What is the mechanism of action of the Coronary Sinus Reducer in refractory angina? A randomised placebo-controlled study

冠状窦减压器治疗难治性心绞痛的作用机制是什么？

• 批准号: MR/V001620/1
• 负责人: Michael Foley
• 金额: $ 34.47万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV001620%2F1
• 关键词: What; mechanism; action; Coronary; Sinus

BackgroundWith an ageing population and improved survival from heart attacks, a growing number of people are living with coronary artery disease. One of the main treatment aims in coronary artery disease is the prevention of angina, which is chest pain that comes on with exertion. Conventional therapies for angina include medications, coronary stents (coronary angioplasty) and coronary artery bypass surgery. Despite these interventions, approximately 10% of patients with coronary artery disease have ongoing chest pain (refractory angina). Until recently, these patients have had no available treatment options. Refractory angina is an extremely debilitating condition and patients are often confined to their homes due to severe exertional chest pain, leading to a poor quality of life for the majority. Patients with refractory angina frequently visit their general practitioner and emergency departments with chest pain. They often have repeated invasive coronary angiograms without treatment and until recently physicians have not been equipped with an effective therapy to offer to these patients.A novel device for treatment of refractory angina was developed in response to this unmet clinical need - the Coronary Sinus Reducer (CSR). It is an hourglass shaped, stainless steel mesh which is implanted in the coronary sinus (the vessel which drains blood from the heart muscle). This is a simple procedure performed under local anaesthetic, which takes approximately 30 minutes. It is thought to improve the flow of blood to the heart muscle. In a randomised trial with a placebo control arm, CSR improved angina compared to placebo (Coronary Sinus Reducer for treatment of Refractory Angina Trial - COSIRA). ObjectivesThe mechanism through which the CSR exerts its effect is unknown and this fellowship is designed to discover it. In small animal studies, a surgical stitch used to narrow the coronary sinus caused redistribution of blood in the heart muscle, favouring the areas which were most in need. This is thought to be how the CSR acts, but this has never been demonstrated in humans. As we do not know how it works, we cannot identify patients who are most likely to benefit from the device. In this fellowship I will study the how the CSR works in patients with refractory angina.MethodsThis study will enrol 40 patients with refractory angina. I will use cardiac imaging with MRI scans to assess blood flow in the heart muscle and will use ultrasound to measure blood flow in the coronary arteries. We will assess patients' symptoms, using questionnaires, exercise time and a symptom smartphone application, into which patients can input their symptoms daily throughout the study. This study will utilise a placebo control, so that we can understand the true effects of the device. Patients will be randomly assigned 1:1 to the treatment arm, where they will receive a CSR in the normal fashion, or the control arm, where they will have a placebo procedure. Participants and researchers will be blinded to treatment arm. At the end of a 6 month follow up period, the baseline tests will be repeated. The study has been designed in collaboration with the NHLI ORBITA focus group of patients with lived experience of stable angina. I will discover whether the CSR causes improved blood flow to the heart muscle on MRI and I will correlate changes in symptoms and exercise time, with the baseline tests of blood flow, to better understand who would benefit from the device. This fellowship will define the effect that the CSR has on patients with refractory angina, improve our understanding of its mechanism and advance our ability to target therapy in this undertreated group of patients.

背景随着人口老龄化和心脏病生存率的提高，越来越多的人患有冠状动脉疾病。冠状动脉疾病的主要治疗目标之一是预防心绞痛，心绞痛是运动时出现的胸痛。心绞痛的常规治疗包括药物治疗、冠状动脉支架（冠状动脉血管成形术）和冠状动脉搭桥手术。尽管有这些干预措施，约10%的冠状动脉疾病患者仍有持续胸痛（难治性心绞痛）。直到最近，这些患者还没有可用的治疗选择。难治性心绞痛是一种非常虚弱的疾病，患者经常因严重的劳力性胸痛而被限制在家中，导致大多数人的生活质量很差。难治性心绞痛患者经常因胸痛去看全科医生和急诊科。他们经常反复进行有创冠状动脉造影而不进行治疗，直到最近医生还没有为这些患者提供有效的治疗方法。针对这种未满足的临床需求，开发了一种治疗难治性心绞痛的新型器械-冠状窦缩小器（CSR）。它是一个沙漏形的不锈钢网，植入冠状窦（从心肌中排出血液的血管）。这是在局部麻醉下进行的简单程序，大约需要30分钟。它被认为可以改善血液流向心肌。在一项安慰剂对照组的随机试验中，与安慰剂相比，CSR改善了心绞痛（冠状窦减压器治疗难治性心绞痛试验- COSIRA）。在小动物研究中，冠状窦狭窄的手术缝合引起心肌中血液的重新分布，有利于最需要的区域。这被认为是CSR的作用方式，但这从未在人类身上得到证实。由于我们不知道它是如何工作的，我们无法确定最有可能从该设备中受益的患者。在这个奖学金，我将研究如何CSR工程在患者难治性心绞痛。我将使用心脏成像和MRI扫描来评估心肌中的血流量，并将使用超声波来测量冠状动脉中的血流量。我们将使用问卷、运动时间和症状智能手机应用程序评估患者的症状，患者可以在整个研究期间每天输入他们的症状。本研究将使用安慰剂对照，以便我们能够了解器械的真实效果。患者将以1：1的比例随机分配至治疗组，在治疗组中，他们将以正常方式接受CSR，或对照组，在对照组中，他们将接受安慰剂程序。受试者和研究者将对治疗组设盲。在6个月随访期结束时，将重复基线测试。本研究是与NHLI ORBITA焦点组（有稳定型心绞痛生活经历的患者）合作设计的。我将发现CSR是否会改善MRI上心肌的血流量，并将症状和运动时间的变化与血流量的基线测试相关联，以更好地了解谁将从该设备中受益。这项研究将确定CSR对难治性心绞痛患者的影响，提高我们对其机制的理解，并提高我们在这一治疗不足的患者群体中进行靶向治疗的能力。

