Background: The Texas Children’s Hospital Inpatient Cardiovascular Genetics (CVG) service was established in July 2021 with a goal to improve the ethical ordering of timely and appropriate genetic testing for children with congenital heart disease (CHD). The team rounds with the cardiovascular intensive care unit (CICU) once weekly, performs genetic consultations, and facilitates informed consent for genetic testing. The impact of this team on the stated goal has not yet been well established. 

Methods: Consecutive newborn admissions to the CICU were evaluated from 3 cohorts, each spanning a three-month period (August-October) over three years: 2019 and 2020, prior to the initiation of the CVG team, and 2021 after initiation of the team. Inclusion criteria were age <30 days old and critical CHD. During all periods (2019-2021), universal genetic testing was recommended for newborns with CHD per a standard lesion-based algorithm. Genetic testing was assessed for appropriateness, including both adequate testing and lack of unnecessary testing before and after initiation of the team, and by race/ethnicity/language. Yield of testing was also reported. 

Results: One hundred twenty-seven patients met inclusion criteria (2019 n=53, 2020 n=37, 2021 n=37). Following the implementation of the CVG team, the percentage of patients with adequate testing increased from 84.4% to 100% (p = 0.011), inappropriate testing decreased from 26.7% to 0% (p<.001), and the proportion of patients with appropriate testing (both adequate testing and without inappropriate additional testing) increased from 57.8% to 100% (p<.001). While 94.3% of those without evident aneuploidy underwent chromosomal microarray, 34% underwent either panel sequencing or whole exome sequencing. Overall yield of the algorithm in determining an etiologic diagnosis was 26%, with the most common diagnoses being 22q11.2 deletion syndrome (n=6, 5%), Trisomy 21 (n=4, 3%), and Turner syndrome (n=4, 3%). Other chromosomal abnormalities and pathogenic copy number variants (CNVs) were present in 13 patients (10%). Prevalence of chromosomal abnormalities and pathogenic CNVs was stable at 14-16% in each cohort. Yield of sequencing was 6/43 (14%), with variants noted in CHD7, KMT2D, ACTC1, DNAH5, and NODAL. There was no difference between demographic groups (Non-Hispanic Black, Non-Hispanic White, Hispanic English-Speaking, Hispanic Spanish-Speaking, other) in appropriate testing before or after CVG inpatient team initiation, although similar improvements in test appropriateness were noted across demographic groups in 2021.

Conclusion: The implementation of a CVG inpatient consult team can significantly improve the appropriate and timely ordering of genetic testing. Using current algorithms, diagnostic yield of universal genetic testing in newborns with critical CHD is high. Given high yield of gene sequencing, expanded use of sequencing may yield even higher diagnostic rates. Additionally, optimizing test appropriateness conveys cost benefit as inappropriate testing is decreased and diagnostic yield is increased.  User-friendly universal protocols for genetic testing based on CHD lesion may be beneficial for hospitals without a CVG inpatient team and are currently being developed by our team.