scholarly journals Sacubitril/Valsartan Improves Diastolic Function But Not Skeletal Muscle Function in a Rat Model of HFpEF

2021 ◽  
Vol 22 (7) ◽  
pp. 3570
Author(s):  
Antje Schauer ◽  
Volker Adams ◽  
Antje Augstein ◽  
Anett Jannasch ◽  
Runa Draskowski ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Carotid Artery ◽  
Ejection Fraction ◽  
Rat Model ◽  
Muscle Function ◽  
Left Ventricular ◽  
Heart Weight ◽  
Skeletal Muscle Function ◽  
The Impact

The angiotensin receptor/neprilysin inhibitor Sacubitril/Valsartan (Sac/Val) has been shown to be beneficial in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, the impact of Sac/Val in patients presenting with heart failure with preserved ejection fraction (HFpEF) is not yet clearly resolved. The present study aimed to reveal the influence of the drug on the functionality of the myocardium, the skeletal muscle, and the vasculature in a rat model of HFpEF. Female obese ZSF-1 rats received Sac/Val as a daily oral gavage for 12 weeks. Left ventricle (LV) function was assessed every four weeks using echocardiography. Prior to organ removal, invasive hemodynamic measurements were performed in both ventricles. Vascular function of the carotid artery and skeletal muscle function were monitored. Sac/Val treatment reduced E/é ratios, left ventricular end diastolic pressure (LVEDP) and myocardial stiffness as well as myocardial fibrosis and heart weight compared to the obese control group. Sac/Val slightly improved endothelial function in the carotid artery but had no impact on skeletal muscle function. Our results demonstrate striking effects of Sac/Val on the myocardial structure and function in a rat model of HFpEF. While vasodilation was slightly improved, functionality of the skeletal muscle remained unaffected.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

Abstract 2391: Impact of Therapies for Anemia on Outcomes in Patients with Heart Failure in Randomized Clinical Trials

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Howard M Julien ◽  
Preetika Muthukrishnan ◽  
Eldrin F Lewis
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Ejection Fraction ◽  
Serum Creatinine ◽  
Exercise Capacity ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
The Impact

Anemia is common in heart failure (HF) patients and has been well-established as a risk factor for increased risk of HF hospitalization and mortality. Treatment with erythropoietin stimulating agents (ESA) has increased hemoglobin, but outcomes trials are limited and use of ESA has been controversial given disparate results in other populations. This meta-analysis aimed to evaluate the impact of ESA and iron on outcomes in HF patients. A systematic review of four databases was conducted in April 2008 (n = 95 unique trials). Analysis inclusion criteria included randomized controlled trial to ESA/iron with clinically defined HF, yielding 10 eligible trials published between 6/01–3/08. Data was independently extracted and cross-checked for accuracy and reliability (2 investigators). A total of 768 subjects (421 treated and 338 controls) are included (Characteristics in Table 1 ). Randomization to ESA produced a significant improvement in exercise capacity 0.39 standard units [95% CI 0.1– 0.6, p = 0.001], a 5.72% [95% CI 1.2–10.3, p = 0.014] increase in left ventricle ejection fraction and a 0.23 mg/dL [95% CI 0.4 – 0.1 p = 0.001] reduction in serum creatinine. There was no difference in all-cause mortality - RR 0.79 [95% CI 0.49, 1.26, p = 0.320]. Trends were noted in reduced hospitalization rates, decreased brain natriuretic peptide, and improved quality of life. Meta-analysis of randomized studies of treatment of anemia in HF patients suggests significant benefit in exercise capacity, left ventricular ejection fraction, and serum creatinine. There does not appear to be excess mortality with ESA/iron treatment. Despite favorable findings, definitive randomized clinical trials are needed to assess the role of this treatment modality in HF management. Table 1. Baseline Patient and Study Characteristics

scholarly journals Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy

2021 ◽  
Vol 10 (21) ◽  
pp. 4989
Author(s):  
Mohammad Abumayyaleh ◽  
Christina Pilsinger ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Jürgen Kuschyk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Tachyarrhythmias ◽  
Ventricular Ejection Fraction ◽  
One Year ◽  
The Impact

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.

scholarly journals Profile of Hospitalized Hypertensives with Preserved and Reduced Left Ventricular Ejection Fraction in Nigeria

2019 ◽  
Vol 14 ◽  
Author(s):  
Akinsanya Daniel Olusegun-Joseph ◽  
Kamilu M Karaye ◽  
Adeseye A Akintunde ◽  
Bolanle O Okunowo ◽  
Oladimeji G Opadijo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Teaching Hospitals ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Hypertensive Patients ◽  
The Impact

