[Show abstract][Hide abstract] ABSTRACT: Although half of all patients with heart failure (HF) have a normal or near-normal ejection fraction and their prognosis differs little from that of patients with a reduced ejection fraction, the pathophysiology of HF with preserved ejection fraction (HF-PEF) is still poorly understood, and its management poorly supported by clinical trials. Sodium and fluid restriction is the most common self-care measure prescribed to HF patients for management of congestive episodes. However, its role in the treatment of HF-PEF remains unclear. This trial seeks to compare the effects of a sodium- and fluid-restricted diet versus an unrestricted diet on weight loss, neurohormonal activation, and clinical stability in patients admitted for decompensated HF-PEF.Methods/design: This is a randomized, parallel trial with blinded outcome assessment. The sample will include adult patients (aged >=18 years) with a diagnosis of HF-PEF admitted for HF decompensation. The patients will be randomized to receive a diet with sodium and fluid intake restricted to 0.8 g/day and 800 mL/day respectively (intervention group) or an unrestricted diet, with 4 g/day sodium and unlimited fluid intake (control group), and followed for 7 days or until hospital discharge. The primary outcome shall consist of weight loss at 7 days or discharge. The secondary outcome includes assessment of clinical stability, neurohormonal activation, daily perception of thirst and readmission rate at 30 days.
[Show abstract][Hide abstract] ABSTRACT: AimsHome-based interventions for heart failure (HF) patients might be particularly effective in middle-income countries, where social, cultural, and economic constraints limit the effectiveness of HF treatment outside the hospital environment.Methods and resultsHELEN-II was a randomized clinical trial conducted in Brazil designed to evaluate the clinical efficacy of a nurse-based strategy, started after discharge following an acute decompensated HF (ADHF) admission. HELEN-II compares the efficacy of home visits and telephone reinforcement (n = 123) with that of the conventional strategy, which is based on medical follow-up (n = 129). The primary outcome was a composite endpoint of a first visit to the emergency department (≤24 h), a hospital readmission (>24 h), or all-cause death, assessed during the first 6 months of follow-up. Most enrolled subjects were middle-aged (62 ± 13 years) males (63%) in NYHA functional class II–III (84%) with severe LV dysfunction (mean LVEF 29.6 ± 9%). The primary composite endpoint was decreased by 27% in the interventional group (relative risk 0.73; 95% confidence interval 0.54–0.99; P = 0.049). At the end of follow-up, the rate of use of the standard-of-care HF medications was similar in both groups, except for the higher use of furosemide in the interventional group. Also, HF knowledge and self-care were significantly increased in the interventional group.ConclusionsA post-discharge, nurse-led management strategy significantly decreases the morbidity of ADHF patients in the public health system of a developing middle-income country.Trial registrationNCT01213875
European Journal of Heart Failure 07/2014; · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction.
In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.
With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis.
In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).
New England Journal of Medicine 04/2014; 370(15):1383-92. · 51.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The utilisation of bioelectrical impedance analysis (BIA) in heart failure can be affected by many factors and its applicability remains controversial. The present study aimed to verify the adequacy of single-frequency BIA (SF-BIA) and multifrequency BIA (MF-BIA) compared to dual-energy x-ray absorptiometry (DEXA) for evaluating body composition in outpatients with heart failure.Methods
In this cross-sectional study, 55 patients with stable heart failure and left ventricle ejection fraction ≤45% were evaluated for fat mass percentage, fat mass and fat-free mass by DEXA and compared with the results obtained by SF-BIA (single frequency of 50 kHz) and MF-BIA (frequencies of 20 and 100 kHz).ResultsMF-BIA and DEXA gave similar mean values for fat mass percentage, fat mass and fat-free mass, whereas values from SF-BIA were significantly different from DEXA. Both SF-BIA and MF-BIA measures of body composition correlated strongly with DEXA (r > 0.8; P < 0.001), except for fat mass assessed by SF-BIA, which showed a moderate correlation (r = 0.760; P < 0.001). MF-BIA also showed a better agreement with DEXA by Bland–Altman analysis in all measurements. However, both types of equipment showed wide limits of agreement and a significant relationship between variance and bias (Pitmans's test P > 0.05), except MF-BIA for fat-free mass.Conclusions
Compared with DEXA, MF-BIA showed better accuracy than SF-BIA, although both types of equipment showed wide limits of agreement. The BIA technique should be used with caution, and regression equations might be useful for correcting the observed variations, mainly in extreme values of body composition.
