Shunts and Collaterals #2: Pulmonary Arteriovenous Malformations

Pulmonary arteriovenous malformations (PAVMs) are abnormal vascular communications between pulmonary arteries and pulmonary veins that bypass the intervening alveolar capillary network. In the setting of congenital heart disease, particularly after cavopulmonary connections, their clinical significance lies in the creation of an intrapulmonary right-to-left shunt, producing systemic arterial desaturation despite apparently adequate ventilation and unobstructed pulmonary blood flow [1, 2].

1. Normal Pulmonary Capillary Network: The Site of Gas Exchange

Under normal physiology, pulmonary arterial blood enters a dense alveolar capillary bed before returning through the pulmonary veins. This capillary interface has two essential functions:

1. Gas exchange

Deoxygenated blood is exposed to alveolar gas, allowing oxygen uptake and carbon dioxide elimination.

2. Biological filtration

The pulmonary capillary bed also filters small thrombi, air bubbles, and particulate material before they reach the systemic arterial circulation.

Thus, normal pulmonary circulation is not simply a conduit from pulmonary artery to pulmonary vein. It is a finely distributed exchange network, and the integrity of this network is essential for systemic oxygenation.

2. Pulmonary AVMs: A Direct Artery-to-Vein Shortcut

In PAVMs, pulmonary arterial blood communicates directly with pulmonary venous blood without traversing the alveolar capillary bed. As a result, blood returns to the systemic ventricle without effective oxygenation.

The physiological consequences include:

• Right-to-left intrapulmonary shunting
• Systemic arterial desaturation
• Cyanosis that may be disproportionate to intracardiac anatomy
• Limited improvement with supplemental oxygen
• Risk of paradoxical embolic events, because the pulmonary capillary filter is bypassed

A useful conceptual distinction is:

Ventilation failure means oxygen does not reach the alveoli.

Pulmonary AVMs mean blood does not reach the alveolar capillary interface.

This explains why patients may have acceptable airway mechanics and adequate ventilation, yet remain cyanotic because part of the pulmonary blood flow is anatomically excluded from gas exchange.

3. Why Pulmonary AVMs Develop After Glenn or Fontan Circulation

PAVMs are particularly important after superior cavopulmonary connection, including the bidirectional Glenn procedure and the Kawashima-type circulation. In these circulations, systemic venous blood from the upper body flows directly into the pulmonary arteries, while hepatic venous blood may remain excluded from one or both pulmonary vascular beds.

Srivastava and colleagues demonstrated a strong association between exclusion of hepatic venous effluent from the pulmonary arterial circulation and the development of PAVMs. In their series, PAVMs developed in 21% of patients with cavopulmonary anastomosis and hepatic venous exclusion, compared with 1.8% in patients without such physiology [1]. This observation established the clinical concept that hepatic venous blood contains, or carries, a factor necessary for maintaining normal pulmonary vascular architecture.

Mechanistic sequence after Glenn-type physiology

1. The SVC is connected directly to the pulmonary arteries.
2. Hepatic venous return continues to drain to the heart or systemic venous pathway.
3. One or both lungs are deprived of hepatic venous effluent.
4. Abnormal pulmonary vascular remodeling and angiogenesis develop.
5. Diffuse intrapulmonary arteriovenous channels form.
6. Desaturated blood returns through the pulmonary veins to the systemic ventricle.

The result is progressive cyanosis despite adequate cavopulmonary pathway patency.

4. The “Hepatic Factor” Concept

The exact molecular identity of the hepatic factor remains incompletely defined, but the clinical evidence is consistent: pulmonary vascular beds deprived of hepatic venous effluent are prone to developing PAVMs, and redirection of hepatic venous blood can lead to improvement or regression [1, 3, 4].

The hepatic factor concept is supported by several observations:

• PAVMs are common after cavopulmonary connections that exclude hepatic venous blood.
• PAVMs may regress after Fontan completion or hepatic venous flow redirection.
• In Fontan patients, PAVMs may persist or recur if hepatic venous flow streams preferentially to the opposite lung.
• Patients with heterotaxy, interrupted IVC, azygos continuation, and left isomerism are particularly vulnerable because hepatic venous flow distribution may be anatomically complex [3, 4].