Introduction The impact of preserved and reduced left ventricular ejection fraction (LVEF) has been well studied in heart failure, but not in hypertension. We aimed to highlight the prevalence, clinical characteristics, comorbidities and outcomes of hospitalized hypertensives with preserved and reduced LVEF from three teaching hospitals in Nigeria. Methods: This is a retrospective study of hypertensives admitted in 2013 in three teaching hospitals in Lagos, Kano and Ogbomosho, who had echocardiography done while on admission. Medical records and echocardiography parameters of the patients were retrieved and analyzed. Results: 54 admitted hypertensive patients who had echocardiography were recruited, of which 30 (55.6%) had reduced left ventricular ejection fraction (RLVEF), defined as ejection fraction <50%; while 24 (44.4%) had preserved left ventricular ejection fraction (PLVEF). There were 37(61.5%) females and 17 (31.5%) males. Of the male patients 64.7% had RLVEF, while 35.3% had PLVEF. 19(51.4%) of females had RLVEF, while 48.6% had PLVEF. Mean age of patients with PLVEF was 58.83±12.09 vs 54.83± 18.78 of RLVEF; p-0.19. Commonest comorbidity was Heart failure (HF) followed by stroke (found among 59.3% and 27.8% of patients respectively). RLVEF was significantly commoner than PLVEF in HF patients (68.8% vs 31.3%; p- 0.019); no significant difference in stroke patients (46.7% vs 53.3%; p-0.44). Mortality occurred in 1 (1.85%) patient who had RLVEF.         Conclusion: RLVEF was more common than PLVEF among admitted hypertensive patients; they also have more comorbidities. In-hospital mortality is, however, very low in both groups.

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 15172: Murf1 Inhibitor Embl205 is a New Approach for Treatment of Heart Failure With Preserved Ejection Fraction in an Animal Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anett Jannasch ◽  
Antje Schauer ◽  
Virginia Kirchhoff ◽  
Runa Draskowsi ◽  
Claudia Dittfeld ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Skeletal Muscle Atrophy ◽  
Lv Function ◽  
Preserved Ejection Fraction ◽  
The Impact ◽  
Peak Gradient

Background: The novel MuRF1 inhibitor EMBL205 attenuates effectively developing skeletal muscle atrophy and dysfunction in animals with heart failure with preserved ejection fraction (HFpEF, ZSF1 rat model). The impact of EMBL205 on myocardial function in the HFpEF setting is currently unknown and was evaluated in ZSF1 rats. Methods: 20 wks-old female obese ZSF1 rats received EMBL205 (12 wks, conc. of 0.1% in chow; HFpEF-EMBL205). Age-matched untreated lean (con) and obese (HFpEF) ZSF1 rats served as controls. At 32 wks of age left ventricular (LV)-, aortic valve (AV) function and LV end diastolic pressure (LVEDP) was determined by echocardiography and invasive hemodynamic measurements. LV expression of collagen 1A (Col1A) and 3A (Col3A) was assessed by qRT-PCR, MMP2 expression was obtained by zymography and perivascular fibrosis was quantified in histological sections. Results: Development of HFpEF in ZSF1 obese animals is associated with cardiac enlargement and hypertrophy, as evident by increased myocardial weight, an increase in end diastolic volume (EDV) and LV anterior and posterior wall diameters. Diastolic LV-function is disturbed with elevation of E/é, an increased LVEDP and a preserved LV ejection fraction. AV peak velocity and peak gradient are significantly increased and AV opening area (AVA) significantly decreased. Col1A and Col3A expression are increased in HFpEF animals. EMBL205 treatment results in a significant reduction of myocardial weight and a trend towards lower EDV compared to HFpEF group. EMBL205 attenuates the increase in E/é, LVEDP, AV peak gradient and the decrease of AVA. EMBL205 significantly reduces Col3A expression and a trend for Col1A expression is seen. Increased perivascular fibrosis and MMP2 expression in HFpEF is extenuated by EMBL205 treatment (table 1). Conclusions: Application of EMBL205 attenuated the development of pathological myocardial alterations associated with HFpEF in ZSF1rats due to antifibrotic effects.

scholarly journals Skeletal Muscle Function, Structure, and Metabolism in Patients With Heart Failure With Reduced Ejection Fraction and Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Tarek Bekfani ◽  
Mohamed Bekhite Elsaied ◽  
Steffen Derlien ◽  
Jenny Nisser ◽  
Martin Westermann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Ejection Fraction ◽  
Oral Anticoagulation ◽  
Muscle Function ◽  
Muscle Endurance ◽  
Acid Oxidation ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction

Background: Reduced exercise capacity in patients with heart failure (HF) could be partially explained by skeletal muscle dysfunction. We compared skeletal muscle function, structure, and metabolism among clinically stable outpatients with HF with preserved ejection fraction, HF with reduced ejection fraction, and healthy controls (HC). Furthermore, the molecular, metabolic, and clinical profile of patients with reduced muscle endurance was described. Methods: Fifty-five participants were recruited prospectively at the University Hospital Jena (17 HF with preserved ejection fraction, 18 HF with reduced ejection fraction, and 20 HC). All participants underwent echocardiography, cardiopulmonary exercise testing, 6-minute walking test, isokinetic muscle function, and skeletal muscle biopsies. Expression levels of fatty acid oxidation, glucose metabolism, atrophy genes, and proteins as well as inflammatory biomarkers were assessed. Mitochondria were evaluated using electron microscopy. Results: Patients with HF with preserved ejection fraction showed compared with HF with reduced ejection fraction and HC reduced muscle strength (eccentric extension: 13.3±5.0 versus 18.0±5.9 versus 17.9±5.1 Nm/kg, P =0.04), elevated levels of MSTN-2 (myostatin-2), FBXO-32 (F-box only protein 32 [Atrogin1]) gene and protein, and smaller mitochondrial size ( P <0.05). Mitochondrial function and fatty acid and glucose metabolism were impaired in HF-patients compared with HC ( P <0.05). In a multiple regression analysis, GDF-15 (growth and differentiation factor 15), CPT1B (carnitine palmitoyltransferase IB)-protein and oral anticoagulation were independent factors for predicting reduced muscle endurance after adjusting for age (log10 GDF-15 [pg/mL] [B, −54.3 (95% CI, −106 to −2.00), P =0.043], log10 CPT1B per fold increase [B, 49.3 (95% CI, 1.90–96.77), P =0.042]; oral anticoagulation present [B, 44.8 (95% CI, 27.90–61.78), P <0.001]). Conclusions: Patients with HF with preserved ejection fraction have worse muscle function and predominant muscle atrophy compared with those with HF with reduced ejection fraction and HC. Inflammatory biomarkers, fatty acid oxidation, and oral anticoagulation were independent factors for predicting reduced muscle endurance.

scholarly journals Clinical Response to Personalized Exercise Therapy in Heart Failure Patients with Reduced Ejection Fraction Is Accompanied by Skeletal Muscle Histological Alterations

2019 ◽  
Vol 20 (21) ◽  
pp. 5514 ◽  
Author(s):  
Tatiana Lelyavina ◽  
Victoria Galenko ◽  
Oksana Ivanova ◽  
Margarita Komarova ◽  
Elena Ignatieva ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Clinical Response ◽  
Exercise Therapy ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Left Ventricular Ejection ◽  
Histological Alterations ◽  
Before And After

Heart failure (HF) is associated with skeletal muscle wasting and exercise intolerance. This study aimed to evaluate the exercise-induced clinical response and histological alterations. One hundred and forty-four HF patients were enrolled. The individual training program was determined as a workload at or close to the lactate threshold (LT1); clinical data were collected before and after 12 weeks/6 months of training. The muscle biopsies from eight patients were taken before and after 12 weeks of training: histology analysis was used to evaluate muscle morphology. Most of the patients demonstrated a positive response after 12 weeks of the physical rehabilitation program in one or several parameters tested, and 30% of those showed improvement in all four of the following parameters: oxygen uptake (VO2) peak, left ventricular ejection fraction (LVEF), exercise tolerance (ET), and quality of life (QOL); the walking speed at LT1 after six months of training showed a significant rise. Along with clinical response, the histological analysis detected a small but significant decrease in both fiber and endomysium thickness after the exercise training course indicating the stabilization of muscle mechanotransduction system. Together, our data show that the beneficial effect of personalized exercise therapy in HF patients depends, at least in part, on the improvement in skeletal muscle physiological and biochemical performance.

Effects of moderate heart failure and functional overload on rat plantaris muscle

2002 ◽  
Vol 92 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Espen E. Spangenburg ◽  
Simon J. Lees ◽  
Jeff S. Otis ◽  
Timothy I. Musch ◽  
Robert J. Talmadge ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Function ◽  
Skeletal Muscle Function ◽  
Moderate Heart Failure ◽  
Plasmic Reticulum ◽  
Uptake Rates ◽  
Isoform Expression ◽  
And Control

It is thought that changes in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca2+ uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca2+ uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca2+ uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca2+handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.

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