Athanasios Aessopos

Cardiac status in well-treated patients with thalassemia major.

Abstract:  Objective: To assess cardiac status in a large group of patients with thalassemia major who had been treated in a standard way since their early infancy with intensive transfusions and deferoxamine chelation therapy and who had good compliance with this regimen. Methods and Results: We assessed clinically and echocardiographically 202 thalassemia major patients aged 27.3 ± 6.3 yr and 75 age and sex‐matched healthy controls. Overt cardiac disease was encountered in 14 patients (6.9%), including 5 (2.5%) with congestive heart failure, aged 26–37 yr, and 9 with systolic left ventricular (LV) dysfunction, aged 23–37 yr. Ten patients (5.0%) had a history of pericarditis. Left atrial and LV diameters, LV mass and cardiac output were significantly higher in patients than in controls, while peripheral resistance and LV afterload were significantly lower. Relative LV wall thickness did not differ between patients and controls, but it was significantly lower in patients with overt cardiac disease compared to those without (P < 0.05). Restrictive LV filling was observed in 37.6% of patients and was significantly more frequent in cases with overt cardiac disease (P < 0.01). Pulmonary hypertension was practically absent. Hematological parameters and pulmonary artery pressure levels were not independently associated with the presence of overt cardiac disease. Conclusion: Strict lifelong adherence to the standard transfusion and deferoxamine therapy reduces considerably the occurrence of heart failure, LV dysfunction and pericarditis, prevents early heart failure and pulmonary hypertension, but does not eliminate completely cardiac disease in patients with thalassemia major.

Pulmonary Hypertension in β‐Thalassemia

Abstract: Cardiac involvement represents the leading cause of mortality in both forms of β‐thalassemia, namely, thalassemia major (TM) and thalassemia intermedia (TI), and pulmonary hypertension (PHT) is part of the cardiopulmonary complications of the disease. PHT was initially documented in a small group of TI patients with right heart failure. In a subsequent study of a large 110‐patient series, aged 32.5 ± 11.4 years, age‐related PHT was encountered in nearly 60% of cases, having caused right heart failure in six of them; interestingly, all patients had preserved left ventricular systolic function. Conflicted evidence, however, existed with respect to the development of PHT in heterogeneously treated and young TM populations. To resolve this discrepancy, a recent study compared cardiac disease between two large aged‐matched groups of TM (n= 131) and TI (n= 74) patients, both treated uniformly in the currently accepted manner (regular transfusion and chelation therapy in TM, absence of any particular treatment in TI); well‐treated TM patients, in contrast to TI patients, did not develop PHT, while systolic left ventricular dysfunction was present only in TM cases. PHT in β‐thalassemia results from a rather complex pathophysiology, in which chronic tissue hypoxia seems to hold a key role. Although both forms of the disease share a common molecular background, the diverse severity of the genetic defect and of the resulting clinical phenotype require a different therapeutic approach. Regular lifelong therapy in TM patients eliminates chronic hypoxia, thereby preventing PHT, whereas the absence of systematic treatment in TI leads to a cascade of reactions that compensate for chronic anemia, but at the same time allow the development of PHT.

Pulmonary Hypertension Associated With Hemoglobinopathies Prevalent But Overlooked

Hemoglobinopathies constitute a heterogeneous group of hereditary hemoglobin disorders characterized by either reduced (thalassemias) or defective (sickle cell disease) globin chain synthesis that results in chronic hemolytic anemia. They represent the most common monogenetic disorders in humans, and although traditionally confined to specific geographic areas and populations (the Mediterranean Basin and the Middle and Far East in the case of β-thalassemia; Sub-Saharan Africa and African-Americans in the case of sickle cell disease), they have currently expanded to a global distribution because of the immigration of those populations to the Western world.1 Although their clinical severity is variable, the hemoglobinopathies are generally demanding conditions, particularly in the homozygous state, characterized by reduced survival, multiorgan complications, frequent hospitalizations, and need for lifelong management, thus posing a significant medical and socioeconomic burden. Cardiovascular complications are among the leading causes of mortality and morbidity in hemoglobinopathies.1 In the wide spectrum of cardiovascular manifestations of these patients, pulmonary hypertension (PH) holds a prominent place. It has been postulated that hemoglobinopathies, along with HIV infection and schistosomiasis, may be the most common causes of PH worldwide given the high prevalence of PH in those populations.2 ### β-Thalassemia PH is a frequent finding in patients with hemoglobinopathies, but the reported prevalence varies in the different conditions and according to the method used for screening (Table 1). In thalassemia intermedia, a form of β-thalassemia that accounts for 20% to 25% of cases, PH has been recognized as the most striking cardiovascular finding and the main cause of heart failure. In a preliminary report, all 7 patients with thalassemia intermedia with heart failure had preserved systolic left ventricular (LV) function and severe PH as shown by right-sided heart catheterization.8 This initial report was followed by a systematic study of 110 patients with thalassemia intermedia with a mean …

