511 Cardio-vascular remodelling during sacubitril/valsartan therapy in patients with heart failure and reduced ejection fraction

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 < 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.

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 22 (Supplement_1) ◽  
Author(s):  
S Monosilio ◽  
D Filomena ◽  
S Cimino ◽  
M Neccia ◽  
F Luongo ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Sacubitril/valsartan is a well-established therapeutic option for patients with heart failure with reduced ejection fraction (HFrEF). While it was clearly demonstrated to improve patients’ clinical conditions, its potential role in inducing left ventricle (LV) reverse remodeling is still under investigation.  Purpose to evaluate clinical and echocardiographic effect of sacubitril/valsartan on a cohort of patients with HFrEF after six months of therapy. Methods 36 patients with HFrEF eligible to start a therapy with sacubitril/valsartan were enrolled. A standard and advanced echocardiographic evaluation was performed before starting the therapy and after six months of follow up (FU). Off-line analysis of left ventricle global longitudinal strain (GLS), longitudinal strain of the free wall of the right ventricle (RVFWSL) and left atrial strain (LAS) was conducted. Clinical and biochemical parameters were evaluated as well. Results At six months of FU NYHA class improved in the vast majority of patients (NYHA class III at baseline vs FU: 56% vs 5%, p 0.001). We observed a significant reduction in LV end-diastolic (99.62 ± 33.24 vs 91.54 ± 33.36, p 0.043) and end-systolic (69.99 ± 26.01 vs 58.68 ± 25.7, p 0.001) volumes and an improvement of LV ejection fraction (30.4 ± 5.02 vs 37.3 ± 6.4, p < 0.001). After six months of therapy, GLS significantly improved (-9.71 ± 2.87 vs -13.04 ± 3.14, p < 0.001). No differences in left and right atrial volumes (respectively 56.6 ± 29 vs 54 ± 30, p 0.349; 54.7 ± 23.7 vs 48.3 ± 19, p 0.157), RVFWSL (-16,5 ± 5,4 vs -16,8 ± 1,5) and LAS (14 ± 6 vs 19 ± 8, p 0.197) were found at FU.  Conclusion Left ventricular function evaluated with standard and advanced echocardiographic parameters improved after six months of therapy with sacubitril/valsartan in HFrEF patients. Reduction in LV volumes was found as well. Echo Analysis Baseline Echo Analysis (n= 36) 6 Months FU Echo Analysis (n= 36) p LVEDVi, mL/m2 99, 62 ± 33,24 91,54 ± 33,36 0,043 LVESVi, mL/m2 69,99 ± 26,01 58,68 ± 25,7 0,001 LVEF, % 30,4 ± 5, 02 37,3 ± 6,4 < 0,001 E/E’ average 12,16 ± 3,74 9,71 ± 1,33 0,023 LS Endo Average ,% -9,71 ± 2,87 -13,04 ± 3,14 < 0,001 LVEF left ventricular ejection fraction, LVEDVi: left ventricular end diastolic volume indexed, LVESVi: left ventricular end systolic volume indexed; LS: longitudinal strain


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 <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<0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p<0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p<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


