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

背景心绞痛是胸痛的一种症状，一般认为是由于流向心脏的血流量减少，从而导致氧气减少。心绞痛通常在运动时加重，休息后缓解。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测量动脉狭窄的严重程度，因为这可以告诉我们狭窄是否导致血流减少。目前的指南建议，如果狭窄处的压降超过20%，则称为显著性，并且需要在称为经皮冠状动脉介入治疗（PCI）的手术中使用金属支架进行治疗。金属支架保持动脉开放，从而使血流正常化，并提供症状缓解。然而，目前尚不清楚的是，为什么当前的指南使用20%压降的特定截止值来缓解症状，因为压降和症状之间的关系从未在临床研究中进行过测试。还有待确定的是，整个人群的一个临界值是否合适，还是应该使用患者个体化方法。如果压力下降和症状之间的这种关系没有被很好地定义，那么很可能许多患有严重心绞痛的患者不符合这一严格的20%压力下降阈值，他们被拒绝接受PCI，这将大大缓解他们的症状。同样，我们可能会为许多符合20%阈值但症状轻微且不需要手术的患者提供PCI。--目标--1.找出导致每位患者心绞痛的真实压力降。确定患者之间的压降如何变化。3.确定同一患者在运动和休息期间的压降变化。--方法--我们将招募58名有心绞痛症状并符合PCI条件的患者，他们的一条动脉有明显狭窄的解剖学证据，并有血流异常的证据。在评估前访视期间，将使用问卷和基于Android的智能手机应用程序评估症状负担。在手术过程中，所有患者将首先使用金属支架通过PCI治疗狭窄，以恢复正常血流。然后通过直接在支架内使用球囊逐渐缩窄冠状动脉腔来建立心绞痛阈值，直到心绞痛发生。这将在患者运动和休息时单独进行，并记录导致心绞痛的狭窄程度。恢复后，将重新引入引起心绞痛的相同程度的狭窄（患者不运动），并分别获得引起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倚，将在他们不知情的情况下在真实的充盈之间进行假球囊充盈（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，该项目将：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差异。如果观察到相当大的变异性，我们可能需要将我们目前的临床实践（对整个人群使用单一预定义的临床阈值20%）变更为更个性化和患者定制的方法。3.确定运动期间（患者通常会出现心绞痛时）的阈值是否与休息时（我们在导管室测量的阈值）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).