Tetralogy of FallotNCT06282926
Role of 3D Echocardiography Knowledge-based Reconstruction in ACHD
An observational study of Tetralogy of Fallot, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The main objective of this study is to evaluate the reproducibility and accuracy of TTE-3DKBR in assessing RV volume and EF compared to the reference method of CMR in a group of ACHD patients with known moderate or severe PR after ToF repair. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tetralogy of Fallot
- What is being tested?
- Echocardiography assessment
- How many people
- 59 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Apr 2024to 26 Sep 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Group 1 of healthy adult volunteers Group 2 of ACHD patients with repaired Tetralogy of Fallot and known moderate or severe pulmonary regurgitation
Who may be able to join
- Group 1 of healthy adult volunteers - Minimum aged of 18 years old without evidence of structural heart disease.
- Group 2 of ACHD patients - ACHD patient minimum aged of 18 years old with diagnosis of moderate or severe pulmonary regurgitation after ToF repair.
Who cannot join
- Group 1 of healthy adult volunteers - No informed consent, evidence of structural heart disease.
- Group 2 of ACHD patients - No informed consent, pacemaker or defibrillator non-compatible with CMR, limited echocardiographic images for image acquisition, and evidence of moderate or severe right ventricle inflow and/or right ventricle outflow tract obstruction.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Three-dimensional Echocardiography Knowledge-based Reconstruction in Monitoring Right Ventricle Remodelling Following Tetralogy of Fallot Repair
The main objective of this study is to evaluate the reproducibility and accuracy of TTE-3DKBR in assessing RV volume and EF compared to the reference method of CMR in a group of ACHD patients with known moderate or severe PR after ToF repair.
As part of the validation study, the reproducibility of the TTE-3DKBR in assessing RV volume and EF will also be tested in a group of healthy adult volunteers. Additionally, TTE-3DKBR evaluation will be compared in both groups to the conventional 2D echocardiography measurements used in routine clinical practice, such as tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging (TDI), fractional area change (FAC), and global longitudinal strain (GLS).
Read more
Another objective of the study is also to evaluate the effects of chronic RV volume overload with an interval of one-year follow-up using TTE-3DKBR and compare it with the conventional non-geometric echocardiography measurements, particularly with GLS.
The study will end when the required number of patients have been enrolled and when the last subject undergoes the research dataset acquisition. The study may be terminated prematurely if it becomes apparent that the recruitment target cannot be met within the projected recruitment phase.
Read the detailed description
Tetralogy of Fallot (ToF) is a complex pathophysiology characterised by different factors that affect the right ventricle (RV) performance. Before surgical repair in childhood, the RV is exposed to pressure load with associated abnormal RV outflow tract (RVOT) hypertrophy and myocardial damage related to prolonged cyanosis. After surgical repair involving a pulmonary valve (PV) transannular patch, the RV may experience chronic volume overload due to significant pulmonary regurgitation (PR). The effects of chronic volume overload often found in adult congenital heart disease (ACHD) patients frequently result in progressive RV dilatation with abnormal geometry and RV dysfunction with associated electromechanical dyssynchrony. All this often leads to re-intervention with PV replacement. In asymptomatic patients with severe PR, the 2020 European ACHD guidelines recommendation for PV replacement gives a class 2a recommendation and evidence level C in cases of progressive RV systolic dysfunction and/or dilatation with a RV indexed end-diastolic volume (EDVi) ≥160 mL/m2, and/or a RV indexed end-systolic volume (ESVi) ≥80 mL/m2. The guidelines also mentioned gaps regarding the need for more longitudinal imaging data to optimise time for re-intervention because the possibility for RV remodelling is, at some point, irreversible.
CMR is widely recognised in the literature as the reference standard imaging technique for accurately quantifying RV volume and ejection fraction (EF) in the ACHD population. However, unlike transthoracic echocardiography (TTE), CMR is not the first-line test used in daily clinical practice.
The echocardiographic requirement of conventional multiple non-geometric (tricuspid annular plane systolic excursion, tissue Doppler imaging, global longitudinal strain) and geometric two-dimensional (2D) parameters (fractional area change, three-dimensional volume and EF) for a more accurate RV size and systolic function assessment is consensual in the literature with global longitudinal strain (GLS) emerging as a simple and effective tool for the management of repaired ToF patients. Also, it is known that conventional three-dimensional (3D) echocardiography systematically underestimates RV volumes and overestimates EF. Therefore, CMR and conventional 3D echo should not be used interchangeably.
Alternatively, 3D knowledge-based reconstruction derived from 2D echocardiography (TTE-3DKBR) has shown to be a valuable tool for RV volume and EF assessment that can complement CMR and maximise the available resources in clinical practice. The literature on TTE-3DKBR in children and adults with ToF indicates a high correlation with CMR, and its potential for clinical follow-up in repaired ToF patients may be relevant. However, the recommendations of the expert consensus documents are also clear that further validation studies are needed before its implementation in clinical practice.
The current longitudinal study aims to further the role of TTE-3DKBR in evaluating the effects of chronic RV volume overload in ACHD repaired ToF patients by assessing its reproducibility and accuracy against CMR and conventional echocardiography measurements, particularly with standard GLS.
- Conditions
- Tetralogy of Fallot
- Being tested
- Echocardiography assessment
- Medical subject headings
- Tetralogy of Fallot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Echocardiography assessmentDiagnostic test
Also called Cardiac Magnetic Resonance
Group 1 will have healthy adult volunteers recruited at the workplace following specific criteria to participate in the study. A research cardiac ultrasound protocol to assess the RV will be performed at two different visits, with a maximum interval of two weeks between them.
Group 2 will have ACHD patients with known moderate or severe pulmonary regurgitation after ToF repair, following specific criteria to participate in the study. This group of patients will be studied in two separate visits. The patients will be recruited during the first visit when attending to an existing hospital appointment for ACHD CMR. A research cardiac ultrasound protocol to assess the RV will be performed on the same day, either before or after the CMR. For all patients who will have a second follow-up visit at the ACHD outpatient clinic within a maximum interval of one year, the same research protocol will be performed, in addition to the usual cardiac ultrasound.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Healthy adult volunteers Receives: Diagnostic Test: Echocardiography assessment | |
| Group 2 | ACHD patients with repaired Tetralogy of Fallot and known moderate or severe pulmonary regurgitation Receives: Diagnostic Test: Echocardiography assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the reproducibility and accuracy of TTE-3DKBR in assessing RV volume and EF compared to the reference method of CMR in a group of ACHD patients with known moderate or severe PR after ToF repair.
To study what is the maximum considered acceptable mean difference between RV volumes measures between CMR and TTE-3DKBR.
Measured: First year of the study
Evaluate the effects of chronic RV volume overload in this population within one-year follow-up using TTE-3DKBR and compare it with the conventional non-geometric echocardiography measurement of GLS.
To study the predictive value of RV volumes using TTE-3DKBR to assess RV systolic dysfunction defined by GLS below -18%.
Measured: Second year of the study
Secondary outcomes (1)
Compare TTE-3DKBR evaluation to the conventional 2D echocardiography measurements used in routine clinical practice (TAPSE, TDI, FAC, and GLS).
To study whether TTE-3DKBR values correlate with conventional 2D echocardiography measurements used in routine clinical practice (TAPSE, TDI, FAC and GLS).
Measured: First year of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start11 Apr 2024
- Primary completion26 Sep 2025 (estimated)
- Study completion26 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tetralogy of FallotStudies of the same condition, open and under way.
- More trials run by Guy's and St Thomas' NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Manchester Metropolitan University
- Responsible party
- Sponsor
- Investigators
- Dario Luis Leal de Freitas, BSc, Principal investigator, Guy's and St Thomas' NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06282926
- Sponsor's protocol ID
- 324811
- Status last verified
- Jul 2025
- First submitted
- 10 Aug 2023
- Last updated
- 25 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Three-dimensional Echocardiography Knowledge-based Reconstruction in Monitoring Right Ventricle Remodelling Following Tetralogy of Fallot Repair
- ClinicalTrials.gov ID
- NCT06282926
- Acronym / sponsor ID
- 324811
- Conditions
- Tetralogy of Fallot
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Guy's and St Thomas' NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Manchester Metropolitan University
- Study start
- 11 Apr 2024 (actual)
- Primary completion
- 26 Sep 2025 (estimated)
- Study completion
- 26 Sep 2025 (estimated)
- First posted
- 28 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of this study is to evaluate the reproducibility and accuracy of TTE-3DKBR in assessing RV volume and EF compared to the reference method of CMR in a group of ACHD patients with known moderate or severe PR after ToF repair.
As part of the validation study, the reproducibility of the TTE-3DKBR in assessing RV volume and EF will also be tested in a group of healthy adult volunteers. Additionally, TTE-3DKBR evaluation will be compared in both groups to the conventional 2D echocardiography measurements used in routine clinical practice, such as tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging (TDI), fractional area change (FAC), and global longitudinal strain (GLS).
Another objective of the study is also to evaluate the effects of chronic RV volume overload with an interval of one-year follow-up using TTE-3DKBR and compare it with the conventional non-geometric echocardiography measurements, particularly with GLS.
The study will end when the required number of patients have been enrolled and when the last subject undergoes the research dataset acquisition. The study may be terminated prematurely if it becomes apparent that the recruitment target cannot be met within the projected recruitment phase.
Detailed description
Tetralogy of Fallot (ToF) is a complex pathophysiology characterised by different factors that affect the right ventricle (RV) performance. Before surgical repair in childhood, the RV is exposed to pressure load with associated abnormal RV outflow tract (RVOT) hypertrophy and myocardial damage related to prolonged cyanosis. After surgical repair involving a pulmonary valve (PV) transannular patch, the RV may experience chronic volume overload due to significant pulmonary regurgitation (PR). The effects of chronic volume overload often found in adult congenital heart disease (ACHD) patients frequently result in progressive RV dilatation with abnormal geometry and RV dysfunction with associated electromechanical dyssynchrony. All this often leads to re-intervention with PV replacement. In asymptomatic patients with severe PR, the 2020 European ACHD guidelines recommendation for PV replacement gives a class 2a recommendation and evidence level C in cases of progressive RV systolic dysfunction and/or dilatation with a RV indexed end-diastolic volume (EDVi) ≥160 mL/m2, and/or a RV indexed end-systolic volume (ESVi) ≥80 mL/m2. The guidelines also mentioned gaps regarding the need for more longitudinal imaging data to optimise time for re-intervention because the possibility for RV remodelling is, at some point, irreversible.
CMR is widely recognised in the literature as the reference standard imaging technique for accurately quantifying RV volume and ejection fraction (EF) in the ACHD population. However, unlike transthoracic echocardiography (TTE), CMR is not the first-line test used in daily clinical practice.
The echocardiographic requirement of conventional multiple non-geometric (tricuspid annular plane systolic excursion, tissue Doppler imaging, global longitudinal strain) and geometric two-dimensional (2D) parameters (fractional area change, three-dimensional volume and EF) for a more accurate RV size and systolic function assessment is consensual in the literature with global longitudinal strain (GLS) emerging as a simple and effective tool for the management of repaired ToF patients. Also, it is known that conventional three-dimensional (3D) echocardiography systematically underestimates RV volumes and overestimates EF. Therefore, CMR and conventional 3D echo should not be used interchangeably.
Alternatively, 3D knowledge-based reconstruction derived from 2D echocardiography (TTE-3DKBR) has shown to be a valuable tool for RV volume and EF assessment that can complement CMR and maximise the available resources in clinical practice. The literature on TTE-3DKBR in children and adults with ToF indicates a high correlation with CMR, and its potential for clinical follow-up in repaired ToF patients may be relevant. However, the recommendations of the expert consensus documents are also clear that further validation studies are needed before its implementation in clinical practice.
