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

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.

Graphical abstract

Figure 1

CONSORT Diagram: Illustration of Patient Recruitment In total, 104 (66.2%) of eligible survivors were evaluated with comprehensive echocardiography.

Central Illustration

Left Ventricular Systolic Function in Long-Term Survivors Treated as Children, Adolescents, and Young Adults With Allo-HSCT Allogeneic hematopoietic stem cell transplantation (allo-HSCT) survivors were found to have significantly reduced left ventricular systolic function with echocardiography compared with healthy control subjects. Most cases were described as mild to moderate global hypokinesis with few cases of valve disease. Significant independent predictors of left ventricular systolic function were age, anthracyclines, graft versus host disease, heart rate, and hypertension. 2D = 2-dimensional; 3D = 3-dimensional; LVEF = left ventricular ejection fraction; GLS = global longitudinal strain; MAPSE = mitral annular plane systolic excursion.