Efficacy and Safety of Sacubitril/Valsartan Therapy for Acute Decompensated Heart Failure with Reduced Ejection Fraction during the Vulnerable Phase: A Multicenter, Assessor-Blinded, Prospective, Observational, Cohort Study

Cardiology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Yun He ◽  
Xuemei Lu ◽  
Yi Zheng ◽  
Mingbao Song ◽  
Bin Shen ◽  
...  

<b><i>Background:</i></b> The 3-month period after hospitalization for acute cardiac failure is a vulnerable phase with the highest risk of mortality and rehospitalization. Safety and efficacy of early initiation of sacubitril/valsartan during the index hospitalization for acute decompensated heart failure (ADHF) is unclear. Therefore, we tested whether sacubitril/valsartan could result in a lower rate of a composite outcome of first hospitalization for heart failure and death from cardiovascular causes compared to inhibition of the renin-angiotensin system alone. <b><i>Methods:</i></b> We enrolled patients hospitalized for ADHF and reduced ejection fraction at 4 sites; patients were divided into a sacubitril/valsartan group or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) group. All patients were followed up for 3 months after discharge. The primary endpoint was outcomes as a composite of death from cardiovascular causes and rehospitalization for heart failure. <b><i>Results:</i></b> In total, 251 patients who received sacubitril/valsartan and 251 patients who received ACEIs/ARBs had similar propensity scores and were included and compared. The primary endpoint was reached in 40 patients (15.9%) treated with sacubitril/valsartan and in 59 patients (23.5%) managed by ACEI/ARB (HR, 0.650; 95% CI: 0.435–0.971; <i>p</i> = 0.035). The NYHA class improved in 72.1% of patients in the sacubitril/valsartan group and in 59.8% of patients in the ACEI/ARB group (HR, 1.303; 95% CI: 1.097–1.548, <i>p</i> = 0.004). The key safety outcomes endpoints did not significantly differ. <b><i>Conclusions:</i></b> Among patients hospitalized with ADHF and reduced left ventricular ejection fraction, we observed that sacubitril/valsartan therapy led to reduction in death from cardiovascular causes and rehospitalizations for heart failure when compared to ACEI/ARB therapy alone during the vulnerable phase. Our results support that sacubitril/valsartan may be administered early in the vulnerable phase after ADHF and improves NYHA class.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Takanari Kimura ◽  
Shungo Hikoso ◽  
Nakatani Daisaku ◽  
Shunsuke Tamaki ◽  
Masamichi Yano ◽  
...  

Background: Sarcopenia is associated with poor prognosis in chronic heart failure. Fat-free mass index (FFMI) is an indicator of resting energy expenditure and has been used for the clinical diagnosis of sarcopenia. However, the prognostic impact of sarcopenia diagnosed by FFMI remains to be elucidated in patients admitted with acute decompensated heart failure (ADHF) and preserved LVEF (HFpEF), relating to gender. Methods: Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a prospective multicenter observational registry for ADHF patients with LVEF ≥50% in Osaka. We studied 621 patients who survived to discharge (men, n=281 and women, n=340). Fat-free mass (FFM) was estimated by the formula [FFM (kg) = 7.38 + 0.02908 х urinary creatinine (mg/day)] and normalized by the square of the patient’s height in meters to calculate FFMI at discharge. Sarcopenia was defined as FFMI <17 kg/m2 in men and <15 kg/m2 in women. The endpoint was all-cause death. Results: During a follow-up period of 1.5±0.8 yrs, 102 patients died (men, n=46 and women, n=56). At multivariate Cox analysis, FFMI was significantly associated with the mortality independently of age, estimated glomerular filtration rate, NT-proBNP and LVEF in both men (p=0.0155) and women (p=0.0223). Patients with sarcopenia had a significantly higher risk of all-cause death than those without sarcopenia in both genders (Figure). Conclusions: In this multicenter study, sarcopenia diagnosed by FFMI was shown to be associated with poor clinical outcome in HFpEF patients admitted with ADHF in both genders.


2020 ◽  
Vol 22 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Masahiro Seo ◽  
Takahisa Yamada ◽  
Shunsuke Tamaki ◽  
Tetsuya Watanabe ◽  
Takashi Morita ◽  
...  

Abstract Aims Cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging provides prognostic information in patients with chronic heart failure (HF). However, there is little information available on the prognostic role of cardiac 123I-MIBG imaging in patients admitted for acute decompensated heart failure (ADHF), especially relating to reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) &lt; 40%], mid-range ejection fraction (HFmrEF; 40% ≤ LVEF &lt; 50%) and preserved ejection fraction (HFpEF; LVEF ≥ 50%). Methods and results We studied 349 patients admitted for ADHF and discharged with survival. Cardiac 123I-MIBG imaging, echocardiography, and venous blood sampling were performed just before discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (late H/M) was measured on the chest anterior view images obtained at 200 min after the isotope injection. The endpoint was cardiac events defined as unplanned HF hospitalization and cardiac death. During a follow-up period of 2.1 ± 1.4 years, 128 patients had cardiac events (45/127 in HFrEF, 28/78 in HFmrEF, and 55/144 in HFpEF). On multivariable Cox analysis, late H/M was significantly associated with cardiac events in overall cohort (P = 0.0038), and in subgroup analysis of each LVEF subgroup (P = 0.0235 in HFrEF, P = 0.0119 in HFmEF and P = 0.0311 in HFpEF). Kaplan–Meier analysis showed that patients with low late H/M (defined by median) had significantly greater risk of cardiac events in overall cohort (49% vs. 25% P &lt; 0.0001) and in each LVEF subgroup (HFrEF: 48% vs. 23% P = 0.0061, HFmrEF: 51% vs. 21% P = 0.0068 and HFpEF: 50% vs. 26% P = 0.0026). Conclusion Cardiac sympathetic nerve dysfunction was associated with poor outcome in ADHF patients irrespective of HFrEF, HFmrEF, or HFpEF.


2022 ◽  
Vol 74 (1) ◽  
Author(s):  
Ahmed El Fol ◽  
Waleed Ammar ◽  
Yasser Sharaf ◽  
Ghada Youssef

Abstract Background Arterial stiffness is strongly linked to the pathogenesis of heart failure and the development of acute decompensation in patients with stable chronic heart failure. This study aimed to compare arterial stiffness indices in patients with heart failure with reduced ejection fraction (HFrEF) during the acute decompensated state, and three months later after hospital discharge during the compensated state. Results One hundred patients with acute decompensated HFrEF (NYHA class III and IV) and left ventricular ejection fraction ≤ 35% were included in the study. During the initial and follow-up visits, all patients underwent full medical history taking, clinical examination, transthoracic echocardiography, and non-invasive pulse wave analysis by the Mobil-O-Graph 24-h device for measurement of arterial stiffness. The mean age was 51.6 ± 6.1 years and 80% of the participants were males. There was a significant reduction of the central arterial stiffness indices in patients with HFrEF during the compensated state compared to the decompensated state. During the decompensated state, patients presented with NYHA FC IV (n = 64) showed higher AI (24.5 ± 10.0 vs. 16.8 ± 8.6, p < 0.001) and pulse wave velocity (9.2 ± 1.3 vs. 8.5 ± 1.2, p = 0.021) than patients with NYHA FC III, and despite the relatively smaller number of females, they showed higher stiffness indices than males. Conclusions Central arterial stiffness indices in patients with HFrEF were significantly lower in the compensated state than in the decompensated state. Patients with NYHA FC IV and female patients showed higher stiffness indices in their decompensated state of heart failure.


2017 ◽  
Vol 8 (7) ◽  
pp. 606-614 ◽  
Author(s):  
Katsuya Kajimoto ◽  
Yuichiro Minami ◽  
Shigeru Otsubo ◽  
Naoki Sato

Background: In acute decompensated heart failure patients with a preserved or reduced ejection fraction, the association of admission and discharge anemia status with outcomes remains unclear. Methods and results: Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4433 patients (2017 with a preserved and 2416 with a reduced ejection fraction) were examined to investigate associations among the anemia status at admission and discharge (no anemia, developed anemia, resolved anemia, or persistent anemia), a preserved or reduced ejection fraction and the primary endpoint (all-cause death and readmission for heart failure). In the preserved ejection fraction group, adjusted analysis showed that either developed or persistent anemia was associated with a significantly higher risk of the primary endpoint relative to no anemia (hazard ratio: 1.53; 95% confidence interval (CI): 1.11–2.11; p=0.009 and hazard ratio: 1.60; 95% CI: 1.26–2.04; p<0.001, respectively), but there was no association between resolved anemia and the primary endpoint (hazard ratio: 0.98; 95% CI: 0.67–1.45; p=0.937). In the reduced ejection fraction group, either developed or resolved anemia was associated with a tendency toward higher risk of the primary endpoint relative to no anemia (hazard ratio: 1.29; 95% CI: 0.95–1.62; p=0.089, and hazard ratio: 1.31; 95% CI: 0.96–1.77; p=0.085, respectively), while persistent anemia was associated with a significantly higher risk of the primary endpoint relative to no anemia (hazard ratio: 1.36; 95% CI: 1.12–1.65; p=0.002). Conclusions: In acute decompensated heart failure patients, the association of admission and discharge anemia status with outcomes differs markedly between patients with a preserved or reduced ejection fraction.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K C Neoh ◽  
D Rasoul ◽  
F Hunt ◽  
D W S Chong

