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临床试验/NCT02792452
NCT02792452已完成不适用

Clinical Value of Stress Echocardiography in Moderate Aortic Stenosis

London North West Healthcare NHS Trust1 个研究点 分布在 1 个国家目标入组 100 人开始时间: 2016年9月最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
100
试验地点
1
主要终点
Death (cardiovascular/all cause)

研究概览

简要总结

The management of symptomatic patients with moderate Aortic Stenosis (AS) remains challenging and tests that would give more definitive answers are needed. The value of increase in Aortic Valve mean Gradient (AVMG), lack of change in Aortic Valve area (AVA) and calculation of valve compliance/resistance during stress echo (SE) in the symptomatic moderate AS population prognostication has to the investigators knowledge not been examined before. Similarly the additive value of myocardial blood flow reserve (MBFR), Computed Tomography (CT) calcium score, speckle tracking echocardiography, carotid ultrasonography, and N-Terminal pro B- type natriuretic peptide B (NT-proBNP) in the prognostication of this population group especially in combination with SE remains unclear.

详细描述

The prevalence of aortic valve stenosis (AS) has increased over the last few decades due to improvement in life expectancy and a growing elderly population. A wealth of data is available on patients with severe AS, whereas the risk stratification and management of patients with symptomatic moderate AS remains contentious.

Stress echocardiography (SE) is a recognised tool for the risk stratification of patients with asymptomatic severe AS. Exercise is the preferred mode of stress in this group, as it provides important prognostic information- such as presence of symptoms, overall exercise capacity and precipitation of hypotension. Significant increase in mean gradient (MG) (MG >20mmHg) is an independent predictor of valve intervention or cardiovascular death, similar to older age, diabetes and high resting gradient and this is recognised in international guidelines as a parameter to risk stratify asymptomatic severe AS. The increase in MG in the context of increasing transvalvular flow during exercise is usually accompanied by little or no change in aortic valve area (AVA). Thus, mechanistically, the increase in MG is associated with worse outcome because it reflects the intrinsic non-compliance of the aortic valve and hence resistance. A compliant valve will open to accommodate the increased flow during stress, whereas a fixed valve orifice will not, resulting in increased gradients. It is therefore advised that these patients with asymptomatic severe AS and significant increase in MG during exercise may be reasonably considered for aortic valve intervention.

In moderate AS current guidelines recommend Aortic Valve replacement (AVR) only when other cardiac surgery (coronary artery bypass grafting) is planned (class IIa). This is because patients with moderate AS are a heterogeneous group with regard to the risk of adverse events: some have indeed rapid progression to severe AS, and/or Left Ventricular (LV) dysfunction and cardiovascular death, whereas others remain stable for many years. Overall moderate AS carries a substantial risk of death or valve intervention, with the estimated likelihood of event free survival at 4 years being 55-60%. Furthermore the presence of symptoms increases the overall likelihood of risk in moderate AS, as there is a significant difference in outcome between minimally symptomatic and symptomatic moderate AS. It maybe hypothesised that patients with moderate AS and symptoms in the absence of myocardial ischaemia due to flow-limiting coronary artery disease likely has the same valve hemodynamics as one with severe AS, particularly decreased valve compliance/increased resistance. These characteristics are likely to manifest during exercise when transvalvular flow is increased resulting in significant increase in gradient with little change in AVA. Accordingly, resting AVA and MG may not be the best parameters for determining suitability for valve intervention, particularly as the overall mortality of symptomatic moderate aortic stenosis approaches that of symptomatic severe AS. However, clear criteria that risk-stratify patients with symptomatic moderate AS and guide timing for intervention do not currently exist.

Accordingly the role of SE could be expanded beyond assessment of risk in asymptomatic severe AS to improve risk stratification in patients with symptomatic moderate AS. This is on the assumption that moderate AS associated with symptoms of breathlessness, chest pain or syncope is likely to have the same characteristics as severe AS. This means that during SE in moderate symptomatic AS one would expect the AVA to remain unchanged, the valve resistance to be elevated and the MG to increase.

Furthermore during SE apart from valve related indices that determine severity (AVA, MG), myocardial blood flow reserve (MBFR) has been shown to correlate with severity of AS; reduced MBFR is seen in severe AS whereas MBFR<1.8 has an accuracy of 85% for distinguishing severe from non-severe AS. It could therefore be that MBFR can also contribute in the risk stratification of symptomatic moderate AS.

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

入选标准

  • Age ≥18 years
  • Moderate AS with AVA between 1-1.4cm2, and AVMG<40 millimetres of Mercury (mmHg); and
  • Left Ventricular Ejection Fraction (LVEF) ≥50%; and
  • Cardiac related symptoms; shortness of breath, chest pain or syncope.

排除标准

  • Inability to exercise and undertake pharmacological stress, ie previously known intolerance to dobutamine;
  • Severe aortic or mitral regurgitation or severe mitral stenosis;
  • Significant pulmonary disease like severe (Chronic Obstructive Pulmonary Disease (COPD) or pulmonary fibrosis;
  • Atrial fibrillation;
  • Inability to provide informed consent;
  • Pregnancy;
  • Other known non-cardiovascular disease associated with poor prognosis like metastatic cancer.

结局指标

主要结局

Death (cardiovascular/all cause)

时间窗: between baseline and two years

Hospitalisation for heart failure

时间窗: between baseline and two years

Aortic valve replacement (TAVI or surgical AVR)

时间窗: between baseline and two years

次要结局

  • Change in AS severity (progression to severe) as measured by quantitive echocardiography(Between baseline and one year)
  • change in LV systolic function as measured by quantitive echocardiography(Between baseline and one year)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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