Evidence mapPaperPMID 40916716Full record

Trial reportEuropean journal of heart failure2025

Ferric derisomaltose augments intrinsic skeletal muscle electron transport chain activity in heart failure: A FERRIC-HF II molecular substudy.

Mohamad F Barakat, Nelson Amaral, Daniel Brayson, George Amin-Youssef, Huda Abu-Own, Salma Ayis, Francesco Papalia, Fadi Jouhra, Adam Nabeebaccus, Mark Monaghan and 7 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in European journal of heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

17 authors.

Mohamad F Barakat *School of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Nelson Amaral *School of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Daniel BraysonSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
George Amin-YoussefKing's College Hospital NHS Foundation Trust, London, UK.
Huda Abu-OwnSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Salma AyisSchool of Population Health and Environmental Sciences, King's College, London, UK.
Francesco PapaliaSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Fadi JouhraSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Adam NabeebaccusSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Mark MonaghanSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Gerry Carr-WhiteSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Alison SleighWolfson Brain Imaging Centre, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Geoffrey Charles-EdwardsSchool of Imaging Sciences and Biomedical Engineering, King's College, London, UK.
Ajay M ShahSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Graham J KempLiverpool Magnetic Resonance Imaging Centre and Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Andrew J MurrayDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Darlington O OkonkoSchool of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.

Funding

British Heart Foundation FS/14/77/30913
6 · The paper itself

Abstract

aimsSkeletal muscle energetic augmentation might be a mechanism via which intravenous iron improves symptoms in heart failure, but no direct measurement of intrinsic mitochondrial function has been performed to support this notion. This molecular substudy of the FERRIC-HF II trial tested the hypothesis that ferric derisomaltose (FDI) would improve electron transport chain activity, given its high dependence on iron-sulfur clusters which facilitate electron transfer during oxidative phosphorylation. METHODS AND

resultsVastus lateralis skeletal muscle biopsies were taken before and 2 weeks after randomization. Mitochondrial complex I, II, and I&II respiration were quantified with respirometry of permeabilized fresh skeletal muscle biopsies. Net respiratory capacities, reflecting respiration that is truly available for adenosine triphosphate generation, were calculated by subtracting non-phosphorylating LEAK respiration. Complex I-V and myoglobin protein levels, and skeletal muscle fibre type composition were assayed. Patients randomised to FDI (n = 21) or placebo (n = 19) were similar (age 66 ± 13 years, 73% men, left ventricular ejection fraction 37 ± 8%, 48% New York Heart Association class III, 50% diabetic). After 2 weeks, total complex I-linked respiration (0.33 [interquartile range 0.24-0.37] vs. 0.19 [0.06-0.27] nmol/min/mg, p = 0.03) and net complex I-linked respiration (0.21 [0.16-0.24] vs. 0.11 [0.04-0.16] nmol/min/mg, p = 0.01) were higher in patients allocated to FDI. There was no intergroup difference in other respiratory states, in mitochondrial abundance as reflected by complex I-V protein levels, and in skeletal muscle myoglobin and oxidative fibre type content.

conclusionsIron repletion induces an early, selective, and potentially direct enhancement of mitochondrial complex I-dependent respiration in the skeletal muscle of heart failure patients. This could be harnessed to optimize repletion protocols to maximize patient benefits.

Indexed as

Ferric CompoundsHeart FailureMaltoseMuscle, SkeletalAgedBiopsyElectron TransportElectron Transport Complex IElectron Transport Complex IIFemaleHumansMaleMiddle AgedMitochondria, MuscleOxidative PhosphorylationElectron Transport Complex IElectron Transport Complex IIFerric CompoundsMaltoseEnergeticsHeart failureIronMitochondriaMuscleRespirometry

Identifiers

PMID40916716
PMCPMC12765364

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.