scholarly journals Darbepoetin-α prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure

2008 ◽  
Vol 295 (6) ◽  
pp. H2475-H2482 ◽  
Author(s):  
Sharad Rastogi ◽  
Makoto Imai ◽  
Victor G. Sharov ◽  
Sudhish Mishra ◽  
Hani N. Sabbah

In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-α (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) ∼25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 μg/kg, n = 7) or to no therapy (HF, n = 7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1α, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1α and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia.

Author(s):  
Tiantian Shen ◽  
Lin Xia ◽  
Wenliang Dong ◽  
Jiaxue Wang ◽  
Feng Su ◽  
...  

Background: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating heart failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. Methods: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized controlled trials(RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model when it appropriate by use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by death and rehospitalization and the secondary outcome was efficacy which was assessed by six-minute walk distance and left ventricular ejection fraction (LVEF),left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV) and brain natriuretic peptide(BNP) Results: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT.MSCs transplantation significantly improved left ventricular ejection fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased left ventricular end-systolic volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, -12.83], p<0.00001 ) and left ventricular end-diastolic volume (LVEDV) by 5.78 ml (MD [95% CI]=-5.78[-12.00, 0.43], p=0.07 ) ,in the MSCs group , BNP was decreased by 133.51 pg/ml MD [95% CI]= -133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Conclusions: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure is safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.


2021 ◽  
Vol 2114 (1) ◽  
pp. 012006
Author(s):  
M K Mohammed ◽  
S I Essa

Abstract Ischemic heart disease is a major causes of heart failure. Heart failure patients have predominantly left ventricular dysfunction (systolic or diastolic dysfunction, or both). Acute heart failure is most commonly caused by reduced myocardial contractility, and increased LV stiffness. We performed echocardiography and gated SPECT with Tc99m MIBI within 263 patients and 166 normal individuals. Left ventricular end systolic volume (LVESV), left ventricular end diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) were measured. For all degrees of ischemia, there was a significant difference between ejection fraction values measured by SPECT and echocardiography, and there were no significant differences among end systolic volume and end diastolic volume value calculated by two methods for all cases. The mean value for EDV (ECHO)/EDV (SPECT) was 1.07 ± 0.31 for degree (1, 2); in the degree 3 the mean value was 1.02 ± 0.08, and 1.005 ± 0.07 for degree 4. The mean value for ESV (ECHO)/ESV (SPECT) was 1.08 ± 0.34 for degree (1, 2); while 1.03 ± 0.12, 1.021 ± 0.128 for degree 3 and 4 respectively. This study was showed a good relation between left ventricular size and ejection fraction measured by SPECT with Tc99m, and echocardiography.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiahui Li ◽  
Lijun Zhang ◽  
Yueli Wang ◽  
Huijuan Zuo ◽  
Rongchong Huang ◽  
...  

Aims: To determine the agreement between two-dimensional transthoracic echocardiography (2DTTE) and cardiovascular magnetic resonance (CMR) in left ventricular (LV) function [including end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF)] in chronic total occlusion (CTO) patients.Methods: Eighty-eight CTO patients were enrolled in this study. All patients underwent 2DTTE and CMR within 1 week. The correlation and agreement of LVEF, LVESV, and LVEDV as measured by 2DTTE and CMR were assessed using Pearson correlation, Kappa analysis, and Bland–Altman method.Results: The mean age of patients enrolled was 57 ± 10 years. There was a strong correlation (r = 0.71, 0.90, and 0.80, respectively, all P &lt; 0.001) and a moderately strong agreement (Kappa = 0.62, P &lt; 0.001) between the two modalities in measurement of LV function. The agreement in patients with EF ≧50% was better than in those with an EF &lt;50%. CTO patients without echocardiographic wall motion abnormality (WMA) had stronger intermodality correlations (r = 0.84, 0.96, and 0.87, respectively) and smaller biases in LV function measurement.Conclusions: The difference in measurement between 2DTTE and CMR should be noticed in CTO patients with EF &lt;50% or abnormal ventricular motion. CMR should be considered in these conditions.


2018 ◽  
Vol 14 (1) ◽  
pp. 3-8
Author(s):  
Mohammad Ashraf Hossain ◽  
Khurshed Ahmed ◽  
Md Faisal Ibn Kabir ◽  
Md Fakhrul Islam Khaled ◽  
Rakibul H Rashed ◽  
...  