Journal of Human Nutrition and Dietetics 03/2014; · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Context: Elevated plasmatic microRNAs (miRs) are observed in heart failure (HF). However, the cardiac origin of these miRs remains unclear. Objective: We calculated transcoronary gradients of miR-29b, miR-133a and miR-423-5p in 17 outpatients with stable systolic HF and in controls without structural cardiac disease. Materials and methods: MicroRNAs were measured by quantitative real-time polymerase chain reaction. Results: Positive transcoronary miR gradients were observed in patients with HF but not in controls (p = 0.03). B-type natriuretic peptide (BNP) moderately correlated with the transcoronary gradients of miR-133a and miR-423-5p. Discussion and conclusions: The difference in transcoronary gradients between HF outpatients and controls suggests that miR-423-5p has a cardiac origin. The positive correlation between miR-423-5p and BNP transcoronary gradients supports this hypothesis.
[Show abstract][Hide abstract] ABSTRACT: MicroRNAs (miRs) are a class of small non-coding RNAs that regulate gene expression. Studies of transgenic mouse models have indicated that deregulation of a single miR can induce pathological cardiac hypertrophy and cardiac failure. The roles of miRs in the genesis of physiological left ventricular hypertrophy (LVH), however, are not well understood.
To evaluate the global miR expression in an experimental model of exercise-induced LVH.
Male Balb/c mice were divided into sedentary (SED) and exercise (EXE) groups. Voluntary exercise was performed on an odometer-monitored metal wheels for 35 days. Various tests were performed after 7 and 35 days of training, including a transthoracic echocardiography, a maximal exercise test, a miR microarray (miRBase v.16) and qRT-PCR analysis.
The ratio between the left ventricular weight and body weight was increased by 7% in the EXE group at day 7 (p<0.01) and by 11% at day 35 of training (p<0.001). After 7 days of training, the microarray identified 35 miRs that were differentially expressed between the two groups: 20 were up-regulated and 15 were down-regulated in the EXE group compared with the SED group (p = 0.01). At day 35 of training, 25 miRs were differentially expressed: 15 were up-regulated and 10 were decreased in the EXE animals compared with the SED animals (p<0.01). The qRT-PCR analysis demonstrated an increase in miR-150 levels after 35 days and a decrease in miR-26b, miR-27a and miR-143 after 7 days of voluntary exercise.
We have identified new miRs that can modulate physiological cardiac hypertrophy, particularly miR-26b, -150, -27a and -143. Our data also indicate that previously established regulatory gene pathways involved in pathological LVH are not changed in physiological LVH.
PLoS ONE 01/2014; 9(4):e93271. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate whether changes in hydration status (reflecting fluid retention) would be detected by bioelectrical impedance vector analysis (BIVA) and phase angle during hospitalization for acute decompensated heart failure (ADHF) and after clinical stabilization.
Patients admitted to ADHF were evaluated at admission, discharge and after clinical stabilization (3 months after discharge) for dyspnea, weight, brain natriuretic peptide, bioelectrical impedance resistance, reactance, and phase angle. Generalized estimating equations and chi-square detected variations among the three time points of evaluation.
