Endothelial Function and Cardiac Output in RV Pacing

Endothelial Function and Cardiac Output in Right Ventricular Pacing

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.

Study Overview

• Status: Completed
• Conditions: Bradycardia
• Intervention / Treatment: Other: RVP-min; Other: RVP-max

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Ninewells Hospital and Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Dual chamber pacemaker
• Intact AV node function

Exclusion Criteria:

• Unstable angina, heart failure
• Inability to exercise

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

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

Collaborators and Investigators

• Sponsor: University of Dundee
• Investigators: Study Director: Allan Struthers, MD, University of Dundee

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: July 25, 2007
• First Submitted That Met QC Criteria: July 26, 2007
• First Posted (Estimate): July 27, 2007

Study Record Updates

• Last Update Posted (Actual): March 18, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: endothelial function; right ventricular pacing; cardiac output
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Bradycardia
• Other Study ID Numbers: 190906ver3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO