scholarly journals Characterization of left ventricular myocardial sodium-glucose cotransporter 1 expression in patients with end-stage heart failure

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Alex Ali Sayour ◽  
Attila Oláh ◽  
Mihály Ruppert ◽  
Bálint András Barta ◽  
Eszter Mária Horváth ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Expression ◽  
Immunohistochemical Staining ◽  
Systolic Function ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Cardiac Resynchronization ◽  
Sodium Glucose Cotransporter ◽  
Protein Expressions ◽  
End Stage

Abstract Background Whereas selective sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently showed cardiovascular protective effects in large outcome trials independent of the presence of type 2 diabetes mellitus (T2DM), the cardiovascular effects of dual SGLT1/2 inhibitors remain to be elucidated. Despite its clinical relevance, data are scarce regarding left ventricular (LV) SGLT1 expression in distinct heart failure (HF) pathologies. We aimed to characterize LV SGLT1 expression in human patients with end-stage HF, in context of the other two major glucose transporters: GLUT1 and GLUT4. Methods Control LV samples (Control, n = 9) were harvested from patients with preserved LV systolic function who went through mitral valve replacement. LV samples from HF patients undergoing heart transplantation (n = 71) were obtained according to the following etiological subgroups: hypertrophic cardiomyopathy (HCM, n = 7); idiopathic dilated cardiomyopathy (DCM, n = 12); ischemic heart disease without T2DM (IHD, n = 14), IHD with T2DM (IHD + T2DM, n = 11); and HF patients with cardiac resynchronization therapy (DCM:CRT, n = 9, IHD:CRT, n = 9 and IHD-T2DM:CRT, n = 9). We measured LV SGLT1, GLUT1 and GLUT4 gene expressions with qRT-PCR. The protein expression of SGLT1, and activating phosphorylation of AMP-activated protein kinase (AMPKα) and extracellular signal-regulated kinase 1/2 (ERK1/2) were quantified by western blotting. Immunohistochemical staining of SGLT1 was performed. Results Compared with controls, LV SGLT1 mRNA and protein expressions were significantly and comparably upregulated in HF patients with DCM, IHD and IHD + T2DM (all P < 0.05), but not in HCM. LV SGLT1 mRNA and protein expressions positively correlated with LVEDD and negatively correlated with EF (all P < 0.01). Whereas AMPKα phosphorylation was positively associated with SGLT1 protein expression, ERK1/2 phosphorylation showed a negative correlation (both P < 0.01). Immunohistochemical staining revealed that SGLT1 expression was predominantly confined to cardiomyocytes, and not fibrotic tissue. Overall, CRT was associated with reduction of LV SGLT1 expression, especially in patients with DCM. Conclusions Myocardial LV SGLT1 is upregulated in patients with HF (except in those with HCM), correlates significantly with parameters of cardiac remodeling (LVEDD) and systolic function (EF), and is downregulated in DCM patients with CRT. The possible role of SGLT1 in LV remodeling needs to be elucidated.

Abstract 1604: Response to Cardiac Resynchronization Therapy Differs Between Patients With and Without Previous Right Ventricular Pacing

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Andrea M Thelen ◽  
Christopher L Kaufman ◽  
Kevin V Burns ◽  
Daniel R Kaiser ◽  
Aaron S Kelly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Resynchronization Therapy ◽  
Systolic Function ◽  
Radial Strain ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Peak Displacement