Therefore, the issue is not only whether pulmonary blood flow exists, but whether hepatic venous effluent is distributed to the correct pulmonary vascular bed.

5. Angiogenesis as a Final Common Pathway

Several studies suggest that abnormal angiogenesis is a key downstream mechanism in PAVM formation after cavopulmonary connection. Marshall and colleagues proposed that hepatic-derived angiogenic inhibitory factors may normally suppress abnormal pulmonary vascular proliferation, and that their absence may permit vascular remodeling toward arteriovenous channels [5]. Subsequent work has emphasized that altered angiogenic signaling, endothelial remodeling, and changes in pulmonary microvascular architecture may represent the final common pathway of PAVM development [6, 7].

This concept is important because PAVMs after Glenn physiology are usually not isolated, discrete vascular lesions. They are often diffuse microvascular abnormalities, which explains why simple embolization is rarely the definitive solution in this setting.

6. Clinical Presentation

The typical clinical manifestation is progressive systemic desaturation. In single-ventricle patients, this may appear as a gradual decline in oxygen saturation after Glenn or after Fontan completion.

Common findings include:

• Progressive cyanosis
• Exercise intolerance
• Clubbing in chronic cases
• Polycythemia
• Worsening hypoxemia without an obvious intracardiac explanation
• Paradoxical embolic complications in selected patients

In Glenn or Fontan patients, the key diagnostic clue is often:

Desaturation that is greater than expected for the apparent surgical anatomy and hemodynamics.

7. Diagnostic Evaluation

Diagnosis requires demonstration of intrapulmonary right-to-left shunting and assessment of hepatic venous flow distribution.

7.1 Contrast echocardiography

Agitated saline contrast echocardiography is highly sensitive for detecting intrapulmonary shunting. Delayed appearance of microbubbles in the atrium or pulmonary venous return suggests passage through the pulmonary vascular bed rather than an immediate intracardiac shunt. Marianeschi and colleagues emphasized the value of contrast echocardiography, particularly because diffuse PAVMs may be difficult to appreciate by angiography alone [2].

7.2 Pulmonary angiography

Pulmonary angiography can demonstrate rapid pulmonary venous return, diffuse vascular blush, or abnormal artery-to-vein transit. Moore and colleagues described the development of PAVMs after modified Fontan operations using angiographic and contrast-based assessment [8].

7.3 CT or MRI

Cross-sectional imaging is useful when focal PAVMs are suspected, especially in non-congenital or hereditary hemorrhagic telangiectasia–associated disease. In Glenn/Fontan-related PAVMs, however, CT may be less definitive if the lesions are diffuse and microscopic.

7.4 Flow-distribution assessment

In Fontan or heterotaxy patients, the central question is not simply whether PAVMs are present. The more surgical question is:

Does hepatic venous blood reach both lungs adequately and symmetrically?

This may require catheterization, angiography, MRI flow assessment, or computational flow analysis depending on anatomy and institutional practice.

8. Management Principles

Management depends on whether the PAVMs are focal or diffuse.

8.1 Focal PAVMs

Discrete PAVMs may be treated by transcatheter embolization when anatomy is suitable. This strategy is most applicable to isolated or hereditary hemorrhagic telangiectasia–associated PAVMs.

8.2 Diffuse PAVMs after Glenn or Fontan

Diffuse PAVMs after cavopulmonary connection are usually not well suited to coil or plug embolization. The fundamental treatment principle is:

Restore hepatic venous effluent to the affected pulmonary vascular bed.

Therapeutic strategies may include:

• Fontan completion after Glenn or Kawashima physiology
• Revision of the Fontan pathway
• Redirection of hepatic venous flow to the affected lung
• Improvement of hepatic venous mixing within the cavopulmonary circuit
• Hepatic vein–azygous or hepatic vein–pulmonary artery pathway modification in selected heterotaxy anatomies [3, 4, 9, 10]

Imoto and colleagues reported regression of PAVMs after surgical redirection of hepatic venous flow [4]. McElhinney and colleagues showed that in heterotaxy patients with unilateral PAVMs after Fontan completion, pathway reconfiguration—particularly hepatic vein–azygous vein connection—could improve hypoxemia by improving hepatic venous distribution [3]. Sernich and colleagues similarly reported improvement in systemic arterial oxygenation after surgical improvement of hepatic venous mixing [10].

