This is an exploratory single-centre, open label, non-randomised, prospective cohort study comparing rate responsive pacing (RRP) with CRT in patients with confirmed HFpEF and chronotropic incompetence.
Setting:
The study will be conducted in Cardiff and Vale University Health Board, with patients drawn from Cardiology clinics and inpatient wards. Follow-up assessments will be conducted at Cardiff School of Sport, a research facility at a university campus close to the main hospital.
Number of subjects planned:
10 patients. This will be sufficient to establish estimates of variability in the diastolic reserve index (see below), allow estimation of treatment difference and gauge acceptability.
Target population:
Subjects with HFpEF and chronotropic incompetence
Endpoints:
Systolic and diastolic longitudinal reserve index are calculated by the following formulae:
Systolic reserve = Δs' x \[1-(1/s'rest)\] Diastolic reserve = Δe' x \[1-(1/e'rest)\]
These are known to be impaired in patients with HFpEF and are a marker of adaptation to exercise in terms of filling pressures and left ventricular relaxation. Tan et al report a significant difference between the results seen with 56 patients with HFpEF and 27 control subjects on exercise echocardiography with semi-supine bicycle.16 Patient characteristics were similar to those of our proposed study group (Ejection fraction (EF) \>50%, New York Heart Association (NYHA) classification grade II, HFpEF according to Vasan and Levy criteria).28
The investigators will therefore investigate diastolic and systolic reserve index as possible endpoints of a future study into the efficacy of CRT versus RRP in HFpEF patients.
Planned interventions:
Visit 1 - Baseline Assessments: Patients will undergo initial assessment of baseline characteristics by echocardiography, cardiopulmonary exercise testing, 6-minute walk test (6MWT) and Minnesota Living with Heart Failure Questionnaire (MLHFQ). (Visit length: approx. 4 hours)
Visit 2 - Device Implantation (≤ 7 days after baseline assessments completed):
Eligible subjects will undergo implantation of a biventricular pacemaker under normal laboratory conditions. The device will be programme to administer rate-responsive pacing (DDDR). They will return to pacing clinic a week later for a programming check; during this visit, they will also undergo a chest x-ray according to local protocol to ensure correct lead placement (Visit length: 1 day + 2 hours)
Visit 3 - Assessments and Device Reprogramming After 12 weeks, the baseline parameters will be reassessed and patients will then have their device non-invasively reprogrammed to CRT. (Visit length: approx. 4 hours)
Visit 4 - Assessments After a further 12 weeks, the baseline assessments will be repeated. The pacemaker will be non-invasively reprogrammed to DDDR mode and the patient will go home. (Visit length: approx. 4 hours)
Optional extension (pending analysis of results) Visit 5 - Reprogramming If incremental benefit has been demonstrated with CRT above the benefit of RRP, the echocardiograms will be examined to establish the mechanism of improvement. Subjects will be invited to participate in a study extension using multisite technology. The device will be non-invasively reprogrammed to optimise the CRT settings targeted specifically for the mechanism identified. (Visit length: approx. 3 hour)
Visit 6 - Assessments 12 weeks after the final reprogramming, patients will attend for a final set of assessments as per baseline. Participant involvement will then cease. (Visit length: approx. 4 hours)
Total contact time with research team: Approximately 27 hours (22 hours without extension)
