***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Considerable morbidity and mortality are still associated with congestive heart failure ( CHF ) syndromes , despite improvement in therapy . Activation of neurohormonal , inflammatory , and oxidative mechanisms has been shown to contribute to the significant morbidity and mortality . Erythropoietin ( EPO ) is a cytokine known to regulate erythroid proliferation , attenuate apoptosis and oxidative stress , and promote angiogenesis . We prospect ively evaluated the predictive value of baseline EPO , N-terminal pro-B-type natriuretic peptide , and C-reactive protein levels in patients with clinical ly controlled chronic CHF . METHODS One hundred eighty-eight out patients from a CHF clinic had baseline assessment of EPO , N-terminal pro-B-type natriuretic peptide , and C-reactive protein levels and a complete clinical data profile . These patients were followed up for 24 months for any hospitalization due to CHF or mortality . RESULTS Circulating EPO levels were higher in CHF patients and increased in subjects with higher New York Heart Association scores . Levels of EPO ( at a cutoff of 23 mU/mL ) and N-terminal pro-B-type natriuretic peptide ( cutoff at the median of 1556 pg/mL ) were found to be strong predictors of mortality and CHF hospitalization , whereas C-reactive protein levels ( cutoff of 10 mg/L ) predicted CHF hospitalizations but not mortality . Left ventricular ejection fraction was found to be a predictor of mortality but not of CHF hospitalizations . Serum levels of EPO were significantly correlated with N-terminal pro-B-type natriuretic peptide and C-reactive protein levels but not with left ventricular ejection fraction . CONCLUSION If confirmed in large-scale clinical studies , determination of circulating EPO levels may aid in predicting morbidity and mortality in patients with clinical ly controlled congestive CHF BACKGROUND Hyporesponders to erythropoietin-stimulating agents ( ESAs ) have been associated with an increased subsequent risk of death or cardiovascular events . We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy . METHODS As part of a prospect i ve , single blind , r and omized , placebo-controlled study comparing erythropoietin alfa with placebo in older adults ( n = 56 ) with heart failure and a preserved ejection fraction ( HFPEF ) , we performed blood volume analysis with the use of an indicator dilution technique with (131)iodine-labeled albumin . We evaluated differences in plasma volumes and red cell volumes in hyporesponders ( eg , < 1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa ) compared with subjects who were responders and controls . RESULTS Nine of 28 subjects ( 32 % ) assigned to ESA were hyporesponders . Hyporesponders did not differ from responders nor control subjects by any baseline demographic , clinical , or laboratory parameter , including hemoglobin . Hyporesponders had a greater total blood volume expansion ( 1,264.7 ± 387 vs 229 ± 206 mL ; P = .02 ) but less of a red cell deficit ( -96.2 ± 126 vs -402.5 ± 80.6 mL ; P = .04 ) and a greater plasma volume expansion ( + 1,360.8 ± 264.5 vs + 601.1 ± 165.5 mL ; P = .01 ) . Among responders , the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume ( r = 0.91 ; P < .0001 ) as well as a decline in plasma volume ( r = -0.55 ; P = .06 ) . CONCLUSIONS Among older adults with HFPEF and anemia , hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia , suggesting that blood volume analysis can identify a cohort likely to respond to therapy BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) BACKGROUND A number of animal studies and our own clinical trials point towards a possible influence of the renin-angiotensin-system ( RAS ) on erythropoietin ( EPO ) production . In this study we investigated the role of angiotensin II in the regulation of EPO production in humans . METHODS After a hemorrhage of 750 ml as a basic physiological stimulus 72 healthy male volunteers received in a parallel design either placebo ( physiologic electrolyte solution ) for 6 h , angiotensin II i.v . for 6 h ( 1 - 3 microgram min-1 , sufficient to increase systolic blood pressure by 20 mmHg ) , the selective AT1-receptor antagonist losartan , the ACE-inhibitor captopril , angiotensin II + losartan , or angiotensin II + captopril . RESULTS Administration of angiotensin II alone and in combination with captopril result ed in a significantly higher Cmax EPO ( 67 % higher vs. placebo , P < 0.05 ) and AUCEPO ( 0 - 24h ) ( 40 % higher vs. placebo , P < 0.05 ) . In the groups receiving losartan or captopril alone or the combination of angiotensin II + losartan no significant difference of Cmax EPO and AUCEPO(0 - 24h ) compared to placebo could be detected . CONCLUSIONS This study shows in a model of controlled , basic physiological stimulation of renal EPO production that angiotensin II is able to increase EPO levels in humans . This effect of angiotensin II can be blocked by the specific AT1-receptor antagonist