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  

Abstract Background Treatment by sacubitril/valsartan decreases mortality, improves KCCQ score and ejection fraction in patients with heart failure with reduced ejection fraction (HF REF), but there is currently no data to predict response to treatment. Purpose The purpose of our work was to assess whether unbiased clustering analysis, using dense phenotypic data, could identify phenotypically distinct HF-REF subtypes with good or no response after 6 months of sacubitril/valsartan administration. Methods A total of 78 patients in NYHA functional class 2–3 and treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected demographic, clinical, biological and imaging continuous variables. Phenotypic domains were imputed with 5 eigenvectors for missing value, then filtered if the Pearson correlation coefficient was >0.6 and standardized to mean±SD of 0±1. Thereafter, we used agglomerative hierarchical clustering for grouping phenotypic variables and patients, then generate a heat map (figure 1). Subsequently, participants were categorized using Penalized Model-Based Clustering. P<0,05 was considered significant. Results Mean age was 60.4±13.4 yo and 79.0% patients were males. Mean ejection fraction was 29.3±7.0%. Overall, 16 phenotypic domains were isolated (figure 1) and 3 phenogroups were identified (Table 1). Phenogroup 1 was remarkable by isolated left ventricular involvement (LVTDD 64.3±5.9mm vs 73.9±8.7 in group 2 and 63.8±5.7 in group3, p<0.001) with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH (TRMV: 2.93±0.47m/s in group 2 and 3.15±0.61m/s in groupe 3 vs 2.16±0.32m/s in group 1), related to severe DD (phenogroup 2) or MR (phenogroup 3). In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodeled, compared with phenogroup 1. Despite more severe remodeling and more compromised hemodynamic in phenogroups 2 and 3, the echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions (response of treatment, defined by improvement of FE +15% and/or decreased of indexed left ventricule diastolic volume −15% = group 2: 22 (76%); group 3: 18 (60%); group 1: 9 (50%); p=0.17; OR group 2 vs 1: OR=3.14; IC95% [0.9–11.03]; p=0.074; OR group 3 vs 1: OR=1.5; IC95% [0.46–4.87]; p=0.5)). The clinical response was even better in phenogroups 2 and 3 (Group 2: 19 (66%); group 3: 21 (78%) vs group 1: 9 (50%); p=0.05). Heat map Conclusion HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodeling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyue Mee Kim ◽  
In-Chang Hwang ◽  
Wonsuk Choi ◽  
Yeonyee E. Yoon ◽  
Goo-Yeong Cho

AbstractAngiotensin receptor-neprilysin inhibitor (ARNI) and sodium–glucose co-transporter-2 inhibitor (SGLT2i) have shown benefits in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Of the 206 matched patients, 92 (44.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 27.6 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and E/e′ were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.


2021 ◽  
Vol 26 (12) ◽  
pp. 4800
Author(s):  
M. V. Zhuravleva ◽  
S. N. Tereshchenko ◽  
I. V. Zhirov ◽  
S. V. Villevalde ◽  
T. V. Marin ◽  
...  

Aim. To assess the effect of therapy with sodium glucose co-transporter type 2 inhibitor dapagliflozin in patients with heart failure with reduced ejection fraction (CHrEF) on the state cardiovascular mortality target indicators.Material and methods. All adult Russian patients with NYHA class II-IV HFrEF (left ventricular ejection fraction ≤40%) were considered as the target population. The characteristics of patients in the study corresponded to those in the Russian Hospital HF Registry (RUS-HFR). The study suggests that the use of dapagliflozin in addition to standard therapy will be expanded by 10% of the patient population annually in 2022-24. Cardiovascular mortality modeling was performed based on the extrapolation of DAPA-HF study result. The number of deaths that can be prevented was calculated when using dapagliflozin in addition to standard therapy. Further, the contribution of prevented deaths with dapagliflozin therapy to the achievement of federal and regional cardiovascular mortality target indicators (1, 2 and 3 years) was calculated.Results. The use of dapagliflozin in addition to standard therapy for patients with NYHA class II-IV CHrEF with the expansion of dapagliflozin therapy by 10% of the patient population annually will additionally prevent 1729 cardiovascular death in the first year. This will ensure the implementation of cardiovascular mortality target indicators in Russia in 2022 by 11,8%. In the second year, 3769 cardiovascular deaths will be prevented, which will ensure the implementation of target indicators in 2023 by 17,2%. In the third year, 5465 cardiovascular deaths prevented, which will ensure the implementation of implementation of target indicators in 2024 by 18,7%.Conclusion. The use of dapagliflozin in addition to standard therapy for patients with NYHA class II-IV CHrEF will ensure the implementation of implementation of target indicators in 2024 by 18,7%.


Sign in / Sign up

Export Citation Format

Share Document