Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia.
BACKGROUND
Heart failure related to cardiac siderosis remains a major cause of death in transfusion dependent anaemias. Replacement fibrosis has been reported as causative of heart failure in siderotic cardiomyopathy in historical reports, but these findings do not accord with the reversible nature of siderotic heart failure achievable with intensive iron chelation.


METHODS
Ten whole human hearts (9 beta-thalassemia major, 1 sideroblastic anaemia) were examined for iron loading and fibrosis (replacement and interstitial). Five had died from heart failure, 4 had cardiac transplantation for heart failure, and 1 had no heart failure (death from a stroke). Heart samples iron content was measured using atomic emission spectroscopy. Interstitial fibrosis was quantified by computer using picrosirius red (PSR) staining and expressed as collagen volume fraction (CVF) with normal value for left ventricle <3%.


RESULTS
The 9 hearts affected by heart failure had severe iron loading with very low T2* of 5.0 ± 2.0 ms (iron concentration 8.5 ± 7.0 mg/g dw) and diffuse granular myocardial iron deposition. In none of the 10 hearts was significant macroscopic replacement fibrosis present. In only 2 hearts was interstitial fibrosis present, but with low CVF: in one patient with no cardiac siderosis (death by stroke, CVF 5.9%) and in a heart failure patient (CVF 2%). In the remaining 8 patients, no interstitial fibrosis was seen despite all having severe cardiac siderosis and heart failure (CVF 1.86% ±0.87%).


CONCLUSIONS
Replacement cardiac fibrosis was not seen in the 9 post-mortem hearts from patients with severe cardiac siderosis and heart failure leading to death or transplantation, which contrasts markedly to historical reports. Minor interstitial fibrosis was also unusual and very limited in extent. These findings accord with the potential for reversibility of heart failure seen in iron overload cardiomyopathy.


BACKGROUND
ClinicalTrials.gov Identifier: NCT00520559.
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK.|National Heart and Lung Institute, Imperial College, London, UK.
Paul
P
Kirk
National Heart and Lung Institute, Imperial College, London, UK.|CRY Centre for Cardiac Pathology, Royal Brompton Hospital, London, UK.
Mary
M
Sheppard
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK.|National Heart and Lung Institute, Imperial College, London, UK.
John-Paul
JP
Carpenter
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK.|National Heart and Lung Institute, Imperial College, London, UK.
Lisa
L
Anderson
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK.|National Heart and Lung Institute, Imperial College, London, UK.
Taigang
T
He
University of Western Australia, Perth, Australia.
Tim
T
St Pierre
Ospedale Microcitemico, Cagliari, Italy.
Renzo
R
Galanello
Ospedale Microcitemico, Cagliari, Italy.
Gualtiero
G
Catani
Children's Hospital, Los Angeles, USA.
John
J
Wood
Mahidol University, Bangkok, Thailand.
Suthat
S
Fucharoen
The Hatter Cardiovascular Institute, University College Hospital, London, UK.
John B
JB
Porter
The Hatter Cardiovascular Institute, University College Hospital, London, UK.
J Malcolm
JM
Walker
Centro della Microcitemia, Ospedale Galliera, Genoa, Italy.
Gian Luca
GL
Forni
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK. Dj.pennell@rbht.nhs.uk.|National Heart and Lung Institute, Imperial College, London, UK. Dj.pennell@rbht.nhs.uk.
Dudley J
DJ
Pennell
D000293:Adolescent; D000328:Adult; D001344:Autopsy; D001391:Azo Compounds / Q000737:chemistry; D001803:Blood Transfusion / Q000401:mortality; D009202:Cardiomyopathies / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002423:Cause of Death; D002648:Child; D003094:Collagen / Q000032:analysis; D004396:Coloring Agents / Q000737:chemistry; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016027:Heart Transplantation; D006486:Hemosiderosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007501:Iron / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology*; D012720:Severity of Illness Index; D013054:Spectrophotometry, Atomic; D013194:Staining and Labeling / Q000379:methods; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*
D001391:Azo Compounds; D004396:Coloring Agents; C009798:C.I. direct red 80; D003094:Collagen; D007501:Iron
Cardiac MR; Cardiac siderosis; Fibrosis; Heart; Histopathology; Iron; Thalassaemia