Iron-deficiency, Valvular Heart Disease
Conditions
Keywords
ferric carboxymaltose, mitochondrial metabolism, cardiomyocyte
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.
Detailed description
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. Iron deficiency has been shown to be responsible for fatigue and muscle weakness, regardless of the presence of an anemia. Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients, with a prevalence increasing with NYHA class level, and association with mortality. Iron therapy improves the symptoms of heart failure patients and the 6-minute walk test, even in the absence of anemia. 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. There is therefore an opportunity to further explore the impact of iron deficiency and its treatment on mitochondrial energy metabolism of cardiomyocytes. We hypothesize that the activity of the mitochondrial complex I is decreased in the presence of iron deficiency and that the iron treatment corrects this decrease. 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.
Interventions
PROCEDUREmyocardial biopsy
Myocardial biopsy (after opening cardiac cavities under general anesthesia for valvular surgery) for mitochondrial metabolism analyses.
PROCEDUREsternal bone marrow biopsy
Sternal bone marrow biopsy (after sternal opening under general anesthesia for valvular surgery) for the quantification of iron stores
BIOLOGICALblood 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
University Hospital, Angers
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Patients that must be operated for a valvular heart surgery (aortic or mitral) scheduled in the month which follows the anaesthesia consultation (visit of inclusion) * The preoperative iron status is known * Patient signed informed consent
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of the maximal activity of the mitochondrial complex I using spectrometry | At the time of the myocardial biopsy | Measure of the maximal complex I activity using spectrometry on isolated mitochondria from myocardial biopsy. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
France
Outcome results
None listed