Selective Coronary Vein Sampling in Dyssynchronous Heart Failure and Cardiac Resynchronisation Therapy to Assess Physiological Response to Exercise and Characterise Regional Release of Novel Biomarkers
试验速览
- 阶段
- 不适用
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Levels of Various biomarkers measured from different coronary veins at rest and following exertion both pre CRT implant and at 6 months
研究概览
简要总结
Cardiac resynchronisation therapy (CRT) prolongs the life and improves the symptoms in patients with heart failure and electrical dyssynchrony. 30-50% of patients do not improve with the treatment which is both expensive and not without complication. Despite much research, we cannot accurately predict who will not respond. Furthermore, most heart failure patients gets symptoms on exercise and most studies have examined patients at rest. We propose to investigate the effect of exercise on different parts of the left ventricle by sampling various biomarkers of metabolism, myocardial injury and gene expression. We will then repeat the protocol following device insertion to look for changes. This novel work will require a small cohort of patients with heart failure and no electrical dyssynchrony and normal patients to act as controls. We will also measure novel biomarkers at different venous sites relating to different parts of the myocardium to determine whether they can be used to prognosticate or even predict response to CRT.
详细描述
We propose to examine the acute effects of exercise on patients with dyssynchronous electrical activation of the heart and heart failure and to compare the release of novel biomarkers in selective areas of coronary venous drainage by direct cannulation of different veins via the coronary sinus (CS).
The study design will separate patients into a minimally invasive arm (MINARM)and an invasive arm (INARM). The INARM will be recruited from patients in the MINARM.
MINARM
Group 1: 40 patients scheduled for CRT implant Group 2: 15 patients with heart failure and no dyssynchrony Group 3: 15 patients with normal hearts
Group 1:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- 是
入选标准
- •Scheduled for CRT implant
- •Group 2/B -Heart failure without electrical dyssynchrony.
- •Scheduled for angiography for clinical grounds
- •Group 3/C -Patients without known heart disease
- •Scheduled for clinical angiography and found to have normal coronary arteries
排除标准
- •Pregnancy
- •Moderate to severe aortic valve disease
研究组 & 干预措施
Group A
10 patients from Group 1
On the day preceding the CRT implant will attend hospital for a temporary invasive catheter study. The patient will have a radial sheath positioned in the arterial system. A pacing protocol will be performed using a pacing wire inserted into the right atrium. Coronary sinus venous blood sampling will be performed using a catheter placed via the femoral or internal jugular vein. At the chief investigator's discretion a specially designed exercise bicycle that allow supine exercise in the catheter lab will be used rather than the atrial pacing wire.
6 months post implant the patients will return to the catheter laboratory for a further study. This will repeat the protocol but with the device having been on for 6 months. This will require further study as described above.
干预措施: Blood sampling and exercise protocol pre and post CRT implant (Procedure)
Group 1
40 patients undergoing CRT will have venous samples taken from two CS tributaries, peripheral venous and peripheral arterial sites at the time of CRT insertion at the time of device implant. Blood samples will be analysed for metabolites and novel biomarkers They will then undergo repeat sampling at 6 months to assess for changes in the biomarker profile including CS sampling.
干预措施: Central blood sampling pre and post CRT implant (Procedure)
Group 2
A control arm of 15 patients with heart failure and no dyssynchrony will undergo peripheral venous sampling for novel biomarkers and this will be repeated at 6 months. These samples will allow for control against the dyssynchronous heart failure group and also for temporal changes in biomarker expression.
干预措施: Peripheral blood sampling (Procedure)
Group 3
A control arm of 15 patients with normal hearts will undergo peripheral venous sampling for novel biomarkers and this will be repeated at 6 months. These samples will allow for control against the dyssynchronous heart failure group and also for temporal changes in biomarker expression.
干预措施: Peripheral blood sampling (Procedure)
Group B
5 patients form Group 2.
Patients will undergo a pacing or exercise protocol and have venous, coronary sinus and arterial blood sampled. They will revert to Group 2 for 6 month follow up
干预措施: Central blood sampling on one occasion and exercise protocol and 6 month peripheral sampling (Procedure)
Group C
5 patients form Group 3
Patients will undergo a pacing or exercise protocol and have venous, coronary sinus and arterial blood sampled. They will revert to Group 3 for 6 month follow up
干预措施: Central blood sampling on one occasion and exercise protocol and 6 month peripheral sampling (Procedure)
结局指标
主要结局
Levels of Various biomarkers measured from different coronary veins at rest and following exertion both pre CRT implant and at 6 months
时间窗: 2 years
Biomarkers and metabolites to be assessed include but are not limited to O2, lactate, glucose, CKMB, hs trop, galectin3, Soluble St2, Nt proBNP, cardiac myosin binding protein C, 10 different micro RNA associated with myocardial stress/damage
次要结局
未报告次要终点