Plasma High Sensitivity Troponin T Levels in Adult Survivors of Childhood Leukaemias: Determinants and Associations with Cardiac Function

Abstract

BackgroundWe sought to quantify plasma high sensitivity cardiac troponin (hs-cTnT) levels, their determinants, and their associations with left ventricular (LV) myocardial deformation in adult survivors of childhood acute leukaemias.Methods and ResultsOne hundred adult survivors (57 males) of childhood acute leukaemias, aged 24.1±4.2 years, and 42 age-matched controls (26 males) were studied. Plasma cTnT was determined using a highly sensitive assay. Genotyping of NAD(P)H oxidase and multidrug resistance protein polymorphisms was performed. Left ventricular function was assessed by conventional, three-dimensional, and speckle tracking echocardiography. The medians (interquartile range) of hs-cTnT in male and female survivors were 4.9 (4.2 to 7.2) ng/L and 1.0 (1.0 to 3.5) ng/L, respectively. Nineteen survivors (13 males, 6 females) (19%) had elevated hs-cTnT (>95th centile of controls). Compared to those without elevated hs-TnT levels, these subjects had received larger cumulative anthracycline dose and were more likely to have leukaemic relapse, stem cell transplant, and cardiac irradiation. Their LV systolic and early diastolic myocardial velocities, isovolumic acceleration, and systolic longitudinal strain rate were significantly lower. Survivors having CT/TT at CYBA rs4673 had higher hs-cTnT levels than those with CC genotype. Functionally, increased hs-cTnT levels were associated with worse LV longitudinal systolic strain and systolic and diastolic strain rates.ConclusionsIncreased hs-cTnT levels occur in a significant proportion of adult survivors of childhood acute leukaemias and are associated with larger cumulative anthracycline dose received, history of leukaemic relapse, stem cell transplant, and cardiac irradiation, genetic variants in free radical metabolism, and worse LV myocardial deformation.

Natural history of myocardial deformation in children, adolescents, and young adults exposed to anthracyclines: Systematic review and meta‐analysis

“…Abnormal GCS was common in patients treated with anthracycline therapy alone (23%) . Cheung et al and Mavinkurve‐Groothuis et al both showed significant reductions of GCS in patients compared to controls (14% and 30% decrease, respectively). Both Cheung's and Mavinkurve‐Groothius' papers reported significant decreases in GCSr (11% and 19%, respectively).…”

“…Cheung et al, Mavinkurve‐Groothuis et al, and Christiansen et al all showed that GLS was significantly reduced in patients vs controls (between 6.4% and ~7.6% decrease). Changes in strain rate were variable: Cheung et al's paper showed no significant change in systolic or diastolic Sr while Mavinkurve‐Groothuis et al's showed a significant 13% decrease in GLSr in patients.…”

“…Cheung et al, Mavinkurve‐Groothuis et al, and Christiansen et al all showed that GLS was significantly reduced in patients vs controls (between 6.4% and ~7.6% decrease). Changes in strain rate were variable: Cheung et al's paper showed no significant change in systolic or diastolic Sr while Mavinkurve‐Groothuis et al's showed a significant 13% decrease in GLSr in patients. When comparing patients treated with anthracyclines‐only to patients treated with anthracyclines and MSRT, Yu et al showed that patients with dual therapy had significantly lower GLS compared to those treated with mono‐therapy; however, GLSr showed no change between the two groups.…”

Cardiac biomarkers indicate a need for sensitive cardiac imaging among long-term childhood cancer survivors exposed to anthracyclines

“…Gender-specific reference values for the paediatric age group remain unavailable. Cheung et al (4) recently reported on elevated highsensitivity cTnT in 19% of the adult survivors associating with an impaired left ventricular function. Despite the fact that they used gender-specific reference values, all their survivors had levels below 14 ng/L, like the patients in our study.…”

“…Novel, high-sensitivity methods in the analysis of cardiac troponin T (cTnT) in plasma enable the detection of even subclinical myocardial damage (3,4). Published studies on cardiac troponin among childhood cancer survivors have Abbreviations cTnAAbs, Troponin-specific autoantibodies; cTnI, Cardiac troponin I; cTnT, Cardiac troponin T; MRI, Magnetic resonance imaging; NT-proBNP, N-terminal pro-brain natriuretic peptide; RT3DE, Real-time three-dimensional echocardiography; SD, Standard deviation.…”