Is there a difference between clinical angina and experimentally inducible angina? A placebo-controlled experiment in stable coronary artery disease

背景：当心脏因动脉狭窄导致血流量不足时，患者经常会感到胸痛。我们称这种症状为“心绞痛”。我们可以用药片治疗心绞痛；但有时这还不够，所以医生会用金属支架（血管成形术）打开狭窄的血管。不幸的是，有些病人甚至在这之后仍然感到疼痛。也许疼痛并不是由狭窄引起的？心脏病专家可以检测血管狭窄是否限制了血液流动，因此应该进行血管成形术。然而，目前还没有测试表明病人的疼痛实际上是由狭窄而不是其他原因引起的。因此，心脏病专家无法判断血管成形术是否会减轻疼痛。这是一个重要的问题，因为血管成形术不能真正缓解不是由狭窄引起的疼痛，但这种血管成形术仍然存在风险，每年要花费NHS数千万英镑。目的：主要目的是测试我们是否能够确定哪些患者的胸痛确实是由动脉狭窄引起的。在65例接受血管成形术的患者中，我将：描述血管成形术前后胸痛的类型。患者将记录血管成形术前后1个月每次胸痛发作的部位、性质和严重程度。他们将在智能手机应用程序上录制这些剧集。这样，我们就会知道手术的效果如何，哪些疼痛通过血管成形术得到了缓解。检查疼痛是否是由动脉狭窄引起的。在正常的血管成形术中，一个微型气球被充气以扩大金属支架。这种气球膨胀会暂时阻塞血液流动，并经常引起疼痛。我们将进行几次这样的气球充气，故意限制血液流动，并要求患者实时描述他们的疼痛。据推测，如果病人的心绞痛真的是由动脉狭窄引起的，那么阻塞动脉应该会重现疼痛。然而，如果动脉狭窄不是他们疼痛的原因，他们在实验过程中感受到的任何疼痛都将是不同的。我的实验的一个独特之处在于它是盲的，这意味着有时我们真的会阻塞动脉，而有时只是假装阻塞（安慰剂）。疼痛应该伴随着真实的发作而来，而不是假装的。检验症状相近的患者是否对血管成形术有更好的反应。如果这种故意阻塞动脉的测试显示出与患者通常的心绞痛非常相似的疼痛，我推测这些患者将从血管成形术中得到极大的缓解。相反，如果这个测试产生了一种非常不同的疼痛，我推测这些病人不会从血管成形术中得到这么多的缓解。应用和益处：每年有超过50万例血管成形术用于治疗心绞痛。这是我们NHS的主要成本。血管成形术在打开动脉方面技术非常出色。但是，如果病人的症状实际上不是由动脉狭窄引起的，即使是辉煌的血管成形术也不能缓解他们的症状。我们还没有充分研究症状的本质与动脉狭窄的关系。多年来，这一直是心脏病学的盲点。我的研究试图通过采取一种新的、个性化的、基于症状的心绞痛和血管成形术来解决这个问题。如果成功，这项研究将开创一种新的诊断测试。这样的测试可以告诉我们哪些病人是由动脉狭窄引起的真正的心绞痛，哪些病人是其他原因引起的胸痛。有了这种诊断能力，心脏病专家可以更好地定制治疗方案；确定支架最能缓解症状的患者，同时防止因其他原因引起症状的患者与血管成形术相关的不必要费用和风险。

Context:Patients often experience chest pain when the heart is short of blood flow due to a narrowing in an artery. We call this symptom 'angina'. We can treat angina with tablets; but sometimes this is not enough, and so doctors open up the narrowing with a metal stent (angioplasty). Unfortunately, some patients still have pains even after this. Perhaps the pain was not caused by the narrowing after all? Cardiologists can test whether a narrowing is restricting blood flow and therefore should have angioplasty. However, there is currently no test to say that a patient's pain is actually caused by the narrowing rather than something else. As a result, cardiologists cannot tell whether angioplasty will alleviate the pain or not. This is an important problem because angioplasty cannot genuinely relieve pain that was not caused by the narrowing, yet such angioplasties still carry risks and cost the NHS tens of millions of pounds per year.Objectives:The principal aim is to test whether we can identify which patients have chest pain that is truly caused by a narrowed artery. In 65 patients who have been referred for angioplasty I will:1. Describe the pattern of chest pain before and after angioplasty.Patients will record the site, nature and severity of each episode of chest pain they experience for 1 month before and 1 month after angioplasty. They will record these episodes on a smartphone application. In this way, we will know how effective the procedure was and which pains were relieved with angioplasty.2. Test whether the pain is actually caused by a narrowed artery.During a normal angioplasty, a miniature balloon is inflated to expand the metal stent. This balloon inflation temporarily blocks blood flow and often causes pain. We will conduct several such balloon inflations to intentionally restrict blood flow and ask the patient to describe their pain in real time. Presumably, if the patient's angina was really caused by the narrowed artery, then blocking the artery should recreate the pain. However, if the narrowed artery was not the cause of their pain, any pain they feel during the experiment would be different in nature. A unique feature of my experiment is that it will be blinded, which means sometimes we really will block the artery and other times it will only be pretend (placebo). The pain should come with the real episodes and not the pretend ones.3. Test whether patients with closely matching symptoms have a better response to angioplasty.If this test, of intentionally blocking the artery, shows a pain closely resembling the patient's usual angina, I speculate that these patients will get a great relief of pain from the angioplasty procedure. In contrast, if this test produces a very different type of pain, I speculate that these patients will not get so much relief from the angioplasty. Applications and benefits:More than 500,000 angioplasty procedures are performed each year for the treatment of angina. This is a major cost to our NHS. Angioplasty is technically excellent at opening the artery. But if a patient's symptoms were not in fact caused by the narrowed artery, even brilliant angioplasty cannot relieve their symptoms. We have not studied enough how the nature of symptoms relates to the narrowed artery. This has been a blind spot in cardiology for many years. My research seeks to resolve this by taking a fresh, personalized, symptom-based approach to angina and angioplasty. If successful, this research could pioneer a new diagnostic test. Such a test could tell us which patients have real angina caused by a narrowed artery, and which patients have chest pain from another source. With this diagnostic ability, cardiologists could better tailor their treatments; identifying the patients in whom stents could most help symptoms, whilst preventing the unnecessary cost and risk associated with angioplasty in those whose symptoms were caused by something else.