Ignite Creation Date:
2024-07-17 @ 10:47 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06472102
Status:
RECRUITING
Last Update Posted:
2024-06-24
First Post:
2024-06-15
Brief Title:
Cardioneuroablation Fragmented Atrial Potentials Intracardiac Echocardiography and Computed Tomography
Sponsor:
Centre of Postgraduate Medical Education
Organization:
Centre of Postgraduate Medical Education
Study Overview
Official Title:
Value of fRagmented Atrial electrOgrams Computed Tomography and Intracardiac Echocardiography for Identification of optiMal Sites for Radio-frequency Delivery During cArdioneuroablation for Asystolic Reflex syNcope
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Roman5
Brief Summary:
Cardioneuroablation CNA is a new method for the treatment of asystolic reflex syncope however optimal methods for identification of presumed sites of ganglionated plexi GP which are the target for CNA and are located in the epicardial fat have not yet been established This study will compare the accuracy of three methods used for identification of these areas intracardiac recordings of fractionated atrial electrograms intracardiac echocardiography and computed tomography The study group will consist of 100 patients undergoing CNA in our institution The procedure will be performed in a standard manner with the use of extracardiac vagal stimulation as the intraprocedural end-point Correlation between the three methods used for localisation of optimal sites for CNA as well as their predictive value for achieving effective CNA will be computed
Detailed Description:
Cardioneuroablation CNA is a new method for the treatment of asystolic reflex syncope Although the procedure is becoming more and more popular many important issues remain unresolved One such a problem is the optimal method for identification of presumed sites of ganglionated plexi GP which are located in the epicardial fat surrounding myocardium and are the target for CNA Several methods have been used including anatomical approach using computed tomography CT intracardiac echocardiography ICE and 3D electro-anatomical mapping EAM as well as electrophysiological methods which include high-frequency stimulation and recording of fragmented atrial potentials FP
Areas of FAP are sought to represent nerve fibers endings extending from GPs to myocardium The technique was first described by in 2004 and spectral analysis with fast Fourier transformation was used to identify these areas Next the time-domain quantification of FAP characteristics was performed It was found that a high number of deflections at least 4 identified the presumed areas of GPs Later on this method was further developed and it has been shown that FAP-guided CNA was associated with shorter procedure and fluoroscopy times The currently advocated approach is to evaluate FAP for the number of deflections at filter settings of 200-500 Hz or 100-500 Hz If 3 deflections are present these sites are tagged as ablation targets
However the role of FAP for the identification of optimal sites for GPs ablation is still debatable Reproducibility of the results of spectral analysis of GPs areas has not been well established Also sensitivity and specificity of both spectral and time-domain analysis of FAP have not been established The sensitivity of 72 and specificity of 91 values were calculated for patients undergoing ablation for atrial fibrillation and not CNA were based on reflex bradycardiaasystole during RF delivery mainly at posterior left atrial LA wall and not by extra cardiac vagal stimulation ECVS after ablation at typical sites for septal GPs In fact specificity may be limited because FAP may represent areas of scarred atrial tissue pulmonary vein PV potentials or fragmented electrograms at such areas in the right atrium RA as slow pathway region coronary sinus CS os or RA-superior vena cava SVC junction Moreover the adipose tissue surrounding the heart can infiltrate the atrial myocardium causing heterogeneous activation resulting in the presence of FAP In addition the sensitivity may also be limited since effective RF applications which cause total vagal denervation confirmed by ECVS can be sometimes performed at the areas with no FAP To date no study examined prospectively and blindly characteristics of FAP in effective and non-effective sites confirmed by ECVS in patients undergoing CNA due to reflex asystolic syncope
Intracardiac echocardiography This is another tool used for anatomical localisation of presumed GP areas With ICE areas of epicardial fat in the so-called pyramidal space containing paraseptal inferior GP as well as space between right superior PV RSPV and SVC containing superior paraseptal GP can be visualised The correlation between ICE-identified areas of GPs and other tools like CT or FAP has not yet been established
Computed tomography Lastly CT can be used during anatomical approach to identify target sites for CNA Current techniques enable visualisation of pericardial fat Also density of the epicardial fat which may correspond to the density of GPs can be quantified using CT
Whether the CT- ICE- and FAB-based localisation of presumed GPs areas perfectly overlap each over or there is a significant difference in their localisations is not known
Aims
1 To assess the predictive value of FAP for identification of presumed areas of GPs localisation
2 To examine differences in FAP characteristics between superior and inferior paraseptal GPs areas
3 To assess the anatomical concordance between FAP- ICE- and CT-based sites targeted during CNA
4 To describe the FAP ICE and CT-based characteristics of the sites where vagal denervation was achieved as assessed by ECVS
