Impact of Iron Deficiency and Its Correction on Mitochondrial Metabolism of the Cardiomyocyte (MitoCardioFer)

NCT03541213 | Completed

• 1 other identifier: 2017-A00904-49
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Iron is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and iron-sulfur proteins of the respiratory chain. Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients. Iron therapy improves symptoms and physical performances of heart failure patients, even in the absence of anemia. As a result, the correction of iron deficiency is now proposed as one of the therapies for heart failure. However, the pathophysiology of the association between cardiac dysfunction and iron deficiency is still poorly understood. The investigators previously developed a mouse model of iron deficiency without anemia, in which the investigators observed impaired physical performances, a decrease of left ventricular ejection fraction, and a decrease in mitochondrial complex I activity. These abnormalities were normalized after iron injection. These animal data suggest that iron deficiency is responsible for left ventricular dysfunction secondary to mitochondrial I complex abnormalities, and that iron therapy corrects them. Iron deficiency is very common in the preoperative period of cardiac surgery, affecting 40 to 50% of patients. During this surgery, it is possible to perform a myocardial biopsy without risk to the patient. The purpose of this study is to verify in patients requiring valvular heart surgery, if iron deficiency is responsible for a decrease in mitochondrial complex I activity and a decrease in cardiac function during the perioperative period, and to verify whether iron treatment improves these abnormalities.

Conditions

Iron-deficiency; Valvular Heart Disease

Keywords

ferric carboxymaltose; mitochondrial metabolism; cardiomyocyte

Outcome Measures

Primary Outcomes (1)

• Measure of the maximal activity of the mitochondrial complex I using spectrometry

  Measure of the maximal complex I activity using spectrometry on isolated mitochondria from myocardial biopsy.

  At the time of the myocardial biopsy

Secondary Outcomes (5)

• Measure of the maximal activity of the others mitochondrial complexes using spectrometry (Complexes II, III and IV)

  At the time of the myocardial biopsy

• Quantification of the number of mitochondria per cardiomyocyte using Western-Blot

  At the time of the myocardial biopsy

• Quantification and analysis of the complex I assemblage using BN-PAGE

  At the time of the myocardial biopsy

• Quantification of myoglobin in cardiomyocytes using Western-Blot

  At the time of the myocardial biopsy

• Cardiac function using echocardiography in pre-, intra- and post-operative periods

  At the time of the myocardial biopsy

Study Arms (3)

Control group

OTHER

Patients with no iron deficiency prior to inclusion and who did not receive intravenous iron prior to inclusion. Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms)

Procedure: myocardial biopsy; Procedure: sternal bone marrow biopsy; Biological: blood sample

Iron deficiency group

OTHER

Patients with iron deficiency who did not receive intravenous iron prior to inclusion. Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms)

Procedure: myocardial biopsy; Procedure: sternal bone marrow biopsy; Biological: blood sample

Iron treated group

OTHER

Patients with iron deficiency who received intravenous iron prior to inclusion (greater than or equal to 1 g ferric carboxymaltose). Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms)

Procedure: myocardial biopsy; Procedure: sternal bone marrow biopsy; Biological: blood sample

Interventions

myocardial biopsy PROCEDURE

Myocardial biopsy (after opening cardiac cavities under general anesthesia for valvular surgery) for mitochondrial metabolism analyses.

Control group; Iron deficiency group; Iron treated group

sternal bone marrow biopsy PROCEDURE

Sternal bone marrow biopsy (after sternal opening under general anesthesia for valvular surgery) for the quantification of iron stores

Control group; Iron deficiency group; Iron treated group

blood sample BIOLOGICAL

blood sample (under general anesthesia for valvular surgery, using the arterial catheter already in place) for hepcidin quantification (hormone not dosed in the usual martial assessment)

Control group; Iron deficiency group; Iron treated group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• The preoperative iron status is known
• Patient signed informed consent

You may not qualify if:

• Refusal of the patient to participate
• Refusal of the surgeon or the anaesthetist who are responsible of patient management
• Patients with a known iron overload (for example : hemochromatosis)
• Counter-indication in the realization of a sternal bone marrow biopsy or myocardial biopsy (for example : endocarditis)
• Adult patients under legal guardianship
• Pregnancy

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (1)

CHU Angers - DEPARTEMENT D'ANESTHESIE REANIMATION

Angers, 49100, France

Location

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Heart Valve Diseases

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• RINEAU Emmanuel, MD

  University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 3 groups will be performed depending on the presence or absence of a pre-operative iron deficiency and whether they had an iron treatment preoperatively (before their inclusion in the study). However, patient management will not be different in the different groups from their inclusion in the study. Therefore we can consider that there is a single interventional group.

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: May 30, 2018
• Study Start: January 23, 2019
• Primary Completion: September 7, 2020
• Study Completion: September 7, 2020
• Last Updated: July 29, 2022

Record last verified: 2022-07

Locations

FR (1)