Sacubitril/ Valsartan in Advanced Heart Failure: Is it Just a Matter of Contractility or are there Effects on the Pulmonary Circulation? A Real Life Monocentric Experience

Background: Sacubitril/valsartan (S/V), an angiotensin receptor neprilysin inhibitor (ARNI), is the first drug to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction. S/v had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, compared with subjects receiving enalapril. However, the mechanisms are not clear. The aim of this prospective, non-randomized study was to assess the clinical and instrumental effects of this agent in patients with HFrEF and pulmonary hypertension. Methods: To investigate the effects of S/V in HFrEF, we selected 40 consecutive patients (31 males, 9 females, mean age 64±19 years) in the NYHA class II-III, because they had left ventricular ejection fraction ≤35% at echocardiography. Etiology: 22 CHD, 3 Myocarditis, 15 IDCM. Results: 2 patients took the maximum dose of 97/103 mg, 2 stopped the therapy due to a creatinine increase, all the others took the dose of 49/52 mg. During a mean ± SD follow-up of 24±6 months, no patients died. PASP decreased from 42.71 to 36 mm/Hg (p <0.0001); 6MWT improved from 402 m to 453 m (p <0.0001). Mean LVEF increased from 28.9% to 31.5% p <0.005); NYHA mean class improved from 1.95 to 1.70. An AICD was implanted in 20 patients. Conclusion: These preliminary data suggest that in patients with severe heart failure, S/V is able to improve 6MWT and PASP, even in the absence of a significant improvement of ventricular contractility. S/v may reduce the fluid retention and pulmonary vasoconstriction that contribute to heart failure symptoms.

Download Full-text

Effect of Sacubitril/Valsartan Combined with Dapagliflozin on Long-Term Cardiac Mortality in Heart Failure with Reduced Ejection Fraction

Angiology ◽

10.1177/00033197211047329 ◽

2021 ◽

pp. 000331972110473

Author(s):

Umut Karabulut ◽

Kudret Keskin ◽

Dilay Karabulut ◽

Ece Yiğit ◽

Zerrin Yiğit

Keyword(s):

Heart Failure ◽

Combination Therapy ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cardiac Mortality ◽

Ventricular Ejection Fraction ◽

Reduced Ejection Fraction ◽

Neprilysin Inhibitor

The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.

Download Full-text

P971 The echocardiographic phenotype in patients with cardiac amyloidosis and heart failure with preserved ejection fraction

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.603 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

M D M Perez Gil ◽

V Mora Llabata ◽

A Saad ◽

A Sorribes Alonso ◽

V Faga ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cardiac Amyloidosis ◽

Nyha Class ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Ventricular Ejection Fraction ◽

