Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-16T19:16:08.977Z Has data issue: false hasContentIssue false
  • English
  • Français

Treatment strategies for protein-losing enteropathy in Fontan-palliated patients

Published online by Cambridge University Press:  04 May 2020

Anastasia Schleiger ,
Stanislav Ovroutski ,
Björn Peters Open the ORCID record for Björn Peters [Opens in a new window] ,
Stephan Schubert ,
Joachim Photiadis ,
Felix Berger  and
Peter Kramer Open the ORCID record for Peter Kramer [Opens in a new window]
Anastasia Schleiger
Affiliation:
Department of Congenital Heart Disease/Pediatric Cardiology, Berlin, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany
Stanislav Ovroutski
Affiliation:
Department of Congenital Heart Disease/Pediatric Cardiology, Berlin, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany
Björn Peters
Affiliation:
Department of Congenital Heart Disease/Pediatric Cardiology, Berlin, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany
Stephan Schubert
Affiliation:
Department of Congenital Heart Disease/Pediatric Cardiology, Berlin, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany
Joachim Photiadis
Affiliation:
Department of Congenital Heart Surgery, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany
Felix Berger
Affiliation:
Department of Congenital Heart Disease/Pediatric Cardiology, Berlin, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany Department of Pediatric Cardiology, Charité – Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353Berlin, Germany Partner Site Berlin, DZHK (German Center for Cardiovascular Research), Oudenarder Straße 16, 13347Berlin, Germany
Peter Kramer*
Affiliation:
Department of Congenital Heart Disease/Pediatric Cardiology, Berlin, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany
*
Author for correspondence: Peter Kramer, MD, Department of Congenital Heart Disease/Pediatric Cardiology Berlin, German Heart Center Berlin, Augustenburger Platz 1, 13353Berlin, Germany. Tel: +49 304 593 2800; Fax: +49 304 593 2900. E-mail: kramerpeter@dhzb.de
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Protein-losing enteropathy is an infrequent but severe condition occurring after Fontan procedure. The multifactorial pathogenesis remains unclear and no single proposed treatment strategy has proven universally successful. Therefore, we sought to describe different treatment strategies and their effect on clinical outcome and mortality.

Material and Methods:

We performed a retrospective observational study. From the total cohort of 439 Fontan patients treated in our institution during the study period 1986–2019, 30 patients (6.8%) with protein-losing enteropathy were identified. Perioperative, clinical, echocardiographic, laboratory, and invasive haemodynamic findings and treatment details were analysed.

Results:

Median follow-up after disease onset was 13.1 years [interquartile range 10.6]. Twenty-five patients received surgical or interventional treatment for haemodynamic restrictions. Medical treatment, predominantly pulmonary vasodilator and/or systemic anti-inflammatory therapy with budesonide, was initiated in 28 patients. In 15 patients, a stable remission could be achieved by medical or surgical procedures (n = 3 each), by combined multimodal therapy (n = 8), or ultimately by cardiac transplantation (n = 1). Phrenic palsy, bradyarrhythmia, Fontan pathway stenosis, and absence of a fenestration were significantly associated with development of protein-losing enteropathy (p = 0.001–0.48). Ten patients (33.3%) died during follow-up; 5-year survival estimate was 96.1%. In unadjusted analysis, medical therapy with budesonide and pulmonary vasodilator therapy in combination was associated with improved survival.

Conclusions:

Protein-losing enteropathy is a serious condition limiting survival after the Fontan procedure. Comprehensive assessment and individual treatment strategies are mandatory to achieve best possible outcome. Nevertheless, relapse is frequent and long-term mortality substantial. Cardiac transplantation should be considered early as treatment option.

Keywords

Protein-losing enteropathyFontan operationtreatment strategieslate mortality
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 5 , May 2020 , pp. 698 - 709
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.)

