{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:36:47Z","timestamp":1787017007575,"version":"build-2736575974"},"reference-count":30,"publisher":"BMJ","issue":"6","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Heart"],"accepted":{"date-parts":[[2014,9,29]]},"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brain natriuretic peptide (BNP) levels are elevated in patients with repaired Tetralogy of Fallot (rTOF), the clinical significance of which remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Ninety consecutive adults (\u226516\u2005years) with rTOF (mean age 32.7\u00b111.3\u2005years, 64% men) were prospectively recruited from a single tertiary centre, together with 15 age-matched and gender-matched controls. Patients with rTOF had elevated BNP (8.9 (5.9\u201314.6) vs 5.4 (2.2\u20137.5) pmol\/L; p&lt;0.01), and BNP activation was common even in asymptomatic patients. Also, atrial natriuretic peptide (6.9 (4.0\u20139.9) vs 3.3 (1.0\u20134.0) pmol\/L; p&lt;0.01), endothelin-1 (1.14 (0.94\u20131.48) vs 0.75 (0.44\u20130.93) pmol\/L; p&lt;0.01) and renin (55.0 (45.5\u201366.5) vs 18.6 (12.0\u201322.7) pmol\/L; p&lt;0.01) were elevated at baseline compared with controls. Interactions between BNP with endothelin-1, cardiothoracic ratio and right atrial area were evident. Eight deaths occurred over a median follow-up of 10\u2005years. On Cox regression analysis, BNP emerged as a strong predictor of death (HR 1.16 per 10\u2005pmol\/L, 95% CI 1.05 to 1.29; p&lt;0.01). Survival receiver operating curve analysis revealed an optimum cut-off of BNP \u226515\u2005pmol\/L (=52\u2005pg\/mL), above which BNP was related to significantly increased mortality (HR 5.40, 95% CI 1.29 to 22.6; p&lt;0.01); absolute mortality at 5\u2005years 19% vs 3% in patients with BNP \u226415\u2005pmol\/L. BNP was also a predictor of sustained arrhythmia (HR 2.06 per 10\u2005pmol\/L, 95% CI 1.32 to 3.21; p&lt;0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Neurohormonal activation is present in adults with rTOF including asymptomatic patients. BNP level \u226515\u2005pmol\/L is associated with a fivefold increased risk of death. These data suggest that BNP measurement in patients with rTOF should be incorporated in the periodic risk stratification assessment of these patients under lifelong follow-up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/heartjnl-2014-306398","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T23:59:07Z","timestamp":1414540747000},"page":"447-454","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Neurohormonal activation and its relation to outcomes late after repair of tetralogy of Fallot"],"prefix":"10.1136","volume":"101","author":[{"given":"Ee Ling","family":"Heng","sequence":"first","affiliation":[{"name":"Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK"},{"name":"NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan P","family":"Bolger","sequence":"additional","affiliation":[{"name":"East Midlands Congenital Heart Centre, Glenfield Hospital, University Hospitals of Leicester, Leicester, UK and Cardiovascular Biomedical Research Unit, University of Leicester"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kempny","sequence":"additional","affiliation":[{"name":"Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periklis A","family":"Davlouros","sequence":"additional","affiliation":[{"name":"Cardiology Department, Patras University Hospital, Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Brompton Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Swan","sequence":"additional","affiliation":[{"name":"Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselm","family":"Uebing","sequence":"additional","affiliation":[{"name":"Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dudley J","family":"Pennell","sequence":"additional","affiliation":[{"name":"NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Gatzoulis","sequence":"additional","affiliation":[{"name":"Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK"},{"name":"NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya V","family":"Babu-Narayan","sequence":"additional","affiliation":[{"name":"Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK"},{"name":"NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, 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