAC and ARNI groups did not show significant differences compared to those in the CTL group. Serum brain natriuretic peptide (BNP) in ARNI group (605±221 pg/ml) was significantly increased than that in VAL (391±57 pg/ml) and SAC (357±91 pg/ml) groups, but not CTL group (393±192 pg/ml). Although the rate of atherosclerotic area in aorta was 16.3±5.8% after treatment, there were no significant differences between the groups. In the CTL group, left ventricular ejection fraction (LVEF, 81.6±4.8%) and fractional shortening (FS, 44.8±5.8%) at baseline were significantly reduced after treatment (67.8±8.2% and 33.3±6.1%). Interestingly, LVEF (76.6±6.7%) and FS (40.1±6.1%) after treatment in the ARNI group were significantly preserved compared to those in the CTL group. In real time polymerase chain reaction analysis of LV after treatment, relative mRNA expression of BNP and angiogenetic factors including ATPase sarcoplasmic/endoplasmic reticulum Ca transporting 2, vascular endothelial growth factor A, cluster of differentiation 34 in ARNI group were significantly increased than those in the CTL group. Transforming growth factor-β in ARNI group was significantly reduced than that in the CTL group. Conclusion Although ARNI did not suppress atherosclerosis in mice, it preserved LVEF via improving angiogenetic ability.

Angiology ◽  
2021 ◽  
pp. 000331972110473
Author(s):  
Umut Karabulut ◽  
Kudret Keskin ◽  
Dilay Karabulut ◽  
Ece Yiğit ◽  
Zerrin Yiğit

The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tsutomu Kawai ◽  
Takahisa Yamada ◽  
Tetsuya Watanabe ◽  
Shunsuke Tamaki ◽  
Shungo Hikoso ◽  
...  

Backgrounds: Although B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP ) are interrelated parameters in assessment heart failure severity and prognosis, the ratio of NT-proBNP to BNP (NT-proBNP/BNP) are affected by various clinical factors, such as renal function. However, little is known about the influence of inflammation on NT-proBNP/BNP in patients with heart failure and preserved ejection fraction (HFpEF). Methods and Results: Patients data were extracted from PURSUIT-HFpEF registry, which is a multicenter prospective observational study including patients hospitalized for acute heart failure with left ventricular ejection fraction of >50%. Of 871 patients, data of BNP and NT-proBNP was available in 654 patients. The median baseline concentration of BNP was 474 pg/ml (299-720), NT-proBNP was 3310 pg/ml (1740-6840), and NT-proBNP/BNP was 7.6 (5.0-11.8). In multivariable linear regression analyses, older age [odds ratio (OR); 1.05, 95% confidence interval (CI); 1.02-1.09, p=0.001], higher creatinine [OR; 2.63, 95% CI; 1.66-4.16, p<0.001], and higher C-reactive protein (CRP) [OR; 1.17, 95% CI; 1.06-1.28, p<0.001] were significantly associated with a higher NT-proBNP/BNP (>median value of 7.6). However, other factors expected to affect NT-proBNP/BNP, such as atrial fibrillation and body mass index, were not associated with a higher NT-proBNP/BNP in this study. Patients in the highest CRP quartile had significantly higher NT-proBNP/BNP than those with other quartiles. Conclusion: In HFpEF patients, concomitant inflammation was associated with high NT-proBNP/BNP, which indicated that we need a careful interpretation on these two natriuretic peptides of patients with HFpEF and inflammatory status, such as infection.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Carlo Fino ◽  
Isabelle Piazza ◽  
Bruno Vito Domenico ◽  
Philippe Pibarot ◽  
Attilio Iacovoni ◽  
...  

