Why Long-Term Glenn Circulation Fails

The bidirectional Glenn (BDG) provides reliable early palliation, but its physiology is inherently time-limited. Deterioration typically reflects the interplay of age-related venous return redistribution, collateral channels, loss of hepatic venous–derived protection with pulmonary arteriovenous malformations (PAVMs), and aortopulmonary collateral (APC) burden. Below, your original framework is retained and sharpened with quantitative data and mechanistic evidence.

1) Growth-Related Hemodynamic Shifts

In infancy, the SVC contributes a large share of systemic venous return, which BDG routes efficiently to the lungs. With growth, the caval flow ratio progressively shifts toward the IVC, reducing SVC flow available to drive pulmonary perfusion and lowering arterial saturations for the same pulmonary vascular resistance (PVR). Contemporary 4D-flow CMR and computational studies demonstrate an age-linked inversion of SVC:IVC dominance by school age, which also disrupts hepatic flow distribution (HFD) and sets up conditions favoring desaturation and maldistributed hepatic blood to the lungs [1].

Clinical take-home. Even with stable PVR, a child whose SVC fraction is declining can show worsening SpO₂ and diminished exercise reserve; this is physiology, not necessarily “pump failure.”

2) Venovenous Collateral Formation (SVC → IVC and other pathways)

Chronic SVC hypertension and geometric pressure gradients across the cavopulmonary pathway promote venovenous collaterals (VVCs) that siphon blood away from the pulmonary arteries. In a modern BDG→Fontan cohort (n=586), VVC prevalence was ~12% before Fontan and associated with higher pulmonary artery pressures and lower SaO₂; however, when carried to completion, long-term survival after Fontan was not different between those with and without VVCs [2]. Classic catheterization series after BDG also showed collateral frequency rises with higher SVC–RA gradients, underscoring the pressure-driven nature of this adaptation [3].

Clinical take-home. VVCs explain “unexpected” cyanosis and can be palliated with transcatheter closure in selected patients, but durable correction often requires addressing the upstream pressure driver (e.g., PA distortion, elevated PVR).

3) Pulmonary Arteriovenous Malformations (PAVMs) from Hepatic-Factor Deprivation

The BDG excludes hepatic venous effluent from one or both lungs. A robust body of work links this hepatic-factor deprivation to angiogenic dysregulation and PAVM formation, producing intrapulmonary right-to-left shunt and progressive desaturation [4]. Recent reviews reinforce the concept that hepatic venous blood has protective, anti-angiogenic properties; restoring balanced hepatic flow (e.g., with Fontan completion or surgical redirection) often leads to PAVM regression [5].

Clinical take-home. Worsening cyanosis in a child with otherwise acceptable flows should prompt evaluation for PAVMs, especially when hepatic venous return is unbalanced or excluded.

4) Aortopulmonary Collaterals (APCs) — Volume Load and Venous Hypertension

Chronic hypoxemia and under-filled pulmonary arterial beds stimulate APCs that, while improving oxygenation transiently, impose systemic-to-pulmonary shunt volume on a circulation designed for passive venous return. Quantitative CMR work demonstrates that APC flow can be substantial and is more prominent in the pre-Fontan stage, increasing pleural effusions and recovery time after Fontan; mechanistically, APCs volume-load the Glenn circuit and raise venous pressures [6].

Clinical take-home. When cyanosis coexists with high Glenn pressures and large APC burden, prioritize reducing APC flow (medical optimization, targeted embolization) while preparing for Fontan, which often normalizes loading conditions.

5) Imaging, Surveillance, and Anatomic Pitfalls

• CMR vs. catheterization before Fontan. Randomized data show CMR-guided evaluation can safely substitute for routine diagnostic catheterization in many candidates, with no penalty in long-term outcomes [7].
• Anatomic risk (bilateral BDG/right atrial isomerism). After bilateral Glenn, SVC pathway obstruction is more frequent—particularly in heterotaxy—with implications for SVC pressure and collateralization, though Fontan completion and late outcomes may remain comparable when addressed proactively [8].

Clinical take-home. Use CMR (with flow quantification) to track SVC/IVC contributions, hepatic flow distribution, APC burden, and branch PA geometry. Reserve catheterization for targeted hemodynamic questions or transcatheter therapy.

Summary

Why Glenn fails long-term: As children grow, SVC flow falls and IVC flow rises → less energy to drive pulmonary perfusion and altered hepatic flow distribution [1]. SVC hypertension fosters VVCs that bypass the lungs [2,3]. Hepatic-factor deprivation promotes PAVMs, worsening right-to-left shunt [4,5]. APCs develop with chronic hypoxia, volume-loading the BDG and raising venous pressures [6]. Surveillance with CMR flow mapping can quantify these components and guide therapy, while attention to bilateral Glenn pathways prevents occult SVC obstruction [7,8]. Collectively, these mechanisms explain why BDG is an intermediate, time-limited solution and why timely Fontan completion (to restore balanced hepatic flow and adequate pulmonary driving pressure) is the durable endpoint for most patients.

References

[1] Govindarajan V, Marshall L, Sahni A, Cetatoiu MA, Eickhoff EE, Davee J, St Clair N, Schulz NE, Hoganson DM, Hammer PE, Ghelani SJ, Prakash A, del Nido PJ, Rathod RH. Impact of age-related change in caval flow ratio on hepatic flow distribution in the Fontan circulation. Circ Cardiovasc Imaging. 2024;17(4):e016104.

[2] Nguyen Cong MBH, Schaeffer T, Osawa T, Palm J, Niedermaier C, Piber N, Matsubara M, Heinisch PP, Georgiev S, Hager A, Ewert P, Hörer J, Ono M. Systemic venous collaterals between Glenn and Fontan: prevalence, therapy, and impact on outcomes. Cardiol Young. 2025;35(3):497-504.

[3] Magee AG, McCrindle BW, Mawson J, Benson LN, Williams WG, Freedom RM. Systemic venous collateral development after the bidirectional cavopulmonary anastomosis: prevalence and predictors. J Am Coll Cardiol. 1998;32(2):502-508.

[4] Kavarana MN, Jones JA, Stroud RE, Bradley SM, Ikonomidis JS, Mukherjee R. Pulmonary arteriovenous malformations after the superior cavopulmonary shunt: mechanisms and clinical implications. Expert Rev Cardiovasc Ther. 2014;12(6):703-713.

[5] Spearman AD, Ginde S. Pulmonary vascular sequelae of palliated single ventricle circulation: arteriovenous malformations and aortopulmonary collaterals. J Cardiovasc Dev Dis. 2022;9(9):309.

[6] Latus H, Apitz C, Binder W, Kerst G, Hofbeck M. Aortopulmonary collateral flow is related to pulmonary artery size and affects early postoperative outcome after Fontan procedure. PLoS One. 2013;8(11):e81684.

[7] Brown DW, Gauvreau K, Moran AM, Jenkins KJ, Perry SB, del Nido PJ, Geva T. Cardiac magnetic resonance versus routine catheterization before bidirectional Glenn anastomosis: long-term follow-up of a randomized trial. J Thorac Cardiovasc Surg. 2013;145(5):1179-1186.e3.

[8] Imai K, Hoashi T, Okuda N, Miyata H, Kurosaki K, Fujimura Y, Miyazaki A, Iwamoto Y, Ichikawa H. Impact of bilateral bidirectional Glenn anastomosis on staged Fontan strategy and Fontan circulation. Eur J Cardiothorac Surg. 2021;60(4):930-938.