Natural history and prognostic significance of anaemia and iron deficiency in ambulatory patients with heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F.J Graham ◽  
G Masini ◽  
P Pellicori ◽  
J.G.F Cleland ◽  
S Kazmi ◽  
...  

Abstract Background Anaemia and iron deficiency (ID) are both common and associated with adverse outcomes in patients with heart failure (HF). However, the incidence of and recovery from anaemia and ID and their impact on prognosis are not well described. Methods Between 2001 and 2018, patients with suspected HF referred to a clinic serving a local population of ∼500,000 were invited to be enrolled in a long-term registry. HF was defined as relevant symptoms or signs with either at least moderate systolic dysfunction on echocardiography or raised plasma concentration of amino-terminal pro-B type natriuretic peptide (NT-proBNP ≥125pg/ml). ID was defined as a transferrin saturation (TSAT) of <20%, anaemia was defined as a haemoglobin (Hb) of <13.0 g/dL in men and <12.0 g/dL in women. At 1-year follow-up, 872 patients had repeat assessments for ID. Patients were grouped into four phenotypes according to the presence or absence of anaemia and/or ID. Those who developed or recovered from ID and anaemia were assessed separately. Survival analysis was conducted at 5 years after the one-year visit. Results The prevalence of ID and anaemia at baseline was 40% and 29% respectively. At baseline and at one-year, 53% of patients had either ID, anaemia or both. Compared to other groups, those with both anaemia and ID were older, had worse renal function and higher median NT-proBNP. In patients with TSAT >20% without anaemia at baseline, 23% had ID at 1 year, 14% were anaemic and 6% developed both. At one year, 11% of patients with anaemia and ID at baseline had normal values for both compared to 16% of those with anaemia but not ID. In patients with ID without anaemia at baseline, 51% remained iron deficient at one year, irrespective of initial Hb. At 5-years, survival was markedly worse for those with anaemia at baseline compared to those without anaemia, irrespective of iron status. Compared to those who had normal TSATs and Hb, those with both anaemia and ID had the worst survival (HR=2.35; 1.77–3.11; p<0.001), followed by those with anaemia without ID (HR=1.93; 1.40–2.67; p<0.001) and those with isolated ID (HR=1.34; 1.01–1.78; p=0.046). Compared to patients who never had anaemia or ID, patients who developed (HR 2.01; 1.41–2.88; p<0.001) or recovered from (HR 2.21; 1.45–3.39; p<0.001) anaemia or ID (HR 1.61; 1.14–2.28; 0.007 and HR 1.63; 1.16–2.28; 0.005 respectively) had a worse prognosis. Conclusions About 30% of patients with HF who have neither anaemia nor ID will develop such problems within a year and this associated with a worse prognosis. Recovery from ID and anaemia is also common, but this is not associated with a better prognosis. Factors leading to the development of anaemia and ID may be driving prognosis rather than anaemia and ID themselves Funding Acknowledgement Type of funding source: None

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3077-3077
Author(s):  
Lia Phillips ◽  
Marc Richmond ◽  
Cindy Neunert ◽  
Gary M. Brittenham

