Digoxin associated with greater transplant-free survival in high versus low-risk interstage patients

Abstract Background Digoxin has been associated with reduced interstage mortality for patients with functional single ventricles with aortic hypoplasia/ductal-dependent systemic circulation. The NEONATE score can stratify patients by risk of death or transplant (DTx) based on clinical factors. We suspected a variable transplant-free survival benefit of digoxin in high- versus low-risk patients. Methods National Pediatric Cardiology Quality Improvement Collaborative patients discharged following stage 1 palliation with complete data were categorized as high- or low-risk based on a modified NEONATE score. The primary outcome of DTx was evaluated. A mixed-effect regression evaluated associations between digoxin prescription and risk factors. Results 1,199 patients were included; 399 (33%) were high-risk. Baseline demographics were similar between cohorts. Blalock-Taussig shunt (BTS)or Hybrid operation, post-operative extracorporeal membrane oxygenation, opiate prescription, and significant tricuspid regurgitation or arch obstruction were more common in high-risk patients. Odds of DTx were 65% lower in high-risk patients prescribed digoxin compared to those who were not (p = 0.001). Digoxin prescription was associated with 60.8% lower DTx in the high risk cohort (7.8% vs. 19.9%; p = 0.001). There was no significant difference in the death/transplant rate according to digoxin prescription in the low-risk cohort (4.7% vs. 5.7%; p = 0.46). BTS, aortic arch obstruction, and significant tricuspid regurgitation were most strongly associated with deriving a benefit from digoxin. Conclusions Digoxin use is associated with a significant improvement in transplant-free survival in high- but not low-risk interstage patients. A tailored approach to the use of digoxin in interstage patients may be warranted.