Background: Because of the importance of identifying factors that affect late outcomes in the increasing population of those with tetralogy of Fallot (TOF), we aimed to determine the effect of a 22q11.2 microdeletion on adult mortality, while accounting for pulmonary atresia, known to be enriched in 22q11.2 deletion syndrome (22q11.2DS).
Methods: We studied 612 individuals with TOF recruited as adults at a single centre, 80 (13.1%) with molecularly confirmed 22q11.2 deletions and 532 without 22q11.2DS, followed for a total of 5961.3 person-years. Using a case-control design, Cox proportional hazard regression and Kaplan-Meier curves, we evaluated the effect of a 22q11.2 deletion on mortality and survival.
Results: All-cause mortality was 1.87% per person-year in the 22q11.2DS-TOF group and 0.80% in the other-TOF group. The presence of a 22q11.2 microdeletion was a significant predictor of adult mortality in TOF (hazard ratio, 5.00; P < 0.0001), after accounting for pulmonary atresia (hazard ratio, 2.71; P = 0.0106) and other factors. Overall, individuals with 22q11.2DS died on average 17.7 years earlier (P = 0.0055) than others with TOF, predominantly of cardiovascular causes, with proportionately more sudden cardiac deaths in those with 22q11.2DS-TOF (n = 5 [38.5%] vs n = 5 [11.9%], other-TOF; P = 0.0447). Kaplan-Meier curves showed reduced survival for those with 22q11.2DS (P < 0.0001); probability of survival to age 45 years, without pulmonary atresia, was 72% (22q11.2DS-TOF) and 98% (other-TOF).
Conclusions: The results suggest that the 22q11.2 deletion significantly contributes to premature mortality in adults with TOF, mediated only in part by greater anatomic complexity. The interpretation of late outcome data in TOF will likely benefit from further genetic subtyping.
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