Abstract Introduction: The overall aim of our study was to determine if iron deficiency has harmful effects on cardiac function in children with chronic heart failure. Heart failure in children is a complex, heterogeneous disorder leading to a final common pathway of cardiomyocyte dysfunction and attrition. Cellular, animal, and human studies have shown that iron deficiency causes cardiomyocyte dysfunction that can be reversed with iron treatment. Cellular studies of human iron-deficient cardiomyocytes have shown that supplemental iron restores impaired contractility and relaxation. Animal studies have found that cardiomyocyte-specific deletions or alterations of critical iron proteins (transferrin receptor 1, hepcidin, ferroportin) produce cardiomyocyte iron deficiency (without anemia) and result in ultimately fatal cardiac dysfunction that can be rescued with intravenous (IV) iron. Over half of adults with chronic heart failure are iron deficient. Meta-analysis of small randomized clinical trials has shown that IV iron significantly reduces recurrent hospitalization, cardiovascular mortality, and all-cause mortality in iron deficient adults with heart failure. European Society of Cardiology, American College of Cardiology and American Heart Association guidelines recommend consideration of IV iron therapy for adult iron-deficient patients with heart failure. The prevalence and consequences of iron deficiency in children with heart failure have not been established. Previously, two small retrospective studies of children with heart failure have reported that 56% to 96% were iron deficient, with increased morbidity and mortality. The goals of our study of children with heart failure were to determine (i) how often iron status is assessed, (ii) the prevalence of iron deficiency, and (iii) the effects of iron deficiency on cardiac function in patients with cardiomyopathy. Methods: We retrospectively reviewed electronic medical records to identify pediatric patients ages 1-21 years old seen at Columbia University Irving Medical Center Pediatric Heart Failure clinic with absolute iron deficiency during 2010-2020. Heart failure was defined as presence of symptoms or systolic dysfunction by echocardiography. Patients were excluded with a history of heart transplant, isolated diastolic failure, or renal failure requiring dialysis. In adults with heart failure, a transferrin saturation <20% has a sensitivity of 94% and a specificity of 84% in identifying absolute iron deficiency, as determined from a bone marrow aspirate, and iron stores were present in 100% of patients with a transferrin saturation ≥30% (Circ Heart Fail. 2018;11:e0045). In children with heart failure, we used these criteria to define absolute iron deficiency as a transferrin saturation <20% and iron sufficiency as a transferrin saturation ≥30%. Patients with an intermediate transferrin saturation are likely a mixture of absolute and functional iron deficiency, and of iron sufficiency and were excluded from our analysis of cardiomyopathy. Cardiac ejection fraction was evaluated by an echocardiogram performed within 3 months of measurement of transferrin saturation. Results: Of 579 patients with heart failure, only 159 (27%) had any type of laboratory iron studies. Of patients with iron studies, 81 (51%) were evaluated as outpatients; 49% as inpatients. The cause of heart failure was cardiomyopathy (52%), congenital heart disease (34%), acute myocarditis (6%), and other (8%). In the 82 patients with heart failure due to cardiomyopathy, 39 (48%) were iron deficient and 16 (20%) iron sufficient. In the iron deficient children with cardiomyopathy, the left ventricular ejection fraction was lower than in the iron sufficient patients (median 21% vs. 37%; p=0.03 (Mann-Whitney); Figure). The groups did not differ significantly with respect to hemoglobin (Figure), sex, age, or New York Heart Association class. Conclusion: We report a clinically important decrease in cardiac ejection fraction in children with heart failure due to cardiomyopathy who have absolute iron deficiency. Potentially, iron treatment could safely and effectively reverse the harmful effect of iron deficiency on heart function and prospective randomized trials of oral and intravenous iron therapy are urgently needed. Measurement of iron status should routinely be included in the evaluation of children with heart failure. Figure 1 Figure 1. Disclosures Neunert: Novartis: Research Funding.


2019 ◽  
Vol 21 (Supplement_M) ◽  
pp. M32-M35 ◽  
Author(s):  
Ewa A Jankowska ◽  
Michał Tkaczyszyn ◽  
Marcin Drozd ◽  
Piotr Ponikowski

Abstract The 2016 ESC/HFA heart failure (HF) guidelines emphasize the importance of identifying and treating iron deficiency (ID) in patients with HF. Iron deficiency can occur in half or more of HF sufferers, depending on age and the phase of the disease. Iron deficiency can be a cause of anaemia, but it is also common even without anaemia, meaning that ID is a separate entity, which should be screened for within the HF population. Although assessment of iron stores in bone marrow samples is the most accurate method to investigate iron status, it is not practical in most HF patients. Levels of circulating iron biomarkers are an easily available alternative; especially, ferritin and transferrin saturation (Tsat). In patients with HF serum ferritin level <100 µg/L (regardless of Tsat value) or between 100 and 299 µg/L with Tsat <20% are considered as recommended criteria for the diagnosis of ID, criteria which have been used in the clinical trials in HF that have led to a recommendation to treat ID with intravenous iron. We discuss the optimal measures of iron biomarkers in patients with HF in order to screen and monitor iron status and introduce some novel ways to assess iron status.


