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

Rennes University Hospital

Status: Completed

Conditions: HFE-Associated Hereditary Hemochromatosis; Myocardial Iron Overload

Treatments: Device: Echocardiography at rest; Biological: Urinary pregnancy test; Biological: Iron and cardiac markers; Biological: Pregnancy test; Device: Electrocardiogram (EKG); Device: 3Tesla cardiac MRI; Device: 3Tesla abdominal MRI

Study type: Interventional

Funder types: Other

Identifiers

NCT02099214

2013-A01843-42

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

66 participants in 2 patient groups

Patients with HFE hereditary haemochromatosis

Experimental group

Description:

The patients (40) will undergo a medical examination in order to analyse their medical history, cardiovascular parameters and check inclusion and non-inclusion criterions. Then will be performed : * An electrocardiogram * Blood tests : iron and cardiac markers (serum iron, serum transferrin, transferrin saturation, serum ferritin, NT-proBNP), beta-hCG if needed, serum bank * A 3Tesla cardiac MRI repeated twice (in order to respect the reproducibility criterion) * A 3Tesla abdominal MRI * An echocardiography at rest.

Treatment:

Biological: Pregnancy test

Biological: Iron and cardiac markers

Device: 3Tesla cardiac MRI

Device: 3Tesla abdominal MRI

Device: Echocardiography at rest

Device: Electrocardiogram (EKG)

Healthy volunteers

Experimental group

Description:

The healthy volunteers (10 men and 10 women) will undergo : * A urinary pregnancy test (if applicable) * A 3Tesla cardiac MRI repeated twice (in order to respect the reproducibility criterion) * An echocardiography at rest.

Treatment:

Device: 3Tesla cardiac MRI

Biological: Urinary pregnancy test

Device: Echocardiography at rest