Comparison of Cardiac Imaging Techniques for Diagnosing Coronary Artery Disease
Comparison of Cardiac Imaging Techniques for Diagnosing Coronary Artery Disease
A large number of cardiac catheterizations are performed each year, primarily to diagnose
 heart disease. However, a cardiac catheterization is an invasive procedure which is
 associated with serious complications such as heart infarction, stroke, and death. Therefore,
 there is a need for non-invasive procedures to diagnose coronary heart disease. The purpose
 of this study is, therefore, to assess the diagnostic accuracy of non-invasive cardiac
 imaging modalities for the detection of heart disease in patients presenting for the first
 time to the cardiologist with chest pain.
Coronary artery disease (CAD) remains the leading cause of morbidity and mortality in Western
 civilized countries. Early detection of CAD allows optimal therapeutic management in order to
 decrease morbidity and mortality. In the Netherlands 80,000 invasive coronary angiographies
 are performed each year. Invasive coronary angiography (ICA), particularly in conjunction
 with fractional flow reserve (FFR) measurements, is considered the gold standard in
 diagnosing and evaluating the severity of CAD in the current era. FFR measurements during ICA
 are useful in determining whether a coronary stenosis is functionally important. An FFR <
 0.80 is considered abnormal, reflecting a hemodynamic significant coronary stenosis. ICA has
 superior spatial and temporal resolution compared with non-invasive imaging techniques.
 However, ICA is an invasive procedure which is associated with a low, though significant,
 complication rate including bleeding, coronary artery dissections, cerebral embolism, cardiac
 arrhythmias, myocardial infarction and death. Moreover, ICA provides only limited information
 on the presence of atherosclerotic plaques not associated with luminal stenosis. Furthermore,
 conventional catheter angiography without the advent of FFR measurements, is not able to
 provide information about the hemodynamic significance of a significant luminal stenosis (≥
 70%), i.e. whether a coronary artery stenosis is leading to myocardial perfusion
 abnormalities. Therefore, there is a need for non-invasive imaging techniques for diagnosing
 and evaluating the hemodynamic significance of CAD. Non-invasive techniques can serve as a
 gatekeeper for invasive coronary angiographies in order to decrease the number of purely
 diagnostic invasive angiographies and associated morbidity and mortality. The detection and
 management of cardiovascular disease increasingly utilize non-invasive cardiac imaging in
 patients with suspected or known CAD. By more accurately identifying patients who are
 eligible for coronary revascularization with the use of non-invasive cardiac imaging, the
 number of unnecessary invasive diagnostic coronary angiographies can be decreased.

 Study design

 Positron emission tomography:

 PET images will be acquired using a Gemini Time-of-Flight (TF) 64 scanner (Philips
 Healthcare, Best, The Netherlands). Quantitative myocardial perfusion at rest and during
 hyperemia in ml -1. min -1. g -1 of myocardial tissue will be measured using
 oxygen-15-labelled water (H215O). Pharmacological stress is induced by infusion of adenosine
 intravenously at a rate of 140 µg/kg/min. Two minutes after the start of adenosine
 vasodilation reaches a steady state and H215O will be given intravenously as a bolus followed
 with the start of a 6-minutes emission scan. Directly after the PET sequence, a low dose CT
 attenuation scan (CTAC) is acquired after which the infusion of adenosine is terminated.
 Technetium-99m sestamibi is injected intravenously after the second CTAC scan. A stress
 SPECT-scan is performed 45 minutes after the stress PET scan.

 Single photon emission computed tomography:

 SPECT imaging will be performed according to standard clinical protocols for myocardial
 perfusion imaging. All patients will undergo SPECT-imaging(Symbia T2, Siemens, The Hague, The
 Netherlands) on a during hyperaemia induced by infusion of adenosine at a rate of
 140mcg/kg/min, using a dose of 400 megabecquerel (MBq) of Technetium (99mTc) tetrofosmin.
 Tetrofosmin will be administered during adenosine induced stress during the time of the PET
 stress perfusion scan. Directly after the stress SPECT-sequence, a low dose CT-attenuation
 scan (CTAC) will be performed. A SPECT- rest imaging scan will be performed 72 hours after
 the stress SPECT scan on the day of the catheterization.

 Computed tomography:

 Patients will undergo a coronary calcium score (CTCAC) and CT coronary angiography scan on a
 256-slice CT scanner (Philips Brilliance iCT, Philips Healthcare, Best, the Netherlands).
 Prospective ECG-gating (Step & Shoot Cardiac, Philips Healthcare, Best, The Netherlands) at
 75 % of the R-R interval will be performed in order to minimize radiation burden.

 Invasive coronary angiography:

 ICA will be performed via a transfemoral of transradial approach according to the standard
 procedure. Iodized contrast will be given intracoronary during the procedure to evaluate the
 coronary artery lumen. The operator and an interventional cardiologist blinded to the
 findings obtained with non-invasive imaging will evaluate the ICA images. ICA imaging will be
 performed with a biplane or monoplane cardiovascular X-ray system (Allura Xper FD 10/10,
 Philips Healthcare, Best, The Netherlands) in at least two orthogonal directions. After
 primary coronary angiography, FFR will be measured in all coronary arteries, using a
 0.014-inch sensor tipped guide wire. A stenosis with a FFR < 0.80 will be considered as a
 hemodynamic significant stenosis. Clinical decision making will be based on the findings
 obtained with ICA and FFR measurements and will be made by the interventional cardiologist.
Inclusion Criteria:

 -  First presentation to cardiologist with suspected coronary artery disease

 -  No documented prior history of coronary artery disease

 -  Intermediate pre-test likelihood for coronary artery disease as defined by Diamond and
 Forrester criteria

 -  Clinically referred for invasive coronary angiography

 -  Age above 40 years

 Exclusion Criteria:

 -  History of severe chronic obstructive pulmonary disease (COPD) or chronic asthma

 -  Pregnancy

 -  Renal failure ( i.e. estimated glomerular filtration rate < 45 mL/min)

 -  Use of sildenafil (Viagra) or dipyridamole (Persantin) that can not be terminated.

 -  Contra-indications for β-blockers

 -  Allergic reaction to iodized contrast

 -  Concurrent or prior (within last 30 days) participation in other research studies
 using investigational drugs

 -  Claustrophobia

 -  Significant co-morbidities

 -  Atrial fibrillation, second or third degree atrioventricular block

 -  Tachycardia

 -  Acute myocardial infarction

 -  Heart failure

 -  Left ventricle ejection fraction estimated < 50%

 -  Cardiomyopathies

 -  Previous radiation exposure in the diagnostic work-up

 -  Subjects intended for short-term medical treatment or an invasive coronary
 intervention

 -  No informed consent