{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:19:13Z","timestamp":1767212353102,"version":"3.44.0"},"reference-count":44,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002129","name":"Heart Foundation","doi-asserted-by":"publisher","award":["2013T091"],"award-info":[{"award-number":["2013T091"]}],"id":[{"id":"10.13039\/100002129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2023,3,9]]},"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Cardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment\u2014including blood sampling and speckle tracking echocardiography\u2014occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We included 45 patients with ToF repair aged 4.3 (3.4 \u2013 6.5) months and 16 patients with PVR aged 10.4 (7.8 \u2013 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (\u221218\u00b14 to \u221213\u00b14 to \u221220\u00b12, p &lt; 0.001 for each comparison) and RV GLS (\u221219\u00b15 to \u221214\u00b14 to 20\u00b14, p &lt; 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients\u2019 sex, rather than ToF-related phenotypes in a subset of the study population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>Netherlands Trial Register: NL5129.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2022-002238","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T10:53:51Z","timestamp":1680778431000},"page":"e002238","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Ventricular function and biomarkers in relation to repair and pulmonary valve replacement for tetralogy of Fallot"],"prefix":"10.1136","volume":"10","author":[{"given":"Jelle P G","family":"van der Ven","sequence":"first","affiliation":[{"name":"Netherlands Heart Institute, Utrecht, The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC Sophia Children Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"G\u00fcnthel","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Netherlands Heart Institute, Utrecht, The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC Sophia Children Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian P","family":"Kamphuis","sequence":"additional","affiliation":[{"name":"Netherlands Heart Institute, Utrecht, The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Leiden Univerisity Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolaas A","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiology, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Breur","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Wilhelmina Children's Hospital\/University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf M F","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ad J J C","family":"Bogers","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurens","family":"Koopman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC Sophia Children Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arend D J","family":"Ten Harkel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Leiden Univerisity Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Christoffels","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-1537","authenticated-orcid":false,"given":"Willem A","family":"Helbing","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC Sophia Children Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"2025081709290728000_10.1.e002238.1","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.17174.1","article-title":"Current outcomes and treatment of tetralogy of fallot","volume":"8","author":"van der Ven","year":"2019","journal-title":"F1000Res"},{"key":"2025081709290728000_10.1.e002238.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-017-1579-8"},{"key":"2025081709290728000_10.1.e002238.3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.4103\/0971-9784.166465","article-title":"Mechanisms of oxidative stress and myocardial protection during open-heart surgery","volume":"18","author":"Baikoussis","year":"2015","journal-title":"Ann Card Anaesth"},{"key":"2025081709290728000_10.1.e002238.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.02.073"},{"key":"2025081709290728000_10.1.e002238.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-013-0802-5"},{"key":"2025081709290728000_10.1.e002238.6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.604157"},{"key":"2025081709290728000_10.1.e002238.7","doi-asserted-by":"publisher","DOI":"10.1016\/1010-7940(90)90022-R"},{"key":"2025081709290728000_10.1.e002238.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(10)62503-9"},{"key":"2025081709290728000_10.1.e002238.9","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000268"},{"key":"2025081709290728000_10.1.e002238.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2008.02.006"},{"key":"2025081709290728000_10.1.e002238.11","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.echo.2014.08.005","article-title":"Echocardiographic nomograms for chamber diameters and areas in caucasian children","volume":"27","author":"Cantinotti","year":"2014","journal-title":"J Am Soc Echocardiogr"},{"key":"2025081709290728000_10.1.e002238.12","unstructured":"NN . CVD-III validation data v2.1: OLINK proteomics. n.d. Available: www.olink.com\/downloads"},{"key":"2025081709290728000_10.1.e002238.13","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0095192","article-title":"Homogenous 96-plex pea immunoassay exhibiting high sensitivity, specificity, and excellent scalability","volume":"9","author":"Assarsson","year":"2014","journal-title":"PLoS One"},{"key":"2025081709290728000_10.1.e002238.14","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.119.015022","article-title":"Associations between blood biomarkers, cardiac function, and adverse outcome in a young Fontan cohort","volume":"10","author":"van den Bosch","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"2025081709290728000_10.1.e002238.15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"2025081709290728000_10.1.e002238.16","doi-asserted-by":"publisher","DOI":"10.2307\/2346101"},{"key":"2025081709290728000_10.1.e002238.17","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2025081709290728000_10.1.e002238.18","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with deseq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2025081709290728000_10.1.e002238.19","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.echo.2018.01.006","article-title":"Normative data for left and right ventricular systolic strain in healthy caucasian italian children by two-dimensional speckle-tracking echocardiography","volume":"31","author":"Cantinotti","year":"2018","journal-title":"J Am Soc Echocardiogr"},{"key":"2025081709290728000_10.1.e002238.20","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1093\/ehjci\/jeac022","article-title":"Right ventricular longitudinal strain in the clinical routine: a state-of-the-art review","volume":"23","author":"Muraru","year":"2022","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"2025081709290728000_10.1.e002238.21","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1007\/s00246-020-02355-6","article-title":"Left and right ventricular impairment shortly after correction of tetralogy of Fallot","volume":"41","author":"Terol","year":"2020","journal-title":"Pediatr Cardiol"},{"key":"2025081709290728000_10.1.e002238.