Reduced global longitudinal strain in long-term survivors of childhood, adolescent, and young adult cancer: a population comparison study

Abstract Introduction The diagnosis of subclinical myocardial damage by the study of Global Longitudinal Strain (GLS) has been the subject of many studies in acute and sub-acute cardiotoxicity. However, the place of the assesment of GLS is less known in long-term survivors of childhood, adolescent, and young adult cancer. Objective To evaluate the prevalence and determinants of reduced GLS in long-term survivors exposed to chemotherapy, with or without radiotherapy, before the age of 21 years, with preserved Left Ventricular Ejection Fraction (LVEF). Methods We performed a descriptive cross-sectional study of patients surviving one year or more of cancer treated with anthracyclines with or without mediastinal radiotherapy. A reference group of sex- and age-matched healthy subjects was recruited to determine the normal cut-off value of GLS. We evaluate the GLS with the speckle tracking technique on 2D echocardiography. The prevalence of the decrease of GLS and the predictor factors like received treatments, cardiovascular risk factors and echocardiographic data were investigated. Results The study involved 104 patients, matched to 104 healthy subjects. The cutoff value for GLS was 17.3%. The sex ratio was 1.3. The mean age was 25 years. The mean age at cancer diagnosis was 13.4 ± 5.13 years. The mean time from completion of treatment to recruitment was 10.67 +/- 5.80 years. Chemotherapy was administered alone in 80.8% of patients and combined with mediastinal radiotherapy in 19.2%. All patients received anthracyclines. The mean cumulative doses of Doxorubicin and mediastinal radiotherapy were 245.75 ± 75.14 mg/m2 and 34.6 ± 6.19 Gy, respectively. Dyslipidemia involved 12.6% of patients, obesity 8.7%, metabolic syndrome 3,8 %, hypertriglyceridemia 9.7%, and prehypertension 24.3%. The mean value of ultrasensitive troponin T, NT-proBNP, and GDF 15 was 5.79 ± 3.18 pg/ml, 64.4 ± 135.1 pg/ml, and 621.64 ± 306.11 pg/ml, respectively. The mean LVEF was 60.6 ± 5.6%. The prevalence of decreased GLS was 32%. Impaired GLS was significantly associated in multivariate analysis with the number of years since the end of treatment (OR = 4.76 - p = 0.009), obesity (OR = 15.07 - p = 0.02) and hypertriglyceridemia (OR = 7.25 - p = 0.03). Biomarkers were not useful for the diagnosis of subclinical late cardiotoxicity. Conclusion A substantial proportion of cancer survivors exposed to chemotherapy, with or without radiotherapy, exhibit reduced GLS despite preserved LVEF, consistent with subclinical myocardial dysfunction. These findings underscore the need for structured long-term cardiovascular fellow-up and aggressive management of modifiable cardiovascular risk factors in this high-risk population.