Special Report -Thalassemia Cardiomyopathy History, Present Considerations, and Future Perspectives Dimitrios T. Kremastinos, MD, PhD; Dimitrios Farmakis, MD, PhD; Athanasios Aessopos, MD, PhD; George Hahalis, MD, PhD; Eftychia Hamodraka, MD; Dimitrios Tsiapras, MD; Andre Keren, MD Abstract—-Thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia that typically requires life-long transfusion therapy. Although traditionally prevalent in the Mediterranean basin, Middle East, North India, and Southeast Asia, immigration of those populations to North America and Western Europe has rendered -thalassemia a global health problem. Cardiac complications represent the primary cause of mortality and one of the major causes of morbidity in those patients. Heart disease is mainly expressed by a particular cardiomyopathy that progressively leads to heart failure and death. The -thalassemia cardiomyopathy is mainly characterized by 2 distinct phenotypes, a dilated phenotype, with left ventricular dilatation and impaired contractility and a restrictive phenotype, with restrictive left ventricular filling, pulmonary hypertension, and right heart failure. The pathophysiology of the disorder is multifactorial, with a central role of myocardial iron overload and the significant contribution of immunoinflammatory mechanisms. Patients’ management is demanding and requires a multidisciplinary approach, preferably in specialized centers. (Circ Heart Fail. 2010;3:451-458.) Key Words: heart failure  heart disease  cardiomyopathy  thalassemia  iron overload -Thalassemia: A Geographical and Historical Perspective The word “thalassemia” comes FROM the Greek word “thalassa” (sea) because of the high prevalence of the disease in the countries bordering the Mediterranean Sea. -thalassemia had been traditionally prevalent in and con- fined to the Mediterranean basin, Middle East, North India, Southeast Asia and the Indochina Peninsula. However, im- migration of those populations to USA., Canada, and Western European countries has resulted in a more universal distribu- tion of the disease. 1–3 Therefore, -thalassemia should cur- rently be considered a global rather than a regional health problem. During the past few decades, an impressive improvement in patients’ survival has been noticed. In the mid-1960s, only 37% of patients in a small group of 41 patients with thalassemia major were alive at the age of 16 years. 4 In contrast, a 95% survival was encountered among patients of similar age, 30 years later. 5 At the beginning of the new millennium, survival at the age of 35 years was 50% according to the UK thalassemia registry 2 and 65% according to an Italian study, 6 whereas a 83% survival rate beyond 40 years was reported in 2004. 7 Such a favorable advance on outcome during the elapsing decades in thalassemia major has been accounted for by the adoption of a systematic treatment approach (Figure 1). More specifically, patients in 1960s were managed by occasional blood transfusions, which merely prolonged short-term survival by maintaining very low, just life-compatible hemoglobin levels. 4 In the subse- quent decade, regular blood transfusions were initiated, aim- ing at maintenance of a hemoglobin concentration of at least 10 g/dL. At the same time, iron chelation therapy with parenteral deferoxamine was introduced in mid-1970s to manage the deleterious effects of transfusional iron overload. In 1980s, it became clear that patients should be closely monitored and managed in specialized centers. At that time period, a study using M-mode echocardiography was per- formed in a group of 60 patients with thalassemia major, 14 of whom suffered from advanced congestive heart failure. That study revealed a dilated-type cardiomyopathy with no significant difference of the bulk of blood transfusions between patients with heart failure and age-matched patients without heart failure, hence rising questions about the definite role of iron in the pathogenesis of heart disease. 8 The recent introduction of novel, oral iron chelators, including de- feriprone in 2000, initially as monotherapy and then in combination with deferoxamine, and deferasirox in 2007, has significantly enhanced the efficacy of chelation therapy; this in turn may result in further improvement in patients’ survival. 9 Received October 5, 2009; accepted February 4, 2010. From the Second Department of Cardiology (D.T.K., D.F., E.H.), Attikon University Hospital, Athens, Greece; First Department of Internal Medicine (A.A.), Laiko General Hospital, Athens, Greece; Department of Cardiology (G.H.), Patras University Hospital, Patras, Greece; Onassis Cardiac Surgery Center (D.T.), Athens, Greece; and Department of Cardiology (A.K.), Hadassah University Hospital, Jerusalem, Israel. Correspondence to Dimitrios T. Kremastinos, MD, PhD, FESC, FACC, Second Department of Cardiology, Athens University Medical School, Attikon University Hospital, 1 Rimini St, Athens 12462, Greece. E-mail dimitrios_farmakis@yahoo.com © 2010 American Heart Association, Inc. Circ Heart Fail is available at http://circheartfailure.ahajournals.org DOI: 10.1161/CIRCHEARTFAILURE.109.913863 451 by guest on March 9, 2016 http://circheartfailure.ahajournals.org/ Downloaded from