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Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia.

ABSTRACT: 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.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%.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%).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.ClinicalTrials.gov Identifier: NCT00520559.

SUBMITTER: Kirk P

PROVIDER: S-EPMC5367003 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia.

Kirk Paul P Sheppard Mary M Carpenter John-Paul JP Anderson Lisa L He Taigang T St Pierre Tim T Galanello Renzo R Catani Gualtiero G Wood John J Fucharoen Suthat S Porter John B JB Walker J Malcolm JM Forni Gian Luca GL Pennell Dudley J DJ

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 20170327 1

<h4>Background</h4>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.<h4>Methods</h4>Ten whole human hearts (9 beta-thalassemia major, 1 sideroblastic anaemia) were examined for iron loading an ...[more]

PMID: 28343449

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Project description:BackgroundIron overload cardiomyopathy remains the major cause of death in patients with transfusion-dependent thalassemia. Cardiac T2* magnetic resonance imaging is costly yet effective in detecting cardiac iron accumulation in the heart. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and is depressed in cases of thalassemia. We evaluated whether HRV could be used as an indicator for early identification of cardiac iron deposition.MethodsOne hundred and one patients with transfusion-dependent thalassemia were enrolled in this study. The correlation between recorded HRV and hemoglobin, non-transferrin bound iron (NTBI), serum ferritin and cardiac T2* were evaluated.ResultsThe median age was 18 years (range 8-59 years). The patient group with a 5-year mean serum ferritin >5,000 ng/mL included significantly more homozygous ?-thalassemia and splenectomized patients, had lower hemoglobin levels, and had more cardiac iron deposit than all other groups. Anemia strongly influenced all domains of HRV. After adjusting for anemia, neither serum ferritin nor NTBI impacted the HRV. However cardiac T2* was an independent predictor of HRV, even after adjusting for anemia. For receiver operative characteristic (ROC) curve analysis of cardiac T2* ?20 ms, only mean ferritin in the last 12 months and the average of the standard deviation of all R-R intervals for all five-minute segments in the 24-hour recording were predictors for cardiac T2* ?20 ms, with area under the ROC curve of 0.961 (p<0.0001) and 0.701 (p = 0.05), respectively.ConclusionsHemoglobin and cardiac T2* as significant predictors for HRV indicate that anemia and cardiac iron deposition result in cardiac autonomic imbalance. The mean ferritin in the last 12 months could be useful as the best indicator for further evaluation of cardiac risk. The ability of serum ferritin to predict cardiac risk is stronger than observed in other thalassemia cohorts. HRV might be a stronger predictor of cardiac iron in study populations with lower somatic iron burdens and greater prevalence of cardiac iron deposition.

Project description:Simple Summary In European Union abattoirs, the safety of meat is dependent on the favorable opinion from an official veterinarian, in accordance with the current legislation. From this perspective, the feedback generated from the ante-mortem visit and the post-mortem inspection can be investigated to control the health and welfare conditions of the animals in the pre-slaughter phases. From this perspective, we evaluated the ante-mortem and post-mortem inspection outcomes of slaughtered pigs in northern Albania and correlated the results in order to gain insight into the conditions and injuries of pigs slaughtered outside the European context and to extend knowledge on the possible relationship between ante-mortem and post-mortem relief. Dyspnea and tail, skin, and ear lesions were the most frequently observed conditions before slaughter, while pleuritis, pneumonia, liver alterations, white spots on the liver, and pericarditis were the most frequent lesions after slaughter. A significant increase in the total number of post-mortem findings was also observed as the number of ante-mortem findings increased. Overall, the prevalence of the findings observed in this study falls within the broad range of the data in the literature, but additional information should be collected during meat inspection so as to better understand the relationship between ante- and post-mortem outcomes. Abstract In June 2014, Albania was granted EU candidate status, thus starting a process of compliance with the membership criteria. In this context, a modern meat inspection approach in line with the European legislation was applied to a pig slaughterhouse in northern Albania in order to investigate the ante-mortem (AM) and post-mortem (PM) conditions and the relationship between these findings. For this purpose, 3930 pigs divided into 35 batches were evaluated over a 3-month period. The most frequent AM conditions recorded were tail lesions and dyspnea (9.1%), followed by skin (8.9%) and ear lesions (8.5%), while in the PM inspections, pleuritis was the most frequently observed condition (10.2%), followed by pneumonia (8.5%), liver alterations (5.7%), milk spot liver (3.8%), and pericarditis (3.3%). With the exception of liver alterations, the other PM lesions mentioned were positively associated with lesions on the ears (OR = 1.036; p < 0.001) and skin (OR = 1.026; p = 0.011) and dyspnea (OR = 1.021; p = 0.005), confirming the link between these variables and the health and welfare conditions of pigs on farms. Overall, the evidence that emerged from this Albanian slaughterhouse can be considered in line with other European contexts, especially in light of the considerable variability in the data present in the literature.

Project description:Introduction:The burden of iron deficiency anaemia during pregnancy and post-partum continues to remain high especially in India. Challenges to treatment include gastrointestinal side effects and non compliance to oral iron therapy. Newer parenteral formulations need to be explored as alternatives. Methods:Meta-analysis of randomized controlled trials published between years 2011 and 2018 comparing anaemic pregnant and post-partum women treated with intravenous iron sucrose versus oral iron was performed. The primary outcomes were mean maternal haemoglobin, serum ferritin and haematocrit at the end of 1st, 2nd, 4th and 6th weeks and comparison of adverse effects. Results:Eighteen studies including 1633 antenatal women were randomly assigned to intravenous iron sucrose (n?=?821) or oral iron [ferrous sulphate, ferrous ascorbate or fumarate] group (n?=?812) in ten trials . Another eight studies compared iron sucrose infusion with oral iron in 713 post-partum women who were randomly assigned to intravenous iron sucrose group (n?=?351) or oral iron group (n?=?362). Cumulative analysis of all the time points indicates that the estimated mean values of Hb in the intravenous iron sucrose and oral iron groups were 10.11 g/dl and 9.33 g/dl, respectively, in antenatal group, while it was 10.57 g/dl and 9.74 g/dl in post-partum. The estimated mean ferritin level from first week to six weeks was 63.1 ?g/l and 28.6 ?g/l, respectively, in intravenous and oral iron groups. Cumulative estimate of haematocrit in the intravenous sucrose and oral iron over 6 weeks showed that the mean values in the respective groups were 30.5% and 29.5% in antenatal and 33.8% and 31.6%, respectively, in post-partum groups. Sensitivity analysis confirmed the reliability and consistency of the results. Oral iron was associated with significant gastrointestinal side effects. There was no significant difference in birthweight between the groups. Conclusion:This meta-analysis demonstrates that intravenous iron sucrose is more effective than oral iron therapy for pregnant and post-partum women with iron deficiency anaemia. It is an effective and safe alternative to address the problem of iron deficiency especially in those who require rapid replacement of iron stores though medical personnel for intravenous administration of drug is required.Trial registration CRD42015024343.

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Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia.

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Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia.

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