The Glenn procedure is a standard palliative stage in the Fontan pathway for patients with single-ventricle physiology. Compared with a primary Fontan operation, it significantly reduces perioperative mortality (1). However, with increasing long-term survival, follow-up studies have shown that approximately 25% of patients develop clinically significant pulmonary arteriovenous malformations (PAVMs) after the Glenn procedure, and the risk increases with time (2). PAVMs—defined as abnormal direct communications between the pulmonary arteries and veins—create a right-to-left shunt that leads to hypoxemia. Among these, diffuse PAVMs are particularly rare but severe, resulting in profound cyanosis, hemoptysis, reduced exercise tolerance, and even heart failure (3, 4). The pathogenesis of PAVMs is complex and not yet fully understood. Although transcatheter embolization is effective for isolated lesions, the treatment of diffuse disease remains challenging.

Here, we report a case of diffuse PAVMs in a child with complex congenital heart disease after Glenn palliation. The malformations were successfully reversed by total cavopulmonary connection (TCPC), with marked improvement in oxygenation. This case provides insight into the underlying mechanisms and clinical management of Glenn-associated diffuse PAVMs.

Diffuse PAVMs are a rare but serious complication in patients with single-ventricle physiology following the Glenn procedure. The fundamental pathology involves abnormal communications between the pulmonary arteries and veins, resulting in right-to-left shunting and reduced arterial oxygen content. This mechanism represents one of the major causes of progressive cyanosis and hypoxemia in the late postoperative period (4). In the present case, the patient developed progressive cyanosis and decreased exercise tolerance after the bidirectional Glenn procedure, and was diagnosed with diffuse PAVMs at the age of five, consistent with the typical clinical course of this complication.

Although the exact mechanism of PAVM formation remains incompletely understood, the most widely accepted explanation is the “hepatic factor hypothesis”. In the Glenn circulation, pulmonary blood flow derives entirely from the superior vena cava, excluding the inferior vena cava and hepatic venous return. The absence of hepatic venous effluent may result in loss of protective factors and subsequent pulmonary vascular dysregulation (5). Clinical evidence suggests that after a classic unilateral Glenn shunt, PAVMs commonly develop in the ipsilateral lung, especially in the overperfused lower lobes (6). Bilateral diffuse PAVMs are typically seen when both lungs lack hepatic venous perfusion (7). Similarly, PAVMs frequently occur after the Kawashima procedure when hepatic veins drain directly into the atrium rather than the pulmonary arteries (3). Restoration of hepatic venous flow to the pulmonary circulation—most commonly through completion of the TCPC—can lead to gradual regression of PAVMs (2). The significant improvement observed in this patient following TCPC supports this mechanism.

The nature and action of the so-called hepatic factor remain to be fully elucidated. It has been proposed that PAVMs may result from an imbalance between proangiogenic and antiangiogenic mediators within the pulmonary circulation, leading to abnormal vascular proliferation and direct arteriovenous communications (8). Non-pulsatile flow, uneven perfusion distribution, and specific biochemical signaling from the superior vena cava may also contribute (9). On a molecular level, miR-25-3p has been shown to promote angiogenesis via the Akt/mTOR and HIF-1α/VEGF pathways (10), while dysregulation of the TGF-β signaling pathway may be involved in PAVM formation, particularly in complex cardiac malformations such as heterotaxy syndrome (2).

For diagnosis, contrast-enhanced echocardiography is the preferred screening tool, where microbubbles appearing in the left heart 3–6 cardiac cycles after injection indicate intrapulmonary right-to-left shunting. Contrast-enhanced CT angiography (CTA) provides detailed visualization of the location, distribution, and size of PAVMs, while pulmonary angiography remains the gold standard for definitive diagnosis and potential interventional therapy. Integrating data from pulse oximetry, imaging studies, perfusion scans, and contrast echocardiography can improve diagnostic accuracy.

The cornerstone of PAVM management is restoration of hepatic venous blood flow to the pulmonary circulation. For isolated or focal lesions, transcatheter embolization is an effective and minimally invasive treatment. However, diffuse or multifocal PAVMs remain challenging to manage (7). Surgical restoration of hepatic venous flow, most commonly through TCPC completion, remains the most effective strategy to reverse extensive PAVMs and improve oxygenation. Brown et al. reported that a delay exceeding two years between the Kawashima procedure and hepatic venous inclusion was an independent risk factor for PAVM development (3), emphasizing the importance of timely reintroduction of hepatic venous return.

In selected patients, partial preservation of antegrade pulmonary blood flow (APBF) during the Glenn procedure may help prevent PAVM formation. Behrend et al. (11) found that maintaining APBF in high-risk patients could sustain oxygenation, promote pulmonary artery growth, and improve outcomes after TCPC completion. However, excessive APBF may increase ventricular volume load and the risk of pleural effusions. Thus, individualized evaluation based on anatomic and physiologic characteristics is required to balance its potential benefits and risks.

In summary, although diffuse PAVMs are a rare but serious complication following the Glenn procedure, their reversibility provides an opportunity for effective intervention. This case highlights the importance of vigilance for PAVMs in patients presenting with progressive hypoxemia after Glenn palliation. Early restoration of hepatic venous flow to the pulmonary circulation—or, when appropriate, preservation of APBF—may prevent or reverse PAVM development. Prompt recognition and timely management are crucial to improving long-term outcomes.