Iron Deficiency Research Articles

Nutritional Indicators of Bone Nonunion: A Systematic Review.

Background/Objectives: Bone nonunion remains a clinical challenge in orthopedic surgery with significant impacts on mental and physical wellbeing for patients. There are several previously established risk factors of nonunion that are connected to nutrition, but this has yet to be substantially explored. This review seeks to assess all studies that present associations between nutrition and nonunion to understand the potential for clinical relevance in nonunion prevention. Methods: Case-control and cohort studies comparing nonunion risk based on nutritional factors were gathered through PubMed in July 2024. Data were extracted with dual verification through Covidence and assessed for bias using the Newcastle-Ottawa Scale. Results: A total of 21 studies were included in this literature review. Vitamin D deficiency was a significant risk factor of nonunion in six studies and not significant in six other studies. Albumin was significant in three of the five studies addressing this lab value. Iron deficiency anemia was significant in a study assessing its impact on nonunion. Calcium was not significant in the one study mentioned. ICD-10-coded malnutrition was significant in one of the two studies. Sarcopenia, nutritional care plans, and dietitian-diagnosed malnutrition were statistically significant clinical indicators for predicting nonunion, but food insecurity was insignificant. Conclusions: Vitamin D, calcium, albumin, iron deficiency anemia, sarcopenia, and clinically diagnosed malnutrition have all been associated with an increased risk of nonunion in observational studies and should be considered when preventing nonunion development.

Gambaran Pengetahuan dan Sikap Remaja Putri Terhadap Kepatuhan Konsumsi Tablet Besi

Adherence to iron (Fe) tablet consumption is 1 tablet every week throughout the year. Adherence to iron tablet consumption is still very low due to low knowledge and attitudes about iron tablet consumption. This study aims to determine the description of knowledge and attitudes of adolescent girls towards compliance with iron tablet consumption at SMA Negeri 1 Bengkunat Pesisir Barat in 2023. The design used was descriptive with 39 respondents. Total sampling technique. The results showed a good level of knowledge of 14 respondents (36%), sufficient knowledge of 20 respondents (51.2%) and less knowledge of 5 respondents (12.8%). Attitude results, 16 respondents (41%) had a positive attitude and 23 respondents (59%) had a negative attitude. The results of compliance showed 9 respondents (23%) were compliant and 30 respondents (77%) were not compliant. The conclusion is that the majority of respondents' knowledge level is lacking, and they have a negative attitude and are not compliant with iron tablet consumption. Suggestions for further research are able to apply the provision of Health Education to compliance with iron tablet consumption as a prevention of iron deficiency anemia.

Intervention on Anemia prevention among adolescent girls: A quasi-experimental study on providing meatballs chips modified to increase hemoglobin levels

Adolescent girls are at higher risk of anemia due to menstrual cycle, with iron deficiency from daily food intake being the most common cause. Therefore, this study aimed to determine the effect of fried meatballs modified with a combination of local ingredients, such as chicken liver flour, moringa oleifera leaves, soybean tempeh flour, and mackerel fish, abbreviated as Tioek chips, on changes in haemoglobin levels on adolescent girls in Kupang City and Kupang Regency. The results show that foods modified with nutritious local ingredients such as Tioek chips can be classified as an affordable and delicious alternative to healthy snacks to prevent anemia.

Effect of Iron Deficiency Anemia on HbA1c Levels in a cohort of patients with Type 2 diabetes mellitus in a tertiary care hospital

