title: BNP predicts chemotherapy-related cardiotoxicity and death: comparison with gated equilibrium radionuclide ventriculography.
abstract: Cardiotoxicity is a dose-limiting side-effect of cancer chemotherapeutics such as anthracyclines. The drug-induced cardiac toxicity is currently monitored with repeated assessments of the left ventricular ejection fraction (LVEF) using multigated equilibrium radionuclide ventriculography (MUGA) or echocardiography. However, the plasma cardiac biomarker B-type natriuretic peptide (BNP) has been suggested for early identification of cardiac dysfunction. The aim of the study was to compare LVEF obtained by MUGA and plasma BNP as predictors of developing congestive heart failure (CHF) or death in a population of anthracycline-treated cancer patients.
  
  
  METHODS
  We prospectively followed 333 cancer patients referred to our department for routine monitoring of LVEF with MUGA and measurement of BNP, January-December 2004. Study end points were hospitalization for CHF and death during follow-up 2004-2010. Data were obtained from the Danish National Patient Registry.
  
  
  RESULTS
  During follow-up (mean 1,360 days), 21 of the patients were admitted to hospital with a diagnosis of CHF and 194 of the patients died. BNP levels were significantly higher and LVEF lower in the group of patients that developed CHF. Using cut-off points of BNP>100 pg/ml (HR 5.5; CI 1.8-17.2; p = 0.003) and LVEF <50% (HR 7.9; CI 3.0-21.4; p<0.001) both significantly predicted CHF. Using the same cut-off points only BNP (HR 1.9; CI 1.3-2.9; p = 0.002) and not LVEF (HR 1.1; CI 0.7-1.8; p = 0.58) was predictive of overall death. In multivariate Cox analysis both BNP and LVEF were independent predictors of CHF while age remained the only independent predictor of overall death.
  
  
  CONCLUSIONS
  In cancer patients treated with cardiotoxic chemotherapy both BNP and LVEF can significantly predict subsequent hospitalization with CHF. In addition, BNP and not LVEF has a prognostic value in detecting overall death. This prospective study based on the hitherto largest study population supports BNP as a clinical relevant method for monitoring chemotherapy-related cardiac failure and death.
authors.affiliation: Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet and University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Skovgaard
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet and University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Philip
authors.initials: P
authors.lastname: Hasbak
authors.affiliation: Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet and University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D015637:Gated Blood-Pool Imaging; D006333:Heart Failure / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D016277:Ventricular Function, Left / Q000502:physiology; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D020097:Natriuretic Peptide, Brain