Atrial dysfunction as a marker of iron cardiotoxicity in thalassemia major

Li, Walter; Coates, Thomas D.; Wood, John C.

doi:10.3324/haematol.11958

Cited by 19 publications

(16 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 In patients with β-thalassaemia major, T2* values below 10 ms predict potentially lethal cardiac iron levels and cardiac dysfunction (Figure 2). 21,22 In addition to predicting cardiac function, cardiac T2* correlates with endothelial dysfunction and arterial stiffness. 21,23 Resulting increases in peripheral vascular resistance decrease left atrial size, left ventricular size, and cardiac output.…”

Section: Clinical Relevance Of Cardiac T2* Measurementsmentioning

confidence: 99%

Cardiac iron across different transfusion-dependent diseases

2008

View full text Add to dashboard Cite

SummaryIron overload occurs in patients who require regular blood transfusions to correct genetic and acquired anaemias, such as β-thalassaemia major, sickle cell disease, and myelodysplastic syndromes. Although iron overload causes damage in many organs, accumulation of cardiac iron is a leading cause of death in transfused patients with β-thalassaemia major. The symptoms of cardiac iron overload will occur long after the first cardiac iron accumulation, at a point when treatment is more complex than primary prevention would have been. Direct measurement of cardiac iron using T2* magnetic resonance imaging, rather than indirect methods such as measuring serum ferritin levels or liver iron concentration have contributed to earlier recognition of myocardial iron loading and prevention of cardiac toxicity. Cardiac siderosis occurs in all transfusional anaemias, but the relative risk depends upon the underlying disease state, transfusional load, and chelation history. All three available iron chelators can be used to remove cardiac iron, but each has unique physical properties that influence their cardiac efficacy. More prospective trials are needed to assess the effects of singleagent or combination iron chelation therapy on the levels of cardiac iron and cardiac function. Ultimately, iron chelation therapies should be tailored to meet individual patient needs and lifestyle demands.

show abstract

Section: Clinical Relevance Of Cardiac T2* Measurementsmentioning

confidence: 99%

Cardiac iron across different transfusion-dependent diseases

2008

View full text Add to dashboard Cite

show abstract

“…To maintain normal systemic blood pressure in the presence of high cardiac output, the body has to lower the systemic vascular resistance through peripheral arterial vasodilation, which leads to wide pulse pressures and low diastolic blood pressure. 70,75,76 The increased cardiac output may lead to flow murmurs on cardiac auscultation. The ejection fraction is increased because of decreased afterload and increased preload.…”

Section: Adaptive Cardiac Physiology In Tm In Absence Of Cardiac Ironmentioning

confidence: 99%

“…Limited data suggest that decreased left atrial function is a more sensitive marker of iron toxicity than left ventricular ejection fraction (LVEF), 76,80 but further data are needed. (2) Impaired right ventricular (RV) function, which may be caused by the increased vulnerability of the RV to the effects of iron deposition because of its thin wall.…”

Section: Clinical Cardiac Manifestations Of Iron Overloadmentioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

326

172

View full text Add to dashboard Cite

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.

show abstract

“…Smoldering and chronic ATLL can be treated with 6 to 9 million units/day of interferon alpha plus zidovudine 800-1000 mg/day with a 5-year OS of 100% (6) . The better response is seen for wild type p53 and low interferon regulating factor type 4 (IRF-4) patients.…”

Section: Discussionmentioning

confidence: 99%