Coronary microvascular dysfunction (CMD) is a common cause of treatment- resistant angina that lacks evidence-based treatment options. The coronary sinus reducer (CSR) is an hourglass-shaped stainless steel mesh, designed to create a controlled narrowing of the coronary sinus (CS). By augmenting CS pressure, CSR implantation was shown to improve myocardial perfusion, potentially providing a novel treatment for patients with CMD. REDUCE CMD is a placebo-controlled study of CSR in 50 patients with CMD. The main study endpoints are the change in coronary flow reserve from baseline to 6 months in the CSR-arm versus the placebo arm, and the difference in number of daily episodes of angina recorded on the ORBITA-app at 6 month follow-up in the CSR-arm versus the placebo arm.

Inclusion criteria

1. Coronary microvascular dysfunction in the left anterior descending coronary artery (LAD) as expressed by abnormal absolute coronary flow reserve (CFR<2.5) confirmed during the index study procedure using the continuous thermodilution technique and saline-induced coronary hyperaemia.
2. Angina - Canadian Cardiovascular Society Class II-IV on at least two anti-anginals or maximally tolerated medical therapy if less than two.
3. Patient understands the nature of the procedure and provides written informed consent for the study prior to enrolment.

Exclusion criteria

1. Age < 18 years.
2. Absence of symptoms reported on the ORBITA-app during the 2-week screening period.
3. Presence of hemodynamically significant epicardial stenoses based on both non- hyperaemic pressure ratio (NHPR; iFR≤0.89, or RFR≤0.89, or dFR/dPR≤0.89) or fractional flow reserve (FFR≤0.80) assessments.
4. Prior positive acetylcholine provocation test with respect to epicardial vasospasm following the COVADIS criteria.
5. Mean right atrial pressure ≥15 mmHg
6. Severe pulmonary hypertension.
7. Coronary sinus anatomy not suitable for CSR implantation.
8. Pregnancy or planned pregnancy within the next 12 months.
9. Recent acute coronary syndrome (within 3 months).
10. Recent revascularization with PCI (within 6 months).
11. Severe arrhythmias, including chronic atrial fibrillation with persistent rapid ventricular response (>100bpm despite medication).
12. Indication for cardiac resynchronization therapy.
13. Severe left ventricular impairment (left ventricular ejection fraction <35%).
14. NYHA class IV or decompensated heart failure or hospitalization due to heart failure within 90 days before the index procedure.
15. Recent implantation of a permanent pacemaker or defibrillator lead in the right ventricle or atrium (within 90 days before the index procedure).
16. Presence of a pacemaker lead in the coronary sinus.
17. Severe valvular heart disease.
18. History of tricuspid valve replacement or repair.
19. Contra-indication to short term dual antiplatelet therapy or lifelong aspirin treatment.
20. Currently enrolled in another investigational device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints.
21. Known inability to tolerate contrast medium.
22. Life expectancy <1 year.