Tachycardia, Atrioventricular Nodal ReentryAVNRTmapNCT04764123
Typical and Atypical AVNRT High-resolution Mapping
An observational study of Tachycardia, Atrioventricular Nodal Reentry, run by Cardiovascular Research Society, Greece.
Trial summary
This study is aimed at : 1. Identifying the exact location of the circuit of typical and atypical AVNRT by applying high-resolution electroanatomic mapping. 2. Investigating the possibility that the recently described "ring tissues" participate in the AVNRT circuit. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Tachycardia, Atrioventricular Nodal Reentry
- What is being tested?
- AVNRT mapping
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2021to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with typical or atypical AVNRT admitted for electrophysiological study and ablation.
Who may be able to join
- Patients with atypical or typical AVNRT
- Patients able to provide informed consent
Who cannot join
- Age <16 or >75 years
- Known heart failure
- Severe comorbidities with estimated life expectancy < 6 months
Trial locations and contacts
No sites are listed yet.
About this study
Official title: To Investigate Whether Remnants of the "Ring Tissues" Constitute the Substrate of the Circuit of Atrioventricular Nodal Reentrant Tachycardia
This study is aimed at :
- Identifying the exact location of the circuit of typical and atypical AVNRT by applying high-resolution electroanatomic mapping.
- Investigating the possibility that the recently described "ring tissues" participate in the AVNRT circuit.
Read the detailed description
Background The exact circuit of atrioventricular nodal reentrant tachycardia still remains unknown despite advances in high-density mapping, tissue histochemistry, and connexin genotyping. Theoretical calculations have derived a range of 0.8 to 5.2 cm for the length of the slow pathway, whereas that of the fast pathway should be within the range of 2.4 to 11.2 cm. Recent histology data also indicate that the distance of the right inferior extension of the atrioventricular node within the tricuspid vestibule, as judged histologically, and as measured from the site of penetration of the conduction axis in 31 hearts, is 8.2±2.4 mm, with a range from 5.2 to 13.6 mm. These results are compatible with theoretical calculations of the slow pathway previously performed by the investigators. On 3-dimensional reconstructed fluoroscopic images, the average distance between the compact AV node and the ablating electrode in cases of successful AVNRT ablation, however, is 17.2±1.6 to 17.8±0.9 mm. This clearly suggests that successful ablation interrupts the AVNRT circuit at a point beyond the identifiable right posterior extension, and at a consistent area on the the septal isthmus between the CS ostium and the TV. This site is beyond the histologically identifiable inferior extensions of the node.
There is additional evidence in animal studies that the right inferior extension continues within the vestibule of the tricuspid valve as "ring tissue", ie a remnant of the primary ring, while the left atrial vestibule is derived from the initial atrioventricular canal of the developing heart, which is itself known to be slow conducting but cannot be distinguished histologically from the left atrial myocardium. In the human heart, the primary ring extends through the atrioventricular node, and includes the bundle of His, which is rapidly conducting.
Hypothesis The investigators hypothesized that, in humans, the extent of ring tissues varies in such a way that some subjects are susceptible to atrioventricular nodal re-entry, whereas others are not. Thus, the entirety of the tricuspid vestibule, or even part of the mitral vestibule, are parts of the re-entry circuit, at least in some atypical forms with prolonged His-atrial intervals. The circumference of the right atrioventricular orifice has been measured at between 9 and 11 centimeters in patients aged less than 65 years, whereas that of the mitral orifice is from 7 to 9 centimeters. The possibility of the vestibules being involved in the circuit, therefore, cannot theoretically be excluded. Recently, high-density mapping of the re-entry circuit has provided valuable insights into the electrophysiologic patterns of this arrhythmia, identifying the circuit in the vicinity of the nodal area. All these mapping studies, however, were conducted in patients with typical AVNRT. In this setting, the remnants of the ring tissues might be short enough as not to allow proper discrimination of the circuit limbs. The investigators propose to apply high-resolution electroanatomic mapping in patients with both typical atypical AVNRT in which the circuit may contain longer circuit components. Mapping should be focused on both the septal area and the tricuspid, and, if feasible, the mitral ring.
