Evidence map›Paper›PMID 30779710›Full record

ArticleJCI insight2019

Iron-deficiency anemia reduces cardiac contraction by downregulating RyR2 channels and suppressing SERCA pump activity.

Yu Jin Chung, Antao Luo, Kyung Chan Park, Aminah A Loonat, Samira Lakhal-Littleton, Peter A Robbins, Pawel Swietach

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07277140 (Impact of Iron Deficiency With and Without Anemia on Arrhythmic Events and Resting ECG Abnormalities in Patients Hospitalized With Heart Failure), which is not on this map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07277140 not yet recruitingnot on this mapstarted 2025, after this paper: background citation

Impact of Iron Deficiency With and Without Anemia on Arrhythmic Events and Resting ECG Abnormalities in Patients Hospitalized With Heart Failure

TypeobservationalSponsorAssiut UniversityRan2025 to 2027Enrolled300ConditionsHeart Failure, Iron Deficiency
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

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  18. Iron Deficiency and Deranged Myocardial Energetics in Heart Failure.International journal of environmental research and public health · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 2 countries.

Yu Jin ChungDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Antao LuoDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Kyung Chan ParkDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Aminah A LoonatDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Samira Lakhal-LittletonDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Peter A RobbinsDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Pawel SwietachDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
University of Oxford · GB

Funding

British Heart Foundation FS/12/63/29895British Heart Foundation PG/12/2/29324British Heart Foundation RG/15/9/31534
6 · The paper itself

Abstract

Iron deficiency is present in ~50% of heart failure (HF) patients. Large multicenter trials have shown that treatment of iron deficiency with i.v. iron benefits HF patients, but the underlying mechanisms are not known. To investigate the actions of iron deficiency on the heart, mice were fed an iron-depleted diet, and some received i.v. ferric carboxymaltose (FCM), an iron supplementation used clinically. Iron-deficient animals became anemic and had reduced ventricular ejection fraction measured by magnetic resonance imaging. Ca2+ signaling, a pathway linked to the contractile deficit in failing hearts, was also significantly affected. Ventricular myocytes isolated from iron-deficient animals produced smaller Ca2+ transients from an elevated diastolic baseline but had unchanged sarcoplasmic reticulum (SR) Ca2+ load, trigger L-type Ca2+ current, or cytoplasmic Ca2+ buffering. Reduced fractional release from the SR was due to downregulated RyR2 channels, detected at protein and message levels. The constancy of diastolic SR Ca2+ load is explained by reduced RyR2 permeability in combination with right-shifted SERCA activity due to dephosphorylation of its regulator phospholamban. Supplementing iron levels with FCM restored normal Ca2+ signaling and ejection fraction. Thus, 2 Ca2+-handling proteins previously implicated in HF become functionally impaired in iron-deficiency anemia, but their activity is rescued by i.v. iron supplementation.

Indexed as

Myocardial ContractionAdministration, IntravenousAnemia, Iron-DeficiencyAnimalsCalciumCalcium-Binding ProteinsCells, CulturedDisease Models, AnimalDown-RegulationFerric CompoundsHeart FailureHumansIronMagnetic Resonance ImagingMaleMaltoseCalciumCalcium-Binding Proteinsferric carboxymaltoseFerric CompoundsIronMaltosePhospholambanryanodine receptor 2. mouseRyanodine Receptor Calcium Release ChannelSarcoplasmic Reticulum Calcium-Transporting ATPasesCalcium signalingCardiologyExcitation contraction couplingHeart failure

Identifiers

PMID30779710
PMCPMC6483648
OpenAlexW2915455414

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.