title: On myocardial siderosis and left ventricular dysfunction in hemochromatosis.
abstract: BACKGROUND
  Chronically increased intestinal iron uptake in genetic hemochromatosis (HC) may cause organ failure. Whilst iron loading from blood transfusions may cause dilated cardiomyopathy in conditions such as thalassemia, the in-vivo prevalence of myocardial siderosis in HC is unclear, and its relation to left ventricular (LV) dysfunction is controversial. Most previous data on myocardial siderosis in HC has come from post-mortem studies.
  
  
  METHODS
  Cardiovascular magnetic resonance (CMR) was performed at first presentation of 41 HC patients (58.9 ± 14.1 years) to measure myocardial iron and left ventricular (LV) ejection fraction (EF).
  
  
  RESULTS
  In 31 patients (genetically confirmed HFE-HC), the HFE genotype was C282Y/C282Y (n = 30) and C282Y/H63D (n = 1). Patients with other genotypes (n = 10) were labeled genetically unconfirmed HC. Of the genetically confirmed HFE-HC patients, 6 (19%) had myocardial siderosis (T2* <20 ms). Of these, 5 (83%) had heart failure and reduced LVEF which was correlated to the severity of siderosis (R2 0.57, p = 0.049). Two patients had follow-up scans and both had marked improvements in T2* and LVEF following venesection. Myocardial siderosis was present in 6/18 (33%) of patients with presenting ferritin ≥ 1000 μg/L at diagnosis but in 0/13 (0%) patients with ferritin <1000 μg/L (p = 0.028). Overall however, the relation between myocardial siderosis and ferritin was weak (R2 0.20, p = 0.011). In the 10 genetically unconfirmed HC patients, 1 patient had mild myocardial siderosis but normal EF. Of all 31 patients, 4 had low LVEF from other identifiable causes without myocardial siderosis.
  
  
  CONCLUSIONS
  Myocardial siderosis was present in 33% of newly presenting genetically confirmed HFE-HC patients with ferritin >1000 μg/L, and was the commonest cause of reduced LVEF. Heart failure due to myocardial siderosis was only found in these HFE-HC patients, and was reversible with venesection. Myocardial iron was normal in patients with other causes of LV dysfunction.
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Carpenter
authors.forename: Agata E
authors.initials: AE
authors.lastname: Grasso
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Farrukh
authors.initials: F
authors.lastname: Shah
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D006432:Hemochromatosis / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D000071020:Hemochromatosis Protein; D006486:Hemosiderosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D018962:Phlebotomy; D011446:Prospective Studies; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins