Prospective comparison of cardiac PET/CT, SPECT/CT perfusion imaging and CT coronary angiography with invasive coronary angiography

Coronary artery disease (CAD) is the leading cause of death in the western
industrialized world. An early and accurate diagnosis of CAD allows to initiate
adequate treatment in order to reduce morbidity and mortality. The gold
standard for the diagnosis of CAD is invasive coronary angiography (ICA), to
visualize a luminal stenosis of one of the major coronary artery branches, in
conjunction with fractional flow reserve (FFR) measurements, to evaluate the
potential hemodynamic significance of such a stenosis. Unfortunately, the
invasive nature if ICA and its associated complications such as bleeding,
cerebral vascular accidents due to embolization, cardiac arrhythmias, and even
death warrants the use of non-invasive techniques to accurate act as a
gate-keeper for catheterization-lab referral in order to reduce the number of
purely diagnostic ICAs. Single photon emission tomography (SPECT) with
99Tc-technetium labeled flow tracers is most frequently used to non-invasively
visualize regional flow impairment to detect flow limiting stenoses. Although
sensitivity of SPECT is fairly accurate (~85-90%), specificity is somewhat
hampered (~75-80%) due to attenuation artifacts.(3) Positron emission
tomography (PET), with routine correction of attenuation, significantly reduces
the number false positive scans by reducing attenuation artifacts. Moreover,
the greater spatial resolution of PET and its ability to express perfusion
quantitatively, significantly enhances sensitivity. PET, however, is currently
only used on a limited scale due to its high costs and technical demands
concerning the manufacturing and administration of PET perfusion tracers. In
recent years, however, both SPECT and PET systems have been fused with computed
tomography (CT). As the density map obtained with the CT equipment allows to
correct for tracer attenuation, SPECT/CT is expected to enhance its specificity
by reducing attenuation artifacts and may even approach the diagnostic accuracy
of PET. Data to substantiate this hypothesis are, however, lacking.
Furthermore, previous studies have demonstrated that infarctions may have an
impact not only on the perfusion in the infarct related territory, but also on
perfusion in non-infarct related vascular territories. The current study will,
therefore, determine the impact of chronic myocardial infarctions on PET and
SPECT perfusion imaging. The current myocardial perfusion imaging criteria for
ischemia are probably not appropriate for patients with a previous myocardial
infarction. Subsequently the diagnostic accuracy of myocardial perfusion
imaging in these specific patient population will be determined using invasive
coronary angiography and fractional flow reserve measurements as the reference
standard.

The aim of this study is to perform a head-to-head comparison between SPECT/CT
and PET/CT in comparison with conventional catheter-based coronary angiography
and FFR measurements, to establish the diagnostic value of the modern cardiac
myocardial perfusion scanners in patients with a previous myocardial
infarction.

Prospective single center trial

Benefits and risks assessment

Risk assessment:

Participants will be exposed to a total of 1.8 mSv for the entire PET protocol
(0.8 mSv for the entire PET session and 1.0 mSv for the attenuation correction
scans). SPECT/CT generates a radiation dose of 5 mSv, and conventional invasive
coronary angiography carries a radiation dose of 5 mSv.
In conclusion, participants will be exposed to a total radiation dose of
approximately 12 mSv, equaling maximal annually radiation dose of 20 mSv for
healthcare employees. By comparison, a single CT abdomen produces a radiation
dose of approximately 15 mSv.

To minimize the risk of contrast-induced nephropathy, glomerular filtration
rate must exceed 45 ml/min. Furthermore, metformin needs to be discontinued on
the day of the MRI scan and 48 hours after MRI in subjects with a glomerular
filtration rate beneath 60 ml/min in order to prevent metformin induced lactic
acidosis and contrast induced nephropathy.

Appropriate medication is present to abolish side-effects of contrast-agents
and adenosine.


Benefits:

- Patients receive additional information regarding the functional and
anatomical status of their hearts.
- Invasive coronary imaging and potential percutaneous coronary interventions
are facilitated by additional information obtained with myocardial perfusion
imaging.
- Lungs and part of the digestive tract will be evaluated for coincident
pathological findings with the use of MRI.