scholarly journals Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Domingo Pascual-Figal ◽  
Antoni Bayés-Genis ◽  
Paola Beltrán-Troncoso ◽  
Pedro Caravaca-Pérez ◽  
Alicia Conde-Martel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Clinical Syndrome ◽  
Tolerability Profile ◽  
Compensatory Mechanism ◽  
Reduced Ejection Fraction ◽  
Clinical Benefits ◽  
Reduction Of Mortality ◽  
Ventricular Filling ◽  
The Impact

Heart failure (HF) is a clinical syndrome characterized by the presence of dyspnea or limited exertion due to impaired cardiac ventricular filling and/or blood ejection. Because of its high prevalence, it is a major health and economic burden worldwide. Several mechanisms are involved in the pathophysiology of HF. First, the renin-angiotensin-aldosterone system (RAAS) is over-activated, causing vasoconstriction, hypertension, elevated aldosterone levels and sympathetic tone, and eventually cardiac remodeling. Second, an endogenous compensatory mechanism, the natriuretic peptide (NP) system is also activated, albeit insufficiently to counteract the RAAS effects. Since NPs are degraded by the enzyme neprilysin, it was hypothesized that its inhibition could be an important therapeutic target in HF. Sacubitril/valsartan is the first of the class of dual neprilysin and angiotensin receptor inhibitors (ARNI). In patients with HFrEF, treatment with sacubitril/valsartan has demonstrated to significantly reduce mortality and the rates of hospitalization and rehospitalization for HF when compared to enalapril. This communication reviews in detail the demonstrated benefits of sacubitril/valsartan in the treatment of patients with HFrEF, including reduction of mortality and disease progression as well as improvement in cardiac remodeling and quality of life. The hemodynamic and organic effects arising from its dual mechanism of action, including the impact of neprilysin inhibition at the renal level, especially relevant in patients with type 2 diabetes mellitus, are also reviewed. Finally, the evidence on the demonstrated safety and tolerability profile of sacubitril/valsartan in the different subpopulations studied has been compiled. The review of this evidence, together with the recommendations of the latest clinical guidelines, position sacubitril/valsartan as a fundamental pillar in the treatment of patients with HFrEF.

scholarly journals Progression of Valvular Calcification is Associated with 10-Year Change in Left Ventricular Structure and Incident Heart Failure: MESA

2020 ◽  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Aortic Valve Calcification ◽  
Reduced Ejection Fraction ◽  
Valvular Calcification ◽  
Ventricular Structure ◽  
Ventricular Filling ◽  
The Impact

Heart failure (HF) is a leading cause of morbidity.1 It results from impairment in ventricular filling or relaxation and can be broadly classified as heart failure with preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF).2 Strategies for preventing HF are paramount. Prevalent coronary artery calcium and extracoronary calcification are associated with future coronary heart disease3-7 and HF8 events. Less is known about the impact of progression of valvular calcification (VC) (mitral annular [MAC] and aortic valve calcification [AVC]) on HF risk.

Abstract 17470: Racial Disparities in Goal Directed Medical Therapy in Patients With Systolic Heart Failure- A Single Center Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ayesha Azmeen ◽  
Naga Vaishnavi Gadela ◽  
Vergara Cunegundo
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Racial Disparities ◽  
Beta Blockers ◽  
Systolic Heart Failure ◽  
The United States ◽  
Clinical Syndrome ◽  
Single Center ◽  
Geographic Variations ◽  
Reduced Ejection Fraction

Introduction: Heart failure(HF) is a clinical syndrome that is widely prevalent affecting approximately 6.5 million people in the United States. It accounts for the ever-rising health care costs in the US due to recurrent hospitalizations. Despite advancements in medical management, the mortality and the rate of hospitalizations continues to be high with geographic variations and racial disparities. Through this descriptive study, we sought to analyze the health disparities among Hispanic, African American (AA) and Caucasian population in a single-center. Methods: We identified a total of 178 patients with HF with reduced ejection fraction from our outpatient clinic by utilizing the ICD-10 codes. Patients with ejection fraction >50% have been excluded. A retrospective chart review of their ethnic background, medications, and number of heart failure exacerbations per year has been performed. Results: 178 patients (mean age 62 years, 35.56% of females) including Hispanics (n=102), AA(n=44), and Caucasians (n=32) were included in the study. Although all patients were started on Beta-blockers, only 76.4% and 37.2% of Hispanics were started on ACEi/ARBs and spironolactone respectively. Similarly, 72.7% and 45.4% of AA were started on ACEi/ARBs and spironolactone respectively. This is in contrast to Caucasians population, where a majority of patients were on started on GDMT; 90% and 75% were started on ACEi/ARBs and spironolactone respectively. This was also reflected by the number of admissions due to HF exacerbations which ranged from 2-4/year for Hispanics and AA populations and 0-1/year for Caucasians. Conclusions: GDMT for HF is known to reduce heart failure exacerbations, mortality and the ever rising cost of the healthcare system. We have observed that despite recommendations to initiate GDMT in all patients with HF with reduced ejection fraction, racial disparities exist. Physicians should be mindful of initiating GDMT in all patients.

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).

Abstract 354: The Role of the Liver Heart Axis During Cardiac Remodeling

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Soichiro Usui ◽  
Shin-ichiro Takashima ◽  
Kenji Sakata ◽  
Masa-aki Kawashiri ◽  
Masayuki Takamura
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Cardiac Remodeling ◽  
Pressure Overload ◽  
Normal Subjects ◽  
Serum Levels ◽  
Lung Weight ◽  
Reduced Ejection Fraction ◽  
Hepatic Expression

Background: Hepatokine selenoprotein P (SeP) contributes to insulin resistance and hyperglycemia in patients with type 2 diabetes. Although clinical studies suggest the insulin resistance is an independent risk factor of heart failure and inhibition of SeP protects the heart from ischemia reperfusion injury, the role of SeP in pathogenesis of chronic heart failure is not well understood. Objective: We examined the role of SeP in the regulation of cardiac remodeling in response to pressure overload. Methods and Results: We measured serum SeP levels in 22 patients for heart failure with reduced ejection fraction (HFrEF; LVEF<50%) and 22 normal subjects. Serum levels of SeP were significantly elevated in patients with HFrEF compared to in normal subjects (3.55 ± 0.43 vs 2.98 ± 0.43, p<0.01). To examine the role of SeP in cardiac remodeling, SeP knockout (KO) and wild-type (WT) mice were subjected to pressure overload (transverse aortic constriction (TAC)) for 2 weeks. The mortality rate following TAC was significantly decreased in SeP KO mice compared to WT mice (22.5 % in KO mice (n=40) vs 52.3 % in WT mice (n=39) p<0.01). LV weight/tibial length (TL) was significantly smaller in SeP KO mice than in WT mice (6.75 ± 0.24 vs 8.33 ± 0.32, p<0.01). Lung weight/TL was significantly smaller in SeP KO than in WT mice (10.46 ± 0.44 vs 16.38 ± 1.12, p<0.05). Interestingly, hepatic expression of SeP in WT was significantly increased by TAC. To determine whether hepatic overexpression of SeP affects TAC-induced cardiac hypertrophy, a hydrodynamic injection method was used to generate mice that overexpress SeP mRNA in the liver. Hepatic overexpression of SeP in SeP KO mice lead to a significant increase in LV weight/TL and Lung weight/TL after TAC compared to that in other SeP KO mice. Conclusions: These results suggest that serum levels of SeP were elevated in patients with heart failure with reduced ejection fraction and cardiac pressure overload induced hepatic expression of SeP in mice model. Gene deletion of SeP attenuated cardiac hypertrophy and dysfunction in response to pressure overload in mice. SeP possibly plays a pivotal role in promoting cardiac remodeling through the liver-heart axis.