Methods Patients The study group consists of consecutive patients undergoing CNA in our institution Patients are offered CNA if they have severe recurrent symptoms due to reflex syncope with ECG documented asystole 3 seconds especially if associated with injury or recurrent presyncope with persistent reflex bradycardia The patients have to have a history of ineffective prior non-pharmacological treatment and positive baseline atropine test sinus rate acceleration 30 and no AV block following 2 mg of intravenous atropine All patients gave informed written consent to undergo CNA and to participate in the study Research Grant CMKP 172024 Ethics Committee approval 422024
Cardioneuroablation The procedure is performed under general anaesthesia with muscle relaxation using a 35 mm irrigated tip catheter Navistar ThermoCool SmartTouch with contact force module and electroanatomical mapping EAM system Carto 3 Biosense Webster US The ablation index is set at 500 except coronary sinus CS where the target value is 350 Intracardiac echocardiography ICE Acuson SC2000 Siemens Germany AcuNav Ultrasound Catheter Biosense Webster US is used throughout the whole procedure and serves for guiding ablation including identification of epicardial fat tissue with presumed GP areas Thus the ICE images and EAM are used as anatomical approach to perform CNA
The ECVS is performed using two diagnostic catheters positioned in the right and left jugular veins utilizing neurostimulator designed by Dr Pachon Sao Paulo Brazil pulse amplitude of 1 Vkg body weight up to 70 V 50 ms width 50 Hz frequency delivered over 5 sec Complete bilateral vagal denervation of both sinus and AV nodes no sinus arrest slowing of sinus rate no more than 10 compared with baseline and no AV block with PR interval no longer than at baseline documented on ECVS is the end-point of CNA
Ablation is started in LA at the anterior antrum of the right superior PV RSPV where the superior paraseptal GP SPSGP is located followed by ablation of the inferior paraseptal GP IPSGP at the floor of LA Next these GPs are ablated from the RA If the intraprocedural endpoints of CNA are not achieved by ablation of paraseptal GPs additional applications in the LA at the sites of superior and postero-lateral LA GPs are performed followed by applications in the CS The procedure is performed using pure anatomical approach based on ICE and EAM and the operator is blinded to the CT and FAP results The amplitude of distal and proximal recordings from the ablation catheter are truncated to zero and CT images merged with the CARTO system at the beginning of the procedure are not displayed during CNA
The ECVS is performed after each RF application to assess whether this specific burn caused no vagal denervation 10 change in sinus pause or AVB still present partial vagal denervation 10-90 shortening in sinus pause or lower degree of AVB still present or complete vagal denervation 90 reduction of sinus pause duration and no AVB If after achieving complete vagal denervation additional consolidating RF applications are performed ECVS is not repeated and these sites are not taken in the analysis
At the end of the procedure atropine test is performed in order to assess the residual if present vagal nerve activity The value of 10 of increase in sinus rate following atropine injection 2 mg iv is taken as complete vagal denervation Regardless of the results of this test further RF applications are not performed and the procedure is completed
Fragmented electrogram recording and analysis For the purpose of comparing FAB between superior and inferior septal GPs FAP are recorded at each site during constructing EAM before starting RF applications For the purpose of assessing predictive value of FAP characteristics FAP are recorded before each RF application as previously described
Bipolar endocardial potential recordings at each site of RF application are analysed at an ECG speed of 400 mms and filter setting 100-500 Hz Three FAP parameters are measured - number of deflections maximal amplitude and total FAP duration
The measurements of the number of deflections are performed according to Aksu et al and Lellouche et al Number of deflections is assessed as the number of turning points positive to negative direction or vice versa in each FAP The FAP is defined as atrial electrogram with 3 deflections however other cut-off values for the number of deflections are also tested
The amplitude of FAP is measured in mV as the difference between the most negative and the most positive deflection The duration of FAP is measured in milliseconds from the onset of the first deflection to the end of the last deflection
All atrial electrograms are divided into 1 normal AP with 3 deflections 2 low-amplitude FAP with amplitude difference between maximal positive and maximal negative deflection 07 mV and 3 high-amplitude FAP with amplitude 07 mV
The analysis of FAP is performed off-line by an investigator who is blinded to the procedural details including which GP was ablated and what was the ECVS result after each RF application In order to overcome possible spontaneous variability of FAP characteristics caused by electrode movements in a beating heart the mean value of three consecutive FAP recordings is taken as a final parameter
Intra- and inter-observer variability of FAP measurements will be also assessed
Computed tomography is performed using the Somatom goTop Siemens Germany tomograph After acquisition the images are sent for further processing and reconstruction to the inHeart platform Acquisition will be performed according to the protocol used by the inHeart In brief as many as possible complementary scans are acquired In this protocol the acquisition is focused on the maximum filling volume of the atria The acquisition window is set on the systolic cardiac phase 200-400ms from R wave The amount of contrast and parameter settings are refined according to patient age and possible renal failure During the arterial phase the acquisition mode is prospective sequential All the technical details are in the inHeart brochure
