title: Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy.
abstract: BACKGROUND
  Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity.
  
  
  RESULTS
  We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0) years. The overall incidence of cardiotoxicity was 9% (n=226). The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity occurred within the first year. Twenty-five (11%) patients had full recovery, and 160 (71%) patients had partial recovery. At multivariable analysis, end-chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09; 95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were independent correlates of cardiotoxicity.
  
  
  CONCLUSIONS
  Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment. Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function.
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.). daniela.cardinale@ieo.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cardinale
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colombo
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Giulia
authors.initials: G
authors.lastname: Bacchiani
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Ines
authors.initials: I
authors.lastname: Tedeschi
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Meroni
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Maurizio
authors.initials: M
authors.lastname: Civelli
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lamantia
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Nicola
authors.initials: N
authors.lastname: Colombo
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Cesare
authors.initials: C
authors.lastname: Fiorentini
authors.affiliation: From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Cipolla
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D066126:Cardiotoxicity / Q000175:diagnosis / Q000628:therapy; D015331:Cohort Studies; D004317:Doxorubicin / Q000009:adverse effects*; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced* / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: anthracyclines; cardiomyopathies; cardiotoxicity; drug therapy; heart failure; recovery of function