Digoxin Use in Infants with Single Ventricle Physiology: Secondary Analysis of the Pediatric Heart Network Infant Single Ventricle Trial Public Use Dataset

Pediatr Cardiol. 2018 Aug;39(6):1200-1209. doi: 10.1007/s00246-018-1884-x. Epub 2018 May 24.

Abstract

Digoxin has been associated with reduced interstage mortality after Norwood procedure. We sought to determine its association with survival and change in weight-for-age Z-score (WAZ) before the superior cavopulmonary connection (SCPC) surgery and at 14 months in a heterogeneous group of single ventricle infants. We performed a post-hoc analysis of the Pediatric Heart Network Infant Single Ventricle public use dataset to determine associations between digoxin and survival, transplant-free survival, and change in WAZ pre-SCPC and at 14 months. Sub-analyses of survival and transplant-free survival were performed for subjects who underwent Damus-Kaye-Stansel (DKS)/Norwood. Propensity score weighting was used in Cox hazard-proportion models. Of 229 subjects, 82 (36%) received digoxin and 147 (64%) received no digoxin. Pre-SCPC and 14-month survival and transplant-free survival were not significantly different between the digoxin and no digoxin groups for the main cohort and DKS/Norwood sub-group. However, in DKS/Norwood subjects there was a trend towards improved interstage transplant-free survival in the digoxin group (95.7 vs. 89.6%, p = 0.08). Digoxin was associated with a greater decrease in WAZ from birth to pre-SCPC (- 1.96 ± 0.19 vs. - 1.31 ± 0.18, p < 0.001) and birth to 14 months (- 0.64 ± 0.15 vs. - 0.19 ± 0.15, p = 0.03). Digoxin was not associated with improved survival during the interstage or at 14 months in a mixed single ventricle cohort, but there was a trend towards improved interstage transplant-free survival in post-Norwood infants. As digoxin was associated with poorer weight gain, further research is needed to identify the risks/benefits for anatomic subtypes of infants with single ventricles.

Keywords: Digoxin; Single ventricle; Survival.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Cardiotonic Agents / therapeutic use*
  • Child
  • Databases, Factual
  • Digoxin / therapeutic use*
  • Double-Blind Method
  • Female
  • Heart Ventricles / surgery
  • Humans
  • Hypoplastic Left Heart Syndrome / drug therapy*
  • Hypoplastic Left Heart Syndrome / mortality
  • Hypoplastic Left Heart Syndrome / surgery
  • Infant
  • Infant, Newborn
  • Male
  • North America
  • Norwood Procedures / adverse effects
  • Norwood Procedures / methods*
  • Patient Discharge
  • Propensity Score
  • Survival Analysis
  • Treatment Outcome

Substances

  • Cardiotonic Agents
  • Digoxin