Deep Phenotypic Analysis for Transposition of the Great Arteries and Prognosis Implication

Background Transposition of the great arteries (TGA) consists of about 3% of all congenital heart diseases and 20% of cyanotic congenital heart diseases. It is always accompanied by a series of other cardiac malformations that affect the surgical intervention strategy as well as prognosis. In this study, we comprehensively analyzed the phenotypes of the patients who had TGA with concordant atrioventricular and discordant ventriculoarterial connections and explored their association with prognosis. Methods and Results We retrospectively reviewed 666 patients with a diagnosis of TGA with concordant atrioventricular and discordant ventriculoarterial connections in Fuwai Hospital from 1997 to 2019. Under the guidance of the Human Phenotype Ontology database, patients were classified into 3 clusters. The Kaplan-Meier method was used to analyze the prognosis, and the Cox proportional regression model was used to investigate the risk factors. In this 666-patient TGA cohort, the overall 5-year survival rate was 94.70% (92.95%-96.49%). Three clusters with distinct phenotypes were obtained by the Human Phenotype Ontology database. Kaplan-Meier analysis revealed a significant difference in freedom from reintervention among 3 clusters (P<0.001). To eliminate the effect of surgeries, we analyzed patients who only received an arterial switch operation and still found a significant difference in reintervention (P=0.019). Conclusions We delineated a big cardiovascular phenotypic profile of an unprecedentedly large TGA cohort and successfully risk stratified them to reveal prognostic significance. Also, we reported the outcomes of a large TGA population in China.