scholarly journals Stearoyl-CoA Desaturase (SCD) Induces Cardiac Dysfunction with Cardiac Lipid Overload and Angiotensin II AT1 Receptor Protein Up-Regulation

2021 ◽  
Vol 22 (18) ◽  
pp. 9883
Author(s):  
Joshua Abd Alla ◽  
Yahya F. Jamous ◽  
Ursula Quitterer
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Dysfunction ◽  
Fatty Acid Synthase ◽  
Left Ventricular ◽  
At1 Receptor ◽  
Receptor Protein ◽  
Cardiac Lipid ◽  
Stearoyl Coa Desaturase ◽  
The Impact

Heart failure is a major cause of death worldwide with insufficient treatment options. In the search for pathomechanisms, we found up-regulation of an enzyme, stearoyl-CoA desaturase 1 (Scd1), in different experimental models of heart failure induced by advanced atherosclerosis, chronic pressure overload, and/or volume overload. Because the pathophysiological role of Scd1/SCD in heart failure is not clear, we investigated the impact of cardiac SCD upregulation through the generation of C57BL/6-Tg(MHCSCD)Sjaa mice with myocardium-specific expression of SCD. Echocardiographic examination showed that 4.9-fold-increased SCD levels triggered cardiac hypertrophy and symptoms of heart failure at an age of eight months. Tg-SCD mice had a significantly reduced left ventricular cardiac ejection fraction of 25.7 ± 2.9% compared to 54.3 ± 4.5% of non-transgenic B6 control mice. Whole-genome gene expression profiling identified up-regulated heart-failure-related genes such as resistin, adiponectin, and fatty acid synthase, and type 1 and 3 collagens. Tg-SCD mice were characterized by cardiac lipid accumulation with 1.6- and 1.7-fold-increased cardiac contents of saturated lipids, palmitate, and stearate, respectively. In contrast, unsaturated lipids were not changed. Together with saturated lipids, apoptosis-enhancing p53 protein contents were elevated. Imaging by autoradiography revealed that the heart-failure-promoting and membrane-spanning angiotensin II AT1 receptor protein of Tg-SCD hearts was significantly up-regulated. In transfected HEK cells, the expression of SCD increased the number of cell-surface angiotensin II AT1 receptor binding sites. In addition, increased AT1 receptor protein levels were detected by fluorescence spectroscopy of fluorescent protein-labeled AT1 receptor-Cerulean. Taken together, we found that SCD promotes cardiac dysfunction with overload of cardiotoxic saturated lipids and up-regulation of the heart-failure-promoting AT1 receptor protein.

scholarly journals A REVIEW ON COMPARATIVE STUDY ON THE SAFETY AND EFFECTIVENESS OF SACUBITRIL-VALSARTAN COMBINATION WITH ACE/ARB THERAPY IN CARDIAC PATIENTS

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Bhagya Suresh ◽  
Mathew George ◽  
Lincy Joseph
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Left Ventricular ◽  
At1 Receptor ◽  
Receptor Blocker ◽  
Left Ventricular Ejection ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Cv Disease

Cardiovascular (CV) disease is a major cause of morbidity and mortality in the developing and the developed world, and represents a major barrier to sustainable human development. Ischemic heart disease, cerebrovascular disease, cardiomyopathy and heart failure (HF), and hypertension among others represent major forms of CV disease. Heart failure (HF) is among the key contributors to the CV-related health care burden, a uninterrupted concern despite the utilization of clinically tried guideline-directed therapies. The most common cause for HF is reduced left cavum heart muscle perform. ARBs produce equivalent mortality benefits with fewer adverse effects than ACE inhibitors. Angiotensin converting enzyme (ACEI) reduces the combined risk of death or hospitalization, slow progression of HF, and reduced rate of reinfarction. Sacubitril/valsartan could be a first-in-class twin action molecule of the neprilysin (NEP) substance sacubitril (AHU-377) and therefore the angiotensin II (Ang II) sort one (AT1) receptor blocker (ARB) valsartan. The beneficial antihypertensive and HF effects of sacubitril/valsartan are mediated through the inhibition of NEP in catabolizing the natriuretic peptides (NPs) and the blockade of Ang II, AT1 receptor with valsartan. These actions of sacubitril/ valsartan end in general dilation and inflated symptoms and symptoms, resulting in decrease in peripheral tube resistance and plasma volume contraction, all necessary actions for the lowering of BP and improving HF symptoms. Keywords:  cardiovascular disease, left ventricular ejection fraction, angiotensin II receptor blocker, angiotensin converting enzyme, sacubitril/valsartan.