Background: Chronic heart failure (CHF) is the most common and prognostically unfavorable outcome of many diseases of the cardiovascular system. Recent data suggest that beta-blockers are beneficial in patients with CHF. Among β-blocker class of drugs, bisoprolol is a highly selective β1-adrenergic receptor blocker whereas Carvedilol is non-selective. Many large-scale trials have confirmed that both these β-blockers are superior to placebo and other β-blockers. This study was designed to compare the effects of carvedilol and bisoprolol in patients with chronic HF in a single center.Methods: It was a quasi experimental study. A total of 288 cases of heart failure were selected by purposive sampling, from January 2017 to June 2017. Each patient was allocated into either of the two groups, and was continued receiving treatment with either bisoprolol (Group-I) or carvedilol (Group-II). Each patient was evaluated clinically and echocardiographically at the beginning of treatment (baseline) and at the end of 3rd month. Echocardiography was performed to find out change in left ventricular systolic function.Result: After 3 months of treatment, ejection fraction was found higher in the bisoprolol group (42.6 ± 6.5 versus 38.3 ± 4.6%; P < 0.05). Ejection fraction (EF) changes were 8.4% in bisoprolol group and 4.1% in carvedilol group. A significant reduction in left ventricular end-systolic volume (21.9±2.5 in group I versus 14.9±5.7 in group II; P < 0.05) and left ventricular systolic diameter (3.2±0.1 in group I versus 2.3±0.5 in group II; P<0.05) occurred after 3 months of treatment. But no significant differences were observed in left ventricular end-diastolic volume (10.1±3.2 versus 6.1±6.4; P=0.101) and left ventricular diastolic diameter (1.7±0.8 versus 1.3±0.8; P=0.081) between groups. Three months after treatment, heart rate was reduced in the bisoprolol group from 87.7±9 to 74.5±8.1 and carvedilol group from 88.8±9.1 to 80.1±8.7. Differences in heart rate responses between 2 groups were not statistically significant (P=0.113). Assessment of blood pressure three months later of treatment shows, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were improved in both group but difference between two groups were statistically non significant (p>0.05).Conclusion: In this study, bisoprolol was superior to carvedilol in increasing left-ventricular ejection fraction, improving left ventricular end systolic volume and left ventricular end systolic diameter but no significant difference was observed in LV end diastolic volume, LV end diastolic diameter, heart rate and blood pressure.University Heart Journal Vol. 14, No. 1, Jan 2018; 3-8


2008 ◽  
Vol 295 (5) ◽  
pp. H2149-H2155 ◽  
Author(s):  
Sharad Rastogi ◽  
Victor G. Sharov ◽  
Sudhish Mishra ◽  
Ramesh C. Gupta ◽  
Brent Blackburn ◽  
...  

Acute intravenous infusion of ranolazine (Ran), an anti-ischemic/antiangina drug, was previously shown to improve left ventricular (LV) ejection fraction (EF) without a concomitant increase in myocardial oxygen consumption in dogs with chronic heart failure (HF). This study examined the effects of treatment with Ran alone and in combination with metoprolol (Met) or enalapril (Ena) on LV function and remodeling in dogs with HF. Dogs ( n = 28) with microembolization-induced HF were randomized to 3 mo oral treatment with Ran alone [375 mg twice daily (bid); n = 7], Ran (375 mg bid) in combination with Met tartrate (25 mg bid; n = 7), Ran (375 mg bid) in combination with Ena (10 mg bid; n = 7), or placebo (PL; Ran vehicle bid; n = 7). Ventriculographic measurements of LV end-diastolic volume (EDV) and end-systolic volume (ESV) and LV EF were obtained before treatment and after 3 mo of treatment. In PL-treated dogs, EDV and ESV increased significantly. Ran alone prevented the increase in EDV and ESV seen in the PL group and significantly increased EF, albeit modestly, from 35 ± 1% to 37 ± 2%. When combined with either Ena or Met, Ran prevented the increase in EDV, significantly decreased ESV, and markedly increased EF compared with those of PL. EF increased from 35 ± 1% to 40 ± 1% with Ran + Ena and from 34 ± 1% to 41 ± 1% with Ran + Met. Ran alone or in combination with Ena or Met was also associated with beneficial effects at the cellular level on histomorphometric parameters such as hypertrophy, fibrosis, and capillary density as well as the expression for pathological hypertrophy and Ca2+ cycling genes. In conclusion, Ran prevented progressive LV dysfunction and global and cellular myocardial remodeling, and Ran in combination with Ena or Met improved LV function beyond that observed with Ran alone.


