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Featured researches published by Lisa J. Anderson.


The Lancet | 2002

Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia

Lisa J. Anderson; Beatrix Wonke; Emma Prescott; S Holden; J. Malcolm Walker; Dudley J. Pennell

BACKGROUND Despite the introduction of the parenteral iron chelator desferrioxamine more than 30 years ago, 50% of patients with thalassaemia major die before the age of 35 years, predominantly from iron-induced heart failure. The only alternative treatment is oral deferiprone, but its long-term efficacy on myocardial iron concentrations is unknown. METHODS We compared myocardial iron content and cardiac function in 15 patients receiving long-term deferiprone treatment with 30 matched thalassaemia major controls who were on long-term treatment with desferrioxamine. Myocardial iron concentrations were measured by a new magnetic-resonance T2* technique, which shows values inversely related to tissue iron concentration. FINDINGS The deferiprone group had significantly less myocardial iron (median 34.0 ms vs 11.4 ms, p=0.02) and higher ejection fractions (mean 70% [SD 6.5] vs 63% [6.9], p=0.004) than the desferrioxamine controls. Excess myocardial iron (T2* <20 ms) was less common in the deferiprone group than in the desferrioxamine controls (four [27%] vs 20 [67%], p=0.025), as was severe (T2* <10 ms) iron overload (one [7%] vs 11 [37%], p=0.04). The odds ratio for excess myocardial iron in the desferrioxamine controls versus the deferiprone group was 5.5 (95% CI 1.2-28.8). INTERPRETATION Conventional chelation treatment with subcutaneous desferrioxamine does not prevent excess cardiac iron deposition in two-thirds of patients with thalassaemia major, placing them at risk of heart failure and its complications. Oral deferiprone is more effective than desferrioxamine in removal of myocardial iron.


British Journal of Haematology | 2004

Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance.

Lisa J. Anderson; Mark Westwood; S Holden; Bernard A. Davis; Emma Prescott; Beatrix Wonke; John B. Porter; J. Malcolm Walker; Dudley J. Pennell

Heart failure from iron overload causes 71% of deaths in thalassaemia major, yet reversal of siderotic cardiomyopathy has been reported. In order to determine the changes in myocardial iron during treatment, we prospectively followed thalassaemia patients commencing intravenous desferrioxamine for iron‐induced cardiomyopathy during a 12‐month period. Cardiovascular magnetic resonance assessments were performed at baseline, 3, 6 and 12 months of treatment, and included left ventricular (LV) function and myocardial and liver T2*, which is inversely related to iron concentration. One patient died. The six survivors showed progressive improvements in myocardial T2* (5·1 ± 1·9 to 8·1 ± 2·8 ms, P = 0·003), liver iron (9·6 ± 4·3 to 2·1 ± 1·5 mg/g, P = 0·001), LV ejection fraction (52 ± 7·1% to 63 ± 6·4%, P = 0·03), LV volumes (end diastolic volume index 115 ± 17 to 96 ± 3 ml, P = 0·03; end systolic volume index 55 ± 16 to 36 ± 6 ml, P = 0·01) and LV mass index (106 ± 14 to 95 ± 13, P = 0·01). Iron cleared more slowly from myocardium than liver (5·0 ± 3·3% vs. 39 ± 23% per month, P = 0·02). These prospective data confirm that siderotic heart failure is often reversible with intravenous iron chelation with desferrioxamine. Myocardial T2* improves in concert with LV volumes and function during recovery, but iron clearance from the heart is considerably slower than from the liver.


Journal of Magnetic Resonance Imaging | 2003

A Single Breath-Hold Multiecho T2* Cardiovascular Magnetic Resonance Technique for Diagnosis of Myocardial Iron Overload

Mark Westwood; Lisa J. Anderson; David N. Firmin; Peter D. Gatehouse; Clare C. Charrier; Beatrix Wonke; Dudley J. Pennell

To assess tissue iron concentrations by the use of a gradient echo T2* multiecho technique.


Circulation | 2011

On T2* Magnetic Resonance and Cardiac Iron

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; Renzo Galanello; 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

Background— 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. Methods and Results— 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. Conclusions— 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.


European Heart Journal | 2009

Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms

C Parsai; Bart Bijnens; G.R Sutherland; Aigul Baltabaeva; Piet Claus; Maciej Marciniak; Vince Paul; Mike Scheffer; Erwan Donal; Geneviève Derumeaux; Lisa J. Anderson

AIM To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.


Journal of Cardiovascular Magnetic Resonance | 2006

Myocardial Iron Loading in Patients with Thalassemia Major on Deferoxamine Chelation

Mark A. Tanner; Renzo Galanello; Carlo Dessì; Mark Westwood; Gill Smith; Sunil V. Nair; Lisa J. Anderson; John Malcolm Walker; Dudley J. Pennell

BACKGROUND Heart failure secondary to myocardial iron loading remains the leading cause of death in thalassemia major (TM). We used cardiovascular magnetic resonance (CMR) to assess the prevalence of myocardial iron overload and ventricular dysfunction in a large cohort of TM patients maintained on conventional chelation treatment with deferoxamine. METHODS A mobile CMR scanner was transported from London, UK, to Sardinia, Italy where 167 TM patients were assessed for myocardial iron loading, B-natriuretic peptide (BNP), and ferritin. In patients with myocardial iron loading CMR assessments of ventricular function were also made. RESULTS Myocardial iron loading (T2* < 20 ms) was present in 108 (65%) patients, which was severe (T2* < 8 ms) in 22 (13%). Impaired (< 56%) left ventricular (LV) ejection fraction (EF) was present in 5%, 20% and 62% of patients with mild, moderate or severe iron loading. Increasing myocardial iron was related to impaired LVEF (Rs = 0.57, p < 0.001), weakly related to serum ferritin (Rs = -0.34, p < 0.001), and not related to liver iron (Rs = 0.11, p = 0.26). BNP was weakly related to myocardial iron (Rs = -0.35, p < 0.001) and was abnormal in only 5 patients. CONCLUSIONS Myocardial siderosis was found in two-thirds of thalassemia major patients on maintenance deferoxamine treatment. This was combined with a high prevalence of impaired LV function, the severity of which tracked the severity of iron deposition. BNP was not useful to assess myocardial siderosis.