Introduction: Studies have reported that HbA1c levels can be changed by iron deficiency (ID) which is the commonest nutritional anaemia globally. This study was aimed at determining the effect of iron deficiency anaemia (IDA) on HbA1c levels in a cohort of type 2 diabetes mellitus (T2DM) attending a tertiary care hospital in Sri Lanka. Methods: A retrospective analytical study was performed for a period of six months from January 2021. Laboratory records of 281 adult T2DM patients both, anaemic (n=135) with Hb <12g/dL in females and <13g/dL males and transferrin saturation <16%, and nonanaemic (n=146) with Hb >12g/dL in females and >13g/dL in males were analyzed. Data were analyzed using (SPSS) version 20, descriptive statistical methods, Pearson’s Correlation test, independent sample t-test, one-way analysis of variance (ANOVA) and Chi-Square test were used. P<0.05 was considered significant. Results: Out of the total 281 patients diagnosed with T2DM, 150 were female, and 131 were male, spanning an age range of 22 to 96 years. The mean ± standard deviation (SD) values for HbA1c in both anaemic and non-anemic groups were 7.4±2.2% g/dL and 7.3±2.36% g/dL, respectively. Importantly, no statistically significant relationship was observed between the two groups (p=0.889). Furthermore, there was no significant correlation between HbA1c levels with serum iron (p=0.617), total Iron Binding Capacity (TIBC) (p=0.340), and transferrin saturation (p=0.168). Conclusion: The study reveals, HbA1c in T2DM patients with and without IDA show no significant difference. Therefore, HbA1c could be reliably used in monitoring patients with T2DM and IDA. Keywords: T2DM, HbA1c, iron deficiency anaemia, red blood cell indices

Building An Android-Based Application For Teenage Women's Reproductive Health Education

Background: Improper nutritional intake during adolescence can cause health problems, such as: impaired physical growth, increased risk of iron deficiency (Iron Deficiency Anemia), decreased intellectual capacity, impaired bone health, impaired sexual organ function, impaired concentration and performance at school, eating disorders and obesity, as well as malnutrition, but teenagers' knowledge about nutrition is very limited. Teenagers easily adapt to digital literacy. Providing digital interventions can have a positive impact on various aspects of health so that efforts to empower teenagers through increasing health promotion and early detection of adolescent health problems digitally are growing rapidly. Aim: The aim of this research is to explore the needs of young women for Android-based nutritional and reproductive health educational applications. Method: The qualitative research method is in-depth interviews via the Zoom application, WhatsApp video call, or WhatsApp voice call. Result: The results of qualitative research show that young women prefer educational media that is easy and fast in providing health information so that educational efforts via smartphones, namely Android-based applications, are an effective solution in providing precise and accurate information about nutritional intake and reproductive health. Keywords: Reproductive Health, Young Women, Application

Blood cell HbA1c measured by enzymatic assay show higher than whole blood HbA1c in patients with iron deficiency anemia

Blood cell HbA1c measured by enzymatic assay show higher than whole blood HbA1c in patients with iron deficiency anemia

Compliance with weekly iron folic acid supplementation and associated factors among secondary school adolescent girls, in Jimma Arjo District, West Ethiopia, 2022: A mixed method cross-sectional Study

Background: Iron deficiency anemia is a prevalent and major public health problem in low- and middle-income countries among adolescent girls. The risk of Iron deficiency anemia and its consequences are prevented by taking and complying with a weekly iron-folic acid supplement. However, there was no information regarding compliance and its associated factors in Ethiopia. The study aimed to determine the magnitude of compliance with weekly Iron-folic acid supplementation and associated factors among Jimma Arjo secondary school adolescent girls. Methods: Institutional-based cross-sectional study was conducted on 417 adolescent girls in three secondary schools of Jimma Arjo, West Ethiopia from March 1st to 31st, 2022 using interviewer-administered structured and semi-structured questionnaires. Bivariable and multivariable logistic regression analyses were used to determine the association of variables. Results: Compliance with iron-folic acid supplementation was 29.3% with 95% CI (24.9, 33.3). Mother`s secondary level of education (AOR=4.94 (95% CI:2.45,9.94)), awareness of anemia (AOR=4.23 (95% CI:2.35,7.61)), good knowledge about iron-folic acid supplementation (AOR=3.96 (95% CI:2.17,7.22)), lack of iron-folic acid supplementation (AOR=0.42 (95% CI:0.23,0.75)), and iron-folic acid supplementation side effects (AOR=0.17 (95% CI:0.08,0.37)) were factors significantly associated with iron-folic acid supplementation compliance. Misconceptions about iron-folic acid supplementation, forgetfulness of tablet, lack of access to drinking water, and irregularity of school weekly iron-folic acid supplementation days were identified as the main barriers to adolescent girls' compliance with iron-folic acid supplementation in a qualitative study. Conclusions: Weekly iron-folic acid supplementation compliance was low at 29.3%. Scheduled health education, parental participation in the program, access to drinking water, refresher training for school focal persons, and fixed weekly iron-folic acid supplementation days can improve compliance with iron-folic acid supplementation and are recommended.