Aims of the Study
This study, therefore, is aimed at :
- Identifying the exact location of the circuit of typical and atypical AVNRT by applying high-resolution electroanatomic mapping.
- Investigating the possibility that the recently described "ring tissues" participate in the AVNRT circuit.
Methods Clinical Studies Patients Patients with typical and atypical AVNRT will be recruited following informed consent. The investigators anticipate to study 30 patients with typical, and 10 patients with atypical AVNRT within the next two years.
Definitions AVNRT is diagnosed by fulfillment of established criteria during detailed atrial and ventricular pacing maneuvers. Typical (slow-fast) AVNRT is defined by an atrial-His/His-atrial ratio (AH/HA) >1, and HA interval ≤70 ms. Atypical AVNRT is defined by delayed retrograde atrial activation with HA>70 ms.
Mapping Electroanatomic mapping will be performed with CARTO, Rhythmia or Ensite programs at the operator's discretion. High-resolution mapping of the atrial vestibules is inherently difficult in this setting, nonetheless, because of the problems in separating a large ventricular electrogram from the atrial tracing. During atrioventricular nodal reentry, all these areas should show a fused signal consisting of nodal activation. Any mapping system will struggle to annotate the fused signal appropriately in the window and during tachycardia. It may also preferentially annotate the His bundle electrogram because of its high frequency (dv/dt). The implication of this error is that a site annotated as representing the earliest atrial activity may be representing activity in the His bundle. Conversely, a site marked as late may, in fact, be early, being obscured by far field ventricular activity. These limitations may also apply to animal models using micro-electrode mapping. To overcome this problem, pacing maneuvers with ventricular extrastimuli are used to differentiate atrial from ventricular electrogram components where activation appeared to be superimposed owing to simultaneous local activation. In addition, the investigators will exclude points that result in discrepant activation relative to the surrounding isochronal information due to the movement of the CS reference catheter. Activation points from ectopic beats will be excluded manually. The voltage map will be automatically acquired according to the same criteria. After automated mapping, an offline retrospective analysis will be performed by 2 independent observers, in order to manually over-read the sites of earliest atrial activation, at an override activation strength of 100 mV in cases in which (1) the earliest activation on automated mapping appeared diffuse or (2) automated annotation tagged the local ventricular component at the annulus. The His-bundle signal is generally automatically annotated by the system.
Entrainment Entrainment of AVNRT is feasible at sites close to the nodal extensions. Attempts will be made to entrain the tachycardia from various points on the TV annulus in order to investigate potential participation of the right-sided ring tissue into circuit.
Catheter ablation Being on the operation discretion, before conventional catheter ablation of the slow pathway, at least two 30 sec lesions will be delivered on the TV annulus near the isthmus, if this feasible. Interruption of the tachycardia or evoked junctional beats will be sought. Conventional catheter ablation of the slow pathway will be performed as previously described.
Histology Studies Databases from human hearts specimens will be examined and tissue-characterized in an attempt to identify the presence and extent of "ring tissues" in the human myocardium.
- Being tested
- AVNRT mapping
- Keywords
- Atrioventricular, Nodal Reentry, Tachycardia
- Medical subject headings
- Tachycardia, Atrioventricular Nodal Reentry, Tachycardia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVNRT mappingDiagnostic test
Also called Electroanatomic mapping
AV annuli mapping during AVNRT
| Study group | Role | What they receive |
|---|---|---|
| AVNRT Cohort | Patients admitted for electrophysiological study and ablation due to AVNRT tachycardia.
During the study and before the ablation high density electroanatomical mapping will be performed. Receives: Diagnostic Test: AVNRT mapping |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participation of ring tissues in the AVNRT Circuit
Tachycardia entrainment by pacing at the anatomical ring tissue site or tachycardia termination with successful ablation at the ring tissue site
Measured: 2 years
Secondary outcomes (1)
Fast and slow pathway activation time in the circuit of AVNRT.
TIme in ms required for fast and slow pathway activation during tachycardia.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start1 Jun 2021 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tachycardia, Atrioventricular Nodal ReentryStudies of the same condition, open and under way.
