scholarly journals Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register

Author(s):  
Maria Concetta Pastore ◽  
Giulia Elena Mandoli ◽  
Alberto Giannoni ◽  
Giovanni Benfari ◽  
Frank Lloyd Dini ◽  
...  

Abstract Background This sub-study deriving from a multicenter Italian register (DISCOVER-ARNI) investigated whether sacubitril/valsartan in adjunction of optimal medical therapy(OMT) could reduce the rate of implantable cardioverter-defibrillator(ICD) indications for primary prevention in heart failure with reduced ejection fraction(HFrEF) according to European guidelines indications, and its potential predictors. Methods In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centers were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Results Of 351 patients, 225(64%) were ICD carriers and 126(36%) were not ICD carriers (of whom 13 had not indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV)EF≤35% and New York Heart Asscociation(NYHA) class=II-III, 69(60%) did not show ICD indications; 44(40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation>moderate, left atrial volume index(LAVi), and LV global longitudinal strain(GLS) significantly varied between the groups. With ROC curves, age≥75 years, LAVi≥42ml/m2 and LV GLS≥-8.3% were associated with ICD indications persistence (AUC=0.65,=0.68,=0.68 respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/hemorrhagic risks and unnecessary costs deriving from ICDs.

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Maria Concetta Pastore ◽  
Giulia Elena Mandoli ◽  
Alberto Giannoni ◽  
Giovanni Benfari ◽  
Frank Lloyd Dini ◽  
...  

Abstract Aims This sub-study deriving from a multicentre Italian register (DISCOVER-ARNI) investigated whether sacubitril/valsartan in adjunction of optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator(ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical and echocardiographic data were collected at baseline and after 6 months of therapy. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had not indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV)EF ≤ 35% and New York Heart Association (NYHA) class = II–III, 69(60%) did not show ICD indications; 44(40%) still fulfilled ICD criteria (Figure 1). Age, atrial fibrillation, mitral regurgitation>moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With ROC curves, age ≥ 75 years, LAVi ≥ 42 ml/m2 and LV GLS ≥ −8.3% were associated with ICD indications persistence (AUC = 0.65, 0.68, and 0.68, respectively). With univariate and multivariate analysis, age and LV GLS emerged as the only significant predictors of ICD indications at follow-up. Conclusions Sacubitril/valsartan provided early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline advanced age and reduced LV GLS were markers of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Giulia Elena Mandoli ◽  
Maria Concetta Pastore ◽  
Alberto Giannoni ◽  
Giovanni Benfari ◽  
Frank Lloyd Dini ◽  
...  

Abstract Aims Sacubitril/valsartan have changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects morbidity and mortality partly mediated by left ventricular reverse remodelling (LVRR). The aim of this multicentre study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic indexes including speckle tracking echocardiography (STE) indexes were used to predict LVRR [defined as LV end-systolic volume reduction and ejection fraction (LVEF) improvement > 10% at follow-up] at 6 months follow-up as the primary endpoint. Changes in symptoms (NYHA class) and neurohormonal activations [N-terminal-pro-brain natriuretic peptide (NTproBNP)] were also evaluated as secondary endpoints. The final population (excluding patients with poor acoustic windows and missing data) consists of 341 patients [mean age: 65 ± 10 years; 18% female, median LVEF 30% (interquartile range: 25–34)]. At 6 months follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥35%), 55 (16%) early incomplete response (LVRR and LVEF <35%), 204 (60%) no response (no LVRR and LVEF <35%). Non-ischaemic etiology, a lower left atrial volume index and a higher global longitudinal strain were all independent predictors of LVRR at multivariable logistic analysis (all P < 0.01). LA strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P < 0.05) (Figure 1). Conclusions STE parameters at baseline could be useful to predict LVRR and clinical response to sacubitril-valsartan, and thus could be used as a guide for treatment in patients with HFrEF.


2021 ◽  
Vol 76 (3) ◽  
pp. 298-306
Author(s):  
Alexey S. Ryazanov ◽  
Evgenia V. Shikh ◽  
Konstantin I. Kapitonov ◽  
Mariya V. Makarovskaya ◽  
Alexey A. Kudryavtsev

Background. Compared with enalapril, sacubitril/valsartan reduces mortality from cardiovascular diseases and the number of hospitalizations for heart failure in patients with heart failure and reduced ejection fraction (HFrEF). These benefits may be related to effects on hemodynamics and cardiac remodeling. The aim of the study is to determine the effect of sacubitril/valsartan on aortic stiffness and cardiac remodeling compared with enalapril in HFrEF. Materials and methods. In this long-term outpatient study, 100 patients with HFrEF received sacubitril/valsartan or enalapril. The primary endpoint was the change in arterial impedance (aortic stiffness characteristic) over a 12-month follow-up. Secondary endpoints included changes in N-terminal cerebral natriuretic propeptide (NT-proBNP), ejection fraction, left atrial volume index, E/e index, left ventricular end-systolic and end-diastolic volumes; left ventricular-arterial index (Ea/Ees). Results. During 12 months of follow-up, 100 patients showed significant differences between the groups with respect to changes in arterial impedance, which decreased from 224.0 to 207.9 dynes s/ cm5 in the sacubitrile/valsartan group and increased from 213.5 to 214.1 dyne s/cm5 in the enalapril group (difference between groups: 9.3 dynes s/ cm5; 95% CI: from 16.9 to 12.8 dynes s/cm5; p = 0.69). Also, there were intergroup differences in the change in left ventricular ejection fraction and Ea/Ees index. NT-proBNP level, left ventricular end-diastolic and systolic volume index, left atrial volume index, E/e index were reduced in the sacubitril/valsartan group. Conclusions. Treatment with sacubitril/valsartan compared with enalapril resulted in a significant reduction in aortic stiffness in HFrEF.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Luca Monzo ◽  
Ilaria Ferrari ◽  
Carlo Gaudio ◽  
Francesco Cicogna ◽  
Claudia Tota ◽  
...  

Abstract Aims Current guidelines recommend an implantable cardiac defibrillator (ICD) in patients with symptomatic heart failure and reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) ≤35%] despite ≥3 months of optimal medical therapy. Recent observations demonstrated that sacubitril/valsartan induces beneficial reverse cardiac remodelling in eligible HFrEF patients. Given the pivotal role of LVEF in the selection of ICD candidates, we sought to assess the impact of sacubitril/valsartan on ICD eligibility and its predictors in HFrEF patients. Methods and results We retrospectively evaluated 48 chronic HFrEF patients receiving sacubitril/valsartan and previously implanted with an ICD in primary prevention. We assumed that ICD was no longer necessary if LVEF improved >35% (or > 30% in asymptomatics) at follow-up. Over a median follow-up of 11 months, sacubitril/valsartan induced a significant drop in LV end-systolic volume (−16.7 ml/m2, P = 0.023) and diameter (−6.8 mm, P = 0.022), resulting in a significant increase in LVEF (+3.9%, P < 0.001). As a consequence, 40% of previously implanted patients resulted no more eligible for ICD at follow-up. NYHA class improved in the 50% of population. A dose-dependent effect was noted, with higher doses associated to more reverse remodelling. Among patients deemed no more eligible for ICD, lower NYHA class [odds ratio (OR): 3.73 (95% CI: 1.05–13.24), P = 0.041], better LVEF [OR: 1.23 (95% CI: 1.01–1.48), P = 0.032], and the treatment with the intermediate or high dose of sacubitril/valsartan [OR: 5.60 (1.15–27.1), P = 0.032] were the most important predictors of status change. Conclusions In symptomatic HFrEF patients, sacubitril/valsartan induced beneficial cardiac reverse remodelling and improved NYHA class. These effects resulted in a significant reduction of patients deemed eligible for ICD in primary prevention.


2020 ◽  
Vol 9 (4) ◽  
pp. 906 ◽  
Author(s):  
Matteo Castrichini ◽  
Paolo Manca ◽  
Vincenzo Nuzzi ◽  
Giulia Barbati ◽  
Antonio De Luca ◽  
...  

Sacubitril/valsartan reduces mortality in heart failure with reduced ejection fraction (HFrEF) patients, partially due to cardiac reverse remodeling (RR). Little is known about the RR rate in long-lasting HFrEF and the evolution of advanced echocardiographic parameters, despite their known prognostic impact in this setting. We sought to evaluate the rates of left ventricle (LV) and left atrial (LA) RR through standard and advanced echocardiographic imaging in a cohort of HFrEF patients, after the introduction of sacubitril/valsartan. A multi-parametric standard and advanced echocardiographic evaluation was performed at the moment of introduction of sacubitril/valsartan and at 3 to 18 months subsequent follow-up. LVRR was defined as an increase in the LV ejection fraction ≥10 points associated with a decrease ≥10% in indexed LV end-diastolic diameter; LARR was defined as a decrease >15% in the left atrium end-systolic volume. We analyzed 77 patients (65 ± 11 years old, 78% males, 40% ischemic etiology) with 76 (28–165) months since HFrEF diagnosis. After a median follow-up of 9 (interquartile range 6–14) months from the beginning of sacubitril/valsartan, LVRR occurred in 20 patients (26%) and LARR in 33 patients (43%). Moreover, left ventricular global longitudinal strain (LVGLS) improved from −8.3 ± 4% to −12 ± 4.7% (p < 0.001), total left atrial emptying fraction (TLAEF) from 28.2 ± 14.4% to 32.6 ± 13.7% (p = 0.01) and peak atrial longitudinal strain (PALS) from 10.3 ± 6.9% to 13.7 ± 7.6% (p < 0.001). In HFrEF patients, despite a long history of the disease, the introduction of sacubitril/valsartan provides a rapid global (i.e., LV and LA) RR in >25% of cases, both at standard and advanced echocardiographic evaluations.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Sara Monosilio ◽  
Domenico Filomena ◽  
Federico Luongo ◽  
Matteo Neccia ◽  
Michele Sannino ◽  
...  

Abstract Aims Sacubitril/valsartan (S/V) benefits in patients with heart failure and reduced ejection fraction (HFrEF) are partially related to cardiac reverse remodelling, in terms of volumes reduction and function improvement. Effects on vascular remodelling are less investigated. To evaluate cardiac and vascular remodelling in a cohort of patients with HFrEF after 6 months of therapy with S/V. Methods and results 50 patients with HFrEF eligible to start a therapy with sacubitril/valsartan were enrolled. Clinical evaluation and standard and advanced echocardiography were performed at baseline and after 6 months of follow-up (FU). Standard left ventricular dimension and function parameters and global longitudinal strain (GLS) were calculated. Non-invasive pressure-volume curves (P-V loop) estimation was assessed with an off-line dedicated software using ST-E derived time-resolved LV volumes and brachial pressure as input. The following haemodynamic parameters were calculated based on P–V loop curves: left ventricular elastance (Ees), arterial elastance (Ea), and ventricular-arterial coupling (VAC). At 6 months F/U, a reduction of NYHA class in the vast majority of patients was detected (NYHA Class ≥ II, baseline vs. F/U = 100% vs. 50%; P &lt; 0.001). Systolic and diastolic blood pressure were lower, in comparison with baseline values (119 ± 16 vs. 126 ± 11 mmHg; P = 0.002 and 71 ± 8 vs. 78 ± 8 mmHg; P = 0.001, respectively). At echocardiographic evaluation, left ventricular end-diastolic and end-systolic volumes decreased and ejection fraction and GLS significantly improved (Table). Moreover, a significant reduction of Ea and a significant improvement of Ees and VAC was observed (Table). 511 Table 1 Conclusions Therapy with S/V in HFrEF patients determines both cardiac and vascular remodelling reflecting the complex mechanisms behind clinical improvement.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Johnsen ◽  
M Sengeloev ◽  
P Joergensen ◽  
N Bruun ◽  
D Modin ◽  
...  

