Early detection of cardiac iron deposition in patients with thallassemia, what is the best strategy?

Abstract

b-Thallassemia is an inherited disorder of haemoglobin synthesis, resulting in chronic haemolytic anemia. Adequate blood transfusions and continuous chelation therapy are the milestones of treatment. In adults, the major haemoglobin is haemoglobin A, a tetramer consisting of one pair of a chains and one pair of b chains. Normally the ratio of a to b chains is one. In patients with thallassemia production of b chains is diminished. The excess a chains are unstable and incapable of forming soluble teramers. These chains precipitate in the cell, leading to a variety of clinical manifestations [1]. Thallassemias arise from over 100 mutations, that affect every step for production of normal haemoglobin. The frequency for genetic abnormalities associated with b-thallassemia approaches 0.1 in South Mediterranean areas in Europe. Both sexes are equally affected [2]. The bthallassemia syndromes are remarkable for their heterogeneity and clinical expression of the genetic abnormality [3]. Patients with a b-thallassemia mutation on each chromosome usually exhibit some degree of a-globin inclusion body formation, with consequent anemia, hemolysis and varying degrees of ineffective erythropoiesis [1]. The clinical syndrome associated with this genetic disorder is called thallassemia major. Patients, who are heterozygotes for b-thallassemia are mostly asymptomatic. This, because the erythrocyte is able to catabolize some of the excess unpaired a-globulin chains [1]. The syndrome is usually described as thallassemia minor or thallassemia intermediate. In patients with b-thallassemia major cardiac abnormalities occur frequently next to disorders of the liver and spleen, skeletal abnormalities and kidney and endocrine abnormalities [4]. Heart failure and rhythm disturbances are the main cause of death in adults with thallassemia major. In a recently published multicenter study 5% of patients aged 16–24 years and 23% of patients older than 25 years had heart disease requiring medication [5]. In another study congestive heart failure was observed in 5.4% of patients with thallassemia intermedia. Eight percent of these patients had a history of acute pericarditis [4]. The most prominent finding in patients with thallassemia major is left ventricular dysfunction, which is mainly due to severe anemia and iron overload because of the regular blood transfusions required to avoid hypoxia [6]. The estimation of iron stores in the heart would be very helpful in order to evaluate the efficacy of chelation therapy and determine the cardiac risk. Although the iron storage proteins like hemosiderin and ferritin are mostly intracellular, serum ferritin is highly correlated with the amount of iron deposition L. H. B. Baur (&) Department of Cardiology, Atrium Medical Centre Parkstad, University of Maastricht, Maastricht, The Netherlands e-mail: lbr01@atriummc.nl