The intestine responds to heart failure by enhanced mitochondrial fusion through glucagon-like peptide-1 signalling

2019 ◽  
Vol 115 (13) ◽  
pp. 1873-1885 ◽  
Author(s):  
Genki Naruse ◽  
Hiromitsu Kanamori ◽  
Akihiro Yoshida ◽  
Shingo Minatoguchi ◽  
Tomonori Kawaguchi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Mitochondrial Dynamics ◽  
Left Ventricular ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Atp Content ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Impact

Abstract Aims Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone secreted by the intestine. Its receptor (GLP-1R) is expressed in various organs, including the heart. However, the dynamics and function of the GLP-1 signal in heart failure remains unclear. We investigated the impact of the cardio-intestinal association on hypertensive heart failure using miglitol, an α-glucosidase inhibitor known to stimulate intestinal GLP-1 production. Methods and results Dahl salt-sensitive (DS) rats fed a high-salt diet were assigned to miglitol, exendin (9-39) (GLP-1R blocker) and untreated control groups and treated for 11 weeks. Control DS rats showed marked hypertension and cardiac dysfunction with left ventricular dilatation accompanied by elevated plasma GLP-1 levels and increased cardiac GLP-1R expression as compared with age-matched Dahl salt-resistant (DR) rats. Miglitol further increased plasma GLP-1 levels, suppressed adverse cardiac remodelling, and mitigated cardiac dysfunction. In cardiomyocytes from miglitol-treated DS hearts, mitochondrial size was significantly larger with denser cristae than in cardiomyocytes from control DS hearts. The change in mitochondrial morphology reflected enhanced mitochondrial fusion mediated by protein kinase A activation leading to phosphorylation of dynamin-related protein 1, expression of mitofusin-1 and OPA-1, and increased myocardial adenosine triphosphate (ATP) content. GLP-1R blockade with exendin (9-39) exacerbated cardiac dysfunction and led to fragmented mitochondria with disarrayed cristae in cardiomyocytes and reduction of myocardial ATP content. In cultured cardiomyocytes, GLP-1 increased expression of mitochondrial fusion-related proteins and ATP content. When GLP-1 and exendin (9-39) were administered together, their effects cancelled out. Conclusions Increased intestinal GLP-1 secretion is an adaptive response to heart failure that is enhanced by miglitol. This could be an effective strategy for treating heart failure through regulation of mitochondrial dynamics.

Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters

1994 ◽  
Vol 267 (6) ◽  
pp. H2297-H2304 ◽  
Author(s):  
F. Nakamura ◽  
M. Nagano ◽  
R. Kobayashi ◽  
J. Higaki ◽  
H. Mikami ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Cardiac Dysfunction ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Lv Function ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
At1 Antagonist

We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.

Central angiotensin II AT1-receptor antagonism in normal and heart-failed sheep

1995 ◽  
Vol 269 (2) ◽  
pp. H425-H432
Author(s):  
M. T. Rademaker ◽  
M. A. Fitzpatrick ◽  
C. J. Charles ◽  
C. M. Frampton ◽  
A. M. Richards ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
At1 Receptor ◽  
Ang Ii ◽  
Left Ventricular Pacing ◽  
Plasma Arginine ◽  
The Brain

The role of the brain renin-angiotensin system (RAS) in heart failure was examined by administering intracerebroventricular (ICV) infusions of the angiotensin II (ANG II) type 1 (AT1)-receptor antagonist losartan (0.1 followed by 0.5 mg.kg-1.3 h-1) to six concious sheep before (nonpaced) and after induction of heart failure by rapid left ventricular pacing (paced). In both nonpaced and paced states, ICV losartan abolished drinking, induced a significant diuresis (P < 0.05) and anti-natriuresis (P < 0.05), and increased plasma renin activity (P < 0.05) and ANG II (P < 0.01) and aldosterone levels (0.1 > P > 0.05). Plasma arginine vasopressin was suppressed by ICV losartan only in the paced state (P < 0.05). Hemodynamics were not altered by ICV losartan in the nonpaced animals. In the paced state, however, significant reductions in left ventricular systolic, mean arterial, and left atrial pressures were observed (decrements of 13 +/- 7, 12 +/- 5, and 3.4 +/- 0.7 mmHg, respectively, all P < 0.05). In conclusion, ANG II within the brain participates in the regulation of thirst and body electrolyte and fluid homeostasis in normal and heart-failed sheep and appears to play a role in regulating resting hemodynamic status in this model of heart failure.

Myocardial β-adrenoceptors in pacing-induced heart failure: regulation by enalapril?

