Variants of significance: medical genetics and surgical outcomes in congenital heart disease.

PURPOSE OF REVIEW: This article reviews the current understanding and limitations in knowledge of the effect genetics and genetic diagnoses have on perioperative and postoperative surgical outcomes in patients with congenital heart disease (CHD). RECENT FINDINGS: Presence of a known genetic diagnosis seems to effect multiple significant outcome metrics in CHD surgery including length of stay, need for extracorporeal membrane oxygenation, mortality, bleeding, and heart failure. Data regarding the effects of genetics in CHD is complicated by lack of standard genetic assessment resulting in inaccurate risk stratification of patients when analyzing data. Only 30% of variation in CHD surgical outcomes are explained by currently measured variables, with 2.5% being attributed to diagnosed genetic disorders, it is thought a significant amount of the remaining outcome variation is because of unmeasured genetic factors. SUMMARY: Genetic diagnoses clearly have a significant effect on surgical outcomes in patients with CHD. Our current understanding is limited by lack of consistent genetic evaluation and assessment as well as evolving knowledge and discovery regarding the genetics of CHD. Standardizing genetic assessment of patients with CHD will allow for the best risk stratification and ultimate understanding of these effects.

Learning to Crawl: Determining the Role of Genetic Abnormalities on Postoperative Outcomes in Congenital Heart Disease.

Background Our cardiac center established a systematic approach for inpatient cardiovascular genetics evaluations of infants with congenital heart disease, including routine chromosomal microarray (CMA) testing. This provides a new opportunity to investigate correlation between genetic abnormalities and postoperative course. Methods and Results Infants who underwent congenital heart disease surgery as neonates (aged ≤28 days) from 2015 to 2020 were identified. Cases with trisomy 21 or 18 were excluded. Diagnostic genetic results or CMA with variant of uncertain significance were considered abnormal. We compared postoperative outcomes following initial congenital heart disease surgery in patients found to have genetic abnormality to those who had negative CMA. Among 355 eligible patients, genetics consultations or CMA were completed in 88%. A genetic abnormality was identified in 73 patients (21%), whereas 221 had negative CMA results. Genetic abnormality was associated with prematurity, extracardiac anomaly, and lower weight at surgery. Operative mortality rate was 9.6% in patients with a genetic abnormality versus 4.1% in patients without an identified genetic abnormality (P=0.080). Mortality was similar when genetic evaluations were diagnostic (9.3%) or identified a variant of uncertain significance on CMA (10.0%). Among 14 patients with 22q11.2 deletion, the 2 mortality cases had additional CMA findings. In patients without extracardiac anomaly, genetic abnormality was independently associated with increased mortality (P=0.019). CMA abnormality was not associated with postoperative length of hospitalization, extracorporeal membrane oxygenation, or >7 days to initial extubation. Conclusions Routine genetic evaluations and CMA may help to stratify mortality risk in severe congenital heart disease with syndromic or nonsyndromic presentations.