Bradycardia
Conditions
Keywords
Bradycardia
Brief summary
The purpose of this clinical project is to evaluate the efficacy of the presence of Right Ventricular Apical (RVA) pacing induced ventricular dyssynchrony as a guiding parameter for bi-ventricular pacing in patients with bradycardia and normal left ventricular ejection fraction (LVEF). The results of this project may provide with the evidence based medicine for guidelines expansion of using Cardiac resynchronization therapy (CRT) in patients with Heart Block and normal LVEF (LVEF \>45%).
Detailed description
All eligible patients willing to provide written informed consent were invited to participate in the study, and then randomized 1:2 to either the Control Group or Echo-guided Group. Patients randomized into the Control Group were implanted with a dual chamber pacemaker (DDDR) device (St. Jude Medical) standard therapy. Patients randomized into the Echo-guided Group were implanted with a cardiac resynchronization therapy pacemaker (CRT-P) device (St. Jude Medical), which was programmed to DDDR pacing mode (CRT-P OFF) at implant. For each Echo-guided Group patient, presence of RVA pacing induced ventricular dyssynchrony was assessed within 24-hour of implant using the standardized criteria of Doppler echocardiography. The Echocardiography Core Laboratory (Echo Core Lab) then analyzed each image and the treatment allocation of the Echo-guided Group was done within 72-hour post implant based on the Echo Core Lab outcomes: * Patients with the presence of RVA pacing induced ventricular dyssynchrony were allocated to the CRT-P standard therapy with CRT-P turned ON * Patients with the absence of RVA pacing induced ventricular dyssynchrony were allocated to the DDDR standard therapy with CRT-P remained OFF Patients meeting all the inclusion criteria and not meeting any of the exclusion criteria were eligible for the study. Data was collected at the following study visits:Enrollment, Implant & Randomization, Pre-discharge (PDH) (≤ 72 hours post implant), Month 1 follow-up visit: 30 ± 14 days post implant, Month 3 follow-up visit: 90 ± 14 days post implant, Month 6 follow-up visit: 180 ± 14 days post implant and Month 12 follow-up visit: 365 ± 14 days post implant
Interventions
DEVICECRT-P OFF
CRT Pacemaker
DEVICECRT-P ON
CRT Pacemaker
DEVICEDDDR
Dual-chamber, rate-modulated pacemaker
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient meets current indications for implantation of a DDDR pacemaker * Patient is geographically stable and willing to comply with the required follow-up schedule * Patient has LVEF \>45% * Patient has atrioventricular block (IIo or above) * Patient has adequate echocardiographic images to measure LV volumes and LVEF
Exclusion criteria
* Patient has permanent atrial fibrillation (AF) * Patient has unstable angina or an acute coronary syndrome * Patient has undergone percutaneous coronary intervention or coronary artery bypass surgery within the previous 3 months * Patient's life expectancy is less than 1 year * Patient is less than 18 years old * Patient is pregnant * Patient has received a heart transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LVEF | 12 months | Left Ventricular Ejection Fraction (LVEF) for assessment of Left ventricular (LV) systolic function |
| LVESV | 12 months | Left ventricular end-systolic volume (LVESV) for assessment of LV remodeling |
Countries
Australia, China, India, Italy, Thailand
Participant flow
Recruitment details
The enrollment target was 177 patients. There were 8 centers from Asia Pacific and 1 center from Italy in the study. From Feb 2013 to Dec 2014, only 98 subjects out of 177 target enrolments were recruited into the study. Sample size was not reached due to difficulty in enrollment.
Participants by arm
| Arm | Count |
|---|---|
| CRT-P OFF Echo-guided Group - DDDR Standard Therapy | 30 |
| CRT-P ON Echo-guided Group - CRT-P Standard Therapy | 34 |
| DDDR Control Group - DDDR Standard Therapy | 34 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 0 | 2 | 3 |
| Overall Study | Difficulty in cannulating the lateral ve | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | CRT-P OFF | CRT-P ON | DDDR | Total |
|---|---|---|---|---|
| Age, Continuous | 67.53 years STANDARD_DEVIATION 11.99 | 68.41 years STANDARD_DEVIATION 13.22 | 72.29 years STANDARD_DEVIATION 9.84 | 69.49 years STANDARD_DEVIATION 11.82 |
| Atrial Fibrillation History None | 30 participants | 32 participants | 33 participants | 95 participants |
| Atrial Fibrillation History Paroxysmal | 0 participants | 2 participants | 1 participants | 3 participants |
