Ignite Creation Date:
2024-05-06 @ 3:55 AM
Last Modification Date:
2024-10-26 @ 11:41 AM
Study NCT ID:
NCT02412176
Status:
UNKNOWN
Last Update Posted:
2021-06-11
First Post:
2015-03-24
Brief Title:
Right Ventricular Apical Versus True Mid-septal Pacing
Sponsor:
Charles University Czech Republic
Organization:
Charles University Czech Republic
Study Overview
Official Title:
A Comparison Between Right Ventricular Apical Pacing and True Mid-septal Pacing Verified With Computed Tomography a Randomized Study
Status:
UNKNOWN
Status Verified Date:
2021-06
Last Known Status:
RECRUITING
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:
MS-R
Brief Summary:
Background Right ventricular RV artificial apical pacing can negatively impact synchrony of left ventricular contraction The pacing from the septum of the RV can present an advantage in terms of less expressed dyssynchrony and reduced negative impact on left ventricular LV function However results of randomized studies comparing apical and septal pacing are not uniform All these results have been affected by improper implantation of the septal lead with many apparently septal leads being in fact implanted off-septum The aim of the study is to compare true septal pacing with other RV pacing locations
MethodsDesign This is a prospective randomized single center study Patients with standard indications for cardiac pacing with the expectation of high percentage RV pacing will be enrolled They will be randomized into apical and septal pacing The real location of leads in patients randomized to septal pacing will be confirmed using cardiac CT After cardiac CT three groups of patients will be created 1 apical pacing 2 true septal in which the position of the lead has been verified to be in the septum and 3 apparent septal in which the position of the lead was found to be off-septum Primary end-point are changes in standard echocardiographic parameters LV ejection fraction LV end-systolic volume and LV end-diastolic volume and the concentration of N-terminal pro brain natriuretic peptide NT-proBNP from baseline to 6 months 1 year and three years Secondary end-points are changes in echo-parameters of LV synchrony
Discussion It is hypothesized that correct septal pacing will be associated with reduce negative impact on the function of the left ventricle ie smaller decreases in LV EF and smaller increases in LVEDV LVESV and NT-proBNP and less expressed LV dyssynchrony
MethodsDesign This is a prospective randomized single center study Patients with standard indications for cardiac pacing with the expectation of high percentage RV pacing will be enrolled They will be randomized into apical and septal pacing The real location of leads in patients randomized to septal pacing will be confirmed using cardiac CT After cardiac CT three groups of patients will be created 1 apical pacing 2 true septal in which the position of the lead has been verified to be in the septum and 3 apparent septal in which the position of the lead was found to be off-septum Primary end-point are changes in standard echocardiographic parameters LV ejection fraction LV end-systolic volume and LV end-diastolic volume and the concentration of N-terminal pro brain natriuretic peptide NT-proBNP from baseline to 6 months 1 year and three years Secondary end-points are changes in echo-parameters of LV synchrony
Discussion It is hypothesized that correct septal pacing will be associated with reduce negative impact on the function of the left ventricle ie smaller decreases in LV EF and smaller increases in LVEDV LVESV and NT-proBNP and less expressed LV dyssynchrony
Detailed Description:
METHODSDESIGN The study is planned as prospective multicenter randomized study The study was approved by the local ethics committee and written informed consent will be obtained before enrollment of patients
Inclusion criteria will be the following
1 Indication for cardiac pacing based on recent guidelines of European Society of Cardiology 5
2 High degree atrio-ventricular AV block AV block 21 or second degree AV block with resulting heart rate below 50 or atrial fibrillation with slow conduction to ventricles
3 A high probability of needing significant ventricular stimulation more than 50
4 Written informed consent
Exclusion criteria will be the following
1 The absence of written informed consent
2 Renal insufficiency creatinine level more than 130 µmoll
3 History of Iodine allergy
4 Claustrophobia
5 Significant valve disease ie mitral insufficiency 75 and worse moderate or severe aortic stenosis
6 Recent within three months acute coronary syndrome
7 Planned cardiac surgery coronary artery bypass grafting valve surgery
8 Ejection fraction of left ventricle less than 50
9 Expected life expectancy less than 3 years
10 Expected non-compliance
