Although atherosclerosis is a systemic disease, its manifestations are focal and eccentric,
and each coronary obstruction progresses, regresses, or remains quiescent in an independent
manner. The focal and independent nature of atherosclerosis cannot be due solely to the
presence of systemic risk factors such as hyperlipidemia, diabetes mellitus, cigarette
smoking, and hypertension. Local factors that create a unique local environment are a major
determinant of the behavior of atherosclerosis in a susceptible individual.
The vascular endothelium is in a unique and pivotal position to respond to the extremely
dynamic forces acting on the vessel wall due to the complex 3-D geometry of the artery.
Mechanical forces in general, and fluid shear stress (endothelial shear stress [ESS]) in
particular, elicit a large number of humoral, metabolic and structural responses in
Regions of disturbed flow, with low and oscillatory ESS (< 1.0 Pa), are intensely
pro-atherogenic, pro-inflammatory, and pro-thrombotic, and correlate well with the
localization of atherosclerotic lesions. These sites demonstrate intense accumulation of
lipids, inflammatory cells, and matrix degrading enzymes which promote the formation of
high-risk thin-cap fibroatheroma.
In contrast, physiologic laminar flow (1.0-2.5 Pa) is generally vasoprotective. However, as
the obstruction progresses and further limits blood flow through a narrowed lumen, flow
velocity and ESS may increase excessively (> 2.5 Pa) at the neck, and decrease abnormally at
the outlet, increasing the likelihood of platelet activation and thrombus formation.
Identification of an early atherosclerotic plaque likely to progress and acquire
characteristics leading to likelihood of rupture and, consequently, to precipitate an acute
coronary event or rapid luminal obstruction, would permit more definitive pharmacologic or
perhaps mechanical intervention prior to the occurrence of a cardiac event. The potential
clinical value of identifying and "eradicating" plaques destined to become vulnerable before
they actually become vulnerable is enormous.
The purpose of the PREDICTION Trial is to identify high-risk coronary lesions at an early
time point in their evolution, to follow the natural history of these lesions over a 6-10
month period, and to confirm that these high-risk lesions are likely to rupture and cause an
acute coronary syndrome (ACS) or develop rapid progression of a flow-limiting obstruction.
The hypothesis is that local segments in the coronary arteries with low ESS and excessive
expansive remodeling will be the sites where atherosclerotic plaque develops, progresses, and
becomes high-risk, leading to a new cardiac event. This study is being conducted in Japan as
patients are clinically evaluated with followup coronary angiography and IVUS in a routine
manner at 6-10 months following their initial percutaneous coronary intervention (PCI) for an
This is a natural history and a clinical outcomes study in patients who initially present
with an ACS. The natural history portion of the study is designed to describe the temporal
progression of atherosclerosis in segments of coronary arteries with low ESS and expansive
remodeling using intracoronary vascular profiling techniques utilizing intravascular
ultrasound (IVUS) and coronary angiography. The clinical outcomes portion of the study is
designed to evaluate the efficacy of coronary vascular profiling to predict segments of
coronary arteries that will become areas of rapid plaque growth or rupture leading to
recurrent major clinical coronary events.
Five hundred (500) patients with acute coronary syndrome undergoing PCI for a culprit lesion
are to be enrolled in the study to undergo coronary vascular profiling at the time of the
index catheterization procedure. Up to 374 consecutive patients with at least one low ESS
subsegment are to have follow-up coronary angiography and IVUS at 6-10 months to allow for at
least 300 patients with analyzable intracoronary vascular profiling data for assessment of
lesion natural history. All patients are to have a one-year clinical follow-up to assess for
new cardiac events, followed by two additional years of extended clinical followup.