title: Anthracycline-induced cardiomyopathy: long-term effects on myocardial cell integrity, cardiac adrenergic innervation and fatty acid uptake.
abstract: Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemotherapy. Limited data is available on the physiological mechanisms responsible for anthracycline-induced heart failure or its recovery. We studied four patients with a history of severe anthracycline-induced heart failure manifested 2-116 months earlier by using radionuclide ventriculography for the measurement of left ventricular function, indium-111-antimyosin scintigraphy for the detection of myocardial cell injury and iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innervation. Myocardial perfusion and fatty acid utilization were assessed with iodine-123-paraphenyl pentadecanoid acid (pPPA) and single photon emission computed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had normal or near normal left ventricular ejection fraction (LVEF) (47 and 52%), whereas the patients with symptoms of heart failure had low ejection fractions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction tended to have higher antimyosin uptake suggesting more severe, persistent myocyte injury. All but one patient showed normal fatty acid utilization. These data suggest that patients with a history of severe anthracycline-induced cardiomyopathy have persistent myocardial cell injury and adrenergic dysfunction up to 10 years after the development of heart failure. These findings seem to be present regardless of recovery of left ventricular function.
authors.affiliation: Department of Medicine, Kuopio University Hospital, 70211 Kuopio, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Nousiainen
authors.forename: E
authors.initials: E
authors.lastname: Vanninen
authors.forename: E
authors.initials: E
authors.lastname: Jantunen
authors.forename: J
authors.initials: J
authors.lastname: Remes
authors.forename: J
authors.initials: J
authors.lastname: Kuikka
authors.forename: J
authors.initials: J
authors.lastname: Hartikainen
mesh_terms: D019797:3-Iodobenzylguanidine; D000293:Adolescent; D000320:Adrenergic Fibers / Q000502:physiology; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000911:Antibodies, Monoclonal; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000473:pathology; D005227:Fatty Acids / Q000493:pharmacokinetics*; D005260:Female; D006321:Heart / Q000294:innervation; D006333:Heart Failure / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013318:Stroke Volume; D015899:Tomography, Emission-Computed, Single-Photon; D016277:Ventricular Function, Left
chemical_list: D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D005227:Fatty Acids; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; C058899:imciromab pentetate