Rationale and Objectives
Although myocardial perfusion positron emission tomography (PET), using either cyclotron-produced ammonia or generator-produced rubidium 82, has reported excellent diagnostic capabilities in the detection of coronary artery disease (CAD) in individual studies, the technique is not widely used in practice. This may be driven by cost and availability or by unawareness of performance. The purpose of our study was to conduct an evidence-based evaluation of PET in the diagnosis of CAD.
Materials and Methods
We examined studies from January 1977 to July 2007 using MEDLINE and EMBASE. A study was included if it ( ) used PET as a diagnostic test for CAD and ( ) used catheter x-ray angiography as the reference standard (≥50% diameter stenosis). Analysis was performed on a subject and coronary territory level.
Results
Nineteen studies (1442 patients) met the inclusion criteria. On a patient level, PET demonstrated a sensitivity of 0.92 (95% confidence interval [CI]: 0.90–0.94) and specificity of 0.85 (CI: 0.79–0.90), with a positive likelihood ratio (LR+) of 6.2 (CI: 3.3–11.8) and negative likelihood ratio (LR−) of 0.11 (CI: 0.08–0.14). On a coronary territory level (n = 1130), PET showed a sensitivity of 0.81 (CI: 0.77–0.84) and specificity of 0.87 (CI: 0.84–0.90), with an LR+ of 5.9 (CI: 4.5-7.9) and an LR− of 0.19 (CI: 0.09–0.38).
Conclusion
PET demonstrates excellent diagnostic properties in the diagnosis of CAD, especially at the patient level. The capabilities appear superior to those reported in meta-analyses for perfusion imaging with Tl-201 and sestamibi, or anatomical imaging with coronary MDCT angiography or MRA. Given that previous studies have found PET to be cost-effective and the current findings of excellent sensitivity and specificity, the modality should be more widely considered as an initial test in the diagnosis of CAD.
Coronary artery disease (CAD), secondary to atherosclerosis, is the leading cause of mortality in the United States, underlying or contributing to approximately 650,000 deaths per year ( ). While catheter-based x-ray angiography evaluation of the coronary lumen is generally used as the clinical reference standard, the invasive procedure carries small but significant risks; thus, a potential noninvasive alternative would be valuable. Radionuclide myocardial perfusion imaging is one of the most common used diagnostic tests in the assessment of CAD and largely performed by thallium-201 or a technetium-99m perfusion tracer via single-photon emission computed tomography (SPECT). However, myocardial perfusion positron emission tomography (PET), which has several advantages over SPECT, including better spatial resolution, higher counting efficiencies, and excellent attenuation correction, resulting in single-center studies demonstrating robust sensitivity and specificity, is less commonly performed throughout the world. This is likely driven by the greater availability and lesser costs of SPECT, but lack of awareness regarding the diagnostic properties of PET in the diagnosis of CAD may also be a factor. Moreover, PET has become more prevalent and less expensive in the last decade, given its widespread use in oncological imaging. The purpose of our study was to provide an evidence-based evaluation of the clinical utility of PET for coronary artery disease; thus, we performed a comprehensive meta-analysis of all currently published studies comparing PET with catheter-based x-ray angiography as the gold standard.
Methods
Data Sources and Searches
MEDLINE and EMBASE for English and non-English literature published from January 1977 to July 2007 were searched evaluating for the presence of CAD in native or non-native coronary arteries by PET and catheter-based x-ray angiography in the same patients. The search included medical subject headings for positron emission tomography, myocardial perfusion , and coronary angiography with the exploded term coronary artery disease. Moreover, we evaluated bibliographies of retrieved articles, review articles, and textbooks. The retrieved studies were examined for potentially duplicate or overlapping data. Given that meeting abstracts provide insufficient information regarding their data and lack of finality regarding the results, they were excluded.