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2010.06.008"},{"key":"2025081709290728000_10.1.e002238.23","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/chd.12544","article-title":"Comparison of valvar and right ventricular function following transcatheter and surgical pulmonary valve replacement","volume":"13","author":"Li","year":"2018","journal-title":"Congenit Heart Dis"},{"key":"2025081709290728000_10.1.e002238.24","first-page":"675","article-title":"Notch-tnf signalling is required for development and homeostasis of arterial valves","volume":"38","author":"Wang","year":"2017","journal-title":"Eur Heart J"},{"key":"2025081709290728000_10.1.e002238.25","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.cca.2011.01.035","article-title":"Serum tartrate-resistant acid phosphatase isoform 5A (tracp5a) as a potential risk marker in cardiovascular disease","volume":"412","author":"Janckila","year":"2011","journal-title":"Clin Chim Acta"},{"key":"2025081709290728000_10.1.e002238.26","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s11239-021-02582-5","article-title":"Novel multi-marker proteomics in phenotypically matched patients with ST-segment myocardial infarction: association with clinical outcomes","volume":"53","author":"Shavadia","year":"2022","journal-title":"J Thromb Thrombolysis"},{"key":"2025081709290728000_10.1.e002238.27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0208042","article-title":"Proteomic analysis of heart failure hospitalization among patients with chronic kidney disease: the heart and soul study","volume":"13","author":"Dubin","year":"2018","journal-title":"PLoS One"},{"key":"2025081709290728000_10.1.e002238.28","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1055\/s-0039-1696973","article-title":"Longitudinally measured fibrinolysis factors are strong predictors of clinical outcome in patients with chronic heart failure: the bio-shift study","volume":"119","author":"van den Berg","year":"2019","journal-title":"Thromb Haemost"},{"key":"2025081709290728000_10.1.e002238.29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.14740\/jocmr4459","article-title":"Soluble urokinase plasminogen activator receptor as a diagnostic and prognostic biomarker in cardiac disease","volume":"13","author":"Velissaris","year":"2021","journal-title":"J Clin Med Res"},{"key":"2025081709290728000_10.1.e002238.30","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-019-0709-6","article-title":"Platelet integrin \u03b1IIb\u03b23: signal transduction, regulation, and its therapeutic targeting","volume":"12","author":"Huang","year":"2019","journal-title":"J Hematol Oncol"},{"key":"2025081709290728000_10.1.e002238.31","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aer190"},{"key":"2025081709290728000_10.1.e002238.32","doi-asserted-by":"crossref","first-page":"531","DOI":"10.5152\/akd.2014.4950","article-title":"Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: relationship to cardiac functions","volume":"14","author":"Kili\u00e7","year":"2014","journal-title":"Anadolu Kardiyol Derg"},{"key":"2025081709290728000_10.1.e002238.33","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3109\/1354750X.2016.1153722","article-title":"Matrix metalloproteinases as candidate biomarkers in adults with congenital heart disease","volume":"21","author":"Baggen","year":"2016","journal-title":"Biomarkers"},{"key":"2025081709290728000_10.1.e002238.34","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1016\/j.ijcard.2012.08.059","article-title":"Circulating biomarkers of collagen type I metabolism mark the right ventricular fibrosis and adverse markers of clinical outcome in adults with repaired tetralogy of fallot","volume":"167","author":"Chen","year":"2013","journal-title":"Int J Cardiol"},{"key":"2025081709290728000_10.1.e002238.35","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0492"},{"key":"2025081709290728000_10.1.e002238.36","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s11239-020-02221-5","article-title":"Biomarkers of platelet activation and cardiovascular risk in the DAPT trial","volume":"51","author":"Berg","year":"2021","journal-title":"J Thromb Thrombolysis"},{"key":"2025081709290728000_10.1.e002238.37","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.118.009555","article-title":"Temporal patterns of 14 blood biomarker candidates of cardiac remodeling in relation to prognosis of patients with chronic heart failure-the bio- SH I FT study","volume":"8","author":"Bouwens","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"2025081709290728000_10.1.e002238.38","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3109\/00365513.2012.704065","article-title":"Tissue inhibitor of matrix metalloproteinases 4 (Timp4) in a population of young adults: relations to cardiovascular risk markers and carotid artery intima-media thickness. the cardiovascular risk in young finns study","volume":"72","author":"Oikonen","year":"2012","journal-title":"Scand J Clin Lab Invest"},{"key":"2025081709290728000_10.1.e002238.39","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41569-020-0381-0","article-title":"Cardiac natriuretic peptides","volume":"17","author":"Goetze","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"2025081709290728000_10.1.e002238.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.01.034"},{"key":"2025081709290728000_10.1.e002238.41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/VHRM.S166157","article-title":"Biomarkers in acute myocardial infarction: current perspectives","volume":"15","author":"Aydin","year":"2019","journal-title":"Vasc Health Risk Manag"},{"key":"2025081709290728000_10.1.e002238.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2012.07.067"},{"key":"2025081709290728000_10.1.e002238.43","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1007\/s00109-019-01857-y","article-title":"Gene-Environment regulatory circuits of right ventricular pathology in tetralogy of Fallot","volume":"97","author":"Zhao","year":"2019","journal-title":"J Mol Med (Berl)"},{"key":"2025081709290728000_10.1.e002238.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2005.11.005"}],"container-title":["Open Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/openhrt-2022-002238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T16:29:15Z","timestamp":1755448155000},"score":1,"resource":{"primary":{"URL":"https:\/\/openheart.bmj.com\/lookup\/doi\/10.1136\/openhrt-2022-002238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,4,6]]},"published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1136\/openhrt-2022-002238"],"URL":"https:\/\/doi.org\/10.1136\/openhrt-2022-002238","relation":{},"ISSN":["2053-3624"],"issn-type":[{"type":"electronic","value":"2053-3624"}],"subject":[],"published":{"date-parts":[[2023,4]]}}}