End-points there are three unique primary end-points 1 changes in left ventricular end-systolic volume LVESV over time from baseline to 6 months and 3 years 2 changes in the left ventricular ejection fraction LV EF over time from baseline to 6 months and 3 years and 3 changes in concentration of N-terminal pro brain natriuretic peptide NT-proBNP from baseline to 6 months up to three years
Secondary endpoints are changes in echocardiography parameters of left ventricular synchrony changes in left ventricular end-diastolic volume LVEDV over time and changes in the quality of life as assessed by the Minnesota Living with Heart Failure questionnaire over time from baseline to 6 months and 3 years
Power calculation and statistical analysis The sample size calculation was based on the following assumptions the power of the test 08 and a statistical significance border 005 Based on information from previous trials regarding the effect of pacing on left ventricular volumes and parameters it is assumed that there will be at least a 10 difference in the change of LV end-systolic volume LVESV measured from baseline to 3 years follow-up between the group paced from apex and the group with true septal pacing Based on previous results regarding the efficacy of true septal pacing based on recent fluoroscopy criteria it is assumed that approximately 40 of those randomized to the septal group will not have the lead located in the septum but in the anterior wall This means that 70 patients are needed in the apical group 70 in the septal group and 70 in the apparent septal group to achieve statistical significance Data analysis will be performed using standard tests chi-square Student t-test Kruskal-Wallis test etc For data description standard descriptive statistical methods will be used absolute and relative frequencies for categorical data and the median with 5-95 percentiles for continuous data For categorical variables statistical analysis will be done using the χ2 or the Fisher exact test for continuous variables the Student t-test Mann-Whitney U test or Kruskal-Wallis test will be used Kaplan-Meier curves will be calculated for visualizing the occurrence of end-points during follow-up The influence of patient characteristics on the occurrence of end-points will be calculated using logistic regression and the Cox proportional risk model when appropriate
Data analysis In the primary analysis three groups of patients will be analyzed 1 patients randomized to RV apical pacing apex group 2 patients with true septal pacing true septal group ie those randomized to septal pacing in whom the location of the lead was confirmed using cardiac CT to actually be in the septum and 3 patients with apparent septal pacing apparent septal group ie those randomized to septal pacing in whom the lead location will be found to off-septum based on cardiac CT The primary goal of the study will be to confirm that true septal pacing is associated with fewer prominent negative effects on the left ventricle A secondary goal is to determine if off-septum placement ie apparent septal group has similar negative consequences for the left ventricle as those seen in apical pacing In a secondary analysis the two original groups will be compared ie the groups randomized to apical vs septal pacing
Echocardiographic evaluation All patients will undergo echocardiography before implantation and during follow-up Echocardiography will be done in the left lateral decubitus position Imaging will be performed using a commercially available echocardiographic system VIVID 7 General Electric Ultrasound Milwaukee USA Images will be obtained using a 35 Mega Hertz transducer at a depth of 16 cm in the parasternal long and short axis and apical two- and four-chamber images views Standard 2D and colour Doppler data triggered by the Q R S complex will be saved in cine-loop format A minimum of three consecutive beats will be recorded from each view and the images will be digitally stored for off-line analysis EchoPac 700 General Electric Ultrasound Milwaukee USA Left ventricular end-systolic volume LVESV LV end-diastolic volume LVEDV and LV EF will be measured from the apical two- and four-chamber images using the modified biplane Simpsons rule 10 Parameters of interventricular and left ventricular dyssynchrony will be measured off-line using tissue Doppler
Conventional tissue Doppler-based dyssynchrony indices will be determined 11 the standard deviation SD in time to peak velocity in 12 mid and basal segments Ts SD12 the difference in time to peak velocity between anteroseptal and posterior wall Ts AsP the difference in time to peak velocity between the septal and lateral wall Ts SL as well as the maximal difference in time to peak velocity in 6 basal segments Ts Diff6 Moreover newer recently published parameters of dyssynchrony such as apical rocking or septal flash will also be measured 12