Journal of Magnetic Resonance Imaging | 2003

Interscanner reproducibility of cardiovascular magnetic resonance T2* measurements of tissue iron in thalassemia

Mark Westwood; Lisa J. Anderson; David N. Firmin; Peter D. Gatehouse; Christine H. Lorenz; Beatrix Wonke; Dudley J. Pennell

To assess interscanner reproducibility of tissue iron measurements in patients with thalassemia using gradient echo T2* measurements on two different MRI scanners.


European Heart Journal | 2003

Tissue Doppler echocardiography in patients with thalassaemia detects early myocardial dysfunction related to myocardial iron overload.

M Vogel; Lisa J. Anderson; S Holden; J.E Deanfield; Dudley J. Pennell; John Malcolm Walker

AIMS To compare an echocardiographic method for detecting abnormal cardiac function before development of overt cardiomyopathy with a recently validated technique of quantifying myocardial iron load. METHODS AND RESULTS We examined thalassaemia patients whose myocardial iron load had been evaluated with magnetic resonance imaging (MRI). By tissue Doppler echocardiography, myocardial velocities were sampled continuously from base to apex in the RV and LV free wall, and the septum in 52 patients aged 29.2 (14.2-43.1) years and 52 age-matched controls. Ninety-six percent of patients had normal LV ejection fraction by MRI. Thirty-eight (73%) had abnormal iron loading of the myocardium, and 33 of those had regional wall motion abnormalities detected in the septum (n=29), LV (n=2), RV (n=1), and septum plus LV (n=1). The incidence of wall motion abnormalities was significantly higher (P<0.04) in patients with myocardial iron overload (87%) than in the 14 without (35%). Furthermore, myocardial iron overload was suggested by a low T2(*)(15.1+/-15.8 ms) in patients with wall motion abnormalities vs those with normal wall motion (T2(*): 30+/-19 ms) (P<0.007). CONCLUSIONS Wall motion abnormalities may represent an early sign of cardiac disease despite preserved global function. The regional abnormalities are related to iron overload and easily detectable with tissue Doppler echocardiography.


Journal of Magnetic Resonance Imaging | 2010

International reproducibility of single breathhold T2* MR for cardiac and liver iron assessment among five thalassemia centers.

Paul Kirk; Taigang He; Lisa J. Anderson; Michael Roughton; Mark A. Tanner; Wynnie W.M. Lam; Wing Y. Au; Winnie C.W. Chu; Godfrey Chi-Fung Chan; Renzo Galanello; Gildo Matta; Mark A. Fogel; Alan R. Cohen; Ru San Tan; Kevin K’o Wen Chen; Ivy Ng; Angie Lai; Suthat Fucharoen; Jiraporn Laothamata; Suporn Chuncharunee; Sutipong Jongjirasiri; David N. Firmin; Gillian C. Smith; Dudley J. Pennell

To examine the reproducibility of the single breathhold T2* technique from different scanners, after installation of standard methodology in five international centers.


Circulation | 2008

Patient Selection and Echocardiographic Assessment of Dyssynchrony in Cardiac Resynchronization Therapy

Lisa J. Anderson; Chinami Miyazaki; G.R Sutherland; Jae Kuen Oh

Appropriate cardiac resynchronization therapy (CRT) enhances quality of life and improves survival in patients with refractory heart failure due to systolic dysfunction and mechanical dyssynchrony. On the assumption that the main therapeutic mechanism of CRT is the correction of dyssynchronous myocardial contraction, imaging-based measures of dyssynchrony have been intensely investigated with the aim of predicting response to therapy. Numerous echocardiographic dyssynchrony parameters have been proposed, but no large prospective trial have been published to prove the clinical utility of any of these indexes. Moreover, the methodology to derive the proposed dyssynchrony indexes has not been standardized. Therefore, the purpose of this article is to critically review the current status of proposed dyssynchrony indexes by echocardiography for patient selection and to recommend future investigations in this area. The adverse effects of dyssychronous activation1 and the ability to correct these abnormalities with biventricular stimulation2 were described long ago, but the potential therapeutic application was not realized until an unprecedented study in 1990 reported recovery from intractable heart failure in 16 patients implanted with conventional dual-chamber pacemakers programmed to a short atrioventricular (AV) delay.3 Although these results could not be reproduced in prospective studies4,5 and improvements could only be demonstrated short-term in highly selected patients,6 the race to find a pacing therapy for heart failure had begun. On the hypothesis that the disappointing results of dual-chamber pacing in prospective studies were due to cancelling or overcoming the beneficial effects of AV synchronisation by the adverse effect of RV pacing-induced dyssynchrony,7,8 Cazeau and colleagues proposed a 4-chamber pacing mode and reported the first successful permanent implant in 1994.9 Early randomized controlled trials confirmed short-term improvements in functional capacity and quality of life for patients.10–13 However it was the Comparison of Medical Therapy, Pacing, and Defibrillation in …

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Dudley J. Pennell

National Institutes of Health

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John B. Porter

University College London

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C Parsai

St George's Hospital

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David N. Firmin

National Institutes of Health

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Carol J. Whelan

University College London

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