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

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

Interventions

PROCEDURE

myocardial biopsy

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

PROCEDURE

sternal bone marrow biopsy

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

BIOLOGICAL

blood sample

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)

Sponsors & Collaborators

• University Hospital, Angers

  lead OTHER_GOV

Principal Investigators

• RINEAU Emmanuel, MD · University Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-01-23

Primary Completion

2020-09-07

Completion

2020-09-07

Countries

• France

Study Locations