Testing Arm 1: treatment with Shockwave Reducer against a placebo for refractory angina

Exclusion

• −The CS diameter at the most proximal end of the planned implant region (2-4 cm distal to the coronary sinus ostium) is less than 9.5 mm or greater than 13.0 mm
• −Known allergy to stainless steel or nickel
• −Subjects must be unable to complete the required COSIRA-II exercise tolerance test due to lower limb amputation (above the ankle) or other physiologic condition with documented chronic mobility or balance issues that require the use of a walking aid (e.g., wheelchair, cane, rollator, crutches, or knee walker).
• −Recent (within 30 days prior to enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →) troponin or CKMB positive acute coronary syndrome (NSTEMI or STEMI) Note: subjects with an elevated troponin or CKMB without acute coronary syndrome may still be enrolled
• −Recent successful revascularization by either CABG or PCI within six months prior to enrollment
• −Note: Successful revascularization is defined as any CABG procedure, or any PCI procedure with a reduction of one or more lesions to \<50% diameter stenosis
• −Note: Subjects with successful revascularization by either CABG or PCI that occurred less than six months prior to enrollment may still be approved for participation in the trial if revascularization was completed six months prior to procedure and CSEC approves subject participation
• −Recent unsuccessful PCI (e.g., failed attempt to open a chronic total occlusion) within 30 days prior to enrollment
• −Note: Subjects with unsuccessful PCI that occurred less than 30 days prior to enrollment may still be approved for participation in the trial if PCI was completed 30 days prior to procedure and CSEC approves subject participation
• −The predominant manifestation of angina is dyspnea
• −Has extra-coronary contributory causes of angina - e.g., untreated hyperthyroidism, untreated anemia (hgb \<10 g/dL), uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg despite medications), atrial fibrillation with rapid ventricular response (consistently \>100 bpm despite medications) or other tachyarrhythmia, severe aortic stenosis, hypertrophic cardiomyopathy with left ventricular outflow tract obstruction or asymmetric septal hypertrophy (concentric left ventricular hypertrophy is not an exclusion criterionExclusion criteriaThe things that would prevent someone from taking part.Read more →), or epicardial vasospasm disease/coronary artery vasospasm (CAS)/vasospastic angina (VSA)
• −NYHA Class III or IV heart failure (HF), decompensated HF or hospitalization due to HF during the 90 days prior to enrollment
• −Life threatening rhythm disorders or any rhythm disorders that would require future placement of an internal defibrillator and/or pacemaker
• −Severe chronic obstructive pulmonary disease (COPD) as indicated by a forced expiratory volume in one second (FEV1) that is less than 55% of the predicted value, or need for home daytime oxygen or oral steroids
• −Severe valvular heart disease (any valve)
• −Moderate or severe RV dysfunction by echocardiography
• −Pacemaker electrode/lead is present in the coronary sinus
• −A Class I indication is present for an implantable defibrillator or cardiac resynchronization therapy according to ACCF/AHA/HRS guidelines
• −Recent implantation of a new pacemaker or defibrillator lead with electrode in the right atrium within 90 days of enrollment
• −Chronic severe renal failure (estimated eGFR less than 30 mL/min/1.73m2 by the MDRD formula) or subjects on chronic dialysis
• −Any clinical condition that might interfere with the trial protocolProtocolThe detailed plan a study must follow.Read more → or the subject's ability to be compliant with the trial protocol (e.g., active alcohol or drug abuse, dementia, magnetic resonances imaging (MRI) planned within 8 weeks of procedure)
• −Currently enrolled in another investigational device or drug trial that has not reached its primary endpointPrimary endpointThe single main question the study is designed to answer.Read more → or that might clinically interfere with the current trial endpointsEndpointThe specific thing a study measures to answer its question.Read more → or procedures
• −Inability to tolerate dual antiplatelet therapy for 6 months if not on a chronic oral anticoagulant, or inability to tolerate a P2Y12 inhibitor for at least 6 months if on a chronic oral anticoagulant
• −Comorbidities limiting life expectancy to less than one year
• −Subject is currently hospitalized for definite or suspected COVID-19
• −Subject has previously been symptomatic with or hospitalized for COVID-19 and has been asymptomatic for \<8 weeks prior to enrollment or has not returned to his or her prior baselineBaselineYour starting measurements, taken before treatment begins.Read more → (pre-COVID-19) clinical condition
• −Subject is asymptomatic but has had a positive PCR or antigen test for COVID-19 within the past 4 weeks prior to enrollment
• −Angiographic/Hemodynamic Exclusion Criteria:
• −\) Coronary anatomy amenable to revascularization of ischemic myocardial territory by either PCI or CABG with at least moderate likelihood of long-term alleviation of angina or angina equivalent symptoms, as per the assessment of the local heart team.
