New Heart Failure Biomarkers in Long-Term Follow-up after Childhood Cancer

Objectives: New biomarkers for heart failure have been introduced with interesting results in adult heart failure patients, especially in patients with preserved ejection fraction. Patients in follow-up after childhood cancer may suffer from anthracycline-induced heart failure that is not easy to detect early by standard echo and laboratory parameters. We aimed to evaluate new biomarkers for heart failure with preserved ejection fraction (HFpEF) in children, adolescents, and young adults in follow-up after childhood cancer.

Methods: In addition to standard echo parameters for left ventricular function (EF [ejection fraction] and FS [shortening fraction]) and routine laboratory parameters for heart failure (NTproBNP and troponin T [TnT]), markers for myocardial inflammation (interleukin-6 [IL-6]), extracellular matrix remodeling (CITP [C-terminal telopeptide of type-I collagen] and PIIINP [intact N-terminal propeptide of type III procollagen]), and other heart failure biomarkers (galectin 3 and soluble ST2 [sST2]) were measured at least 8 years (median 13 years [IQR: 10–15]) after diagnosis of childhood cancer in 50 patients and compared with 50 healthy controls.

Result: EF (median 58.5% [IQR: 54.3–61.8]) and FS (31% [IQR: 29–35.8]) were normal in all patients. In addition, routine parameters of heart failure (NTproBNP and TnT), inflammation (IL-6), and sST2 were not significantly different between study and control groups (study vs. control: NTproBNP: median, 45 vs. 51.5 ng/L; p = 0.14; TnT: median 6 vs. 6 ng/L; p = 0.48; IL-6: median 0.68 vs. 0.68 pg/mL; p = 0.29; sST2: 26.1 vs. 23.9; p = 0.35). In contrast, parameters for extracellular matrix remodeling (CITP: median 8.2 vs. 13.6 mcg/L; p < 0.0001, PIIINP: median 6 vs. 10.2 mcg/L; p < 0.0001), and galectin, 3 (median, 6.5 vs. 6.1; p = 0.01) were significantly different between the two groups.

Conclusion: Standard echo and laboratory parameters used during cardiac evaluation in follow-up after childhood cancer seem less sensitive in detecting early remodeling processes in contrast to newer biomarkers used in HFpEF. The detection of myocardial remodeling processes at an early stage might give the opportunity to begin heart failure treatment earlier with the potential to delay its negative influence on cardiac function.