1) The GISE-SHOCKCALCIUM REGISTRY aims to evaluate the efficacy and safety of coronary lithotripsy for treating severe calcified lesions by enrolling 2000 patients across 50 sites in Italy. 2) The primary endpoint is target lesion failure at 1 year and secondary endpoints include in-hospital and 30-day target lesion failure as well as angiographic and imaging outcomes. 3) Subgroup analyses will evaluate outcomes in patients with complex lesion characteristics like bifurcations or small vessels.

1. THE GISE- SHOCKCALCIUM REGISTRY
An Investigator Driven Italian All-comers Registry of Calcified Lesions
Treated with Intravascular Lithotripsy
Principal Investigators: Prof. Carlo Di Mario & Prof.Giuseppe Tarantini

2. Trials in Literature
- DISRUPT CAD I (Brinton TJ, et al. Circulation. 2019)
60 pts. Clinical success 95%, device success 98.3%, stent delivery 100%
Safety outcome: 30 days MACE (% of cardiac death, MI or TVR) 5%; 6 months MACE (% of cardiac death, MI or TVR) 8.5%.
- DISRUPT CAD II (Ali ZA, et al. Circ Cardiovasc Interv. 2019)
129 pts. Follow-up (in Hospital and at 30 days): In hospital MACE: 5.8%; 30-days MACE: 7.6%; 100% successful delivery of IVL;
100% successful stent delivery; 100% angiographic success; 94% clinical success (7NQWMI)
- DISRUPT CAD III trial (Hill J. et al, J Am Coll Cardiol. 2020)
384 pts. Follow-up (in hospital and at 30 days): MACE: 7.0% and 7.8%, respectively; TVR: 0.5% and 1.6%; all MI (4th definition of
MI) 6.8% and 7.3%. MI according to SCAI definition: 2.6%. TVR 0.5% and 2.6%.
- Intravascular Lithotripsy for the Treatment of Severely Calcified Coronary Lesions: A patient-level pooled analysis of The Disrupt
CAD I, II, III and IV studies (Kereiakes D.J, Di Mario C. et al, JACC Interv)
628 pts. In-hospital MACE (cardiac death, all MI, TVR): 6.5%; 30-days MACE: 7.3%; procedural success < 50% and < 30: 93.2% and
92.4 respectively. TLF at 30 days: 7.2%.

3. 628 patients, it represents the largest cohort of
patients treated with IVL
JACC: CARDIOVASCULAR INTERVENTIONS 2021

4. - Multicenter European registry (Aziz, Bathia et al Catheter Cardiovasc Interv. 2020)
190 pts, 200 lesions, 6 centers, period 14 months
Procedural success 99%, complication 3%
Follow-up (222 days): Cardiac death (1%), target vessel myocardial infarction (0.5%), target lesion revascularization (1.5%),
MACE 2.6%
- Multicenter European registry (Aksoy, Salazar et al, Circ Cardiovasc Interv. 2019)
71 pts, 78 lesions, 3 centers, period 12 months
4 coronary dissections type B, 7 balloon rupture, NO MACE
NO Follow-up
- Multicenter Spanish registry (Cubero-Gallego, Millan et al, Rev Esp Cardiol 2020)
57 pts, 66 lesions, 5 centers, period 12 months
Procedural success 98%, balloon rupture 13%
NO Follow-up
- New Zealand Multicenter registry 1-year outcome (Wong et al J Invasive Cardiol 2020)
44 pts, 1 center, period 7 months
Follow-up (1 year): 1 Cardiovascular death, 3 NSTEMI (2 in-stent restenosis, 1 non TLR)

5. Italy had the highest penetration of IVL in Europe in the first year after release with:
• approximately 1000 patients treated in 2019
• an exponential growth of active centers and patients treated in 2020 (more than 2000 patients until
November 2020 despite the difficulties in hospitalization created by the COVID pandemic).
THE GISE- SHOCKCALCIUM REGISTRY
Rationale
Aim of this prospective, observational, multicenter Italian IVL registry is:
• To evaluate the efficacy and safety of coronary lithotripsy for treatment of severe calcified lesions.
IVL procedures will be distinguished into:
• elective (planned intention to use IVL)
• bail-out (application only when conventional methods left lesion grossly under-expanded)

6. Prospective,
observational,
multicenter, single-arm
THE GISE- SHOCKCALCIUM REGISTRY
Study design
2000 patients, 50 sites in Italy
Enrollment 24 months

7. Sample size 2000 pts
Event Rate 12%
THE GISE- SHOCKCALCIUM REGISTRY
Sample size estimation and simulations results

8. THE GISE- SHOCKCALCIUM REGISTRY
Major End-points
 Primary composite safety endpoint: Target lesion failure (TLF) at 1 year
⍅clinically or ischemia driven
*CK-MB level >3x ULN through discharge (peri-procedural MI) and using the 4 th Universal Definition of MI beyond discharge
 Secondary safety endpoints: in-hospital and 30-days TLF
• Cardiovascular death, or
• Myocardial infarction*, or
• Target lesion revascularization⍅
• Cardiovascular death, or
• Myocardial infarction*, or
• Target lesion revascularization⍅
 Secondary safety endpoints: definitive or probable stent thrombosis (ST)
Timing of ST:
• Acute: 0-24h
• Subacute: >24h-30day
• Late: 30 day-1 year

