High and intermediate risk SPECT-CT optimization study

Both physician and patient will benefit from an imaging technique that provides
both anatomical and functional information of coronary artery disease,
preferably in a one stop, one shop, and non-invasive modality. Currently
invasive coronary angiography is the reference standard for evaluating the
anatomic severity and Single-Photon Emission Computed Tomography (SPECT) is the
current reference test for the assessment of the functional severity of
coronary artery disease. Multislice computed tomography coronary angiography
(MSCT-CA) has been proposed as non invasive imaging modality for anatomical
evaluation of patients with suspected CAD. With the 64-slice MSCT high positive
and negative predictive values for significant coronary artery stenosis have
been reported not only in native coronary arteries but also in coronary artery
bypass grafts. Fusion of MSCT-CA and SPECT images could lead to the
non-invasive imaging modality by which the anatomic and functional extend of
CAD is fully evaluated, without the risk of complications induced by the
invasive nature of routine coronary angiography.
Allthough a recent multicenter and multivendor 64-slice MSCT-CA study states
that its value lies mainly in ruling out significant CAD; it lacks a sufficient
positive predictive value to relieably demonstrate obstrictive coronary artery
disease.
Fusion of MSCT-CA and SPECT images could lead to the non-invasive imaging
modality by which the anatomic and functional extend of CAD is fully evaluated,
without the risk of complications induced by the invasive nature of routine
coronary angiography.

The primary objective is to compare whether results from fusion imaging of
MSCT-CA and myocardial perfusion SPECT lead to similar or different therapeutic
choices as compared to results from myocardial perfusion SPECT and invasive
coronary angiography in patients with known CAD and recurrent angina or with an
intermediate to high pretest likelihood of CAD.

Secondary objectives are:
1. Comparing the performance of the MSCT-CA and SPECT scan images in diagnosing
hemodynamically significant coronary artery disease versus invasive coronary
angiography and SPECT.
2. The additive value of fusion images of the MSCT-CA and SPECT by direct
overlay technique will be evaluated for their incremental value in diagnosing
hemodynamically significant coronary artery disease versus separate MSCT-CA and
SPECT images.

The study is designed as a single centre cross-sectional cohort study. A series
of 400 patients, with known CAD and recurrent angina or an intermediate to high
pre-test likelihood of CAD, will be included. Patients with a history of
percutaneous coronary intervention (PCI) or coronary bypass grafting (CABG)
will be included in the trial. All patients will be recruited in our outpatient
clinic. After informed consent has been obtained, all patients included in the
study will undergo a systematic diagnostic work-up which includes MSCT-SPECT
imaging and coronary angiography. On the first day SPECT images will be
obtained after physiological or pharmacological stress directly followed by an
MSCT-CA scan. An abnormal perfusion pattern, showing a defect in at least a
single segment, after stress will lead to a rest SPECT scan on the second day
of imaging. A normal perfusion pattern after stress SPECT imaging will exclude
the subject from further SPECT imaging. On the second day of imaging a rest
SPECT scan will be performed if perfusion defects were visualized by the stress
SPECT images. This will be followed by a standard coronary angiogram using
fractional flow reserve (FFR) to determine the functional severity of an
intermediate coronary stenosis. All imaging procedures will be performed within
a period of two weeks. Afterwards the treatment plan is routinely discussed in
the so-called *heart-team* meeting between a thoracic surgeon and a
cardiologist, and actual medical or revascularization therapy is carried out.
After one year follow up data will be collected on medication use, ischemic
cardiac events, presence of heart failure symptoms, cardiac arrhythmias,
revascularization procedures, hospitalization, device therapy (f.i. pacemakers)
and survival.
The relevance of the diagnostic process using MSCT-SPECT imaging as the sole
modality will be evaluated through comparing the therapeutic modalities chosen
by a panel of cardiologists, a thoracic surgeon, a radiologist and a nuclear
medicine physician. In three sessions the panel will evaluate three different
data sets, one including SPECT and CAG data, one including MSCT-SPECT data and
one including all imaging data. Additional panel sessions will be scheduled,
with the addition of 1-year follow up data to the decision-making process, when
the first panel sessions lead to a significant difference in the given
therapeutic advice.

By performing an extra Multislice CT Angiography the sudy subjects will be
exposed to an extra radiation dose of approximately 10 MSv.
Also, in this protocol the sudy subjects will be exposed to iodide containing
contrast agents. The use of these agents bares a small risk of a
hypersensibility reaction or contrast induced renal insufficiency.
These risk are additive to the risks that the subjects are exposed to during
the routine diagnostic evaluation; the invasive coronary angiogram and the
SPECT scan.