scholarly journals Usefulness of myocardial work assessment for the understanding of mechanisms underlying sacubitril/valsartan efficacy in patients with heart failure and reduced ejection fraction

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
F Luciano ◽  
C Santoro ◽  
V Capone ◽  
O Casciano ◽  
ME Canonico ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Blood Pressure Reduction ◽  
Left Ventricular ◽  
Reduced Ejection Fraction ◽  
Risk Of Death ◽  
Patients With Heart Failure ◽  
Constructive Work ◽  
Global Work ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: None. Background  Sacubitril/valsartan has shown the ability in reducing the risk of death and of hospitalization in patients with HF (heart failure) and is recommended in patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite conventional therapies. Strain imaging derived myocardial work (MW) is an emerging tool for the evaluation of left ventricular (LV) mechanics by incorporating both systolic deformation and afterload burden in the analysis. Aim of the study To evaluate in a prospective fashion the impact of sacubitril/valsartan therapy in HF patients on MW derived parameters in relation with standard echocardiographic indices. Methods We recruited thirteen HF patients with indication to sacubitril/valsartan therapy according to current guidelines. Sacubitril/valsartan therapy titrated at the maximum tolerated dose. A comprehensive echo-Doppler exam, including speckle tracking derived assessment of global longitudinal strain (GLS) (in absolute value), was performed before and after a three months therapy with sacubitril/valsartan. Parameters of MW such as global work index (GWI), global constructive work (GCW) global wasted work (GWW) and global work efficiency (GWE) were calculated according to standardized procedures. Patients with more than mild aortic and mitral stenosis and/or regurgitation were excluded. Other exclusion criteria included permanent and/or persistent atrial fibrillation and inadequate echo images. Results The 13 patients (M/F = 11/2, age: 57 ± 8.2 years, aetiology: idiopathic in 3 patients, ischaemic in 7 patients and chemotherapy related cardiotoxicity in 3 patients, NYHA Class: II in 7 and III in 6 patients). All patients tolerated sacubitril/valsartan therapy. After the three months therapy an improvement of  LVEF (from 32.3 ± 2% to 36.2± 6%, p = 0.015), GLS (from 9.8 ± 1% to 11.6 ± 2%, p = 0.019), GWI (from 845.0 ± 175.0 mmHg% to 1091.6 ± 336.8 mmHg%, p = 0.003), GCW (from  993.4± 211.6 mmHg% to 1262.7 ± 404 mmHg%, p = 0.002) and GWE (from 77 ± 11% to 81 ± 10%, p = 0.002) was observed, without significant changes in GWW (from 190 ± 121 mmHg% to 211 ± 145 mmHg%, p = 0.307). We also found a positive correlation between the magnitude of LVEF improvement and the baseline values of GCW (r = 0.66, p = 0.014). This relation remained significant even after adjusting for the extent of systolic blood pressure reduction (r = 0.54, p = 0.033). Conclusion Three months sacubitril/valsartan therapy significantly improves standard and advanced indices of LV systolic function. This improvement is due to the increase of constructive work more than to the reduction of wasted work and the increase of LVEF can be predicted by the global constructive work levels at baseline. MW assessment may help to understand the mechanisms underlying the sacubitril/valsartan therapy efficacy in HF patients. Abstract Figure.

scholarly journals 164 Effect of cardiac contractility modulation therapy on myocardial work in patients with heart failure with reduced ejection fraction

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Daniele Masarone ◽  
Stefano De Vivo ◽  
Vittoria Errigo ◽  
Antonio D’ Onofrio ◽  
Giuliano D’Alterio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Contractility Modulation ◽  
Reduced Ejection Fraction ◽  
Constructive Work ◽  
Global Work ◽  
The Impact

