Glenn Circulation #7: High-Risk Indicators for Fontan Completion

After bidirectional Glenn palliation, Fontan completion represents the transition from partial cavopulmonary connection to total cavopulmonary circulation. This is not merely an anatomic extension of the Glenn pathway; it is a profound physiologic conversion in which the entire systemic venous return must traverse the pulmonary vascular bed without a subpulmonary ventricle.

Therefore, Fontan candidacy depends on a narrow physiologic balance:

• Low pulmonary vascular resistance
• Unobstructed pulmonary arteries and pulmonary veins
• Good systemic ventricular systolic and diastolic function
• Competent systemic atrioventricular valve
• Adequate respiratory mechanics and extracardiac reserve

Your current slide appropriately organizes these concerns into hemodynamic, anatomic, syndromic, and functional domains. The central message is that a “successful Glenn” does not automatically mean a “safe Fontan.” The more precise question is:

Can this patient tolerate Fontan physiology—not only immediately after surgery, but over years of passive venous circulation?

1. Hemodynamics and Ventricular Function

Key high-risk indicators

• PVRi > 3 Wood units·m² at any point after Glenn
• Use of pulmonary vasodilator therapy within 1 year before Fontan promotion
• Moderate or greater systemic AV valve regurgitation
• Moderate or greater systemic ventricular dysfunction
• End-diastolic pressure > 12 mmHg

Among all pre-Fontan risk domains, pulmonary vascular resistance, ventricular performance, and AV valve competence are the most fundamental. In the Glenn circulation, only the superior vena caval return passes directly into the pulmonary arteries. After Fontan completion, the inferior vena caval return is added, and the entire systemic venous circulation must flow passively through the lungs.

This means that even a modest increase in pulmonary vascular resistance may become clinically important. Elevated PVRi increases the pressure required to drive blood across the pulmonary vascular bed. In Fontan physiology, this translates into higher systemic venous pressure, reduced preload delivery to the ventricle, and lower cardiac output.

Earlier staged-palliation studies identified AV valve regurgitation, ventricular dysfunction, and elevated pulmonary artery pressure or resistance as important predictors of adverse outcomes during progression through single-ventricle palliation [1]. Classic experience with high-risk Fontan candidates also emphasized elevated pulmonary artery pressure, elevated pulmonary vascular resistance, and distorted pulmonary artery anatomy as major reasons to delay or stage Fontan completion through bidirectional cavopulmonary anastomosis [2–4].

Why elevated PVR is dangerous

Fontan flow is pressure-dependent and energy-limited. There is no right ventricle to actively propel blood through the pulmonary arteries. Therefore, the driving force for pulmonary blood flow is the pressure gradient between systemic venous pressure and pulmonary venous atrial pressure.

If PVR is elevated:

1. Fontan pressure rises
2. Systemic venous congestion increases
3. Pulmonary blood flow decreases
4. Ventricular preload falls
5. Cardiac output becomes limited

This physiology explains why elevated PVRi, high mean pulmonary artery pressure, or the need for pulmonary vasodilator therapy should be interpreted as warning signs before Fontan completion.

A particularly important modern concept is the interaction between PVRi and cardiac index. Patients with elevated PVRi and low cardiac index represent a high-risk phenotype because they have both an obstructed passive pulmonary circuit and limited forward systemic output. In Fontan failure, the combination of pulmonary vascular disease and impaired cardiac index is strongly associated with adverse outcomes [7].

2. Systemic AV Valve Regurgitation

Systemic AV valve regurgitation is not a secondary detail in Fontan assessment. It is a major determinant of long-term Fontan efficiency.

Mechanism of risk

Moderate or severe systemic AV valve regurgitation causes:

• Volume loading of the single ventricle
• Elevation of atrial pressure
• Reduction in effective forward output
• Transmission of elevated filling pressure backward into the pulmonary venous and systemic venous pathways

In a biventricular circulation, a ventricle may partially compensate for volume loading. In Fontan physiology, however, there is limited reserve. AV valve regurgitation increases ventricular workload while simultaneously worsening the pressure environment required for passive pulmonary flow.

Several studies of single-ventricle palliation have identified moderate or severe AV valve regurgitation as an important risk factor for failure to progress or adverse outcomes [1,5,6]. Late Fontan outcome studies also support the concept that valvar dysfunction contributes to major adverse events, including arrhythmia, heart failure, transplantation, and death [8].