Background: Previous large studies on the effects of cardiac resynchronization therapy (CRT) in patients with heart failure have generally excluded patients previously paced from the right ventricle (RV). Previously RV paced patients (RVp) can exhibit an iatrogenic cause of dyssynchrony and reduced systolic function and thus, may respond differently to CRT than patients not previously RV paced (nRVp). The purpose of this study was to test the hypothesis that RVp patients have greater improvements in left ventricular systolic function, volumes, and dyssynchrony in response to CRT than nRVp. Methods: Standard echocardiograms with tissue Doppler imaging were performed before and after chronic CRT in RVp (n = 21, 16 male) and nRVp (n = 70, 54 male) heart failure patients. Ejection fraction (EF), left ventricular end diastolic (LVEDV) and systolic (LVESV) volumes were calculated using the biplane Simpson’s method. Longitudinal dyssynchrony was calculated as the standard deviation of time to peak displacement (TT-12) of 12 segments in the apical views. Using mid-ventricular short axis views and speckle-tracking methods, radial dyssynchrony (Rad dys ) was calculated as the maximal time difference between six myocardial segments for peak radial strain. Echo response was defined as ≥ 15% reduction in LVESV. Results are reported as mean ± SD. Results: Significant baseline differences (p < 0.05) were observed between groups (RVp vs. nRVp) for age (74 ± 13 vs. 67 ± 13 year), follow-up time (6.1 ± 1.8 vs. 4.6 ± 2.1 months), LVEDV (154.3±50.8 vs.185.3±56.9 mL), and a trend for LVESV (112.4 ± 40.6 vs. 134.9 ± 47 mL, p = 0 .05). No differences were observed for EF, etiology of heart failure, and dyssynchrony measures between groups at baseline. Echo response rate was significantly ( p < 0.05) greater in RVp (76%) than nRVp (57%). After adjusting for baseline differences, RVp had greater improvement in EF (14 ± 9 vs. 8 ± 7%, p < 0.05) and LVESV (−33 ± 18 vs. −20 ± 21%, p < 0.05). After adjustment for follow-up time, no difference was observed for change in dyssynchrony between groups. Conclusion: RVp patients upgraded to CRT exhibit greater improvements in systolic function and ventricular remodeling as compared to nRVp patients.

Surgical therapy for heart failure

2018 ◽  
pp. 157-174
Author(s):  
Stephen Westaby
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Acute Coronary Syndromes ◽  
Symptomatic Relief ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Coronary Syndromes ◽  
Artery Disease ◽  
End Stage ◽  
Age Range

Congestive heart failure affects 23 million people worldwide, and is the final pathway for many diseases that affect the myocardium. Successful intervention in acute coronary syndromes together with improved management of idiopathic dilated cardiomyopathy and dysrhythmia provide an ever-increasing number of advanced heart failure patients spread over a wide age range. In Western countries, coronary artery disease is responsible for about 70% of patients with idiopathic dilated cardiomyopathy and valvular heart disease accounting for 15%. Since 10% of patients older than 65 years suffer systolic left ventricular dysfunction, the numbers with heart failure will double within the next 25 years. For end-stage patients, cardiac transplantation provides the benchmark for increased longevity and symptomatic relief. However, the vast majority of patients are over 65 years of age or are referred with established comorbidity, which precludes transplantation.

Abstract 417: Cardiac Akap12 Signalosome Overexpression Exacerbation of Heart Failure and β-arrestin Signaling Pathway

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Hanan Qasim ◽  
Arfaxad Reyes Alcaraz ◽  
Bradley K McConnell
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Systolic Function ◽  
Left Ventricular ◽  
Control Groups ◽  
Expression Levels ◽  
Anchoring Protein ◽  
The Impact

Background: Heart failure (HF) is responsible for 1 out of 8 deaths per year in the U.S.A. andis the major cause of death globally. In HF, chronic β-adrenergic receptor (β-AR)stimulation leads to reduced cardiac function due in part to β-AR desensitization.β-arrestins are proteins that play a major role in desensitizing G protein-coupledreceptors (GPCRs) such as β-AR. Previously we reported enhanced cardiacfunction in mice lacking functional A Kinase Anchoring Protein 12 (AKAP12). Inthis study, we aim to investigate the impact of AKAP12 overexpression(oxAKAP12) on HF progression through assessing β-arrestins. Our central hypothesis is that cardiac AKAP12 overexpression potentiates HF developmentby influencing β-arrestin signaling downstream of the β-AR. Methods: HF was developed in WT and oxAKAP12-Tg mice (8-10) weeks old males andfemales, through chronic Isoproterenol (ISO) administration (60mg/kg/day for 14days). Left ventricular homogenates were used for gene expression analysis.Furthermore, AKAP12 was transiently overexpressed in AC16 cells (humancardiomyocytes cell line), to asses protein expression levels and Gαs pathwayactivity, upon treatment with 100 nM of ISO. Results: Cardiac oxAKAP12 in both males and females reduced left ventricular ejectionfraction (EF) by 14.5±2.5% and fractional shortening (FS) by 22.7±2% after 14-days of chronic ISO treatment when compared to control groups. β-arrestin-1gene expression levels were significantly lower (p=0.022) in oxAKAP12 malehomogenates treated with ISO (14 days) compared to control groups.Interestingly, female homogenates overexpressing AKAP12 showed significantlyhigher β-arrestin-1 gene expression levels (p<0.0001) with ISO treatment,compared to control groups. In AC16 cells overexpressing AKAP12 and treatedwith ISO, Gαs activity and β-arrestin-1 protein expression levels were bothreduced by 50% compared to AC16 ISO treated groups. Conclusion: Cardiac oxAKAP12 negatively influences systolic function in both male andfemale mice, potentially through affecting β-arrestin signaling pathway. Thus,designing novel drugs to inhibit AKAP12 is promising to ameliorate HF.

