BACKGROUND: Cardiac dysfunction remains the major cause of death in beta-thalassemia. Aim of this study was to assess early myocardial damage in thalassemic patients with no symptoms or echocardiographic evidence of dysfunction at routine monitoring. METHODS: Twenty patients (seven females; median 25 yr [first quartile 22,third quartile 28]) with beta-thalassemia underwent radionuclide angiography (RNA) at rest and during low-dose dobutamine infusion (5-10 gamma/kg/min). Right and left ventricular ejection fractions (EF) were determined by first-pass method and gated equilibrium acquisition, respectively. Twenty-four-hour Holter monitoring with time-domain heart rate variability (HRV) assessment and echocardiographic follow-up (21 months [5,27]) were performed. RESULTS: Eleven patients showed regional wall motion abnormalities at RNA; left ventricular EF, HR and diastolic measurements significantly increased after dobutamine infusion. Patients with abnormal RNA right ventricular EF (n = 8, <0.45) showed lower echocardiographic left ventricular EF at the enrollment (0.54 [0.50,0.61] vs. 0.62 [0.56,0.67], P = 0.02) than those with a normal right ventricular EF. Patients with reduced standard deviation of the averages of RR intervals in all 5-minute periods of entire recording (SDANN) (n = 6, <100 ms), a measure of HRV, had lower echocardiographic left ventricular EF (0.53 [0.49,0.62] vs. 0.62 [0.56,0.66], P = 0.03) and lower fractional shortening (0.28 [0.25,0.32] vs. 0.36 [0.30,0.39], P = 0.003) at the enrollment than those with normal SDANN. No significant association was found between RNA and HRV measurements and follow-up left ventricular function. CONCLUSIONS: Right ventricular dysfunction and abnormal HRV may represent the early features of cardiac disease in thalassemic patients with no evidence of ventricular dysfunction at routine evaluation.