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CATSCAN (coronary assessment by
CT scanning and catheter angiography):
Protocol of a multi-center trial
M. Garcia * Cleveland Clinic Foundation, Cleveland OH, USA.
M. Hoffmann * University of Ulm Hospital, Ulm, Germany.
J. Lessick * Philips Medical Systems, Cleveland OH, USA.
* on behalf of the CATSCAN investigators
This article presents the protocol of the be an appropriate screening tool for specific
CATSCAN multi-center trial, which has been patient populations scheduled for CA.
implemented with the object of assessing the
effectiveness of computed tomography (CT) in Background
The CATSCAN multi- evaluating coronary artery disease. Recent
center trial is intended to advances in CT technology have provided the In 1958, Mason Sones pioneered direct
assess the effectiveness of ability to acquire high resolution, diagnostic visualization of the coronary arteries, creating a
CT in evaluating coronary quality images of the coronary arteries. We new paradigm in the practice of medicine.
artery diease. therefore propose to establish the clinical utility Direct visualization of the coronary arteries by
of cardiac CT through a prospective, blinded invasive catheterization still represents the
comparison study with diagnostic conventional cornerstone of the evaluation of coronary artery
angiography (CA). disease. Since the early days, technical advances
have resulted in a steady decline in complications
Patient criteria related to this procedure. However, high cost and
The subjects will be drawn from patients with the technical skills required limit the widespread
suspected coronary artery disease scheduled for use of this procedure for evaluating the coronary
conventional angiography, observing the inclusion anatomy in the majority of the population at risk.
and exclusion criteria and following full written Furthermore, fluoroscopic coronary angiography
consent by the patients. In this study, 234 patients can only evaluate luminal irregularities, and cannot
will be prospectively enrolled from 11 medical provide accurate characterization of the plaque
centers worldwide. Each patient will receive a composition in the vessel wall, which may be a
cardiac CT examination within 1 to 14 days prior more important factor in predicting the risk of
to the conventional angiography examination. future development of acute coronary syndromes.
Anticipated outcome In clinical practice, exercise or pharmacologic
It is expected that CT will prove to be a useful stress testing with electrocardiographic,
tool for the evaluation of coronary artery disease. echocardiographic or scintigraphic perfusion
With the establishment of a high negative imaging are often performed in patients with
predictive value and good sensitivity, CT could known or suspected coronary artery disease.
Author Journal Year Modality # Pts Non-Acc Sens Spec PPV NPV
Table 1. Summary of published
Achenbach2 NEJM 1998 EBCT 125 25% 92% 94% 78% 98%
articles.
Kim 1
NEJM 2001 MRI 109 16% 93% 42% 70% 81%
Nieman4 Lancet 2001 CT – 4 35 27% 83% 90% 81% 97%
Achenbach 5
Circ 2001 CT – 4 64 32% 85% 76% 59% 98%
Knez6 AJC 2001 CT – 4 44 6% 78% 98% 85% 96%
Becker 7
JCAT 2002 CT – 4 28 5% 81% 90% 97% 89%
Nieman8 Circ 2002 CT – 12 59 0% 95% 86% 80% 97%
Ropers 9
Circ 2003 CT – 12 77 12% 92% 93% 79% 97%
Mollet10 JACC 2004 CT – 16 128 7% 92% 95% 79% 98%
Hoffmann 11
Lancet subm CT – 16 103 7% 96% 84% 89% 95%
30 MEDICAMUNDI 48/3 2004/11
Although these tests are clinically useful and carry abnormal segments analyzed raises questions
important prognostic value, their diagnostic about the positive predictive ability.
yield is limited to those patients with more
advanced and obstructive disease. Moreover, a Ropers et al. [9] reported sensitivity and specificity
significant number of patients undergoing stress of 79% and 97%, respectively, for detecting >
testing present false positive or false negative 50% stenosis in vessels > 1.5 mm in diameter.
results. However, in their series, 12% of the arterial
segments were excluded from analysis after having
From the literature (Table 1), it appears that been deemed non-accessible.
