Reduced Left Ventricular Contractile Reserve Identified by Low Dose Dobutamine Echocardiography as an Early Marker of Cardiac Involvement in Asymptomatic Patients with Thalassemia Major

Abstract

Patients with beta thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac involvement can be present in thalassemic patients without clinical manifestations of heart failure. The purpose of this study was to assess the contractile reserve of the left ventricle in patients with normal baseline two-dimensional (2-D) echocardiographic findings using low dose dobutamine echocardiography. The underlying hypothesis was that, at an early stage, structural impairment of the myocardial wall due to myocardial iron deposits and/or secondary fibrotic changes could be so subtle so as not to impair resting systolic function, but is severe enough to blunt or even exhaust the contractile response to inotropic stimulation. Twenty-four consecutive patients (13 men and 11 women; ages 18 +/- 3.8 years) with beta thalassemia major undergoing evaluation for bone marrow transplantation entered the study. By selection, all were asymptomatic, without clinical signs of cardiac failure, and had normal regional and global systolic function at baseline echocardiographic study. A control group of 16 age and sex matched subjects was also studied. All underwent baseline, 2-D, and Doppler study, as well as dobutamine stress (up to 5 &mgr;g/kg per min) 2-D echocardiographic study. Patients and controls showed comparable values of indexes of global (ejection fraction: 0.64 +/- 0.06 vs 0.65 +/- 0.05, P = NS) and regional (systolic thickening of posterior wall: 90 +/- 34 vs 91 +/- 34%, P = NS) function at baseline. Left ventricular diastolic filling was evaluated with Doppler echocardiography. Peak flow velocity in early diastole was increased in thalassemic patients compared to controls (114 +/- 16 vs 96 +/- 18 cm/sec, P < 0.01), and flow velocity deceleration time was reduced (139 +/- 17 vs 157 +/- 20 msec, P < 0.01). At peak dobutamine, thalassemic patients showed a blunted contractile response compared to controls for indexes of both global (ejection fraction: 0.62 +/- 0.06 vs 0.69 +/- 0.05, P < 0.01) and regional (% systolic thickening of posterior wall: 91 +/- 36 vs 130 +/- 39%, P < 0.01) function. When individual patient analysis was performed, echocardiographic parameters were beyond the 95% confidence limits obtained from normal controls in 5 (21%) of the 24 study patients by one or more Doppler diastolic indexes, in 6 (25%) by indexes of contractile reserve, and in 11 (46%) by one of either diastolic function or contractile reserve indexes. These data demonstrate that the "iron heart" of asymptomatic thalassemic patients is a weak heart. Even if the regional and global systolic functions are similar to normals under resting conditions, the application of an inotropic challenge unmasks the weakness of these hearts, which can be identified at an earlier stage of their natural history through the blunted contractile response following the infusion of low dose dobutamine. The information on contractile reserve is not redundant, but rather incr...

Cardiac mortality in β‐thalassemia major: resting but not dobutamine stress echocardiography predicts mortality among initially cardiac disease‐free patients in a prospective 12‐year study

“…Thus we extend findings from the previous studies 16 showing that neither profound changes nor categorical cut-off points but rather progressive baseline reductions in LVEF below 60% were independent predictors of mortality. We also confirmed an inadequate response to inotropic challenge as demonstrated by impaired LV thickening 10 and reduced contractile reserve in patients with b-TM. 10,11 However, no association was found between diastolic LV filling or serial DSE indices and mortality.…”

“…Prior investigations have demonstrated the survival benefit of chelation treatment 1–4. In comparison, the current study did not include soft endpoints,1,7,8,13 whereas patients were older,5,7,10,11,16 cardiac disease‐free at entry,1,5,7–9 at relatively lower risk,1,5,8 and on longer desferrioxamine treatment 1,7–9…”

Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major

“…In our hands, dobutamine at doses up to 40 g/kg per minute often led to unacceptable symptoms such as flushing and lightheadedness. Although lowdose dobutamine (5 g/kg per minute) has been reported to expose underlying cardiomyopathy in thalassemia patients using echocardiography, 50 no peer-reviewed papers have been published on its effects on LVEF in thalassemia patients using MUGA.…”

Evaluation of cardiac status in iron‐loaded thalassaemia patients following bone marrow transplantation: improvement in cardiac function during reduction in body iron burden

“…We have previously shown (Mariotti et al, 1996), in approximately half of the patients with thalassaemia and no clinical signs of cardiac dysfunction prior to bone marrow transplantation, alterations in both left ventricular diastolic function and contractile reserve, expressed by a reduced increase in left ventricular function after low-dose dobutamine infusion. In this study we report the potential for reversal of this dysfunction in thalassaemic patients who have undergone marrow transplantation and post-transplantation phlebotomy (Angelucci et al, 1997) to reduce body iron burden.…”