Introduction
Pulmonary arteriovenous malformations (PAVMs) represent a common complication of the bidirectional cavopulmonary anastomosis (Glenn) performed as first-stage surgical palliation for univentricular congenital heart disease. In the Glenn shunt, a preparatory procedure for Fontan operation, the superior vena cava blood flow is directed to the pulmonary arteries while the hepatic venous blood enters the right atrium and is excluded from the pulmonary blood flow. Although the lack of hepatic venous effluent directly perfusing the pulmonary arteries and the loss of pulsatile pulmonary blood flow have been identified as major etiological factors contributing to the development of PAVMs, their pathogenetic mechanism still remains unclear (1). Spearman et al. (2) suggested that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) could be a potential hepatic factor candidate involved in the pathogenesis of PAVMs after surgical palliation for patients with univentricular heart.
Relevant Subsection
In addition to patients undergoing univentricular palliation, PAVMs could be spontaneously present also in some children with heterotaxy, polysplenia, and left isomerism of the atrial appendages, although they have never undergone surgical treatment (3–7). In all of these previously reported patients, there was an interruption of the hepatic portion of the inferior vena cava with azygos continuation to superior vena cava and spontaneous pulmonary arteriovenous fistulas (3–7). This peculiar congenital pattern of systemic venous drainage could be associated with evident or “cryptic” intrahepatic disease. This combination of defects can result in an increased intrapulmonary shunting (8, 9) also without any surgical intervention (3–7). It is well-known that after Fontan repair with hepatic vein inclusion, PAVMs can completely regress. Anyway, Kim et al. demonstrated that in some patients who underwent Fontan completion, the PAVMs only partially resolved. All of them had left isomerism with azygos continuation of the inferior vena cava and the hepatic vein conduit on the contralateral side to the superior vena cava receiving azygos drainage. This would result in an imbalance of hepatic venous blood perfusion to the lungs bilaterally, which could lead to persistent PAVMs (10).
Conclusion
In conclusion, the study conducted by Spearman et al. identified VEGFR1 as a possible factor implicated in the pulmonary microvascular remodeling and therefore potentially involved in the development of PAVMs in patients with palliated univentricular heart. However, also patients without univentricular heart but with the same abnormal hepatic venous flow distribution could develop PAVMs. So, these patients might profit from surgical redirection of hepatic venous blood into the pulmonary arteries.
Further studies should focus on detecting hepatic factor candidates in order to improve pathogenetic insights and find possible treatment strategies.
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Statements
Author contributions
All authors wrote and critically revised the manuscript.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Summary
Keywords
congenital heart disease, Fontan operation, pulmonary arteriovenous malformation (PAVM), left isomerism, azygos continuation
Citation
Putotto C, Marino B and Versacci P (2021) Commentary: sVEGFR1 Is Enriched in Hepatic Vein Blood—Evidence for a Provisional Hepatic Factor Candidate?. Front. Pediatr. 9:782779. doi: 10.3389/fped.2021.782779
Received
24 September 2021
Accepted
19 October 2021
Published
08 November 2021
Volume
9 - 2021
Edited by
Christian Apitz, Ulm University Medical Center, Germany
Reviewed by
Sarah Nordmeyer, Charité – Universitätsmedizin Berlin, Germany; Dietmar Schranz, University Hospital Frankfurt, Germany
Updates
Copyright
© 2021 Putotto, Marino and Versacci.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Paolo Versacci paolo.versacci@uniroma1.it
This article was submitted to Pediatric Cardiology, a section of the journal Frontiers in Pediatrics
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.