Endothelial Function and Cardiac Output in RV Pacing
Condition: Bradycardia
MeSH terms: Bradycardia
Study type: Interventional

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.
    

Intervention name(s): RVP-min; RVP-max
Intervention type(s): Other; Other
Intervention description(s): DDD pacing with long AV delay; DDD pacing with short AV delay
Other intervention name(s): DDD Long; DDD short
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: right ventricular pacing; endothelial function; cardiac output