Gastrointestinal Angiodysplasia Resolution After Transcatheter Aortic Valve Implantation

Heyde syndrome is the cooccurrence of aortic stenosis and gastrointestinal bleeding secondary to vascular lesions, including angiodysplasias. Several studies have demonstrated cessation of gastrointestinal bleeding after transcatheter aortic valve implantation (TAVI), but the etiology and effects on vascular lesions are largely unknown. To examine the associations of TAVI with gastrointestinal vascular lesions and identify factors associated with recovery among patients with iron deficiency anemia and severe aortic stenosis. In this prospective, single-center cohort study, patients with iron deficiency anemia on the TAVI waiting list from September 2020 to February 2022 were assessed by capsule endoscopy. Those with vascular lesions were reassessed 6 months after TAVI. Endoscopic images were anonymized and evaluated by 2 independent researchers. Data were analyzed from September 2022 to August 2024. TAVI. The primary outcome was the mean difference in the number of vascular lesions before vs after TAVI. A total of 24 patients (mean [SD] age, 77.4 [7.1] years; 18 [75.0%] male) underwent capsule endoscopy, and vascular lesions were present in 18 patients (75.0%). TAVI was performed in 15 of 18 patients with vascular lesions, of whom 11 agreed to a second capsule endoscopy. The mean (SD) number of vascular lesions across the gastrointestinal tract decreased from 6.4 (5.6) lesions before TAVI to 2.0 (2.1) lesions 6 months after TAVI (P = .04). The number of vascular lesions decreased in 9 of 11 patients (81.8%), including 6 patients (54.5%) who no longer had typical angiodysplasias. Resolution of angiodysplasias was less frequent in patients who had multiple valvular heart disease before TAVI (0 of 3 patients) vs those without multiple valvular heart disease (6 of 8 patients [75.0%]) and in patients with significant paravalvular leakage after TAVI (2 of 5 patients [40.0%]) vs those without significant leakage (4 of 6 patients [66.7%]). In this cohort study of 24 patients with iron deficiency anemia and severe aortic stenosis, angiodysplasias were present in 75.0% of patients. TAVI was associated with reduced size and number of angiodysplasias in these patients. These findings suggest that TAVI not only improves aortic stenosis but may also reduce gastrointestinal bleeding by resolving vascular lesions, offering a dual benefit for patients with Heyde syndrome.

Inflammatory biomarkers and hepcidin levels in Iron deficiency anemia among women of reproductive age

Inflammatory biomarkers and hepcidin levels in Iron deficiency anemia among women of reproductive age

Effect of Intravenous Iron on Functional Capacity in Patients with Ischemic Cardiomyopathy