Abstract Background Novel echocardiographic software allows for layer-specific evaluation of myocardial deformation by 2-dimensional speckle tracking echocardiography. Endocardial, epicardial- and whole wall global longitudinal strain (GLS) may be superior to conventional echocardiographic parameters in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose The purpose of this study was to investigate the prognostic value of endocardial-, epicardial- and whole wall GLS in patients with HFrEF in relation to all-cause mortality. Methods We included and analyzed transthoracic echocardiographic examinations from 1,015 patients with HFrEF. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. A p value in a 2-sided test &lt;0.05 was considered statistically significant. Cox proportional hazards regression models were constructed, and both univariable and multivariable hazard ratios (HRs) were calculated. Results During a median follow-up time of 40 months, 171 patients (16.8%) died. A lower endocardial (HR 1.17; 95% CI (1.11–1.23), per 1% decrease, p&lt;0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p&lt;0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p&lt;0.001) GLS were all associated with higher risk of death (Figure 1). Both endocardial (HR 1.12; 95% CI (1.01–1.23), p=0.027), epicardial (HR 1.13; 95% CI (1.01–1.26), p=0.040) and whole wall (HR 1.13; 95% CI (1.01–1.27), p=0.030) GLS remained independent predictors of mortality in the multivariable models after adjusting for significant clinical parameters (age, sex, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty and diabetes) and conventional echocardiographic parameters (left ventricular (LV) ejection fraction, LV mass index, left atrial volume index, deceleration time, E/e', E-velocity, E/A ratio and tricuspid annular plane systolic excursion). No other echocardiographic parameters remained an independent predictors after adjusting. Furthermore, endocardial, epicardial and whole wall GLS had the highest C-statistics of all the echocardiographic parameters. Conclusion Endocardial, epicardial and whole wall GLS are independent predictors of all-cause mortality in patients with HFrEF. Furthermore, endocardial, epicardial and whole wall GLS were superior prognosticators of all-cause mortality compared with all other echocardiographic parameters. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev and Gentofte Hospital


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
E Sakaguchi ◽  
A Yamada ◽  
M Hoshino ◽  
K Takada ◽  
N Hoshino ◽  
...  

Abstract Purposes We examined how changes in left ventricular (LV) global longitudinal strain (GLS) were associated with prognosis in patients with preserved LV ejection fraction (LVEF) after congestive heart failure (HF) admission. Methods We studied 123 consecutive patients (age 70 ± 15 years, 55% male) who had been hospitalized due to congestive HF with preserved LVEF (&gt; 50%). The exclusion criteria were atrial fibrillation and inadequate echo image quality for strain analyses. The patients underwent speckle-tracking echocardiography and measurement of plasma NT-ProBNP levels on the same day at the time of hospital admission as well as in the stable condition after discharge. Differences in GLS, LVEF and NT-ProBNP (delta GLS, LVEF and NT-ProBNP ; 2nd – 1st measurements) were calculated. The study end points were all-cause mortality and cardiac events. Results Mean periods of echo performance after hospitalization were 2 ±1days (1st echo) and 240 ± 289 days (2nd echo), respectively. During the follow-up (974 ± 626 days), 12 patients died and 25 patients were hospitalized because of HF worsening. In multivariate analysis, delta GLS and follow-up GLS were prognostic factors, whereas baseline and follow-up LVEF, NT-ProBNP, changes in LVEF and NT-ProBNP could not predict cardiac events. Delta GLS (p = 0.002) turned out to be the best independent prognosticator. Receiver operating characteristics analysis revealed that -0.6% of delta GLS was the optimal cut-off value to predict cardiac events and mortality (sensitivity 76%, specificity 67%, AUC 0.75). Kaplan-Meier analysis showed that patients with delta GLS more than -0.6% experienced significantly less cardiac events during the follow-up period (p &lt; 0.0001, log-rank). Conclusion A change in LV GLS after congestive HF admission was a predictor of the prognosis in patients with preserved LVEF. It would be useful to check the changes in GLS in those with preserved LVEF after discharge.


2020 ◽  
Vol 9 (6) ◽  
pp. 1897 ◽  
Author(s):  
Francesco Giallauria ◽  
Giuseppe Vitale ◽  
Mario Pacileo ◽  
Anna Di Lorenzo ◽  
Alessandro Oliviero ◽  
...  

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.


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.


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