Abstract
ObjectivesCongenitally 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 human phenotype ontology (HPO) instruction and elucidating the relationship between phenotypes and prognosis in patients with ccTGA.MethodsA retrospective review of 270 patients diagnosed with ccTGA in Fuwai hospital from 2009 to 2020 and cross-sectional follow-up were performed. 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.ResultsThe 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.ConclusionsHuman phenotype ontology-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.
Highlights
Corrected transposition of the great arteries, a rare and anatomically complex congenital heart disease with an incidence of 1 in 33,000 live births approximately, is characterized by atrioventricular and ventricular-arterial discordance [1]
By retrospectively reviewing records from 2009 to 2020, we identified 380 patients who were admitted to Fuwai hospital and underwent surgeries with the diagnosis of corrected transposition of the great arteries (ccTGA) by Chinese
For the first time, we comprehensively summarized the cardiovascular phenotypes of patients with ccTGA and analyzed the effects of these combined phenotypes contributing to clinical outcomes integrated with different surgical strategies
Summary
Corrected transposition of the great arteries (ccTGA), a rare and anatomically complex congenital heart disease with an incidence of 1 in 33,000 live births approximately, is characterized by atrioventricular and ventricular-arterial discordance [1]. The human phenotype ontology (HPO), a comprehensive resource for systematically defining and logically organizing human phenotypes, enables computational inference and complex algorithms that support combinatorial genomic and phenotypic analysis [3]. It has been used in multiple fields, genotype-phenotype analysis for genetic syndromes [4], neurodevelopmental diseases [5–7], hereditary hemorrhagic telangiectasia [8], and myofibrillar myopathies [9]. We have succeeded in grouping patients with Ebstein’s anomaly by employing HPO and EMR [15]
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