Longitudinal Assessment of Cardiac Function After Craniospinal Irradiation in Pediatric Central Nervous System Tumor Survivors

Figures

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  Figure 1. Completeness of Echocardiographic Variables by Time Since Radiation Exposure Bar graph showing the number of patients with ≥1 echocardiographic measurement by time since radiation exposure. Patients contributed a variable number of assessments over follow-up, with decreasing data availability at later time intervals. E/A ratio = early to late mitral inflow velocity ratio; GLS = global longitudinal strain; LVEF = left ventricular ejection fraction; MV E/E’ = mitral valve E to e’ ratio.

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  Figure 2. Trajectories of Echocardiographic Parameters by Time Since Radiation Exposure Modeled trajectories of LVEF (M-mode), LVSF (M-mode), GLS, MV E/E’ lateral, and E/A ratio by years postradiation. Lines represent model-estimated means; shaded areas denote 95% CIs; P values reflect overall trends. LVEF, LVSF, and GLS declined over time since radiation (LVEF P = 0.006; LVSF and GLS P < 0.001). MV E/E’ lateral remained unchanged across age and time. E/A ratio showed a borderline association with time since radiation (P = 0.056). LVSF = left ventricular shortening fraction; other abbreviations as in Figure 1.

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  Figure 3. Cumulative Incidence of Abnormal Echocardiographic Parameters Following Radiation Therapy Cumulative incidence curves for abnormal echocardiographic parameters following radiation therapy, estimated using competing risk models with death as a competing event and administrative censoring at 12 years, GLS <16% (left) and LVSF <28% (right). Shaded areas represent 95% CIs; numbers at risk are shown below the x-axis. No patients developed LVEF <50% during follow-up; therefore, LVEF is not shown. Abbreviations as in Figures 1 and 2.

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  Figure 4. Effect Modification of Echocardiographic Trajectories Predicted trajectories from adjusted multivariable models demonstrating effect modification of systolic function over time. (A) LVEF (M-mode) by age at diagnosis across months since radiation (interaction P = 0.041). (B) LVSF (M-mode) by age at diagnosis across months since radiation (interaction P < 0.001). (C) GLS by sex across attained age (interaction P = 0.015). (D) LVEF (M-mode) by endocrine comorbidities across attained age (interaction P = 0.037). (E) LVSF (M-mode) by cyclophosphamide cumulative dose across attained age (interaction P = 0.002). Shaded areas represent 95% CIs. Abbreviations as in Figures 1 and 2.

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  Central Illustration. Long-Term Cardiac Function After Craniospinal Irradiation in Pediatric Central Nervous System Tumor Survivors Longitudinal trajectories of left ventricular systolic function (LVEF, LVSF) and GLS show progressive declines over time despite low mean heart radiation doses, whereas diastolic function remains stable. Age at diagnosis, sex, and endocrine comorbidities modify cardiac trajectories. CNS = central nervous system; CSI = craniospinal irradiation; other abbreviations as in Figures 1 and 2.