{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:12Z","timestamp":1787018112776,"version":"build-2736575974"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Postoperative sinus tachycardia is a poorly understood complication following the Fontan procedure. The molecular signaling cascades triggering acute tachycardia remain uncharacterized, limiting therapeutic innovation. Here, we present a retrospective study leveraging serum proteomics and machine learning to identify the molecular drivers of postoperative Fontan sinus tachycardia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We integrated a clinically relevant ovine Fontan model with continuous telemetric heart rate monitoring and human patient data. Serum proteomics coupled with least absolute shrinkage and selection operator and Boruta machine learning algorithms were used to identify protein panels predictive of postoperative sinus tachycardia. Cross\u2010species validation was performed by comparing proteomic signatures from sheep and pediatric patients undergoing Glenn or Fontan surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Ovine Fontan animals demonstrated significant heart rate elevation beginning on postoperative day 1, peaking at postoperative day 3 (159.4\u00b111.7\u2009bpm versus preoperative, 105.3\u00b110.5\u2009bpm;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.0002), before trending toward baseline by postoperative day 10. This pattern was mirrored in human patients with a more modest magnitude. Surgical controls did not exhibit tachycardia. The principal component most correlated with heart rate (principal component 1:\n                      <jats:italic toggle=\"no\">r<\/jats:italic>\n                      =0.78,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =2.2\u00d710\n                      <jats:sup>\u22124<\/jats:sup>\n                      ) was enriched for inflammatory and neural pathways. The Boruta algorithm identified an 11\u2010protein panel with strong predictive power (area under the receiver operating characteristic curve, 0.963). Cross\u2010species comparison demonstrated that angiotensinogen, angiotensin\u2010converting enzyme, and pentraxin 3 were similarly dysregulated in both species postoperatively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This study provides molecular evidence implicating a dysregulated neurohormonal\u2013inflammatory axis in acute postoperative Fontan sinus tachycardia and establishes a foundation for developing targeted diagnostics and therapeutics for this complication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.126.049852","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:25:12Z","timestamp":1783740312000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Serum Proteomic Profiling Implicates a Dysregulated Neurohormonal\u2013Inflammatory Axis in Post\u2010Fontan Sinus Tachycardia"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-8907","authenticated-orcid":false,"given":"Felipe","family":"Takaesu","sequence":"first","affiliation":[{"name":"Georgia Institute of Technology and Emory University School of Medicine","place":["Atlanta, USA"]},{"name":"Emory University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5808-2147","authenticated-orcid":false,"given":"Delaney J.","family":"Villarreal","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital","place":["Columbus, USA"]},{"name":"The Ohio State University College of Medicine","place":["Columbus, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Zhou","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology and Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital","place":["Columbus, USA"]},{"name":"The Ohio State University College of Medicine","place":["Columbus, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7521-3607","authenticated-orcid":false,"given":"Mackenzie E.","family":"Turner","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital","place":["Columbus, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Logan","family":"Spiess","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital","place":["Columbus, USA"]},{"name":"West Virginia University School of Medicine","place":["Morgantown, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0071-2874","authenticated-orcid":false,"given":"Jennifer C.","family":"Kievert","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital","place":["Columbus, USA"]},{"name":"The Ohio State University College of Medicine","place":["Columbus, USA"]},{"name":"Nationwide Children's Hospital","place":["Columbus, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-3719","authenticated-orcid":false,"given":"Cameron M.","family":"DeShetler","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide 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