Endothelial Function and Cardiac Output in RV Pacing

Study Overview
=================
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.

Official Title
-----------------
Endothelial Function and Cardiac Output in Right Ventricular Pacing

Conditions
-----------------
Bradycardia

Intervention / Treatment
-----------------
* Other: RVP-min
* Other: RVP-max


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Dual chamber pacemaker Intact AV node function Exclusion Criteria: Unstable angina, heart failure Inability to exercise

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: RVP-min|DDD pacing with long AV delay|
|Other: RVP-max|DDD pacing with short AV delay|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-type Natriuretic Pepetide |  | 1 week | 
| 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). | 1 week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
right ventricular pacing, endothelial function, cardiac output