- 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cardiovascular Research Society, Greece
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University
- Responsible party
- Principal investigator, Dr D Katritsis, Cardiovascular Research Society, Greece
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04764123
- Sponsor's protocol ID
- 2021
- Acronym
- AVNRTmap
- Status last verified
- Feb 2021
- First submitted
- 23 Jan 2021
- Last updated
- 25 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Investigate Whether Remnants of the "Ring Tissues" Constitute the Substrate of the Circuit of Atrioventricular Nodal Reentrant Tachycardia
- ClinicalTrials.gov ID
- NCT04764123
- Acronym / sponsor ID
- AVNRTmap / 2021
- Keywords
- Atrioventricular, Nodal Reentry, Tachycardia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Cardiovascular Research Society, GreeceUniversity, hospital or other
- Collaborators
- Johns Hopkins University
- Study start
- 1 Jun 2021 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 21 Feb 2021 (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.
This study is aimed at :
- Identifying the exact location of the circuit of typical and atypical AVNRT by applying high-resolution electroanatomic mapping.
- Investigating the possibility that the recently described "ring tissues" participate in the AVNRT circuit.
Detailed description
Background The exact circuit of atrioventricular nodal reentrant tachycardia still remains unknown despite advances in high-density mapping, tissue histochemistry, and connexin genotyping. Theoretical calculations have derived a range of 0.8 to 5.2 cm for the length of the slow pathway, whereas that of the fast pathway should be within the range of 2.4 to 11.2 cm. Recent histology data also indicate that the distance of the right inferior extension of the atrioventricular node within the tricuspid vestibule, as judged histologically, and as measured from the site of penetration of the conduction axis in 31 hearts, is 8.2±2.4 mm, with a range from 5.2 to 13.6 mm. These results are compatible with theoretical calculations of the slow pathway previously performed by the investigators. On 3-dimensional reconstructed fluoroscopic images, the average distance between the compact AV node and the ablating electrode in cases of successful AVNRT ablation, however, is 17.2±1.6 to 17.8±0.9 mm. This clearly suggests that successful ablation interrupts the AVNRT circuit at a point beyond the identifiable right posterior extension, and at a consistent area on the the septal isthmus between the CS ostium and the TV. This site is beyond the histologically identifiable inferior extensions of the node.
There is additional evidence in animal studies that the right inferior extension continues within the vestibule of the tricuspid valve as "ring tissue", ie a remnant of the primary ring, while the left atrial vestibule is derived from the initial atrioventricular canal of the developing heart, which is itself known to be slow conducting but cannot be distinguished histologically from the left atrial myocardium. In the human heart, the primary ring extends through the atrioventricular node, and includes the bundle of His, which is rapidly conducting.
Hypothesis The investigators hypothesized that, in humans, the extent of ring tissues varies in such a way that some subjects are susceptible to atrioventricular nodal re-entry, whereas others are not. Thus, the entirety of the tricuspid vestibule, or even part of the mitral vestibule, are parts of the re-entry circuit, at least in some atypical forms with prolonged His-atrial intervals. The circumference of the right atrioventricular orifice has been measured at between 9 and 11 centimeters in patients aged less than 65 years, whereas that of the mitral orifice is from 7 to 9 centimeters. The possibility of the vestibules being involved in the circuit, therefore, cannot theoretically be excluded. Recently, high-density mapping of the re-entry circuit has provided valuable insights into the electrophysiologic patterns of this arrhythmia, identifying the circuit in the vicinity of the nodal area. All these mapping studies, however, were conducted in patients with typical AVNRT. In this setting, the remnants of the ring tissues might be short enough as not to allow proper discrimination of the circuit limbs. The investigators propose to apply high-resolution electroanatomic mapping in patients with both typical atypical AVNRT in which the circuit may contain longer circuit components. Mapping should be focused on both the septal area and the tricuspid, and, if feasible, the mitral ring.
Aims of the Study
This study, therefore, is aimed at :
- Identifying the exact location of the circuit of typical and atypical AVNRT by applying high-resolution electroanatomic mapping.
- Investigating the possibility that the recently described "ring tissues" participate in the AVNRT circuit.
