Cardiac structure, function and exercise capacity in long-term survivors of acute lymphoblastic leukaemia
P H Johnsen, C A Frederiksen, S H Poulsen, B K Albertsen, G Wood, S Riddersholm, T L Frandsen, L Andres-Jensen, K A A Myhr, K Schmeigelow, S L M Rubak, M T Skipper, W Y KimAbstract
Background
Survival after acute lymphoblastic leukaemia (ALL) now exceeds 90% following intensive chemotherapy. Anthracyclines remain integral to treatment but are associated with chemotherapy-related cardiac dysfunction (CTRCD), ranging from subclinical myocardial impairment to overt heart failure. Conventional surveillance relies primarily on two-dimensional (2D) left ventricular ejection fraction (LVEF), which may be insufficiently sensitive to detect early or subtle myocardial changes. Advanced echocardiographic techniques and cardiopulmonary exercise testing (CPET) may improve long-term cardiovascular risk assessment in cancer survivors.
Purpose
To evaluate long-term cardiac structure, function and exercise capacity in survivors of ALL using advanced echocardiography and CPET, and to compare findings with non-exposed controls.
Methods
In this cross-sectional study, survivors of ALL diagnosed between 2008 and 2018 were included together with age- and sex-matched controls without prior exposure to chemotherapy. Transthoracic echocardiography was performed, including tissue Doppler imaging, speckle-tracking echocardiography (global longitudinal strain, GLS) and three-dimensional (3D) volumetric assessment. Cardiac chamber sizes were indexed to body surface area. Cardiorespiratory fitness was assessed using symptom-limited CPET on a cycle ergometer, with peak oxygen uptake (VO2peak) as the primary exercise endpoint.
Results
A total of 291 survivors (median 6.9 years since diagnosis) and 332 controls completed echocardiography and CPET. Survivors demonstrated modest but consistent reductions in left ventricular systolic function assessed by 2D LVEF (53.8 ± 4.9% vs 55.0 ± 4.7%, p = 0.004), GLS (-17.4 ± 2.2% vs -18.1 ± 2.2%, p < 0.001) and 3D LVEF (54.6 ± 7.4% vs 56.4 ± 6.7%, p = 0.004). Right ventricular systolic function was also reduced, with lower tricuspid annular plane systolic excursion (21.7 ± 3.7 mm vs 23.4 ± 4.2 mm, p < 0.001). Survivors had smaller indexed cardiac chamber volumes (all p < 0.001). Exercise capacity was significantly impaired in survivors, with lower VO2peak compared with controls (34.6 ± 8.1 vs 41.6 ± 7.9 mL/kg/min, p < 0.001). Mean BMI values in both groups were within the normal range according to age-specific reference standards; however, survivors had a significantly higher BMI than controls as well as higher waist-to-height ratio.
Conclusion
Long-term survivors of ALL demonstrated only subtle differences in echocardiographic parameters including smaller cardiac dimensions, marginally reduced biventricular systolic function as well as reduced exercise capacity compared with non-exposed controls. Survivors had higher waist-to-height ratio and were less physical active. The observed findings may reflect chemotherapy-related cardiac dysfunction or alternatively represents physical deconditioning. Further longitudinal studies are required to further clarify causality and clinical implications.