Study Selection
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Data Extraction and Quality Assessment
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Data Synthesis and Statistical Analysis
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Assessment of Heterogeneity
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Results
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Table 1
Characteristics of Included Studies
First Author (Ref.) Year Journal Patients ( N ) Excluded Male (%) Mean Age, yr (SD) PET Radiotracer Stressor Selection Stenosis Abramson ( ) 2000Journal of Nuclear Cardiology 19 0 0 59 (10) F-18 deoxyglucose (FDG) Treadmill n = 8, dipyridamole n = 11 Women referred for chest pain ≥50% Bateman ( ) 2006Journal of Nuclear Cardiology 112 0 46 67 (NS) Rubidium-82 Dipyridamole Matched case-control ≥70% Botsch ( ) 1994European Journal of Nuclear Medicine 34 0 NS 56 (NS) Rubidium-82 Exercise Suspected CAD ≥50% Go ( ) 1990Journal of Nuclear Medicine 202 0 NS NS Rubidium-82 Dipyridamole Suspected CAD ≥50% Gould ( ) 1986Journal of the American College of Cardiology 31 0 NS NS 27 rubidium-82/23 nitrogen-13 (N-13) Dipyridamole-handgrip stress Suspected CAD CFR<3.0 Grover-McKay ( ) 1992American Heart Journal 16 0 6 50 (11) Rubidium-82 Dipyridamole-handgrip stress 16 with known CAD ≥50% Laubenbacher ( ) 1993Journal of Nuclear Medicine 29 0 NS 61 (11) Nitrogen-13 (N-13) Dipyridamole or adenosine Suspected CAD ≥75% Marwick ( ) 1992Journal of the American Society of Echocardiography 74 0 81 60 (4) Rubidium-82 Dipyridamole-handgrip stress Known CAD >50% Muzik ( ) 1998Journal of the American College of Cardiology 31 0 74 62 (12) Nitrogen-13 (N-13) Adenosine 31 with CAD ≥70% Namdar ( ) 2005Journal of Nuclear Medicine 25 0 88 62 (NS) Nitrogen-13 (N-13) PET/CT Known CAD >50% Sampson ( ) 2007Journal of the American College of Cardiology 64 0 39 62 (15) Rubidium-82 PET/CT (dipyridamole, adenosine, dobutamine) Suspected CAD ≥70% Santana ( ) 2007Journal of Nuclear Medicine 53 NS 29 NS Rubidium-82 PET/CT (adenosine) Known or Suspected CAD ≥50% Schelbert ( ) 1982American Journal of Cardiology 45 0 78 NS Nitrogen-13 (N-13) Dipyridamole 32 with CAD/13 normal volunteers >50% Simone ( ) 1992American Journal of Physiologic Imaging 225 NS 80 57 (NS) Rubidium-82 Dipyridamole Suspected CAD ≥67% Stewart ( ) 1991American Journal of Cardiology 81 0 64 57 (12) Rubidium-82 Dipyridamole-handgrip stress Suspected CAD >50% Tamaki ( ) 1985European Journal of Nuclear Medicine 25 0 NS 53 (NS) Nitrogen-13 (N-13) Exercise 19 known CAD/6 normal volunteers NS Tamaki ( ) 1988Journal of Nuclear Medicine 51 0 NS 56 (NS) Nitrogen-13 (N-13) Exercise Known CAD >50% Williams ( ) 1994Journal of Nuclear Medicine 287 NS NS NS Rubidium-82 Dipyridamole Suspected CAD 67 Yonekura ( ) 1987American Heart Journal 40 2 95 52 (NS) Nitrogen-13 (N-13) Exercise 40 with known CAD >75%
NS, not specified.
