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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* <20ms). 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 marked improvements in T2* and LVEF following venesection. Myocardial siderosis was present in 6/18 (33%) of patients with presenting ferritin >=1000mug/L at diagnosis but in 0/13 (0%) patients with ferritin <1000mug/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. CONCLUSION: Myocardial siderosis was present in 33% of newly presenting genetically confirmed HFE-HC patients with ferritin >1000mug/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.
Journal of Cardiovascular Magnetic Resonance 03/2013; 15(1):24. · 3.72 Impact Factor
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ABSTRACT: PURPOSE: To compare myocardial T1 against T2 and T2* in patients with thalassemia major (TM) for myocardial iron characterization. MATERIALS AND METHODS: A total of 106 TM patients (29 ± 10 years; 58 males) were studied on a 1.5 Tesla scanner using dedicated T1, T2*, and T2 relaxometry sequences. A single mid-ventricular short axis slice was acquired within a breath-hold. RESULTS: In patients with myocardial iron overload (T2* < 20 ms; n = 52), there were linear correlations between T2 and T2* (r = 0.82; P = 0.0), and between T1 and T2* (r = 0.83; P = 0.0). In patients with no myocardial iron (n = 54), T2* values were scattered with no significant correlation against T2 or T1. For all patients (n = 106) there was a strong linear correlation (r = 0.93; P = 0.0) between myocardial T1 and T2. CONCLUSION: In patients with iron overload, myocardial T2 and T1 are correlated with T2*. In patients with low or normal myocardial iron concentration, other factors become dominant in affecting T2* values as shown by scattered T2* data. Myocardial T1 correlates linearly with T2 measurements in all patients suggesting that these two relaxation parameters avoid extrinsic magnetic field inhomogeneity effects and may potentially provide improved myocardial tissue characterization. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
Journal of Magnetic Resonance Imaging 01/2013; · 2.70 Impact Factor
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ABSTRACT: There were 83 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR) in 2011, which is an 11% increase in the number of articles since 2010. The quality of the submissions continues to increase. The editors had been delighted with the 2010 JCMR Impact Factor of 4.33, although this fell modestly to 3.72 for 2011. The impact factor undergoes natural variation according to citation rates of papers in the 2 years following publication, and is significantly influenced by highly cited papers such as official reports. However, we remain very pleased with the progress of the journal's impact over the last 5 years. Our acceptance rate is approximately 25%, and has been falling as the number of articles being submitted has been increasing. In accordance with Open-Access publishing, the JCMR articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. For this reason, the Editors feel it is useful to summarize the papers for the readership into broad areas of interest or theme, which we feel would be useful, so that areas of interest from the previous year can be reviewed in a single article in relation to each other and other recent JCMR articles [1]. The papers are presented in broad themes and set in context with related literature and previously published JCMR papers to guide continuity of thought in the journal. We hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality manuscripts to JCMR for publication.
Journal of Cardiovascular Magnetic Resonance 11/2012; 14(1):78. · 3.72 Impact Factor
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ABSTRACT: PURPOSE: To propose an automated truncation method for myocardial T2* measurement and evaluate this method on a large population of patients with iron loading in the heart and scanned at multiple magnetic resonance imaging (MRI) centers. MATERIALS AND METHODS: A total of 550 thalassemia patients were scanned at 20 international centers using a variety of MR scanners (Siemens, Philips, or GE). A single mid-ventricular short axis slice was imaged. All patient data were anonymized before the T2* were measured by expert observers using standard techniques. These same datasets were then retrospectively processed using the proposed automated truncation method by another independent observer and the resulting T2* measurements were compared with those of expert readings. RESULTS: The T2* measurements using the automated method showed good agreement with those measured by expert observers using standard techniques (P = 0.95) with a low coefficient of variation (1.6%). CONCLUSION: This study demonstrates feasibility and good reproducibility of a new automated truncation method for myocardial T2* measurement. This approach simplifies the overall analysis and can be easily incorporated into T2* analysis software to facilitate further development of a fully automated myocardial tissue iron quantification. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
Journal of Magnetic Resonance Imaging 08/2012; · 2.70 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 05/2012; 12:1-1. · 3.72 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P293. · 3.72 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:O77. · 3.72 Impact Factor
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ABSTRACT: Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR).
We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading.
In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01).
In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis.
