Side Branch FFR After Provisional Stenting

Coronary artery bifurcation lesion is a common lesion subset in PCI accounting for 15-20% of
the total number of interventions. Treatment of coronary artery bifurcation lesions
represents a challenging area in interventional cardiology. When compared with
non-bifurcation interventions, bifurcation interventions have a lower rate of procedural
success, higher procedural costs, longer hospitalization and a higher clinical and
angiographic restenosis. Factors contributing to this adverse outcome include limitations of
angiography in assessment of side-branch (SB) disease severity and the lack of established
angiographic predictors of SB patency and lumen compromise. Better understanding of the
underlying plaque morphology and plaque composition may facilitate more effective treatment
of bifurcation lesions.

Intravascular imaging has provided new understanding of mechanisms associated with SB
compromise following bifurcation PCI. Plaque shift has been traditionally considered as the
principal mechanism for side-branch compromise after main vessel intervention. Rotational
atherectomy(RA) has been advocated for the treatment of bifurcation lesions, since it can
effectively remove plaque with minimal injury to adjacent normal arterial segments and
potentially reduce plaque shifting, the "snow plow" effect. Intravascular ultrasound (IVUS)
has been used for guidance in bifurcation lesions, aiding the visualization of plaque
morphology at the main vessel and the side-branches and helping the selection of stent size
and length as well as the selection of stenting strategy. However, due to the low spatial
resolution of IVUS, all attempts for three-dimensional visualization have only focused on
visualization of the luminal contour and not on the vessel morphology or the vessel-stent
interaction. Optical coherence tomography (OCT) has ~10 times higher resolution than IVUS,
which allows precise evaluation of the microstructure of the vessel wall including lipid
pool, fibrous cap, calcification, and thrombus. OCT has been shown to constitute a valuable
tool for PCI guidance and also the utility of three-dimensional (3D) renderings for assessing
the mechanism of side-branch compromise following intervention in bifurcation lesions. The
recent development of OCT with online 3D reconstruction allows the operator to obtain a 3D
visualization of the lesion and may provide a unique tool for guidance during complex
bifurcation PCI and potentially improve stenting results. 3D OCT has been used to visualize
jailed side branches after implantation of bioresorbable scaffolds in the main branch and
develop a new classification system based on the number of SB compartments. In addition, its
potential clinical application in guiding the rewiring of the distal compartment of the SB
ostium (jailed with stent struts after MB stenting) to minimize the risk of floating struts
was demonstrated It is important to note that while OCT, 3D-OCT, and 3D-QCA (such as that
used in the ORBID trial) are imaging modalities that can be used to answer important research
questions, their wide-spread adoption in daily clinical practice has been very limited.
Intravascular ultrasound (IVUS) is used more frequently as part of a PCI guidance strategy in
daily clinical practice.

Fractional flow reserve (FFR) is a pressure-derived, lesion specific index used to determine
the functional significance of coronary artery stenosis. Several studies showed that FFR is a
safe and feasible method to assess the significance of an ostial SB stenosis after
provisional stenting. Quantitative coronary angiography (QCA) has been shown to be unreliable
in assessing the functional significance of SB after stent implantation in MV (the area under
the curve 0.64, 41.5% sensitivity and 83.1% specificity) suggesting that treatment decisions
for jailed SB should not be based on angiographic findings alone. A recent report
demonstrated a better ability of post-PCI 3D-OCT to predict the functional significance for
SB ostial lesions caused by a jailed SB outcome.

A previous study (ORBID) of 30 patients was done at Mount Sinai Hospital and aimed to
identify the predictors of side branch (SB) ostial stenosis developed after provisional
stenting of the main vessel (MV) using Optical Coherence Tomography (OCT). The study Showed
that High lipid content of the MV lesion and a contralateral location of lipid in the
bifurcation area may contribute to SBOS after provisional stenting.

The objective of this study is to analyze the incidence of SB compromise after provisional
main vessel stenting in calcified bifurcation lesions of CAD patients, determine the
incidence and OCT predictors of functionally significant SB stenosis defined as FFR ≤ 0.8 and
to compare the FFR values with 3D-OCT measurements of jailed SB ostium after MV stenting.

Stable CAD patients with bifurcation lesions in whom provisional stenting strategy is
planned, who have moderate or severe calcification in the main vessel lesion identified by
angiography, SB stenosis 30-70% and SB reference diameter > 2mm will be enrolled in the
study.

Moderate calcification will be defined as radiopaque density observed only during the cardiac
cycle and typically involving only one side of the vascular wall, and severe calcification
will be defined as radiopaque density noted without cardiac motion prior to contrast
injection and involving both sides of the arterial wall. After completion of diagnostic
angiogram and confirmation of subject eligibility, subjects will be randomly assigned to
Rotational Atherectomy (RA) or Cutting Balloon Angioplasty (CBA)/Percutaneous Transluminal
Coronary Angioplasty (PTCA) group in a 1:1 fashion.

Patients in both groups will undergo PCI with stent implantation according to current
standards of care. Lesion preparation including lesion pre-dilation, scoring or sculpting
balloon angioplasty, and use of atherectomy and protection devices will be performed at the
operator's discretion, followed by MV stenting. The operator will also decide in both groups
about the length and size of the implanted stent. Procedural optimization, such as
post-dilation or additional stent implantation will be performed based only on the
angiographic findings, according to the discretion of the operator.

Inclusion Criteria:

- All patients over 18 years of age presenting with stable coronary artery disease.

- Patients must have a clinical indication for coronary intervention.

- Creatinine Kinase Myocardial-Band Isoenzyme (CK-MB) must be less than or equal to the
upper limit of lab normal (ULN) value within eight hours prior to the procedure.

- The target lesion must be a de novo calcified bifurcation coronary lesion that hasn't
been previously treated with any interventional procedure for which provisional main
vessel stenting strategy is planned after reviewing angiogram.

- The target vessel must be a native coronary artery with

1. stenosis ≥70% and <100%, or

2. Stenosis ≥50% and <70% with evidence of clinical ischemia via positive stress
test, or FFR ≤ 0.8, or IVUS or OCT minimal lumen area ≤ 4.0 mm2.

- The target lesion should have SB DS 30 - 70%.

- The target main vessel reference diameter must be ≥2.5 mm and ≤ 4.0 mm.

- The SB reference diameter must be > 2 mm by coronary angiogram.

- The target vessel must have a Thrombolysis in Myocardial Infarction (TIMI) flow grade
3 at baseline.

Exclusion Criteria:

- Patients with ostial left main artery lesions or ostial right coronary artery lesions

- Female patients with child bearing potential not taking adequate contraceptives or
currently breastfeeding

- Known allergy to acetylsalicylic acid or clopidogrel.

- Planned surgery within 12 months.

- History of bleeding diathesis

- Major surgery within 15 days

- Life expectancy < 12 months.

- Patients with kidney dysfunction (CrCl<30)