1994 ◽  
Vol 72 (6) ◽  
pp. 667-672 ◽  
Author(s):  
Christine Forster ◽  
George O. A. Naik ◽  
Giulia Larosa
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Radioligand Binding ◽  
Left Ventricular ◽  
Converting Enzyme Inhibitors ◽  
Failure Group ◽  
End Stage Heart Failure ◽  
End Stage ◽  
The Impact ◽  
Enalapril Treatment

In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in β-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial β-adrenoceptors in dogs paced (250 beats∙min−1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial β-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in β-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the β-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. We conclude that enalapril prevents or reverses the myocardial β-adrenoceptor abnormality seen in heart failure and promotes angiotensin II formation.Key words: congestive heart failure, enalapril, cardiac β-adrenoceptors, angiotensin II formation.

scholarly journals Biomarkers-based personalized follow-up in chronic heart failure improves patient’s outcomes and reduces care associate cost

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antonio Leon-Justel ◽  
Jose I. Morgado Garcia-Polavieja ◽  
Ana Isabel Alvarez-Rios ◽  
Francisco Jose Caro Fernandez ◽  
Pedro Agustin Pajaro Merino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hospital Admissions ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Secondary Outcome ◽  
Ventricular Ejection Fraction ◽  
Number Of Patients ◽  
Ed Visits ◽  
The Impact

Abstract Background Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). Methods This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. Results Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. Conclusions A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.

scholarly journals Oxidative Stress as A Mechanism for Functional Alterations in Cardiac Hypertrophy and Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 931
Author(s):  
Anureet K. Shah ◽  
Sukhwinder K. Bhullar ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Critical Role ◽  
Pressure Overload ◽  
Hypertrophied Heart ◽  
Vasoactive Hormones

Although heart failure due to a wide variety of pathological stimuli including myocardial infarction, pressure overload and volume overload is associated with cardiac hypertrophy, the exact reasons for the transition of cardiac hypertrophy to heart failure are not well defined. Since circulating levels of several vasoactive hormones including catecholamines, angiotensin II, and endothelins are elevated under pathological conditions, it has been suggested that these vasoactive hormones may be involved in the development of both cardiac hypertrophy and heart failure. At initial stages of pathological stimuli, these hormones induce an increase in ventricular wall tension by acting through their respective receptor-mediated signal transduction systems and result in the development of cardiac hypertrophy. Some oxyradicals formed at initial stages are also involved in the redox-dependent activation of the hypertrophic process but these are rapidly removed by increased content of antioxidants in hypertrophied heart. In fact, cardiac hypertrophy is considered to be an adaptive process as it exhibits either normal or augmented cardiac function for maintaining cardiovascular homeostasis. However, exposure of a hypertrophied heart to elevated levels of circulating hormones due to pathological stimuli over a prolonged period results in cardiac dysfunction and development of heart failure involving a complex set of mechanisms. It has been demonstrated that different cardiovascular abnormalities such as functional hypoxia, metabolic derangements, uncoupling of mitochondrial electron transport, and inflammation produce oxidative stress in the hypertrophied failing hearts. In addition, oxidation of catecholamines by monoamine oxidase as well as NADPH oxidase activation by angiotensin II and endothelin promote the generation of oxidative stress during the prolonged period by these pathological stimuli. It is noteworthy that oxidative stress is known to activate metallomatrix proteases and degrade the extracellular matrix proteins for the induction of cardiac remodeling and heart dysfunction. Furthermore, oxidative stress has been shown to induce subcellular remodeling and Ca2+-handling abnormalities as well as loss of cardiomyocytes due to the development of apoptosis, necrosis, and fibrosis. These observations support the view that a low amount of oxyradical formation for a brief period may activate redox-sensitive mechanisms, which are associated with the development of cardiac hypertrophy. On the other hand, high levels of oxyradicals over a prolonged period may induce oxidative stress and cause Ca2+-handling defects as well as protease activation and thus play a critical role in the development of adverse cardiac remodeling and cardiac dysfunction as well as progression of heart failure.