scholarly journals Induction of Ankrd1 in Dilated Cardiomyopathy Correlates with the Heart Failure Progression

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Julius Bogomolovas ◽  
Kathrin Brohm ◽  
Jelena Čelutkienė ◽  
Giedrė Balčiūnaitė ◽  
Daiva Bironaitė ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Expression Patterns ◽  
Clinical Manifestations ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Expression Levels ◽  
Potential Marker ◽  
End Stage

Progression of idiopathic dilated cardiomyopathy (IDCM) is marked with extensive left ventricular remodeling whose clinical manifestations and molecular basis are poorly understood. We aimed to evaluate the clinical potential of titin ligands in monitoring progression of cardiac remodeling associated with end-stage IDCM. Expression patterns of 8 mechanoptotic machinery-associated titin ligands (ANKRD1,ANKRD2,TRIM63,TRIM55,NBR1,MLP,FHL2, andTCAP) were quantitated in endomyocardial biopsies from 25 patients with advanced IDCM. When comparing NYHA disease stages, elevatedANKRD1expression levels marked transition from NYHA < IV to NYHA IV.ANKRD1expression levels closely correlated with systolic strain depression and short E wave deceleration time, as determined by echocardiography. On molecular level, myocardialANKRD1and serum adiponectin correlated with lowBAX/BCL-2ratios, indicative of antiapoptotic tissue propensity observed during the worsening of heart failure. ANKRD1 is a potential marker for cardiac remodeling and disease progression in IDCM.ANKRD1expression correlated with reduced cardiac contractility and compliance. The association ofANKRD1with antiapoptotic response suggests its role as myocyte survival factor during late stage heart disease, warranting further studies on ANKRD1 during end-stage heart failure.

scholarly journals Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1190
Author(s):  
Alex Ali Sayour ◽  
Mihály Ruppert ◽  
Attila Oláh ◽  
Kálmán Benke ◽  
Bálint András Barta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Protein Expression ◽  
Volume Overload ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Strong Positive Correlation ◽  
Sodium Glucose Cotransporter ◽  
Hemodynamic Overload

Myocardial sodium-glucose cotransporter 1 (SGLT1) has been shown to be upregulated in humans with heart failure (HF) with or without diabetes. In vitro studies have linked SGLT1 to increased nitro-oxidative stress in cardiomyocytes. We aimed to assess the relation between left ventricular (LV) SGLT1 expression and the extent of nitro-oxidative stress in two non-diabetic rat models of chronic heart failure (HF) evoked by either pressure (TAC, n = 12) or volume overload (ACF, n = 12). Sham-operated animals (Sham-T and Sham-A, both n = 12) served as controls. Both TAC and ACF induced characteristic LV structural and functional remodeling. Western blotting revealed that LV SGLT1 protein expression was significantly upregulated in both HF models (both p < 0.01), whereas the phosphorylation of ERK1/2 was decreased only in ACF; AMPKα activity was significantly reduced in both models. The protein expression of the Nox4 NADPH oxidase isoform was increased in both TAC and ACF compared with respective controls (both p < 0.01), showing a strong positive correlation with SGLT1 expression (r = 0.855, p < 0.001; and r = 0.798, p = 0.001, respectively). Furthermore, SGLT1 protein expression positively correlated with the extent of myocardial nitro-oxidative stress in failing hearts assessed by 3-nitrotyrosin (r = 0.818, p = 0.006) and 4-hydroxy-2-nonenal (r = 0.733, p = 0.020) immunostaining. Therefore, LV SGLT1 protein expression was upregulated irrespective of the nature of chronic hemodynamic overload, and correlated significantly with the expression of Nox4 and with the level of myocardial nitro-oxidative stress, suggesting a pathophysiological role of SGLT1 in HF.