Journal of Cardiovascular Magnetic Resonance 01/2012; 14:8. · 3.72 Impact Factor
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ABSTRACT: To assess whether black blood T2* cardiovascular magnetic resonance is superior to conventional white blood imaging of cardiac iron in patients with thalassaemia major (TM).
We performed both conventional white blood and black blood T2* CMR sequences in 100 TM patients to determine intra and inter-observer variability and presence of artefacts. In 23 patients, 2 separate studies of both techniques were performed to assess interstudy reproducibility.
Cardiac T2* values ranged from 4.5 to 43.8 ms. The mean T2* values were not different between black blood and white blood acquisitions (20.5 vs 21.6 ms, p=0.26). Compared with the conventional white blood diastolic acquisition, the coefficient of variance of the black blood CMR technique was superior for intra-observer reproducibility (1.47% vs 4.23%, p<0.001), inter-observer reproducibility (2.54% vs 4.50%, p<0.001) and inter-study reproducibility (4.07% vs 8.42%, p=0.001). Assessment of artefacts showed a superior score for black blood vs white blood scans (4.57 vs 4.25; p<0.001).
Black blood T2* CMR has superior reproducibility and reduced imaging artefacts for the assessment of cardiac iron, in comparison with the conventional white blood technique, which make it the preferred technique for clinical practice.
Journal of Cardiovascular Magnetic Resonance 03/2011; 13:21. · 3.72 Impact Factor
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John-Paul Carpenter,
Taigang He,
Paul Kirk,
Michael Roughton,
Lisa J Anderson,
Sofia V de Noronha,
Mary N Sheppard,
John B Porter,
J Malcolm Walker,
John C Wood, [......],
Gianluca Forni,
Gualtiero Catani,
Gildo Matta,
Suthat Fucharoen,
Adam Fleming,
Michael J House,
Greg Black,
David N Firmin,
Timothy G St Pierre,
Dudley J Pennell
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ABSTRACT: Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically via its reciprocal, T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans are limited.
Twelve human hearts were studied from transfusion-dependent patients after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure (n=4). After cardiovascular magnetic resonance R2* measurement, tissue iron concentration was measured in multiple samples of each heart with inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean ± SD global myocardial iron causing severe heart failure in 10 patients was 5.98 ± 2.42 mg/g dry weight (range, 3.19 to 9.50 mg/g), but in 1 outlier case of heart failure was 25.9 mg/g dry weight. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] (R²=0.910, P<0.001), leading to [Fe]=45.0×(T2*)⁻¹·²² for the clinical calibration equation with [Fe] in milligrams per gram dry weight and T2* in milliseconds. Midventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron.
These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration. The iron values are of considerable interest in terms of the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in vivo by cardiovascular magnetic resonance of the midseptum.
Circulation 03/2011; 123(14):1519-28. · 14.74 Impact Factor
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ABSTRACT: Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure.
We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR), and following this, late gadolinium enhancement (LGE) was used to determine the presence of macroscopic myocardial fibrosis.
The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms). Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* < 20 ms at the time of scan.
This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible.
Journal of Cardiovascular Magnetic Resonance 01/2011; 13:8. · 3.72 Impact Factor
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Gillian C Smith,
Francisco Alpendurada, John Paul Carpenter,
Mohammed H Alam,
Vasili Berdoukas,
Markissia Karagiorga,
Vasili Ladis,
Antonio Piga,
Athanassios Aessopos,
Efstathios D Gotsis,
Mark A Tanner,
Mark A Westwood,
Renzo Galanello,
Michael Roughton,
Dudley J Pennell
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ABSTRACT: Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs.
In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment.
From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p=0.008), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p=0.001). This was associated with a 27% increase in T2* (p<0.001) and 3.1% increase in LVEF (p<0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p=0.38), or RVEF (70.0 to 69.9%, p=0.93) whereas the T2* increased by 13% (p<0.001), but with no change in LVEF (0.32%; p=0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL (p=0.014) and 1.16% for RVEF (p=0.009). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p<0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p=0.012).
In this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.
