Serum biomarkers for detection of cardiomyopathy in survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.

Abstract

e21526 Background: Childhood cancer survivors are at increased risk for cardiovascular morbidity and mortality. Little is known about the utility of cardiac biomarkers (NT-proBNP, cardiac troponin-T [TnT]) for long-term surveillance. Methods: Cross-sectional analyses of 1213 survivors ≥18 years of age and ≥10 years from cancer diagnosis (786 exposed to cardiotoxic therapy [174 radiation therapy (RT) alone, 366 anthracycline alone, 246 both] and 427 unexposed). TnT > 0.01 ng/ml and NT-proBNP levels > 97.5th percentile age- and sex-specific cutoffs were considered abnormal. Three-dimensional left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function and cardiomyopathy (CM) according to the CTCAE v4.03 were evaluated. Generalized linear models estimated risk ratios (RR) and 95% confidence intervals (CI). Results: Among survivors (median 8.7 [range 0.0-23.6] years at diagnosis; 35.5 [range 19.1-62.2] years at evaluation), NT-proBNP and TnT were abnormal in 22.5% and 0.4%, respectively. A dose-dependent increased risk for abnormal NT-proBNP was seen with exposure to chest RT (referent no RT, 1- < 20 Gy RR 1.62 [CI 1.07-2.46], 20- < 30 Gy RR 1.68 [1.23-2.30], ≥30 Gy RR 3.66 [2.89-4.64]; p for trend < 0.0001) and anthracycline (referent no anthracycline, 1-200mg/m2 RR 1.39 [1.01-1.91], 201-350mg/m2 RR 2.28 [1.74-2.99], > 350mg/m2 RR 2.99 [2.27-3.95]; p for trend < 0.0001). Survivors with CM at the time of evaluation had abnormal NT-proBNP (grade 2 CM RR 1.46, CI 1.08-1.99; grade 3-4 CM 2.66, 2.02-2.39). However, among exposed survivors previously undiagnosed with clinical CM, NT-proBNP had poor sensitivity and moderate specificity in identifying those with new onset of abnormal LVEF ( < 53%), GLS or diastolic dysfunction: sensitivity (29%, 30%, 33%), specificity (75%, 77%, 76%). Also, 132 (20.2%) had abnormal NT-proBNP with normal LVEF (≥53%). Conclusions: Abnormal NT-proBNP levels were prevalent and associated with prior cardiotoxic therapy and established CM but were not sensitive for detection of new onset CM. Longitudinal follow-up is needed to determine whether abnormal NT-proBNP in the large number of survivors without CM is predictive of future CM.