Pregnancy in patients with well-treated β-thalassemia: Outcome for mothers and newborn infants

OBJECTIVE Our purpose was to investigate the course and outcome of pregnancy in women with well-treated beta-thalassemia. STUDY DESIGN Twenty-two pregnancies, including one twin pregnancy, in 19 women were studied. Pregnancy was advised when patients had received a prolonged intensive treatment with hypertransfusions and iron chelation and had echocardiographically normal resting left ventricular performance. All conceptions were spontaneous. Cardiac function, along with hematologic, endocrinologic, and hepatic parameters were initially assessed and monitored throughout pregnancy and for 2 to 9 years post partum. Babies were delivered by elective cesarean section. RESULTS Twenty-one healthy newborn infants were delivered. A spontaneous abortion and a case of exomphalos also occurred. Gestation, delivery, and recovery were surprisingly uneventful, and no significant cardiac complications were encountered. CONCLUSION Pregnancy can be safe for mothers and babies, provided that women with thalassemia have been started early on intensive treatment and have a normal resting cardiac performance.

Pseudoxanthoma Elasticum Lesions and Cardiac Complications as Contributing Factors for Strokes in β-Thalassemia Patients

BACKGROUND AND PURPOSE Pseudoxanthoma elasticum (PXE) lesions, which lead to intracranial hemorrhages and cardiac complications, predisposing to thrombotic strokes, are frequent findings in beta-thalassemia. Nevertheless, the association of these lesions with strokes in thalassemic patients has not been previously discussed. METHODS Ten beta-thalassemic patients who developed an intracranial hemorrhage or a thrombotic stroke were reviewed. RESULTS In the group of the four patients presenting with hemorrhage, one had PXE lesions, one had cardiac abnormalities, and one both PXE and cardiac disorders. In the group presenting with thrombotic stroke, all six patients had cardiac abnormalities and platelet count elevation due to splenectomy. Three also had PXE findings. No other predisposing factor for stroke was present. CONCLUSIONS Cardiac complications and PXE may be risk factors for strokes in beta-thalassemia. Their frequent coexistence leads to a therapeutic dilemma in patients requiring antithrombotic therapy.

Reversal of heart failure in thalassemia major by combined chelation therapy: a case report

Abstract:  In patients with thalassemia major (TM) who are non‐compliant with long‐term desferrioxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional hemosiderosis. Combined chelation therapy with DFO and deferiprone has maximized the efficacy of the therapy and reduced cardiological complications. The aim of this report is to present the results of this combination in a desperate case of heart failure.