• −Note: If a pathway to coronary revascularization is present which, in the opinion of the local heart team, is reasonably low risk and reasonably likely to provide long-term symptom relief and the subject refuses the revascularization procedure, the patient is ineligible for randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →
• −Procedural Angiographic/Hemodynamic Randomization Exclusion Criteria:
• −Mean right atrial pressure greater than 15 mmHg assessed during the final screeningScreeningThe checks done before joining, to see whether a study fits.Read more → procedure for eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more → assessment and potential randomization
• −Anomalous or abnormal CS anatomy (e.g., tortuosity, aberrant branch, persistent left superior vena cava \[SVC\]) as demonstrated by angiogram
• −Single-armArmOne of the groups in a study, each receiving something different.Read more → Registry (UnblindedOpen-labelEveryone knows which treatment is being given — nothing is hidden.Read more →, Non-Randomized Treatment Arm) InclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more →/Exclusion Criteria:
• −Subject can be included in the single-arm registry if they fall into one of the three categories with inclusions and exclusion criteria as described below.
• −Predominant right coronary disease subjects (RCA):
• −Reversible ischemia: Subjects with evidence of either exercise or pharmacologically induced reversible ischemia by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFR-CT, FFR, iFR, or other non-hyperemic FDA approved or cleared tests (such as DFR or RFR) in the distribution of the right coronary artery (RCA), performed within 12 months prior to enrollment.
• −Note: If the subject has evidence of ischemia in both the LCA and RCA distributions, the extent of ischemia must be greater in the RCA distribution
• −Note: The qualifying assessment must be performed after any myocardial infarction, CABG, or successful PCI within the prior 12 months. If the anti-anginal medication regimen is permanently changed after the assessment of ischemia, the test must be repeated. For subjects with multiple assessments, the one performed closest to enrollment will serve as the qualifying study
• −Obstructive CAD: Three-vessel coronary angiography performed within the 12 months prior to enrollment demonstrating obstructive CAD (visually assessed diameter stenosis of ≥70% or ≥50% - \<70% with fractional flow reserve (FFR) value of ≤0.80 or an iFR or other FDA-approved/cleared non-hyperemic physiological assessment (such as DFR or RFR) of ≤0.89 in one or more lesions) in the RCA (main epicardial vessels or branches) that is not suitable for and will not be treated with PCI or CABG as determined by the local heart team.
• −Note: The qualifying assessment must be performed after any myocardial infarction, PCI or CABG within the prior 12 months. For subjects with multiple assessments, the one performed closest to enrollment will serve as the qualifying study
• −In addition to the above inclusion criteria, subjects must meet all inclusion criteria (except clinical inclusion #5 and angiographic inclusion #1) and none of the exclusion criteria of the main randomized trial
• −Non-obstructive coronary artery disease subjects (ANOCA)
• −Abnormal Coronary Flow Reserve (CFR): subjects must have either abnormal PET CFR (\< 2.0), abnormal perfusion CMR (cardiac MRI) CFR (\<1.85), or abnormal invasive CFR (\<2.5) in at least one main epicardial coronary artery performed within 12 months prior to enrollment
• −Note: Subjects may or may not have evidence of either exercise or pharmacologically induced reversible ischemia by stress echo, nuclear study, PET, perfusion MRI, or CT perfusion
• −Non-obstructive CAD: subjects have non-obstructive coronary disease (estimated diameter stenosis in all coronary lesions is \<50% and (if performed) FFR ≥0.81 or a non-hyperemic test is ≥0.90) demonstrated on three-vessel coronary angiography performed within the 12 months prior to enrollment. If an estimated diameter stenosis is ≥50% to \<70%, the patient may still qualify if FFR ≥0.81 or a non-hyperemic test is ≥0.90 in that vessel. If both FFR and a non-hyperemic test are performed, both must be negative.
• −Note: The qualifying 3-vessel angiogram must be performed after any myocardial infarction, PCI or CABG within the 12 months prior to enrollment. For patients with multiple 3-vessel angiograms, the one performed closest to enrollment will serve as the qualifying study
• −In addition to the above inclusion criteria, subjects must meet all inclusion criteria (except clinical inclusion #5 and angiographic inclusion #1) and none of the exclusion criteria of the main randomized trial
• −Subjects unable to complete ETT
• −In addition to the above inclusion criteria, subjects must meet all inclusion criteria (except clinical inclusion #6) and none of the exclusion criteria of the main randomized trial
• −Prior to inclusion in single-arm registry, all subjects will be reviewed by the Central Screening Eligibility Committee to ensure that they meet registry inclusion criteria and are not eligible for enrollment into the randomized study.
• −Pregnant or planning pregnancy within the next 12 months (women of reproductive potential must have a negative pregnancy test within 7 days of the procedure)
• −Subject is part of a vulnerable population who, in the judgment of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, is unable to give Informed ConsentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the SponsorSponsorThe organisation responsible for the study overall.Read more →, members of the armed forces, and persons kept in detention.
• −Note: some dyspnea may be present with exertion, but the predominant symptom that limits activity must be angina (i.e., chest pain, pressure, tightness, heaviness, or discomfort, with or without radiation to the neck, jaw, shoulders, arms, or other location)