Academic Journal
Failing Fontan Following Total Cavopulmonary Connection: Extracardiac Biomarkers Reveal 2 Distinct Phenotypes With Divergent Clinical Courses.
| Τίτλος: | Failing Fontan Following Total Cavopulmonary Connection: Extracardiac Biomarkers Reveal 2 Distinct Phenotypes With Divergent Clinical Courses. |
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| Συγγραφείς: | Matsubara M; Department of Congenital and Pediatric Heart Surgery, TUM University Hospital, German Heart Center, Munich, Germany; Division of Congenital and Pediatric Heart Surgery, University Hospital of Munich, Ludwig- Maximilians-Universität München, Munich, Germany; Europäisches Kinderherzzentrum München, Munich 80636, Germany.; Department of Cardiovascular Surgery, Tokyo Metropolitan Children's Medical Center, Tokyo 183-8561, Japan., Aldogan H; Department of Congenital and Pediatric Heart Surgery, TUM University Hospital, German Heart Center, Munich, Germany; Division of Congenital and Pediatric Heart Surgery, University Hospital of Munich, Ludwig- Maximilians-Universität München, Munich, Germany; Europäisches Kinderherzzentrum München, Munich 80636, Germany., Schaeffer T; Department of Congenital and Pediatric Heart Surgery, TUM University Hospital, German Heart Center, Munich, Germany; Division of Congenital and Pediatric Heart Surgery, University Hospital of Munich, Ludwig- Maximilians-Universität München, Munich, Germany; Europäisches Kinderherzzentrum München, Munich 80636, Germany., Ruda C; Department of Congenital and Pediatric Heart Surgery, TUM University Hospital, German Heart Center, Munich, Germany; Division of Congenital and Pediatric Heart Surgery, University Hospital of Munich, Ludwig- Maximilians-Universität München, Munich, Germany; Europäisches Kinderherzzentrum München, Munich 80636, Germany., Röhlig C; Department of Congenital Heart Disease and Pediatric Cardiology, TUM University Hospital, German Heart Center, Munich 80636, Germany., Palm J; Department of Congenital Heart Disease and Pediatric Cardiology, TUM University Hospital, German Heart Center, Munich 80636, Germany., Piber N; Department of Cardiovascular Surgery, TUM University Hospital, German Heart Center, Munich 80636, Germany., Hager A; Department of Congenital Heart Disease and Pediatric Cardiology, TUM University Hospital, German Heart Center, Munich 80636, Germany., Ewert P; Department of Congenital Heart Disease and Pediatric Cardiology, TUM University Hospital, German Heart Center, Munich 80636, Germany., Hörer J; Department of Congenital and Pediatric Heart Surgery, TUM University Hospital, German Heart Center, Munich, Germany; Division of Congenital and Pediatric Heart Surgery, University Hospital of Munich, Ludwig- Maximilians-Universität München, Munich, Germany; Europäisches Kinderherzzentrum München, Munich 80636, Germany., Ono M; Department of Congenital and Pediatric Heart Surgery, TUM University Hospital, German Heart Center, Munich, Germany; Division of Congenital and Pediatric Heart Surgery, University Hospital of Munich, Ludwig- Maximilians-Universität München, Munich, Germany; Europäisches Kinderherzzentrum München, Munich 80636, Germany. |
| Πηγή: | Interdisciplinary cardiovascular and thoracic surgery [Interdiscip Cardiovasc Thorac Surg] 2026 Aug 03; Vol. 41 (8). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9918540787006676 Publication Model: Print Cited Medium: Internet ISSN: 2753-670X (Electronic) Linking ISSN: 2753670X NLM ISO Abbreviation: Interdiscip Cardiovasc Thorac Surg Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Oxford, England] : Oxford University Press, [2023]- |
| Ιατρικοί όροι (MeSH): | Fontan Procedure*/adverse effects , Heart Defects, Congenital*/surgery , Heart Defects, Congenital*/blood , Protein-Losing Enteropathies*/blood , Protein-Losing Enteropathies*/etiology , Protein-Losing Enteropathies*/diagnosis , Heart Failure*/blood , Heart Failure*/etiology , Heart Failure*/diagnosis , Peptide Fragments*/blood , Natriuretic Peptide, Brain*/blood , Heart Bypass, Right*/adverse effects, Biomarkers/blood ; Humans ; Female ; Male ; Phenotype ; Treatment Failure ; Retrospective Studies ; Child ; Lymphocyte Count ; Risk Factors ; Child, Preschool ; Time Factors |
| Περίληψη: | Objectives: Failing Fontan is an increasingly recognized complication after total cavopulmonary connection (TCPC), yet longitudinal biomarker data remain scarce. We aimed to characterize the incidence, biomarker trajectories, and prognostic determinants of failing Fontan. Methods: All patients who underwent primary TCPC (n = 650) or conversion to TCPC (n = 19) at our centre between 1994 and 2022 were reviewed. Lymphocyte count, N-terminal pro-brain natriuretic peptide (NT-proBNP) and its zlog value, and Fibrosis-4 index were assessed at 1 year before, 6 months before, at onset, and at last follow-up. Patients were classified into protein-losing enteropathy (PLE)/plastic bronchitis (PB) and heart failure phenotypes. Results: Failing Fontan developed in 78 primary TCPC patients (12.0%) and 12 conversion patients (63.2%). Conversion patients developed failing Fontan earlier (P < .001), but survival after onset was comparable. Lymphocyte counts declined before onset (2.49 to 0.89 × 10³/µL, P < .001) and the Fibrosis-4 index increased (0.060 to 0.330, P < .001). Phenotypes showed divergent profiles: zlog-NT-proBNP at onset was 0.71 in PLE/PB versus 5.34 in heart failure (P < .001). Lymphocytopenia (LP) predicted mortality early (hazard ratio 6.77, P = .013) but appeared protective at last follow-up (hazard ratio 0.18, P = .049), reflecting a phenotypic shift. On multivariable analysis, lower lymphocyte count independently predicted mortality (hazard ratio 2.44, P = .041), while stent implantation was independently associated with lower mortality (hazard ratio 0.32, P = .040). Conclusions: Lymphocyte counts and the Fibrosis-4 index change progressively before clinical onset and may serve as early warning biomarkers. The prognostic interpretation of LP depends on the underlying phenotype, underscoring the need for phenotype-aware monitoring. (© The Author(s) 2026. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.) |
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| Grant Information: | Förderverein des Deutschen Herzzentrums München |
| Contributed Indexing: | Keywords: Fib 4; NT-proBNP; failing Fontan; lymphocytopenia; total cavopulmonary connection |
| Substance Nomenclature: | 0 (Biomarkers) 0 (pro-brain natriuretic peptide (1-76)) 0 (Peptide Fragments) 114471-18-0 (Natriuretic Peptide, Brain) |
| Entry Date(s): | Date Created: 20260730 Date Completed: 20260821 Latest Revision: 20260823 |
| Update Code: | 20260823 |
| PubMed Central ID: | PMC13496394 |
| DOI: | 10.1093/icvts/ivag213 |
| PMID: | 42530872 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2753-670X |
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| DOI: | 10.1093/icvts/ivag213 |