2019 ◽  
Vol 7 (2) ◽  
pp. 10-16
Author(s):  
Aditya Mahaseth ◽  
Jay Narayan Shah ◽  
Bikash Nepal ◽  
Biplave Karki ◽  
Jeet Ghimire ◽  
...  

Background and Objectives: Iron Deficiency is the commonest nutritional deficiency worldwide, affecting more than one-third of the population, its association with Heart Failure with or without anemia is of growing interest. As iron supplementation improves prognosis in patients with Heart Failure, Iron Deficiency is an attractive therapeutic target – a hypothesis that has recently been tested in clinical studies. This study is designed to estimate the prevalence and pattern of iron deficiency (ID) in heart failure (HF) with reduced ejection fraction patients with or without anemia. Material and methods: It was a single center hospital based cross sectional observational study. A total of 60 male and female patients with diagnosis of heart failure based on the Framingham Criteria, who gave consent for the study were included. They underwent laboratory evaluation including hemoglobin concentration, serum iron, transferrin saturation percentage, serum ferritin, total iron binding capacity. Serum ferritin <100 μg/l was used to diagnose absolute ID. Functional ID was defined as a serum ferritin level of 100–300 μg/l and a transferrin saturation of <20 %. Anemia was defined as hemoglobin (Hb) <13 g/dl for males and <12 g/dl for females, based on World Health Organization definition. Results: Using the above definitions iron deficiency was found in 28 (46.67%) patients. 36.67% patients had absolute iron deficiency and 10% patients had functional iron deficiency. Females had a higher non statistically significant iron deficiency than males 63.16% vs 39.02%. 15 patients (48.38%) with iron deficiency did not have anemia, and 11 (35.5%) of those patients had absolute iron deficiency. Conclusion: Iron deficiency is prevalent in patients with heart failure and reduced ejection fraction irrespective of anemia and hemoglobin levels. Many of those patients can have functional iron deficiency. Measurement of iron status should be a routine during workup of heart failure patients and further studies are needed to determine the prognostic value of iron status measurement and the influences of treatment of iron deficiency in heart failure patients. Many such trials are now underway.  


2021 ◽  
Vol 8 ◽  
Author(s):  
Caterina Rizzo ◽  
Rosa Carbonara ◽  
Roberta Ruggieri ◽  
Andrea Passantino ◽  
Domenico Scrutinio

Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value &lt;100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is &lt;20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO2 (the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.


2021 ◽  
pp. 1-8
Author(s):  
Kriti Puri ◽  
Joseph A. Spinner ◽  
Jacquelyn M. Powers ◽  
Susan W. Denfield ◽  
Hari P. Tunuguntla ◽  
...  

Abstract Introduction: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure. Methods: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test. Results: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy. Conclusions: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.


2019 ◽  
Vol 15 (1) ◽  
pp. 18-21 ◽  
Author(s):  
Saroj Thapa ◽  
Madhab Lamsal ◽  
Sanjay Kumar Sah ◽  
Rajendra Kumar Chaudhari ◽  
Basanta Gelal ◽  
...  

Background: Iron deficiency is the most common nutritional deficiency in the world. The relation between thyroid hormones and iron status is bidirectional. The aim of this study was to assess iron nutrition status and evaluate its relationship with thyroid hormone profile among children of Eastern Nepal. Methods: A  community based cross-sectional study was conducted in eastern Nepal. A total of 200 school children aged 6-12 years were recruited after taking informed consent from their guardians. Blood samples were collected and assayed for free thyroid hormones (fT3 and fT4), thyroid stimulating hormone (TSH), serum iron, total iron binding capacity (TIBC) concentration and percentage transferrin saturation was calculated. Results: The mean serum iron and TIBC was 74.04 µg/dl and 389.38 µg/dl respectively. The median transferring saturation was 19.21%. The overall prevalence of iron deficiency (Transferrin saturation < 16%) was 34% (n=68). The mean concentration of fT3 and fT4 was 2.87 pg/ml and 1.21 ng/dl respectively, while the median TSH concentration was 3.03 mIU/L. Median TSH concentration in iron deficient group (3.11 µg/dl) and iron sufficient group (2.91 µg/dl) was not significantly different. Among iron deficient children 5.9% had   subclinical hypothyroidism (n=4). Iron status indicators were not significantly correlated with thyroid profile parameters in the study population. Conclusions: The prevalence of iron deficiency is high and iron   deficiency does not significantly alter the thyroid hormone profile in the study region.