losartan but not by the ACE-inhibitor captopril . The result may be interpreted as a hint that one signal for the control of EPO production in humans may be mediated by angiotensin II (AT1)-receptors Background Anaemia and iron deficiency are frequent following major surgery . The present study aims to identify the iron deficiency patterns in cardiac surgery patients at their admission to a cardiac rehabilitation programme  , and to determine which perioperative risk factor(s ) may be associated with functional and absolute iron deficiency . Design This was a retrospective study on prospect ively collected data . Methods The patient population included 339 patients . Functional iron deficiency was defined in the presence of transferrin saturation < 20 % and serum ferritin ≥100 µg/l . Absolute iron deficiency was defined in the presence of serum ferritin values < 100 µg/l . Results Functional iron deficiency was found in 62.9 % of patients and absolute iron deficiency in 10 % of the patients . At a multivariable analysis , absolute iron deficiency was significantly ( p = 0.001 ) associated with mechanical prosthesis mitral valve replacement ( odds ratio 5.4 , 95 % confidence interval 1.9–15 ) and tissue valve aortic valve replacement ( odds ratio 4.5 , 95 % confidence interval 1.9–11 ) . In mitral valve surgery , mitral repair carried a significant ( p = 0.013 ) lower risk of absolute iron deficiency ( 4.4 % ) than mitral valve replacement with tissue valves ( 8.3 % ) or mechanical prostheses ( 22.5 % ) . Postoperative outcome did not differ between patients with functional iron deficiency and patients without iron deficiency ; patients with absolute iron deficiency had a significantly ( p = 0.017 ) longer postoperative hospital stay ( median 11 days ) than patients without iron deficiency ( median nine days ) or with functional iron deficiency ( median eight days ) . Conclusions Absolute iron deficiency following cardiac surgery is more frequent in heart valve surgery and is associated with a prolonged hospital stay . Routine screening for iron deficiency at admission in the cardiac rehabilitation unit is suggested BACKGROUND Erythropoietin ( Epo ) , a growth factor produced by the kidney , is important in heart failure patients to promote oxygen delivery to tissues . Seventy-two chronic heart failure ( CHF ) patients at our outpatient clinic were subjected to morning serum Epo-level measurements and classified according to NYHA criteria . RESULTS Forty-eight patients of classes III and IV had a significantly elevated serum Epo-level of 42.9+/-40.3 mIU/ml ( mean+/-1 S.D. ) when compared to the mean level of 24 patients of classes I and II who had a normal range mean value of 13.4+/-6.2 mIU/ml ( P<0.05 ) . Patients on angiotensin-converting enzyme ( ACE ) inhibitors showed a trend towards lower serum Epo-levels compared to patients treated with angiotensin-II type-1 receptor antagonists ( AT(1 ) antagonists ) ( levels : 33.3+/-35.6 mIU/ml and 43.6+/-38.1 mIU/ml ) . This trend did not , however , reach statistical significance ( P=0.36 ) . CONCLUSION We suggest that a desirable Epo increase in class III and IV CHF patients could be achieved by either recombinant human Epo administration or , possibly , by appropriate selection of the concomitant medical therapy . A large prospect i ve study shall investigate the possible advantage of AT(1 ) antagonists over ACE-inhibitors with regard to Epo effect Background : Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events . We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency ( CHOIR ) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin ( Hb ) irrespective of treatment target and r and omized allocation . Methods : We performed a post hoc analysis from the CHOIR trial . Inclusion criteria were Hb < 11.0 g/dl and estimated glomerular filtration rates of 15 - 50 ml/min/1.73 m2 . To be included in the present analysis , subjects needed to be free of the composite event at 4 months , receive epoetin-alfa , and have ≥1 postbaseline Hb measurement . The mean weekly dose of epoetin-alfa received up to the time of first event or censure was the main exposure variable , while the achieved Hb at month 4 was the confounder representing the subject 's underlying response to treatment . The primary outcome was the composite of death , heart failure hospitalization , stroke , or myocardial infa rct ion . A Cox proportional hazard regression model was used in time-to-event analysis . Results : Among 1,244 subjects with complete data , the average weekly dose of epoetin-alfa ranged 143.3-fold from 133 to 19,106 units/week at the time of first event or censure . Cox proportional hazard analysis found that those in the middle tertile of Hb achieved ( > 11.5 to < 12.7 g/dl 
    Output:
    
Conclusion Anaemia in heart failure is overwhelmingly characterized by impaired erythropoietin production , which is exacerbated with age , female sex , left ventricular ejection fraction , inflammation and disease severity