Apical Rotation ◽

Dynamic Torsion

Abstract BACKGROUND New echocardiographic phenotypes of heart failure (HF) are focused on myocardial systolic involvement of the left ventricle (LV), either endocardial and/or transmural. PURPOSE. To study the pattern of myocardial involvement in patients (p) with HF with preserved left ventricular ejection fraction (pLVEF) and cardiac amyloidosis (CA). METHODS. Comparative study of 16 p with CA and HF with pLVEF, considering as cut point LVEF > 50%, in NYHA class ≥ II / IV, and a control group of 16 healthy people. Longitudinal Strain (LS) and Circumferential Strain (CS) were calculated using 2D speckle-tracking echocardiography, along with Mitral Annulus Plane Systolic Excursion (MAPSE) and Base-Apex distance (B-A). Also, the following indexes were calculated: Twist (apical rotation + basal rotation, º); Classic Torsion (TorC): (twist/B-A, º/cm); Torsion Index (Tor.I): (twist/MAPSE, º/cm) and Deformation Index (Def.I): (twist/LS, º). We suggest the introduction of these dynamic torsion indexes as Tor.I and Def.I that include twist per unit of longitudinal systolic shortening of the LV instead of using TorC which is the normalisation of twist to the end-diastolic longitudinal diameter of the LV. RESULTS There were no differences of age between the groups (68.2 ± 11.5 vs 63.7 ± 2.8 years, p = 0.14). Global values of LS and CS were lower in p with CA indicating endocardial and transmural deterioration during systole, while TorC and Twist of the LV remained conserved in p with CA. However, there is an increase of dynamic torsion parameters such as Tor.I and Def.I that show an increased Twist per unit of longitudinal shortening of the LV in the CA group (Table). CONCLUSIONS In p with CA and HF with pLVEF, the impairment of LS and CS indicates endocardial and transmural systolic dysfunction. In these conditions, LVEF would be preserved at the expense of a greater dynamic torsion of the LV. Table LS (%) CS (%) Twist (º) TorC (º/cm) Tor.I (º/cm) Def.I (º/%) CA pLVEF (n = 16) -11.7 ± 4.2 17.2 ± 4.8 19.8 ± 8.3 2.5 ± 1.1 27.7 ± 13.5 -1.8 ± 0.9 Control Group (n = 15) -20.6 ± 2.5 22.7 ± 4.9 21.7 ± 6.1 2.7 ± 0.8 16.4 ± 4.7 -1.0 ± 0.3 p < 0.001 < 0.01 0.46 0.46 < 0.01 < 0.01 Dynamic Torsion Indexes and Classic Torion Parameters in pLVEF CA patients vs Control group.

Download Full-text

The central arterial stiffness parameters in decompensated versus compensated states of heart failure: a paired comparative cohort study

The Egyptian Heart Journal ◽

10.1186/s43044-021-00236-8 ◽

2022 ◽

Vol 74 (1) ◽

Author(s):

Ahmed El Fol ◽

Waleed Ammar ◽

Yasser Sharaf ◽

Ghada Youssef

Keyword(s):

Heart Failure ◽

Arterial Stiffness ◽

Ejection Fraction ◽

Pulse Wave ◽

Nyha Class ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Class Iii ◽

Ventricular Ejection Fraction ◽

Reduced Ejection Fraction

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.

Download Full-text

P1236EFFECTS OF SACUBITRIL-VALSARTAN IN HEART FAILURE WITH PRESERVED EJECTION FRACTION IN PATIENTS UNDERGOING PERITONEAL DIALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1236 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Sha Fu ◽

Zhenjian Xu ◽

Baojuan Lin ◽

Junzhe Chen ◽

Qiuyan Huang ◽

...

Keyword(s):

Heart Failure ◽

Peritoneal Dialysis ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Matched Pair ◽

Preserved Ejection Fraction ◽

Ventricular Ejection Fraction ◽

Nyha Classification ◽

Neprilysin Inhibitor

Abstract Background and Aims Angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril–valsartan is a landmark drug in heart failure with reduced ejection fraction (HFrEF), however, it remains unclear in patients with heart failure with preserved ejection fraction (HFpEF), especially the data of ARNI treatment on peritoneal dialysis (PD) patients with HFpEF are lacking. The present study was designed to determine the efficacy and safety of sacubitril–valsartan in patients with HFpEF undergoing peritoneal dialysis. Method We assigned end stage renal disease (ESRD)patients, receiving peritoneal dialysis for 3 months, with New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≥ 50%, and elevated level of N-terminal pro–B-type natriuretic peptide (NT-proBNP) to receive sacubitril/valsartan treatment. Patients were regularly followed up after medication treatment. Wilcoxon matched-pair signed-rank (2 samples) tests were applied to investigate the alterations in Clinical and biochemical parameters as the efficacy before and after taking sacubitril–valsartan, and safety was also assessed. Results Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels (p=0.002) and heart rate (p=0.031) were markedly decreased after treatment with sacubitril/valsartan, signs and symptoms of heart failure (21/21 versus 15/21, p=0.021) and NYHA classification were notably improved after 3-12 months follow-up. Conclusion The present data suggested that sacubitril/valsartan treatment in the patients with HFpEF undergoing peritoneal dialysis was effective and safe, which is the first study about sacubitril/valsartan treatment for the PD patients with HFpEF, and it may bring the hope for these patients due to no other effective methods at present.