Magnetic Resonance Imaging (MRI), Electron
Beam Computed Tomography (EBCT) and Mollet et al. [10] and Hoffmann et al. [11] have
Multi-Detector Computed Tomography (MDCT) recently presented independent prospective
scanning are the only imaging modalities that evaluations of lesion detection using 16-slice
have been shown to be capable of non-invasive MDCT scanners. All of these studies suggest that
imaging of the coronary arterial tree. A multi- CT may be an appropriate technique for accessing
center trial published by Kim et al. [1] using MRI patients suspected of having coronary artery disease.
showed promising results. However, this technique
Modern MDCT
remains limited by the complex protocols, Recent advances in retrospective gating protocols
scanners can provide
lengthy acquisitions, inadequate accessibility jointly developed by Philips, the Cleveland
noninvasive
and high cost. Clinic Foundation and the Munich-Pasing Clinic
information on the
[12], together with the use of controlled
coronary lumen and
With the use of ECG-gating, both EBCT and pharmacologic heart-rate modulation, have been
plaque morphology.
MDCT have been shown to provide adequate shown to improve image quality and may further
visualization of the coronary arteries. EBCT can reduce the number of non-accessible arteries.
provide cross-sectional images with excellent
temporal resolution, although it has limited While these results are encouraging, they reflect
spatial resolution in the vertical plane and relatively the experience of individual investigators at their
low signal-to-noise characteristics [2]. The high own centers. Furthermore, they lack rigorous
cost and few clinical applications of current evaluation by off-site blinded analysis and
EBCT systems limit the widespread use of this assessment of interobserver agreement.
technology.
To date, no multi-center trials have been published
Since MDCT has a broad range of applications, comparing coronary computed tomography (CT)
from vascular imaging to soft tissue, bone and imaging with conventional angiography (CA) for
internal organs, it has become widely available in the detection of coronary artery stenoses.
emergency rooms, hospital radiology Additionally, the literature fails to exploit the
departments and outpatient imaging centers. ability of CT to quantify stenosis severity.
Recent advances in MDCT technology have Furthermore, no standardized protocol for
made it possible to acquire ECG-gated, sub- coronary CT angiography exists; rather, individual
millimeter isotropic 3D cardiac datasets with a investigators and institutions have developed their
temporal resolution between 53 and 210 ms, own unique protocols. We therefore proposed
within a single breath-hold (as low as 14 seconds) to establish a common coronary CT angiography
[3]. Modern MDCT scanners can provide protocol, and have designed a large-scale study
information, non-invasively, on the coronary to test its clinical utility in comparison with
lumen and plaque morphology. conventional angiography.
Several studies have compared 4-slice MDCT The CATSCAN multi-center trial
scanners to CA [4-7]. These relatively small The CATSCAN study
studies have consistent results with respect to the Study objectives will compare multi-
negative predictive value (average = 95%). The CATSCAN study (Coronary Assessment by slice CT and coronary
However, the percentage of non-accessible Computed Tomographic Scanning and Catheter angiography in the
segments ranged from 5% to 32%. More recent Angiography) is a multi-center, blinded trial detection of stenoses.
studies have been published using 12- and 16- designed to compare the ability of multislice CT
slice MDCT. and diagnostic coronary angiography to detect
arterial stenoses. A total of 234 patients will be
Nieman et al. [8] published their initial results prospectively enrolled from 11 different recruiting
in 59 patients in 2002. Their reported 97% centers worldwide (Table 2). Each center is
negative predictive value appears excellent when required to complete a quantifying phase
considering that no segments were excluded from (6 patients) to ensure adequate image quality and
the analysis, but the relatively low number of study protocol compliance. MEDICAMUNDI 48/3 2004/11 31
Institution Site Investigator(s)
Table 2. Current trial participants.
