Pulmonary arteriovenous malformations after the superior cavopulmonary shunt: mechanisms and clinical implications

Abstract

Children with functional single ventricle heart disease are commonly palliated down a staged clinical pathway toward a Fontan completion procedure (total cavopulmonary connection). The Fontan physiology is fraught with long-term complications associated with lower body systemic venous hypertension, eventually resulting in significant morbidity and mortality. The bidirectional Glenn shunt or superior cavopulmonary connection (SCPC) is commonly the transitional stage in single ventricle surgical management and provides excellent palliation. Some studies have demonstrated lower morbidity and mortality with the SCPC when compared with the Fontan. Unfortunately the durability of the SCPC is significantly limited by the development of pulmonary arteriovenous malformations (PAVMs) which have been commonly attributed to the absence of hepatic venous blood flow and the lack of pulsatile flow to the affected lungs. Abnormal angiogenesis has been suggested as a final common pathway to PAVM development. Understanding these fundamental mechanisms through the investigation of angiogenic pathways associated with the pathogenesis of PAVMs would help to develop medical therapies that could prevent or reverse this complication following SCPC. Such therapies could improve the longevity of the SCPC, potentially eliminate or significantly postpone the Fontan completion with its associated complications, and improve long-term survival in children with single ventricle disease.

Keywords::

• angiogenesis
• cavopulmonary connection
• congenital heart disease
• Fontan operation
• pulmonary arteriovenous malformations
• single ventricle
• superior

Financial & competing interest disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Children with single ventricle disease undergo standard staged surgical palliation comprising Norwood, superior cavopulmonary connection (SCPC, also known as Glenn shunt) and culminating with a Fontan procedure. Unfortunately, Fontan physiology is fraught with medium- and long-term complications related to lower body systemic venous hypertension and – in the absence of complications such as development of pulmonary arteriovenous malformations (PAVMs) – it may be clinically beneficial to leave children with the SCPC.

• The development – and progression – of PAVMs after the SCPC results in progressive hypoxia and cyanosis.

• Two major theories that may explain the etiology of PAVMs: the absence of hepatic venous effluent in the venous return to the lungs receiving blood through the SCPC; and lack of pulsatile flow to the lungs directly receiving venous blood.

• PAVMs likely form due to aberrant angiogenesis. Key angiogenic factors and pathways have been associated with PAVM development in animal models of SCPC.

• Identifying mechanistic (cause–effect) roles for these angiogenic pathways in PAVM development could lead to the development of therapies to prevent or reverse PAVMs and improve the durability of the SCPC.

• Potential benefits of targeted therapy could include the delaying and/or elimination of the Fontan procedure, which may lead to improvement in the quality of life and longevity of children with single ventricle congenital heart disease.

Notes