Were included 57 patients: mean age was 61±13 years, 65% were male, LVEF was 25±8%. During hospitalization there were improvements in clinical parameters and increase in resistance/height (from 250±72 to 302±59 Ohms/m, p<0.001), reactance/height (from 24±10 to 31±9 Ohms/m, p<0.001) and phase angle (from 5.3±1.6 to 6±1.6 degrees, p=0.007). From discharge to chronic stability, both clinical and BIVA parameters remained stable. At admission, 61% of patients had significant congestion by BIVA, and they lost more weight and had higher improvement in dyspnea during hospitalization (p<0.05). At discharge, more patients were in the upper half of the graph (characterizing some degree of dehydration), while at chronic stability normal hydration status was more prevalent (p<0.001).
BIVA and phase angle were able to detect significant changes in hydration status during ADHF, which paralleled the clinical course of recompensation, both acutely and chronically. The classification of congestion by BIVA at admission identified patients with more pronounced changes in weight and dyspnea during compensation.
[Show abstract][Hide abstract] ABSTRACT: Abstract Context: Matrix metalloproteinases are involved in atherosclerosis and plaque vulnerability. Objective: To investigate serum levels and genetic polymorphisms of matrix metalloproteinases (MMPs) -1, -3 and -9 in patients submitted to carotid endarterectomy. Methods: Genetic polymorphisms were evaluated using polymerase chain reaction (PCR-RFLP); serum levels were measured using ELISA; histological sections were stained with Picrosirius Red to analyze the fibrous cap thickness, lipid core and collagen content and with hematoxylin--eosin to detect the presence of intraplaque hemorrhage. Results: MMP-9 serum levels were significantly higher in patients with a thinner fibrous cap (p = 0.033) or acute or recent intraplaque hemorrhage (p = 0.008) on histology, as well as in patients with previous stroke (p = 0.009) or peripheral vascular disease (p = 0.049). No consistent associations were observed between different MMP genotypes and fibrous cap thickness, lipid core, collagen content or intraplaque hemorrhage. Conclusions: MMP-9 serum levels were consistently associated with markers of carotid atherosclerosis and lesion vulnerability, whereas specific MMP genotypes were not.
[Show abstract][Hide abstract] ABSTRACT: QRS duration is considered to be an indicator of adverse outcome in patients with heart failure (HF), and genetic polymorphisms may be involved in this conductivity impairment. We studied the prognostic impact of the QRS widening rate (QRS-WR) on patients with HF and the influence of the matrix metalloproteinases gene polymorphisms on the QRS-WR.
This prospective cohort study included 184 patients with left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] < 45%). The QRS-WR was calculated as the difference between 2 electrocardiogram assessments (in ms) divided by the time elapsed between each evaluation (months). The MMP-1 -1607 1G/2G, MMP-2 -790G/T and -1575G/A, MMP-3 -1171 5A/6A, MMP-9 -1562 C/T and R279Q, and MMP-12 -82A/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism.
Patients were predominantly white (68%) men (67%) in New York Heart Association functional classes I and II (77%). Patients with HF with a QRS-WR ≥ 0.5 ms/month had more HF-related deaths and more combined clinical events than those with a QRS-WR < 0.5 ms/month (P = 0.03 and P = 0.01, respectively). After adjusting for other covariates, the QRS-WR remained an independent predictor of combined clinical events (hazard ratio, 1.6; 95% confidence interval, 1.1-2.5; P = 0.02). The MMP-1 2G2G genotype was associated with nearly a 2-fold increase in QRS-WR (P = 0.03). Conversely, patients with the MMP-3 5A5A genotype and a nonischemic cause of HF were protected against QRS enlargement (P = 0.03).
QRS-WR retains prognostic value in patients with chronic HF receiving guideline-based pharmacologic treatment. MMP gene polymorphisms can influence the rate of QRS enlargement over time.
The Canadian journal of cardiology 11/2013; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Contemporaneous challenges in heart failure management include strategies to rationally use health economic resources and relative donor shortage to adequately offer electric devices (cardiac resynchronization therapy [CRT] and implantable cardioverter defibrillators [ICD]), ventricular assist devices (VADs) and heart transplant, respectively. These issues are particularly important in countries with middle-income rates and limited structured heart transplant centers, such as Brazil. Use of CRT and ICDs need to follow strict guidelines, further customized to public financial health conditions. Experience with VADs in is the early days in Brazil and will require extreme caution to allocate health public resources to develop VAD programs in highly selected centers. Chagas' disease is epidemiologically important in Brazil; outcomes of patients with Chagas' on electric devices are unclear while these patients fare better post-transplant than non-Chagas' patients. Thus, heart transplant remains an attractive option regarding both favorable outcomes and resource allocation for advanced heart failure patients in Brazil.
