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

Background

With 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). Objectives

The 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. Methods

This 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.