Fontan Outcomes in Oligemia vs Plethora in Univentricular CHD

Comparison of Outcomes of Pulmonary Oligemia Versus Pulmonary Plethora in Cyanotic Congenital Heart Disease With Univentricular Heart After Fontan Procedure

This prospective cohort study evaluates differences in clinical outcomes between pulmonary oligemia and pulmonary plethora in patients with cyanotic congenital heart disease and univentricular heart physiology undergoing staged palliation culminating in the Fontan procedure.Fifty-two patients will be classified into two groups based on pulmonary blood flow characteristics and followed for approximately 1.5 years after the Fontan procedure. Outcomes include mortality, morbidity, pulmonary hemodynamics, functional capacity, neurocognitive status, and quality of life.

Study Overview

• Status: Recruiting
• Conditions: Univentricular Heart; Congenital Heart Disease (CHD)
• Intervention / Treatment: Procedure: Fontan Procedure

Detailed Description

Univentricular heart physiology represents a complex form of congenital heart disease requiring staged surgical palliation. The Fontan procedure has improved survival; however, outcomes remain variable and are influenced by pulmonary vascular conditions. Pulmonary blood flow abnormalities-oligemia (reduced flow) and plethora (increased flow)-may affect lung development from fetal life. Oligemia has been associated with pulmonary hypoplasia, impaired alveolar formation, and increased pulmonary vascular resistance, which may adversely affect Fontan circulation.

This prospective cohort study aims to compare outcomes between patients with oligemia and those with plethora. Participants will undergo standard clinical care, including staged procedures (Bidirectional Glenn and Fontan), and comprehensive assessments (clinical, laboratory, imaging, and hemodynamic). Follow-up will be conducted for approximately 1.5 years post-Fontan.

The study will evaluate mortality, morbidity, pulmonary hemodynamics, biomarkers (NT-proBNP, ET-1, Activin-A), exercise capacity, neurocognitive outcomes, and quality of life. Findings are expected to improve risk stratification and management strategies in univentricular CHD.

• Study Type: Observational
• Enrollment (Estimated): 52

Contacts and Locations

• Study Contact: Name: Sisca Natalia Siagian, MD; Phone Number: +6281212716332; Email: sisca.ped.car@gmail.com

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta, DKI Jakarta, Indonesia, 11420
      • Recruiting
      • National Cardiovascular Center Harapan Kita
      • Contact: Sisca Natalia Siagian, MD; Phone Number: +6281212716332; Email: sisca.ped.car@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will involve a cohort of clinically diagnosed patients with univentricular heart physiology who are undergoing the Fontan procedure as their final intervention.

Description

Inclusion Criteria:

• Diagnosed cyanotic CHD
• Univentricular heart physiology
• Planned staged palliation including Fontan procedure
• Informed consent obtained (patient or guardian)

Exclusion Criteria:

