Abstract Body (Do not enter title and authors here): Background: Patients with single ventricle congenital heart disease palliated to Fontan circulation have increased all-cause mortality compared to age-matched controls. The reason for this increased mortality is not clear and cannot be fully explained by the underlying cardiac disease alone. We hypothesize that premature biologic aging contributes to this increased mortality.
Methods: We collected demographic, clinical data and blood from patients with Fontan circulation and controls with structurally normal hearts. We assessed biologic age using telomere length (TL) measured by quantitative PCR from buffy coat DNA. Telomeres are repeating nucleoprotein structures at the end of chromosomes which shorten with age. Between group differences were assessed using t-test. Data was presented as mean±SD and p<0.05 was considered significant.
Results: Mean age was 15.6±8.1 years in the Fontan cohort (N=122) vs. 18±15.8 years in controls (N=30). 63% were males in the Fontan cohort vs. 73% in controls. The Fontan cohort had a trend toward shorter TL vs. controls (1.07±0.15 vs. 1.17±0.2; p=NS). The TL difference of 0.1 suggests that the Fontan cohort is 9 years biologically older than controls. In both groups, there was a trend towards shorter TL with increasing age but was most prominent in Fontan cohort (Fig a). Patients with single right ventricles had shorter TL vs. those with single left ventricles (1.04±0.17 vs. 1.10±0.2; p=0.03), with the single right ventricle patients being 5.4 years biologically older (Fig b). The hypoplastic left heart syndrome cohort had the shortest TL of 1.0±0.14 (15 years biologically older than control) and the most co-morbidities: protein losing enteropathy (20.4%), pulmonary hypertension (6%), endocarditis (2%), stroke (12%) and cirrhosis (2%) compared to the other groups. Interestingly, there was no association between TL and systolic ventricular function by echocardiogram.
Conclusions: We show for the first time, premature biologic aging in the Fontan circulation, its association with increased comorbidities and with single right ventricles being most at risk. Premature aging may predispose to heightened all-cause mortality and predispose to early onset of age-related diseases.