Background: Iron deficiency is common in heart failure with reduced ejection fraction. Intravenous (IV) iron supplementation has been found to reduce morbidity in heart failure. However, the effect of IV iron on Bangladeshi patients with heart failure are not known. Objects: The study was done to see the effect of IV iron on functional capacity in Bangladeshi patients with ischaemic cardiomyopathy (ICM) and iron deficiency. Methodology: In this quasi-experimental study, out of 80 hospitalized patients with ICM and iron deficiency, 40 were given IV ferric carboxymaltose (FCM) in addition to standard therapy of heart failure, while another 40 were randomized to standard therapy alone. Primary outcome measure was changes in six-minute walk test (6MWT) distance, while secondary outcome measures were changes in New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and plasma NT-proBNP at Weeks 4 and 12. Results: 6MWT distance improved significantly in patients receiving IV iron therapy compared to the patients not receiving IV iron. LVEF improved and plasma NT-proBNP decreased significantly in IV irontreated patients than in patients receiving standard therapy. However, improvement in NYHA functional class was not statistically significant. Conclusion: In Bangladeshi patients with ICM and iron deficiency, IV FCM on top of standard heart failure therapy was associated with improved functional capacity. J Inv Clin Cardiol 2023; 5(2): 32-37

Anaemia Profile and Inflammation Markers in Stunted Children Under Two Years in Indonesia

Background: Stunting is a common issue affecting children who suffer from chronic malnutrition in Indonesia. The Indonesian government has introduced supplementary food programs for stunted children, but the results have been less satisfactory. This may be due to the presence of anaemia and comorbid diseases. Haematology tests and inflammation markers are necessary to identify these conditions. This study aimed to examine the anaemia profiles and inflammation markers in stunted children under two years old. Methods: A cross-sectional descriptive design with cluster samples and consecutive analysis was used. The study was conducted between December 2023 and March 2024 at the West Nusa Tenggara Hospital and Palabuhanratu Sukabumi Hospital laboratories. Samples were obtained from various Public Health Centres in Sukabumi, West Java, North Maluku, and West Nusa Tenggara. Data collection comprised interviews, measurements, and the assessment of haematology, biochemical, and inflammatory markers. Statistical analysis was conducted using SPSS version 20, which includes descriptive analysis, correlation, comparison, and chi-square tests. Results: Two hundred and ten stunted children were identified with various anaemias and comorbidities. These anaemias included suspected thalassemia (38.1%), iron deficiency (18.1%), and anaemia of chronic diseases (13.3%). Based on the inflammatory markers obtained, TB was suspected (21.4%), inflammatory bowel disease (18.1%) was suspected, and allergic proctocolitis was suspected (31.9%). Conclusions: Analysis of the anaemia profiles and inflammatory markers revealed various types of anaemia and suspected comorbidities in stunted children. It is recommended that anaemia profiles and inflammation markers be assessed at the primary healthcare level.

Low Iron Diet Improves Clinical Arthritis in the Mouse Model of Collagen-Induced Arthritis.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal (51 mg/kg) or a low iron diet (5 mg/kg) starting four weeks before the first immunization. From day 4 after the second collagen booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. Concentrations of mouse anti-bovine and anti-mouse collagen type 2 IgG antibodies were measured by ELISA; blood cell counts were performed and mediators of inflammation, tissue matrix degradation, oxygenation and oxidative stress were measured in the mouse sera of both diet groups at the end of the experiment by bead-based multiplex assay. Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) were quantified in whole paw tissue by ELISA. Quantitative PCR was performed in the tissues for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to compare cross-sectional data. Nonlinear regression models were used for longitudinal data of the arthritis scores. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p < 0.001). The immune response against bovine and mouse type 2 collagen did not differ between the two diet groups. Mice fed a low iron diet exhibited significantly lower serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), a central regulator of inflammation and tissue matrix degradation (p < 0.05). In addition, a low iron diet led to a significant reduction in red blood cell indices, indicating restricted iron uptake and latent iron deficiency, but had no effect on hemoglobin concentrations or red blood cell counts. There were no differences between the dietary groups in Fe2+ or Fe3+ content in the paws. Based on calculation of the GSH/GSSG ratio and high MDA levels, high oxidative stress and lipid peroxidation were likewise detected in the paws of both diet groups of mice. Consequently, no differences associated with gene expression of key regulators of iron metabolism and ferroptosis could be detected between the paws of both diet groups. Conclusions: Restricted dietary iron intake alleviates immune-mediated inflammation in CIA without causing anemia. This finding suggests a promising option for dietary treatment of arthritis in inflammation. The underlying mechanism causing reduced arthritis may be linked to the complex regulatory network of TIMP-1 and appears to be independent from the local iron levels, oxidative stress and ferroptosis in the synovial tissues.