Download Full-text

P3547Real world experience of sacubitril/valsartan: insights on tolerability and outcome from a specialised heart failure clinic

European Heart Journal ◽

10.1093/eurheartj/ehz745.0410 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 1

Author(s):

K C Neoh ◽

D Rasoul ◽

F Hunt ◽

D W S Chong

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Nyha Class ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

National Database ◽

Mineralocorticoid Receptor Antagonist ◽

Ventricular Ejection Fraction ◽

Reduced Ejection Fraction ◽

Patient Reported

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.

Download Full-text

PREDICTORS OF WEIGHT LOSS IN PATIENTS WITH CHRONIC HEART FAILURE AND REDUSED LEFT VENTRICULAR EJECTION FRACTION

EUREKA Health Sciences ◽

10.21303/2504-5679.2019.00999 ◽

2019 ◽

Vol 5 ◽

pp. 3-11

Author(s):

Kateryna Voitsekhovska ◽

Leonid Voronkov

Keyword(s):

Heart Failure ◽

Weight Loss ◽

Chronic Heart Failure ◽

Left Ventricular Ejection Fraction ◽

Ejection Fraction ◽

Nyha Class ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Vasodilator Response

Chronic heart failure (CHF) is a heterogeneous syndrome with a poor prognosis. Aim of the work – to define predictors of body weight (BW) loss in patients with CHF and a reduced left ventricular ejection fraction (LVEF). Materials and methods. 120 patients with stable CHF and LVEF ≤35 %, II-IV NYHA class were examined. Patients were divided into two groups according to the value of BW loss for 6 months: the first group - loss of BW <6 %, the second - ≥ 6 %. Results. Out of the 120 patients who were studied, a BW loss of ≥ 6 % occurred in 59 (49.2 %) patients. According to the results of binary logistic regression, predictors of BW loss of ≥6 % in patients with CHF and LVEF ≤ 35 % were: age, coronary heart disease, anaemia, and the number of hospitalizations over the last year. People with poorer quality of life, bigger number of points on the Beck depression scale and DEFS, with lower levels of physical activity and worse endothelium-dependent vasodilator response; higher sizes of the right atrium, right ventricle, and pulmonary artery systolic pressure, E / E '. Higher levels of C-reactive protein (CRP), uric acid are associated with a risk of losing BW≥6 %. Conclusions. Weight loss ≥ 6 % is observed in 49.2 % of patients with CHF and LVEF≤35 %. According to multivariate analysis, independent predictors of BW loss of ≥6 % in patients with CHF and LVEF≤35 % are age, CRP level, III-IV NYHA class, lower cholesterol levels, as well as lower rates of flow-dependent vasodilator response and hip circumference.

Download Full-text

Resynchronization in Heart Failure: What to choose?

10.22541/au.162273123.35290271/v1 ◽

2021 ◽

Author(s):

Mohammad El Baba ◽

Moses Wananu ◽

Marwan Refaat ◽

Jayakumar Sahadevan

Keyword(s):

Heart Failure ◽

Biventricular Pacing ◽

Nyha Class ◽

Systolic Dysfunction ◽

Severe Heart Failure ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Left Ventricular Ejection ◽

Resynchronization Therapy ◽

Ventricular Ejection Fraction

Achieving Cardiac resynchronization therapy (CRT) with Biventricular pacing(BiVP) pacing for patients with moderate-to-severe heart failure (HF), left ventricular (LV) systolic dysfunction and ventricular dyssynchrony is well established and is currently the standard of care. Multiple studies have demonstrated significant improvement in quality of life, functional status, and exercise capacity in patients with New York Heart Association (NYHA) class III and IV heart failure who underwent resynchronization therapy1,2. In addition, resynchronization therapy is associated with survival benefit3. However, one third of patients do not respond to BIVP. New modalities for resynchronization have emerged namely His bundle pacing (HBP) and left ventricular septal pacing (LVSP). In this paper, we will review the benefits and limitations of BiVP and also the role of new pacing modalities such as HBP and LVSP in patients with HF with reduced left ventricular ejection fraction (LVEF) and electrical dysynchrony.