Elastic tissue abnormalities in inherited haemolytic syndromes

Over the last years, the significant prolongation of survival of patients with β thalassaemia, as a result of the intensification of treatment, in combination with the closer and systematic follow-up of patients, has gradually broadened the clinical spectrum of the disease with previously unknown manifestations. In this context, a set of clinical and laboratory signs similar to those of inherited pseudoxanthoma elasticum (PXE) have been noticed [1]. PXE is a rare hereditary connective tissue disorder, characterized by generalized degeneration of the elastic fibres with cutaneous, ocular and vascular manifestations [2]. This abnormality may lead to several serious and life-threatening complications, such as blindness, premature coronary artery disease, and cerebral and gastrointestinal haemorrhage [2]. The occurrence of PXE findings in β thalassaemia patients has led, and continues to lead, an increasing number of investigators to study various aspects of the phenomenon and a growing body of evidence is being accumulated [1]. Accordingly, the potential risk of PXErelated complications prompted Cianciulli et al . to perform a long-term follow-up of thalassaemia cases, while other groups expanded the investigation to other inherited haemolytic syndromes and re-evaluated some similar findings observed previously in sickle cell disease (SCD) [3]. The first manifestations of a potential elastic tissue defect associated with haemoglobinopathies were angioid streaks, which represent breaks in the elastic fibres in the membrane of Bruch and are the typical ocular findings in inherited PXE. Angioid streaks have been described in SCD since the late 1950s [4]. Subsequent studies have reported a frequency of angioid streaks in SCD ranging from 1% to 22%, depending on the patients’ age [5–7]. In β thalassaemia, an age-related occurrence of 20% was reported [1]. Angioid streaks have also been encountered in sickle thalassaemia with a frequency of 10% [8]. Sporadically, they have been seen in α thalassaemia (haemoglobin H disease) [9], haemoglobin AC disease (haemoglobin C trait carrier) [10] and β thalassaemia minor [11,12]. In a large series of angioid streaks, 50% of cases had PXE on diagnosis [13]. The possibility of a similar diffuse connective tissue disorder in SCD was raised by the report of the PXE syndrome in at least seven adult cases with SCD [14]. However, blind skin biopsies, performed in SCD patients with angioid streaks, failed to reveal any evidence of PXE [5,7]. In contrast, an autopsy series of unselected SCD patients revealed histopathological findings in the dermis and the arterial walls of multiple organs identical to those found in PXE [15]. A clearer relationship was introduced by Lippman et al . in 1985. Based on histopathology and biochemical analysis of skin biopsies, these investigators concluded that SCD appears to be associated with a wide spectrum of elastic tissue disorders resembling PXE, although less severe than PXE [16]. Subsequently, accumulated evidence from the literature has supported the concept of an underlying, generalized elastic tissue defect in the same haemoglobinopathies that were previously associated with angioid streaks. In β thalassaemia, the occurrence of PXE findings proved to be more profound and structurally identical to the inherited PXE [17]. In a 100-patient group with β thalassaemia, 16% of cases had PXE cutaneous lesions, 20% had angioid streaks and 26% had at least one of the two findings; however, none of the patients under the age of 19 years nor any of the 70 family members of cases with PXE findings showed any skin or ocular lesions [18]. The study by Cianciulli et al . confirms the high incidence of PXE-like skin, ocular and arterial manifestations in patients with β thalassaemia as well as their positive correlation with age [3]. In a previous study, the incidence of at least one of these findings reached the impressive percentage of 85% in older thalassaemic patients, aged over 30 years, with calcification of First Department of Internal Medicine, University of Athens, Medical School, ‘Laiko’ General Hospital, Athens 115 27, Greece (A. Aessopos, D. Farmakis, D. Loukopoulos).

The heart in sickle cell disease.

Cardiovascular abnormalities are often apparent in sickle cell disease, as in other chronic anaemias. Tissue oxygen extraction and cardiac output are increased, while the activated endothelium along with the sickling process and the vaso-occlusion of the small blood vessels strain further the cardiovascular system. Evidence for a specific myocardial lesion attributable to the sickle cell disease is ambiguous through different studies. This article attempts to review the literature about cardiac disease in sickle cell anaemia.

Aneurysmatic dilatation of ascending aorta in a patient with β-thalassemia and a pseudoxanthoma elasticum-like syndrome

The development of a diffuse elastic tissue defect resembling pseudoxanthoma elasticum (PXE) is a recently established and frequently encountered clinical entity in β-thalassemia. The clinical spectrum of this disorder is not yet completely understood as it is continuously being enriched with novel complications that are often serious. We present here a thalassemia intermedia patient with typical PXE manifestations and a fusiform aneurysmatic dilatation of the ascending thoracic aorta, a previously unknown complication in these patients. An aortic aneurysm has itself a notable morbidity, while it may also impair the particularly susceptible cardiac function of β-thalassemia patients, hence affecting the overall prognosis of the main disease.

Hypocalcemic heart failure in thalassemic patients.

Hypocalcemic cardiomyopathy in primary or secondary hypoparathyroidism is usually refractory to conventional treatment of cardiac failure. We report the case of a thalassemic patient with severe cardiac failure that might have been attributed to several factors, such as hemosiderosis, hypomagnesemia, and hypocalcemia, refractory to conventional cardiac therapy. Cardiac echocardiography showed impaired biventricular performance, and laboratory analyses revealed hypoparathyroidism due to hemosiderosis. When concomitant treatment of heart failure and calcium supplementation was initiated, correction of hypocalcemia resulted in clinical and laboratory improvement, providing strong evidence in support of our hypothesis about hypocalcemic myocardiopathy.