Left Ventricular Systolic Function in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation

Richard J Massey; Phoi P Diep; Ellen Ruud; Marta M Burman; Anette B Kvaslerud; Lorentz Brinch; Svend Aakhus; Lars L Gullestad; Jan O Beitnes

doi:10.1016/j.jaccao.2020.06.011

Left Ventricular Systolic Function in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation

JACC CardioOncol. 2020 Sep 15;2(3):460-471. doi: 10.1016/j.jaccao.2020.06.011. eCollection 2020 Sep.

Authors

Richard J Massey^{1

2}, Phoi P Diep^{2

3

4}, Ellen Ruud^{2

3}, Marta M Burman^{2

3

4}, Anette B Kvaslerud^{1

2}, Lorentz Brinch⁵, Svend Aakhus^{6

7}, Lars L Gullestad^{1

2

8}, Jan O Beitnes¹

Affiliations

¹ Department of Cardiology, Oslo University Hospital, Oslo, Norway.
² Department of Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Hematology and Oncology, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
⁴ Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
⁵ Department of Hematology, Oslo University Hospital, Oslo, Norway.
⁶ Department of Circulation and Imaging, Faculty of Medicine and Health Science, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
⁷ Clinic of Cardiology, St. Olavs Hospital, Trondheim, Norway.
⁸ KG Jebsen Center for Cardiac Research, University of Oslo, and Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway.

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a potentially curative therapy for malignant and nonmalignant diseases, is being increasingly used in younger patients. Although allo-HSCT survivors have an established increased risk of cardiovascular disease, there is limited knowledge of the long-term effects on cardiac function in survivors.

Objectives: The purpose of this study was to describe left ventricular (LV) systolic function in long-term allo-HSCT survivors treated in childhood, adolescence, or early adulthood.

Methods: Our cross-sectional cohort study included 104 patients (56% women), age 18 ± 10 years at time allo-HSCT with 17 ± 6 years of follow-up. Echocardiography included 2-dimensional (2D) and 3-dimensional (3D) analyses and speckle tracking imaging. In total, 55 healthy control subjects with a similar age, sex, and body mass index were used for comparison. Left ventricular systolic dysfunction (LVSD) was defined as reduced 2D left ventricular ejection fraction (LVEF) of <52% in men and <54% in women, and/or a reduced global longitudinal strain (GLS) of ≥-17%. Multivariable linear regression was used to determine independent predictors of 2D-LVEF and GLS.

Results: Allo-HSCT survivors had significantly reduced LV systolic function compared with control subjects: 2D-LVEF (55.2 ± 5.8% vs. 59.0 ± 2.9%; p < 0.001), 3D LVEF (54.0 ± 5.1% vs. 57.6 ± 2.7%; p < 0.001), and GLS (-17.5 ± 2.2% vs. -19.8 ± 1.4%; p < 0.001). LVSD was found in 44.2%, of whom 28.3% were symptomatic. Clinical factors independently associated with 2D-LVEF and/or GLS included age, anthracyclines, graft versus host disease (GVHD), heart rate, and hypertension. In the 45% of survivors pre-treated with anthracyclines, the effect of anthracyclines on 2D-LVEF and GLS was dose-dependent.

Conclusions: LVSD is common in long-term survivors of allo-HSCT treated in their youth. Pre-HSCT therapies with anthracyclines, age, heart rate, hypertension, and graft versus host disease are associated with measures of LV function.

Keywords: CV, cardiovascular; GLS, global longitudinal strain; GVHD, graft versus host disease; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; NYHA, New York Heart Association; allo-HSCT, allogeneic hematopoietic stem cell transplantation; anthracyclines; cardiovascular risk factors; echocardiography; graft versus host disease; heart failure; left ventricular systolic function.