The Effect of Angiotensin Receptor Inhibitors and Neprilysin on Aortic Stiffness in Patients with Heart Failure and Reduced Ejection Fraction

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 ◽  
Author(s):  
Xingxue Pang ◽  
Ruoyi Liu ◽  
Li Xu ◽  
Xin Tao ◽  
Xuezeng Hao ◽  
...  

Abstract Objective To assess the value of left atrium volume index(LAVI)for diagnosing heart failure with preserved ejection fraction (HFpEF) based on the invasive determination of left ventricular end-diastolic pressure (LVEDP).Methods A total of 710 cases of patients with dyspnea (LVEF≥50%) were enrolled in this retrospective study. Left ventricular end-diastolic pressure (LVEDP) was measured through selective coronary angiography. According to the value of LVEDP, cases were divided into the HFpEF group ( LVEDP≥15mmHg) and the control group (LVEDP<15mmHg). LAVI was calculated based on cardiac compartment diameter, as measured by echocardiography, and body surface area (BSA). Differences of LAVI between the HFpEF group and the control group, and between subgroups in the HFpEF group were analyzed.Results The difference in LAVI between the control group and the HFpEF group was statistically significant (41.35±2.28vs.46.78±2.63ml/m2, p=0.008). LVEDP was positively correlated with LAVI (Pearson: r=0.787, P<0.001). When LAVI took the best cutoff value of 43.7 mm/m2, the sensitivity and specificity of diagnosis of HFpEF were 92.0% and 88.9%. When the boundary value of LAVI was from 41.7 to 45.7 mm/m2, the sensitivity of the diagnosis of ejection fraction retention heart failure was from 97.4% to 64.4% and the specificity was from 51.2.0% to 92.2%.Conclusion In patients with dyspnea after exclusion of heart failure with reduced ejection fraction (HFrEF), LAVI is positively correlated with LVEDP. LAVI can be used to diagnose HFpEF when HFrEF is excluded.


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 13 (7) ◽  
Author(s):  
Adam D. DeVore ◽  
Anne S. Hellkamp ◽  
Laine Thomas ◽  
Nancy M. Albert ◽  
Javed Butler ◽  
...  

Background: Among patients with heart failure (HF) with reduced ejection fraction (EF), improvements in left ventricular EF (LVEF) are associated with better outcomes and remain an important treatment goal. Patient factors associated with LVEF improvement in routine clinical practice have not been clearly defined. Methods: CHAMP-HF (Change the Management of Patients with Heart Failure) is a prospective registry of outpatients with HF with reduced EF. Assessments of LVEF are recorded when performed for routine care. We analyzed patients with both baseline and ≥1 follow-up LVEF assessments to describe factors associated with LVEF improvement. Results: In CHAMP-HF, 2623 patients had a baseline and follow-up LVEF assessment. The median age was 67 (interquartile range, 58–75) years, 40% had an ischemic cardiomyopathy, and median HF duration was 2.8 years (0.7–6.8). Median LVEF was 30% (23–35), and median change on follow-up was 4% (−2 to −13); 19% of patients had a decrease in LVEF, 31% had no change, 49% had a ≥5% increase, and 34% had a ≥10% increase. In a multivariable model, the following factors were associated with ≥5% LVEF increase: shorter HF duration (odds ratio [OR], 1.21 [95% CI, 1.17–1.25]), no implantable cardioverter defibrillator (OR, 1.46 [95% CI, 1.34–1.55]), lower LVEF (OR, 1.15 [95% CI, 1.10–1.19]), nonischemic cardiomyopathy (OR, 1.24 [95% CI, 1.09–1.36]), and no coronary disease (OR, 1.20 [95% CI, 1.03–1.35]). Conclusions: In a large cohort of outpatients with chronic HF with reduced EF, improvements in LVEF were common. Common baseline cardiac characteristics identified a population that was more likely to respond over time. These data may inform clinical decision making and should be the basis for future research on myocardial recovery.


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&gt;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.


2020 ◽  
Author(s):  
Sorina Baldea Mihaila ◽  
Andreea E Velcea ◽  
Roxana C Rimbas ◽  
Anca Andronic ◽  
Lavinia Matei ◽  
...  

