BACKGROUND: Late cardiotoxic effects of doxorubicin are increasingly a problem for patients who survive childhood cancer. Cardiotoxicity is often progressive, and some patients have disabling symptoms. Our objective was to identify risk factors for late cardiotoxicity. METHODS: We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier. Measurements of blood pressure and left ventricular function, contractility (measured as the stress-velocity index), end-diastolic posterior-wall thickness, end-diastolic dimension, mass, and afterload (measured as end-systolic wall stress) were compared with sex-specific values from a cohort of 296 normal subjects. RESULTS: All echocardiographic measurements were abnormal at follow-up a minimum of two years after the end of therapy, with more frequent and severe abnormalities in female patients. In a multivariate analysis, female sex and a higher cumulative dose of doxorubicin were associated with depressed contractility (P < or = 0.001), and there was an interaction between these two variables. Independent and significant associations were found between a higher rate of administration of doxorubicin and increased afterload (P < or = 0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P < or = 0.001); between a younger age at diagnosis and reduced left-ventricular-wall thickness and mass and increased afterload; and between a longer time since the completion of doxorubicin therapy and reduced left-ventricular-wall thickness and increased afterload (P < or = 0.001). CONCLUSIONS: Female sex and a higher rate of administration of doxorubicin were independent risk factors for cardiac abnormalities after treatment with doxorubicin for childhood cancer; the prevalence and severity of abnormalities increased with longer follow-up.
BACKGROUND: Late cardiotoxic effects of doxorubicin are increasingly a problem for patients who survive childhood cancer. Cardiotoxicity is often progressive, and some patients have disabling symptoms. Our objective was to identify risk factors for late cardiotoxicity. METHODS: We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier. Measurements of blood pressure and left ventricular function, contractility (measured as the stress-velocity index), end-diastolic posterior-wall thickness, end-diastolic dimension, mass, and afterload (measured as end-systolic wall stress) were compared with sex-specific values from a cohort of 296 normal subjects. RESULTS: All echocardiographic measurements were abnormal at follow-up a minimum of two years after the end of therapy, with more frequent and severe abnormalities in female patients. In a multivariate analysis, female sex and a higher cumulative dose of doxorubicin were associated with depressed contractility (P < or = 0.001), and there was an interaction between these two variables. Independent and significant associations were found between a higher rate of administration of doxorubicin and increased afterload (P < or = 0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P < or = 0.001); between a younger age at diagnosis and reduced left-ventricular-wall thickness and mass and increased afterload; and between a longer time since the completion of doxorubicin therapy and reduced left-ventricular-wall thickness and increased afterload (P < or = 0.001). CONCLUSIONS: Female sex and a higher rate of administration of doxorubicin were independent risk factors for cardiac abnormalities after treatment with doxorubicin for childhood cancer; the prevalence and severity of abnormalities increased with longer follow-up.
Authors: Kevin C Oeffinger; Ann C Mertens; Melissa M Hudson; James G Gurney; Jacqueline Casillas; Hegang Chen; John Whitton; Mark Yeazel; Yutaka Yasui; Leslie L Robison Journal: Ann Fam Med Date: 2004 Jan-Feb Impact factor: 5.166
Authors: Steven E Lipshultz; William T Shearer; Bruce Thompson; Kenneth C Rich; Irene Cheng; E John Orav; Sulekha Kumar; Ricardo H Pignatelli; Louis I Bezold; Philip LaRussa; Thomas J Starc; Julie S Glickstein; Sharon O'Brien; Ellen R Cooper; James D Wilkinson; Tracie L Miller; Steven D Colan Journal: J Am Coll Cardiol Date: 2011-01-04 Impact factor: 24.094
Authors: Steven E Lipshultz; Kirk A Easley; E John Orav; Samuel Kaplan; Thomas J Starc; J Timothy Bricker; Wyman W Lai; Douglas S Moodie; George Sopko; Mark D Schluchter; Steven D Colan Journal: Lancet Date: 2002-08-03 Impact factor: 79.321