Journal of Cardiovascular Magnetic Resonance 01/2011; 13:34. · 3.72 Impact Factor
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John-Paul Carpenter,
Taigang He,
Paul Kirk,
Lisa Anderson,
John Porter,
Malcolm Walker,
Renzo Galanello,
Fabrice Danjou,
Gianluca Forni,
Antonis Kattamis, [......],
Tuncay Hazirolan,
Ana Almeida,
Yesim Aydinok,
Mirella Rangelova,
Amal El-Beshlawy,
Mohsen Elalfy,
Ibrahim Alnasser,
Shahina Daar,
Juliano Fernandes,
Dudley Pennell
Journal of Cardiovascular Magnetic Resonance. 01/2011;
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ABSTRACT: Myocardial T2* cardiovascular magnetic resonance (CMR) provides a rapid and reproducible measure of cardiac iron loading and is being increasingly used worldwide for monitoring of transfusion-dependent thalassaemia patients. Although myocardial siderosis (T2* <20 ms) is associated with impaired left ventricular (LV) function, little is known of its relation with right ventricular (RV) function. The aim of this study was to investigate the relationship between cardiac T2* and RV function.
A retrospective analysis of 319 patients with beta-thalassaemia major presenting for their first CMR scan was performed (45.1% male, mean age 25.6 years). In patients with normal myocardial T2* (>20 ms), the RV ejection fraction (EF) was within the normal range in 98% of patients. When myocardial T2* was <20 ms, there was a progressive and significant decline in RV EF. There was a linear relationship between RV and LV EF.
Myocardial iron deposition is strongly associated with RV dysfunction, which mirrors the decrease in LV function seen with worsening cardiac iron loading. Right ventricular dysfunction may play a significant role in heart failure associated with myocardial siderosis.
European Heart Journal 04/2010; 31(13):1648-54. · 10.48 Impact Factor
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John-Paul Carpenter,
Francisco Alpendurada,
Monica Deac,
Alicia Maceira,
Maciej Garbowski,
Paul Kirk,
J Malcolm Walker,
John B Porter,
Farrukh Shah,
Winston Banya,
Taigang He,
Gillian C Smith,
Dudley J Pennell
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ABSTRACT: We aimed to define reference ranges for right ventricular (RV) volumes, ejection fraction (EF) in thalassemia major patients (TM) without myocardial iron overload.
RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance). All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 +/- 4.1% vs 61.6 +/- 6%, p = 0.0009; females 66.3 +/- 5.1% vs 62.6 +/- 6.4%, p = 0.017), which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%). RV end-diastolic volume index was higher in male TM patients (mean 98.1 +/- 17.3 mL vs 88.4 +/- 11.2 mL/m2, p = 0.027), with a higher upper limit (132 vs 110 mL/m2) but this difference was of borderline significance for females (mean 86.5 +/- 13.6 mL vs 80.3 +/- 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2). The cardiac index was raised in TM patients (males 4.8 +/- 1.0 L/min vs 3.4 +/- 0.7 L/min, p < 0.0001; females 4.5 +/- 0.8 L/min vs 3.2 +/- 0.8 L/min, p < 0.0001). No differences in RV mass index were identified.
The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients.
Journal of Cardiovascular Magnetic Resonance 04/2010; 12:24. · 3.72 Impact Factor
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Journal of Cardiovascular Magnetic Resonance. 01/2010;
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Journal of Cardiovascular Magnetic Resonance. 01/2010;
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Journal of Cardiovascular Magnetic Resonance. 01/2010;
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The international journal of cardiovascular imaging 11/2009; 25(8):785-8. · 2.15 Impact Factor
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ABSTRACT: According to WHO data, approximately 56,000 babies are born each year with a major thalassaemia, including at least 30,000 who require lifelong transfusions to survive. Of those transfused, under 40% obtain adequate chelation therapy. An estimated 100,000 patients worldwide are currently living with regular transfusions, but at least 3,000 die each year in their teens or early 20s from uncontrolled iron overload, mainly due to heart failure. With no physiological excretory pathway, iron from transfused blood accumulates in the liver, heart, endocrine and other organs causing tissue damage and impairment in function. Chelating agents can remove the excess iron and prevent complications, the most serious of which is death from heart failure due to myocardial siderosis. Progressive cardiac iron loading eventually leads to left ventricular (LV) dilatation and reduction in LV ejection fraction but this is a late manifestation of severe myocardial siderosis and once clinical evidence of heart failure has developed, the prognosis is poor.
Heart (British Cardiac Society) 08/2009; 95(20):1646-7. · 4.22 Impact Factor
