{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:04:36Z","timestamp":1789535076692,"version":"build-2803163510"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Accelerated biological aging occurs when biological age outpaces chronological age. Congenital heart disease is associated with an increased risk for age\u2010related 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">In this case\u2013control 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\u2010copy gene ratio.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Median age was 14.90 (interquartile range [IQR], 10.99\u201320.69) years in the Fontan cohort (N=90) and 15.20 (IQR, 11.11\u201316.42) years in controls (N=59). The Fontan cohort had shorter telomeres compared with controls (telomeric DNA to single\u2010copy gene ratio, 1.04 [IQR, 0.96\u20131.14] versus 1.13 [IQR, 0.96\u20131.24];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.021). Patients with systemic right ventricles had shorter telomeres (telomeric DNA to single\u2010copy gene ratio, 1.02 [IQR, 0.93\u20131.08] versus 1.05 [IQR, 1.00\u20131.17];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.047). Lower superior vena cava saturation (\u03b2=0.007 [95% CI, 0.002, 0.012];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.013), lower cardiac index (\u03b2=0.06 [95% CI, 0.012\u20130.108];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.016) and higher systemic vascular resistance (\u03b2=\u22120.007 [95% CI, \u22120.014 to \u22120.001];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.023) were associated with shorter telomeres. At a median follow\u2010up of 13.07\u2009months, 46.7% of patients with telomere loss (&gt;50\u2009bp loss\/y) experienced an increase in comorbidities, compared with just 20.5% in those with no change or an increase in telomere length (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">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\u2010related decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.048352","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:55:26Z","timestamp":1788965726000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Accelerated Aging Fontan Phenotype Is Associated With Systemic Right Ventricles and Adverse Hemodynamics"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-0744","authenticated-orcid":false,"given":"Jennifer P.","family":"Woo","sequence":"first","affiliation":[{"name":"Stanford University","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4154-0199","authenticated-orcid":false,"given":"Annabelle Grace Binti","family":"Vincent","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9458-5813","authenticated-orcid":false,"given":"Ankit","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0221-9925","authenticated-orcid":false,"given":"Sushrima","family":"Gan","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0773-3045","authenticated-orcid":false,"given":"Shoko","family":"Ichimura","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9312-2338","authenticated-orcid":false,"given":"Anastasia D.","family":"Egorova","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center","place":["Leiden, The Netherlands"]},{"name":"Leiden University Medical Center","place":["Leiden, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gruschen R.","family":"Veldtman","sequence":"additional","affiliation":[{"name":"Helen DeVos Children's Hospital","place":["Grand Rapids, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5893-0831","authenticated-orcid":false,"given":"Tony","family":"Wyss\u2010Coray","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, 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