Survival and desferrioxamine in thalassaemia major.

Modell, Bernadette; Letsky, Elizabeth A.; Flynn, Denis; Pető, Richárd; Weatherall, D. J.

doi:10.1136/bmj.284.6322.1081

Cited by 183 publications

(74 citation statements)

References 12 publications

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“…[22][23][24] In our study chelation therapy with desferrioxamine was found to prevent the development of LVRFP, as reported by others. 25 On the other hand, Spirito et al did not find any influence of chelation therapy on the LV filling pattern.…”

Section: Discussionsupporting

confidence: 68%

Survival in Thalassaemia Major Patients Prognostic Value of Doppler-Demonstrated Left Ventricular Restrictive Filling Pattern

Efthimiadis

Hassapopoulou

Tsikaderis

et al. 2006

Circ J

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ongestive heart failure is the main cause of death in transfusion-dependent homozygous -thalassaemia (thalassaemia major (TM)) patients. When symptoms of heart failure appear, death usually occurs within 1 year. 1,2 Although cardiac death is the most common cause of death in patients with TM, early markers of cardiac function with prognostic impact on survival have not yet been adequately defined. Deposition of iron in the heart is the major determinant of survival in these patients. 3,4 Left ventricular (LV) restrictive filling pattern (RFP), as assessed by Doppler-echocardiography, is a well-recognized feature of TM patients with normal LV systolic function, 5 although debated by some authors. 6,7 LVRFP, as assessed by Doppler-echocardiography, is characterized by an increase of the peak early to peak late filling velocity ratio (>2) and/or shortened deceleration time of early filling (<150 ms) because of impaired ventricular compliance. 8,9 Doppler-demonstrated LVRFP is an ominous sign in a variety of cardiac diseases with concomitant systolic heart failure, 10-13 but the clinical significance of restrictive physiology in TM patients has not yet been well established.The purpose of this longitudinal study was to investigate Circulation Journal Vol.70, August 2006the impact of the Doppler-demonstrated LV filling pattern and also the impact of compliance with chelation therapy on survival in a cohort of asymptomatic TM adult patients with normal LV systolic function throughout a 15-year observation period. Methods Patients and Study ProtocolAll patients gave written informed consent and the protocol of this study was reviewed and approved by the institutional review board. Sixty-five consecutive TM patients, who were followed-up in the Thalassaemia Unit, were considered candidates for the analysis. All patients initially underwent clinical evaluation, chest X-ray, 12-lead ECG and Doppler-echocardiography from May 1989 to August 1989, in order to obtain baseline data, and then they were examined periodically by clinical examination and Dopplerechocardiography up to the end of the data collection (May 2004). The endpoint of the study was death from cardiovascular causes. Patients' inclusion criteria were: (1) age ≥14 years at the initial examination, (2) normal LV end-diastolic diameter (=55 mm) and normal LV systolic function (fractional shortening =30%), as assessed by echocardiography and (3) absence of any symptom of cardiac and/or pulmonary pathology.Among the 65 patients initially evaluated, 20 were excluded for the following reasons: 11 were <14 years of age; 4 had LV fractional shortening <30%; 5 died from non-car- Methods and ResultsThe study group comprised 45 asymptomatic transfusion-dependent patients with TM and normal LV systolic function. All patients were chelated with desferrioxamine. They were regularly evaluated by clinical and Doppler-echocardiographic studies throughout the 15-year follow-up period. The patients were categorized into 2 groups according to baseline data: those with LVRFP an...

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Section: Discussionsupporting

confidence: 68%

Survival in Thalassaemia Major Patients Prognostic Value of Doppler-Demonstrated Left Ventricular Restrictive Filling Pattern

Efthimiadis

Hassapopoulou

Tsikaderis

et al. 2006

Circ J

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“…The introduction of deferoxamine infusion in the 1970s had a profound effect on reducing mortality in TM, 2,277 and this was dominated by a reduction in iron overload-related cardiac mortality. More recently, deferiprone was introduced into clinical care in many countries (European approval in 1999 and US Food and Drug Administration approval in 2011), either as monotherapy or in combination with deferoxamine.…”

Section: Cardiac Mortality and Iron Chelationmentioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

331

172

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This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non–cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.

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“…W randomizowanym badaniu, przeprowadzonym wśród dzieci z TDT, porównywano deferoksaminę z placebo, uzyskując zmniejszenie wartości LIC do 25,9 mg/g suchej tkanki wątroby w porównaniu z 42,2 mg/g w grupie kontrolnej [60]. W badaniu włoskim, obejmującym 977 chorych na TDT, obserwowano mniej zgonów w grupie leczonej deferoksaminą niż w grupie otrzymującej placebo [61,62]. Co więcej, Brittenham i wsp.…”

Section: Monoterapia Chelatorami żElaza a Leczenie Skojarzoneunclassified

“…W 2000 roku Modell i wsp. [61] opublikowali wyniki rejestru retrospektywnego talasemii, w którym stwierdzono, że około 50% chorych na talasemię b umiera przed 35. rokiem życia, gdyż schemat leczenia jest zbyt uciążliwy, aby chory mógł w pełni współpracować i poddawać się leczeniu. Z kolei Kirk i wsp.…”

Section: Monoterapia Chelatorami żElaza a Leczenie Skojarzoneunclassified