2.1

Study design and population

This prospective monocentric observational Registry enrolled only patients with ST elevation myocardial infarction (STEMI) and multi-vessel disease (MVD), thus eligible for a two-step procedure. The PCI of the culprit lesion was performed with at least one Orsiro stent. The second procedure was then deferred accordingly to the severity of the non-culprit lesion and the presence of symptoms and signs of residual ischemia to 30-days, 90-days and 180-days. During the second procedure, the stent deployed at the infarct-related site was analysed by OCT.

2.2

The Orsiro Sirolimus Eluting Stent

The Orsiro-DES is a cobalt-chromium stent with strut thickness 60 μm and 80 μm stent struts (the lowest for the stent with a diameter ranging from 2.25 to 3.0 while 80 μm thickness is for the 3.5 and 4.0 diameter stents), coated with a poly-L-lactide (PLLA) polymer that delivers sirolimus drug over 12–14 weeks and degrades over one to two years. It presents a unique thin-layer, amorphous silicon carbide coating (PROBIO) that reduces interaction between the metal stent and the surrounding tissue and blood by acting as a diffusion barrier aiming to improve the biocompatibility of the material by reducing thrombogenicity and encouraging re-endothelialisation.

2.3

Interventional Procedure

The PCI was routinely performed with the standard techniques via femoral or radial approach using 6 or 7 French guiding catheters. Patients not preloaded with oral aspirin and/or clopidogrel received a loading dose of intravenous aspirin (500mg) and clopidogrel (600mg), prasugrel (60mg) or ticagrelor (180mg) as standard practice in our Catheterization Laboratory. Intravenous heparin (70 UI/Kg body weight) was administered before the procedure with subsequent boluses aiming at achieving an activated clotting time (ACT) between 250 and 300sec. Manual thrombectomy was performed in all cases and the use of GP IIb/IIIa inhibitors was left to operator’s discretion. All lesions were finally treated with the study device implantation. The deferred PCI of the non-culprit lesion was routinely performed with the aforementioned standard techniques and the Orsiro stent previously deployed at the infarct related artery (IRA) was analyzed with the frequency domain optical coherence tomography (FD-OCT).

2.4

OCT acquisition

FD-OCT acquisitions were performed using the Ilumien system (St Jude, Minneapolis, MN, USA) with a motorized automatic pullback according with international guidelines . The OCT catheter was inserted distal to the treated segment and the pullback continued until either the guiding catheter was reached or the maximal pullback length (54 mm) was completed. Two sequential pull-backs were combined to enable assessment of the entire stented segment when required. OCT was used only during the deferred PCI, none of the stent analysed were implanted under OCT guidance.

2.5

OCT analysis

The OCT measurements were performed off-line using the LightLab Imaging workstation (LightLab St Jude, Minneapolis, MN, USA) by two blinded operators unaware of the timing of the stent implanted. Divergent opinions were resolved by consensus. Coverage and apposition of the stent struts were analysed with strut- and cross section-level. The analysis of contiguous cross-sections was performed at 1 mm intervals within the entire stented segment and on 5mm proximal and distal to the stent in order to identify edge dissections defined as a disruption of the vessel luminal surface at the stent edge with visible flap. Struts were considered suitable for analysis only in the presence of a bright signal-intense structure with perpendicular shadow. Number of struts was determined in each cross section analysed. Thickness of the tissue coverage on the luminal side of each strut was measured at the middle of the long axis of the strut. The inner and outer strut’s contours were delineated for each strut and its distance to the lumen contour was calculated automatically to determine strut level intimal thickness. Measured tissue thickness > 0 μm was defined as coverage. Neointimal hyperplasia was calculated as the average of thickness of the tissue coverage of the luminal side of each strut. Coverage and apposition of the stent struts were analysed with strut- and cross section-level . Struts were classified as malapposed if protruding into the lumen at a distance greater than the sum of the strut and polymer thickness (71 μm and 91 μm for the 2.25, 2.5 and 3.0 stent diameter and 3.5, 4.0 stent diameter respectively) plus the minimal axial OCT resolution (20 μm) Fig. 2 .

OCT cross-section images of strut coverage at 30-days (A), 90-days (B) and 180-days (C). Panel D shows two contiguous well struts apposed with the characteristic high backscattering provided by the metal surface representative of apposed and covered struts (white arrow). Please note in panel E and F two contiguous malapposed struts, one covered (*) while the second uncovered (**).

Each stent strut was classified as:

• 1)
  

  Apposed and covered: strut well apposed to the vessel wall with tissue coverage;

  
  
• 2)
  

  Apposed and uncovered: strut apposed to the vessel wall without tissue coverage;

  
  
• 3)
  

  Malapposed and covered: strut malapposed to the vessel wall with tissue coverage;

  
  
• 4)
  

  Malapposed and uncovered: strut malapposed to the vessel wall without tissue coverage.

Non-analyzable frames were defined as frames in which in which more than 45° of the lumen border was not visualized for the presence of side branches or for inadequate blood clearance during imaging acquisition. In these cases, the next following or preceding frame of appropriate image quality was used for the analysis.

2.6

Clinical follow up

In-hospital, 30 days, and cumulative 12 months major adverse cardiovascular events (MACE) were defined as death, myocardial infarction and repeat revascularization including coronary artery bypass graft (CABG) and/or PCI. Twelve-lead electrocardiograms were recorded before, immediately after each procedure and at hospital discharge.

2.7

Statistical analysis

Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as numbers with percentage. Continuous variables were compared using student’s t-test. Categorical variables were compared using chi-square test. A P value > 0.05 was considered statistically significant.