Abstract Aims Cardiac contractility modulation therapy (CCMT) has been shown to reduce hospitalizations and to improve quality of life in heart failure patients with reduced ejection fraction (HFrEF) who remain symptomatic despite disease-modifying therapies. Strain imaging derived myocardial work (MW) is an emerging tool for evaluating left ventricular mechanics by incorporating systolic deformation and afterload burden in the analysis. To evaluate prospectively the impact of CCMT in HFrEF patients on MW derived parameters in relation to standard echocardiographic indices. Methods and results We recruited 12 HFrEF patients with indications to CCMT according to current clinical practice. A comprehensive echo-Doppler evaluation, including speckle tracking derived assessment of global longitudinal strain (GLS), was performed before and after three months from the CCM device implantation. Parameters of MW such as global work index (GWI), global constructive work (GCW) global wasted work (GWW), and global work efficiency (GWE) were calculated according to standardized procedures. Median values (interquartile range) were compared for all those parameters from baseline and 3-month follow-up with Wilcoxon Rank Sum test for continuous variables. At three months from CCM implant an improvement of LVEF [from 32% (27–34) to 36% (29–39), P < 0.05], GLS [from 7.4% (6.2–11.2) to 9.9% (7.5–9.4), P < 0.05], GWI [from 461 mmHg (372–613) to 589 mmHg (413–696), P < 0.05], GCW [from 800 mmHg (620–930) to 970 mmHg (644–1009), P = 0.236], and GWE [from 73% (65–78) to 85% (78–87), P < 0.05] was observed, with a consistent reduction of GWW [from 161 mmHg (148–227) to 125 mmHg (101–188), P < 0.05]. We also found a positive correlation between the magnitude of LVEF improvement and the baseline values of GCW (r = 0.727, P = 0.011). Conclusions At 3 months, CCMT significantly improves standard and advanced left ventricular systolic function indices. This improvement is due to the increase of constructive work and a reduction of wasted work. In addition, the increase of left ventricular ejection fraction can be predicted by the global constructive work levels at baseline.

scholarly journals P791 Left atrial stiffness as a predictor of cardiac events in patients with heart failure and reduced ejection fraction: the impact of diabetes

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
I Bytyci ◽  
N R Pugliese ◽  
A Bajraktari ◽  
M Mazzola ◽  
G Bajraktari ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Ventricular Remodeling ◽  
Systolic Function ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
The Impact

Abstract Background and Aim Diabetes mellitus (DM) affects left ventricular remodeling in patients with heart failure (HF), but its effect on left atrial (LA) remodeling and their combined effect on survival and other clinical events (CE) remain to be elucidated. We evaluated in this study the relationship between DM and left atrial (LA) remodeling in a group of HF patients with reduced ejection fraction (HFrEF), Methods This studied 136 consecutive HFrEF patients (65 ± 11 years), 36 diabetics, using conventional and tissue Doppler echocardiography. LA dimension and function were measured and cavity stiffness was calculated with the formula: LA stiffness = E/e’ratio/LA strain. Results The age, gender, LV end-systolic dimension, LV end-diastolic dimension, LV EF and BNP level did not differ between diabetic and non-diabetic patients. Diabetic patients with HFrEF had higher NYHA functional class (p = 0.02), reduced right ventricle (RV) systolic function (p = 0.01) and increased LA stiffness (p = 0.02) . At follow up of 55 ± 37 months, survival free from CE was 69% in non-diabetics compared with 44.4% in diabetics (X2 12.7; p< 0.0001). The CE free survival was lower in patients with increased LA stiffnes, irrespective of the presence of DM: 1) Patients with HFrEF without DM and normal LA stiffness (85%); 2) Patients with HFrEF without DM and with increased LA stiffness (50%); 3) Patients with HFrEF with DM and with normal LA stiffness (71%) and patients with HFrEF with DM and with increased LA stiffness (27%) (X2 29.6; p< 0.0001, Figure 1). Conclusion Compromised LA stiffness as surrogate of LA remodeling is associated with poor outcome in patients with heart failure and reduced EF. The presence of diabetes in patients with HFrEF and increased LA stiffness has incremental prognostic value. Abstract P791 Figure.

