Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-25T14:44:17.193Z Has data issue: false hasContentIssue false
  • English
  • Français

Poor efficacy of oral iron replacement therapy in pediatric patients with heart failure

Published online by Cambridge University Press:  11 October 2021

Kriti Puri Open the ORCID record for Kriti Puri [Opens in a new window] ,
Joseph A. Spinner ,
Jacquelyn M. Powers ,
Susan W. Denfield ,
Hari P. Tunuguntla ,
Swati Choudhry ,
William J. Dreyer  and
Jack F. Price
Kriti Puri
Affiliation:
Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Joseph A. Spinner
Affiliation:
Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Jacquelyn M. Powers
Affiliation:
Section of Hematology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Susan W. Denfield
Affiliation:
Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Hari P. Tunuguntla
Affiliation:
Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Swati Choudhry
Affiliation:
Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
William J. Dreyer
Affiliation:
Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Jack F. Price*
Affiliation:
Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
*
Author for correspondence: Jack F. Price, MD, Professor of Pediatrics, Lille Frank Abercrombie Section of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, 6651 Main Street, Legacy Tower MC E1920, Houston, TX77030, USA. Tel: 832-826-5048; Fax: 832-825-5899. E-mail: jfprice@texaschildrens.org
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

Paediatric heart failureiron deficiencyiron replacement therapy
Type
Original Article
Information
Cardiology in the Young , Volume 32 , Issue 8 , August 2022 , pp. 1302 - 1309
Check for updates
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Presentations: Poster presentation at the annual meeting of the International Society of Heart and Lung Transplantation in April 2020 (virtual due to COVID-19).

