title: Neurohormonal activation and its relation to outcomes late after repair of tetralogy of Fallot.
abstract: BACKGROUND
  Brain natriuretic peptide (BNP) levels are elevated in patients with repaired Tetralogy of Fallot (rTOF), the clinical significance of which remains uncertain.
  
  
  RESULTS
  Ninety consecutive adults (≥ 16 years) with rTOF (mean age 32.7 ± 11.3 years, 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 (5.9-14.6) vs 5.4 (2.2-7.5) pmol/L; p<0.01), and BNP activation was common even in asymptomatic patients. Also, atrial natriuretic peptide (6.9 (4.0-9.9) vs 3.3 (1.0-4.0) pmol/L; p<0.01), endothelin-1 (1.14 (0.94-1.48) vs 0.75 (0.44-0.93) pmol/L; p<0.01) and renin (55.0 (45.5-66.5) vs 18.6 (12.0-22.7) pmol/L; p<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 years. On Cox regression analysis, BNP emerged as a strong predictor of death (HR 1.16 per 10 pmol/L, 95% CI 1.05 to 1.29; p<0.01). Survival receiver operating curve analysis revealed an optimum cut-off of BNP ≥ 15 pmol/L (=52 pg/mL), above which BNP was related to significantly increased mortality (HR 5.40, 95% CI 1.29 to 22.6; p<0.01); absolute mortality at 5 years 19% vs 3% in patients with BNP ≤ 15 pmol/L. BNP was also a predictor of sustained arrhythmia (HR 2.06 per 10 pmol/L, 95% CI 1.32 to 3.21; p<0.05).
  
  
  CONCLUSIONS
  Neurohormonal activation is present in adults with rTOF including asymptomatic patients. BNP level ≥ 15 pmol/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.
authors.affiliation: Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK.
authors.forename: Ee Ling
authors.initials: EL
authors.lastname: Heng
authors.affiliation: East Midlands Congenital Heart Centre, Glenfield Hospital, University Hospitals of Leicester, Leicester, UK and Cardiovascular Biomedical Research Unit, University of Leicester.
authors.forename: Aidan P
authors.initials: AP
authors.lastname: Bolger
authors.affiliation: Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kempny
authors.affiliation: Cardiology Department, Patras University Hospital, Patras, Greece.
authors.forename: Periklis A
authors.initials: PA
authors.lastname: Davlouros
authors.affiliation: Department of Haematology, Royal Brompton Hospital, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Davidson
authors.affiliation: Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK.
authors.forename: Lorna
authors.initials: L
authors.lastname: Swan
authors.affiliation: Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK.
authors.forename: Anselm
authors.initials: A
authors.lastname: Uebing
authors.affiliation: NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK.
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.affiliation: Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gatzoulis
authors.affiliation: Department of Adult Congenital Heart Disease, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK.
authors.forename: Sonya V
authors.initials: SV
authors.lastname: Babu-Narayan
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain; D018377:Neurotransmitter Agents / Q000097:blood* / Q000502:physiology*; D011183:Postoperative Complications / Q000097:blood* / Q000453:epidemiology*; D011379:Prognosis; D011446:Prospective Studies; D013771:Tetralogy of Fallot / Q000601:surgery*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018377:Neurotransmitter Agents; D020097:Natriuretic Peptide, Brain
keywords: CONGENITAL HEART DISEASE