scholarly journals 586 Effect of sacubitril/valsartan combination in an experimental model of heart failure

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Antonella De Angelis ◽  
Donato Cappetta ◽  
Marialucia Telesca ◽  
Gabriella Bellocchio ◽  
Konrad Urbanek ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Left Ventricle ◽  
Diastolic Function ◽  
Cardiac Tissue ◽  
Function Analysis ◽  
Social Burden ◽  
Systolic And Diastolic Function ◽  
Tail Cuff

Abstract Aims The majority of elderly patients with heart failure has a preserved ejection fraction (HFpEF) that constitutes a syndrome characterized by frequent hospitalizations and high mortality. Despite the growing social burden of HFpEF, the comprehension of its pathophysiology is incomplete, and treatment remains largely undefined. Ageing itself may contribute independently to deterioration of diastolic function. Methods and results An 18-month-old female Fischer 344 rats were treated with oral administration of either sacubitril/valsartan (60 mg/kg/die, 1:1 ratio) or valsartan alone (30 mg/kg/die) for 12 weeks. Tail-cuff method was used to monitor blood pressure weekly. Echocardiography and left ventricle catheterization were employed to assess systolic and diastolic function, at baseline, and before sacrifice. Cardiac tissue was used for molecular biology and histochemistry assays. Tail-cuff analysis indicated a comparable decrease in blood pressure between treatments. Hypertrophy also showed a significant reduction with both treatments. On the contrary, myocardial function analysis demonstrated that no treatment was efficacy on diastolic dysfunction. The lack of improvement of cardiac function could be attributed to the inability of the treatments to counteract the accumulation of fibrotic tissue in the left ventricle, which, in turn, is attributable to the failure to reduce the inflammatory process and oxidative stress, and to the inability to modulate angiotensin II pathway. Conclusions Our results evidenced that both sacubitril/valsartan or valsartan treatment was able to improve diastolic function and pro-fibrotic remodelling, partly due to a lack of effect on classical and non-classical pathways of angiotensin II.

Effect of Left Bundle Branch Block on Systolic and Diastolic Function of Left Ventricle in Heart Failure

Angiology ◽  
2004 ◽  
Vol 55 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Kurtuluş Özdemir ◽  
Bülent Behlül Altunkeser ◽  
Bayram Korkut ◽  
Mehmet Tokaç ◽  
Hasan Gök
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Diastolic Function ◽  
Left Bundle Branch Block ◽  
Bundle Branch Block ◽  
Systolic And Diastolic Function

Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1–7)

2007 ◽  
Vol 292 (2) ◽  
pp. H736-H742 ◽  
Author(s):  
Justin L. Grobe ◽  
Adam P. Mecca ◽  
Melissa Lingis ◽  
Vinayak Shenoy ◽  
Tonya A. Bolton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Cardiac Remodeling ◽  
Cardiac Tissue ◽  
Interstitial Fibrosis ◽  
Chronic Hypertension ◽  
Ang Ii ◽  
Myocyte Hypertrophy ◽  
Chronic Infusion

Cardiac remodeling, which typically results from chronic hypertension or following an acute myocardial infarction, is a major risk factor for the development of heart failure and, ultimately, death. The renin-angiotensin system (RAS) has previously been established to play an important role in the progression of cardiac remodeling, and inhibition of a hyperactive RAS provides protection from cardiac remodeling and subsequent heart failure. Our previous studies have demonstrated that overexpression of angiotensin-converting enzyme 2 (ACE2) prevents cardiac remodeling and hypertrophy during chronic infusion of angiotensin II (ANG II). This, coupled with the knowledge that ACE2 is a key enzyme in the formation of ANG-(1–7), led us to hypothesize that chronic infusion of ANG-(1–7) would prevent cardiac remodeling induced by chronic infusion of ANG II. Infusion of ANG II into adult Sprague-Dawley rats resulted in significantly increased blood pressure, myocyte hypertrophy, and midmyocardial interstitial fibrosis. Coinfusion of ANG-(1–7) resulted in significant attenuations of myocyte hypertrophy and interstitial fibrosis, without significant effects on blood pressure. In a subgroup of animals also administered [d-Ala7]-ANG-(1–7) (A779), an antagonist to the reported receptor for ANG-(1–7), there was a tendency to attenuate the antiremodeling effects of ANG-(1–7). Chronic infusion of ANG II, with or without coinfusion of ANG-(1–7), had no effect on ANG II type 1 or type 2 receptor binding in cardiac tissue. Together, these findings indicate an antiremodeling role for ANG-(1–7) in cardiac tissue, which is not mediated through modulation of blood pressure or altered cardiac angiotensin receptor populations and may be at least partially mediated through an ANG-(1–7) receptor.

