Hostname: page-component-65b85459fc-jtdgp Total loading time: 0 Render date: 2025-10-15T17:39:03.367Z Has data issue: false hasContentIssue false
  • English
  • Français

N-terminal pro-brain natriuretic peptide serum levels reflect attrition of the Fontan circulation

Published online by Cambridge University Press:  09 June 2020

Djoeke Wolff Open the ORCID record for Djoeke Wolff [Opens in a new window] ,
Joost P. van Melle ,
Tineke P. Willems ,
Beatrijs Bartelds ,
Mark-Jan Ploegstra ,
Hans Hillege ,
Tjark Ebels  and
Rolf M. F. Berger
Djoeke Wolff*
Affiliation:
Center for Congenital Heart Diseases, Department of Pediatric Cardiology/Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Joost P. van Melle
Affiliation:
Center for Congenital Heart Diseases, Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Tineke P. Willems
Affiliation:
Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Beatrijs Bartelds
Affiliation:
Center for Congenital Heart Diseases, Department of Pediatric Cardiology/Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Department of Pediatric Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands
Mark-Jan Ploegstra
Affiliation:
Center for Congenital Heart Diseases, Department of Pediatric Cardiology/Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Hans Hillege
Affiliation:
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Tjark Ebels
Affiliation:
Center for Congenital Heart Diseases, Department of Cardiothoracic Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Rolf M. F. Berger
Affiliation:
Center for Congenital Heart Diseases, Department of Pediatric Cardiology/Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
*
Address for correspondence: Djoeke Wolff, MD PhD, Beatrix Children's Hospital, Department of Pediatric Cardiology, Hanzeplein 1, 9700 RBGroningen, the Netherlands. Fax: +31 50 361 1787; Tel: +31 (0)50 3611508. E-mail: djoekewolff@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

N-terminal pro-brain natriuretic peptide has an established role in the diagnosis and prognosis of heart failure. In Fontan patients, this peptide is often increased, but its diagnostic value in this particular non-physiologic, univentricular circulation is unclear. We investigated whether N-terminal pro-brain natriuretic peptide represents ventricular function or other key variables in Fontan patients.

Methods and results:

Ninety-five consecutive Fontan patients ≥10 years old who attended the outpatient clinic of the Center for Congenital Heart Diseases in 2012–2013 were included. Time since Fontan completion was 16 ± 9 years. Median N-terminal pro-brain natriuretic peptide was 114 (61–264) ng/l and was higher than gender-and age-dependent normal values in 54% of the patients. Peptide Z-scores were higher in patients in NYHA class III/IV compared to those in class I/II, but did not correlate with ventricular function assessed by MRI and echocardiography, nor with peak exercise capacity. Instead, peptide Z-scores significantly correlated with follow-up duration after Fontan completion (p < 0.001), right ventricular morphology (p = 0.004), indexed ventricular mass (p = 0.001), and inferior caval vein diameter (p < 0.001) (adjusted R2 = 0.615).

Conclusions:

N-terminal pro-brain natriuretic peptide levels in Fontan patients correlate with functional class, but do not necessarily indicate ventricular dysfunction. Increased peptide levels were associated with a longer existence of the Fontan circulation, morphologic ventricular characteristics, and signs of increased systemic venous congestion. Since the latter are known to be key determinants of the performance of the Fontan circulation, these findings suggest increase in N-terminal pro-brain natriuretic peptide levels to indicate attrition of the Fontan circulation, independent of ventricular function.