• Refusal to participate
• Incomplete clinical data
• Inability to complete follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pulmonary Oligemia; Patients with cyanotic CHD and univentricular physiology characterized by reduced pulmonary blood flow.	Procedure: Fontan Procedure; Standard staged palliation including Bidirectional Glenn and Fontan procedure. No experimental intervention; observational classification only.
Pulmonary Plethora; Patients with cyanotic CHD and univentricular physiology characterized by increased pulmonary blood flow.	Procedure: Fontan Procedure; Standard staged palliation including Bidirectional Glenn and Fontan procedure. No experimental intervention; observational classification only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause mortality following completion of Fontan procedure.	From recruitment through study completion (an average of 1 year post-Fontan)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Postoperative Complications	Assessment of postoperative morbidity defined as the occurrence of complications (e.g., arrhythmia, infection, thrombosis, or other clinically significant adverse events) following the Fontan procedure. Measurement Tool: Clinical assessment and medical record review Unit of Measure: Number of participants with ≥1 complication	From Fontan procedure through study completion (up to 12 months post-Fontan)
Number of Participants with Rehospitalization	Assessment of rehospitalization defined as any unplanned hospital admission after discharge following the Fontan procedure. Measurement Tool: Medical record review Unit of Measure: Number of participants rehospitalized (≥1 admission)	From hospital discharge post-Fontan through study completion (up to 12 months post-Fontan)
Concentration of Activin-A in Blood	Measurement of circulating Activin-A concentration as a biomarker of pulmonary vascular remodeling and inflammation in patients with univentricular congenital heart disease undergoing staged palliation. Blood samples will be collected at predefined perioperative time points. Measurement Tool: Enzyme-linked immunosorbent assay (ELISA) or equivalent validated immunoassay Unit of Measure: Picograms per milliliter (pg/mL)	Baseline (pre-BCPS procedure), Perioperative at Stage II (Bidirectional Cavopulmonary Shunt [BCPS]), Perioperative at Stage III (Fontan procedure)
Concentration of Activin-A in Pulmonary Artery Tissue	Measurement of Activin-A concentration in pulmonary artery tissue obtained during surgical procedures, reflecting local vascular remodeling and inflammatory activity. Measurement Tool: Enzyme-linked immunosorbent assay (ELISA) or equivalent validated immunoassay on homogenized tissue samples Unit of Measure: Picograms per milligram of tissue (pg/mg)	- At time of tissue collection during Stage II (Bidirectional Cavopulmonary Shunt [BCPS]) - At time of tissue collection during Stage III (Fontan procedure) Analysis performed within 1 month after each collection
Distance Covered in Six-Minute Walk Test (6MWT)	Assessment of functional exercise capacity using the six-minute walk test (6MWT), performed according to standardized protocol. Measurement Tool: Six-minute walk test (6MWT) Unit of Measure: Distance in meters (m) Interpretation: More distance covered means higher exercise capacity	Follow-up (6 months post-Fontan procedure)
Neurodevelopmental Score Using Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-IV)	Assessment of neurocognitive and developmental function in pediatric patients using the Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-IV). The instrument evaluates multiple domains including cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, and adaptive behavior. Raw scores are converted into standardized composite scores based on age-specific norms. Measurement Tool: Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-IV) Unit of Measure: Standard score (composite score), typically ranging from 40 to 160, with a mean of 100 and standard deviation of 15 Higher scores indicate better neurodevelopmental performance	Follow-up (6 months post-Fontan procedure)
Cognitive Function Score Using Montreal Cognitive Assessment (MoCA)	Assessment of cognitive function in adult patients using the Montreal Cognitive Assessment (MoCA), a screening tool evaluating domains including memory, executive function, attention, language, visuospatial ability, and orientation. Measurement Tool: Montreal Cognitive Assessment (MoCA) Unit of Measure: Score on a scale from 0 to 30, where higher scores indicate better cognitive function; a score of 26 or above is considered normal	Follow-up (6 months post-Fontan Procedure)
Quality of Life Score Using Child Health Questionnaire (CHQ)	Assessment of quality of life in pediatric patients using the Child Health Questionnaire (CHQ). The instrument evaluates multiple health domains, which are aggregated into Physical Health Summary (PhS) and Psychosocial Summary (PsS) scores. Measurement Tool: Child Health Questionnaire (CHQ) Unit of Measure: Score on a scale from 0 to 100 (higher scores indicate better health status)	Follow-up (6 months post-Fontan procedure)