Abstract Background: Left ventricular volumes (LVVs) and ejection fraction (LVEF) are key elements for the evaluation and follow-up of patients with heart failure with reduced ejection fraction (HFrEF). Therefore, a feasible and reproducible imaging method to be used by both experienced and in-training echocardiographers is mandatory. Aims: To establish if, in a large echo lab, echocardiographers in-training provide feasible and more reproducible results for the evaluation of patients with HFrEF, when using three-dimensional (3DE) vs. two-dimensional echocardiography (2DE). Methods: 60 patients with HFrEF (46 males, age 58±17) underwent standard transthoracic 2D acquisitions and 3D multi-beat full-volumes of the LV. One expert-user in echocardiography (Expert), and 3 echocardiographers with different levels of training in 2DE (Beginner, Medium, and Advanced) measured the 2D LVVs and LVEFs on the same consecutive images of patients with HFrEF. Afterward, the Expert performed a one-month training in 3DE analysis of the users, and both the Expert and trainees measured the 3D LVVs and LVEF of the same patients. Measurements provided by the Expert and all trainees in echo where compared.Results: 6 patients were excluded from the study due to a poor image quality. Mean end-diastolic LVV of the remaining 54 patients was 214±75 ml with 2DE, and 233±77 ml with 3DE. Mean LVEF was 35±10% with 2DE, and 33±10% with 3DE.When compared with the Expert user, the trainees showed acceptable reproducibility of the 2DE measurements, according to their level of expertise in 2DE (ICCs ranging from 0.75 to 0.94). However, after the short training in 3DE, they provided feasible and more reproducible measurements of the 3D LVVs and LVEF than with 2DE (ICCs ranging from 0.89 to 0.97).Conclusions: 3DE is a feasible, fast-learning, and more reproducible method for the assessment of LVVs and LVEF than 2DE, regardless of the basic level of expertise in 2DE of the trainees in echocardiography. In echo labs with a wide range of experience of the staff, 3DE might be a more accurate method for the follow-up of patients with HFrEF.


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&gt;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.


2020 ◽  
Vol 9 (10) ◽  
pp. 3159
Author(s):  
Daniele Masarone ◽  
Vittoria Errigo ◽  
Enrico Melillo ◽  
Fabio Valente ◽  
Rita Gravino ◽  
...  

Background: right ventricle-pulmonary artery (RV-PA) coupling assessed by measuring the tricuspid anular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio has been recently proposed as an early marker of right ventricular dysfunction in patients with heart failure with a reduced ejection fraction (HFrEF). Methods: As the effects of sacubitril/valsartan therapy on RV-PA coupling remain unknown, this study aimed to analyse the effect of this drug on TAPSE/PASP in patients with HFrEF. We retrospectively analysed all outpatients with HFrEF referred to our unit between October 2016 and July 2018. Results: At the 1-year follow-up, sacubitril/valsartan therapy was associated with a significant improvement in TAPSE (18.26 ± 3.7 vs. 19.6 ± 4.2 mm, p < 0.01), PASP (38.3 ± 15.7 vs. 33.7 ± 13.6, p < 0.05), and RV-PA coupling (0.57 ± 0.25 vs. 0.68 ± 0.30 p < 0.01). These improvements persisted at the 2-year follow-up. In the multivariable analysis, the improvement in the RV-PA coupling was independent of the left ventricular remodelling. Conclusions: in patients with HFrEF, sacubitril/valsartan improved the RV-PA coupling; however, further trials are necessary to evaluate the role of sacubitril/valsartan in the treatment of right ventricle (RV) dysfunction either associated or not associated with left ventricular dysfunction.


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 &gt; 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 &lt;35%), 204 (60%) no response (no LVRR and LVEF &lt;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 &lt; 0.01). LA strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P &lt; 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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.J Vazquez Andres ◽  
A Hernandez Vicente ◽  
M Diez Diez ◽  
M Gomez Molina ◽  
A Quintas ◽  
...  

Abstract Introduction Somatic mutations in hematopoietic cells are associated with age and have been associated with higher mortality in apparently healthy adults, especially due to atherosclerotic disease. In animal models, somatic mutations are associated with atherosclerosis progression and myocardial dysfunction, especially when gene TET2 is affected. Preliminary clinical data, referred to ischemic heart failure (HF), have associate the presence of these acquired mutations with impaired prognosis. Purpose To study the prevalence of somatic mutations in patients with heart failure with reduced ejection fraction (HFrEF) and their impact on long-term prognosis. Methods We studied a cohort of elderly patients (more than 60 years old) hospitalized with HFrEF (LVEF&lt;45%). The presence of somatic mutations was assessed using next generation sequencing (Illumina HiSeq 2500), with a mutated allelic fraction of at least 2% and a panel of 55 genes related with clonal hematopoiesis. Patients were followed-up for a median of three years. The study endpoint was a composite of death or readmission for worsening HF. Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression models were performed adjusting for age, sex and LVEF. Results A total of 62 patients (46 males (74.2%), age 74±7.5 years) with HFrEF (LVEF 29.7±7.8%) were enrolled in the study. The ischemic etiology was present in 54% of patients. Somatic mutations in Dnmt3a or Tet2 were present in 11 patients (17.7%). No differences existed in baseline characteristics except for a higher prevalence of atrial fibrillation in patients with somatic mutations (70% vs. 40%, p=0.007). During the follow-up period, 40 patients (64.5%) died and 38 (61.3%) had HF re-admission. The KM survival analysis for the combined event is shown in Figure 1. Compared with patients without somatic mutations and after adjusting for covariates, there was an increased risk of adverse outcomes when the somatic mutations were present (HR 3.6, 95% CI [1.6, 7.8], p=0.0014). This results remains considering death as a competing risk (Gray's test p=0.0097) and adjusting for covariates (HR = 2.21 95% CI [0.98, 5], p=0.0556). Conclusions Somatic mutation are present in patients with HFrEF and determine a higher risk of adverse events in the follow-up. Further studies are needed to assess the clinical implications of these findings. Figure 1 Funding Acknowledgement Type of funding source: None


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