Coronary Sinus Reducer Implantation in Patients With Ischaemia and Non-obstructed Coronary Arteries and Coronary Microvascular Dysfunction.

Symptomatic angina in patients with ischaemia and non-obstructed coronary arteries (INOCA) is common and associated with increased morbidity and adverse outcomes. Myocardial ischaemia often arises from coronary microvascular dysfunction (CMD). Current treatments are limited, and novel evidence-based therapies are needed to address this large unmet clinical need. The Coronary Sinus Reducer (CS Reducer) is a new treatment for refractory angina, which creates a focal narrowing in the coronary sinus that increases back pressure and redistributes blood into ischaemic myocardium at the level of the microcirculation. However the precise mechanism remains unknown. This study will be a randomised double-blinded sham-controlled pilot study (REMEDY-PILOT) to confirm acceptability of CS Reducer implantation, demonstrate feasibility to recruit and quantify its effect on myocardial perfusion. A nested mechanistic substudy within REMEDY-PILOT will test the hypothesis that CS Reducer implantation alters measures of invasive coronary microcirculatory physiology as the mechanistic basis for observed changes in quantitative CMR stress perfusion, symptoms and quality of life.

Inclusion criteria

• Age >18 years
• Ongoing symptomatic angina, CCS Class II-IV, for ≥3 months despite background treatment with at least two anti-anginal drugs at the maximal tolerated dose.
• Patients willing to consider no change in anti-anginal drug treatment for the duration of their participation in the trial.
• Unobstructed coronary arteries with ≤50% epicardial stenoses demonstrated on coronary angiography.
• Stress-induced hypoperfusion on CMR (Global MPR ≤ 2.2).
• Willingness to comply with the specified follow-up evaluation and to be contactable during the period of the trial.
• Understands the nature of the trial procedures and provides written informed consent.

Exclusion criteria

• Epicardial CAD in a main coronary artery (stenoses >50%, RFR≤0.92 or FFR≤0.80), percutaneous coronary intervention (PCI; within previous 6 months, stent insertion for acute Type 1 MI or chronic total occlusion (CTO)), coronary artery bypass grafting, or confirmed Type 1 myocardial infarction (MI).
• Abnormal coronary sinus anatomy (tortuosity, aberrant branch, persistent left superior vena cava)
• Coronary sinus diameter unsuitable for device implantation at operator discretion
• Mean right atrial pressure >15mmHg at time of implantation
• Structural heart disease including left ventricular hypertrophy with raised LV mass index; cardiomyopathy; severe valvular heart disease; previous valve replacement; significant myocardial bridge on angiography; LVEF<45% by CMR.
• Clinically or angiographically diagnosed coronary vasospasm
• Previous hospitalisation for decompensated heart failure
• Pacemaker or defibrillator electrode in the right atrium, right ventricle or coronary sinus
• Documented arrhythmia requiring planned implantation of a permanent pacemaker or defibrillator
• Chronic kidney disease (creatinine >200 micromol/L; established on renal replacement therapy; functioning renal transplant)
• Haemoglobin <80g/L
• Contraindications to receiving dual antiplatelet therapy
• Severe chronic obstructive pulmonary disease (FEV1 <55% predicted)
• Moribund patients with life expectancy < 1year
• Known allergy to nickel or steel
• Current enrolment in another investigational device or drug trial
• Contraindications to CMR or receiving intravenous adenosine
• Pregnancy