2015 ◽  
Vol 9s1 ◽  
pp. CMC.S18744 ◽  
Author(s):  
Peter L. M. Kerkhof

Heart failure (HF) may be accompanied by considerable alterations of left ventricular (LV) volume, depending on the particular phenotype. Two major types of HF have been identified, although heterogeneity within each category may be considerable. All variants of HF show substantially elevated LV filling pressures, which tend to induce changes in LV size and shape. Yet, one type of HF is characterized by near-normal values for LV end-diastolic volume (EDV) and even a smaller end-systolic volume (ESV) than in matched groups of persons without cardiac disease. Furthermore, accumulating evidence indicates that, both in terms of shape and size, in men and women, the heart reacts differently to adaptive stimuli as well as to certain pharmacological interventions. Adjustments of ESV and EDV such as in HF patients are associated with (reverse) remodeling mechanisms. Therefore, it is logical to analyze HF subtypes in a graphical representation that relates ESV to EDV. Following this route, one may expect that the two major phenotypes of HF are identified as distinct entities localized in different areas of the LV volume domain. The precise coordinates of this position imply unique characteristics in terms of the actual operating point for LV volume regulation. Evidently, ejection fraction (EF; equal to 1 minus the ratio of ESV and EDV) carries little information within the LV volume representation. Thus far, classification of HF is based on information regarding EF combined with EDV. Our analysis shows that ESV in the two HF groups follows different patterns in dependency of EDV. This observation suggests that a superior HF classification system should primarily be founded on information embodied by ESV.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Zhi Zuo ◽  
Anne Subgang ◽  
Alireza Abaei ◽  
Wolfgang Rottbauer ◽  
Detlef Stiller ◽  
...  

The objective of this work was the assessment of the reproducibility of self-gated cardiac MRI in mice at ultra-high-field strength. A group of adult mice (n=5) was followed over 360 days with a standardized MR protocol including reproducible animal position and standardized planning of the scan planes. From the resulting CINE MRI data, global left ventricular (LV) function parameters including end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and left ventricular mass (LVM) were quantified. The reproducibility of the self-gated technique as well as the intragroup variability and longitudinal changes of the investigated parameters was assessed. Self-gated cardiac MRI proved excellent reproducibility of the global LV function parameters, which was in the order of the intragroup variability. Longitudinal assessment did not reveal any significant variations for EDV, ESV, SV, and EF but an expected increase of the LVM with increasing age. In summary, self-gated MRI in combination with a standardized protocol for animal positioning and scan plane planning ensures reproducible assessment of global LV function parameters.


2006 ◽  
Vol 291 (4) ◽  
pp. H1573-H1579 ◽  
Author(s):  
Joost Lumens ◽  
Tammo Delhaas ◽  
Theo Arts ◽  
Brett R. Cowan ◽  
Alistair A. Young

With aging, structural and functional changes occur in the myocardium without obvious impairment of systolic left ventricular (LV) function. Transmural differences in myocardial vulnerability for these changes may result in increase of transmural inhomogeneity in contractile myofiber function. Subendocardial fibrosis and impairment of subendocardial perfusion due to hypertension might change the transmural distribution of contractile myofiber function. The ratio of LV torsion to endocardial circumferential shortening (torsion-to-shortening ratio; TSR) during systole reflects the transmural distribution of contractile myofiber function. We investigated whether the transmural distribution of systolic contractile myofiber function changes with age. Magnetic resonance tissue tagging was performed to derive LV torsion and endocardial circumferential shortening. TSR was quantified in asymptomatic young [age 23.2 (SD 2.6) yr, n = 15] and aged volunteers [age 68.8 (SD 4.4) yr, n = 16]. TSR and its standard deviation were significantly elevated in the aged group [0.47 (SD 0.12) aged vs. 0.34 (SD 0.05) young; P = 0.0004]. In the aged group, blood pressure and the ratio of LV wall mass to end-diastolic volume were mildly elevated but could not be correlated to the increase in TSR. There were no significant differences in other indexes of systolic LV function such as end-systolic volume and ejection fraction. The elevated systolic TSR in the asymptomatic aged subjects suggests that aging is associated with local loss of contractile myofiber function in the subendocardium relative to the subepicardium potentially caused by subclinical pathological incidents.


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