Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients

Idarubicin has been shown to have similar or superior antileukemic activity to daunorubicin with less cumulative cardiotoxicity. However, data of acut e cardiovascular effects of idarubicin are scanty but may have clinical sig nificance in predicting late cardiovascular complications. In the present s tudy we evaluated prospectively acute neurohumoral and cardiovascular effec ts of idarubicin containing induction chemotherapy in 10 patients with newl y diagnosed AML or MDS. Idarubicin was administered intravenously 12 mg/m(2 ) on d 1, 3 and 5 as a part of the induction chemotherapy. Serial measureme nts of plasma atrial natriuretic peptide (ANP) and brain natriuretic peptid e (BNP) were performed at baseline and the day following each idarubicin in fusion. Echocardiography was performed to assess cardiac systolic and diast olic function. Signal averaged electrocardiography (ECG) was recorded to ob serve myocardial late potentials associated with possible myocardial injury . In addition, ambulatory ECG recording was performed to assess arrhythmias . Plasma concentrations of ANP increased from 18.2 +/- 1.5 pmol/l to 27.8 /- 3.5 pmol/l (p = 0.011), to 30.2 +/- 3.0 pmol/l (p = 0.002) and to 40.8 /- 6.0 pmol/l (p = 0.006) after the first, second and third doses of idarub icin, respectively. Similarly, plasma concentration of BNP increased from 6 .2 +/- 1.9 to 9.0 +/- 1.8 pmol/l (p = 0.049) and 17.5 +/- 8.1 pmol/l (p = 0 .203) after the first and third idarubicin infusion. Concomitantly, there w as a trend towards an increase in left ventricular end diastolic diameter ( LVEDD) (50.2 +/- 1.8 to 54.4 +/- 2.2 mm, p = 0.070). The increase in plasma BNP concentrations correlated significantly with the increase in LVEDD (r = 0.624; p = 0.002). No significant ECG changes or arrhythmias were associa ted with idarubicin infusions except in 1 patient who developed abnormal my ocardial late potentials. Our results show that idarubicin causes acute neu rohumoral activation associated with increased LVEDD indicating subclinical myocardial dysfunction. Whether these acute changes predict late clinical cardiomyopathy should be evaluated in prospective studies with larger numbe r of patients and with higher cumulative! anthracycline doses.