Plasma high sensitivity troponin T levels in adult survivors of childhood leukaemias: determinants and associations with cardiac function

PLoS One. 2013 Oct 21;8(10):e77063. doi: 10.1371/journal.pone.0077063. eCollection 2013.

Abstract

Background: We 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 results: One 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 (>95(th) 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.

Conclusions: Increased 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Anthracyclines / therapeutic use
  • Chemoradiotherapy
  • Child
  • Echocardiography / methods
  • Gene Frequency
  • Genotype
  • Heart / physiopathology
  • Humans
  • Leukemia / blood*
  • Leukemia / genetics
  • Leukemia / therapy*
  • Linear Models
  • Male
  • Multidrug Resistance-Associated Proteins / genetics
  • Myocardium / metabolism
  • NADPH Oxidases / genetics
  • Neoplasm Recurrence, Local
  • Stem Cell Transplantation
  • Survivors*
  • Troponin T / blood*
  • Young Adult

Substances

  • Anthracyclines
  • Multidrug Resistance-Associated Proteins
  • Troponin T
  • multidrug resistance-associated protein 2
  • NADPH Oxidases
  • CYBA protein, human
  • NCF4 protein, human
  • multidrug resistance-associated protein 1

Grant support

Children’s Cancer Foundation (Hong Kong). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.