Abstract Background Sacubitril/Valsartan has been shown to improve symptoms and outcomes in patients with heart failure (HF) reduced ejection fraction in a single large randomised controlled trial. However, real-world data on its effect is limited. Purpose Our centre operates a dedicated HF clinic for the initiation and titration of Sacubitril/Valsartan in suitable patients. We report on patient tolerability and incidence of adverse effects. We also assessed change in New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF) post-treatment, as well as HF hospitalisation and mortality at 6 months. Methods We conducted a retrospective review of all patients seen in the clinic between January 2016 to January 2019. Patient demographics and pre-initiation treatments were recorded. We compared NYHA class and LVEF category as measured by echocardiography, at initiation and post-titration to the maximum tolerated dose. Data on HF admissions were obtained from electronic hospital records and mortality from a national database. Results A total of 179 patients were initiated on Sacubitril/Valsartan and included in the study. Mean age was 71 years (41–90), and 138 (77%) were male. Half of the patient cohort (89) had an ischaemic aetiology. Prior to initiation, all patients were established on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Almost all were on a beta-blocker (99%) and mineralocorticoid receptor antagonist (98%). 56 patients (31%) had a Cardiac Resynchronisation Therapy (CRT) device and 31 (17%) had an Implantable Cardioverter-Defibrillator (ICD). Only 4 patients (2%) had to discontinue treatment completely due to an adverse reaction. Among them, 3 patients sustained an acute kidney injury (AKI) while 1 patient had increased breathlessness. 40 patients (22%) reported symptomatic hypotension which required dose reduction. 7 patients (4%) sustained an AKI. 2 patients reported a rash and 1 patient reported nausea. Figure 1 shows the change in NYHA class after establishment on Sacubitril/Valsartan. Data on change in LVEF post establishment of Sacubitril/Valsartan was available in 124 patients and is shown in figure 2. A total of 133 patients had completed titration of treatment by July 2018 and included in the analysis of 6-month outcome. 13 patients had one HF hospitalisation and all-cause mortality was 4.5% (6 patients). Only 1 patient had heart failure documented as the primary cause of death. Change in NYHA class and LVEF Conclusion In our cohort of well treated HF patients with reduced ejection fraction, 40% of patients experienced an improvement in NYHA class after establishment on Sacubitril/Valsartan while 35% of patients also experienced a significant improvement in LVEF. Treatment was well tolerated and the discontinuation rate was low when managed in a dedicated HF clinic focused on initiation of Sacubitril/Valsartan.


2021 ◽  
Vol 23 (4) ◽  
pp. 839-844
Author(s):  
O. N. Ogurkova ◽  
E. V. Kruchinkina ◽  
A. M. Gusakova ◽  
T. E. Suslova ◽  
V. V. Ryabov

The development and progression of heart failure is associated with a variety of pathophysiological mechanisms, of particular interest is the study of the inflammatory response as a fundamental link in the pathogenesis of CHF and its main component – decompensation. An open, non-randomized, prospective study was carried out to evaluate the clinical and morphological features of subclinical inflammation in patients with acute decompensation of ischemic chronic heart failure with a reduced ejection fraction. The study included 25 patients with decompensated ischemic CHF with left ventricular ejection fraction < 40% aged 35 to 75 years (60.12±9.3 y. o.). In this study the dynamics of the serum content of C-reactive protein (CRP), N-terminal fragment of the brain natriuretic peptide precursor protein (NT-proBNP), soluble ST2(sST2), insulin-like growth factor-1 receptor (IGF-1R), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNFα) was performed by multiplex immunoassay using the FLEXMAP 3D. All studied patients were divided into two groups depending on the diagnosed myocarditis: patients with no signs of myocarditis and patients with myocarditis. It was found that in the group of patients with diagnosed myocarditis there was an increased content of CRP, IGF-1R, IL-6 and IL-10, TNFα compared to the group of patients without myocarditis. The median concentrations of the NT-proBNP and sST2 in both groups did not differ. At the follow-up visit a year later, there was a decrease in the content of CRP, NT-proBNP, IL-6 in both groups. In the group of patients with myocarditis, an increase in the content of sST2, IGF-1R, IL-10 was observed. Thus, the study carried out in dynamics revealed significant differences in the degree of changes in the serum activity of pro- and anti-inflammatory cytokines and biomarkers of cardiovascular risk in patients with decompensated heart failure with systolic dysfunction with diagnosed myocarditis and in its absence. 


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