Discussion:

Using a large multicenter national database, we reported the outcomes of 3,009 infants with truncus arteriosus who underwent surgical repair. The study provides descriptive but relevant information with regards to demographics, national trends, in-hospital complications, and outcomes in infants with truncus arteriosus. The overall mortality in truncus arteriosus is 10.8%. A recent report from the society of thoracic surgeons congenital heart surgery database showed a similar mortality rate of 9.6% in truncus arteriosus repair, which is the second-highest rate of mortality after Norwood procedure (9). Aiming to identify predictors of mortality in this disease, a multivariate regression analysis was used, and we also analyzed the outcomes in subjects with 22q11.2 deletion syndrome. The main findings in this study were as follows: (1) Patient characteristics that were associated with mortality were a non-White race, prematurity, and Medicaid insurance. (2) 22q11.2 deletion syndrome was associated with an inverse risk of death despite having more non-cardiac comorbidities. (3) 22q11.2 deletion syndrome patients had a longer length of hospital stay and higher cost of hospitalization.
To address the first finding of insurance disparities, Erickson and colleagues showed in their study that infants with congenital heart disease and private insurance are cared for at hospitals with lower surgical mortality and that non-White children with Medicaid insurance were less likely to use a hospital with lower mortality rate (10). In addition, prematurity carries a major risk factor for increased mortality in infants with congenital heart disease, and preterm birth rates vary by race and ethnicity. Socioeconomic and ethnic-racial disparities are a major risk for prematurity (11). Studies have shown that non-Hispanic Black women are 2.5 times more likely to have preterm birth versus White women (12). The dynamics and interplay between these three risk factors (preterm birth, non-White race, and government insurance) are challenging, and the coexistence of these factors is not uncommon. The second main finding in this study was the presence of an inverse risk of death associated with 22q11.2 deletion syndrome. The baseline characteristics for these patients are similar to subjects without -22q11.2 deletion syndrome. Many researchers have examined the operative mortality in truncus arteriosus and some have found that 22q11.2 deletion syndrome does not necessarily increase surgical risk (13–15), while others reveal that 22q11.2 deletion is an independent risk factor for late mortality (16, 17). However , the results of our study are in agreement with the results of a study by Michielon and colleagues, which found that 22q11.2 deletion syndrome was an inverse risk for death in patients with truncus arteriosus (18). It could also be that the complex cardiac pathology and challenging nature of the repair with its prolonged postoperative course could have much more of an impact than the impact of the diagnosis of 22q11.2 deletion on truncus arteriosus. , One could also hypothesize that the cardiac morphology and anatomy in these patients is different from patients without 22q11.2 deletion syndrome. A study by McElhinney reviewed details of cardiac features in truncus patients with 22q11.2 deletion and showed that patients with 22q11.2 deletion had a higher frequency of right-sided aortic arch and abnormal aortic arch branching. Most importantly, interrupted aortic arch, which could impact operative mortality, occurred at a similar frequency in those with and without 22q11.2 deletion syndrome. In McElhinney’s study, there was a statistically insignificant trend for a lower incidence of moderate-severe truncal valve insufficiency in patients with 22q11.2 deletion (11% vs. 33%) which could impact surgical mortality, suggesting that factors other than chromosome 22q11.2 deletion are the main determinants of the functional and morphological characteristics of the truncal valve (19). Previous studies have shown the association with poor surgical outcomes in subjects with truncal valve regurgitation, interrupted aortic arch and coronary artery anomalies (20). One of the limitations of our study is the inability to review patient charts and cardiac imaging to evaluate for the presence of postoperative truncal valve regurgitation or the details of coronary anatomy in these patients. Future studies that also evaluate the cardiac anatomy in 22q11.2 deletion syndrome will likely be able to evaluate our finding of an inverse death risk that is associated with 22q11.2 syndrome in truncus arteriosus.
Lastly, this study reported prolonged hospitalization and increased cost of hospitalization in patients with truncus arteriosus. This is similar to the study done by Ghimire et al, who showed that the diagnosis of 22q11.1 deletion is associated with longer hospital stay and higher hospitalization cost (21). The 22q11.2 group had far more non-cardiac comorbidities and had higher rates of postoperative complications. Feeding issues were more common in 22q11.2 deletion syndrome, a higher percentage of these patients had a gastrostomy tube during the index hospitalization. Airway anomalies were present more frequently in 22q11.2 deletion and this was associated with a higher frequency of tracheostomy procedure. Immunological dysfunction is not uncommon in infants with 22q11.2 deletion (22), and it was not surprising to find higher rates of septicemia and fungal infection in the 22q11.2 deletion group. Therefore, it was not unexpected to have a prolonged postoperative hospitalization in patients with 22q11.2 deletion, modifications in the perioperative care of this subpopulation to address these complications are warranted to further shorten the postoperative course and decrease the cost of hospitalization.
Limitations: There are several limitations to this study, the study relied on the ICD-9 & ICD-10 codes for the diagnosis of truncus arteriosus and 22q11.2 deletion syndrome, it didn’t describe how the chromosomal deletion diagnosis was reached. The study span is over a span of two decades; the field of molecular genetic testing and genomic profiling has evolved dramatically; this could have affected the accuracy of the genetic screening method over the years of the study. The database does not provide details of cardiac anatomy, mainly coronary artery anomalies, postoperative truncal valve insufficiency, and aortic arch obstruction. The database lacks information on cardiac bypass and surgical procedure techniques, which have evolved over the course of these two decades and therefore is subject to an era effect. These factors would impact the surgical outcomes in truncus arteriosus. The current study benefited from the large sample size, some limitations are inherent to all retrospective studies using administrative databases. Incorrect or missing data may exist. We rely mainly on ICD diagnostic and procedure codes to gather information, and we were not able to refer to specific patient hospital charts to determine the cause of death. The lack of validation of the data collected by chart review is a source of potential bias for errors. However, in a large study such as ours, the patients’ volume likely offset these inaccuracies. Another limitation of our study is the restriction to the hospitalization period, and this prevented us from evaluating long-term outcomes.