Surgical implication

Before Fontan completion, systemic AV valve regurgitation should be evaluated carefully:

1. Severity
2. Mechanism
3. Annular dilation
4. Leaflet tethering or prolapse
5. Ventricular morphology
6. Feasibility and durability of repair

If moderate or greater regurgitation is present, the decision is not simply whether to proceed with Fontan. The more important surgical question is whether the valve should be repaired before or at the time of Fontan completion, and whether the expected repair will be durable enough for long-term Fontan physiology.

3. Systemic Ventricular Dysfunction and High EDP

A Fontan circulation requires not only a strong ventricle, but also a compliant ventricle.

High-risk findings

• Moderate or greater systemic ventricular systolic dysfunction
• Elevated ventricular end-diastolic pressure, especially EDP > 12 mmHg
• Restrictive ventricular filling
• Ventricular hypertrophy or adverse remodeling
• Persistent volume loading from AV valve regurgitation or systemic-to-pulmonary collaterals

High EDP is particularly important because it reflects impaired ventricular filling conditions. In Fontan physiology, pulmonary venous return must enter the ventricle at low downstream pressure. If ventricular filling pressure is elevated, the passive Fontan pathway faces resistance not only at the pulmonary vascular level but also at the ventricular diastolic level.

This produces a “double-load” problem:

• Upstream resistance: elevated PVR or PA obstruction
• Downstream resistance: elevated atrial or ventricular filling pressure

When both are present, Fontan completion becomes substantially more fragile.

Clinical interpretation

A ventricle may appear acceptable by systolic function alone, but still be poorly suited for Fontan physiology if it is stiff, hypertrophied, or has elevated EDP. Therefore, pre-Fontan evaluation should include both systolic and diastolic assessment. Catheterization-derived filling pressures remain important, especially when echocardiographic function appears borderline or when clinical findings suggest poor reserve.

4. Pulmonary Artery Anatomy and Prior PA Intervention

High-risk indicators

• Pulmonary artery stenting after Glenn
• Surgical pulmonary artery intervention after Glenn
• Branch pulmonary artery stenosis
• PA distortion at the Glenn anastomosis
• Unbalanced pulmonary blood flow distribution

The pulmonary arteries are the “conduit” through which Fontan flow must pass. Because there is no subpulmonary pump, the Fontan circulation is extremely sensitive to geometric obstruction, branch PA narrowing, or flow imbalance.

A history of PA stenting or surgical PA reconstruction after Glenn should be interpreted as evidence of a vulnerable pulmonary pathway. Even when the lesion has been treated, the need for intervention suggests that pulmonary artery growth, geometry, or flow distribution may not be ideal.

Classic studies of high-risk Fontan staging identified pulmonary artery distortion and elevated pulmonary vascular resistance as important adverse features [2,3]. The bidirectional Glenn was historically valuable because it allowed time for pulmonary artery rehabilitation, reduction of ventricular volume load, and reassessment before Fontan completion [2,3].

Practical pre-Fontan checklist

Before proceeding to Fontan completion, the team should confirm:

1. No significant residual branch PA stenosis
2. Adequate PA size
3. Balanced right and left pulmonary blood flow
4. Acceptable mean PA pressure
5. No significant Glenn anastomotic obstruction
6. No major aortopulmonary collateral burden
7. No pulmonary venous obstruction

In surgical terms, a technically completed Fontan may still fail if the pulmonary arterial bed is anatomically narrow, distorted, or unevenly distributed.

5. Pulmonary Venous Intervention and Pulmonary Venous Pathway Risk

Pulmonary venous disease is one of the least tolerated substrates for Fontan physiology.

Why pulmonary venous obstruction is critical

Any pulmonary venous obstruction increases pulmonary venous pressure, which secondarily increases pulmonary vascular resistance and impairs forward flow across the Fontan circuit. In a circulation without a subpulmonary ventricle, this can rapidly lead to:

• Elevated Fontan pressure
• Pleural effusions
• Low cardiac output
• Pulmonary edema or lymphatic congestion
• Early Fontan failure

A history of pulmonary venous intervention after Glenn suggests that the pulmonary venous pathway may have been unstable, restenotic, or anatomically vulnerable. Even if the immediate obstruction has been relieved, the presence of prior pulmonary venous disease should prompt careful reassessment before Fontan completion.

6. History of Intact Atrial Septum

A history of an intact atrial septum is not always listed in classic Fontan risk models, but it is physiologically meaningful.

An intact or restrictive atrial septum can expose the pulmonary venous atrium and pulmonary vascular bed to elevated pressure. Depending on timing and severity, this may contribute to pulmonary venous hypertension, impaired pulmonary vascular development, or abnormal pulmonary vascular reactivity.