Keywords

Fontan physiologyheart defectscongenitalnatriuretic peptides

Information

Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 6 , June 2020 , pp. 753 - 760
Copyright
© The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Fontan, F, Baudet, E.Surgical repair of tricuspid atresia. Thorax 1971; 26: 240–248.CrossRefGoogle ScholarPubMed
Kreutzer, G, Galindez, E, Bono, H, De Palma, C, Laura, JP.An operation for the correction of tricuspid atresia. J Thorac Cardiovasc Surg 1973; 66: 613–621.CrossRefGoogle ScholarPubMed
Deal, BJ, Jacobs, ML.Management of the failing Fontan circulation. Heart 2012; 98: 1098–1104.CrossRefGoogle ScholarPubMed
Wolff, D, van Melle, JP, Ebels, T, Hillege, H, van Slooten, YJ, Berger, RMF.Trends in mortality (1975-2011) after one- and two-stage Fontan surgery, including bidirectional Glenn through Fontan completion. Eur J Cardiothorac Surg 2014; 45: 602–609.CrossRefGoogle ScholarPubMed
McMurray, JJ, Adamopoulos, S, Anker, SD, et al.ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33: 1787–1847.Google Scholar
van Veldhuisen, DJ, Linssen, GC, Jaarsma, T, et al.B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J Am Coll Cardiol 2013; 61: 1498–1506.CrossRefGoogle ScholarPubMed
Brunner-La Rocca, HP, Eurlings, L, Richards, AM, et al.Which heart failure patients profit from natriuretic peptide guided therapy? A meta-analysis from individual patient data of randomized trials. Eur J Heart Fail 2015; 17: 1252–1261.CrossRefGoogle ScholarPubMed
Koch, AM, Zink, S, Singer, H, Dittrich, S.B-type natriuretic peptide levels in patients with functionally univentricular hearts after total cavopulmonary connection. Eur J Heart Fail 2008; 10: 60–62.CrossRefGoogle ScholarPubMed
Burchill, LJ, Redington, AN, Silversides, CK, et al.Renin-ngiotensin-aldosterone system genotype and serum BNP in a contemporary cohort of adults late after Fontan palliation. Int J Cardiol 2015; 197: 209–215.CrossRefGoogle Scholar
Bongers, B, Hulzebos, E, van Brussel, M, et al.Pediatric Norms for Cardiopulmonary Exercise Testing. 1st ed. Den Bosch: Uitgeverij Boxpress; 2015.Google Scholar
Wasserman, K, Hansen, JE, Sue, DY, et al.Principles of Exercise Testing and Interpretation: Including Pathophysiology and Clinical Applications. Lippincott Williams & Wilkins, Philadelphia, USA; 1987.CrossRefGoogle Scholar
Clerico, A, Zanizotto, M, Prontera, Cet al.State of art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study. Clinica Chimica Act 2012; 414: 112–119.CrossRefGoogle ScholarPubMed
Freling, HG, van Wijk, K, Jaspers, K, et al.Impact of right ventricular endocardial trabeculae on volumes and function assessed by MRI in patients with tetralogy of Fallot. Int J Cardiovasc Imaging 2013; 29: 625–631.CrossRefGoogle ScholarPubMed
Jaspers, K, Freling, HG, van Wijk, K, Romijn, EL, Greuter, MJ, Willems, TP.Improving the reproducibility of MR-derived left ventricular volume and function measurements with a semi-automatic threshold-based segmentation algorithm. Int J Cardiovasc Imaging 2013; 29: 617–623.CrossRefGoogle ScholarPubMed
Koerbin, G, Abhayaratna, WP, Potter, JM, Apostoloska, S, Telford, RD, Hickman, PE.NTproBNP concentrations in healthy children. Clin Biochem 2012; 45(15): 1158–1160.CrossRefGoogle ScholarPubMed
Nir, A, Lindinger, A, Rauh, M, et al.NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol 2009; 30: 3–8.CrossRefGoogle ScholarPubMed
Fradley, MG, Larson, MG, Cheng, S, et al.Reference limits for N-terminal-pro-B-type natriuretic peptide in healthy individuals (from the Framingham Heart Study). Am J Cardiol 2011; 108(9): 1341–1345.CrossRefGoogle Scholar
Waterbolk, TW, Bink-Boelkens, MT, Elzenga, NJ, Beaufort-Krol, GC, Ebels, T.The right auricle tunnel as intercaval tunnel in total cavopulmonary connection may prevent atrial flutter. Eur J Cardiothorac Surg 1998; 14: 590–595.CrossRefGoogle ScholarPubMed
Brozena, S, Jessup, M.Pathophysiologic strategies in the management of congestive heart failure. Annu Rev Med 1990; 41: 65–74.CrossRefGoogle ScholarPubMed
Litwin, SE, Grossman, W.Diastolic dysfunction as a cause of heart failure. J Am Coll Cardiol 1993; 22: 49A–55A.CrossRefGoogle ScholarPubMed
Gewillig, M, Kalis, N.Pathophysiological aspects after cavopulmonary anastomosis. Thorac Cardiovasc Surg 2000; 48: 336–341.CrossRefGoogle ScholarPubMed
Hirsch, JC, Golderberg, C, Bove, ELet al.Fontan operation in the current era: a 15-year single institution experience. Ann surg 2008; 248: 402–410.Google ScholarPubMed
Khairy, P, Fernandes, SM, Mayer, JEet al.Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation 2008; 117: 85–92.CrossRefGoogle ScholarPubMed
