BACKGROUND:Noninvasive assessment of coronary artery disease (CAD) in obese patients is challenging due to suboptimal image quality. We performed a prespecified secondary analysis of obese patients from the second Phase III trial of flurpiridaz-18F positron emission tomography (PET). METHODS:In total, 604 patients with suspected CAD underwent flurpiridaz-18F PET and 99mTc-single-photon emission computerized tomography (SPECT) myocardial perfusion imaging (MPI) before invasive coronary angiography (ICA) across 48 sites. MPI images were interpreted by three blinded experts. The primary endpoint was sensitivity and specificity for diagnosing CAD (≥50% stenosis on quantitative coronary angiography), requiring the lower 95% confidence interval to exceed 60% by 2 same blinded expert core lab readers, assessed using one-sided z-test (α = 0.025). Sensitivity and specificity were compared between PET and SPECT and between obese (body mass index [BMI] ≥30 kg/m2) and nonobese patients. RESULTS:Of 578 evaluable patients, 298 (51.6%) were obese (mean age: 62.0 years, 64.4% male, mean BMI: 35.6 kg/m2) and 117 (39.3%) had CAD by ICA. In obese patients, flurpiridaz-18F PET MPI met the primary endpoint, with lower 95% confidence limits greater than 60% and one-sided P < 0.025 by the same 2 readers (Readers 1 and 2). Sensitivity across 3 readers ranged from 70.1% to 88.0% and specificity ranged from 53.6% to 74.0%. In obese patients, flurpiridaz-18F PET MPI showed significantly higher sensitivity compared to 99ᵐTc-SPECT MPI by Readers 1 and 3 (Reader 1: 72.6% vs 60.7%, P = 0.01; Reader 3: 88.0% vs 74.4%, P = 0.002), with non-inferior specificity by the same two readers (Reader 1: 68.0% vs 61.3%; Reader 3: 53.6% vs 50.8%; P < 0.01 for noninferiority, for both), noting that the primary endpoint was met by a partially overlapping reader pair (Readers 1 and 2). Diagnostic performance of flurpiridaz-18F PET was higher than SPECT across BMI categories. No statistically significant difference in diagnostic performance was observed between obese and nonobese patients (Sensitivity P = 0.26, specificity P = 0.25 and accuracy P = 1.0). CONCLUSION:Flurpiridaz-18F PET MPI demonstrates high diagnostic efficacy for detecting CAD across BMI categories in obese patients compared to ICA and 99mTc-SPECT, with no loss of diagnostic performance in obese relative to nonobese patients. CLINICAL TRIAL REGISTRATION:NCT03354273.

BACKGROUND:A recent phase 3 study of the PET perfusion tracer F-18 flurpiridaz (flurpiridaz) met the primary efficacy endpoint for the detection of CAD, demonstrating statistically higher sensitivity, non-inferior specificity compared to Tc-99m-tetrofosmin/sestamibi SPECT (Tc99m-SPECT) in the general population. This study reports a pre-specified subgroup analysis examining the diagnostic accuracy of flurpiridaz in women. METHODS:Patients with suspected CAD underwent rest-stress flurpiridaz PET and Tc99m-SPECT before invasive coronary angiography in the US, Canada, and Europe. The primary endpoint was sensitivity and specificity by 2 expert readers (majority rule between 3 blinded readers) for the diagnosis of significant CAD defined as a stenosis ≥50%. Secondary endpoints included comparison of the diagnostic performance of flurpiridaz PET and Tc99m-SPECT. RESULTS:188 women were included in the subgroup analysis. Flurpiridaz met the pre-specified primary endpoint of sensitivity [82.9% (95% CI: 71.4, 94.4), P = 0.0014] and specificity [72.8% (95%CI: 65.6, 80),P = 0.0008]. Flurpiridaz sensitivity was significantly higher than Tc99m-SPECT [82.9% vs 65.9%, difference: 17.1% (-1.5%, 35.6%), P = 0.0448] and specificity was non-inferior [72.8% vs 66%, difference:6.8% (-3.4%, 17.0%) P = 0.0004]. Diagnostic certainty was significantly higher for women undergoing flurpiridaz PET compared to Tc99m-SPECT (82.4% v 48.9%). PET perfusion image quality was better than Tc99m-SPECT for rest and pharmacological stress images (P < 0.0001). The summed difference score was significantly higher for flurpiridaz (5.3 v 3.5). Radiation exposure was significantly lower for flurpiridaz than same day rest/stress Tc99m-SPECT (6.2 v 11.2 mSv). CONCLUSIONS:This pre-specified secondary analysis of the ARORA study in women, demonstrates high diagnostic accuracy of flurpiridaz PET to detect obstructive CAD. In women, the diagnostic performance of flurpiridaz PET for detection of CAD was significantly higher than with 99mTc-SPECT.

