Fractional flow reserve calculation from 3D quantitative coronary angiography and TIMI frame count

Assessment of stenosis severity by invasive coronary angiography (ICA) is
important regarding the need for coronary revascularisation: percutaneous
coronary intervention (PCI) or coronary artery bypass graft (CABG). Currently,
in patients with stable coronary artery disease (CAD), the guidelines recommend
to re-vascularise only in hemodynamic significant lesions. Visual estimation of
stenosis severity frequently fails to accurately identify the ischemic
potential of a lesion. Fractional flow reserve (FFR) is nowadays the golden
standard to assess whether a lesion is hemodynamically significant. FFR is
defined as the ratio of maximal blood flow in a stenotic artery to normal
maximal flow. It is measured during ICA by mean of a coronary pressure-wire
that measures the pressure distal of a stenosis. A FFR value of 0.8 or less is
considered hemodynamically significant. FFR-guided revascularisation is
associated with favourable clinical outcome. Despite the clinical benefits, the
employment of FFR has been slow, possibly due to high cost and extra procedure
time of the operation. Recently, a new technique that can accurately and
rapidly calculate FFR without the need for an intra-coronary pressure wire has
been developed. This technique is based on calculations from 3D quantitative
coronary angiography (QCA) and TIMI (thrombolysis in myocardial infarction)
frame count. One previous pilot study demonstrated good correlation and
agreement of the calculated FFR with conventional pressure-wire FFR. The
technique is called QCA-FFR. It provides a facilitation in measuring FFR and
has therefore great potential to enlarge the applicability of FFR.
The Leiden University Medical Center (LUMC) measures FFR on daily basis by the
judgement of the interventional cardiologist. This project will provide more
insight into the feasibility and diagnostic value of QCA-FFR in our center and
would certainly position the LUMC as a pioneer center in this technique.

Primary Objective:
The primary objective is to assess the feasibility of QCA-FFR in our centre.

Secondary Objective:
To assess the correlation and agreement of QCA-FFR with conventional
pressure-wire based FFR. The pressure-wire derived FFR will serve as a
reference standard when assessing the value of QCA-FFR.

If the primary and secondary objective appear a success, this pilot-study will
serve as a start up for a larger study.

Study subjects are patients who are referred for diagnostic ICA and in who the
interventional cardiologist decides to perform invasive FFR measurement to
decide to perform PCI yes or no. The subjects in which no conventional
pressure-wire FFR is performed will be excluded. The clinical diagnostic path
will not be interfered by this study, because the invasive FFR will be used in
the decision making process and the decision to perform FFR measurement is
based on clinical grounds.

During regular diagnostic ICA, multiple orientating angiographic projections
from different angles are made to assess the patency of all coronary arteries.
For QCA-FFR, two angiographic projections with > 25 º between them are needed
from the vessel of interest. These projections will be obtained from the
clinically indicated orientating projections.
During pressure-wire FFR measurement, first, adenosine is infused
(intravenously or intracoronary,140 ug/kg/min) to induce maximal coronary blood
flow. When steady-state hyperemia is achieved, the FFR is calculated by mean of
a intracoronary pressure-wire distal to the stenosis. For QCA-FFR, during
steady-state hyperemia, one extra contrast enhanced projection is needed to
obtain the required data to calculate QCA-FFR.

Post-processing of the obtained data will be done with validated software
(QAngio XA 3D research edition 1.0, Medis Special BV, Leiden, the Netherlands),
which is available in the LUMC. Calculation of the QCA-FFR will be done by an
independent observer blinded for the pressure-wire FFR.

The subjects will be exposed to a small extra amount of radiation and contrast
agent. The additional radioation will be estimated at 0.69 mSv, equal to seven
2-sided chest x-rays. Only subjects with good renal function will be included
to minimize the risk for contrast induced nephropathy.