[Show abstract][Hide abstract] ABSTRACT: Most reports regarding the obesity paradox have focused on body mass index (BMI) to classify obesity and the prognostic values of other indirect measurements of body composition remain poorly examined in heart failure (HF). Objective: To evaluate the association between BMI and other indirect, but easily accessible, body composition measurements associated with the risk of all-cause mortality in HF.
Anthropometric parameters of body composition were assessed in 344 outpatients with a left ventricular ejection fraction (LVEF) of <50% from a prospective HF cohort that was followed-up for 30 ± 8.2 months. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis.
HF patients were predominantly male, of non-ischemic etiology, and had moderate to severe LV systolic dysfunction (mean LVEF = 32 ± 9%). Triceps skinfold (TSF) was the only anthropometric index that was associated with HF prognosis and had significantly lower values in patients who died (p = 0.047). A TSF > 20 mm was present in 9% of patients that died and 22% of those who survived (p = 0.027). Univariate analysis showed that serum creatinine level, LVEF, and NYHA class were associated with the risk of death, while Cox proportional hazard regression analysis showed that TSF > 20 was a strong independent predictor of all-cause mortality (hazard ratio = 0.36; 95% confidence interval = 0.13-0.97, p = 0.03).
Although BMI is the most widely used anthropometric parameter in clinical practice, our results suggested that TSF is a better predictive marker of mortality in HF outpatients.
Arquivos brasileiros de cardiologia 09/2013; · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metabolic syndrome (MS) is associated with increased cardiovascular risk. It is not clear whether myocardial changes showed in this syndrome, such as diastolic dysfunction, are due to the systemic effects of the syndrome, or to specific myocardial effects.
Compare diastolic function, biomarkers representing extracellular matrix activity (ECM), inflammation and cardiac hemodynamic stress in patients with the MS and healthy controls.
MS patients (n=76) and healthy controls (n=30) were submitted to a clinical assessment, echocardiographic study, and measurement of plasma levels of metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), ultrasensitive-reactive-C-Protein (us-CRP), insulin resistance (HOMA-IR) and natriuretic peptide (NT-proBNP).
MS group showed lower E' wave (10.1 ± 3.0 cm/s vs 11.9 ± 2.6 cm/s, p = 0.005), increased A wave (63.4 ± 14.1 cm/s vs. 53.1 ± 8.9 cm/s; p < 0.001), E/E' ratio (8.0 ± 2.2 vs. 6.3 ± 1.2; p < 0.001), MMP9 (502.9 ± 237.1 ng/mL vs. 330.4±162.7 ng/mL; p < 0.001), us-CRP (p = 0.001) and HOMA-IR (p < 0.001), but no difference for TIMP1 or NT-proBNP levels. In a multivariable analysis, only MMP9 was independently associated with MS.
MS patients showed differences for echocardiographic measures of diastolic function, ECM activity, us-CRP and HOMA-IR when compared to controls. However, only MMP9 was independently associated with the MS. These findings suggest that there are early effects on ECM activity, which cannot be tracked by routine echocardiographic measures of diastolic function.