Practical interpretation

A history of intact atrial septum should prompt careful review of:

• Neonatal pulmonary venous decompression
• Prior atrial septectomy or septostomy
• Pulmonary venous Doppler patterns
• Pulmonary artery pressure and PVRi
• Lung development and pulmonary vascular reactivity
• Residual atrial-level obstruction

This factor should not be treated as an isolated contraindication, but rather as a marker that the pulmonary vascular bed may have experienced adverse loading earlier in life.

7. Genetic and Syndromic Factors

High-risk syndromic associations

• Trisomy 21
• Kabuki syndrome
• Noonan syndrome
• Alagille syndrome

Genetic and syndromic diagnoses do not automatically exclude Fontan completion. However, they often indicate that the patient’s risk is not purely intracardiac.

These conditions may be associated with:

• Pulmonary hypertension
• Airway obstruction
• Abnormal lymphatic development
• Hepatic disease
• Branch pulmonary artery stenosis
• Growth failure
• Feeding difficulty
• Immune dysfunction
• Developmental delay
• Reduced functional reserve

For example, Trisomy 21 may be associated with pulmonary hypertension, airway obstruction, and sleep-disordered breathing. Noonan syndrome may be associated with lymphatic abnormalities, hypertrophic ventricular physiology, and pulmonary valve or branch PA disease. Alagille syndrome may involve branch pulmonary artery stenosis and hepatic disease, both of which are highly relevant to Fontan candidacy.

Surgical implication

In syndromic patients, Fontan candidacy should not be determined by catheterization numbers alone. The decision should integrate:

1. Cardiac anatomy
2. Pulmonary vascular resistance
3. Pulmonary artery and venous anatomy
4. Airway and respiratory status
5. Lymphatic risk
6. Hepatic function
7. Growth and nutrition
8. Functional capacity

The Fontan circulation has limited reserve. Therefore, extracardiac disease can convert an anatomically feasible Fontan into a physiologically fragile Fontan.

8. Functional and Respiratory Status

High-risk indicators

• Non-ambulatory status
• Difficulty with ambulation
• History of tracheostomy
• Need for noninvasive positive-pressure ventilation

Functional and respiratory status are increasingly recognized as important components of Fontan risk assessment, even when they are not always captured in older surgical risk models.

Why ambulation matters

Ambulation is not only a developmental milestone. In Fontan physiology, skeletal muscle contraction—especially from the lower extremities—contributes to venous return from the IVC territory. A non-ambulatory patient may have:

• Reduced venous return augmentation
• Lower exercise capacity
• Greater venous stasis
• Reduced ability to increase cardiac output with activity

Why respiratory mechanics matter

Spontaneous breathing assists Fontan flow by generating negative intrathoracic pressure. Positive-pressure ventilation has the opposite effect: it can increase intrathoracic pressure, reduce systemic venous return, and impair passive pulmonary blood flow.

Therefore, tracheostomy dependence, chronic respiratory insufficiency, or need for NIPPV should be viewed as major warning signs. These factors may not prohibit Fontan completion, but they should prompt careful multidisciplinary evaluation before surgery.

9. Risk Is Cumulative, Not Binary

No single risk factor should automatically determine the Fontan decision. The more important issue is the cumulative Fontan substrate.

A patient with one mild risk factor may still tolerate Fontan physiology. However, multiple moderate risk factors can interact and create a high-risk circulation.

For example:

• Mildly elevated PVRi
• Borderline ventricular function
• Mild-to-moderate AV valve regurgitation
• Prior PA intervention
• Poor growth or respiratory support

Individually, each finding may appear manageable. Together, they may define a fragile Fontan candidate.

This cumulative-risk concept is supported by long-term Fontan outcome studies showing that late complications are not determined by a single variable alone, but by the interaction of ventricular function, pulmonary vascular load, arrhythmia burden, end-organ effects, and surgical history [8–11].

10. Practical Framework for Fontan Readiness

A patient after Glenn should be considered ready for Fontan completion only when the following domains are acceptable.