Cleveland Clinic Foundation, Cleveland OH, USA Mario Garcia [Principal Investigator]
Washington Hospital Center, Washington DC, USA Augusto Pichard, Guy Weigold
Caritas Saint Elizabeth's Medical Center, Jeffery Mendel
Boston MA, USA
Vanderbilt University, Nashville TN, USA Ronald Arildsen, Ernest Madu
University of Maryland Medical System, Charles White
Baltimore MD, USA
Rambam Hospital, Rambam, Israel Robert Dragu, Eduard Ghersin
University Medical Center Utrecht, Matthias Prokop
Utrecht, the Netherlands
St Mary’s Hospital, London, UK Andrew Wright
Munich Pasing Clinic, Munich, Germany Ralph Haberl, Eike Boehme
Teikyo University, Tokyo, Japan Shigeru Suzuki, Naoyuki Yokoyama
Ochsner Clinic Foundation, New Orleans LA, USA John Reilly
Ulm University Hospital, Ulm, Germany Martin Hoffmann [CT Core Lab]
Cleveland Clinic Cardiovascular Coordinating Center, Sorin Brener
Cleveland OH, USA [Angiography Core Lab]
Inclusion criteria Exclusion criteria
Table 3. Inclusion/exclusion criteria.
30 to 75 years old Coronary interventions (including PTCA
and/or stents) within the last 3 months
Suspected coronary artery disease or
coronary obstruction Previous heart surgery (including coronary
bypass grafting)
Scheduled for conventional angiography for
clinical indication within the next 1 to 14 Cardiac rhythm other than sinus
days
Presence of internal cardiac pacemakers
Meets specific criteria for intermediate or and/or defibrillators
high probability of CAD
Hemodynamically unstable
Mentally competent and providing consent
Contraindications to iodine contrast
in writing after being fully informed, and
discussion with the treating physician Contraindications to beta-blockers
Renal insufficiency (Creatinine > 1.5 mg/dl)
Diabetes requiring drug therapy
Inability to sustain a breath-hold for
25 seconds
Inability to comply with the protocol
requirements
Body Mass Index > 40
Women of childbearing age
Decompensated heart failure
Resting heart rate > 100 bpm
Resting heart rate > 75 bpm if PR interval
>200 ms
32 MEDICAMUNDI 48/3 2004/11
The overall aims of the study are: calcium score is equal to or greater than 600,
• To determine the utility of CT angiography then the CT protocol will be terminated at this
for evaluating CAD in patients referred for point. If the score is less than 600, the patient
coronary angiography for evaluation of will proceed with the entire CT protocol.
suspected CAD
• To compare the accuracy of CT and A contrast-enhanced, ECG-tagged coronary CT
conventional angiography in quantifying luminal angiography examination will be performed.
coronary artery stenosis Contrast delivery will use a biphasic injection
• To determine the reproducibility of CT protocol followed by a saline chaser. Specific rates
angiographic interpretation across different and volumes will vary based on patient weight
investigators. and heart rate. After injection of the contrast,
the CT examination will begin when the image
The primary hypothesis of the study is that CT intensity in the aorta reaches a pre-defined
coronary angiography is able to detect >50% threshold. To reduce the radiation dose to the CT is able to detect
luminal narrowing in coronary artery segments patient, the tube current will be modulated > 50% luminal
> 2.0 mm in diameter with > 85% sensitivity during the cardiac RR-interval. The location of narrowing in coronary
and > 85% specificity with 95% statistical the modulation will vary based on the patient artery segments
confidence. heart rate. Data from the examination will be > 2.0 mm in diameter.
retrospectively reconstructed at specific phases
The recruiting centers will be responsible for during the cardiac RR-interval.
acquiring the data from the CT and CA
examinations, and submitting the data to a CT Cardiac CT data will be analyzed by the site
Core Laboratory and an Angiography Core investigator and by the CT Core Laboratory,
Laboratory, respectively. The core laboratories both blinded to the conventional angiography
will independently interpret the data. An results. All CT data analysis will be performed on
independent adjudicator will review and resolve a dedicated workstation (Extended Brilliance
any discrepancies in segment definition between Workspace, Philips Medical Systems). The
core laboratories. The Cleveland Clinic calcium scoring examination will be evaluated
Cardiovascular Coordinating Center (C5) will while the patient is on the CT scanner. The
independently analyze the results and provide Agatston and Mass scores will be recorded.
statistical findings.