Methods Clinical Studies Patients Patients with typical and atypical AVNRT will be recruited following informed consent. The investigators anticipate to study 30 patients with typical, and 10 patients with atypical AVNRT within the next two years.
Definitions AVNRT is diagnosed by fulfillment of established criteria during detailed atrial and ventricular pacing maneuvers. Typical (slow-fast) AVNRT is defined by an atrial-His/His-atrial ratio (AH/HA) >1, and HA interval ≤70 ms. Atypical AVNRT is defined by delayed retrograde atrial activation with HA>70 ms.
Mapping Electroanatomic mapping will be performed with CARTO, Rhythmia or Ensite programs at the operator's discretion. High-resolution mapping of the atrial vestibules is inherently difficult in this setting, nonetheless, because of the problems in separating a large ventricular electrogram from the atrial tracing. During atrioventricular nodal reentry, all these areas should show a fused signal consisting of nodal activation. Any mapping system will struggle to annotate the fused signal appropriately in the window and during tachycardia. It may also preferentially annotate the His bundle electrogram because of its high frequency (dv/dt). The implication of this error is that a site annotated as representing the earliest atrial activity may be representing activity in the His bundle. Conversely, a site marked as late may, in fact, be early, being obscured by far field ventricular activity. These limitations may also apply to animal models using micro-electrode mapping. To overcome this problem, pacing maneuvers with ventricular extrastimuli are used to differentiate atrial from ventricular electrogram components where activation appeared to be superimposed owing to simultaneous local activation. In addition, the investigators will exclude points that result in discrepant activation relative to the surrounding isochronal information due to the movement of the CS reference catheter. Activation points from ectopic beats will be excluded manually. The voltage map will be automatically acquired according to the same criteria. After automated mapping, an offline retrospective analysis will be performed by 2 independent observers, in order to manually over-read the sites of earliest atrial activation, at an override activation strength of 100 mV in cases in which (1) the earliest activation on automated mapping appeared diffuse or (2) automated annotation tagged the local ventricular component at the annulus. The His-bundle signal is generally automatically annotated by the system.
Entrainment Entrainment of AVNRT is feasible at sites close to the nodal extensions. Attempts will be made to entrain the tachycardia from various points on the TV annulus in order to investigate potential participation of the right-sided ring tissue into circuit.
Catheter ablation Being on the operation discretion, before conventional catheter ablation of the slow pathway, at least two 30 sec lesions will be delivered on the TV annulus near the isthmus, if this feasible. Interruption of the tachycardia or evoked junctional beats will be sought. Conventional catheter ablation of the slow pathway will be performed as previously described.
Histology Studies Databases from human hearts specimens will be examined and tissue-characterized in an attempt to identify the presence and extent of "ring tissues" in the human myocardium.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AVNRT Cohort | – | Diagnostic Test: AVNRT mappingPatients admitted for electrophysiological study and ablation due to AVNRT tachycardia. During the study and before the ablation high density electroanatomical mapping will be performed. |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with typical or atypical AVNRT admitted for electrophysiological study and ablation.
Key inclusion criteria (2 listed)
- Patients with atypical or typical AVNRT
- Patients able to provide informed consent
Key exclusion criteria (3 listed)
- Age <16 or >75 years
- Known heart failure
- Severe comorbidities with estimated life expectancy < 6 months
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 |
|---|---|---|
| AVNRT mappingAlso: Electroanatomic mappingAV annuli mapping during AVNRT | Diagnostic test | AVNRT Cohort |
Primary outcome
Participation of ring tissues in the AVNRT Circuit
Time frame: 2 years
Tachycardia entrainment by pacing at the anatomical ring tissue site or tachycardia termination with successful ablation at the ring tissue site
1 secondary outcome
Fast and slow pathway activation time in the circuit of AVNRT.
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2021.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Tachycardia, Atrioventricular Nodal Reentry, run by Cardiovascular Research Society, Greece.
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 3 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: status not confirmed, as of the sponsor's last update on 25 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Demosthenes G Katritsis, MD, PhD (+306944845505, dkatrits@dgkatritsis.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participation of ring tissues in the AVNRT Circuit (time frame: 2 years). 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 Feb 2021.