High-Risk Indicators for Fontan Completion – #1 Hemodynamics & Function

In a Fontan circulation, all systemic venous blood must traverse the pulmonary vascular bed without the help of a subpulmonary ventricle. Cardiac output is therefore governed by a narrow pressure gradient:

Systemic veins → Pulmonary arteries → Pulmonary veins/atrium → Single ventricle

Any rise in pulmonary vascular resistance (PVR) or ventricular filling pressure compresses this gradient and the system compensates with chronic systemic venous hypertension—the hallmark of Fontan physiology.[1] Frontiers

Because the Glenn and Fontan stages merely re-route venous return without adding a pump, hemodynamics at the post-Glenn stage largely foreshadow the future Fontan. Careful evaluation of ventricular function, atrioventricular valve (AVV) competence, pulmonary vascular load, and filling pressures is therefore crucial when deciding on Fontan completion.

1. Hemodynamic Principles Relevant to Fontan Candidacy

After a bidirectional Glenn (BDG), the superior vena cava is connected directly to the pulmonary arteries, and pulmonary blood flow from the SVC becomes passive. Flow is determined by:

• Central venous pressure (CVP)
• Pulmonary vascular resistance (PVR)
• Ventricular end-diastolic pressure (EDP)
• The geometry and energy loss within the cavopulmonary pathway

A “Fontan-ready” circulation therefore requires:

1. Low PVR – unobstructed pulmonary arteries with good compliance
2. Preserved systolic function of the single systemic ventricle
3. Low EDP – a compliant ventricle that fills at low pressure
4. Minimal systemic AVV regurgitation, to avoid chronic volume load and rising filling pressures

If one or more of these conditions is abnormal at the Glenn stage, multiple series show increased risk of death or transplant before Fontan, difficulty reaching Fontan completion, and late Fontan failure.[2–5] PubMed+3PubMed+3PubMed+3

2. Evidence-Based High-Risk Indicators

2.1 Systemic AV Valve Regurgitation (> mild)

• In several BDG cohorts, AVV regurgitation greater than mild has emerged as one of the strongest predictors of death, transplant, or failure to progress to Fontan.[2–4] PubMed+2PubMed+2
• Friedman et al. showed that > mild AVVR pre-BDG increased the hazard of death or transplant 7.5-fold and independently reduced the likelihood of ever reaching Fontan completion.[2] PubMed
• Scheurer et al. similarly identified AVVR as an independent risk factor for death or transplantation after BDG.[3] PubMed
• Nichay et al. found that both pre- and post-operative AVVR were associated with “unfavorable outcomes” (death, Glenn takedown, or non-suitability for Fontan).[4] ResearchGate

Conceptually: AVVR imposes a chronic volume load on the single ventricle, raising EDP, promoting ventricular dilatation/dysfunction, and further elevating venous pressure. In many patients, AVV repair or replacement is a prerequisite for safe Fontan.

2.2 Ventricular Dysfunction (especially systolic EF ≤ 45%)

• In adult cohorts with late Fontan failure, ventricular dysfunction—both systolic and diastolic—is much more prevalent than elevated PVR. Sallmon et al. reported that 77% of adults with failing Fontan had ventricular dysfunction (EF ≤45% and/or EDP ≥12 mmHg), whereas elevated indexed PVR was present in only 19%.[5] PubMed
• EF declined from about 60% to 47% over time, while PVRi remained essentially unchanged—supporting the idea that ventricular disease, not pulmonary vasculopathy, is the dominant driver of late failure.[5] PubMed

For Fontan candidacy, ≥ moderate systolic dysfunction of the systemic ventricle should therefore be regarded as a major red flag. These ventricles require higher filling pressures to maintain output, which is incompatible with the low-pressure requirements of a Fontan circulation.

2.3 Elevated End-Diastolic Pressure (EDP)

• Elevated EDP reflects a stiff, non-compliant ventricle due to hypertrophy, fibrosis, or long-standing pressure/volume overload.
• Adult data suggest that systemic ventricular EDP ≥12 mmHg is common among patients with late Fontan failure and is associated with worse survival.[5] PubMed
• Several contemporary cohorts and reviews now treat EDP thresholds in the 12–13 mmHg range as markers of significant diastolic dysfunction, often associated with a several-fold increase in death, transplant, or Fontan takedown risk.[5] PubMed

In the pre-Fontan Glenn setting, an EDP in this range implies that the transpulmonary gradient will be small once the inferior vena cava is connected, forcing systemic venous pressure even higher to maintain flow. Clinically, this translates into a higher likelihood of prolonged effusions, ascites, lymphatic complications, and liver congestion after Fontan.

2.4 Pulmonary Vascular Resistance and Pulmonary Vasodilator Therapy

• Historically, “good” PVR was considered a prerequisite for Fontan. However, in modern series of late Fontan failure, significant increases in PVRi are less common than ventricular dysfunction.[5] PubMed
• Nonetheless, PVRi > 3 Wood units·m² at any point post-Glenn is usually taken as a high-risk feature, reflecting a pulmonary vascular bed poorly suited to a passive circuit.