Prognostic role of myocardial work in patients with heart failure and reduced ejection fraction treated by sacubitril/valsartan

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Galli ◽  
Y Bouali ◽  
C Laurin ◽  
A Gallard ◽  
A Hubert ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Rank Test ◽  
Reduced Ejection Fraction ◽  
Non Invasive ◽  
Patients With Heart Failure ◽  
Increase Risk ◽  
Echocardiographic Examination ◽  
Constructive Work

Abstract Background The non-invasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (MACEs). Purposes of this study were to evaluate 1) the short and medium term effect of Sacubitril/Valsartan treatment on MW parameters; 2) the prognostic value of MW in this specific group of patients. Methods 79 patients with HFrEF (mean age: 66±12 years; LV ejection fraction: 28±9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan. Results Sacubitril/Valsartan significantly increased global myocardial constructive work (CW) (1023±449 vs 1424±484 mmHg%, p<0.0001) and myocardial work efficiency (WE) [87 (78–90) vs 90 (86–95), p<0.0001]. During FU (2.6±0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LVEF and WE, CW was the only predictor of MACEs (Table 1). A CW<910 mmHg (AUC=0.81, p<0.0001, Figure 1A) identified patients at particularly increase risk of MACEs [HR 11.09 (1.45–98.94), p=0.002, log-rank test p<0.0001] (Figure 1 B). Conclusions In patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan therapy allows the prediction of MACEs. Funding Acknowledgement Type of funding source: None

Prognostic value of global longitudinal layer specific strain for patients with heart failure with reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Johnsen ◽  
M Sengeloev ◽  
P Joergensen ◽  
N Bruun ◽  
D Modin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Prognostic Value ◽  
Left Ventricular ◽  
Volume Index ◽  
Funding Source ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Echocardiographic Parameters

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

Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Total Mortality ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

Comparison of the prognosis and outcome of heart failure with reduced ejection fraction patients treated with sacubitril/valsartan according to age

2021 ◽  
Author(s):  
Mohammad Abumayyaleh ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Christina Pilsinger ◽  
Katherine Sattler ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Older Patients ◽  
Left Ventricular ◽  
Adult Patients ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
The Impact

The treatment with sacubitril/valsartan in patients suffering from chronic heart failure with reduced ejection fraction increases left ventricular ejection fraction and decreases the risk of sudden cardiac death. We conducted a retrospective analysis regarding the impact of age differences on the treatment outcome of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction. Patients were defined as adults if ≤65 years (n = 51) and older if >65 years of age (n = 76). The incidence of ventricular arrhythmias at 1-year follow-up was comparable in both groups (30.8 vs 26.5%; p = 0.71). The mortality rate in adult patients is significantly lower as compared with older patients (2 vs 14.5%; log-rank = 0.04). Older patients may suffer remarkably more side effects than adult patients (21.1 vs 11.8%; p = 0.03).

1409Use of phenomapping to determine response of treatment by sacubitril/valsartan in patients with heart failure with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Heat Map ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

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.

scholarly journals Effect of Empagliflozin on the Clinical Stability of Patients with Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial

Circulation ◽  
2020 ◽  
Author(s):  
Milton Packer ◽  
Stefan D. Anker ◽  
Javed Butler ◽  
Gerasimos S. Filippatos ◽  
João Pedro Ferreira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Functional Class ◽  
Hazard Ratio ◽  
Double Blind ◽  
Reduced Ejection Fraction ◽  
Risk Of Death ◽  
Nyha Functional Class ◽  
Patients With Heart Failure

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure. Methods: We randomly assigned 3730 patients with class II-IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite endpoints. Results: Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 vs 519 patients; empagliflozin vs placebo, respectively; hazard ratio 0.76, 95% CI: 0.67-0.87), P <0.0001. This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio 0.67, 95% CI 0.50-0.90, P=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (hazard ratio 0.64, 95% CI: 0.47-0.87, P=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 vs 414), hazard ratio 0.67, 95% CI: 0.56-0.78, P<0.0001. Additionally, patients assigned to empagliflozin were 20-40% more likely to experience an improvement in NYHA functional class and were 20-40% less likely to experience worsening of NYHA functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (hazard ratio 0.70, 95% CI: 0.63-0.78), P<0.0001. Conclusions: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03057977

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