Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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%).
Conclusion:
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.
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%).
Conclusion:
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.
Date Issued
2017-03-27
Date Acceptance
2017-03-01
Citation
JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, 2017, 19 (1)
ISSN
1097-6647
Publisher
BIOMED CENTRAL LTD
Journal / Book Title
JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
Volume
19
Issue
1
Copyright Statement
© 2017 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor
National Institutes of Health
British Heart Foundation
Royal Brompton & Harefield NHS Foundation Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000397731100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
5 R01 DK066084-02
PG/09/074/27961
Dr Harith Alam
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Radiology, Nuclear Medicine & Medical Imaging
Cardiovascular System & Cardiology
Thalassaemia
Cardiac siderosis
Cardiac MR
Iron
Heart
Fibrosis
Histopathology
CARDIOVASCULAR MAGNETIC-RESONANCE
BETA-THALASSEMIA MAJOR
HYPERTENSIVE HEART-DISEASE
HYPERTROPHIC CARDIOMYOPATHY
MYOCARDIAL FIBROSIS
CHELATION-THERAPY
OVERLOAD
QUANTIFICATION
T2-ASTERISK
COLLAGEN
Nuclear Medicine & Medical Imaging
1102 Cardiovascular Medicine And Haematology
Publication Status
Published
Article Number
ARTN 36