Left ventricular function and its longitudinal change in Swiss childhood cancer survivors - Results from the CardioOnco Study

Background/PurposeChildhood cancer survivors (CCS) are at risk for cardiac late effects. Echocardiographic assessment of cardiac function by left ventricular ejection fraction (LVEF) is recommended for survivors treated with known cardiotoxic treatments (anthracyclines; heart-relevant radiotherapy). The evidence on cardiotoxicity of other systemic anticancer therapies is conflicting and longitudinal changes in heart function are understudied. We assessed cardiac function in CCS; factors associated with LVEF and longitudinal changes in LVEF. MethodsIn this prospective, multicenter cohort study, we invited CCS aged [&ge;]18 years, diagnosed <21 years, survived [&ge;]5 years, and received any systemic anticancer therapy or heart-relevant radiotherapy between 1976-2019. We invited them for an echocardiographic assessment including 2-dimensional LVEF (reduced LVEF: <54% for females; <52% for males). We stratified CCS in anthracyclines only, heart-relevant radiotherapy only, both, and a standard risk group exposed to any other systemic anticancer treatment and compared groups using ANOVA- and t-tests. We performed multivariable linear regression to investigate sociodemographic, treatment-, and lifestyle-related factors (hypertension, smoking, dyslipidemia, diabetes, overweight/obesity), and multilevel modelling to assess LVEF changes over time. ResultsWe assessed 487 CCS (median age: 32 years, IQR: 24-39) with a median time since diagnosis of 24 years (IQR 17-31). Overall prevalence of reduced LVEF was 7.2% (35/487), 7.3% (19/260) for anthracyclines only, 3.6% (1/28) for heart-relevant radiotherapy only, 9.4% (8/85) for both, and 6.1% (7/114) for the standard risk group. Male CCS were at risk for reduced LVEF [{beta} coefficient for male sex = -1.37; 95%CI -2.36, -0.37], and higher cumulative anthracycline dose (per 100 mg/m{superscript 2}) was associated with reduced LVEF ({beta} -0.83; 95%CI -1.20, -0.45). Heart-relevant radiotherapy, other systemic anticancer treatments, and lifestyle were not associated with LVEF. We found a slight annual improvement of LVEF 0.24% among 140 participants followed up for a median of 4.3 years, however, there was no indication of statistical significance (p=0.12). ConclusionThis first nationwide study found that a substantial proportion of survivors had reduced LVEF, especially males and those treated with anthracyclines. While cardiac function appeared stable over a four-year period, long-term changes remain uncertain, emphasizing the importance of ongoing cardiac surveillance in this vulnerable population.