Local arterial stiffness measured by ultrafast ultrasound imaging in childhood cancer survivors treated with anthracyclines

Abstract

Background: There is conflicting literature regarding the long-term effect of anthracycline treatment on arterial stiffness. This study assessed local arterial stiffness using ultrafast ultrasound imaging (UUI) in anthracycline treated childhood cancer survivors, at rest and during exercise.

Methods: 20 childhood cancer survivors (mean age 21.02 ± 9.45 years) treated with anthracyclines (mean cumulative dose 200.7 ± 126.80 mg/m²) and 21 healthy controls (mean age 26.00 ± 8.91 years) were included. Participants completed a demographic survey, fasting bloodwork for cardiovascular biomarkers, and performed a submaximal exercise test on a semi-supine bicycle. Pulse wave velocity (PWV) was measured in the left common carotid artery by direct pulse wave imaging using UUI at rest and submaximal exercise. Both PWV at the systolic foot (PWV-SF) and dicrotic notch (PWV-DN) were measured. Central (carotid-femoral) PWV was obtained by applanation tonometry. Carotid measurements were taken by conventional ultrasound. Measures were compared using two-tailed Students t-test or Chi-squared test, as appropriate.

Results: There was no statistically significant difference (p > 0.05) between childhood cancer survivors and healthy controls in demographic parameters (age, sex, weight, height, BMI), blood biomarkers (total cholesterol, triglycerides, LDL-c, HDL-c, hs-CRP, fasting glucose, insulin, Hb A1c), cardiovascular parameters (intima media thickness, systolic and diastolic blood pressure, heart rate, carotid diameters, distensibility) or PWV measured by UUI at rest or at exercise. There was also no difference in the cardiovascular adaptation between rest and exercise in the two groups (p > 0.05). Multivariate analysis revealed age (p = 0.024) and LDL-c (p = 0.019) to be significant correlates of PWV-SF in childhood cancer survivors, in line with previously published data.

Conclusion: We did not identify a significant impact of anthracycline treatment in young survivors of childhood cancer on local arterial stiffness in the left common carotid artery as measured by UUI.

Keywords: anthracycline; arterial stiffness; cancer survivor; pediatrics; ultrafast ultrasound imaging.

Figure 1

PWV-SF and PWV-DN measurement using UUI. 2D space-time graph representing displacement of superficial common carotid artery wall. X-axis represents time in the form of frame number. Y-axis represents position of arterial wall segment in relation to the ultrasound probe. Red represents movement towards probe. Blue represents movement away from the probe. Sloped vertical lines represent pulse waves. Dotted lines represent the slope of pulse wave, thus representing the velocity. Purple line represents ECG tracing, and blue line represents aortic pressure, time matched to space-time graph. Aortic valve opening and closure are represented by black vertical ellipses.

Figure 2

Study protocol. Diagram representation of study protocol. Participants underwent an exercise trial on a semi-supine bicycle ergometer such that patients were sitting and leaning back at about a 120° angle with their neck stable and exposed. Their arms were free and resting on arm rests such that blood pressure measurements could be consistently taken. BP measurements on the right arm were taken at each increase in exercise load following the Bruce protocol. There was a continuous 12-lead electrocardiogram (ECG) including heart rate monitoring. PWV measurements (by UUI and tonometry), as well as carotid parameter measurements were taken at rest and submaximal exercise.

Figure 3

PWV-SF comparisons. Measurements of pulse wave velocity at the systolic foot, as measured with UUI, represented on a box and whisker plot. X-axis defines group (oncology or control) and condition (rest or exercise). Y-axis represents PWV (m/s). Mean PWV +/− SD listed under each box. p < 0.05 considered significant, and represented in bold.

Figure 4

PWV-DN comparisons. Measurements of pulse wave velocity at the dicrotic notch, as measured with UUI, represented on a box and whisker plot. X-axis defines group (oncology or control) and condition (rest or exercise). Y-axis represents PWV (m/s). Mean PWV +/− SD listed under each box. p < 0.05 considered significant, and represented in bold.

Figure 5

Intra-observer (left) and inter-observer (right) variability. Bland-Altman plots representing inter- and intra-observer variability. Each point represents one PWV measurement. Left panel demonstrates intra-observer analysis. Measured as repeated analysis − original analysis. Right panel demonstrated inter-observer analysis. Measured as Observer 2 − Observer 1.