Cardiac Resynchronisation Therapy Versus Rate-responsive Pacing in Heart Failure With Preserved Ejection Fraction

NCT03338374 | Completed

• 1 other identifier: 17/WA/0004 190938
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Half of patients with heart failure have normal heart pumping function (Heart failure with Preserved Ejection Fraction, HFpEF), most commonly characterised by breathlessness on exercise. A number of mechanisms are responsible, but frequently patients are unable to raise their heart rate on exercise. This can be treated by a 'rate-responsive pacemaker' (RRP), which detects exercise and increases the heart rate accordingly. Some beneficial effects on echocardiographic parameters have been reported with exercise programmes. However, evidence based treatment options are limited in this group and therapy mainly relies on water tablets and treatment of blood pressure. Cardiac resynchronisation therapy (CRT) is a technique using specialised 'biventricular' pacemakers that is well established in heart failure with reduced pump function. Patients who respond to this treatment have lower risk of death and hospitalisation and usually feel better. CRT is not currently used in HFpEF. The PROSPECT trial showed that some patients with relatively preserved heart function exhibited similar benefits to those with poor pump function, but this has not been formally tested. CRT aims to make the heart beat in a more synchronised way. Patients with HFpEF commonly have evidence of reduced heart synchronisation. The investigators plan to assess the feasibility of using a prospective cohort study to assess the incremental benefit of CRT over and above RRP in patients with HFpEF. 10 patients with HFpEF and insufficient heart rate will be recruited and will undergo exercise testing, heart scanning and symptom questionnaires. A biventricular pacemaker will be implanted and programmed to RRP for 12 weeks before repeating the tests. After this, the investigators will non-invasively programme the pacemaker to CRT for 12 weeks and repeat the functional tests. If incremental benefit is shown with CRT the echocardiograms will be analysed in detail to determine the mechanism of change. The study participants will be invited to continue their involvement in a study extension. This will involve non-invasively programming the pacemakers to optimise their function guided by the results of the echocardiograms in the first two phases of the study. After a further 12 weeks, the functional assessments will be repeated. If no benefit is seen with CRT after initial analysis, the participant involvement will end.

Conditions

Diastolic Heart Failure

Keywords

Cardiac chronotropy; Cardiac resynchronisation therapy; Rate responsive pacemaker; Heart failure with preserved ejection fraction

Outcome Measures

Primary Outcomes (2)

• Diastolic reserve index

  The change in e' between rest and exercise, as measured by tissue Doppler in the septal and/or lateral left ventricular walls on echocardiography. To be expressed using the formula: \[change in e'\] x \[1-(1/e' at rest)\]. e' is the peak diastolic velocity of the myocardium during passive left ventricular filling.

  After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing

• Systolic reserve index

  The change in s' between rest and exercise, as measured by tissue Doppler in the septal and/or lateral left ventricular walls on echocardiography. To be expressed using the formula: \[change in s'\] x \[1-(1/s' at rest)\]. s' is the peak systolic velocity of the myocardium.

  After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing

Secondary Outcomes (8)

• Global longitudinal strain

  After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing

• Left ventricular torsion

  After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing

• Exercise duration

  After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing

• Oxygen carrying capacity

  After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing

• Distance walked in a six-minute walk test

  After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing

Other Outcomes (1)

• Drop-out rate

  At 24 weeks (or if study extension used, then following completion of this 6-week extension)

Study Arms (1)

Biventricular Pacemaker

EXPERIMENTAL

All subjects to be in a single study group experiencing all interventions.

Device: Biventricular pacemaker

Interventions

Biventricular pacemaker DEVICE

All subjects will receive a biventricular pacemaker at implantation. Programming will initially be to dual-chamber, dual-function rate-responsive pacing for 12 weeks; following reassessment, device will be reprogrammed to biventricular pacing for a further 12 weeks. Optional study extension: if incremental benefit is shown for biventricular pacing above dual chamber, the mechanism will be sought using echocardiographic evidence and the devices will be optimised according to this mechanism of action to see whether further benefit can be achieved.

Also known as: Rate responsive pacing

Biventricular Pacemaker

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed HFpEF as described above
• Chronotropic incompetence as described above
• Ongoing exertional breathlessness of NYHA Grade II or worse
• Ability to understand and sign written consent form
• Males and females, age \>18 years
• Ability to participate in follow-up appointments at 3 and 6 months post-implantation
• Ability to complete a cardiopulmonary exercise test

You may not qualify if:

• Any contraindication to implantation of permanent pacemaker, namely unresolved infective process or sepsis, vascular access difficulties, advanced neoplastic process, expected lifespan less than 1 year or patient choice
• Ejection fraction \<50%
• Known valvular disease graded severe or moderate-to-severe
• Cardiac arrhythmia (paroxysmal or persistent) within 1 year of recruitment
• Exertional chest pain suggestive of angina or personal history of coronary artery disease without subsequent revascularisation, or coronary angiogram within the past 5 years demonstrating \>50% stenosis in ≥ 1 epicardial coronary artery
• Significant chronic lung disease (FEV1 \<80%)
• Inability to complete follow-up process for any reason not defined above

Sponsors & Collaborators

• Cardiff and Vale University Health Board: lead
• Abbott: collaborator
• Cardiff Metropolitan University: collaborator

Study Sites (2)

Cardiff and Vale University Health Board

Cardiff, Mid Glamorgan, CF14 4XW, United Kingdom

Location

Cardiff Metropolitan University

Cardiff, Mid Glamorgan, CF23 6XD, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure, Diastolic

Interventions

Cardiac Resynchronization Therapy Devices

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pacemaker, Artificial; Electrodes; Electrical Equipment and Supplies; Equipment and Supplies

Study Officials

• Zaheer Yousef, MD

  Cardiff and Vale University Health Board

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Fellow

Model Details: Exploratory single-centre, open label, non-randomised, prospective cohort study

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: November 9, 2017
• Study Start: November 27, 2017
• Primary Completion: May 30, 2022
• Study Completion: May 30, 2022
• Last Updated: June 2, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)