scholarly journals Resynchronization therapy in end-stage heart failure

2021 ◽  
Vol 5 (4) ◽  
pp. 206-211
Author(s):  
D.V. Shumakov ◽  
◽  
D.I. Zybin ◽  
M.A. Popov ◽  
V.V. Dontsov ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Resynchronization Therapy ◽  
Heart Transplant ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Left Ventricular Ejection ◽  
Resynchronization Therapy ◽  
End Stage Heart Failure ◽  
End Stage

Heart failure (HF) is a common condition, and its overall prevalence is constantly growing. HF ultimately progresses to end-stage disease that is refractory to optimal medical therapy and requires implantable devices or heart transplant. In recent years, cardiac resynchronization therapy (CRT) has been generally accepted in patients with NYHA class III or IV, reduced left ventricular ejection fraction (less than 35%), and the wide QRS complex (>120 msec). CRT improves the efficacy of heart ventricle function and, as a result, physical performance and quality of life. Reverse cardiac remodeling occurs at a pathophysiological level that improves systolic function. Patients with end-stage HF who are on the heart transplant list are a specific group in whom CRT is considered a “bridge” to surgery. This review paper discusses state-of-the-art, advances, and unresolved issues in this area. KEYWORDS: cardiac resynchronization therapy, heart failure, left ventricular remodeling, ejection fraction, heart transplant. FOR CITATION: Shumakov D.V., Zybin D.I., Popov M.A. et al. Resynchronization therapy in end-stage heart failure. Russian Medical Inquiry. 2021;5(4):206–211 (in Russ.). DOI: 10.32364/2587-6821-2021-5-4-206-211.

Potential Therapeutic Benefits of Sodium-Glucose Cotransporter 2 Inhibitors in the Context of Ischemic Heart Failure: A State-Of-The-Art Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Mauro Gitto ◽  
Dimitrios A. Vrachatis ◽  
Gianluigi Condorelli ◽  
Konstantinos Papathanasiou ◽  
Bernhard Reimers ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Function ◽  
Coronary Revascularization ◽  
Deep Understanding ◽  
Active Role ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Therapeutic Benefits ◽  
Sodium Glucose Cotransporter

: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-diabetic agents that block the reabsorption of glucose in the proximal convoluted tubule of the nephron, thereby contributing to glycosuria and lowering blood glucose levels. SGLT2 inhibitors have been associated with improved cardiovascular outcomes in patients with diabetes, including a reduced risk of cardiovascular death and hospitalizations for heart failure. Recently, DAPA-HF and EMPEROR REDUCED trials showed the beneficial cardiovascular effect of SGLT2 inhibitors in patients with heart failure with consistently reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Moreover, some exploratory studies suggested that these drugs improve Left Ventricular (LV) systolic function and oppose LV adverse remodeling in patients with HFrEF. However, the exact mechanisms that mediated for this benefit are not fully understood. Beyond glycemic control, enhanced natriuresis, increased erythropoiesis, improved endothelial function, changes in myocardial metabolism, anti-inflammatory and anti-oxidative properties may all play an active role in SGLT2 inhibitors’ cardiovascular benefits. A deep understanding of the pathophysiological interplay is key to define which HF phenotype could benefit more from SGLT2 inhibitors. Current clinical evidence on the comparison of different HF etiologies is limited to posthoc subgroup analysis of DAPA-HF and EMPEROR-REDUCED, which showed similar outcomes in patients with or without ischemic HF. On the other hand, in earlier studies of patients suffering from diabetes, rates of classic ischemic endpoints, such as myocardial infarction, stroke or coronary revascularization, did not differ between patients treated with SGLT2 inhibitors or placebo. The aim of this review is to discuss whether SGLT2 inhibitors may improve prognosis in patients with ischemic HF, not only in terms of reducing re-hospitalizations and improving left ventricular function but also by limiting coronary artery disease progression and ischemic burden.

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