CATSCAN (coronary assessment by CT scanning and catheter angiography by zte15176

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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




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