References

Powers, JM, Mahoney, DH. Iron Deficiency in Infants and Children <12 Years: Screening, Prevention, Clinical Manifestations, and Diagnosis. UpToDate, Waltham, MA, 2020.Google Scholar
Baker, RD, Greer, FR. Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics 2010; 126: 1040–1050. DOI 10.1542/peds.2010-2576.CrossRefGoogle Scholar
Brotanek, JM, Gosz, J, Weitzman, M, et al. Iron deficiency in early childhood in the United States: risk factors and racial/ethnic disparities. Pediatrics 2007; 120: 568–575.CrossRefGoogle ScholarPubMed
Goyal, A, Zheng, Y, Albenberg, LG, et al. Anemia in children with inflammatory bowel disease: a position paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2020; 71: 563–582.CrossRefGoogle ScholarPubMed
Baracco, R, Saadeh, S, Valentini, R, et al. Iron deficiency in children with early chronic kidney disease. Pediatr Nephrol 2011; 26: 2077–2080.CrossRefGoogle ScholarPubMed
Puri, K, Price, JF, Spinner, JA, et al. Iron deficiency is associated with adverse outcomes in pediatric heart failure. J Pediatr 2020; 216: 58–66.e1.CrossRefGoogle ScholarPubMed
Higgins, D, Otero, J, Jefferis Kirk, C, et al. Iron laboratory studies in pediatric patients with heart failure from dilated cardiomyopathy. Am J Cardiol 2017; 120: 2049–2055.CrossRefGoogle ScholarPubMed
von Haehling, S, Ebner, N, Evertz, R, et al. Iron deficiency in heart failure: an overview. JACC Heart Fail 2019; 7: 36–46.CrossRefGoogle ScholarPubMed
Lewis, GD, Malhotra, R, Hernandez, AF, et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: the IRONOUT HF randomized clinical trial. JAMA 2017; 317: 1958–1966, Published correction appears in JAMA 2017;317: 2453.CrossRefGoogle ScholarPubMed
Ponikowski, P, van Veldhuisen, DJ, Comin-Colet, J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency†. Eur Heart J 2015; 36: 657–668.CrossRefGoogle ScholarPubMed
van Veldhuisen, DJ, Ponikowski, P, van der Meer, P, et al. Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation 2017; 136: 1374–1383.CrossRefGoogle ScholarPubMed
Puri, K, Jeewa, A, Adachi, I, et al. Prevalence of anemia and iron deficiency in pediatric patients on ventricular assist devices. ASAIO J 2018; 64: 795–801.CrossRefGoogle ScholarPubMed
WHO (WHO/NMH/NHD/MNM/11.1).Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and mineral nutrition information system. World Health Organization, Geneva, 2011. Retrieved December 1, 2020, from https://www.who.int/vmnis/indicators/haemoglobin/en/ Google Scholar
WHO/NHD/01.3. Iron deficiency anaemia: assessment, prevention, and control. A guide for programme managers, Table A5. Retrieved December 1, 2020, fromhttp://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf Google Scholar
Ross, R. The ross classification for heart failure in children after 25 years: a review and an age-stratified revision. Pediatr Cardiol 2012; 33: 1295–1300.CrossRefGoogle Scholar
Centers for Disease Control and Prevention. Retrieved April 21, 2021, fromhttps://www.cdc.gov/growthcharts/clinical_charts.htm Google Scholar
Klip, IT, Comin-Colet, J, Voors, AA, et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 2013; 165: 575–582.e3.CrossRefGoogle ScholarPubMed
Anker, SD, Kirwan, BA, van Veldhuisen, DJ, et al. Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis. Eur J Heart Fail 2018; 20: 125–133.CrossRefGoogle ScholarPubMed
KDIGO. KDIGO clinical practice guideline for anemia in chronic kidney disease, 2012. Retrieved April 1, 2021, fromhttps://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-Anemia-Guideline-English.pdf Google Scholar
Lasa, JJ, Gaies, M, Bush, L, et al. Epidemiology and outcomes of acute decompensated heart failure in children. Circ Heart Fail 2020; 13: e006101.CrossRefGoogle ScholarPubMed
Alvarez, JA, Orav, EJ, Wilkinson, JD, et al. Pediatric Cardiomyopathy Registry Investigators. Competing risks for death and cardiac transplantation in children with dilated cardiomyopathy: results from the pediatric cardiomyopathy registry. Circulation 2011; 124: 814–823.CrossRefGoogle ScholarPubMed
Singh, RK, Canter, CE, Shi, L, et al. Survival without transplantation among children with dilated cardiomyopathy. J Am Coll Cardiol 2017; 70: 2663–2673.CrossRefGoogle ScholarPubMed
Alexander, PM, Daubeney, PE, Nugent, AW, et al. National Australian Childhood Cardiomyopathy Study. Long-term outcomes of dilated cardiomyopathy diagnosed during childhood: results from a national population-based study of childhood cardiomyopathy. Circulation 2013; 128: 2039–2046.CrossRefGoogle ScholarPubMed
Rossano, JW, Kim, JJ, Decker, JA, et al. Prevalence, morbidity, and mortality of heart failure-related hospitalizations in children in the United States: a population-based study. J Card Fail 2012; 18: 459–470.CrossRefGoogle ScholarPubMed
Hoes, MF, Grote Beverborg, N, Kijlstra, JD, et al. Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function. Eur J Heart Fail 2018; 20: 910–919. DOI 10.1002/ejhf.1154.CrossRefGoogle ScholarPubMed
Charles-Edwards, G, Amaral, N, Sleigh, A, et al. Effect of iron isomaltoside on skeletal muscle energetics in patients with chronic heart failure and iron deficiency. Circulation 2019; 139: 2386–2398.CrossRefGoogle ScholarPubMed
Yancy, CW, Jessup, M, Bozkurt, B, et al. ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136: e137–e161.CrossRefGoogle Scholar
Powers, JM. Iron Requirements and Iron Deficiency in Adolescents. UpToDate, Waltham, MA, 2020.Google Scholar
Ganz, T. Hepcidin and iron regulation, 10 years later. Blood 2011; 117: 4425–4433. DOI 10.1182/blood-2011-01-258467.CrossRefGoogle ScholarPubMed
Powers, JM, Nagel, M, Raphael, JL, Mahoney, DH, Buchanan, GR, Thompson, DI. Barriers to and facilitators of iron therapy in children with iron deficiency anemia. J Pediatr 2020; 219: 202–208. DOI 10.1016/j.jpeds.2019.12.040.CrossRefGoogle ScholarPubMed
Powers, JM, Daniel, CL, McCavit, TL, Buchanan, GR. Deficiencies in the management of iron deficiency anemia during childhood. Pediatr Blood Cancer 2016; 63: 743–745. DOI 10.1002/pbc.25861.CrossRefGoogle ScholarPubMed