Mechanisms of Excess Risk in Aortic STEnosis After Aortic Valve Replacement
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 192
- 试验地点
- 1
- 主要终点
- Heart failure death or hospitalisation for heart failure.
研究概览
简要总结
Aortic stenosis (AS) is caused by narrowing of one of the main heart valves. Replacing the valve is the only treatment to prevent the heart from failing or death. The timing of replacement is currently often too late - half of patients are left with permanent scarring and a quarter die within 3.5 years.
Studies are underway to see if earlier replacement makes a difference. But for those with scarring of the heart, there is currently no tailored treatment. I want to change this by understanding why and how patients with scar are dying and what the investigators can do to prevent this.
In this study, the investigators will use a heart scan (MRI) to detect scarring before valve replacement. After replacement, patients will receive a tiny monitor (paper clip size), which the investigators inject underneath the skin. This monitor continuously checks the heartbeat and can detect increased body fluid due to heart failure. The investigators will monitor patients for an average of 3 years to see if scarring is linked to abnormal heart rhythms and heart failure.
Once the investigators know how and why, the investigators can target patients with available medications and design studies using specialised treatments, eg defibrillator implantation, to protect patients with scar from dying.
详细描述
Valvular heart disease (VHD) affects around 1.5 million people above the age of 65 across the UK and is set to nearly double by 2050. Aortic Stenosis (AS) is the most common VHD in the UK, affecting 3% of those over 75 with more than 11,000 people requiring aortic valve replacement (AVR) in the UK each year (>100,000 world-wide). Current guidelines recommend AVR to improve survival and symptom status when AS symptoms emerge or there is a reduction in left ventricle (LV) function (1), but years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators, and others, have shown that these changes lead to an excess in morbidity and mortality, but the mechanisms of increased risk is unclear.
Patients undergoing aortic valve replacement for severe aortic stenosis have a shorter life expectancy compared with the general population (2). Years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators and others have shown that these changes to the heart muscle are associated with poor outcome. But the mechanism of how heart muscle damage leads to excess mortality is poorly understood.
The proposed study will enhance our understanding of the residual risk after AVR and reveal the modes and substrate of mortality. Heart failure and heart rhythm disturbances (arrhythmias) are likely downstream effects of heart muscle damage, but without understanding the mode of death (heart failure, arrhythmia or other), the investigators are unable to target therapeutic strategies to improve outcomes.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Patients with symptomatic severe aortic stenosis referred for surgical or transcatheter AVR (one out of: effective orifice area [EOA] <1.0 cm2 , indexed EOA of 0.6cm/m2, peak velocity >4.0 m/s or mean gradient >40mmHg).
排除标准
- •More than moderate valve disease other than AS
- •Diagnosis of dilated or hypertrophic cardiomyopathy, pregnancy/breast feeding
- •eGFR <30ml/min, CMR incompatible devices
- •Inability to complete the protocol
- •Other conditions that would prevent participation in the study.
- •Adenosine perfusion will not be performed in patients with AV block, severe asthma/COPD or LVEF<40%.
结局指标
主要结局
Heart failure death or hospitalisation for heart failure.
时间窗: 5 years after aortic valve replacement
Burden of non-sustained VT
时间窗: 2.5 years after aortic valve replacement.
As assessed on implantable cardiac monitor (approximate battery life 2.5 years)
次要结局
- Heart failure symptoms(At 6 weeks and 12 months post aortic valve surgery)
- All-cause mortality (all-cause and cardiovascular via NHS spine/death registration)(5 years after aortic valve replacement)
- Burden of other serious arrhythmias requiring change in management(2.5 years after aortic valve replacement)
- change in functional capacity (6-minute walk test)(At 6 weeks and 12 months after aortic valve replacement.)