Blood ◽  
1976 ◽  
Vol 48 (3) ◽  
pp. 449-455 ◽  
Author(s):  
JD Cook ◽  
CA Finch ◽  
NJ Smith

Abstract The iron status of a population of 1564 subjects living in the northwestern United States was evaluated by measurements of transferrin saturation, red cell protoporphyrin, and serum ferritin. The frequency distribution of these parameters showed no distinct separation between normal and iron-deficient subjects. When only one of these three parameters was abnormal (transferrin saturation below 15%, red cell protoporphyrin above 100 mug/ml packed red blood cells, serum ferritin below 12 ng/ml), the prevalence of anemia was only slightly greater (10.9%) than in the entire sample (8.3%). The prevalence of anemia was increased to 28% in individuals with two or more abnormal parameters, and to 63% when all three parameters were abnormal. As defined by the presence of at least two abnormal parameters, the prevalence of iron deficiency in various populations separated on the basis of age and sex ranged from 3% in adolescent and adult males to 20% in menstruating women. It is concluded that the accuracy of detecting iron deficiency in population surveys can be substantially improved by employing a battery of laboratory measurements of the iron status.


Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000901
Author(s):  
Anette Borger Kvaslerud ◽  
Amjad Iqbal Hussain ◽  
Andreas Auensen ◽  
Thor Ueland ◽  
Annika E Michelsen ◽  
...  

ObjectiveThe aim of this study was to evaluate the prevalence and prognostic implication of iron deficiency (ID) and anaemia in patients with severe aortic stenosis (AS).MethodsIn an observational study of consecutive patients referred for aortic valve replacement (AVR), we assessed a wide range of biomarkers of iron status, including the definition of ID commonly applied in patients with chronic heart failure (ferritin <100 µg/L or ferritin 100–299 µg/L with a transferrin saturation <20%). The endpoints were short-term (one-year) and long-term (median 4.7 years, IQR: 3.8–5.5) mortality and major adverse cardiovascular events (MACE) within the first year after inclusion.Results464 patients were included in this substudy. 91 patients (20%) received conservative treatment and 373 patients (80%) received AVR. ID was detected in 246 patients (53%). 94 patients (20%) had anaemia. Patients with ID had an overall worse clinical profile than patients without ID. During follow-up, 129 patients (28%) died. Neither ID as defined above, soluble transferrin receptor nor hepcidin were associated with short-term or long-term mortality or MACE independent on treatment allocation. Anaemia was associated with one-year mortality in conservatively treated patients.ConclusionsID and anaemia are prevalent in patients with severe AS. In our cohort, ID did not provide independent prognostic information on top of conventional risk factors. More studies are required to determine how to correctly diagnose ID in patients with AS.Trial registration numberNCT01794832.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3828-3828
Author(s):  
Jose Manuel Calvo-Villas ◽  
María Francisca Zapata ◽  
Ivan Alvarez ◽  
Silvia de la Iglesia ◽  
Jorge Cuesta ◽  
...  

