Estimation of Myocardial Iron Overload by 3 Tesla MRI in HFE Hereditary Haemochromatosis

Estimation of Myocardial Iron Overload by 3 Tesla MRI and Cardiac Functional Consequences in Patients With HFE Hereditary Haemochromatosis. Pilot Study

Hereditary haemochromatosis (HHC) is a frequent disease in Brittany (5 to 7‰), responsible first for biological disorder in blood iron parameters and minor clinical disorders, before evolving to potential life-threatening consequences such as diabetes, liver cirrhosis and congestive heart failure.

The improvement of screening and treatments made those severe affections rare enough not to evaluate myocardial iron overload a systematic part of the starting check-up. Nonetheless this myocardial iron overload might have severe implications on cardiac function on a long term basis.

A single trial was conducted on limited number of patients with 1.5 Tesla MRI, which showed a myocardial iron overload (defined by a myocardium T2* value <20ms) in 19% of the subjects.

The main objective of this study is to precisely estimate cardiac iron overload in treatment naive patients with newly diagnosed HFE hereditary haemochromatosis with a 3 Tesla MRI, more sensitive than the 1.5 Tesla one, in order to later appreciate its correlation with cardiac morbidity in HHC.

Since the wide use of phlebotomy was implemented the incidence of congestive heart failure in HHC became quite low. As such, the interest towards the initial diagnosis and cardiological follow-up has been lesser. A subclinical myocardial iron overload can nevertheless exist and eventually lead to functional consequences in the medium and long term if neglected, even evolve into heart failure and preserved ejection fraction.

The expected aftermath of this study is :

• The estimation of the frequency of myocardial iron overload measured by 3 Tesla MRI in patient with HFE hereditary haemochromatosis;
• The assessment of its consequences on heart function;
• The appreciation of a cardiological assessment strategy in patients with HFE hereditary haemochromatosis.

Inclusion Criteria:

Patients :

• Adults older than 18 ;
• Newly diagnosed with HFE hereditary haemochromatosis by genetic testing (homozygous for the C283Y mutation on HFE gene);
• Treatment-naive;
• Showing a ferritin level higher than 200µg/l for women and higher than 300µg/L for men;
• Affiliated to French Social Security;
• Having given a written informed consent.

Healthy volunteers:

• Adults older than 18;

• Presenting all the following criterions:

  • Normal cardiovascular physical examination: no signs of cardiac insufficiency, no pathological cardiac murmur, normal EKG (regular sinus rhythm, no high degree AV nor ventricular blocks, no rhythm anomaly),
  • Body Mass Index <27 kg/m²,
  • Normal routine blood biology (blood count, MCV, serum iron, ferritin, transferrin saturation);

• Affiliated to French Social Security;

• Having given a written informed consent.

Exclusion Criteria:

Patients :

MRI-related criterions :

• Cardiac pacemaker or implanted defibrillator ;
• Non MRI-compatible prosthetic cardiac valve;
• Non MRI-compatible clips/stents/coils/etc.;
• Cochlear implant;
• Peripheral or neuronal stimulator;
• Intra-ocular or brain metallic foreign bodies , foreign body in the eyes' vicinity, shrapnel or firearm wound;
• Less than 4 weeks-old stents, less than 6 weeks-old osteosynthesis materials;
• Claustrophobia;
• Pumps, tattoos, permanent makeup, intrauterine device, patches;
• Non-removable metallic or magnetic material in the vicinity of the analysed field.

Other criterions :

• Haemodynamic instability / Acute respiratory insufficiency / Altered general status / Need for continuous monitoring incompatible wih MRI confines;
• Pregnancy, breast feeding;
• History of blood transfusion or iron supplementation;
• Blood donation in the last 3 months;
• Infection in the 7 days prior to the first visit;
• Stay in altitude (>1500m) in the past 2 months;
• Adults under legal protective regimen or deprived of liberty.

Healthy volunteers

• Alcohol abuse (>20g per day for women, >30g per day for men);
• Active tobacco intoxication or smoking cessation in the 6 last months;
• Personal cardiovascular medical history;
• Cardiovascular functional signs.