The Value of Stress Testing in Patients with Known Coronary Artery Disease
By Michael H. Crawford, MD, Editor
SYNOPSIS: A comparison of adenosine stress singe photon emission CT, PET, and MRI in stable patients with known coronary artery disease (CAD) showed PET to be more sensitive for detecting invasive fractional flow reserve-identified ischemic lesions. Patients with known CAD and new symptoms should be referred directly to invasive coronary angiography.
SOURCE: Driessen RS, van Diemen PA, Raijmakers P, et al. Functional stress imaging to predict abnormal coronary fractional flow reserve: The PACIFIC 2 study. Eur Heart J 2022; Jun 16:ehac286. doi: 10.1093/eurheartj/ehac286. [Online ahead of print].
How valuable is stress testing for patients with known coronary artery disease (CAD) and new symptoms? Driessen et al conducted a prospective comparison of cardiac PET, singe photon emission CT (SPECT), and MRI perfusion imaging to invasive coronary angiography in patients with prior CAD.
PACIFIC 2 was a prospective, controlled, clinical, single-center, head-to-head comparative study conducted from 2014 to 2020, which ended early because of COVID-19. Patients with symptoms suggestive of myocardial ischemia, a history of myocardial infarction (MI) or a percutaneous coronary intervention (PCI), and who were referred for invasive coronary angiography (ICA) were recruited. The major exclusion criteria were contraindications to adenosine infusion or iodinated contrast, devices precluding MRI, coronary artery bypass graft surgery (CABG), atrial fibrillation, and acute MI. The imaging studies were two-day rest-stress, conducted with adenosine infusion, followed by ICA within two weeks. ICA included an assessment of fractional flow reserve (FFR). Hemodynamically significant lesions were those with an FFR ≤ 80 or a diameter stenosis ≥ 90%. Of the 3,489 patients screened, 189 were enrolled (mean age, 63 years; 81% men). For various reasons, a few patients did not undergo all three stress tests. The mean time to complete the entire protocol was five days.
In about 90% of patients, the noninvasive imaging studies were considered to be of average or good quality. Hemodynamically significant coronary stenoses were found in 63% of patients by FFR or ICA. The sensitivity per patient for detecting significant coronary lesions was higher for PET (81%) than it was for SPECT (67%; P = 0.016) or MRI (66%; P = 0.014). Specificity was not significantly different between the noninvasive tests (range, 61% to 65%). Diagnostic accuracy also was higher for PET (75%) than SPECT (65%; P = 0.03) and MRI (64%; P = 0.052). The authors concluded there was not an appreciable clinical difference in accuracy between the three techniques for diagnosing FFR- or ICA-defined significant CAD in stable symptomatic patients with prior MI or PCI. However, the overall diagnostic performance of these noninvasive stress tests was discouraging, and their added value in such a population is questionable.
The superior diagnostic ability of PET in patients with known CAD may be more related to technical issues than anything else. Here, PET was a quantitative analysis of regional blood flow, whereas SPECT and MRI were qualitative assessments of differences in perfusion. These patients with prior PCI and MI probably produce mixed pictures of large and small vessel obstructions, which may be better assessed with a quantitative technique. Also, the gold standard in this study was invasive FFR, which concerns specific lesions. Reductions in such large vessel blood flow may be easier to detect with a quantitative approach. In addition, 27% of patients exhibited multivessel occlusive lesions. Any balanced flow errors would be easier to overcome with a quantitative measure. Quantitative techniques for SPECT and MRI are in development; when fully deployed, these may improve accuracy.
What is more troubling is the overall performance of these techniques was worse than what was reported in studies of patients without known CAD (the accuracy of PET and MRI were 85%, and SPECT was 77%).1 Of course, an unknown diagnosis group is going to produce more normal studies. Also, in PACIFIC 2, the authors did not stop the patients’ medications for the stress studies, which could have increased the number of false-negatives.
The strengths of the study include the fact it was a prospective, head-to-head comparison in patients with known CAD. Also, each stress study was analyzed by a core lab that was blinded to the results of the other tests. In addition, FFR was used as the reference standard, not eyeballing the angiograms. There were weaknesses, too. Because they had to stop early, the authors did not recruit the optimal number of patients. MRI could not be tolerated in 18 patients, which reduced the sample size of this analysis. Investigators used (15O)H2O for PET rather than the more common rubidium 82 or (13N) ammonia. Coronary CT angiography with FFR was not used. There are no outcome data, which may be a better way of determining the value of a diagnostic test. Finally, researchers did not employ exercise stress testing, which might be a better stressor than an adenosine infusion.
Importantly, this study addresses the poorly studied issue of how best to evaluate the stable patient with known CAD and new symptoms. The usual stress test to demonstrate ischemia before proceeding to ICA for patients without known disease could be the preferred approach. However, I concur with the authors in that perhaps a direct referral to ICA makes more sense for such patients.
1. Danad I, Raijmakers PG, Driessen RS, et al. Comparison of coronary CT angiography, SPECT, PET, and hybrid imaging for diagnosis of ischemic heart disease determined by fractional flow reserve. JAMA Cardiol 2017;2:1100-1107.
A comparison of adenosine stress singe photon emission CT, PET, and MRI in stable patients with known coronary artery disease (CAD) showed PET to be more sensitive for detecting invasive fractional flow reserve-identified ischemic lesions. However, the sensitivity was disappointing; thus, patients with known CAD and new symptoms should be referred directly to invasive coronary angiography.
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