Author + information
- Received March 24, 2015
- Revision received June 2, 2015
- Accepted June 4, 2015
- Published online March 1, 2016.
- Klaus Murbraech, MDa,∗ (, )
- Torgeir Wethal, MD, PhDb,
- Knut B. Smeland, MDc,d,
- Harald Holte, MD, PhDd,
- Jon Håvard Loge, MD, PhDe,f,
- Espen Holte, MDb,
- Assami Rösner, MD, PhDg,
- Håvard Dalen, MD, PhDh,i,
- Cecilie E. Kiserud, MD, PhDc,d and
- Svend Aakhus, MD, PhDa,j
- aDepartment of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- bDepartment of Cardiology, St. Olavs Hospital, University of Trondheim, Trondheim, Norway
- cNational Advisory Unit on Late Effects after Cancer Treatment, Oslo University Hospital, Oslo, Norway
- dDepartment of Oncology, Oslo University Hospital, Oslo, Norway
- eFaculty of Medicine, University of Oslo, Oslo, Norway
- fRegional Centre for Excellence in Palliative Care, Oslo University Hospital, Oslo, Norway
- gDepartment of Cardiology, University Hospital North Norway, Tromsoe, Norway
- hDepartment of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway
- iDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
- jFaculty of Medicine, University of Trondheim, Trondheim, Norway
- ↵∗Reprint requests and correspondence:
Dr. Klaus Murbraech, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Pb 4950 Nydalen, 0424 Oslo, Norway.
Objectives 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/m2, 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.
- autologous hematopoietic stem cell transplantation
- lymphoma survivors
- radiation therapy
- valvular dysfunction
The study was supported by South-Eastern Norway Regional Health Authority and Extrastiftelsen, and received no funding from the medical industry.
Dr. E. Holte has received honoraria from Actelion Pharmaceuticals Ltd. for lecture, field of pulmonary hypertension. Dr. Dalen has positions at MI Lab, a Centre of Research-based Innovation that is funded by the Research Council of Norway and industry. One of the industry partners is GE Vingmed Ultrasound. The Centre has a total budget of 24 million NOK for the 8-year period from 2007 to 2014, and the contribution from GE Vingmed Ultrasound to this budget is 7 million NOK. GE Vingmed Ultrasound had no role in this manuscript, such as planning of the study, data acquisition, drafting or revision of the manuscript or supply of ultrasound equipment. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 24, 2015.
- Revision received June 2, 2015.
- Accepted June 4, 2015.
- American College of Cardiology Foundation