AUTHOR=He Qiyu , Shen Huayan , Shao Xinyang , Chen Wen , Wu Yafeng , Liu Rui , Li Shoujun , Zhou Zhou 

TITLE=Cardiovascular Phenotypes Profiling for L-Transposition of the Great Arteries and Prognosis Analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.781041

DOI=10.3389/fcvm.2021.781041

ISSN=2297-055X

ABSTRACT=Objectives: Congenitally corrected transposition of the great arteries (ccTGA) is a rare and complex congenital heart disease with the characteristics of double discordance. Enormous co-existed anomalies are the culprit of prognosis evaluation and clinical decision. We aim at delineating a novel ccTGA clustering modality under HPO instruction and elucidating the relationship between phenotypes and prognosis in ccTGA patients. 
Methods: A retrospective review of 270 patients diagnosed with ccTGA in Fuwai hospital from 2009 to 2020 and cross-sectional follow-up was performed. Human Phenotype Ontology (HPO)-instructed clustering method was administered in ccTGA risk stratification. Kaplan-Meier survival, Landmark analysis, and cox regression analysis were used to investigate the difference of outcomes among clusters. 
Results: The median follow-up time was 4.29 (2.07-7.37) years. A total of three distinct phenotypic clusters were obtained after HPO-instructed clustering with 21 in cluster 1, 136 in cluster 2, and 113 in cluster 3. Landmark analysis revealed significantly worse mid-term outcomes in all-cause mortality (p=0.021) and composite endpoints (p=0.004) of cluster 3 in comparison with cluster 1 and cluster 2. Multivariate analysis indicated that pulmonary arterial hypertension (PAH), atrioventricular septal defect (AVSD), and arrhythmia were risk factors for composite endpoints. Moreover, the surgical treatment was significantly different among the three groups (p<0.001) and surgical strategies had different effects on the prognosis of the different phenotypic clusters.
Conclusions: HPO-instructed clustering can be a potentially powerful tool for phenotypic risk stratification in patients with complex congenital heart diseases, which may improve prognosis prediction and clinical decision.