| Baseline Left Ventricular Ejection Fraction (LVEF) | 65.19 % STANDARD_DEVIATION 8.42 | 63.14 % STANDARD_DEVIATION 8.7 | 64.72 % STANDARD_DEVIATION 7.51 | 64.31 % STANDARD_DEVIATION 8.18 |
| Baseline Left Ventricular End Diastolic Volume (LVEDV) | 84.72 ml STANDARD_DEVIATION 31.14 | 104.28 ml STANDARD_DEVIATION 34.08 | 88.78 ml STANDARD_DEVIATION 35.27 | 92.91 ml STANDARD_DEVIATION 34.36 |
| Baseline Left Ventricular End Systolic Volume (LVESV) | 32.93 ml STANDARD_DEVIATION 15.92 | 41.55 ml STANDARD_DEVIATION 20.22 | 36.92 ml STANDARD_DEVIATION 23.85 | 37.31 ml STANDARD_DEVIATION 20.51 |
| Heart Rate | 47.37 bpm STANDARD_DEVIATION 16.55 | 47.68 bpm STANDARD_DEVIATION 10.35 | 49 bpm STANDARD_DEVIATION 14.64 | 48.04 bpm STANDARD_DEVIATION 13.85 |
| PR interval | 227.60 ms STANDARD_DEVIATION 78.5 | 236.27 ms STANDARD_DEVIATION 80.99 | 214.76 ms STANDARD_DEVIATION 56.42 | 227.09 ms STANDARD_DEVIATION 72.6 |
| QRS interval | 114.67 ms STANDARD_DEVIATION 29.83 | 118.82 ms STANDARD_DEVIATION 40.06 | 131.47 ms STANDARD_DEVIATION 36.56 | 121.94 ms STANDARD_DEVIATION 36.31 |
| Rhythm on 12-lead ECG 2:1 Heart Block | 5 participants | 4 participants | 6 participants | 15 participants |
| Rhythm on 12-lead ECG 2nd Degree Heart Block | 3 participants | 2 participants | 1 participants | 6 participants |
| Rhythm on 12-lead ECG Atrial Fibrillation | 0 participants | 0 participants | 1 participants | 1 participants |
| Rhythm on 12-lead ECG Atrioventricular Dissociation (AVD) | 0 participants | 0 participants | 1 participants | 1 participants |
| Rhythm on 12-lead ECG Complete AV block with junctional escape | 0 participants | 1 participants | 0 participants | 1 participants |
| Rhythm on 12-lead ECG Complete Heart Block | 11 participants | 14 participants | 12 participants | 37 participants |
| Rhythm on 12-lead ECG Complete Heart Block with Escape Rhythm | 1 participants | 0 participants | 0 participants | 1 participants |
| Rhythm on 12-lead ECG Heart Block | 0 participants | 1 participants | 0 participants | 1 participants |
| Rhythm on 12-lead ECG Intermitent Pacing | 0 participants | 0 participants | 1 participants | 1 participants |
| Rhythm on 12-lead ECG Sinus | 7 participants | 11 participants | 10 participants | 28 participants |
| Rhythm on 12-lead ECG Sinus Bradycardia | 1 participants | 0 participants | 1 participants | 2 participants |
| Rhythm on 12-lead ECG Ventricular Paced rhythm | 0 participants | 1 participants | 0 participants | 1 participants |
| Rhythm on 12-lead ECG Wenkebach | 2 participants | 0 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 10 Participants | 14 Participants | 12 Participants | 36 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 22 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 30 | 18 / 34 | 12 / 34 |
| serious Total, serious adverse events | 5 / 30 | 11 / 34 | 12 / 34 |
Outcome results
Primary
LVEF
Left Ventricular Ejection Fraction (LVEF) for assessment of Left ventricular (LV) systolic function
Time frame: 12 months
Population: From Feb 2013 to Dec 2014, only 98 subjects out of 177 target enrolments were recruited into the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-P OFF | LVEF | 64.22 % LVEF | Standard Deviation 7.53 |
| CRT-P ON | LVEF | 63.14 % LVEF | Standard Deviation 7.51 |
| DDDR | LVEF | 59.96 % LVEF | Standard Deviation 10.47 |
Comparison: * H01: μ LVEF, 1= μ LVEF, 2a vs H1a: μ LVEF, 1 \< μ LVEF, 2a~* Where μ LVEF, 1 is the mean of LVEF at month 12 in DDDR Gp.~* μ LVEF, 2a is the mean of LVEF at month 12 in CRT-P ON Gp,p-value: 0.1734Wilcoxon (Mann-Whitney)
Comparison: * H03: μ LVEF, 1= μ LVEF, 2b vs H1a: μ LVEF, 1 \< μ LVEF, 2b~* Where μ LVEF, 1 is the mean of LVEF at month 12 in DDDR Gp.~* μ LVEF, 2b is the mean of LVEF at month 12 in the CRT-P OFF Gpp-value: 0.1439Wilcoxon (Mann-Whitney)
Primary
LVESV
Left ventricular end-systolic volume (LVESV) for assessment of LV remodeling
Time frame: 12 months
Population: From Feb 2013 to Dec 2014, only 98 subjects out of 177 target enrolments were recruited into the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT-P OFF | LVESV | 30.52 ml | Standard Deviation 14.73 |
| CRT-P ON | LVESV | 34.54 ml | Standard Deviation 14.74 |
| DDDR | LVESV | 36.38 ml | Standard Deviation 21.73 |
Comparison: * H02: μ LVESV, 1 = μ LVESV, 2a vs H1b: μ LVESV, 1 \> μ LVESV, 2a~* Where, μLVESV, 1 is the mean of LVESV at month 12 in the DDDR Group,~* μLVESV, 2a is the mean of LVESV at month 12 in the CRT-P ON groupp-value: 0.6276Wilcoxon (Mann-Whitney)
Comparison: * H04: μ LVESV, 1 = μ LVESV, 2b vs H1b: μ LVESV, 1 \> μ LVESV, 2b~* Where, μLVESV, 1 is the mean of LVESV at month 12 in the DDDR Group,~* and μLVESV, 2b is the mean of LVESV at month 12 in CRT-P OFF group.p-value: 0.5871Wilcoxon (Mann-Whitney)