Holmgren, D, Westerlind, A, Berggren, H, Lundberg, PA, Wahlander, H.Increased natriuretic peptide type B level after the second palliative step in children with univentricular hearts with right ventricular morphology but not left ventricular morphology. Pediatric Cardiol 2008; 29: 786–792.CrossRefGoogle Scholar
Lechner, E, Schreier-Lechner, EM, Hofer, A, et al.Aminoterminal brain-type natriuretic peptide levels correlate with heart failure in patients with bidirectional Glenn anastomosis and with morbidity after the Fontan operation. J Thorac Cardiovasc Surg 2009; 138: 560–564.CrossRefGoogle ScholarPubMed
De Leval, MR, Kilner, P, Gewillig, M, Bull, C.Total cavopulmonary connection: a logical alternative to atriopulmonary connection for complex Fontan operations. J Thorac Cardiovasc Surg 1988; 96: 682–695.CrossRefGoogle ScholarPubMed
Giannico, S, Corno, A, Marino, Bet al.Total extracardiac right heart bypass. Circulation 1992; 86: 110–117.Google ScholarPubMed
Wolff, D, Ebels, T, van Melle, JP.N-terminal pro brain natriuretic hormone in Fontan patients: heart failure or circulatory failure? Eur J Heart Fail 2013; 15: 602–603.CrossRefGoogle ScholarPubMed
Ohuchi, H, Takasugi, H, Ohashi, H, et al.Abnormalities of neurohormonal and cardiac autonomic nervous activities relate poorly to functional status in Fontan patients. Circulation 2004; 110: 2601–2608.CrossRefGoogle ScholarPubMed
De Vadder, K, Van De Bruaene, A, Gewillig, M, Meyns, B, Troost, E, Budts, W.Predicting outcome after Fontan palliation: a single-centre experience, using simple clinical variables. Acta Cardiol 2014 Feb; 69(1): 7–14.CrossRefGoogle ScholarPubMed
Baggen, VJ, van den Bosch, AE, Eindhoven, JA, et al.Prognostic value of N-terminal Pro-B-Type natriuretic peptide, Troponin-T, and growth-differentiation factor 15 in adult congenital heart disease. Circulation 2017; 135: 264–279.CrossRefGoogle ScholarPubMed
Eindhoven, JA, van den Bosch, AE, Jansen, PR, Boersma, E, Roos-Hesselink, JW.The usefulness of brain natriuretic peptide in complex congenital heart disease. JACC 2012; 60: 2140–2149.CrossRefGoogle ScholarPubMed
Man, BL, Cheung, YF.Plasma brain natriuretic peptide and systemic ventricular function in asymptomatic patients late after the Fontan procedure. Heart Vessels 2007; 22: 398–403.CrossRefGoogle ScholarPubMed
Robbers-Visser, D, Kapusta, L, van Osch-Gevers, L, et al.Clinical outcome 5 to 18 years after the Fontan operation performed on children younger than 5 years. J Thorac Cardiovasc Surg 2009; 138: 89–95.CrossRefGoogle ScholarPubMed
Heck, PB, Muller, J, Weber, R, Hager, A.Value of N-terminal pro brain natriuretic peptide levels in different types of Fontan circulation. Eur J Heart Fail 2013; 15: 644–649.CrossRefGoogle ScholarPubMed
Atz, AM, Zak, V, Breitbart, RE, et al.Factors associated with serum brain natriuretic peptide levels after the Fontan procedure. Congenit Heart Dis 2011; 6: 313–321.CrossRefGoogle ScholarPubMed
Ridderbos, FJ, Wolff, D, Timmer, A, et al.Adverse pulmonary vascular remodeling in the Fontan circulation. J Heart Lung Transplant 2015; 34: 404–413.10.1016/j.healun.2015.01.005CrossRefGoogle ScholarPubMed
Senzaki, H, Masutani, S, Ishido, H, et al.Cardiac rest and reserve function in patients with Fontan circulation. J Am Coll Cardiol 2006; 47: 2528–2535.CrossRefGoogle ScholarPubMed
Szabo, G, Bahrle, S.Contractility-afterload mismatch after the Fontan operation. Cardiol Young 2005; 15 Suppl 3: 35–38.CrossRefGoogle ScholarPubMed
Van Deursen, VM, Damman, K, Hillege, HL, et al.Abnormal liver function in relation to hemodynamic profile in heart failure patients. J Card Fail 2010; 16: 84–90.10.1016/j.cardfail.2009.08.002CrossRefGoogle ScholarPubMed
Wolff, D, van Melle, JP, Dijkstra, H, et al.The Fontan circulation and the liver: a magnetic resonance diffusion-weighted imaging study. Int J Cardiol 2016; 202: 595–600.CrossRefGoogle ScholarPubMed
Kiesewetter, CH, Sheron, N, Vettukattill, JJ, et al.Hepatic changes in the failing Fontan circulation. Heart 2007; 93: 579–584.CrossRefGoogle ScholarPubMed
Law, YM, Ettedgui, J, Beerman, L, Maisel, A, Tofovic, S.Comparison of plasma B-type natriuretic peptide levels in single ventricle patients with systemic ventricle heart failure versus isolated cavopulmonary failure. Am J Cardiol 2006; 98: 520–524.CrossRefGoogle ScholarPubMed
Supplementary material: File

Wolff et al. supplementary material

Wolff et al. supplementary material

Download Wolff et al. supplementary material(File)
File 19.3 KB