The Role of Valvular Fibrosis in Patients with Aortic Stenosis

在主动脉瓣狭窄的患者中，瓣变厚并伴有瓣叶的瘢痕（纤维化）和硬化（钙化）。疾病的进展也是由于心肌的瘢痕形成（纤维化）。这种情况非常常见，影响超过10%的75岁以上患者。没有任何药物治疗被证明可以减缓疾病的进展或提高生存率。瓣膜功能的逐渐下降意味着许多患者需要主动脉瓣置换术，这是目前高收入国家最常见的瓣膜手术形式。我们估计，仅NHS每年就需要花费高达10亿英镑。为了能够开发有效的治疗方法来减缓或阻止主动脉狭窄的进展，了解疾病不同阶段纤维化和钙化之间的平衡将是至关重要的。为了更好地理解这个过程，我们将使用目前可用的扫描技术，包括超声心动图（超声波）和CT扫描，以及最先进的扫描技术，称为正电子发射断层扫描（PET），使用放射性示踪剂（一种无色液体注入静脉以便拍照）。这些放射性示踪剂已在最近的研究中用于调查心脏肌肉和心脏瓣膜疾病。这些测试将帮助我们在研究期间的不同时间点测量主动脉狭窄的严重程度以及纤维化和钙化的活动量。在这项研究中，我们将收集多达2000个CT扫描，超声心动图和来自世界各地的相关匿名临床数据，并使用新的图像分析软件分析图像，我们相信这将改进目前在NHS常规进行的CT扫描分析。我们还将招募85名患者和10名健康志愿者，邀请他们进行超声心动图、CT对比扫描和最先进的PET扫描，用一种新的放射性示踪剂观察主动脉瓣内的疤痕活动，看看疤痕活动何时达到最高，以及它与疾病严重程度的关系。我们将要求这些参与者在12个月后返回进行重复评估，看看放射性示踪剂是否可以预测疾病进展。总的来说，我们希望这项研究能够支持临床广泛采用一种改进的诊断工具，以帮助临床决策，并通过观察疤痕活动确定目标生物标志物，这将有助于潜在的临床试验。

In patients with narrowing of the aortic valve (aortic stenosis), the valve becomes thickened with scarring (fibrosis) and hardening (calcification) of the valve leaflets. Progression of the disease is also due to scarring (fibrosis) of the heart muscle. This condition is very common, affecting more than 10% of patients aged over 75 years. No medical therapy has been shown to slow progression of the disease or improve survival. The progressive decline in valve function means that many patients require aortic valve replacement, now the most common form of valve surgery in high income countries. We estimate this costs up to £1 billion per year for the NHS alone. In order to be able to develop effective treatments to slow down or stop progression of aortic stenosis, understanding the balance between fibrosis and calcification at varying stages of the disease will be crucial. In order to better understand this process, we will use currently available scanning techniques including echocardiography (ultrasound) and CT scans, as well as state-of-the-art scanning technology called Positron Emission Tomography (PET) using radiotracers (a colourless liquid injected into a vein in order to take the pictures). These radiotracers havebeen used in recent research studies investigating heart muscle and heart valve diseases. These tests will help us measure the severity of aortic stenosis and the amount of activity of fibrosis and calcification at different time points during the study.In this study we will collect up to 2000 CT scans, echocardiograms and linked anonymised clinical data from around the world, and analyse the images using new image analysis software which we believe will improve on the current analysis of CT scans done routinely in the NHS. We will also recruit 85 patients and 10 healthy volunteers and invite them for an echocardiogram, CT scan with contrast and state-of-the-art PET scan with a new radiotracer looking at scarring activity within the aortic valve, to see when the scarring activity is at its highest and how it relates to the severity of the disease. We will ask these participants to return 12 months later for repeat assessments, to see if the radiotracer can predict disease progression.Overall we hope this research can support widespread clinical adoption of an improved diagnostic tool to aid clinical decision making, and through looking at scarring activity identify a target biomarker which would be helpful for potential clinical trials.