Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06440291
Status:
RECRUITING
Last Update Posted:
2024-06-03
First Post:
2024-05-28
Brief Title:
Cardioneuroablation for Reflex Syncope and Exercise Capacity
Sponsor:
Centre of Postgraduate Medical Education
Organization:
Centre of Postgraduate Medical Education
Study Overview
Official Title:
Effects of caRdioneurOablation on Exercise perforMance in Patients With Reflex Asystolic syNcope The Roman 3 Study
Status:
RECRUITING
Status Verified Date:
2024-05
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:
Roman3
Brief Summary:
Cardioneuroablation CNA is a new promising method to treat reflex syncope which is due to vagally-induced functional sinus arrest or atrio-ventricular block AVB Although the procedure is effective in 80 of patients there are potential adverse effects associated with the lack of vagal protection One of them is increased sinus rate and possible worsening of exercise capacity However it is not known how often this happens Moreover the most accurate tool to asses exercise capacity - cardiopulmonary exercise testing CPET has not yet been used in this group of patients Therefore the aim of the study is to assess one-year effects of CNA-induced total vagal denervation on cardiorespiratory fitness in patients undergoing CNA due to reflex asystolic syncope
The study group consists of patients undergoing CNA in our institution All patients give informed written consent to undergo CNA and to participate in the study Ethics Committee approval 222024 CNA is performed according to standard protocol used in our institution A symptom-limited cardiopulmonary exercise CPET is performed twice at baseline 1-2 days before CNA and after one year of follow-up Standard CPET parameters are measured Quality of life is measured using a dedicated questionnaire Also a control group of healthy volunteers will undergo CPET to answer the question whether subjects with reflex syncope differ in exercise capacity from healthy people
The study group consists of patients undergoing CNA in our institution All patients give informed written consent to undergo CNA and to participate in the study Ethics Committee approval 222024 CNA is performed according to standard protocol used in our institution A symptom-limited cardiopulmonary exercise CPET is performed twice at baseline 1-2 days before CNA and after one year of follow-up Standard CPET parameters are measured Quality of life is measured using a dedicated questionnaire Also a control group of healthy volunteers will undergo CPET to answer the question whether subjects with reflex syncope differ in exercise capacity from healthy people
Detailed Description:
Introduction Cardioneuroablation CNA is a new promising method to treat reflex syncope which is due to vagally-induced functional sinus arrest or atrio-ventricular block AVB The goal of the procedure is to ablate post-ganglionic endings of the parasympathetic part of the autonomic nervous system ANS located in ganglionated plexi GP in the epicardial fat and in the myocardium Although both sympathetic and parasympathetic nerves are localized in GPs the latter ones only barely regenerate Therefore CNA-induced damage to the parasympathetic part of GP is greater and more durable than that of the sympathetic part of ANS Because increased vagal activity is one of the main mechanisms leading to reflex sinus arrest or atrio-ventricular AV block targeting this part of ANS by CNA may prevent recurrences of reflex syncope Indeed it has been shown that CNA may be effective in approximately 80-90 of very symptomatic subjects with reflex syncope
Lack or diminished parasympathetic drive to the heart may be however associated with adverse effects The main complication which is seen shortly and up to one year after CNA is heart rhythm acceleration which may be symptomatic in approximately one-third of patients In the majority of patients sinus rate gradually slows down over a period of 3-12 months due to partial parasympathetic reinnervation however approximately 6-7 of patients remain severely symptomatic and require heart rate slowing agents Other complaints such as decreased exercise capacity or effort dyspnea can occur in up to 14 of patients and they are usually attributed to faster than needed sinus rate at rest and during exercise
Although in the vast majority of patients the above mentioned symptoms are rather mild and do not decrease the patients acceptance of CNA in some may decrease the quality of life Thus a detailed assessment of the effects of CNA on exercise performance is clinically important However to date no study addressed this issue
There are several methods to assess exercise performance with cardiopulmonary exercise testing CPET being the most accurate and reference tool It measures cardiorespiratory fitness and physiological responses to aerobic exercise in many conditions CPET provides a comprehensive evaluation of the respiratory circulatory and metabolic responses to exercise that cannot be accurately measured by less precise methods such as standard exercise stress test Therefore we have chosen CPET to evaluate the effects of CNA on exercise performance in our patients
Aim To assess one-year effects of CNA-induced total vagal denervation on cardiorespiratory fitness in patients undergoing CNA due to reflex asystolic syncope