References

Mertens, L, Hagler, DJ, Sauer, U, Somerville, J, Gewillig, M. Protein-losing enteropathy after the Fontan operation: an international multicenter study. PLE study group. J Thorac Cardiovasc Surg 1998; 115: 1063–1073.CrossRefGoogle ScholarPubMed
Feldt, RH, Driscoll, DJ, Offord, KP, et al.Protein-losing enteropathy after the Fontan operation. J Thorac Cardiovasc Surg 1996; 112: 672–680.10.1016/S0022-5223(96)70051-XCrossRefGoogle ScholarPubMed
Schumacher, KR, Stringer, KA, Donohue, JE, et al.Fontan-associated protein-losing enteropathy and plastic bronchitis. J Pediatr 2015; 166: 970–977.10.1016/j.jpeds.2014.12.068CrossRefGoogle ScholarPubMed
Powell, AJ, Gauvreau, K, Jenkins, KJ, Blume, ED, Mayer, JE, Lock, JE. Perioperative risk factors for development of protein-losing enteropathy following a Fontan procedure. Am J Cardiol 2001; 88: 1206–1209.10.1016/S0002-9149(01)02066-5CrossRefGoogle ScholarPubMed
John, AS, Johnson, JA, Khan, M, Driscoll, DJ, Warnes, CA, Cetta, F. Clinical outcomes and improved survival in patients with protein-losing enteropathy after the Fontan operation. J Am Coll Cardiol 2014; 64: 54–62.CrossRefGoogle ScholarPubMed
Rychik, J. Protein-losing enteropathy after Fontan operation. Congenit Heart Dis 2007; 2: 288–300.10.1111/j.1747-0803.2007.00116.xCrossRefGoogle Scholar
Rychik, J. Spray, TL. Strategies to treat protein-losing enteropathy. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2002; 5: 3–11.10.1053/pcsu.2002.31498CrossRefGoogle ScholarPubMed
Udink Ten Cate, FE, Hannes, T, Germund, I, et al.Towards a proposal for a universal diagnostic definition of protein-losing enteropathy in Fontan patients: a systematic review. Heart 2016; 102: 1115–1119.CrossRefGoogle ScholarPubMed
Ryerson, L, Goldberg, C, Rosenthal, A, Armstrong, A. Usefulness of heparin therapy in protein-losing enteropathy associated with single ventricle palliation. Am J Cardiol 2008; 101: 248–251.10.1016/j.amjcard.2007.08.029CrossRefGoogle ScholarPubMed
Reinhardt, Z, Uzun, O, Bhole, V, et al.Sildenafil in the management of the failing Fontan circulation. Cardiol Young 2010; 20: 522–525.CrossRefGoogle ScholarPubMed
Thacker, D, Patel, A, Dodds, K, Goldberg, DJ, Semeao, E, Rychik, J. Use of oral budesonide in the management of protein-losing enteropathy after the Fontan operation. Ann Thorac Surg 2010; 89: 837–842.10.1016/j.athoracsur.2009.09.063CrossRefGoogle ScholarPubMed
Cohen, MI, Rhodes, LA, Wernovsky, G, Gaynor, JW, Spray, TL, Rychik, J.Atrial pacing: an alternative treatment for protein-losing enteropathy after the Fontan operation. J Thorac Cardiovasc Surg 2001; 121: 582–583.10.1067/mtc.2001.110681CrossRefGoogle ScholarPubMed
Vyas, H, Driscoll, DJ, Cabalka, AK, Cetta, F, Hagler, DJ. Results of transcatheter Fontan fenestration to treat protein losing enteropathy. Catheter Cardiovasc Interv 2007; 69: 584–589.10.1002/ccd.21045CrossRefGoogle ScholarPubMed
Menon, S, Hagler, D, Cetta, F, Gloviczki, P, Driscoll, D. Role of caval venous manipulation in treatment of protein-losing enteropathy. Cardiol Young 2008; 18: 275–281.10.1017/S1047951108001996CrossRefGoogle ScholarPubMed
Bernstein, D, Naftel, D, Chin, C, et al.Outcome of listing for cardiac transplantation for failed Fontan: a multi-institutional study. Circulation 2006; 114: 273–280.10.1161/CIRCULATIONAHA.105.548016CrossRefGoogle ScholarPubMed
Schumacher, KR, Gossett, J, Guleserian, K, et al.Fontan-associated protein-losing enteropathy and heart transplant: a pediatric heart transplant study analysis. J Heart Lung Transplant 2015; 34: 1169–1176.CrossRefGoogle ScholarPubMed
Schwartz, GJ, Munoz, A, Schneider, MF, et al.New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20: 629–637.10.1681/ASN.2008030287CrossRefGoogle ScholarPubMed
Levey, AS, Stevens, LA, Schmid, CH, et al.A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604–612.CrossRefGoogle ScholarPubMed
Neuhauser, H, Schienkiewitz, A, Schaffrath Rosario, A, Dortschy, R, Kurth, BM. Referenzperzentile für anthropometrische Maßzahlen und Blutdruck aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS). 2nd edition. Berlin: Robert Koch Institut, 2013.Google Scholar
Germany FSOo: Mikrozensus 2017 - Fragen zur Gesundheit - Körpermaße der Bevölkerung. 02 August, 2018. Wiesbaden: Federal Statistical Office of Germany, 2018.Google Scholar