Chronic heart failure diagnosis: HFpEF

ESC CardioMed ◽  
2018 ◽  
pp. 1762-1768
Author(s):  
Daniel N. Silverman ◽  
Sanjiv J. Shah
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiopulmonary Exercise Testing ◽  
Clinical History ◽  
Right Heart Catheterization ◽  
Clinical Syndrome ◽  
Exercise Intolerance ◽  
Heart Catheterization ◽  
Reduced Ejection Fraction ◽  
Treatment Measures

Heart failure (HF) with preserved ejection fraction (HFpEF) is a very common clinical syndrome that is often misdiagnosed or overlooked due to diagnostic challenges with the lack of a specific imaging test or biomarker to make a conclusive diagnosis. Unlike HF with reduced ejection fraction, neither a reduced ejection fraction nor a dilated left ventricle is available to easily make the diagnosis of HFpEF. Furthermore, while echocardiographic evidence of diastolic dysfunction is common in patients with HFpEF, it is not a universal phenomenon. Even natriuretic peptides, which are generally thought to have good negative predictive value for the diagnosis of HF, are frequently not elevated in HFpEF patients. Finally, the cardinal symptoms of HFpEF such as dyspnoea and exercise intolerance are non-specific and may be due to many of the co-morbidities present in patients in whom the HFpEF diagnosis is entertained. This chapter presents a step-wise approach utilizing a careful clinical history, physical examination, natriuretic peptide testing, and echocardiography, which can reliably provide appropriate information to rule in or rule out the HFpEF diagnosis in the majority of patients. If there is still a question about the diagnosis, or if initial general treatment measures for the HF syndrome do not result in clinical improvement, additional testing such as right heart catheterization or cardiopulmonary exercise testing can be performed to further confirm the diagnosis. With a systematic approach to the patient with dyspnoea, the accurate diagnosis of HFpEF can be made reliably so that these high-risk patients can be appropriately treated.

P1634Comparison of inflammation based prognostic scores in patients with stable heart failure with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Arfsten ◽  
A Cho ◽  
S Prausmueller ◽  
G Spinka ◽  
J Novak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Nyha Class ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Reduced Ejection Fraction ◽  
Lymphocyte Ratio ◽  
Nutritional Risk Index ◽  
All Cause Mortality ◽  
The Impact

Abstract Background Elevated inflammatory markers and malnutrition are characteristic for heart failure with reduced ejection fraction (HFrEF) correlating with disease severity and prognosis. Nutritional decline is closely linked to inflammation. Evidence emerges that heart failure can be triggered by inflammation directly, meaning that progression of HF is a function of individual inflammatory host response. We aimed to investigate and compare the impact of well-established inflammation based scores and inflammation-related nutritional scores on survival in HFrEF. Methods Stable HFrEF-patients undergoing routine ambulatory care between 2011 and 2017 have been identified from a prospective registry. Comorbidities and laboratory data at baseline were assessed. All-cause mortality was defined the primary endpoint. The modified Glasgow Prognostic Score (mGPS: 0/1/2 based on CRP and albumin), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) as well as the Nutritional Risk Index (NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight (kg)) and the Prognostic Nutritional Index (PNI = albumin (g l–1) × total lymphocyte count × 109 l–1) were calculated. The association of the scores with HF severity and impact on overall survival were determined. Results Data of 443 patients receiving well titrated guideline directed HF therapy have been analyzed. Median age was 64 years (IQR 53–72), 73% were male. Median body mass index (BMI) was 26.6kg/m2 (IQR 23.8–30.2), median NT-proBNP was 2053pg/ml (IQR 842–4345) with most patients presenting in NYHA class II (178, 40%) and III (173, 39%). The mGPS was 0 for 352 (80%), 1 for 76 (17%) and 2 for 14 (3%) patients, respectively. All scores correlated with HF severity reflected by NT-proBNP [p<0.001 for mGPS, r=−0.48; p<0.001 for PNI] and NYHA class [p<0.001 for mGPS and PNI]. All scores were associated with all-cause mortality in univariate analysis. After adjustment for age, gender and kidney function only mGPS, PLR, NRI and PNI remained significantly associated with outcome. Out of these the ROC were highest for PNI and mGPS [0.674 and 0.652 respectively] and solely these scores remained significantly associated with mortality after including NT-proBNP in the multivariate model [adj.HR 1.87 (95% CI: 1.20–2.91), p=0.006 for mGPS; 0.62 (95% CI: 0.40–0.96), p=0.032 for PNI]. Kaplan Meier analysis confirmed the discriminatory power of mGPS and PNI (Figure 1). Conclusions Enhanced inflammation and malnutrition are more common in advanced heart failure. Among established inflammation and nutritional scores merely mGPS and PNI are associated with survival in HFrEF patients independently of NT-proBNP. This relationship emphasizes the significance of the individual proinflammatory response on prognosis.This easily available score may help clinicians to identify HFrEF patients with worse prognosis with urgent need for intensified therapy and/or alternate treatment options.