To compare cardiorespiratory fitness between subjects with reflex syncope and healthy volunteers
Hypothesis Cardioneuroablation significantly decreases cardiopulmonary fitness in patients with reflex asystolic syncope
There are no differences between patients with syncope and healthy people in cardiorespiratory fitness at baseline whereas post-CNA results of CPET are significantly worse in syncope patients versus controls
Methods Patients The study group will consist of consecutive patients undergoing CNA in our institution Patients are referred for 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 a 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 Ethics Committee approval 222024
Control group This group will consist of healthy volunteers without cardiovascular and other chronic disorders age- and gender-matched with the CNA group This group will not undergo CNA
Cardioneuroablation The procedure is performed under general anesthesia with muscle relaxation using a 35 mm irrigated tip catheter Navistar ThermoCool SmartTouch with contact force module and electroanatomical 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 also used throughout the whole procedure and serves for guiding ablation including identification of presumed GP areas The extra cardiac vagal stimulation 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 usually started in the left atrium LA at the anterior antrum of the right pulmonary vein 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 right atrium 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 CS
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 will be taken as successful vagal denervation
Cardiopulmonary exercise testing A symptom-limited cardiopulmonary exercise CPET will be performed twice at baseline and after one year of follow-up both in the syncope and control patients Exercise tests will be performed on a treadmill with a cardio-pulmonary system Reynolds Medical The same load protocol will be used twice for the same patient All patients will be encouraged to exercise at maximal effort 8 points using the 10-point Borg scale During the exercise test the patients clinical status will be monitored The systolic and diastolic blood pressure will be recorded every 3 minutes of exercise Heart rate heart rate reserve predicted and achieved chronotropic index and percentage of maximum predicted heart rate at peak exercise will be calculated 3 The maximum predicted heart rate will be calculated as 220-age in years The heart rate recovery in 1 minute will be assessed A 12-lead electrocardiogram will be recorded ECG and heart rate parameters ischemia arrhythmia or conduction disturbances during exercise and recovery will be accessed according to the American Heart Association recommendations
Ventilatory and gas exchange parameters will be assessed during the test The peak oxygen uptake VO2 will be averaged from the highest 30 s of exercise Maximum predicted oxygen uptake will be calculated according to the WassermanHansen equations The anaerobic threshold will be calculated using a dual-method approach V-slope and ventilatory equivalent methods Other analyzed cardiopulmonary exercise testing parameters will include oxygen uptake to work rate increment ratio O2WR ventilatory efficiency VEVCO2 slope and breathing reserve at peak exercise calculated as the percentage of maximum voluntary ventilation maximum voluntary ventilation - minute ventilation at peak exercise maximum voluntary ventilation 100 All exercise tests will be supervised and analyzed according to current guidelines
Quality of life Quality of life will be measured using a dedicated questionnaire The Impact of Syncope on Quality-of-Life Questionnaire University of Calgary This questionnaire consists of 9 questions with 6 choices and 3 questions with 5 choices The overall maximum score is 57 The higher the score the poorer the quality of life is
Statistical analysis The results are presented as meanSD or numbers and percentages Differences between variables are analysed using paired two-sided student t-test for normally distributed continuous variables or U Mann Whitney for not-normally distributed variables The Chi square test with Yates correction if appropriate or exact Fisher test are used to compare qualitative parameters A Pearson correlation coefficient is used to assess association between CPET values and QoL results A p value 005 is considered significant
Lack or diminished parasympathetic drive to the heart may be however associated with adverse effects The main complication which is seen shortly and up to one year after CNA is heart rhythm acceleration which may be symptomatic in approximately one-third of patients In the majority of patients sinus rate gradually slows down over a period of 3-12 months due to partial parasympathetic reinnervation however approximately 6-7 of patients remain severely symptomatic and require heart rate slowing agents Other complaints such as decreased exercise capacity or effort dyspnea can occur in up to 14 of patients and they are usually attributed to faster than needed sinus rate at rest and during exercise
Although in the vast majority of patients the above mentioned symptoms are rather mild and do not decrease the patients acceptance of CNA in some may decrease the quality of life Thus a detailed assessment of the effects of CNA on exercise performance is clinically important However to date no study addressed this issue
