Bradycardia
Conditions
Keywords
right ventricular pacing, endothelial function, cardiac output
Brief summary
Pacing from the right ventricle (as is current practice in patients implanted with permanent pacemakers for bradycardia), has been associated with worse outcomes particularly in heart failure patients. Recent clinical trials suggest that chronic right ventricular pacing (VP) is associated with worsening heart failure, increased strokes and atrial fibrillation. Hemodynamically, right VP results in delayed activation and contraction of the LV which can give rise to functional mitral regurgitation, shortened diastolic filling time and thus reduced coronary filling, as well as abnormal arterial pulsatile flow. The mechanisms for the deleterious effects of right VP in heart failure patients have not been previously investigated. Our aim of this study is therefore to investigate the hemodynamic effects of right VP in stable heart failure patients in terms of exercise cardiac output (CO, an important measure of myocardial function and prognosis), as well as endothelial function which may be deranged as a result of abnormal arterial pulsatile flow.
Detailed description
Study Aims The aim of this study is to investigate the effect of right ventricular pacing on CO at rest and exercise, and on endothelial function and B-type natriuretic peptide, BNP, in patients with heart failure. Methods: Thirty patients with dual chamber pacemakers for sinus node disease will be recruited: 15 controls with normal LV function and 15 with stable impaired LV function (ejection fraction \<40%). The pacemaker will be programmed to pace to back-up pacing at 55bpm in the atrial only (AAI, no right VP) for one week (baseline); and than programmed to overdrive pacing at 70-80bpm, randomised to either to dual chamber, DDD (sequential atrial and ventricular pacing) with a short AV delay (to ensure maximal right VP) or AAI (no RV pacing), for 1 week. There will be a crossover after a 1 week washout at backup AAI pacing at 55 bpm. Resting and exercise CO will be measured at the end of each pacing mode intervention using the Inocor system (a validated non invasive method of CO measurement, using inhaled inert gas equilibriums). Endothelial function will be measured non-invasively at the same time points, as will plasma BNP, a measure of LV strain. Patients with unstable heart failure or angina will be excluded. Study Endpoints: Rest and exercise CO; and endothelial function and BNP with and without RV pacing, in patients with preserved and impaired LV function.
Interventions
OTHERRVP-min
DDD pacing with long AV delay
OTHERRVP-max
DDD pacing with short AV delay
Sponsors
University of Dundee
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Dual chamber pacemaker * Intact AV node function
Exclusion criteria
* Unstable angina, heart failure * Inability to exercise
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Function Assessed by Flow Mediated Vasodilatation | 1 week | Flow mediated vasodilatation as measured by reactive hyperaemia peripheral arterial tonometry signal using EndoPAT software, Itamar. A post-occlusion to pre-occlusion ratio is calculated by the EndoPAT software, providing the EndoPAT index (EnFI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| B-type Natriuretic Pepetide | 1 week | — |
| Cardiac Output | 1 week | measured at peak exercise on a standard exercise bicycle, measured non-invasively using the inert gas rebreathing technique (Innocor, Innovision A/S, Odense, Denmark). |
Countries
United Kingdom
Participant flow
Recruitment details
Subjects previously implanted with a dual-chamber pacemaker for SND were recruited from the Ninewells Hospital and Medical School pacemaker clinic. No subject was pacemaker dependent and the indication for pacing was intermittent sinus arrest or sinus bradycardia.
Pre-assignment details
Prior to randomization, as pre-study right ventricular pacing was variable among the subjects, pacing was programmed to produce minimal right ventricular pacing (using single-chamber atrial pacing or dual-chamber mode with long AV delay) for a minimal washout period of ≥1 week.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All subjects had the right ventricular lead implanted at the right ventricular apex. No subject was pacemaker dependent and the indication for pacing was intermittent sinus arrest or sinus bradycardia. Subjects with ongoing angina or heart failure symptoms, known AV node disease, bundle branch block, age \>80 years, atrial fibrillation, or inability to exercise, were excluded. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 67.7 years STANDARD_DEVIATION 8.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Endothelial Function Assessed by Flow Mediated Vasodilatation
Flow mediated vasodilatation as measured by reactive hyperaemia peripheral arterial tonometry signal using EndoPAT software, Itamar. A post-occlusion to pre-occlusion ratio is calculated by the EndoPAT software, providing the EndoPAT index (EnFI)
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RVP-min | Endothelial Function Assessed by Flow Mediated Vasodilatation | 1.96 EndoPAT index (EnFI) | Standard Deviation 0.37 |
| RVP-Max | Endothelial Function Assessed by Flow Mediated Vasodilatation | 1.73 EndoPAT index (EnFI) | Standard Deviation 0.33 |
Secondary
B-type Natriuretic Pepetide
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RVP-min | B-type Natriuretic Pepetide | 104.3 microgrammes /L | Standard Deviation 108 |
| RVP-Max | B-type Natriuretic Pepetide | 112.8 microgrammes /L | Standard Deviation 80.2 |
Secondary
Cardiac Output
measured at peak exercise on a standard exercise bicycle, measured non-invasively using the inert gas rebreathing technique (Innocor, Innovision A/S, Odense, Denmark).
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RVP-min | Cardiac Output | 7.65 L/min | Standard Deviation 3.15 |
| RVP-Max | Cardiac Output | 7.05 L/min | Standard Deviation 2.61 |