Arquivos brasileiros de cardiologia 09/2013; · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIMS: Evaluating myocardial infarct (MI) size prior to intervention is fundamental to ensure accurate results in experimental studies. However, this assessment is performed at late time points. We aimed to evaluate whether measuring plasma cardiac troponin I (cTnI) and performing echocardiographic assessment at earlier time points can predict the occurrence of MI and infarct size. MAIN METHODS: Male Wistar rats were subjected to an MI (n=40) or sham surgery (n=11). cTnI levels were measured 2 and 8 hours after MI. Echocardiographic evaluation was performed at 48 hours and 14 days. After 14 days, the animals were euthanized, and the hearts were removed and paraffin-embedded for Sirius red staining. KEY FINDINGS: cTnI plasma levels increased in the MI group relative to the sham group at 2 hours after MI (7.2 ± 9.4 ng/mL vs. 2.3 ± 1.0 ng/mL; p<0.01) with a further increase at 8 hours after MI (22.2 ± 13.5 ng/mL vs. 1.5 ± 1.7 ng/mL; p<0.001). cTnI levels (8 hours) and echocardiographic outcomes correlated with histological infarct size 14 days after MI (r=0.74, p<0.001 and r=0.84, p<0.001, respectively), but only echocardiography could confidently identify small, medium, and large infarcts. Additionally, using a cutoff value of 4.8 ng/mL we achieved 100% specificity and 91% sensitivity in detecting MI. SIGNIFICANCE: A cutoff value of 4.8 ng/mL for cTnI could be used as early as 8 hours after MI to accurately identify infarct in this model, whereas echocardiographic images taken 48 hours after MI predicted the infarcted area 14 days after MI.
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE The benefits of fluid and sodium restriction in patients hospitalized with acute decompensated heart failure (ADHF) are unclear. OBJECTIVE To compare the effects of a fluid-restricted (maximum fluid intake, 800 mL/d) and sodium-restricted (maximum dietary intake, 800 mg/d) diet (intervention group [IG]) vs a diet with no such restrictions (control group [CG]) on weight loss and clinical stability during a 3-day period in patients hospitalized with ADHF. DESIGN Randomized, parallel-group clinical trial with blinded outcome assessments. SETTING Emergency room, wards, and intensive care unit. PARTICIPANTS Adult inpatients with ADHF, systolic dysfunction, and a length of stay of 36 hours or less. INTERVENTION Fluid restriction (maximum fluid intake, 800 mL/d) and additional sodium restriction (maximum dietary intake, 800 mg/d) were carried out until the seventh hospital day or, in patients whose length of stay was less than 7 days, until discharge. The CG received a standard hospital diet, with liberal fluid and sodium intake. MAIN OUTCOMES AND MEASURES Weight loss and clinical stability at 3-day assessment, daily perception of thirst, and readmissions within 30 days. RESULTS Seventy-five patients were enrolled (IG, 38; CG, 37). Most were male; ischemic heart disease was the predominant cause of heart failure (17 patients [23%]), and the mean (SD) left ventricular ejection fraction was 26% (8.7%). The groups were homogeneous in terms of baseline characteristics. Weight loss was similar in both groups (between-group difference in variation of 0.25 kg [95% CI, -1.95 to 2.45]; P = .82) as well as change in clinical congestion score (between-group difference in variation of 0.59 points [95% CI, -2.21 to 1.03]; P = .47) at 3 days. Thirst was significantly worse in the IG (5.1 [2.9]) than the CG (3.44 [2.0]) at the end of the study period (between-group difference, 1.66 points; time × group interaction; P = .01). There were no significant between-group differences in the readmission rate at 30 days (IG, 11 patients [29%]; CG, 7 patients [19%]; P = .41). CONCLUSIONS AND RELEVANCE Aggressive fluid and sodium restriction has no effect on weight loss or clinical stability at 3 days and is associated with a significant increase in perceived thirst. We conclude that sodium and water restriction in patients admitted for ADHF are unnecessary. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01133236.