Antimicrobial Potency of Nor-Pyochelin Analogues and Their Cation Complexes against Multidrug-Resistant Pathogens.

The opportunistic pathogen Pseudomonas aeruginosa develops increasing resistance toward even the most potent antibiotics. Like other bacteria, the pathogen produces a number of virulence factors including metallophores, which constitute an important group. Pseudomonads produce the iron-chelating metallophore (siderophore) pyochelin, which, in addition to its iron-scavenging ability, is an effector for the transcriptional regulator PchR in its FeIII-bound form (ferripyochelin). In the present study, docking studies predicted a major ferripyochelin binding site in PchR, which prompted the exploration of nor-pyochelin analogues to produce tight binding to PchR, and thereby upregulation of the pyochelin metabolism. In addition, we investigated the effects of using the analogues to bind the antimicrobial cations GaIII and InIII. Selected analogues of nor-pyochelin were synthesized, and their GaIII- and InIII-based complexes were assessed for antimicrobial activity. The results indicate that the GaIII complexes inhibit the pathogens under iron-limited conditions, while the InIII-based systems are more effective in iron-rich media. Several of the GaIII complexes were shown to be highly effective against a multidrug-resistant P. aeruginosa clinical isolate, with minimum inhibitory concentrations (MICs) of ≤1 μg/mL. Similarly, two of the InIII-based systems were particularly effective against the isolate, with an MIC of 8 μg/mL. These results show high promise in comparison with other, traditionally potent antibiotics, as the compounds generally indicated low cytotoxicity toward mammalian cells. Preliminary mechanistic investigations using pseudomonal transposon mutants suggested that the inhibitory effects of the InIII-based systems could be due to acute iron deficiency as a result of InIII-bound bacterioferritin.

Comparative estimation of ascorbic acid (Vitamin C) in Sweet-melon, Watermelon and Cucumber

This research is carried out to provide valuable information for individuals that would want to properly modify their nutrient intake. It would enable individuals to know the quantity of these fruits (Sweet melon, Watermelon and Cucumber) needed to be consumed per day to meet the Recommended Daily Allowance (RDA) of Vitamin C for healthy living. Understanding the relative content of Ascorbic acid in these fruits will help individuals plan their diets and know how to properly incorporate them in foods daily to avoid Vitamin C deficiency health problems. This study determined and compared the vitamin C content in Sweet melon, Watermelon and Cucumber. The extracted juices were analysed for ascorbic acid (Vitamin C) using Iodometric Titration method. Results obtained showed that Sweet melon contain (58.4mg/100cm³), Water melon (22.75mg/100cm³) and Cucumber (16.25mg/100cm³) concentrations of ascorbic acid. The ascorbic acid concentrations being highest in Sweet melon and lowest in Cucumber. Therefore sweet melon is the best source of Vitamin C among the three fruits analyzed. Sweet melon can be recommended for individuals suffering from vitamin C deficiency. It is recommended that nutrition and health education is needed to promote increased consumption of fruits rich in Vitamin C content to avoid diseases caused by its deficiency such as scurvy, Iron deficiency anemia, bone disease in children.

