title: Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients.
abstract: Idarubicin has been shown to have similar or superior antileukemic activity to daunorubicin with less cumulative cardiotoxicity. However, data of acute cardiovascular effects of idarubicin are scanty but may have clinical significance in predicting late cardiovascular complications. In the present study we evaluated prospectively acute neurohumoral and cardiovascular effects of idarubicin containing induction chemotherapy in 10 patients with newly diagnosed AML or MDS. Idarubicin was administered intravenously 12 mg/m2 on d 1, 3 and 5 as a part of the induction chemotherapy. Serial measurements of plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were performed at baseline and the day following each idarubicin infusion. Echocardiography was performed to assess cardiac systolic and diastolic function. Signal averaged electrocardiography (ECG) was recorded to observe 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 idarubicin, 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 was 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 associated with idarubicin infusions except in 1 patient who developed abnormal myocardial late potentials. Our results show that idarubicin causes acute neurohumoral 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 number of patients and with higher cumulative anthracycline doses.
authors.affiliation: Department of Medicine, Kuopio University Hospital and University of Kuopio, Finland. tapio.nousiainen@kuh.fi
authors.forename: T
authors.initials: T
authors.lastname: Nousiainen
authors.forename: E
authors.initials: E
authors.lastname: Jantunen
authors.forename: E
authors.initials: E
authors.lastname: Vanninen
authors.forename: J
authors.initials: J
authors.lastname: Remes
authors.forename: J
authors.initials: J
authors.lastname: Puustinen
authors.forename: A
authors.initials: A
authors.lastname: Rantala
authors.forename: O
authors.initials: O
authors.lastname: Vuolteenaho
authors.forename: J
authors.initials: J
authors.lastname: Hartikainen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D009320:Atrial Natriuretic Factor / Q000097:blood; D004562:Electrocardiography; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects; D007275:Injections, Intravenous; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain; D009490:Neurosecretory Systems / Q000503:physiopathology*
chemical_list: D000903:Antibiotics, Antineoplastic; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D015255:Idarubicin