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Table 2
Per Patient, Per Coronary Territory Analysis
Analysis by Patient Analysis by Coronary Territory First Author (Ref)N TP ( n ) FN ( n ) FP ( n ) TN ( n ) Sensitivity Specificity_N_ TP ( n ) FN ( n ) FP ( n ) TN ( n ) Sensitivity Specificity Abramson ( ) 19 8 1 1 9 0.89 0.90 NS NS NS NS NS NS NS Bateman ( ) 112 61 9 3 39 0.87 0.93 NS NS NS NS NS NS NS Botsch ( ) 29 24 1 0 4 0.96 1.0 NS NS NS NS NS NS NS Go ( ) 202 142 10 11 39 0.93 0.78 NS NS NS NS NS NS NS Gould ( ) 31 21 1 0 9 0.95 1 NS NS NS NS NS NS NS Grover-McKay ( ) 16 15 1 0 0 0.94 0 48 32 3 1 12 0.91 0.92 Laubenbacher ( ) NS NS NS NS NS NS NS 87 14 4 8 61 0.78 0.88 Marwick ( ) 74 63 7 0 4 0.90 1 NS NS NS NS NS NS NS Muzik ( ) NS NS NS NS NS NS NS 93 21 2 17 53 0.91 0.76 Namdar ( ) NS NS NS NS NS NS NS 100 11 24 4 61 0.31 0.94 Sampson ( ) 64 41 3 10 10 0.93 0.50 NS NS NS NS NS NS NS Santana ( ) 53 42 3 2 6 0.93 0.75 159 58 25 12 64 0.70 0.84 Schelbert ( ) 45 31 1 0 13 0.97 1 NS NS NS NS NS NS NS Simone ( ) NS NS NS NS NS NS NS 153 26 3 16 108 0.90 0.87 Stewart ( ) 81 51 9 2 19 0.85 0.90 NS NS NS NS NS NS NS Tamaki ( ) 25 18 1 0 6 0.945 1 NS NS NS NS NS NS NS Tamaki ( ) 51 47 1 0 3 0.98 1 153 80 11 6 56 0.88 0.90 Williams ( ) NS NS NS NS NS NS NS 213 88 13 16 96 0.87 0.86 Yonekura ( ) 38 37 1 0 0 0.89 0.90 114 67 8 1 38 0.89 0.97
NS, not specified.
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Patient-Level Summary Performance Estimates
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Coronary Territory-Level Summary Performance Estimates
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Assessment of Heterogeneity
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Table 3
Quality Assessment
First Author (Ref) Item 1 Item 2 Item 3 Item 4 Item 5 Item 6 Item 7 Item 8 Item 9 Item 10 Score Abramson ( ) Yes Yes Yes No Yes Yes Yes Yes No No 7 Bateman ( ) Yes No Yes No No Yes Yes Yes Yes Yes 7 Botsch ( ) No No Yes No No Yes Yes No No No 3 Go ( ) Yes No Yes No No Yes Yes No Yes No 5 Gould ( ) Yes No Yes No Yes Yes Yes No No No 5 Grover-McKay ( ) Yes No Yes No Yes Yes Yes No No No 5 Laubenbacher ( ) No No Yes No Yes Yes Yes Yes No No 5 Marwick ( ) Yes Yes Yes No Yes Yes Yes No Yes No 7 Muzik ( ) Yes Yes No No Yes Yes Yes No No No 5 Namdar ( ) Yes No Yes No Yes Yes Yes No No No 5 Sampson ( ) Yes No Yes Yes Yes Yes Yes Yes Yes Yes 9 Santana ( ) Yes No Yes No Yes Yes Yes Yes Yes Yes 8 Schelbert ( ) No No Yes No Yes Yes Yes No Yes No 5 Simone ( ) Yes No Yes No No Yes Yes Yes Yes No 6 Stewart ( ) Yes No Yes No Yes Yes Yes No Yes Yes 7 Tamaki ( ) No No Yes No No Yes No No No No 2 Tamaki ( ) Yes Yes Yes No Yes Yes Yes No Yes No 7 Williams ( ) Yes No Yes No No Yes Yes No Yes No 5 Yonekura ( ) Yes No Yes No Yes Yes Yes No Yes Yes 7
Item 1: Was the population clinically relevant, defined as a group of patients covering the spectrum of disease that is likely to be encountered in the current or future use of the test?
Item 2: Was there complete verification by the reference standard?
Item 3: Was there blinded interpretation of the test results?
Item 4: Was there consecutive patient selection?
Item 5: Was there prospective enrollment of patients?
Item 6: Was there adequate description and quality of the imaging procedure?
Item 7: Was the quality of the reference test technically adequate?
Item 8: Was there adequate clinical description of the patient population?
Item 9: Was the sample size ≥35 patients?
Item 10: Was there adequate reporting of results, including summary and subgroup indices of accuracy?
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Discussion
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