scholarly journals Intracellular Dyssynchrony of Diastolic Cytosolic [Ca 2+ ] Decay in Ventricular Cardiomyocytes in Cardiac Remodeling and Human Heart Failure

2013 ◽  
Vol 113 (5) ◽  
pp. 527-538 ◽  
Author(s):  
Felix Hohendanner ◽  
Senka Ljubojević ◽  
Niall MacQuaide ◽  
Michael Sacherer ◽  
Simon Sedej ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Human Heart ◽  
Cyclopiazonic Acid ◽  
Cardiomyocyte Hypertrophy ◽  
Human Heart Failure ◽  
Mitochondrial Density ◽  
Human Cardiomyocytes ◽  
End Stage ◽  
The Impact

Rationale : Synchronized release of Ca 2+ into the cytosol during each cardiac cycle determines cardiomyocyte contraction. Objective: We investigated synchrony of cytosolic [Ca 2+ ] decay during diastole and the impact of cardiac remodeling. Methods and Results: Local cytosolic [Ca 2+ ] transients (1-µm intervals) were recorded in murine, porcine, and human ventricular single cardiomyocytes. We identified intracellular regions of slow (slowCaR) and fast (fastCaR) [Ca 2+ ] decay based on the local time constants of decay (TAU local ). The SD of TAU local as a measure of dyssynchrony was not related to the amplitude or the timing of local Ca 2+ release. Stimulation of sarcoplasmic reticulum Ca 2+ ATPase with forskolin or istaroxime accelerated and its inhibition with cyclopiazonic acid slowed TAU local significantly more in slowCaR, thus altering the relationship between SD of TAU local and global [Ca 2+ ] decay (TAU global ). Na + /Ca 2+ exchanger inhibitor SEA0400 prolonged TAU local similarly in slowCaR and fastCaR. FastCaR were associated with increased mitochondrial density and were more sensitive to the mitochondrial Ca 2+ uniporter blocker Ru360. Variation in TAU local was higher in pig and human cardiomyocytes and higher with increased stimulation frequency (2 Hz). TAU local correlated with local sarcomere relengthening. In mice with myocardial hypertrophy after transverse aortic constriction, in pigs with chronic myocardial ischemia, and in end-stage human heart failure, variation in TAU local was increased and related to cardiomyocyte hypertrophy and increased mitochondrial density. Conclusions: In cardiomyocytes, cytosolic [Ca 2+ ] decay is regulated locally and related to local sarcomere relengthening. Dyssynchronous intracellular [Ca 2+ ] decay in cardiac remodeling and end-stage heart failure suggests a novel mechanism of cellular contractile dysfunction.

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