Background and Objective: Surgical treatment of severe secondary ischemic mitral regurgitation (IMR) may improve symptoms and functional capacity, however there are few data on its effect on long-on the evolution of heart failure. Time-course changes in brain natriuretic peptide (BNP) are a good marker of the heart failure status and outcomes. We investigated the association between the exercise stress echocardiographic (ESE) parameters and the changes in brain natriuretic peptide (BNP) following surgery for secondary IMR. Methods: We prospectively analyzed data on 50 patients (median age: 67, 61-64 y; EF: 35, 34-40%), undergoing mitral valve annuloplasty or replacement and coronary artery bypass graft (CABG). A valve annuloplasty with undersized ring was performed in 20 patients (40%) and a replacement in 30 (60%). A six minute walking test (6-MWT), BNP levels and ESE were performed at 1 year and at median follow-up (FU) of 6 years (4-7). Results: BNP level was: 388 (329-441) pg/ml before surgery, 175 (142-743) pg/ml at 1 y, and 123 (100-979) pg/ml at last FU (p=0.2). The relative changes of BNP from baseline to last FU significantly correlated with exercise tricuspid annulus plane systolic excursion (TAPSE) at last FU (r= -0.7, p<0.001), with preoperative and FU exercise LVEF, respectively ( r=-0.7 p= 0.01) (r=-0.93, p<0.001).On multivariable analysis, preoperative exercise EF was strongly and independently associated with independent BNP levels at last FU and with the changes in BNP from baseline to last FU. Conclusions: Despite surgical treatment of severe secondary IMR, BNP levels progressively increased over time in nearly 50% of the patients. Lower preoperative and 1-year FU exercise-stress EF was associated with increased levels of BNP during FU..


Heart ◽  
2019 ◽  
pp. heartjnl-2019-314826 ◽  
Author(s):  
Céline Bégué ◽  
Stellan Mörner ◽  
Dulce Brito ◽  
Christian Hengstenberg ◽  
John G F Cleland ◽  
...  

ObjectivesN-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM.MethodsWe prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion.ResultsOf 357 patients enrolled, the median age was 52 (IQR: 36–65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10–4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1–2 vs 3–4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001).ConclusionsMR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1331-1331
Author(s):  
Gerard Dine ◽  
Vincent Genty ◽  
Said Brahimi ◽  
Nadia Ali Ammar ◽  
William Mendes ◽  
...  

Abstract The potential cardiotoxicity of chemotherapic drugs is well known. For example anthracycline-based regimens are extremely effective for various hematological malignancies. The main disadvantage is cardiotoxicity particularly, in elderly patients who are frequently treated with a consequent dose reduction. The diagnosis and prognosis in patients with suspected heart failure needs a specific monitoring by echocardiography during and after chemotherapy regimens. We tested the interest of NT-proBNP as alternative marker for the detection of left ventricular dysfunction. Brain or B-type natriuretic peptide (BNP) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP) are considered to be valuable biomarkers for the detection of disease state in patients with suspected heart failure. Methods During 1 year, blood samples of 31 patients with hematological malignancies, treated with usual chemotherapy were selected on a routine basis. Patients had the diagnosis of acute leukemia (AL), B-chronic lymphocytic leukemia (B-CLL), multiple myeloma (MM) and non Hodgkin lymphoma (NHL). Venous blood was drawn in the early morning and centrifuged at 2000 g for 15 minutes. The obtained clear plasma fraction was stored at −20°C until the assay. All plasma samples were analyzed for NT-proBNP using an electro chemiluminescence immuno assay (proBNP kit Roche Diagnostics, Mannheim, Germany) on Elecsys 2010 analyser. All assays were performed blind to clinical informations on the patients. Results The mean age of the patients was 72 (range: 36–88). There were 15 men (48 %) and 16 women (52 %). Five patients were smokers (16 %) and 7 (22.6%) had cardiovascular diseases (4 hypertension, 2 heart failure, 1 pace maker). Only 3 patients had a subnormal renal function. There were 6 patients with AL, 6 with B-CLL, 11 with MM and 8 with NHL. The administered medications were divided in 3 cardio-toxicity stages: 10 (32.25 %) patients received stage 3 cardiotoxicity regimens, 10 (32.25 %) stage 2 and 11 (35.5 %) stage 1. Fourteen patients (45 %) died in relation with hematological malignancies and none in relation with heart failure. But treatment regimens have been reduced, discontinued, modified or stopped in 7 patients after heart failure diagnosis with echocardiography. All these patients received stage 2 or 3 cardiotoxicity chemotherapy regimens and 4 had prior cardiovascular diseases. The mean age was 74 (range: 66–82). Only one patient is alive in this subgroup. Considering the age and the heart state of our 31 patients, chemotherapeutic treatments need or not to be adjust. The cardiac risk at diagnosis was assessed by left-ventricular ejection fraction (VEF) measurement. We shows that NT-proBNP brings reliable results to assess that risk, with a positive correlation to the VEF. Figure Figure Conclusion Despite the limitations of this preliminary study the measurement of the NT-proBNP concentration at baseline and during cardiotoxic regimens in patients with hematological malignancies seems to be a promising method to identify patients with an increased risk of cardiovascular adverse effects for it evolves earlier than VEF and is very well correlate to VEF loss and cardiotoxicity.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sha Fu ◽  
Zhenjian Xu ◽  
Baojuan Lin ◽  
Junzhe Chen ◽  
Qiuyan Huang ◽  
...  