2.1

Study design and population

This prospective monocentric observational Registry enrolled only patients with ST elevation myocardial infarction (STEMI) and multi-vessel disease (MVD), thus eligible for a two-step procedure. The PCI of the culprit lesion was performed with at least one Orsiro stent. The second procedure was then deferred accordingly to the severity of the non-culprit lesion and the presence of symptoms and signs of residual ischemia to 30-days, 90-days and 180-days. During the second procedure, the stent deployed at the infarct-related site was analysed by OCT.

2.2

The Orsiro Sirolimus Eluting Stent

The Orsiro-DES is a cobalt-chromium stent with strut thickness 60 μm and 80 μm stent struts (the lowest for the stent with a diameter ranging from 2.25 to 3.0 while 80 μm thickness is for the 3.5 and 4.0 diameter stents), coated with a poly-L-lactide (PLLA) polymer that delivers sirolimus drug over 12–14 weeks and degrades over one to two years. It presents a unique thin-layer, amorphous silicon carbide coating (PROBIO) that reduces interaction between the metal stent and the surrounding tissue and blood by acting as a diffusion barrier aiming to improve the biocompatibility of the material by reducing thrombogenicity and encouraging re-endothelialisation.

2.3

Interventional Procedure

The PCI was routinely performed with the standard techniques via femoral or radial approach using 6 or 7 French guiding catheters. Patients not preloaded with oral aspirin and/or clopidogrel received a loading dose of intravenous aspirin (500mg) and clopidogrel (600mg), prasugrel (60mg) or ticagrelor (180mg) as standard practice in our Catheterization Laboratory. Intravenous heparin (70 UI/Kg body weight) was administered before the procedure with subsequent boluses aiming at achieving an activated clotting time (ACT) between 250 and 300sec. Manual thrombectomy was performed in all cases and the use of GP IIb/IIIa inhibitors was left to operator’s discretion. All lesions were finally treated with the study device implantation. The deferred PCI of the non-culprit lesion was routinely performed with the aforementioned standard techniques and the Orsiro stent previously deployed at the infarct related artery (IRA) was analyzed with the frequency domain optical coherence tomography (FD-OCT).

2.4

OCT acquisition

FD-OCT acquisitions were performed using the Ilumien system (St Jude, Minneapolis, MN, USA) with a motorized automatic pullback according with international guidelines . The OCT catheter was inserted distal to the treated segment and the pullback continued until either the guiding catheter was reached or the maximal pullback length (54 mm) was completed. Two sequential pull-backs were combined to enable assessment of the entire stented segment when required. OCT was used only during the deferred PCI, none of the stent analysed were implanted under OCT guidance.

2.5

OCT analysis

The OCT measurements were performed off-line using the LightLab Imaging workstation (LightLab St Jude, Minneapolis, MN, USA) by two blinded operators unaware of the timing of the stent implanted. Divergent opinions were resolved by consensus. Coverage and apposition of the stent struts were analysed with strut- and cross section-level. The analysis of contiguous cross-sections was performed at 1 mm intervals within the entire stented segment and on 5mm proximal and distal to the stent in order to identify edge dissections defined as a disruption of the vessel luminal surface at the stent edge with visible flap. Struts were considered suitable for analysis only in the presence of a bright signal-intense structure with perpendicular shadow. Number of struts was determined in each cross section analysed. Thickness of the tissue coverage on the luminal side of each strut was measured at the middle of the long axis of the strut. The inner and outer strut’s contours were delineated for each strut and its distance to the lumen contour was calculated automatically to determine strut level intimal thickness. Measured tissue thickness > 0 μm was defined as coverage. Neointimal hyperplasia was calculated as the average of thickness of the tissue coverage of the luminal side of each strut. Coverage and apposition of the stent struts were analysed with strut- and cross section-level . Struts were classified as malapposed if protruding into the lumen at a distance greater than the sum of the strut and polymer thickness (71 μm and 91 μm for the 2.25, 2.5 and 3.0 stent diameter and 3.5, 4.0 stent diameter respectively) plus the minimal axial OCT resolution (20 μm) Fig. 2 .

OCT cross-section images of strut coverage at 30-days (A), 90-days (B) and 180-days (C). Panel D shows two contiguous well struts apposed with the characteristic high backscattering provided by the metal surface representative of apposed and covered struts (white arrow). Please note in panel E and F two contiguous malapposed struts, one covered (*) while the second uncovered (**).

Each stent strut was classified as:

• 1)
  

  Apposed and covered: strut well apposed to the vessel wall with tissue coverage;

  
  
• 2)
  

  Apposed and uncovered: strut apposed to the vessel wall without tissue coverage;

  
  
• 3)
  

  Malapposed and covered: strut malapposed to the vessel wall with tissue coverage;

  
  
• 4)
  

  Malapposed and uncovered: strut malapposed to the vessel wall without tissue coverage.

Non-analyzable frames were defined as frames in which in which more than 45° of the lumen border was not visualized for the presence of side branches or for inadequate blood clearance during imaging acquisition. In these cases, the next following or preceding frame of appropriate image quality was used for the analysis.

2.6

Clinical follow up

In-hospital, 30 days, and cumulative 12 months major adverse cardiovascular events (MACE) were defined as death, myocardial infarction and repeat revascularization including coronary artery bypass graft (CABG) and/or PCI. Twelve-lead electrocardiograms were recorded before, immediately after each procedure and at hospital discharge.

2.7

Statistical analysis

Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as numbers with percentage. Continuous variables were compared using student’s t-test. Categorical variables were compared using chi-square test. A P value > 0.05 was considered statistically significant.