9. THE GISE- SHOCKCALCIUM REGISTRY
Secondary End-points
*greater than type B from National Heart, Lung, and Blood Institute classification
& evidence of extravasation of dye or blood from the coronary artery during or following the interventional procedure
+ Delivery of IVL across the target lesion and delivery of lithotripsy without serious angiographic complications immediately after IVL
⍅ successful stent delivery with ≤30% residual stenosis and without serious angiographic complications
 Secondary safety endpoints: procedural angiographic safety endpoints
• Severe coronary dissection*
• Coronary perforation&
• Abrupt closure
• Slow flow or no re-flow
 Secondary effectiveness endpoints:
• Device crossing and IVL delivery success+
• Angiographic success⍅
• QCA outcome: acute gain (mm) and percent residual diameter stenosis
• Imaging outcome: calcium burden (calcium arc, length, depth), IVL induced fractures,
final MLA within stent and at maximal calcium arc

10. THE GISE- SHOCKCALCIUM REGISTRY
Inclusion criteria
 Patients is ≥ 18 years of age.
 Patients with calcified coronary artery disease requiring percutaneous revascularization with stent
implantation who require an IVL with the Shockwave catheter.
 Presence of single or multiple calcifications at the lesion site defined 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.
 Ability to tolerate dual antiplatelet agent (i.e. aspirin, clopidogrel, prasugrel, or ticagrelor for 1 year and
single antiplatelet therapy for life)
 Ability to give written informed consent.
 Patient is able and willing to comply with all follow-up assessments

11. THE GISE- SHOCKCALCIUM REGISTRY
Exclusion criteria
 Refusal to participate in this study.
 Calcific lesion within a > 4 mm reference segment of the vessel
 Lesions in LIMA/RIMA or at the distal anastomosis of an SVG
 All the usual relative contraindications to coronary angioplasty according to the clinical practice:
 Patient has active systemic infection
 Patient has a known untreated coagulation disorder
 Patient has allergy to imaging contrast media for which he/she cannot be pre-medicated
 Patient is pregnant or nursing
 Patients whose life expectancy is < 1 year
 Patients due to move abroad within 1 year

12. - In stent restenosis
- Eccentric lesion defined as <180 degrees lesions on IVUS or OCT
- Long calcified lesions defined as calcium length > 40 mm
- Small vessels defined as having a reference diameter measured with IVUS/OCT < 2.5 mm
- Calcified left main disease: defined as any greater than 50% calcific lesion involving the LM and requiring IVL
- Calcified bifurcation lesions: defined as lesions involving a side-branch with greater than 2.5 mm diameter, distinguished
based on the traditional Medina classification and the stenting technique used
- Calcified lesions in saphenous vein grafts (SVG)
- Calcified lesions in diabetic patients
- Calcified lesions in primary angioplasty for STEMI
- Calcified lesions in recent NSTEMI (last symptoms <48 hours)
- Calcified lesions in chronic total occlusions (CTO)
- Treatment of calcified lesions under left ventricular temporary assistance (Impella)
THE GISE- SHOCKCALCIUM REGISTRY:
Pre-planned subgroup analysis

13. - In stent restenosis
- Eccentric lesion defined as <180 degrees lesions on IVUS or OCT
- Long calcified lesions defined as calcium length > 40 mm
- Small vessels defined as having a reference diameter measured with IVUS/OCT < 2.5 mm
- Calcified left main disease: defined as any greater than 50% calcific lesion involving the LM and requiring IVL
- Calcified bifurcation lesions: defined as lesions involving a side-branch with greater than 2.5 mm diameter, distinguished
based on the traditional Medina classification and the stenting technique used
- Calcified lesions in saphenous vein grafts (SVG)
- Calcified lesions in diabetic patients
- Calcified lesions in primary angioplasty for STEMI
- Calcified lesions in recent NSTEMI (last symptoms <48 hours)
- Calcified lesions in chronic total occlusions (CTO)
- Treatment of calcified lesions under left ventricular temporary assistance (Impella)
THE GISE- SHOCKCALCIUM REGISTRY:
Pre-planned subgroup analysis

14. • MLD and reference diameters and derived indices
before PCI, after IVL and after final stent optimization.
• Calcium presence, arc (degrees), length (mm), maximum depth (mm, at OCT), lesion MLA (mm2) and length (mm)
before PCI (including images after pre-dilatation);
• presence, number, depth of calcium fractures post-IVL;
• final MLA and reference area and derived indices after stent implantation.
THE GISE- SHOCKCALCIUM REGISTRY:
Intravascular Imaging sub-studies
Academically motivated centers with proven experience and adequate infrastructure will be offered the possibility to
analyze all angiograms and intravascular imaging studies in order to determine:

15. A period of follow-up is recommended at 30 days and 1 year based on a clinical interview in order to
evaluate patient symptoms and performance status (CCS angina classification and NYHA classification), including
collection of source documents regarding new coronary angiography or intravascular imaging preformed during this
observational period.
THE GISE- SHOCKCALCIUM REGISTRY:
Follow-up