Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04764123 |
| Other study ID # |
2021 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2021 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
February 2021 |
| Source |
Cardiovascular Research Society, Greece |
| Contact |
Demosthenes G Katritsis, MD, PhD |
| Phone |
+306944845505 |
| Email |
dkatrits[@]dgkatritsis.gr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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.
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 :
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.
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.
