Vascular Evaluation for Revascularization: Defining the Indications for Coronary Therapy: A Pilot Study
Vascular Evaluation for Revascularization: Defining the Indications for Coronary Therapy: A Pilot Study
The present prospective, multicenter study will therefore be performed with the primary
 objective of establishing the correlation between fractional flow reserve (FFR) and
 intravascular ultrasound with virtual histology (VH-IVUS)-derived parameters in
 angiographically intermediate coronary lesions. The current study will also examine the
 relative prognostic utility of FFR and VH-IVUS as a tool to defer percutaneous coronary
 intervention (PCI), by assessing the long-term rate (up to 3 years) of lesion-related
 clinical events if deferred by FFR vs. VH-IVUS versus not deferred PCI.
Patient-specific inclusion criteria:

 1. Clinical presentation: stable angina, unstable angina, non-ST segment-elevation
 myocardial infarction (NSTEMI) (Braunwald classification of unstable angina, see
 Attachment 2) or recent STEMI (>48 hours before enrollment).

 2. Patient is scheduled for coronary catheterization with or without percutaneous
 coronary intervention.

 3. Age ≥18 years.

 4. Patient is able to read, understand, and sign the informed consent document.

 5. Patient agrees to all protocol related procedures, including follow-up through 3
 years.

 Lesion-specific inclusion criteria:

 1. The patient has at least one intermediate coronary lesion to be assessed by FFR and
 VH-IVUS, defined as a lesion with a visually-estimated diameter stenosis ≥40% to <80%
 with a visually-estimated angiographic reference segment diameter of 2.75 mm - 4.0 mm.

 2. There may only be one study lesion in the major epicardial coronary artery or its
 branches. All other stenosis in this epicardial coronary artery or its branches must
 be <40% by visual angiographic assessment. E.g.., if the lesion is in the Left
 Anterior Descending(LAD), there may be no other significant lesions (≥40%) in the LAD,
 septals or diagonal branches. A single lesion may have normal or nearly normal
 appearing segments within the lesion as long as it is contained within one CASS
 segment. Moreover, a single lesion may span two or more CASS segments as long as there
 is no normal or nearly normal appearing segments >5mm in length within the lesion.
 However, if a diseased lesion extends across two or more CASS segments and has one or
 more >5 mm lengths of normal or nearly normal appearing segments within the lesion,
 then it is considered 2 separate lesions, and may not be enrolled.

 3. More than 1 intermediate lesion per patient may be enrolled, as long as each lesion
 meets the entry criteria as a study lesion (e.g. one intermediate lesion in 1, 2 or 3
 unique epicardial coronary arteries (LAD vs. LCX vs. RCA), with FFR and VH-IVUS
 performed in each vessel. Thus, up to 3 lesions may be enrolled per patient (one in
 each major epicardial coronary artery).

 4. PCI of any lesion in the target vessel (the main epicardial coronary artery or any of
 its branches) may not have been performed in the preceding 1 year (including during
 the index procedure) and may not be planned within the next 1 year.

 5. Patients undergoing PCI of non-study lesions in non-study target vessels during the
 index procedure may be enrolled if one or more qualifying intermediate lesion is
 otherwise present in a different epicardial vessel, but PCI of all non-study lesions
 must be performed first (including staged procedures) and must be successful and
 uncomplicated before formal enrollment into this study. The PCI cannot occur in the
 epicardial coronary artery or its branches containing the intermediate lesion.

 -  Successful PCI is defined as residual diameter stenosis of <50% in all treated
 lesions with Thrombolysis in Myocardial Infarction (TIMI) -3 flow in all treated
 vessels.

 -  Uncomplicated PCI is defined as the absence of intra-procedural chest pain or
 ST-segment changes lasting >10 minutes, sustained vessel closure, slow or no
 reflow, side branch loss, distal embolization, perforation, residual dissection
 (>type B), or requirement for cardiopulmonary resuscitation, cardioversion or
 defibrillation, pacemaker insertion, intubation, intra-aortic balloon insertion
 or intravenous pressors.

 Patient-specific exclusion criteria:

 1. Prior CABG at any time.

 2. The patient is likely to undergo PCI, CABG or other cardiac surgical procedure within
 1 year of the procedure.

 3. ST-segment elevation myocardial infarction within 48 hours of the procedure.

 4. Cardiogenic shock defined as systolic blood pressure <90 mmHg lasting >30 minutes, not
 responding to intravenous fluids, and/or requiring intravenous pressors or an
 intra-aortic balloon pump or other hemodynamic support device.

 5. Heart failure as defined by New York Heart Association class III or IV (see Attachment
 2).

 6. Respiratory failure requiring intubation or supplementary oxygen.

 7. Left ventricular ejection fraction <30% as determined by 2D echo, nuclear testing,
 magnetic resonance imaging (MRI), or left ventriculography.

 8. Any moderate or severe cardiac valve disease.

 9. Cerebrovascular accident or transient ischemic attack (TIA) within the past 60 days,
 or any permanent neurologic deficit.

 10. Chronic renal insufficiency (serum creatinine > 2.5mg/dl).

 11. History of drug abuse or alcohol abuse or any other condition making it unlikely that
 the patient will comply with all study procedures, including follow-up for 3 years

 12. Any condition with expected survival <2 years.

 13. Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year
 following the index procedure. Female patients of child-bearing potential must have a
 negative pregnancy test done within 7 days prior to the index procedure.

 14. Patients currently participating in another study of an investigational drug or device
 which has not yet reached its primary endpoint.

 15. Oral intake by the patient of any caffeinated beverage within 4 hours of the procedure

 16. Use within 12 hours of theophylline, aminophylline or any xanthine derivative.

 Lesion-specific exclusion criteria:

 1. An unprotected left main coronary stenosis is present (visually assessed %DS ≥40%,
 whether or not requiring treatment). The study lesion cannot be a left main lesion.

 2. The intermediate lesion is in a vessel with thrombus, moderate or severe
 calcification, angulation, or tortuosity. PCI may be performed in such non target
 vessels or lesions prior to study enrollment, however, as long as successful and
 uncomplicated, after which the patient is enrolled in the study.

 3. The study lesion is an ostial lesion (within 5 mm of the aorta or the distal left main
 coronary artery) or is bifurcation lesion requiring planned dual stenting.