Systolic and diastolic dysfunction in long-term adult survivors of childhood cancer

Aim: To assess systolic and diastolic function in adult childhood-cancer survivors (CCS) after treatment entailing potential cardiovascular toxicity. Methods: The study cohort consisted of 277 adult CCS (median age 28 [range 18-48] years), who had been treated with anthracyclines, platinum, and/or radiotherapy between 1976 and 1999, along with 130 healthy sibling controls. The assessments included echocardiography, baroreflex sensitivity measurement, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiography measurements were shortening fraction (SF) (abnormal < 29%) for systolic function and tissue velocity imaging of early diastole (TVI Et) (abnormal < 8.00) cm/sec for diastolic function; systolic function was also assessed by the wall motion score index (WMSI). Results: At 18 (5-31) years post-treatment, the prevalence of both impaired SF and abnormal WMSI was increased in CCS compared to controls (p = 0.003 and p < 0.001, respectively). CCS also had an increased prevalence of diastolic dysfunction compared to the controls (12% versus 1%, p < 0.001). Abnormal SF and/or abnormal diastolic function were found in 43% of CCS. NT-proBNP was higher in CCS and was associated to increased WMSI. Baroreflex sensitivity was lower in CCS and was associated with diastolic dysfunction. Systolic as well as diastolic dysfunction was associated with cumulative dose of anthracyclines and mediastinal irradiation. Conclusion: After treatment with potential cardiovascular toxic therapies, the risk of systolic and diastolic dysfunction in CCS is considerable. Since these abnormalities, in particular diastolic dysfunction, are age related, the observed effects might be considered a sign of precocious cardiac ageing.