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) &amp;lt;30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR &amp;lt;30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT &amp;lt;0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

Myocardial performance improvement after iron replacement in heart failure patients with LVEF &amp;lt;50% and TSAT &amp;lt;20%: The IRON-PATH II echo-substudy

Abstract Background Iron deficiency (ID) is a prevalent comorbidity in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) &amp;lt;50%. ID leads to impaired myocardial global function. Some echocardiographic parameters have demonstrated an additive value in advanced assessment of cardiac performance, like global longitudinal strain (GLS), myocardial work (MW) and its derivatives constructive work (CW), wasted work (WW) and work efficiency (WE). The usual definition of ID may have limitations in rightly identifying systemic iron status, especially those with isolated hypoferritinemia. However, the impact on cardiac function measured by echocardiography after intravenous iron replacement according to TSAT values has never been explored. Purpose Describe the myocardial performance associated with systemic ID defined as TSAT &amp;lt;20% in patients with HF compared to patients with HF without ID (TSAT ≥20%). Afterwards, we aimed to explore changes in myocardial function after iron replacement by echocardiography. Methods The IRON-PATH II was a multicenter, prospective, observational study. The total number of patients to be recruited was 210 in 7 centers across Spain and Portugal. Patients with HF and LVEF ≤50%, without signs of fluid overload or low cardiac output, and haemoglobin ≥11 g/dL were included. The IRON-PATH II echo-substudy included 100 patients who undergone a specific pilot evaluation of echocardiographic. All patients undergone an echocardiography at baseline, ID-patients received a second echocardiography three months after ID replenishment. Results The final study cohort included in the echo-substudy consisted of 98 patients, 41 (42%) were classified in the ID group (TSAT &amp;lt;20%). Regarding the usual definition of ID, 7 patients (15%) in the ID group had TSAT ≥20%, while 4 (7%) in the non-ID group showed TSAT &amp;lt;20%. Mean age was 72±10 years, 22 (22%) were women and most were in NYHA functional class II (71%). Ischemic was the main etiology of HF (50%). The ID group presented worse LV function expressed by LVEF (34% vs. 38%), WW (302[235.5-439,75] mmHg% vs. 209.5[136-297.25] mmHg%) and WE (74±10% vs. 80±10%) (Figure 1). Right ventricle function was also worse in the ID group when measured by fractional area change (FAC) (41.76[33.26-50.33] % vs 46.79[39.23 – 54.94] %) and RV coupling ratio (0.52±0.21 vs 0.64±0.24) but not by TAPSE. Strikingly, no differences were observed in any echocardiographic parameter of myocardial function between the non-ID patients compared with the ID-patients after iron replenishment (Table 1). Conclusions TSAT &amp;lt;20% identified ID status that causes impaired myocardial performance in HF patients. This can be reversed with intravenous iron repletion. This reversible damage to cardiac function can be detected by advanced echocardiographic parameters, both for LV (GLS, WE, MW, WW) and for RV (RVFW strain, RV coupling), but not by LVEF or TAPSE.Figure 1Table 1

Associations of different definitions of iron deficiency with cardiac structure and function, congestion, exercise capacity and prognosis in heart failure