Pulmonary vasodilators

• Small single-centre studies (e.g., Castaldi et al.) have shown that pulmonary vasodilators (PDE-5 inhibitors, endothelin-receptor antagonists) can reduce PVR, increase pulmonary arterial compliance and diameter, and improve cardiac output in selected Glenn/Fontan patients.[8] ResearchGate
• Randomised trials and meta-analyses give a more nuanced picture. A 2019 and a 2021 meta-analysis of pulmonary vasodilators after Fontan showed:
• Modest improvements in functional class, 6-minute walk distance, and peak VO₂
• Small reductions in mean PA pressure,
• No clear signal for improved survival, and overall good tolerability.[6,7] ResearchGate
• A recent single-centre experience from Faccini et al. found that vasodilators were typically used in higher-risk Fontan patients with elevated circuit pressures or complications such as plastic bronchitis, PLE, or refractory effusions, and highlighted the absence of standardised protocols or robust indications.[9] MDPI

Taken together, pulmonary vasodilators may be useful for selected high-risk or symptomatic patients, but current evidence does not support their routine use as a simple means of “making a bad Fontan candidate good.” The decision to start such therapy should be individualized and usually made in the context of catheterization findings and multidisciplinary discussion.

3. Integrating the Diagram: From Glenn to Fontan

On your schematic of the post-Glenn circulation, three lesions converge:

1. High PVR in the pulmonary circuit
2. Systemic AVV regurgitation → chronic volume load
3. Ventricular dysfunction with high EDP

These create a vicious circle:

• AVV regurgitation and ventricular dysfunction → higher EDP
• High EDP plus elevated PVR → loss of transpulmonary gradient
• To preserve pulmonary blood flow, the system raises CVP and systemic venous pressures
• Chronic venous hypertension then manifests as prolonged pleural effusions, ascites, lymphatic failure, and hepatic congestion—even before Fontan completion.

If this hemodynamic state is simply “carried forward” into an extracardiac Fontan, the new circuit begins with almost no reserve. Small postoperative changes—atrial arrhythmia, mild increase in PVR, or further deterioration of ventricular compliance—can rapidly precipitate Fontan failure, prolonged ICU stay, or even early Fontan takedown.

4. Practical Clinical Implications

1. Systematic pre-Fontan assessment
• Detailed echocardiography (AVV regurgitation, systolic/diastolic function)
• Cardiac catheterization (PVRi, EDP, transpulmonary gradient)
• Cross-sectional imaging for pulmonary arteries and systemic venous pathway
2. Red-flag hemodynamic/functional findings
• AVV regurgitation > mild
• ≥ moderate ventricular dysfunction (EF ≤45%)
• EDP ≥12–13 mmHg
• PVRi ≥3 Wood units·m², or elevated mean Glenn/Fontan circuit pressures
3. Management strategies when high-risk indicators are present
• Address the lesion, not just the number: AVV repair/replacement, relief of outflow obstruction, optimization of rhythm and afterload.
• Consider staged or modified Fontan (e.g., fenestrated Fontan, delayed completion) in borderline cases.
• Use pulmonary vasodilators selectively for patients with demonstrable pulmonary vascular disease or refractory symptoms, recognising that evidence for routine use is limited and mixed.[6–9] ResearchGate+1
• In patients with multiple high-risk features, particularly severe ventricular dysfunction and high EDP, ongoing Glenn palliation, advanced heart-failure therapies, or transplant evaluation may be safer than proceeding directly to Fontan.

References

[1] Gewillig M, Brown SC. The Fontan circulation after 45 years: update in physiology. Heart. 2016;102(14):1081-1086.

[2] Friedman KG, Salvin JW, Wypij D, et al. Risk factors for failed staged palliation after bidirectional Glenn in infants who have undergone stage one palliation. Eur J Cardiothorac Surg. 2011;40(4):1000-1006. PubMed

[3] Scheurer MA, Hill EG, Vasuki N, et al. Survival after bidirectional cavopulmonary anastomosis: analysis of preoperative risk factors. J Thorac Cardiovasc Surg. 2007;134(1):82-89. PubMed

[4] Nichay NR, Gorbatykh YN, Dnegilova ES, et al. Risk factors for unfavorable outcomes after bidirectional cavopulmonary anastomosis. Congenit Heart Dis. 2018;13(5):747-755. ResearchGate

[5] Sallmon H, Ovroutski S, Schleiger A, et al. Late Fontan failure in adult patients is predominantly associated with deteriorating ventricular function. Int J Cardiol. 2021;344:87-94. PubMed

[6] Li D, Zhou X, An Q, Feng Y. Pulmonary vasodilator therapy after the Fontan procedure: a meta-analysis. Heart Fail Rev. 2021;26(6):1429-1441. ResearchGate

[7] Wang W, Hu X, Liao W, Huang W. The efficacy and safety of pulmonary vasodilators in patients with Fontan circulation: a meta-analysis of randomized controlled trials. Cardiol Young. 2019;29(9):1103-1111. ResearchGate

[8] Castaldi B, Bordin G, Padalino M, Milanesi O. Hemodynamic impact of pulmonary vasodilators on single-ventricle physiology. J Card Surg. 2017;32(11):684-691. ResearchGate

[9] Faccini A, Avesani M, Biffanti R, et al. The use of vasodilator therapy in Fontan patients: a single-centre experience. Children (Basel). 2025;12(6):751. MDPI