Further examinations before implantation Patients will be asked to complete the Minnesota Living with Heart Failure Questionnaire and the concentration of NT-proBNP in peripheral blood will be measured Afterwards patients will be randomized to RV apical or RV septal pacing Because it can be anticipated that not all leads intended for RV septal implantation will actually end up implanted in the RV septum some will be in the free anterior wall or in the anteroseptal groove the ratio of randomization will be 21 mid-septal vs apical
Implantation will be done using the standard approach ie using the subclavian or cephalic approach Only active fixation leads will be used The position of the lead in the RV apical group will be assessed by displaying the lead in the anteroposterior AP right anterior oblique RAO 30 and left anterior oblique LAO 40 projection and stored For the septal pacing group a 3D stylet with two angulations will be prepared as proposed recently 9 Initially the distal end of a standard stylet will be manually shaped into a smooth large curve in a single plane over a length of about 20 cm using the barrel of a syringe The lead with this J-shape stylet will be advanced into the RV and further to the pulmonary artery Then the stylet will be withdrawn and an additional 90 curve angulation will be created with the distal 3 cm end of the stylet The 3D stylet will be inserted into the lead and by slight counterclockwise torque applied the lead will be withdrawn from the pulmonary artery to the right ventricle A jump is usually seen as the lead falls below the RV outflow tract At that point the lead is quickly advanced and forced against the mid-septum This manipulation will be done using RAO 30 and the target position is in the middle of the cardiac contour Before final lead fixation the position of the lead will be checked in the LAO 40 the lead should point toward the spine with an angle to the horizontal plane between 0 to 60 Perioperative fluoroscopy images will be stored and standard implant parameters will be measured impedance R wave amplitude and threshold
Cardiac CT will be performed 6-12 weeks after implantation to assess the true position of the RV lead in the heart Before cardiac CT lead dislodgement will be excluded by measuring standard lead parameters
Image acquisition CT will be performed using a 256-detector-row CT scanner Brilliance CT 256 Philips Best The Netherlands with a tube voltage of 100 kilo Volt kV collimation of 2x1280625 mm a pitch of 018 a rotation time of 027 s and a slice thickness of 09 mm A tri-phasic injection of 60 mL of contrast media Ultravist 370 Bayer Healthcare Pharmaceuticals New Jersey USA will be used Initially 50 mL of contrast agent will be administered at a flow rate of 40 mLs followed by 20 mL of 50 contrastsaline Subsequently a saline flush of 30 mL will be administered at a flow rate of 30 mLs Bolus tracking will be used for synchronization of the contrast medium injection during scanning The region of interest will be the descending aorta After enhancement reaches 140 hounsfield Units HU there will be 3-s post-threshold delay before the scan is commenced Prospective ECG triggered dose modulation mode step and shoot will be used scanning 70-80 of the R - R interval After examination the displayed dose-length product DLP will be recorded to evaluate radiation dose
Image post-processing Datasets will be transferred to an external workstation Comprehensive Cardiac Analyses Brilliance Workspace v 40 Philips Healthcare Cleveland USA for off-line analysis Axial slices oblique reconstructions and maximum-intensity projection MIP images will be used for precise localization of the RV lead According to the location of RV lead septal group patients will be divided in two sub-groups true septum group ie patients randomize to septal pacing in whom the lead is actually found to be in the septum and apparent septum group ie those randomized to the septal pacing in whom the lead is found to be off-septum and typically in the free anterior wall or in the anteroseptal groove Because the apical position is easily visible with fluoroscopy cardiac CT will be done only in the patients randomized to septal pacing
Post-implantation follow-up and out-patient controls will be done at 6 months 1 year and 3 years During each control standard pacemaker parameters impedance threshold and amplitude will be measured and the percentage of ventricular stimulation will be assessed During each control echocardiography will be done NT-proBNP measured and patients will be asked to fulfill the Minnesota questionnaire
Inclusion criteria will be the following
1 Indication for cardiac pacing based on recent guidelines of European Society of Cardiology 5
2 High degree atrio-ventricular AV block AV block 21 or second degree AV block with resulting heart rate below 50 or atrial fibrillation with slow conduction to ventricles
3 A high probability of needing significant ventricular stimulation more than 50
4 Written informed consent
Exclusion criteria will be the following
1 The absence of written informed consent
2 Renal insufficiency creatinine level more than 130 µmoll
3 History of Iodine allergy