Abstract Background It is uncertain how best to diagnose iron deficiency (ID) in patients with heart failure (HF) as different ID definitions have been proposed with discordant results. Objectives To assess the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in outpatients with HF. Methods ID was defined according to guidelines (G-ID: ferritin &amp;lt;100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation [TSAT] &amp;lt;20%) or as TSAT &amp;lt;20%. Alternative definitions (iron &amp;lt;13 ¼mol/L, ferritin &amp;lt;100 and &amp;lt;300 ng/mL) were explored. Relationship with rest and exercise ultrasound findings, cardiopulmonary exercise testing and a composite endpoint of cardiovascular hospitalisations or all-cause mortality were assessed. Results Of 1502 patients (72% with left ventricular ejection fraction [LVEF] ≥50%), 471 (31%) had TSAT &amp;lt;20%, while 728 (48%) had G-ID. Compared to those without ID, patients with TSAT &amp;lt;20% or G-ID showed impaired cardiac structure and function at rest and peak exercise and lower peak oxygen consumption; they were also more likely to display a discontinuous renal venous flow pattern and more lung B-lines. Only TSAT &amp;lt;20% was associated with significant inferior vena cava dilatation. Lower TSAT, iron and haemoglobin were associated with more severe effort intolerance and ultrasound signs of congestion, while ferritin and LVEF were not (Picture 1). During a median follow-up of 16 months, 62 (4%) patients died, and 244 (16%) were hospitalised for cardiovascular reasons. No patients were hospitalised immediately after the enrolment visit because of clinical findings. At Kaplan-Meier analyses, TSAT &amp;lt;20% was associated with a greater risk of adverse events, as were iron ≤13 ¼mol/L, ferritin ≥300 ng/mL and &amp;lt;100 ng/mL (p &amp;lt;0.01 vs ferritin 100-299 ng/mL) and G-ID (Picture 2). After adjusting for age, sex, diabetes, haemoglobin, estimated glomerular filtration rate (eGFR), NT-proBNP, rest LVEF and peak VO2 &amp;lt;16 mL/kg/min, TSAT &amp;lt;20% and iron ≤13 ¼mol/L were associated with worse outcomes (hazard ratio 2.41, 95% confidence interval 1.85-3.14 and 1.90, 1.46-2.47), while G-ID or ferritin &amp;lt;100 or &amp;lt;300 ng/mL were not (Picture 1). Conclusions In outpatients with HF, TSAT &amp;lt;20% is more consistently associated with echocardiographic signs of poorer functional capacity and multi-organ congestion than other ID definitions. TSAT &amp;lt;20% and iron ≤13 ¼mol/L, but not G-ID or ferritin-based ID, seem to predict a worse prognosis.Picture 1Picture 2

Ferric derisomaltose versus usual care in patients with heart failure, reduced ejection fraction, and iron deficiency: a short-term UK cost-utility analysis based on the IRONMAN RCT

Abstract Background In the IRONMAN trial, patients with heart failure (HF), a reduced ejection fraction and iron deficiency who were randomly assigned to ferric derisomaltose (FDI), rather than usual care, had a lower rate of the composite of hospitalization for heart failure (HHF) and cardiovascular (CV) death (rate ratio, RR, 0.82; 95% CI 0.66 to 1.02; p=0.07). A COVID-19 sensitivity analysis, censoring data at 1 year of follow-up showed a greater magnitude of treatment effect (RR 0.66; 95% CI 0.48 to 0.91; p=0.011). Purpose Patient-level data from IRONMAN were used to evaluate the effectiveness and cost-utility of FDI compared to usual care for patients with a current or recent HHF, or raised plasma natriuretic peptide concentrations, from a UK National Health Service (NHS) perspective. Methods A cost-utility analysis (CUA) was conducted covering the first year after randomization. Numbers-needed-to-treat (NNTs) were calculated for the primary endpoint censored at 1 year. In the CUA model, patient survival and rates of (re)hospitalization due to HF, other CV events, infections, respiratory conditions, and other non-CV events were modeled based directly on data from the IRONMAN RCT. UK-specific costs were obtained from the national schedule of NHS costs. Quality of life was estimated based on EQ-5D-5L data collected from patients included in the IRONMAN RCT. Results were undiscounted and reported as absolute and incremental costs in 2023 pounds sterling, and quality-adjusted life expectancy in quality-adjusted life years (QALYs). A willingness-to-pay threshold of £20,000 per QALY was adopted to allow calculation of a net monetary benefit (NMB), a summary measure of the overall value of FDI in monetary terms, capturing changes in both cost and QALY outcomes. Results The NNT analysis showed that 9 patients would need to be treated with FDI to avoid one composite primary endpoint event (CV death and HHF) over 1 year. Relative to usual care, FDI was associated with an improvement of 0.01 QALYs per patient over 1 year (0.58 versus 0.57 QALYs). Total average costs per-patient were £1,672 for FDI, versus £1,975 for usual care, leading to a saving of £302 per patient with FDI. The cost of iron procurement was more than offset by reductions in costs of (re)hospitalizations (Figure). FDI was therefore dominant over usual care, yielding an NMB of £483 over 1 year. Conclusions This short-term, within-trial CUA suggests that FDI both improves QALYs and reduces healthcare expenditure versus usual care when administered to patients with HF and iron deficiency in the UK. Iron repletion with FDI may be a prudent allocation of healthcare resources in this patient population.Breakdown of costs