JAMA Internal Medicine 05/2013; · 10.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Anemia in heart failure patients and has been associated with increased morbi-mortality. Previous studies have treated anemia in heart failure patients with either erythropoietin alone or combination of erythropoietin and intravenous (IV) iron. However, the effect of IV or oral (PO) iron supplementation alone in heart failure patients with anemia was virtually unknown. AIM: To compare, in a double-blind design, the effects of IV iron versus PO iron in anemic heart failure patients. METHODS: IRON-HF study was a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that enrolled anemic heart failure patients with preserved renal function, low transferrin saturation (TSat) and low-to-moderately elevated ferritin levels. Interventions were Iron Sucrose IV 200mg, once a week, for 5weeks, ferrous sulfate 200mg PO TID, for 8weeks, or placebo. Primary endpoint was variation of peak oxygen consumption (peak VO2) assessed by ergospirometry over 3month follow-up. RESULTS: Eighteen patients had full follow-up data. There was an increment of 3.5ml/kg/min in peak VO2 in the IV iron group. There was no increment in peak VO2 in the PO iron group. Patients' ferritin and TSat increased significantly in both treated groups. Hemoglobin increased similarly in all groups. CONCLUSION: IV iron seems to be superior in improving functional capacity of heart failure patients. However, correction of anemia seems to be at least similar between PO iron and IV iron supplementation.
International journal of cardiology 05/2013; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Treatment of Preserved Cardiac Function with an Aldosterone Antagonist (TOPCAT) is an ongoing randomized controlled trial of spironolactone versus placebo for heart failure with preserved ejection fraction (HFpEF). We sought to describe the baseline clinical characteristics of subjects enrolled in TOPCAT relative to other contemporary observational studies and randomized clinical trials of HFpEF.
METHODS AND RESULTS: Between August 2006 and January 2012, 3445 patients with symptomatic HFpEF from 270 sites in 6 countries were enrolled in TOPCAT. At the baseline study visit, all subjects provided a detailed medical history and underwent physical examination, electrocardiography, quality of life, and laboratory assessment. Key parameters were compared with other large, contemporary HFpEF studies. The mean age was 68.6±9.6 years with a slight female predominance (52%); mean body mass index was 32 kg/m2; and comorbidities were common. History of hypertension (91% prevalence in TOPCAT) exceeded all other major HFpEF clinical trials. However, baseline blood pressure was well controlled (129/76 mm Hg; systolic blood pressure 7-16 mm Hg lower than other similar trials). Other common comorbidities included coronary artery disease (57%), atrial fibrillation (35%), chronic kidney disease (38%) and diabetes mellitus (32%). Self-reported activity levels were low, quality of life scores were comparable with those reported for patients with end-stage renal disease, and the prevalence of moderate or greater depression was 27%.
CONCLUSIONS: TOPCAT subjects share many common characteristics with contemporary HFpEF cohorts. Low activity level, significantly decreased quality of life, and depression were common at baseline in TOPCAT, underscoring the continued unmet need for evidence-based treatment strategies in HFpEF.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00094302.
[Show abstract][Hide abstract] ABSTRACT: Background: Anemia is a prevalent condition in heart failure with multiple potential causes. The complex interaction between iron stores, hepcidin, inflammation and anemia is poorly comprehended. We tested the hypothesis that, in stable heart failure patients with anemia, hepcidin is associated with iron deficiency status irrespective of inflammation. Methods and Results: Stable systolic heart failure outpatients with and without anemia underwent a complete iron panel, erythropoietin, hepcidin and tumor necrosis factor (TNF)-α assessment. Sixty outpatients were studied. Anemic patients (n = 38, mean hemoglobin 11.4 ± 1 g/dl) were older (69.6 ± 9.6 vs. 58 ± 10.8 years old, p < 0.01) compared with nonanemic patients (n = 22, mean hemoglobin 13.8 ± 1.1 g/dl). Iron deficiency was present in 42% of patients with anemia. TNF-α and hepcidin were 29 and 21% higher in patients with anemia, respectively, compared to nonanemic patients; however, no correlations were found between hepcidin and TNF-α levels. Hepcidin levels in the lower tertile (<31.7 ng/ml) were strongly associated with iron deficiency (OR 16.5, 95% CI 2.2-121.2; p < 0.01). Conclusion: In stable heart failure patients with anemia, hepcidin levels may be more importantly regulated by patients' iron stores than by inflammation.