There are several methods to assess exercise performance with cardiopulmonary exercise testing CPET being the most accurate and reference tool It measures cardiorespiratory fitness and physiological responses to aerobic exercise in many conditions CPET provides a comprehensive evaluation of the respiratory circulatory and metabolic responses to exercise that cannot be accurately measured by less precise methods such as standard exercise stress test Therefore we have chosen CPET to evaluate the effects of CNA on exercise performance in our patients
Aim To assess one-year effects of CNA-induced total vagal denervation on cardiorespiratory fitness in patients undergoing CNA due to reflex asystolic syncope
To compare cardiorespiratory fitness between subjects with reflex syncope and healthy volunteers
Hypothesis Cardioneuroablation significantly decreases cardiopulmonary fitness in patients with reflex asystolic syncope
There are no differences between patients with syncope and healthy people in cardiorespiratory fitness at baseline whereas post-CNA results of CPET are significantly worse in syncope patients versus controls
Methods Patients The study group will consist of consecutive patients undergoing CNA in our institution Patients are referred for 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 a 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 Ethics Committee approval 222024
Control group This group will consist of healthy volunteers without cardiovascular and other chronic disorders age- and gender-matched with the CNA group This group will not undergo CNA
Cardioneuroablation The procedure is performed under general anesthesia with muscle relaxation using a 35 mm irrigated tip catheter Navistar ThermoCool SmartTouch with contact force module and electroanatomical 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 also used throughout the whole procedure and serves for guiding ablation including identification of presumed GP areas The extra cardiac vagal stimulation 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 usually started in the left atrium LA at the anterior antrum of the right pulmonary vein 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 right atrium 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 CS
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 will be taken as successful vagal denervation
Cardiopulmonary exercise testing A symptom-limited cardiopulmonary exercise CPET will be performed twice at baseline and after one year of follow-up both in the syncope and control patients Exercise tests will be performed on a treadmill with a cardio-pulmonary system Reynolds Medical The same load protocol will be used twice for the same patient All patients will be encouraged to exercise at maximal effort 8 points using the 10-point Borg scale During the exercise test the patients clinical status will be monitored The systolic and diastolic blood pressure will be recorded every 3 minutes of exercise Heart rate heart rate reserve predicted and achieved chronotropic index and percentage of maximum predicted heart rate at peak exercise will be calculated 3 The maximum predicted heart rate will be calculated as 220-age in years The heart rate recovery in 1 minute will be assessed A 12-lead electrocardiogram will be recorded ECG and heart rate parameters ischemia arrhythmia or conduction disturbances during exercise and recovery will be accessed according to the American Heart Association recommendations
Ventilatory and gas exchange parameters will be assessed during the test The peak oxygen uptake VO2 will be averaged from the highest 30 s of exercise Maximum predicted oxygen uptake will be calculated according to the WassermanHansen equations The anaerobic threshold will be calculated using a dual-method approach V-slope and ventilatory equivalent methods Other analyzed cardiopulmonary exercise testing parameters will include oxygen uptake to work rate increment ratio O2WR ventilatory efficiency VEVCO2 slope and breathing reserve at peak exercise calculated as the percentage of maximum voluntary ventilation maximum voluntary ventilation - minute ventilation at peak exercise maximum voluntary ventilation 100 All exercise tests will be supervised and analyzed according to current guidelines
Quality of life Quality of life will be measured using a dedicated questionnaire The Impact of Syncope on Quality-of-Life Questionnaire University of Calgary This questionnaire consists of 9 questions with 6 choices and 3 questions with 5 choices The overall maximum score is 57 The higher the score the poorer the quality of life is
Statistical analysis The results are presented as meanSD or numbers and percentages Differences between variables are analysed using paired two-sided student t-test for normally distributed continuous variables or U Mann Whitney for not-normally distributed variables The Chi square test with Yates correction if appropriate or exact Fisher test are used to compare qualitative parameters A Pearson correlation coefficient is used to assess association between CPET values and QoL results A p value 005 is considered significant
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