A. Pulmonary vascular pathway

• Low PVRi
• Low mean PA pressure
• No significant branch PA stenosis
• No pulmonary venous obstruction
• Balanced pulmonary blood flow
• Minimal collateral burden

B. Ventricular and valvar function

• Preserved systemic ventricular systolic function
• Acceptable ventricular compliance
• Low EDP
• No more than mild systemic AV valve regurgitation
• No significant outflow obstruction

C. Respiratory and functional reserve

• Stable airway
• No major chronic positive-pressure ventilation requirement
• Adequate ambulation or functional capacity
• Acceptable growth and nutrition
• No uncontrolled pulmonary hypertension

D. Extracardiac reserve

• Acceptable hepatic function
• No severe lymphatic disorder
• Manageable syndromic comorbidities
• Adequate renal and nutritional status
• Realistic long-term Fontan surveillance plan

Key Message

Fontan completion after Glenn requires more than favorable anatomy. It requires a low-resistance pulmonary vascular bed, unobstructed pulmonary arteries and veins, preserved ventricular systolic and diastolic function, competent AV valve function, and adequate extracardiac reserve.

High-risk indicators such as elevated PVRi, pulmonary vasodilator requirement, AV valve regurgitation, ventricular dysfunction, high EDP, PA or pulmonary venous intervention, intact atrial septum, syndromic disease, poor ambulation, and respiratory support should be interpreted as signs that the Fontan circulation may be fragile.

The goal is not simply to complete the Fontan operation. The goal is to create a circulation that can sustain acceptable venous pressure, adequate cardiac output, preserved end-organ function, and long-term quality of life.

References

[1] Lee TM, Aiyagari R, Hirsch JC, Ohye RG, Bove EL, Devaney EJ. Risk factor analysis for second-stage palliation of single ventricle anatomy. Ann Thorac Surg. 2012;93(2):614-619.

[2] Bridges ND, Jonas RA, Mayer JE, Flanagan MF, Keane JF, Castaneda AR. Bidirectional cavopulmonary anastomosis as interim palliation for high-risk Fontan candidates. Early results. Circulation. 1990;82(5 Suppl):IV170-IV176.

[3] Pridjian AK, Mendelsohn AM, Lupinetti FM, Beekman RH 3rd, Dick M 2nd, Serwer G, Bove EL. Usefulness of the bidirectional Glenn procedure as staged reconstruction for the functional single ventricle. Am J Cardiol. 1993;71(11):959-962.

[4] Masuda M, Kado H, Shiokawa Y, Fukae K, Suzuki M, Murakami E, Yasui H. Clinical results of the staged Fontan procedure in high-risk patients. Ann Thorac Surg. 1998;65(6):1721-1725.

[5] Scheurer MA, Hill EG, Vasuki N, Maurer S, Graham EM, Bandisode V, Shirali GS, Atz AM, Bradley SM. Survival after bidirectional cavopulmonary anastomosis: analysis of preoperative risk factors. J Thorac Cardiovasc Surg. 2007;134(1):82-89.

[6] Weisert M, Menteer J, Durazo-Arvizu R, Wood J, Su J. Early prediction of failure to progress in single ventricle palliation: a step toward personalizing care for severe congenital heart disease. J Heart Lung Transplant. 2022;41(9):1268-1276.

[7] Egbe AC, Connolly HM, Miranda WR, Ammash NM, Hagler DJ, Veldtman GR, Borlaug BA. Hemodynamics of Fontan failure: the role of pulmonary vascular disease. Circ Heart Fail. 2017;10(12):e004515.

[8] Elder RW, McCabe NM, Veledar E, Kogon B, Jokhadar M, Rodriguez FH 3rd, McConnell M, Book W. Risk factors for major adverse events late after Fontan palliation. Congenit Heart Dis. 2015;10(2):159-168.

[9] Day RW, Etheridge SP, Veasy LG, Jenson CB, Hillman ND, Russo G, Thorne JK, Doty DB, McGough EC, Hawkins JA. Single ventricle palliation: greater risk of complications with the Fontan procedure than with the bidirectional Glenn procedure alone. Int J Cardiol. 2006;106(2):201-210.

[10] Alsaied T, Bokma JP, Engel ME, Kuijpers JM, Hanke SP, Zuhlke L, Zhang B, Veldtman GR. Predicting long-term mortality after Fontan procedures: a risk score based on 6707 patients from 28 studies. Congenit Heart Dis. 2017;12(4):393-398.

[11] Rychik J, Atz AM, Celermajer DS, Deal BJ, Gatzoulis MA, Gewillig MH, Hsia TY, Hsu DT, Kovacs AH, McCrindle BW, Newburger JW, Pike NA, Rodefeld M, Rosenthal DN, Schumacher KR, Marino BS, Stout K, Veldtman G, Younoszai AK, d’Udekem Y. Evaluation and management of the child and adult with Fontan circulation: a scientific statement from the American Heart Association. Circulation. 2019;140(6):e234-e284.