| Description |
- Background: Single ventricle disease (SVD) is a subtype of congenital heart disease that frequently requires early staged surgical intervention for survival. It is well known that syndromic causes of SVD are associated with worse outcomes. However, the overall effect of variants of uncertain significance (VUSs) found on chromosomal microarray (CMA) has not been explored. Our objective was to explore the impact of CMA VUSs on outcomes in patients with SVD. We hypothesized that VUSs impart no significant effect on clinical outcomes for patients with SVD when compared to normal chromosomal findings while pathogenic variants have a negative impact on mortality and heart failure.
Methods: We conducted a review of consecutive patients with SVD born between 1985-2023 with a CMA and treated at our institution. Primary outcomes included heart failure, heart transplantation, cardiac arrest, and mortality. Secondary outcomes included gastrostomy tube (G-tube) insertion, tracheostomy, and extracorporeal membrane oxygenation (ECMO). We controlled for possible confounding factors such as gestational age, birth weight, and age at diagnosis. Rates of primary and secondary outcomes were compared using Fisher’s exact test. Freedom from event curves were generated using a log-rank test for comparison.
Results: The cohort included 322 consecutive single ventricle patients. The CMA results showed 248 (77.02%) patients having normal CMAs, 42 (13.04%) with VUSs, and 32 (9.94%) with abnormal/pathogenic results. Of those with abnormal CMAs, 22 (68.75%) had a chromosomal abnormality associated with a known genetic syndrome. Analysis using Fisher’s exact test showed lower rates of cardiac arrest and G-tube insertion in VUSs compared to abnormal CMAs (p < 0.05). The one-year survival curve showed higher survival in the normal CMA group compared to the abnormal CMA group (p < 0.05). The cardiac arrest freedom from event curve showed lower event rates in the VUS and normal CMA group compared to the abnormal CMA group (p < 0.05). There was no difference in outcomes between VUSs and normal CMAs.
Conclusions: Individuals with SVD and a VUS on CMA have survival rates comparable to those with normal CMAs. In contrast, abnormal CMAs are associated with reduced survival. These findings suggest that VUSs and normal CMAs may be less susceptible to cardiac arrest which is a critical complication of SVD.
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