Very early detection of low dose anti-cancer therapy-related cardiotoxicity in lymphoma patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.W Liu ◽  
H.Y Chang ◽  
C.H Lee ◽  
W.C Tsai ◽  
P.Y Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cancer Therapy ◽  
Cardiac Dysfunction ◽  
Systolic Dysfunction ◽  
Multivariable Analysis ◽  
Cardiopulmonary Exercise Test ◽  
Left Ventricular ◽  
Funding Source ◽  
Anti Cancer ◽  
All Cause Mortality

Abstract Background and purpose Left ventricular (LV) global peak systolic longitudinal strain (GLS) by speckle-tracking echocardiography is a sensitive modality for the detection of subclinical LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving anti-cancer therapy remains unknown. Methods We prospectively enrolled 74 patients (57.9±17.0 years old, 57% male) with lymphoma who underwent echocardiography prior to chemotherapy, post 3rd and 6th cycle and 1 year after chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) is defined as the reduction of absolute GLS value from baseline of ≥15%. All the eligible patients underwent a cardiopulmonary exercise test (CPET) upon completion of 3 cycles of anti-cancer therapy. The primary outcome was defined as a composite of all-cause mortality and heart failure events. Results Among 36 (49%) patients with CTRCD, LV GLS was significantly decreased after the 3rd cycle of chemotherapy (20.1±2.6% vs. 17.5±2.3%, p&lt;0.001). In the multivariable analysis, male sex and anemia (hemoglobin &lt;11 g/dL) were found to be independent risk factors of CTRCD. Objectively, patients with CTRCD had lower minute oxygen consumption/kg (VO2/kg) and lower VO2/kg value at anaerobic threshold in the CPET. The incidence of the primary composite outcome was higher in the CTRCD group than in the non-CTRCD group (hazard ratio 3.21; 95% CI, 1.04–9.97; p=0.03). Conclusion LV GLS is capable of detecting early cardiac dysfunction in lymphoma patients receiving anti-cancer therapy. Patients with CTRCD not only had a reduced exercise capacity but also a higher risk of all-cause mortality and heart failure events. Change of LVEF and GLS after cancer Tx Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Ministry of Science and Technology (MOST), Taiwan

Role of angiotensin-signalling in anthracycline-induced cardiotoxicity

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Findlay ◽  
J.H Gill ◽  
R Plummer ◽  
C.J Plummer
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Late Onset ◽  
Left Ventricular Systolic Dysfunction ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Funding Source ◽  
Study Results

Abstract   Anthracycline chemotherapy remains a key component of cancer treatment regimens in both paediatric and adult patients. A significant issue with their use is the development of anthracycline-induced cardiotoxicity (AIC), with subclinical AIC and clinical heart failure observed in 13.8% and 3.1% of patients, respectively. The major clinical complication of AIC is the development of late-onset cardiotoxicity, occurring several years after drug administration, presenting as life-threatening heart failure (HF). Determining the relationship between subclinical AIC and late-onset HF, strategies for mitigation of AIC, and impacts upon the cancer survivor population remains a complex challenge. Administration of drugs targeting the angiotensin system, specifically angiotensin converting enzyme inhibitors (ACEi), have been reported to reduce AIC in the clinic. Whilst the therapeutic effect of ACEi in management of left ventricular systolic dysfunction and consequent HF is principally through optimisation of cardiac haemodynamics, the mechanism involved with mitigation of late-onset AIC several years after anthracycline exposure are currently unknown. Using a variety of human cardiomyocyte in vitro models we have previously demonstrated induction of cardiomyocyte hypertrophy by angiotensin II and anthracyclines. Importantly, selective blockade of the angiotensin II receptor 1 (ATR1) on cardiomyocytes mitigated the anthracycline-induced hypertrophic response, implicating synergism between AIC and angiotensin signalling in cardiomyocytes. Adult human ventricular cardiac myocyte AC10 cell-line were treated in vitro with a range of clinically relevant doxorubicin doses for clinically appropriate durations, with AT1 receptor gene expression evaluated using semi-quantitative PCR. Our results confirm a positive correlation between clinically-relevant concentration of doxorubicin and induction of genetic expression of ATR1 in AC10 cells, with up to 200% increases in ATR1 expression observed. Maximal doxorubicin-induced gene expression being observed at 8 and 24-hours, respectively. These preliminary results agreeing with clinical exposure parameters for this drug with protein expression studies being optimised to support these gene expression study results. Our preliminary studies also imply patients developing AIC carry a deleted polymorphism within intron 16 of the ACE gene and increased systemic levels of the ACE product angiotensin II, both with a known association to hypertrophic cardiomyopathy. Taken together, these data support our mechanistic hypothesis that a relationship exists between AIC and modulation of the angiotensin signalling pathway in cardiomyocytes, involving structural cellular changes and asymptomatic cardiac hypertrophy. An elevation in angiotensin II levels, potentially through polymorphisms in ACE, could thereby exacerbate anthracycline-induced hypertrophy and promote the development of late-onset anthracycline-induced HF. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Cancer Research UK funded PhD

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

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