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.