Abstract 13407: A Mouse Model of Heart Failure with Preserved Ejection Fraction (HFpEF) due to Chronic Infusion of a Low Subpressor Dose of Angiotensin II

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Stefano Toldo ◽  
Carlo Marchetti ◽  
Aysar Al Husseini ◽  
Salvatore Carbone ◽  
Jessica Regan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mouse Model ◽  
Diastolic Function ◽  
Low Dose ◽  
Left Ventricular ◽  
Vehicle Group ◽  
Chronic Infusion ◽  
Lv Diastolic Function

Introduction: Heart failure with preserved ejection fracture (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents approximately 50% of all patients with HF, the mechanisms of disease are poorly understood, animal models of HFpEF not due pressure overload are lacking, and therapies for HFpEF are generally ineffective. Hypothesis: A continuous infusion of low dose of angiotensin II (ATII) may be sufficient to induce changes in left ventricular (LV) diastolic function without increasing blood pressure nor induce LV hypertrophy. Methods: Osmotic pumps were implanted subcutaneously in 8 week-old CD1 male mice randomly assigned to the ATII (200 ng/kg/day) or vehicle (N=8/group). Transthoracic echocardiography was performed at baseline and 4 weeks to measure LV dimensions, systolic and diastolic function. Aortic systolic and diastolic pressures (AoP), LV peak systolic and end-diastolic pressures (LVPSP, LVEDP) were measured at LV catheterization. Fibrosis was measured using Masson’s trichrome stain. The expression of Interleukin (IL)-18 mRNA levels, a cytokine associated with impaired cardiomyocyte relaxation, was measured at 4 weeks. Results: When compared to the baseline values or vehicle group, ATII infusion had no effects on AoP, LVPSP and HR, and had no effects on LV dimensions or mass, nor on LVEF (all P>0.2). ATII induced a significant impairment in LV diastolic function as measured by an increase (worsening) of the myocardial performance index (MPI), the LV isovolumetric relaxation time (IVRT) and of LVEDP (Figure). Cardiac expression of IL-18 mRNA was significantly increased 7-fold after ATII infusion (P<0.001), suggesting a potential mechanistic role of IL-18. Conclusion: Chronic infusion of low dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing blood pressure. The use of this mouse model may help understanding the mechanisms leading to HFpEF syndrome in patients.

scholarly journals Predictors of heart failure in patients with major beta-thalassemia

2020 ◽  
Vol 8 ◽  
pp. 670-684
Author(s):  
Ionut Stanca ◽  
Mihaela Rus ◽  
Alice Albu ◽  
Simona Fica
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Right Ventricle ◽  
Diastolic Function ◽  
Systolic Function ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Beta Thalassemia ◽  
Myocardial Mass ◽  
Systolic And Diastolic Function

Cardiomyopathy by loading the myocardium with iron is the cause of heart failure in patients with major beta-thalassemia. In these patients, cardiac systolic function remains normal for a long time, but when signs of heart failure appear, death may occur in the first year, so it is necessary to identify parameters to predict the patient's progress and prognosis.Materials and methods. We enrolled 62 patients with beta-thalassemia major (30 men and 32 women), mean age 29.9 ± 7.3 years. 32.2% of patients had disorders of carbohydrate metabolism, 12.9% associated hypothyroidism, and the mean ferritin was 1060.9 ± 856.6 ng / ml. Patients were evaluated echocardiographically, using tissue doppler technique to assess systolic and diastolic function. Myocardial mass was calculated using standard formulas and the type of left ventricular remodeling (LV) was thus obtained. Depending on the ferritin level, choosing the threshold value of 1000ng / ml, a group subanalysis of the ultrasound parameters of cardiac systolic and diastolic function was performed.Results. All patients had LV ejection fraction above 50% (LVEF), but longitudinal LV systolic dysfunction was observed in 19.3% of patients. Also in patients with serum ferritin values ​​above 1000ng / ml, the parameters of longitudinal systolic function of LV are affected, paradoxically the average value of LVEF being higher in these patients. About a quarter of patients had diastolic dysfunction, but 40.3% had elevated LV filling pressures. We noticed that the batch with ferritin over 1000 ng / ml associated increased LV filling pressures. The evaluation of the function of the right ventricle by tissue Doppler (S wave at the level of the free wall VD) was statistically significantly correlated with the hemoglobin value and we obtained pathological values ​​(S VD <11.5 cm / s) especially in the group with ferritin over 1000ng / ml. We noticed the presence of morphological abnormalities of LV, by increasing myocardial mass and the appearance of LV remodeling, 31% of patients showed severe forms, especially eccentric remodeling. It was observed that there is a risk of negative remodeling of the left ventricle in the group of those with ferritin above 1000ng / ml.Conclusions. The study proves that the evaluation of the systolic and diastolic function of the left and right ventricle by tissue Doppler ultrasound is much more accurate in the early detection of myocardial dysfunction. Ferritin levels above 1000ng / ml have been associated with impaired cardiac function parameters. Also, the remodeling of the left ventricle observed in this group of patients may be the first sign of heart failure.

scholarly journals AB0249 POSITIVE EFFECT OF ANTIRHEUMATIC THERAPY ON THE COURSE OF CHRONIC HEART FAILURE IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1424.3-1425
Author(s):  
I. Kirillova ◽  
D. Novikova ◽  
T. Popkova ◽  
Y. Gorbunova ◽  
E. Markelova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricle ◽  
Disease Activity ◽  
Diastolic Function ◽  
Clinical Course ◽  
Clinical Manifestations ◽  
Antirheumatic Therapy ◽  
Early Ra ◽  
Lv Diastolic Function

Background:Objectives:to evaluate the effect of antirheumatic therapy according to the “treat to target” strategy on the course of chronic heart failure (CHF) in patients with early RA.Methods:The study included 22 patients CHF with valid diagnosis of RA (criteria ACR / EULAR, 2010), 17 (77%) of women, median (Me) age - 60 years, Me disease duration - 7 months; IgM seropositive for rheumatoid factor 10 (45%) and / or antibodies to the cyclic citrulline peptide 22 (100%), DAS28-5.6 [4,8;6,5]. CHF verified in accordance the recommendations for the diagnosis and treatment of CHF Society of Specialists in Heart Failure (2013). The concentration of NT-proBNP was determined by electrochemiluminescence. For all patients was started methotrexate (MT) therapy with a rapid increase in the dose to 30 mg per week subcutaneously. If the MT was not effective enough, after 3 months a biological Disease-Modifying Anti-Rheumatic Drug (bDMARDs) was added to the therapy, predominantly TNF-alpha inhibitors. After 18 months, 10 (45%) patients were in remission and low disease activity, 6 (60%) of patients underwent MT therapy in combination with bDMARDs.Results:In baseline CHF with preserved EF was revealed in 21 (95%) patients, in 1 patient - CHF with reduced EF. After 18 months there was a positive dynamics of improvement of clinical symptoms, echocardiographic indicators (decrease the size of the left atrium (LА) and the index of end-systolic volume of LА, IVRT, E’ LV), diastolic function of the left ventricle (LV). There was no decompensation of CHF. LV diastolic function normalized in 7 (32%) patients who reached the target level of blood pressure, remission (n = 5) and low (n = 2) disease activity, mainly in the treatment of MT and bDMARDs. In patients with RA and CHF, the level of NT-proBNP decreased from 192.2 [151.4; 266.4] to 114.0 [90.4; 163.4] pg / ml (p <0.001), normalized in 16 of 22 (73%) patients (p <0.001) with remission or low RA activity. In 5 (22%) patients, the clinical manifestations of CHF regressed, LV diastolic function and NT-proBNP level normalized.Conclusion:In patients with early RA and CHF anti-rheumatic therapy improves the clinical course of CHF. There were an improvement in the clinical course of CHF, diastolic function of the left ventricle and a decrease in NT-proBNP.Disclosure of Interests:None declared

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