When the CT reconstruction with the epicardial fat is received from the inHeart it is merged with the map obtained in the EAM system Carto-3 Care is taken to make the most accurate matching using right and left pulmonary artery CS and ICE images as the anchor points Next areas of presumed areas of GPs identified by ICE are marked on the EAM using the CartoSound module Biosense Webster US The ICE-based and CT-based areas with epicardial fat are compared visually and also using the Carto system software which enables calculation of the area and volume of a given structure Also visual correlation between ICE-based RF applications points and localisation of epicardial fat areas imaged by CT will be performed As stated before the identification of presumed GPs areas will be based on ICE and EAM whereas CT images will be used after ablation to compare ICE-based and CT-based localisations of epicardial fat and GPs
Areas of FAP are sought to represent nerve fibers endings extending from GPs to myocardium The technique was first described by in 2004 and spectral analysis with fast Fourier transformation was used to identify these areas Next the time-domain quantification of FAP characteristics was performed It was found that a high number of deflections at least 4 identified the presumed areas of GPs Later on this method was further developed and it has been shown that FAP-guided CNA was associated with shorter procedure and fluoroscopy times The currently advocated approach is to evaluate FAP for the number of deflections at filter settings of 200-500 Hz or 100-500 Hz If 3 deflections are present these sites are tagged as ablation targets
However the role of FAP for the identification of optimal sites for GPs ablation is still debatable Reproducibility of the results of spectral analysis of GPs areas has not been well established Also sensitivity and specificity of both spectral and time-domain analysis of FAP have not been established The sensitivity of 72 and specificity of 91 values were calculated for patients undergoing ablation for atrial fibrillation and not CNA were based on reflex bradycardiaasystole during RF delivery mainly at posterior left atrial LA wall and not by extra cardiac vagal stimulation ECVS after ablation at typical sites for septal GPs In fact specificity may be limited because FAP may represent areas of scarred atrial tissue pulmonary vein PV potentials or fragmented electrograms at such areas in the right atrium RA as slow pathway region coronary sinus CS os or RA-superior vena cava SVC junction Moreover the adipose tissue surrounding the heart can infiltrate the atrial myocardium causing heterogeneous activation resulting in the presence of FAP In addition the sensitivity may also be limited since effective RF applications which cause total vagal denervation confirmed by ECVS can be sometimes performed at the areas with no FAP To date no study examined prospectively and blindly characteristics of FAP in effective and non-effective sites confirmed by ECVS in patients undergoing CNA due to reflex asystolic syncope
Intracardiac echocardiography This is another tool used for anatomical localisation of presumed GP areas With ICE areas of epicardial fat in the so-called pyramidal space containing paraseptal inferior GP as well as space between right superior PV RSPV and SVC containing superior paraseptal GP can be visualised The correlation between ICE-identified areas of GPs and other tools like CT or FAP has not yet been established
Computed tomography Lastly CT can be used during anatomical approach to identify target sites for CNA Current techniques enable visualisation of pericardial fat Also density of the epicardial fat which may correspond to the density of GPs can be quantified using CT
Whether the CT- ICE- and FAB-based localisation of presumed GPs areas perfectly overlap each over or there is a significant difference in their localisations is not known
Aims
1 To assess the predictive value of FAP for identification of presumed areas of GPs localisation
2 To examine differences in FAP characteristics between superior and inferior paraseptal GPs areas
3 To assess the anatomical concordance between FAP- ICE- and CT-based sites targeted during CNA
4 To describe the FAP ICE and CT-based characteristics of the sites where vagal denervation was achieved as assessed by ECVS
Methods Patients The study group consists of consecutive patients undergoing CNA in our institution Patients are offered CNA if they have severe recurrent symptoms due to reflex syncope with ECG documented asystole 3 seconds especially if associated with injury or recurrent presyncope with persistent reflex bradycardia The patients have to have a history of ineffective prior non-pharmacological treatment and positive baseline atropine test sinus rate acceleration 30 and no AV block following 2 mg of intravenous atropine All patients gave informed written consent to undergo CNA and to participate in the study Research Grant CMKP 172024 Ethics Committee approval 422024
Cardioneuroablation The procedure is performed under general anaesthesia with muscle relaxation using a 35 mm irrigated tip catheter Navistar ThermoCool SmartTouch with contact force module and electroanatomical mapping EAM system Carto 3 Biosense Webster US The ablation index is set at 500 except coronary sinus CS where the target value is 350 Intracardiac echocardiography ICE Acuson SC2000 Siemens Germany AcuNav Ultrasound Catheter Biosense Webster US is used throughout the whole procedure and serves for guiding ablation including identification of epicardial fat tissue with presumed GP areas Thus the ICE images and EAM are used as anatomical approach to perform CNA
