Disrupt CAD III With the Shockwave Coronary IVL System

The study design is a prospective, multicenter, single-arm, global IDE study to evaluate the safety and effectiveness of the Shockwave Medical Coronary Intravascular Lithotripsy (IVL) System in de novo, calcified, stenotic coronary arteries prior to stenting. Disrupt CAD III is being conducted as a staged pivotal study.

Subject Population: Subjects ≥ 18 years of age with de novo, calcified coronary artery lesions presenting with stable, unstable or silent ischemia that are suitable for percutaneous coronary intervention (PCI). Approximately 392 subjects at 50 sites will be enrolled. A minimum of 50% of the total enrollment will come from the United States.Subjects will be followed through discharge, 30 days, 6, 12 and 24 months.

Eligibility Criteria:
Inclusion Criteria:

1. Subject is ≥18 years of age
2. Subjects with native coronary artery disease (including stable or unstable angina and silent ischemia) suitable for PCI
3. For patients with unstable ischemic heart disease, biomarkers (troponin or CK-MB) must be less than or equal to the upper limit of lab normal within 12 hours prior to the procedure (note: if both labs are drawn, both must be normal).
4. For patients with stable ischemic heart disease, biomarkers may be drawn prior to the procedure or at the time of the procedure from the side port of the sheath.

   1. If drawn prior to the procedure, biomarkers (troponin or CK-MB) must be less than or equal to the upper limit of lab normal within 12 hours of the procedure (note: if both labs are drawn, both must be normal).
   2. If biomarkers are drawn at the time of the procedure from the side port of the sheath prior to any intervention, biomarker results do not need to be analyzed prior to enrollment (note: CK-MB is required if drawn from the sheath).
5. Left ventricular ejection fraction \>25% within 6 months (note: in the case of multiple assessments of LVEF, the measurement closest to enrollment will be used for this criteria; may be assessed at time of index procedure)
6. Subject or legally authorized representative, signs a written Informed Consent form to participate in the study, prior to any study-mandated procedures
7. Lesions in non-target vessels requiring PCI may be treated either:

   1. \>30 days prior to the study procedure if the procedure was unsuccessful or complicated; or
   2. \>24 hours prior to the study procedure if the procedure was successful and uncomplicated (defined as a final lesion angiographic diameter stenosis \<30% and TIMI 3 flow (visually assessed) for all non-target lesions and vessels without perforation, cardiac arrest or need for defibrillation or cardioversion or hypotension/heart failure requiring mechanical or intravenous hemodynamic support or intubation, and with no post-procedure biomarker elevation \>normal; or
   3. \>30 days after the study procedure

   Angiographic Inclusion Criteria
8. The target lesion must be a de novo coronary lesion that has not been previously treated with any interventional procedure
9. Single de novo target lesion stenosis of protected LMCA, or LAD, RCA or LCX (or of their branches) with:

   1. Stenosis of ≥70% and \<100% or
   2. Stenosis ≥50% and \<70% (visually assessed) with evidence of ischemia via positive stress test, or fractional flow reserve value ≤0.80, or iFR \<0.90 or IVUS or OCT minimum lumen area ≤4.0 mm²
10. The target vessel reference diameter must be ≥2.5 mm and ≤4.0 mm
11. The lesion length must not exceed 40 mm
12. The target vessel must have TIMI flow 3 at baseline (visually assessed; may be assessed after pre- dilatation)
13. Evidence of calcification at the lesion site by, a) angiography, with fluoroscopic radio-opacities noted without cardiac motion prior to contrast injection involving both sides of the arterial wall in at least one location and total length of calcium of at least 15 mm and extending partially into the target lesion, OR by b) IVUS or OCT, with presence of ≥270 degrees of calcium on at least 1 cross section
14. Ability to pass a 0.014" guide wire across the lesion

Exclusion Criteria:

1. Any comorbidity or condition which may reduce compliance with this protocol, including follow-up visits
2. Subject is a member of a vulnerable population as defined in 21 CFR 56.111, including 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 Sponsor, members of the armed forces, and persons kept in detention
3. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint
4. Subject is pregnant or nursing (a negative pregnancy test is required for women of child-bearing potential within 7 days prior to enrollment)
5. Unable to tolerate dual antiplatelet therapy (i.e., aspirin, and either clopidogrel, prasugrel, or ticagrelor) for at least 6 months (for patients not on oral anticoagulation)
6. Subject has an allergy to imaging contrast media which cannot be adequately pre-medicated
7. Subject experienced an acute MI (STEMI or non-STEMI) within 30 days prior to index procedure, defined as a clinical syndrome consistent with an acute coronary syndrome with troponin or CK-MB greater than 1 times the local laboratory's upper limit of normal
8. New York Heart Association (NYHA) class III or IV heart failure
9. Renal failure with serum creatinine \>2.5 mg/dL or chronic dialysis
10. History of a stroke or transient ischemic attack (TIA) within 6 months, or any prior intracranial hemorrhage or permanent neurologic deficit
11. Active peptic ulcer or upper gastrointestinal (GI) bleeding within 6 months
12. Untreated pre-procedural hemoglobin \<10 g/dL or intention to refuse blood transfusions if one should become necessary
13. Coagulopathy, including but not limited to platelet count \<100,000 or International Normalized ratio (INR) \> 1.7 (INR is only required in subjects who have taken warfarin within 2 weeks of enrollment)
14. Subject has a hypercoagulable disorder such as polycythemia vera, platelet count \>750,000 or other disorders
15. Uncontrolled diabetes defined as a HbA1c greater than or equal to 10%
16. Subject has an active systemic infection on the day of the index procedure with either fever, leukocytosis or requiring intravenous antibiotics
17. Subjects in cardiogenic shock or with clinical evidence of left-sided heart failure (S3 gallop, pulmonary rales, oliguria, or hypoxemia)
18. Uncontrolled severe hypertension (systolic BP \>180 mm Hg or diastolic BP \>110 mm Hg)
19. Subjects with a life expectancy of less than 1 year
20. Non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA or PFO occlusion, etc.) within 30 days prior to the index procedure
21. Planned non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA or PFO occlusion, etc.) within 30 days after the index procedure
22. Subject refusing or not a candidate for emergency coronary artery bypass grafting (CABG) surgery
23. Planned use of atherectomy, scoring or cutting balloon, or any investigational device other than lithotripsy
24. High SYNTAX Score (≥33) if assessed as standard of care, unless the local heart team has met and recommends PCI is the most appropriate treatment for the patient
25. Unprotected left main diameter stenosis \>30%
26. Target vessel is excessively tortuous defined as the presence of two or more bends \>90º or three or more bends \>75º
27. Definite or possible thrombus (by angiography or intravascular imaging) in the target vessel
28. Evidence of aneurysm in target vessel within 10 mm of the target lesion
29. Target lesion is an ostial location (LAD, LCX, or RCA, within 5 mm of ostium) or an unprotected left main lesion
30. Target lesion is a bifurcation with ostial diameter stenosis ≥30%
31. Second lesion with \>50% stenosis in the same target vessel as the target lesion including its side branches
32. Target lesion is located in a native vessel that can only be reached by going through a saphenous vein or arterial bypass graft
33. Previous stent within the target vessel implanted within the last year
34. Previous stent within 10 mm of the target lesion regardless of the timing of its implantation
35. Angiographic evidence of a dissection in the target vessel at baseline or after guidewire passage