van den Brand, JA, van Boekel, GA, Willems, HL, Kiemeney, LA, Den Heijer, M, Wetzels, JF. Introduction of the CKD-EPI equation to estimate glomerular filtration rate in a Caucasian population. Nephrol Dial Transplant 2011; 26: 3176–3181.CrossRefGoogle Scholar
Meadows, J, Jenkins, KProtein-losing enteropathy: integrating a new disease paradigm into recommendations for prevention and treatment. Cardiol Young 2011; 21: 363–377.10.1017/S1047951111000102CrossRefGoogle ScholarPubMed
Rychik, J, Goldberg, D, Rand, E, et al.End-organ consequences of the Fontan operation: liver fibrosis, protein-losing enteropathy and plastic bronchitis. Cardiol Young 2013; 23: 831–840.10.1017/S1047951113001650CrossRefGoogle ScholarPubMed
Hraska, V.Decompression of thoracic duct: new approach for the treatment of failing Fontan. Ann Thorac Surg 2013; 96: 709–711.10.1016/j.athoracsur.2013.02.046CrossRefGoogle ScholarPubMed
Antonio, M, Gordo, A, Pereira, C, Pinto, F, Fragata, I, Fragata, J.Thoracic duct decompression for protein-losing enteropathy in failing Fontan circulation. Ann Thorac Surg 2016; 101: 2370–2373.CrossRefGoogle ScholarPubMed
Smith, CL, Hoffman, TM, Dori, Y, Rome, JJ. Decompression of the thoracic duct: a novel transcatheter approach. Catheter Cardiovasc Interv 2019; 95: E56–E61.10.1002/ccd.28446CrossRefGoogle Scholar
Schumacher, KR, Cools, M, Goldstein, BH, et al.Oral budesonide treatment for protein-losing enteropathy in Fontan-palliated patients. Pediatr Cardiol 2011; 32: 966–971.10.1007/s00246-011-0029-2CrossRefGoogle ScholarPubMed
Uzun, O, Wong, JK, Bhole, V, Stumper, O.Resolution of protein-losing enteropathy and normalization of mesenteric Doppler flow with sildenafil after Fontan. Ann Thorac Surg 2006; 82: e39–e40.10.1016/j.athoracsur.2006.08.043CrossRefGoogle ScholarPubMed
Donnelly, JP, Rosenthal, A, Castle, VP, Holmes, RD.Reversal of protein-losing enteropathy with heparin therapy in three patients with univentricular hearts and Fontan palliation. J Pediatr 1997; 130: 474–478.10.1016/S0022-3476(97)70214-2CrossRefGoogle ScholarPubMed
Rychik, J, Atz, AM, Celermajer, DS, et al. Evaluation and management of the child and adult with Fontan circulation: a scientific statement from the American Heart Association. Circulation 2019: CIR0000000000000696.CrossRefGoogle Scholar
Cohen, MI, Bush, DM, Ferry, RJ Jr., et al.Somatic growth failure after the Fontan operation. Cardiol Young 2000; 10: 447–457.CrossRefGoogle ScholarPubMed
Vogt, KN, Manlhiot, C, Van Arsdell, G, Russell, JL, Mital, S, McCrindle, BW Somatic growth in children with single ventricle physiology impact of physiologic state. J Am Coll Cardiol 2007; 50: 1876–1883.10.1016/j.jacc.2007.07.050CrossRefGoogle Scholar
Francois, K, Bove, T, Panzer, J, et al.Univentricular heart and Fontan staging: analysis of factors impacting on body growth. Eur J Cardiothorac Surg 2012; 41: e139–e45.10.1093/ejcts/ezs194CrossRefGoogle ScholarPubMed
Goldberg, DJ, Dodds, K, Avitabile, CM, et al.Children with protein-losing enteropathy after the Fontan operation are at risk for abnormal bone mineral density. Pediatr Cardiol 2012; 33: 1264–1268.CrossRefGoogle ScholarPubMed
Johnson, JN, Driscoll, DJ, O’Leary, PW.Protein-losing enteropathy and the Fontan operation. Nutr Clin Pract 2012; 27: 375–384.CrossRefGoogle ScholarPubMed
Menon, SC, Al-Dulaimi, R, McCrindle, BW, et al.Delayed puberty and abnormal anthropometry and its associations with quality of life in young Fontan survivors: a multicenter cross-sectional study. Congenit Heart Dis 2018; 13: 463–469.10.1111/chd.12597CrossRefGoogle ScholarPubMed
Simpson, DE: No central venous pressure protein losing enteropathy relation? Blame the albumin. Eur J Cardiothorac Surg 2014; 46: 146.CrossRefGoogle Scholar
Schumacher, KR, Yu, S, Butts, R, et al.Fontan-associated protein-losing enteropathy and postheart transplant outcomes: A multicenter study. J Heart Lung Transplant 2019; 38: 17–25.10.1016/j.healun.2018.09.024CrossRefGoogle ScholarPubMed
Supplementary material: File

Schleiger et al. supplementary material

Schleiger et al. supplementary material

Download Schleiger et al. supplementary material(File)
File 18.1 KB