Abstract Although an increased level of serum soluble transferrin receptor (sTfR) have been found in both heterozygous β-thalassaemia patients with iron deficiency and in those with more severe genotype (β0), it is not a useful marker of iron deficiency status associated to β-thalassaemia. The aim of this study was to analyse the use of two biochemical parameters (sTfR and sTfR/log of ferritin ratio) to determine the iron status and to evaluate the degree of erythropoietic activity in a group of 221 β-thalassaemic heterozigotes patients (155 β0 and 66 β+). Serum ferritin and transferrin saturation index were measured in order to establish the iron status. Of the whole group, 51 patients were iron defficient (βthal-ID) while the remaining 170 were iron sufficient (βthal-IS). Based on the combination of β-thalassaemia genotype and iron status, patients were classified into four subgroups: β0thalassaemia and iron-sufficient (β0thal-IS) (n=124); β0thalassaemia and iron-deficient (β0thal-ID) (n=31); β+thalassaemia and iron-sufficient (β+thal-IS) (n=46); β+thalassaemia and iron-deficient (β+thal-ID) (n=20). 258 healthy and 56 iron-deficient individuals were used as controls. All the haematological parameters were measured by using analyzer Coulter® GEN-S™. Haemoglobins A2 (Hb A2) and F (HbF) were analysed by high performance liquid chromatography and molecular analysis was performed by real-time PCR and direct sequencing techniques. Chemical, inmunoturbidimetrical and nephelometric methods were used to measure iron status as well as sTfR. Comparison of haemalogical and biochemical parameters between subgroups was performed by using the t-student test and correlation analysis was calculated by using least-squares regression model. Mean sTfR level obtained was 2.63 ± 0.8 mg/dL and 2.57 ± 1.1 mg/dL in βthal-ID and βthal-IS patients respectively (p=0.783). Soluble transferrin receptor showed a positive correlation with HbA2, HbF and reticulocyte count values in βthal-IS patients (r=0.208 [p<0.05], r=0.440 [p<0.0001] and r=0.393 [p<0.00001] respectively) while it did not reach a significant correlation in βthal-ID patients. Mean sTfR/log sFt ratio was 2.75 ± 1.6 and 1.34 ± 0.5 in βthal-ID and βthal-IS patients (p<0.001). Interestingly, sTfR level was significantly higher in β0thal-IS patients when compared with β+thal-IS patients (2.76 ± 0.9 vs 1.42 ± 0.4) (p<0.001) as a result of an increased globin chains imbalance related to the β0 genotype. In the other hand, in the comparison between β0thal-ID and β+thal-ID subgroups neither sTfr level (2.71 ± 0.7 vs 2.40 ± 1.1) (p=0.417) nor sTfR/log sFt ratio (2.93 ± 1.7 vs 2.24 ± 1.3) (p=0.371) showed significant difference. In summary, sTfR/log sFt ratio is a valid parameter for diagnosis of iron deficiency associated to heterozygous β-thalassaemia. Unlike the findings observed in β-thalassaemic heterozigotes with normal iron status, sTfR level is not useful to evaluate the genotype severity in those with iron deficiency. Consequently, iron status should be determined before using sTfR as a parameter to provide a reliable estimation of the ineffective erythropoiesis related to the severity of β-thalassaemia genotypes.


2015 ◽  
Vol 55 (1) ◽  
pp. 44
Author(s):  
Desmansyah Desmansyah ◽  
Rini Purnamasari ◽  
Theodorus Theodorus ◽  
Sulaiman Waiman

Background Iron deficiency is considered to be a major public health problem around the world due to its high prevalence as well as its effect on growth, development, and infection-resistance in children. In malaria-endemic areas, malaria infection is thought to contribute to the occurrence of iron deficiency, by means of hepcidin and hemolysis mechanisms. Objective To assess the prevalence of asymptomatic vivax malaria, compare hemoglobin levels and iron status parameters between vivax malaria-infected and uninfected children, assess the prevalence of iron deficiency, and evaluate a possible correlation between vivax malaria infection and iron deficiency. Methods This cross-sectional study was conducted from February to April 2013 at Sanana City of Sula Islands District, North Maluku. Six parameters were evaluated in 5-11-year-old children: malaria parasite infection, hemoglobin level, serum iron concentration, total iron-binding capacity (TIBC), serum transferrin saturation, and serum ferritin concentration. Results Among 296 children aged 5-11 years, 75 (25.3%) were infected with Plasmodium vivax. In infected children, hemoglobin, serum iron, transferrin saturation, TIBC and serum ferritin were significantly lower than in non-infected children (P<0.01). Using a serum ferritin cut-off of <15 μg/dL, 142 (48.0%) of the children were found to be iron deficient. There was a strong correlation between vivax malaria infection and iron deficiency (OR 3.573; 95%CI 2.03-6.29). ConclusionThe prevalence of asymptomatic vivax malaria infection was 25.3%. The hemoglobin level and iron status parameters in vivax malaria-infected subjects were significantly lower than in uninfected children. The prevalence of iron deficiency was 48.0% for all study subjects. Malaria vivax infection was correlated with iron deficiency in 5-11-year-old children at Sanana City.


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