Risk factors for death or heart transplantation in single ventricle physiology (tricuspid atresia, pulmonary atresia and heterotaxy): a systematic review and meta-analysis

Background We sought to evaluate risk factors (RF) for death or heart transplantation (D-HT) in single ventricle (SV) physiology due to tricuspid atresia (TA), pulmonary atresia-intact ventricular septum (PA-IVS) and heterotaxy-SV (HX), clinical conditions in which outcome data are limited. Methods To conduct a systematic review, we included citations that evaluated occurrence of D-HT in SV physiology of TA, PA-IVS and HX in English articles published between January 1998 and December 2017 based on inclusion and exclusion criteria, following the PRISMA guidelines. Cochrane ROBINS-I risk of bias (ROB) tool for non-randomized studies was used to assess ROB. Meta-analysis was performed if RF data were available in > 3 studies. Results Of 11,629 citations reviewed, 30 met inclusion criteria. All 30 were observational retrospective studies. In all, 1,770 patients were included, 481 died and 21 underwent HT (63 lost to follow-up); 723 patients reached Fontan completion. We found that systemic ventricular dysfunction (odds ratio (OR) 20.7, confidence interval (CI) 10.0 – 42.5, I2=0%) and atrioventricular valve regurgitation (AVR) were associated with risk of D-HT (OR 3.7, CI 1.9 – 6.9, I2 = 14%). RF associations could not be derived for right ventricle dependent coronary circulation, pulmonary arteriovenous malformations, total anomalous pulmonary venous return, arrhythmias and pulmonary atresia to D-HT. Conclusion This systematic review and meta-analysis found a high mortality rate in children born with non-HLHS SV heart disease and points to potential under-utilization of HT. Systemic ventricular dysfunction and AVR were identified as RF for D-HT in this subset of SV with TA, PA-IVS and HX.