Abstract Background and Aims Angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril–valsartan is a landmark drug in heart failure with reduced ejection fraction (HFrEF), however, it remains unclear in patients with heart failure with preserved ejection fraction (HFpEF), especially the data of ARNI treatment on peritoneal dialysis (PD) patients with HFpEF are lacking. The present study was designed to determine the efficacy and safety of sacubitril–valsartan in patients with HFpEF undergoing peritoneal dialysis. Method We assigned end stage renal disease (ESRD)patients, receiving peritoneal dialysis for 3 months, with New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≥ 50%, and elevated level of N-terminal pro–B-type natriuretic peptide (NT-proBNP) to receive sacubitril/valsartan treatment. Patients were regularly followed up after medication treatment. Wilcoxon matched-pair signed-rank (2 samples) tests were applied to investigate the alterations in Clinical and biochemical parameters as the efficacy before and after taking sacubitril–valsartan, and safety was also assessed. Results Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels (p=0.002) and heart rate (p=0.031) were markedly decreased after treatment with sacubitril/valsartan, signs and symptoms of heart failure (21/21 versus 15/21, p=0.021) and NYHA classification were notably improved after 3-12 months follow-up. Conclusion The present data suggested that sacubitril/valsartan treatment in the patients with HFpEF undergoing peritoneal dialysis was effective and safe, which is the first study about sacubitril/valsartan treatment for the PD patients with HFpEF, and it may bring the hope for these patients due to no other effective methods at present.


Cardiology ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 96-99 ◽  
Author(s):  
Henrik Fox ◽  
Thomas Bitter ◽  
Dieter Horstkotte ◽  
Olaf Oldenburg

Sleep-disordered breathing (SDB) is highly prevalent in patients with heart failure (HF), and is known to be associated with a worse prognosis. The severity of central sleep apnea is thought to mirror cardiac dysfunction. The novel angiotensin receptor-neprilysin inhibitor (ARNi) sacubitril has been shown to improve HF, but a relationship between treatment with ARNi and the severity of SDB has not yet been investigated. We report the case of a 71-year-old male with HF and SDB. Treatment with sacubitril/valsartan was associated with improved cardiac function, as shown by a reduction in the level of N-terminal prohormone of brain natriuretic peptide from 3,249 to 1,720 pg/mL, and an improvement in left-ventricular ejection fraction from 30 to 35%. This was accompanied by a marked reduction in the apnea-hypopnea index (from 41 to 19/h). To the best of our knowledge, this is the first case to document parallel improvements in HF and SDB after the initiation of ARNi treatment.


2021 ◽  
Vol 10 (16) ◽  
pp. 3564
Author(s):  
Hiroyuki Naruse ◽  
Junnichi Ishii ◽  
Hiroshi Takahashi ◽  
Fumihiko Kitagawa ◽  
Eirin Sakaguchi ◽  
...  

The prognostic role of D-dimer in different types of heart failure (HF) is poorly understood. We investigated the prognostic value of D-dimer on admission, both independently and in combination with the Get With The Guidelines—Heart Failure (GWTG-HF) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients with preserved left ventricular ejection fraction (LVEF) and acute decompensated HF (HFpEF) or reduced LVEF (HFrEF). Baseline D-dimer levels were measured on admission in 1670 patients (mean age: 75 years) who were hospitalized for worsening HF. Of those patients, 586 (35%) were categorized as HFpEF (LVEF ≥ 50%) and 1084 as HFrEF (LVEF < 50%). During the 12-month follow-up period after admission, 360 patients died. Elevated levels (at least the highest tertile value) of D-dimer, GWTG-HF risk score, and NT-proBNP were all independently associated with mortality in all HFpEF and HFrEF patients (all p < 0.05). Adding D-dimer to a baseline model with a GWTG-HF risk score and NT-proBNP improved the net reclassification and integrated discrimination improvement for mortality greater than the baseline model alone in all populations (all p < 0.001). The number of elevations in D-dimer, GWTG-HF risk score, and NT-proBNP were independently associated with a higher risk of mortality in all study populations (HFpEF and HFrEF patients; all p < 0.001). The combination of D-dimer, which is independently predictive of mortality, with the GWTG-HF risk score and NT-proBNP could improve early prediction of 12-month mortality in patients with acute decompensated HF, regardless of the HF phenotype.


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