Quality of Life Score Using 36-Item Short Form Survey (SF-36)	Assessment of quality of life in adult patients using the 36-item Short Form Survey (SF-36). The instrument includes 8 domains aggregated into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Measurement Tool: 36-item Short Form Survey (SF-36) Unit of Measure: Score on a scale from 0 to 100 (higher scores indicate better health status)	Follow-up (6 months post-Fontan Procedure)
Histopathological Score of Pulmonary Artery Remodeling Using Hematoxylin and Eosin (H&E) Staining	Semi-quantitative assessment of pulmonary artery structural changes (e.g., medial hypertrophy, intimal proliferation, luminal narrowing) using Hematoxylin and Eosin (H&E) staining. A standardized Pulmonary Artery Remodeling Histopathological Scoring System is used to grade the severity of vascular changes. Measurement Tool: Light microscopy using a semi-quantitative histopathological scoring system Unit of Measure: Score on a scale from 0 to 3, where: 0 = no structural abnormality; = mild remodeling; = moderate remodeling; = severe remodeling Higher scores indicate worse pulmonary artery remodeling	At time of tissue collection during BCPS and Fontan procedures; analysis performed within 1 month after each collection
Percentage of Collagen Deposition Using Masson's Trichrome Staining	Quantification of collagen accumulation in pulmonary artery tissue using Masson's Trichrome staining, analyzed via digital image analysis software. Measurement Tool: Image analysis software (e.g., ImageJ or equivalent) Unit of Measure: Percentage (%) of stained area per total vessel area	At time of tissue collection during BCPS and Fontan procedures; analysis performed within 1 month after each collection
Elastin Density Measured by Verhoeff-Van Gieson (VVG) Staining	Evaluation of elastin fiber integrity and distribution in pulmonary artery tissue using Elastica Van Gieson staining. Measurement Tool: Microscopy with image analysis Unit of Measure: Percentage (%) elastin-positive area	At time of tissue collection during BCPS and Fontan procedures; analysis performed within 1 month after each collection
Percentage of PAS-Positive Area in Pulmonary Artery Tissue	Assessment of glycoprotein/glycogen and basement membrane components using Periodic Acid-Schiff (PAS) staining. Measurement Tool: Microscopy with quantitative image analysis Unit of Measure: Percentage (%) PAS-positive area	At time of tissue collection during BCPS and Fontan procedures; analysis performed within 1 month after each collection
Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization	Measurement of mean pulmonary artery pressure (mPAP) obtained from right heart catheterization to assess pulmonary hemodynamics. Measurement Tool: Right heart catheterization Unit of Measure: Millimeters of mercury (mmHg)	Baseline, Post-BCPS preparing for Fontan (average of 3 months post-BCPS procedure), Follow-up (average of 6 months post-Fontan procedure)
Pulmonary Vascular Resistance Measured by Right Heart Catheterization	Calculation of pulmonary vascular resistance (PVR) derived from catheterization data using standard hemodynamic formulas. Measurement Tool: Right heart catheterization with hemodynamic calculation Unit of Measure: Wood units (WU)	Baseline, Post-BCPS preparing for Fontan (average of 3 months post-BCPS procedure), Follow-up (average of 6 months post-Fontan procedure)
McGoon Ratio Assessed by Angiography	Evaluation of pulmonary artery size using the McGoon ratio, calculated as the sum of the diameters of the right and left pulmonary arteries divided by the diameter of the descending aorta, measured from angiographic images. Measurement Tool: Angiography with standardized measurement method Unit of Measure: Ratio (unitless)	Baseline, Post-BCPS preparing for Fontan (average of 3 months post-BCPS procedure), Follow-up (average of 6 months post-Fontan procedure)
Nakata Index Measured by Angiography	Quantification of pulmonary artery size using the Nakata index, calculated as the sum of cross-sectional areas of the right and left pulmonary arteries normalized to body surface area. Measurement Tool: Angiography with body surface area calculation Unit of Measure: mm²/m²	Baseline, Post-BCPS preparing for Fontan (average of 3 months post-BCPS procedure), Follow-up (average of 6 months post-Fontan procedure)

Collaborators and Investigators

• Sponsor: Sisca Natalia Siagian
• Collaborators: National Cardiovascular Center Harapan Kita Hospital Indonesia; LMU Klinikum; Fakultas Kedokteran Universitas Indonesia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: congenital heart disease; univentricular heart; pulmonary hemodynamics; pulmonary blood flow; fontan procedure; oligemia; plethora
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Univentricular Heart; Heart Defects, Congenital; Hypovolemia; Surgical Procedures, Operative; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Anastomosis, Surgical; Vascular Grafting; Cardiac Surgical Procedures; Thoracic Surgical Procedures; Heart Bypass, Right; Norwood Procedures; Fontan Procedure
• Other Study ID Numbers: DP.04.03/D.XIII/6681/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be publicly shared. Data may be available upon reasonable request to the principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No