The current longitudinal study aims to further the role of TTE-3DKBR in evaluating the effects of chronic RV volume overload in ACHD repaired ToF patients by assessing its reproducibility and accuracy against CMR and conventional echocardiography measurements, particularly with standard GLS.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Diagnostic Test: Echocardiography assessmentHealthy adult volunteers |
| Group 2 | – | Diagnostic Test: Echocardiography assessmentACHD patients with repaired Tetralogy of Fallot and known moderate or severe pulmonary regurgitation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Group 1 of healthy adult volunteers Group 2 of ACHD patients with repaired Tetralogy of Fallot and known moderate or severe pulmonary regurgitation
Key inclusion criteria (2 listed)
- Group 1 of healthy adult volunteers - Minimum aged of 18 years old without evidence of structural heart disease.
- Group 2 of ACHD patients - ACHD patient minimum aged of 18 years old with diagnosis of moderate or severe pulmonary regurgitation after ToF repair.
Key exclusion criteria (2 listed)
- Group 1 of healthy adult volunteers - No informed consent, evidence of structural heart disease.
- Group 2 of ACHD patients - No informed consent, pacemaker or defibrillator non-compatible with CMR, limited echocardiographic images for image acquisition, and evidence of moderate or severe right ventricle inflow and/or right ventricle outflow tract obstruction.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Echocardiography assessmentAlso: Cardiac Magnetic ResonanceGroup 1 will have healthy adult volunteers recruited at the workplace following specific criteria to participate in the study. A research cardiac ultrasound protocol to assess the RV will be performed at two different visits, with a maximum interval of two weeks between them. Group 2 will have ACHD patients with known moderate or severe pulmonary regurgitation after ToF repair, following specific criteria to participate in the study. This group of patients will be studied in two separate visits. The patients will be recruited during the first visit when attending to an existing hospital appointment for ACHD CMR. A research cardiac ultrasound protocol to assess the RV will be performed on the same day, either before or after the CMR. For all patients who will have a second follow-up visit at the ACHD outpatient clinic within a maximum interval of one year, the same research protocol will be performed, in addition to the usual cardiac ultrasound. | Diagnostic test | Group 1, Group 2 |
Primary outcome
Evaluate the reproducibility and accuracy of TTE-3DKBR in assessing RV volume and EF compared to the reference method of CMR in a group of ACHD patients with known moderate or severe PR after ToF repair.
Time frame: First year of the study
To study what is the maximum considered acceptable mean difference between RV volumes measures between CMR and TTE-3DKBR.
Evaluate the effects of chronic RV volume overload in this population within one-year follow-up using TTE-3DKBR and compare it with the conventional non-geometric echocardiography measurement of GLS.
Time frame: Second year of the study
To study the predictive value of RV volumes using TTE-3DKBR to assess RV systolic dysfunction defined by GLS below -18%.
1 secondary outcome
Compare TTE-3DKBR evaluation to the conventional 2D echocardiography measurements used in routine clinical practice (TAPSE, TDI, FAC, and GLS).
Time frame: First year of the study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Tetralogy of Fallot
RecruitingPhase 4
Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
Congenital Heart Disease, Repaired Tetralogy of Fallot (rTOF)
RecruitingPhase 1
Beta-blocker Administration for Cardiomyocyte Division
Tetralogy of Fallot, Double Outlet Right Ventricle
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ALTERRA: SAPIEN 3 THV With the Alterra Adaptive Prestent
Pulmonary Disease, Transcatheter Pulmonary Valve Replacement (TPVR)
Recruiting
Investigation of Tetralogy of Fallot in Neonates
Tetralogy of Fallot (TOF), Pulmonary Stenosis
RecruitingObservational study
Volution of Pulmonary Artery Dimensions in Tetralogy of Fallot
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dario Luis Leal de Freitas, BSc principal investigator
Guy's and St Thomas' NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tetralogy of Fallot, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the reproducibility and accuracy of TTE-3DKBR in assessing RV volume and EF compared to the reference method of CMR in a group of ACHD patients with known moderate or severe PR after ToF repair. (time frame: First year of the study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025; AzTrials last refreshed its copy on 1 Nov 2026.