The ECVS is performed using two diagnostic catheters positioned in the right and left jugular veins utilizing neurostimulator designed by Dr Pachon Sao Paulo Brazil pulse amplitude of 1 Vkg body weight up to 70 V 50 ms width 50 Hz frequency delivered over 5 sec Complete bilateral vagal denervation of both sinus and AV nodes no sinus arrest slowing of sinus rate no more than 10 compared with baseline and no AV block with PR interval no longer than at baseline documented on ECVS is the end-point of CNA
Ablation is started in LA at the anterior antrum of the right superior PV RSPV where the superior paraseptal GP SPSGP is located followed by ablation of the inferior paraseptal GP IPSGP at the floor of LA Next these GPs are ablated from the RA If the intraprocedural endpoints of CNA are not achieved by ablation of paraseptal GPs additional applications in the LA at the sites of superior and postero-lateral LA GPs are performed followed by applications in the CS The procedure is performed using pure anatomical approach based on ICE and EAM and the operator is blinded to the CT and FAP results The amplitude of distal and proximal recordings from the ablation catheter are truncated to zero and CT images merged with the CARTO system at the beginning of the procedure are not displayed during CNA
The ECVS is performed after each RF application to assess whether this specific burn caused no vagal denervation 10 change in sinus pause or AVB still present partial vagal denervation 10-90 shortening in sinus pause or lower degree of AVB still present or complete vagal denervation 90 reduction of sinus pause duration and no AVB If after achieving complete vagal denervation additional consolidating RF applications are performed ECVS is not repeated and these sites are not taken in the analysis
At the end of the procedure atropine test is performed in order to assess the residual if present vagal nerve activity The value of 10 of increase in sinus rate following atropine injection 2 mg iv is taken as complete vagal denervation Regardless of the results of this test further RF applications are not performed and the procedure is completed
Fragmented electrogram recording and analysis For the purpose of comparing FAB between superior and inferior septal GPs FAP are recorded at each site during constructing EAM before starting RF applications For the purpose of assessing predictive value of FAP characteristics FAP are recorded before each RF application as previously described
Bipolar endocardial potential recordings at each site of RF application are analysed at an ECG speed of 400 mms and filter setting 100-500 Hz Three FAP parameters are measured - number of deflections maximal amplitude and total FAP duration
The measurements of the number of deflections are performed according to Aksu et al and Lellouche et al Number of deflections is assessed as the number of turning points positive to negative direction or vice versa in each FAP The FAP is defined as atrial electrogram with 3 deflections however other cut-off values for the number of deflections are also tested
The amplitude of FAP is measured in mV as the difference between the most negative and the most positive deflection The duration of FAP is measured in milliseconds from the onset of the first deflection to the end of the last deflection
All atrial electrograms are divided into 1 normal AP with 3 deflections 2 low-amplitude FAP with amplitude difference between maximal positive and maximal negative deflection 07 mV and 3 high-amplitude FAP with amplitude 07 mV
The analysis of FAP is performed off-line by an investigator who is blinded to the procedural details including which GP was ablated and what was the ECVS result after each RF application In order to overcome possible spontaneous variability of FAP characteristics caused by electrode movements in a beating heart the mean value of three consecutive FAP recordings is taken as a final parameter
Intra- and inter-observer variability of FAP measurements will be also assessed
Computed tomography is performed using the Somatom goTop Siemens Germany tomograph After acquisition the images are sent for further processing and reconstruction to the inHeart platform Acquisition will be performed according to the protocol used by the inHeart In brief as many as possible complementary scans are acquired In this protocol the acquisition is focused on the maximum filling volume of the atria The acquisition window is set on the systolic cardiac phase 200-400ms from R wave The amount of contrast and parameter settings are refined according to patient age and possible renal failure During the arterial phase the acquisition mode is prospective sequential All the technical details are in the inHeart brochure
When the CT reconstruction with the epicardial fat is received from the inHeart it is merged with the map obtained in the EAM system Carto-3 Care is taken to make the most accurate matching using right and left pulmonary artery CS and ICE images as the anchor points Next areas of presumed areas of GPs identified by ICE are marked on the EAM using the CartoSound module Biosense Webster US The ICE-based and CT-based areas with epicardial fat are compared visually and also using the Carto system software which enables calculation of the area and volume of a given structure Also visual correlation between ICE-based RF applications points and localisation of epicardial fat areas imaged by CT will be performed As stated before the identification of presumed GPs areas will be based on ICE and EAM whereas CT images will be used after ablation to compare ICE-based and CT-based localisations of epicardial fat and GPs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None