Download Full-text

The PARAGON-HF trial: the sacubitril/valsartan in heart failure with preserved ejection fraction

European Heart Journal Supplements ◽

10.1093/eurheartj/suaa140 ◽

2020 ◽

Vol 22 (Supplement_L) ◽

pp. L77-L81

Author(s):

Edoardo Gronda ◽

Emilio Vanoli ◽

Massimo Iacoviello

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Structural Heart Disease ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Preserved Ejection Fraction ◽

Target Dose ◽

Ventricular Ejection Fraction ◽

Therapeutic Concept ◽

Neprilysin Inhibitor

Abstract Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical condition characterized by large pathophysiology heterogeneity with lack of effective therapies as proven by the disappointing results generated by randomized controlled trials. The innovative therapeutic concept provided by sacubitril–valsartan, a molecule combining angiotensin receptor blocking agent and neprilysin inhibitor has suggested the hypothesis it would have led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and preserved ejection fraction. The PARAGON-HF (ClinicalTrials.gov number, NCT01920711) investigated HF subjects class II to IV HF, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The trial missed the primary outcome of cardiovascular death and HF hospitalization (HFH) in the overall study population. A subgroup analysis addressed significant decrease of HFH in subjects with left ventricular ejection fraction below the median 57% value in the study. The data were consistent with previous post hoc analysis performed in studies where candesartan and spironolactone were investigated in HFpEF. Those results open the door to investigate angiotensin aldosterone and peptidases inhibition efficacy in the unexplored HF middle range ejection fraction, currently lacking of valid evidence.

Download Full-text

Current evidence of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction

Future Cardiology ◽

10.2217/fca-2020-0002 ◽

2020 ◽

Vol 16 (4) ◽

pp. 227-236

Author(s):

Mohammad Abumayyaleh ◽

Ibrahim El-Battrawy ◽

Michael Behnes ◽

Martin Borggrefe ◽

Ibrahim Akin

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Current Evidence ◽

Ventricular Ejection Fraction ◽

Reduced Ejection Fraction ◽

Regulatory Affairs ◽

Neprilysin Inhibitor ◽

Angiotensin Receptor Neprilysin Inhibitor

Heart failure (HF) is one of the most common reasons for hospital admission in western countries. The measurement of the left ventricular ejection fraction is essential for the classification of HF and deciding on HF treatment. The treatment of HF has been improved in both diagnostic and therapeutic fields over the past two decades. The angiotensin receptor-neprilysin inhibitor decreased the cardiovascular mortality in patients with chronic HF with reduced ejection fraction. Sacubitril/valsartan (LCZ696) improves the imbalance between the renin-angiotensin-aldosterone and natriuretic peptide systems. We present the clinical efficacy, real-world experience, safety and tolerability, the relevance of etiology of cardiomyopathy, and gender differences and regulatory affairs of LCZ696 in the treatment of patients with HF with reduced ejection fraction.

Download Full-text

254 Impact of sacubitril/valsartan on implantable defibrillator eligibility in heart failure: a real-world experience

European Heart Journal Supplements ◽

10.1093/eurheartj/suab139.014 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Luca Monzo ◽

Ilaria Ferrari ◽

Carlo Gaudio ◽

Francesco Cicogna ◽

Claudia Tota ◽

...

Keyword(s):

Heart Failure ◽

Primary Prevention ◽

Ejection Fraction ◽

Nyha Class ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Reverse Remodelling ◽

The Impact

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.

Download Full-text