Cardiac PET imaging is increasingly used for myocardial perfusion studies because of its high diagnostic accuracy and low radiation exposure to the patient. However, patient motion can be challenging, affecting a large number of studies. Motion artifacts can lead to inconclusive or false-positive results, complicating clinical interpretation. This article explores the causes of motion artifacts and their characteristic appearance in cardiac PET imaging, highlighting their distinction from true perfusion abnormalities. Strategies for minimizing motion through effective patient positioning and communication are discussed. Understanding and addressing motion artifacts are crucial for optimizing diagnostic accuracy and ensuring the full benefit of cardiac PET imaging.

Abstract Background/Introduction Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. Purpose To further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as >50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET vs. Tc-99m SPECT in the detection of CAD in all patients and in the clinically important subgroups of women, obese [body mass index (BMI) ≥30 kg/m2], and diabetics. Also, PET and Tc-99m SPECT were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET was also evaluated. Methods 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert blinded to clinical and image data. Results 578 patients (age, 63.7±9.5 years) were evaluable. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. The secondary endpoints were also met in the overall population, in women, in obese patients, and in diabetics. Flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p<0.0001), in women (0.84 vs 0.70, p<0.01), and in obese patients (0.79 vs 0.67, p<0.001), but not in diabetics (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p<0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p<0.0001), pharmacological stress images (96% vs 78%, p<0.0001), and treadmill exercise images (97% vs 87%, p<0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT. Conclusion This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI≥30.

BACKGROUND Flurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion im-aging tracer.OBJECTIVES The purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as $50% stenosis by quantitative invasive coronary angiography (ICA).METHODS In this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1-or 2-day rest-stress Tc-99m-labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data.RESULTS A total of 578 patients (age 63.7 +/- 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index $30 kg/m(2), and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flur-piridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated. CONCLUSIONS This second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273)

One of the most exciting and useful advances in nuclear cardiology is the opportunity to measure myocardial blood flow (MBF) routinely as part of myocardial perfusion imaging (MPI) with positron emission tomography (PET). Incorporating MBF into the MPI evaluation improves diagnosis and assessment of

Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI. The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m2; and (3) diabetic patients. This trial’s design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA. This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD. NCT03354273

BACKGROUND Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. OBJECTIVES This study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m-labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as $50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated. METHODS In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 +/- 9.5 years, 31% were women, 55% had body mass index >= 30 kg/m(2), and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data. RESULTS Sensitivity of flurpiridaz PET (for detection of >= 50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 +/- 0.4 mSv vs. 13.4 +/- 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated. CONCLUSIONS Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710) (c) 2020 by the American College of Cardiology Foundation.

OBJECTIVES This study compared the clinical effectiveness of pharmacologic stress myocardial perfusion imaging (MPI) plus positron emission tomography (PET) with single-photon emission computed tomography (SPECT) in patients with known coronary artery disease (CAD) presenting with symptoms suggestive of ischemia. BACKGROUND Although PET MPI has been shown to have higher diagnostic accuracy in detecting hemodynamically significant CAD than SPECT MPI, whether this impacts downstream management has not been formally evaluated in randomized trials. METHODS This study consisted of a single-center trial in which patients with known CAD and suspected ischemia were randomized to undergo PET or attenuation-corrected SPECT MPI between June 2009 and September 2013. Post-test management was at the discretion of the referring physician, and patients were followed for 12 months. The primary endpoint was diagnostic failure, defined as unnecessary angiography (absence of >= 50% stenosis in >= 1 vessel) or additional noninvasive testing within 60 days of the MPI. Secondary endpoints were post-test escalation of antianginal therapy, referral for angiography, coronary revascularization, and health status at 3, 6, and 12 months. RESULTS A total of 322 patients with an evaluable MPI were randomized (n = 161 in each group). At baseline, 88.8% of patients were receiving aspirin therapy, 76.7% were taking beta-blockers, and 77.3% were taking statin therapy. Diagnostic failure within 60 days occurred in only 7 patients (2.2%) (3 [1.9%] in the PET group and 4 [2.5%] in the SPECT group; p = 0.70). There were no significant differences between the 2 groups in subsequent rates of coronary angiography, coronary revascularization, or health status at 3, 6, and 12 months of follow-up (all p values >= 0.20); however, when subjects were stratified by findings on MPI in a post hoc analysis, those with high-risk MPI on PET testing had higher rates of angiography and revascularization on follow-up than those who had SPECT MPI, whereas those undergoing low-risk PET studies had lower rates of both procedures than those undergoing SPECT (interaction between randomized modality *high-risk MPI for 12-month catheterization [p = 0.001] and 12-month revascularization [p = 0.09]). CONCLUSIONS In this contemporary cohort of symptomatic CAD patients who were optimally medically managed, there were no discernible differences in rates of diagnostic failure at 60 days, subsequent coronary angiography, revascularization, or patient health status at 1 year between patients evaluated by pharmacologic PET compared with those evaluated by SPECT MPI. Downstream invasive testing rates with PET MPI were more consistent with high-risk features than those with SPECT MPI. (C) 2019 by the American College of Cardiology Foundation.