All reconstructed phases of the coronary CTA
Patient eligibility criteria examination will be simultaneously reviewed
Patients will be recruited for the study based side-by-side to identify the phase with the least Subjects will be drawn
upon the criteria listed in Table 3. The recruitment amount of cardiac motion. Curved multi-planar from patients
of subjects will be drawn from patients with reformatting (CMPR) will be performed for each scheduled for diagnostic
suspected coronary artery disease scheduled for vessel using automatic and semi-automatic tools. coronary angiography.
diagnostic coronary angiography, observing the The reader will visually evaluate the
inclusion and exclusion criteria and following interpretability and visibility of each segment.
full written consent of the patients. Reasons for poor visibility will be noted.
Coronary CT angiography If any luminal narrowing greater than 20% is
The MDCT imaging protocol will be performed identified from the interactive CMPR images,
1 to 14 days prior to diagnostic coronary angio- the reader will measure the maximum diameter
graphy. All CT examinations will be performed and minimum diameter for each segment using
using a 16-slice CT scanner (Brilliance, Philips the standard manually drawn line measurement
Medical Systems). tool. Measurements will be made in two
orthogonal orientations.
Patient preparation will consist of monitoring a
sinus rhythm for 1 minute and simulating a Conventional diagnostic angiography
25 second breath-hold. Additionally, for patients All diagnostic conventional angiographies will be
with heart rates greater than 55 bpm (65 bpm performed according to the institution's routine
for patients taking oral beta-blockers), clinical procedure, while carefully following
Metoprolol (5 to 15 mg) will be intravenously research-grade image acquisition recommendations
administered to reduce and maintain the heart from the Angiography Core Laboratory in order
rate below 65 bpm. to ensure adequate projections for quantitative
analysis of all segments. Angiography data will
Following preparation, a non-contrast, be analyzed solely by the Angiography Core
prospectively ECG-gated calcium scoring Laboratory, blinded to the CT results. Cine-
examination will be performed. If the Agatston frame selection and edge-detection analysis for MEDICAMUNDI 48/3 2004/11 33
segmental quantitative coronary angiography Conclusion
(QCA) will be performed using end-diastolic
frames at the core laboratory. In summary, the CATSCAN trial is expected to
provide much-needed information on the efficacy
Examples of CT as a viable diagnostic tool to evaluate
Examples of the CT and CA qualifying cases are patients with suspected coronary artery disease.
shown in Figure 1. CT is an attractive alternative because it is non-
Figure 1. Examples of CT and
CA qualifying cases.
Figure 1a. CA: normal RCA.
Figure 1b. CT. normal RCA.
Figure 1c. CA: complete occlusion
of RCA.
Figure 1 d. CT: complete occlusion
of RCA.
Figure 1e. CA: significant stenosis
of LAD.
Figure 1f. CT: significant stenosis
of LAD.
34 MEDICAMUNDI 48/3 2004/11
invasive and less expensive than conventional and reductions in contrast bolus and breath-
coronary angiography. With the establishment hold duration. It is anticipated that these scanners The results of the
of a high negative predictive value and reliable will further improve the reliability and accuracy CATSCAN trial will
sensitivity, CT may play a role in screening of Cardiac CT, and build upon the experience determine whether
patients suspected of having coronary disease - obtained during the CATSCAN trial. MDCT is ready for
acting as a gatekeeper for diagnostic invasive prime-time use.
coronary angiography. Further developments in The results of the CATSCAN trial will not only
CT scanner technology were introduced at provide objective answers to many of the
RSNA 2003 - including the Philips Brilliance CT, concerns raised by many experienced investigators,
40-slice configuration. These new scanners offer but will also determine whether MDCT
improvements in spatial and temporal resolution, angiography is ready for prime-time use
References
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[2] Achenbach S, Moshage W, Ropers D et al. Value of Electron-Beam [8] Nieman K, Cademartiri F, Lemos PA et al. Reliable Noninvasive
Computed Tomography for the Noninvasive Detection of High-Grade Coronary Angiography with Fast Submillimeter Multislice Spiral
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[5] Achenbach S, Giesler T, Ropers D et al. Detection of Coronary Angiography with Multi-Slice Helical Computed Tomography. Lancet
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[6] Knez A, Becker CR, Leber A, et al. Usefulness of Multislice Spiral Identifying Desired Physiological Phases for Cardiac Imaging Using
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Artery Stenoses. Am J Cardiol 2001; 88: 1191-1194.
MEDICAMUNDI 48/3 2004/11 35
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