PET More Accurate for Diagnosing CAD Than SPECT and CT Angiography: PACIFIC Study

A head-to-head comparative study of multiple imaging modalities suggests that positron emission tomography (PET) is the most accurate noninvasive test for the detection of myocardial ischemia.

In a study of 208 symptomatic patients who underwent a series of noninvasive tests, PET yielded the highest diagnostic accuracy, beating out coronary CT angiography (CTA) and single-photon emission CT (SPECT).

Additionally, researchers found that a hybrid diagnostic approach, one that combined a functional and anatomic assessment of the coronary lesion, such as PET/CTA or SPECT/CTA, did not result in an improvement in diagnostic accuracy beyond the single imaging tests alone.

“The reference standard to diagnose coronary artery disease is in the cath lab,” senior investigator Paul Knaapen, MD, PhD (VU University Medical Center, Amsterdam, the Netherlands), told TCTMD. “If you see a stenosis, you determine its hemodynamic significance and that determines whether you need to treat it or not. Obviously, though, this is an invasive procedure, with risks of bleeding, MI, arrhythmias, and more, so we’d like to have a safe, noninvasive gatekeeper to help us select the patients who we think are most likely to have coronary artery disease.”

For Knaapen, the best gatekeeper appears, from this study, to be PET imaging.

“If you were to select one [noninvasive] imaging modality with the highest diagnostic accuracy, it would be PET,” he said. “As an alternative you can use CT or SPECT, which have similar diagnostic accuracy. However, there’s a big difference in sensitivity and specificity between these tests. Coronary CT has very high sensitivity and a very low specificity while SPECT has the opposite pattern.”

The study, known as PACIFIC and led by Ibrahim Danad, MD (VU University Medical Center), was published online August 16, 2017, ahead of print in JAMA Cardiology.

PACIFIC Participants Undergo All Imaging Tests

PACIFIC enrolled patients with new-onset chest pain and suspected coronary artery disease. All patients underwent coronary CTA, PET, and SPECT followed by invasive coronary angiography and fractional flow reserve (FFR) measurements of the coronary arteries within 2 weeks. The physician in the cath lab was blinded to the results of the noninvasive testing, and raw image data from CTA, PET, and SPECT were sent to three independent core laboratories to interpret the findings.

Knaapen said there are few prospective studies evaluating noninvasive testing that includes sending patients to the cath lab. In recent studies, if noninvasive testing is negative, researchers have declined to send patients for coronary angiography given that it might be unethical to expose these patients to the risks of the procedure. In this study, all patients were referred for angiography prior to imaging.  

The prevalence of hemodynamically significant coronary artery disease by FFR was 44.2%. Overall, coronary CTA and SPECT had similar diagnostic accuracy (74% and 77%, respectively; P = 0.51). The diagnostic accuracy of PET was 85%, which was significantly better when compared with the two other modalities. The sensitivity for the detection of myocardial ischemia with PET, coronary CTA, and SPECT was 87%, 90%, and 57%, respectively. The specificity of the three tests was 84%, 60%, and 94%.

Those numbers suggest that use of coronary CTA will lead to overdiagnosis, such that more patients without coronary artery disease may be sent to the cath lab, said Knaapen. On the other hand, there is the potential to miss patients with obstructive coronary disease when SPECT is used.

The researchers also analyzed the performance of imaging modalities when they fused functional and anatomic testing. Hybrid imaging with SPECT and coronary CTA yielded a diagnostic accuracy of 76%, while the combination of PET and CTA resulted in an accuracy of 84%; neither approach improved on PET alone.

“Previous studies have shown that if you combine a CT scan with SPECT or PET you can improve diagnostic accuracy,” Knaapen explained. “We could not reproduce those findings. We didn’t find incremental value of hybrid imaging and this was sort of a shocker. It means that you don’t have to combine a CT scan with perfusion imaging. Either you do a CT scan, a PET scan, or SPECT, but if one is abnormal or normal, it doesn’t need to be followed by another test. It’s not going to increase your diagnostic accuracy. It’s only going to increase your diagnostic uncertainty.”

Searching for the Noninvasive Gatekeeper Test

In an editorial accompanying the study, Pamela Douglas, MD (Duke University School of Medicine, Durham, NC), and Leslee Shaw, PhD (Emory University School of Medicine, Atlanta, GA), write that there has long been a search for a noninvasive test that provides anatomical and functional information and accurately predicts significant flow impairment compared with the gold-standard FFR.

They note that, in PACIFIC, the prevalence of coronary artery disease was significantly higher than in previous studies, pointing to a higher-risk cohort. “The extent to which this influenced accuracy findings is unknown, but one could anticipate a greater prevalence of abnormalities and a higher concordance with angiographic FFR (ie, improved diagnostic sensitivity),” write the editorialists.

To TCTMD, Shaw said the results are not sufficient to support PET imaging as the noninvasive test of choice for diagnosing coronary artery disease in clinical practice. However, in conjunction with data from the EVINCI trial and other observational data, the PACIFIC study suggests PET should be more widely used, she said.

In an email, Shaw noted that the investigators did not use a standard segmental perfusion analysis for PET and SPECT but instead defined abnormalities on PET as a reduction in coronary flow reserve. Coronary flow reserve is a newer measurement and not as established as segmental perfusion, she explained. “So, a more robust analysis incorporating [segmental perfusion and coronary flow reserve] will be needed to understand how PET would be used clinically,” said Shaw. “Unfortunately, the [PET radiotracer oxygen-15] isotope does not have the image quality for segmental perfusion interpretation.”

That said, Shaw noted that the reduction in coronary flow reserve—defined as the ratio of myocardial blood flow at peak hyperemia to rest—correlated well with invasive FFR, which was the study’s diagnostic endpoint. She added that the PACIFIC study is one of the more recent trials using FFR as an endpoint, like the CE-MARC2 study

Before PET is widely adopted in clinical practice, Shaw told TCTMD that a lot more information is needed to help guide patient care, including the relationship of coronary flow reserve and FFR to symptoms. In their editorial, Douglas and Shaw say they’d like to know how these results translate into “effectiveness and not just efficacy,” as well as how changes in testing practices impact patient care and outcomes.   

Regarding the lack of improvement in diagnostic accuracy with hybrid imaging, Douglas and Shaw state the finding is surprising and “contradicts the conventional wisdom that anatomy and function are essential in evaluating coronary artery disease.”