Accelerated Aging Fontan Phenotype Is Associated With Systemic Right Ventricles and Adverse Hemodynamics

Journal of the American Heart Association, vol. 15, pp. e048352

Abstract

Background Accelerated biological aging occurs when biological age outpaces chronological age. Congenital heart disease is associated with an increased risk for age‐related diseases. The role of biological aging in individuals with the most severe forms of congenital heart disease, those with a Fontan circulation, is not known. Methods In this case–control study, we compared the telomere lengths of patients with Fontan circulation with controls and identified factors associated with an accelerated aging phenotype. Biological aging was assessed by leukocyte telomere length through quantitative polymerase chain reaction, expressed as telomeric DNA to single‐copy gene ratio. Results Median age was 14.90 (interquartile range [IQR], 10.99–20.69) years in the Fontan cohort (N=90) and 15.20 (IQR, 11.11–16.42) years in controls (N=59). The Fontan cohort had shorter telomeres compared with controls (telomeric DNA to single‐copy gene ratio, 1.04 [IQR, 0.96–1.14] versus 1.13 [IQR, 0.96–1.24]; P =0.021). Patients with systemic right ventricles had shorter telomeres (telomeric DNA to single‐copy gene ratio, 1.02 [IQR, 0.93–1.08] versus 1.05 [IQR, 1.00–1.17]; P =0.047). Lower superior vena cava saturation (β=0.007 [95% CI, 0.002, 0.012]; P =0.013), lower cardiac index (β=0.06 [95% CI, 0.012–0.108]; P =0.016) and higher systemic vascular resistance (β=−0.007 [95% CI, −0.014 to −0.001]; P =0.023) were associated with shorter telomeres. At a median follow‐up of 13.07 months, 46.7% of patients with telomere loss (>50 bp loss/y) experienced an increase in comorbidities, compared with just 20.5% in those with no change or an increase in telomere length ( P <0.001). Conclusions Individuals with a Fontan circulation have shorter telomeres compared with controls, mirroring an accelerated aging phenotype. This is more pronounced in patients with a systemic right ventricle, those with adverse hemodynamics, and is associated with having a higher burden of comorbidities. Understanding accelerated biological aging will allow for the development of therapies aimed at slowing age‐related decline.

Authors 10

1. Jennifer P. Woo

   Stanford University

   Affiliation as printed

   Stanford University

2. A Vincent

   Stanford University

   Affiliation as printed

   Stanford University

3. Ankit Kushwaha

   Stanford University

   Affiliation as printed

   Stanford University

4. Sushrima Gan

   Stanford University

   Affiliation as printed

   Stanford University

5. Shoko Ichimura

   Stanford University

   Affiliation as printed

   Stanford University

6. Anastasia D. Egorova Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center

7. GRUSCHEN R. VELDTMAN

   Helen DeVos Children's Hospital

   Affiliation as printed

   Helen DeVos Children's Hospital

8. Tony Wyss‐Coray

   Stanford University

   Affiliation as printed

   Stanford University

9. Yann Le Guen

   Stanford University

   Affiliation as printed

   Stanford University

10. Sushma Reddy

    Stanford University

    Affiliation as printed

    Stanford University