Determining patient-individualised placebo-controlled angina thresholds for invasive haemodynamic assessment

--背景--心绞痛是胸痛的一种症状，被认为是由于血液流量减少，从而减少了流向心脏的氧气。心绞痛通常在运动时更严重，休息后就会缓解。心绞痛最常见的原因是供应心脏的动脉变窄。目前，我们通过评估狭窄处的压降来衡量动脉内狭窄的严重程度，因为这可以告诉我们狭窄是否导致血流量减少。目前的指南建议，如果狭窄处的压力下降超过20%，则称为显著，在称为经皮冠状动脉介入治疗(PCI)的过程中使用金属支架是必要的。金属支架使动脉保持畅通，从而使血流正常化并缓解症状。然而，目前尚不清楚的是，为什么目前的指南使用20%的压降来缓解症状，因为压降和症状之间的关系从未在临床研究中得到测试。还有待确定的是，是否应该对整个人群进行一次截断，或者更确切地说，应该使用患者个性化的方法。如果压降和症状之间的这种关系没有明确定义，那么很可能许多患有严重心绞痛的患者不符合严格的20%压降阈值，正在拒绝接受将极大地缓解他们症状的PCI。同样，我们可能会为许多达到20%门槛但症状轻微且不需要手术的患者提供冠状动脉介入治疗。-目标--1.找出导致每位患者心绞痛的真实压降。以确定这一压降在患者之间的变化情况。以确定同一患者在运动和休息之间的压力降是如何变化的。--方法--我们将招募58名患者，他们有心绞痛症状，有资格接受经皮冠状动脉介入治疗，证明他们的一条动脉有显著狭窄的解剖学证据，并有血液流动异常的证据。症状负担将在预评估访问期间使用问卷和基于症状的智能手机应用程序进行评估。在手术过程中，所有患者将首先接受使用金属支架的PCI治疗，以恢复正常血流。然后，通过在支架内直接使用气囊逐渐缩小冠状动脉管腔，建立心绞痛阈值，直到心绞痛刚刚发展。这将在患者运动和休息时分别进行，并记录导致心绞痛的狭窄程度。康复后，将重新引入引起心绞痛的相同狭窄程度(患者不进行运动)，并将分别获得导致运动性心绞痛和静息性心绞痛的确切压降。为了消除患者和观察人员的报告偏差，将在他们不知情的情况下实施真实充气之间的虚假气囊充气(安慰剂对照)。--潜在益处--我的研究将是第一个在双盲安慰剂对照实验条件下确定心绞痛血流动力学阈值的研究。如果成功，这个项目将：1。更准确地表示狭窄处的压降与心绞痛症状之间的关系。2.确定患者之间是否存在变异性。如果观察到相当大的变异性，我们很可能需要改变我们目前的临床实践，即对整个人群使用一个预定义的20%的临床阈值，转向更个性化和患者定制的方法。3.确定运动时(患者通常会出现心绞痛)的阈值与休息时(我们在导管实验室中测量的阈值)是否不同。

-- Background --Angina is a symptom of chest pain that is thought to be caused by a reduction in blood flow, and therefore oxygen, to the heart. Angina is typically worse during exercise and is relieved with rest. The most common cause of angina is narrowing in the arteries supplying the heart. Currently, we measure the severity of a narrowing within an artery by assessing the pressure drop across the narrowing, as this tells us if the narrowing is causing a reduction in blood flow. Current guidelines recommend that if there is a pressure drop of more than 20% across a narrowing, it is called significant, and treatment with a metal stent in a procedure called percutaneous coronary intervention (PCI) is warranted. The metal stent keeps the artery open, thereby allowing blood flow to normalise and offering symptom relief.What remains unclear however, is why the current guidelines use this specific cut-off of a 20% pressure drop for symptom relief as the relationship between a pressure drop and symptoms has never been tested in a clinical study. It also remains to be determined whether one cut-off for the whole population is appropriate or rather a patient-individualised approach should be used. If this relationship between the pressure drop and symptoms is not as well-defined, then it is likely that many patients with significant angina who do not meet this strict 20% pressure drop threshold are being refused PCI that would dramatically relieve their symptoms. Equally, we may be offering PCI to lots of patients who meet this 20% threshold but have minimal symptoms and do not need the procedure. -- Objectives --1. To find the true pressure drop that causes angina for every patient.2. To determine how this pressure drop varies between patients.3. To determine how this pressure drop varies between exercise and rest for the same patient. -- Methods --We will enrol 58 patients who have symptoms of angina and are eligible for PCI, demonstrate anatomical evidence of significant narrowing in one of their arteries and have evidence of blood flow abnormalities. Symptom burden will be assessed during the pre-assessment visit using questionnaires and a symptom-based smartphone application. During the procedure, all patients will first have their narrowing treated with PCI using a metal stent to restore normal flow. The angina thresholds will then be established by progressively narrowing the coronary artery lumen with a balloon directly inside the stent, until angina just develops. This will be performed separately while the patient is exercising and resting, and the degree of narrowing that causes angina will be recorded for both. Following recovery, the identical degree of narrowing that caused angina will be re-introduced (without the patient exercising) and the exact pressure drop causing exercise angina and rest angina will be obtained separately. To eliminate reporting bias from patients and observing staff, false balloon inflations in between real inflations will be applied without their knowledge (placebo-control). -- Potential Benefits --My fellowship will be the first study to identify the haemodynamic threshold for angina under double-blinded placebo-controlled experimental conditions. If successful, this project will:1. Provide a more accurate representation of the relationship between the pressure drop across a narrowing and symptoms of angina. 2. Determine whether there is variability between patients. If considerable variability is observed, it is likely we will need to change our current clinical practice that uses a single predefined clinical threshold of 20% for the whole population to a more personalised and patient-tailored approach. 3. Determine if the thresholds during exercise (when the patient typically gets angina) is different from rest (what we measure in the cath lab).