title: The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia.
abstract: Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.
authors.affiliation: 2nd Department of Medicine - Clinical Hematology, University Hospital, 500 05 Hradec Králové, Czech Republic. jan.hor@post.cz
authors.forename: J M
authors.initials: JM
authors.lastname: Horácek
authors.forename: R
authors.initials: R
authors.lastname: Pudil
authors.forename: M
authors.initials: M
authors.lastname: Tichý
authors.forename: L
authors.initials: L
authors.lastname: Jebavý
authors.forename: A
authors.initials: A
authors.lastname: Strasová
authors.forename: R
authors.initials: R
authors.lastname: Praus
authors.forename: P
authors.initials: P
authors.lastname: Zák
authors.forename: J
authors.initials: J
authors.lastname: Malý
mesh_terms: D000208:Acute Disease; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood*; D052279:Creatine Kinase, MB Form / Q000097:blood; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004452:Echocardiography; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects*; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D020107:Troponin T / Q000097:blood
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D003561:Cytarabine; D020097:Natriuretic Peptide, Brain; D052279:Creatine Kinase, MB Form; D015255:Idarubicin