项目成果

Cardiopulmonary exercise testing and efficacy of percutaneous coronary intervention: a substudy of the ORBITA trial.

经皮冠状动脉干预的心肺运动测试和功效：Orbita试验的典型。

• DOI: 10.1093/eurheartj/ehac260
• 发表时间: 2022-09-01
• 期刊: EUROPEAN HEART JOURNAL
• 影响因子: 39.3
• 作者: Ganesananthan, Sashiananthan;Rajkumar, Christopher A.;Foley, Michael;Thompson, David;Nowbar, Alexandra N.;Seligman, Henry;Petraco, Ricardo;Sen, Sayan;Nijjer, Sukhjinder;Thom, Simon A.;Wensel, Roland;Davies, John;Francis, Darrel;Shun-Shin, Matthew;Howard, James;Al-Lamee, Rasha
• 通讯作者: Al-Lamee, Rasha

Aortic Valve Calcium Score Is Associated With Acute Stroke in Transcatheter Aortic Valve Replacement Patients.

• DOI: 10.1016/j.jscai.2022.100349
• 发表时间: 2022-07
• 期刊: Journal of the Society for Cardiovascular Angiography & Interventions
• 作者: Foley, Michael;Hall, Kerry;Howard, James P;Ahmad, Yousif;Gandhi, Manisha;Mahboobani, Samir;Okafor, Joseph;Rahman, Haseeb;Hadjiloizou, Nearchos;Ruparelia, Neil;Mikhail, Ghada;Malik, Iqbal;Kanaganayagam, Gajen;Sutaria, Nilesh;Rana, Bushra;Ariff, Ben;Barden, Edward;Anderson, Jonathan;Afoke, Jonathan;Petraco, Ricardo;Al-Lamee, Rasha;Sen, Sayan
• 通讯作者: Sen, Sayan

Aortic Valve Calcium Score Is Associated With Acute Stroke in Transcatheter Aortic Valve Replacement Patients

主动脉瓣钙化评分与经导管主动脉瓣置换术患者的急性卒中相关

• DOI: 10.1016/j.carrev.2023.05.250
• 发表时间: 2023
• 期刊: Cardiovascular Revascularization Medicine
• 影响因子: 1.7
• 作者: Foley M

The Placebo-Controlled Effect of Percutaneous Coronary Intervention on Exercise Induced Changes in Anti-Malondialdehyde-LDL Antibody Levels in Stable Coronary Artery Disease: A Substudy of the ORBITA Trial.

经皮冠状动脉干预对运动诱导的抗甲醛-LDL抗体水平的变化的安慰剂控制作用：稳定的冠状动脉疾病：Orbita试验的一种替代。

• DOI: 10.3389/fcvm.2021.757030
• 发表时间: 2021
• 期刊: Frontiers in cardiovascular medicine
• 影响因子: 3.6
• 作者: Hartley A;Shun-Shin M;Caga-Anan M;Rajkumar C;Nowbar AN;Foley M;Francis DP;Haskard DO;Khamis RY;Al-Lamee RK
• 通讯作者: Al-Lamee RK

Remote digital smart device follow-up in prospective clinical trials: early insights from ORBITA-2, ORBITA-COSMIC, and ORBITA-STAR.

• DOI: 10.1093/eurheartjsupp/suac058
• 发表时间: 2022-11
• 期刊: EUROPEAN HEART JOURNAL SUPPLEMENTS
• 影响因子: 1.6
• 作者: Ganesananthan, Sashiananthan;Rajkumar, Christopher A.;Foley, Michael;Francis, Darrel;Al-Lamee, Rasha
• 通讯作者: Al-Lamee, Rasha