9. Surgical Implications

For congenital heart surgeons, PAVMs should be understood as a circulation-design problem as much as a pulmonary vascular problem. In Glenn and Fontan physiology, the surgeon must consider not only the patency of the pathway, but also the streaming pattern of hepatic venous blood.

Important surgical considerations include:

1. After Glenn or Kawashima circulation

Long-standing exclusion of hepatic venous blood from the pulmonary bed increases the risk of PAVM formation.

2. At Fontan completion

The hepatic venous pathway should be designed to promote balanced distribution to both pulmonary arteries.

3. In heterotaxy or interrupted IVC

Hepatic venous flow may stream asymmetrically, making patients vulnerable to unilateral PAVMs even after Fontan completion.

4. In recurrent or persistent desaturation

Evaluation should include not only fenestration, venovenous collaterals, pulmonary artery stenosis, and ventricular function, but also hepatic flow maldistribution.

10. Take-Home Message

Pulmonary AVMs create an intrapulmonary right-to-left shunt by allowing pulmonary arterial blood to bypass the alveolar capillary network and return directly to the pulmonary veins. In Glenn and Fontan physiology, they are strongly associated with absent or maldistributed hepatic venous effluent.

The most important concept is:

Pulmonary AVMs after cavopulmonary connection are often not just abnormal vessels; they are evidence that the pulmonary vascular bed is receiving the wrong venous input.

For single-ventricle palliation, especially in heterotaxy and interrupted IVC anatomy, long-term oxygenation depends not only on pulmonary blood flow volume, but also on which venous blood reaches which lung.

References

[1] Srivastava D, Preminger TJ, Lock JE, Mandell V, Keane JF, Mayer JE Jr, Kozakewich H, Spevak PJ. Hepatic venous blood and the development of pulmonary arteriovenous malformations in congenital heart disease. Circulation. 1995;92(5):1217-1222.

[2] Marianeschi SM, McElhinney DB, Reddy VM. Pulmonary arteriovenous malformations in and out of the setting of congenital heart disease. Ann Thorac Surg. 1998;66(2):688-691.

[3] McElhinney DB, Marx GR, Marshall AC, Mayer JE, Del Nido PJ. Cavopulmonary pathway modification in patients with heterotaxy and newly diagnosed or persistent pulmonary arteriovenous malformations after a modified Fontan operation. J Thorac Cardiovasc Surg. 2011;141(6):1362-1370.e1.

[4] Imoto Y, Sese A, Joh K. Redirection of the hepatic venous flow for the treatment of pulmonary arteriovenous malformations after Fontan operation. Pediatr Cardiol. 2006;27(4):490-492.

[5] Marshall B, Duncan BW, Jonas RA. The role of angiogenesis in the development of pulmonary arteriovenous malformations in children after cavopulmonary anastomosis. Cardiol Young. 1997;7(4):370-374.

[6] Duncan BW, Desai S. Pulmonary arteriovenous malformations after cavopulmonary anastomosis. Ann Thorac Surg. 2003;76(5):1759-1766.

[7] 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.

[8] Moore JW, Kirby WC, Madden WA, Gaither NS. Development of pulmonary arteriovenous malformations after modified Fontan operations. J Thorac Cardiovasc Surg. 1989;98(5 Pt 1):1045-1050.

[9] Premsekar R, Monro JL, Salmon AP. Diagnosis, management, and pathophysiology of post-Fontan hypoxaemia secondary to Glenn shunt related pulmonary arteriovenous malformation. Heart. 1999;82(4):528-530.

[10] Sernich S, Ross-Ascuitto N, Dorotan J, DeLeon S, Ascuitto RJ. Surgical improvement of hepatic venous mixing to resolve systemic arterial hypoxemia associated with post-Fontan pulmonary arteriovenous fistulae. Tex Heart Inst J. 2009;36(5):480-482.