title: Valvular Dysfunction in Lymphoma Survivors Treated With Autologous Stem Cell Transplantation: A National Cross-Sectional Study.
abstract: OBJECTIVE
  This study assessed the prevalence and associated risk factors for valvular dysfunction (VD) observed in adult lymphoma survivors (LS) after autologous hematopoietic stem cell transplantation (auto-HCT), and to determine whether anthracycline-containing chemotherapy (ACCT) alone in these patients is associated with VD.
  
  
  BACKGROUND
  The prevalence of and risk factors for VD in LS after auto-HCT is unknown. Anthracyclines may induce heart failure, but any association with VD is not well-defined.
  
  
  METHODS
  This national cross-sectional study included all adult LS receiving auto-HCT from 1987 to 2008 in Norway. VD was defined by echocardiography as either more than mild regurgitation or any stenosis. Observations in LS were compared with a healthy age- and gender-matched (1:1) control group.
  
  
  RESULTS
  In total, 274 LS (69% of all eligible) participated. Mean age was 56 ± 12 years, mean follow-up time after lymphoma diagnosis was 13 ± 6 years, and 62% of participants were males. Mean cumulative anthracycline dosage was 316 ± 111 mg/m(2), and 35% had received radiation therapy involving the heart (cardiac-RT). VD was observed in 22.3% of the LS. Severe VD was rare (n = 9; 3.3% of all LS) and mainly aortic stenosis (n = 7). We observed VD in 16.7% of LS treated with ACCT alone (n = 177), corresponding with a 3-fold increased VD risk (odds ratio: 2.9; 95% confidence interval: 1.5 to 5.8; p = 0.002) compared with controls. Furthermore, the presence of aortic valve degeneration was increased in the LS after ACCT alone compared with controls (13.0% vs. 2.9%; p < 0.001). Female sex, age >50 years at lymphoma diagnosis, ≥3 lines of chemotherapy before auto-HCT, and cardiac-RT >30 Gy were identified as independent risk factors for VD in the LS.
  
  
  CONCLUSIONS
  In LS, ACCT alone was significantly associated with VD and related to valvular degeneration. Overall, predominantly moderate VD was prevalent in LS, and longer observation time is needed to clarify the clinical significance of this finding.
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Electronic address: sbmurk@ous-hf.no.
authors.forename: Klaus
authors.initials: K
authors.lastname: Murbraech
authors.affiliation: Department of Cardiology, St. Olavs Hospital, University of Trondheim, Trondheim, Norway.
authors.forename: Torgeir
authors.initials: T
authors.lastname: Wethal
authors.affiliation: National Advisory Unit on Late Effects after Cancer Treatment, Oslo University Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Knut B
authors.initials: KB
authors.lastname: Smeland
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway; Regional Centre for Excellence in Palliative Care, Oslo University Hospital, Oslo, Norway.
authors.forename: Jon Håvard
authors.initials: JH
authors.lastname: Loge
authors.affiliation: Department of Cardiology, St. Olavs Hospital, University of Trondheim, Trondheim, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Holte
authors.affiliation: Department of Cardiology, University Hospital North Norway, Tromsoe, Norway.
authors.forename: Assami
authors.initials: A
authors.lastname: Rösner
authors.affiliation: Department of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Håvard
authors.initials: H
authors.lastname: Dalen
authors.affiliation: National Advisory Unit on Late Effects after Cancer Treatment, Oslo University Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Cecilie E
authors.initials: CE
authors.lastname: Kiserud
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Trondheim, Trondheim, Norway.
authors.forename: Svend
authors.initials: S
authors.lastname: Aakhus
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006349:Heart Valve Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D006351:Heart Valves / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D016015:Logistic Models; D008223:Lymphoma / Q000175:diagnosis / Q000453:epidemiology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D015995:Prevalence; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D017741:Survivors; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic
keywords: anthracyclines; autologous hematopoietic stem cell transplantation; echocardiography; lymphoma survivors; radiation therapy; valvular dysfunction