Changes in echocardiographic and analytical parameters after iron replacement in stable heart failure patients. FER-STRAIN study

Abstract Background Iron deficiency replacement with intravenous ferric carboxymaltose (FCM) has demonstrated to improve clinical and prognostic parameters in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Improvement of myocardial contractility is proposed as possible hypothesis and strain could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency. Purpose Evaluate the effect of iron deficiency replacement with FCM in the strain of both ventricles in patients with stable HFrEF. Methods We performed an observational, analytical, longitudinal and prospective study that included 73 patients with stable HFrEF who presented iron deficiency without anemia defined as serum ferritin &amp;lt;100 ug/L or between 100 and 300 ug/L if the transferrin saturation was &amp;lt;20%. They were randomized 2:1 to iron replacement with FCM or control group. A central core lab, blinded to the treatment/control groups performed 3D echocardiograms and strain analysis. Analytical parameters and biomarkers were determined basal and four weeks after the randomization. Results Mean age of the study population was 70 years old, 77% were male, 75% had high blood pressure, 70% dyslipidemia and 41% diabetes. Of the total, 51 patients were assigned to the replacement group and 22 patients to the control group. Mean left ventricular ejection fraction (LVEF) was 33%, without basal differences between both groups. Four weeks after the randomization, a significant improvement of LVEF of 2.47±2.32% (p=0.018) was observed in the replacement group, as well as in the left ventricle global longitudinal strain (LV-GLS) of -0.96±2.08% (p=0.006). In blood tests, a significant improvement of ferritin (130.9±111.98mg/L, p&amp;lt;0.000), hemoglobin (0.3±0.7g/dL, p=0.027) and medium corpuscular volume (1.7±2.16fL, p=0.005), and also an increase of the biomarker myeloperoxidase (40.16±138.36pmol/L, p=0.02) were detected in the treatment group. Nevertheless, these changes were not observed in the control group. Conclusions In patients with stable HFrEF replacement of iron deficiency with FCM is associated with an improvement of myocardial contractility, of LVEF measured by 3D and LV-GLS.Variation of parametersLV-GLS before and after FCM

Improvement of myocardial contractility after iron replacement in stable heart failure patients

Abstract Background Iron deficiency replacement with intravenous ferric carboxymaltose (FCM) has demonstrated to improve clinical and prognostic parameters in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Improvement of myocardial contractility is proposed as possible hypothesis and strain could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency. Purpose Evaluate the effect of iron deficiency replacement with FCM in the strain of both ventricles in patients with stable HFrEF. Methods Observational, analytical, longitudinal and prospective study that included 73 patients with stable HFrEF who presented iron deficiency without anemia defined as serum ferritin &amp;lt;100 ug/L or between 100 and 300 ug/L if the transferrin saturation was &amp;lt;20%. They were randomized 2:1 to iron replacement with FCM or control group. A central core lab, blinded to the treatment/control groups, performed 3D echocardiograms and strain analysis basal and four weeks after the randomization. Results Mean age of the study population was 70 years old, 77% were male, 75% had high blood pressure, 70% dyslipidemia and 41% diabetes. Of the total, 51 patients were assigned to the replacement group and 22 patients to the control group. Mean left ventricular ejection fraction (LVEF) was 33%, without basal differences between both groups. Four weeks after the randomization, a significant improvement of LVEF of 2.47±2.32% (p=0.018) was observed in the replacement group, as well as in the left ventricle global longitudinal strain (LV-GLS) of -0.96±2.08% (p=0.006). Nevertheless, these changes were not observed in the control group. Conclusions In patients with stable HFrEF replacement of iron deficiency with FCM is associated with an improvement of myocardial contractility, of LVEF measured by 3D and LV-GLS.Variation of parametersLV-GLS before and after FCM