Heart Failure With Preserved Ejection Fraction Treated by Cardiac Resynchronisation Therapy Versus Rate Responsive Pacing: A Mechanistic Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Diastolic reserve index
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Diastolic reserve index
时间窗: After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing
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.
Systolic reserve index
时间窗: After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing
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.
次要结局
- 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)
- 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)
- New York Heart Association Function Class(After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing)
- 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)
- Minnesota Living with Heart Failure Quality of Life Score(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)
- Prognostic biomarkers(After 12 weeks of rate responsive pacing and again after 12 weeks of biventricular pacing; study extension: after 6 weeks of optimised pacing)
研究者
Freya Lodge
Clinical Research Fellow
Cardiff and Vale University Health Board