4 Claustrophobia
5 Significant valve disease ie mitral insufficiency 75 and worse moderate or severe aortic stenosis
6 Recent within three months acute coronary syndrome
7 Planned cardiac surgery coronary artery bypass grafting valve surgery
8 Ejection fraction of left ventricle less than 50
9 Expected life expectancy less than 3 years
10 Expected non-compliance
End-points there are three unique primary end-points 1 changes in left ventricular end-systolic volume LVESV over time from baseline to 6 months and 3 years 2 changes in the left ventricular ejection fraction LV EF over time from baseline to 6 months and 3 years and 3 changes in concentration of N-terminal pro brain natriuretic peptide NT-proBNP from baseline to 6 months up to three years
Secondary endpoints are changes in echocardiography parameters of left ventricular synchrony changes in left ventricular end-diastolic volume LVEDV over time and changes in the quality of life as assessed by the Minnesota Living with Heart Failure questionnaire over time from baseline to 6 months and 3 years
Power calculation and statistical analysis The sample size calculation was based on the following assumptions the power of the test 08 and a statistical significance border 005 Based on information from previous trials regarding the effect of pacing on left ventricular volumes and parameters it is assumed that there will be at least a 10 difference in the change of LV end-systolic volume LVESV measured from baseline to 3 years follow-up between the group paced from apex and the group with true septal pacing Based on previous results regarding the efficacy of true septal pacing based on recent fluoroscopy criteria it is assumed that approximately 40 of those randomized to the septal group will not have the lead located in the septum but in the anterior wall This means that 70 patients are needed in the apical group 70 in the septal group and 70 in the apparent septal group to achieve statistical significance Data analysis will be performed using standard tests chi-square Student t-test Kruskal-Wallis test etc For data description standard descriptive statistical methods will be used absolute and relative frequencies for categorical data and the median with 5-95 percentiles for continuous data For categorical variables statistical analysis will be done using the χ2 or the Fisher exact test for continuous variables the Student t-test Mann-Whitney U test or Kruskal-Wallis test will be used Kaplan-Meier curves will be calculated for visualizing the occurrence of end-points during follow-up The influence of patient characteristics on the occurrence of end-points will be calculated using logistic regression and the Cox proportional risk model when appropriate
Data analysis In the primary analysis three groups of patients will be analyzed 1 patients randomized to RV apical pacing apex group 2 patients with true septal pacing true septal group ie those randomized to septal pacing in whom the location of the lead was confirmed using cardiac CT to actually be in the septum and 3 patients with apparent septal pacing apparent septal group ie those randomized to septal pacing in whom the lead location will be found to off-septum based on cardiac CT The primary goal of the study will be to confirm that true septal pacing is associated with fewer prominent negative effects on the left ventricle A secondary goal is to determine if off-septum placement ie apparent septal group has similar negative consequences for the left ventricle as those seen in apical pacing In a secondary analysis the two original groups will be compared ie the groups randomized to apical vs septal pacing
Echocardiographic evaluation All patients will undergo echocardiography before implantation and during follow-up Echocardiography will be done in the left lateral decubitus position Imaging will be performed using a commercially available echocardiographic system VIVID 7 General Electric Ultrasound Milwaukee USA Images will be obtained using a 35 Mega Hertz transducer at a depth of 16 cm in the parasternal long and short axis and apical two- and four-chamber images views Standard 2D and colour Doppler data triggered by the Q R S complex will be saved in cine-loop format A minimum of three consecutive beats will be recorded from each view and the images will be digitally stored for off-line analysis EchoPac 700 General Electric Ultrasound Milwaukee USA Left ventricular end-systolic volume LVESV LV end-diastolic volume LVEDV and LV EF will be measured from the apical two- and four-chamber images using the modified biplane Simpsons rule 10 Parameters of interventricular and left ventricular dyssynchrony will be measured off-line using tissue Doppler
Conventional tissue Doppler-based dyssynchrony indices will be determined 11 the standard deviation SD in time to peak velocity in 12 mid and basal segments Ts SD12 the difference in time to peak velocity between anteroseptal and posterior wall Ts AsP the difference in time to peak velocity between the septal and lateral wall Ts SL as well as the maximal difference in time to peak velocity in 6 basal segments Ts Diff6 Moreover newer recently published parameters of dyssynchrony such as apical rocking or septal flash will also be measured 12
Further examinations before implantation Patients will be asked to complete the Minnesota Living with Heart Failure Questionnaire and the concentration of NT-proBNP in peripheral blood will be measured Afterwards patients will be randomized to RV apical or RV septal pacing Because it can be anticipated that not all leads intended for RV septal implantation will actually end up implanted in the RV septum some will be in the free anterior wall or in the anteroseptal groove the ratio of randomization will be 21 mid-septal vs apical
Implantation will be done using the standard approach ie using the subclavian or cephalic approach Only active fixation leads will be used The position of the lead in the RV apical group will be assessed by displaying the lead in the anteroposterior AP right anterior oblique RAO 30 and left anterior oblique LAO 40 projection and stored For the septal pacing group a 3D stylet with two angulations will be prepared as proposed recently 9 Initially the distal end of a standard stylet will be manually shaped into a smooth large curve in a single plane over a length of about 20 cm using the barrel of a syringe The lead with this J-shape stylet will be advanced into the RV and further to the pulmonary artery Then the stylet will be withdrawn and an additional 90 curve angulation will be created with the distal 3 cm end of the stylet The 3D stylet will be inserted into the lead and by slight counterclockwise torque applied the lead will be withdrawn from the pulmonary artery to the right ventricle A jump is usually seen as the lead falls below the RV outflow tract At that point the lead is quickly advanced and forced against the mid-septum This manipulation will be done using RAO 30 and the target position is in the middle of the cardiac contour Before final lead fixation the position of the lead will be checked in the LAO 40 the lead should point toward the spine with an angle to the horizontal plane between 0 to 60 Perioperative fluoroscopy images will be stored and standard implant parameters will be measured impedance R wave amplitude and threshold
Cardiac CT will be performed 6-12 weeks after implantation to assess the true position of the RV lead in the heart Before cardiac CT lead dislodgement will be excluded by measuring standard lead parameters
Image acquisition CT will be performed using a 256-detector-row CT scanner Brilliance CT 256 Philips Best The Netherlands with a tube voltage of 100 kilo Volt kV collimation of 2x1280625 mm a pitch of 018 a rotation time of 027 s and a slice thickness of 09 mm A tri-phasic injection of 60 mL of contrast media Ultravist 370 Bayer Healthcare Pharmaceuticals New Jersey USA will be used Initially 50 mL of contrast agent will be administered at a flow rate of 40 mLs followed by 20 mL of 50 contrastsaline Subsequently a saline flush of 30 mL will be administered at a flow rate of 30 mLs Bolus tracking will be used for synchronization of the contrast medium injection during scanning The region of interest will be the descending aorta After enhancement reaches 140 hounsfield Units HU there will be 3-s post-threshold delay before the scan is commenced Prospective ECG triggered dose modulation mode step and shoot will be used scanning 70-80 of the R - R interval After examination the displayed dose-length product DLP will be recorded to evaluate radiation dose
Image post-processing Datasets will be transferred to an external workstation Comprehensive Cardiac Analyses Brilliance Workspace v 40 Philips Healthcare Cleveland USA for off-line analysis Axial slices oblique reconstructions and maximum-intensity projection MIP images will be used for precise localization of the RV lead According to the location of RV lead septal group patients will be divided in two sub-groups true septum group ie patients randomize to septal pacing in whom the lead is actually found to be in the septum and apparent septum group ie those randomized to the septal pacing in whom the lead is found to be off-septum and typically in the free anterior wall or in the anteroseptal groove Because the apical position is easily visible with fluoroscopy cardiac CT will be done only in the patients randomized to septal pacing
Post-implantation follow-up and out-patient controls will be done at 6 months 1 year and 3 years During each control standard pacemaker parameters impedance threshold and amplitude will be measured and the percentage of ventricular stimulation will be assessed During each control echocardiography will be done NT-proBNP measured and patients will be asked to fulfill the Minnesota questionnaire
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None