Author + information
- Received December 12, 2019
- Revision received April 28, 2020
- Accepted May 26, 2020
- Published online July 20, 2020.
- Jamshid Maddahi, MDa,b,∗ (, )@DrJMaddahi,
- Joel Lazewatsky, PhDc,
- James E. Udelson, MDd,
- Daniel S. Berman, MDe,
- Rob S.B. Beanlands, MDf,
- Gary V. Heller, MD, PhDg,
- Timothy M. Bateman, MDh,
- Juhani Knuuti, MDi and
- Cesare Orlandi, MDc
- aDivision of Nuclear Medicine, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California
- bDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California
- cLantheus Medical Imaging, North Billerica, Massachusetts
- dTufts Medical Center, Boston, Massachusetts
- eCedars-Sinai Medical Center, Los Angeles, California
- fUniversity of Ottawa Heart Institute, Ottawa, Ontario, Canada
- gMorristown Medical Center, Morristown, New Jersey
- hMid America Heart Institute, Saint Luke’s Hospital, Kansas City, Missouri
- iTurku University, Turku, Finland
- ↵∗Address for correspondence:
Dr. Jamshid Maddahi, 100 UCLA Medical Plaza Suite# 410, Los Angeles, California 9002.
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/m2, 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)
This study was funded by Lantheus Medical Imaging. Drs. Maddahi, Udelson, Berman, Beanlands, Heller, Bateman, and Knuuti have served as consultants for Lantheus Medical Imaging. Drs. Maddahi, Berman, Beanlands, Bateman, and Knuuti have received research grant support from Lantheus Medical Imaging. Drs. Lazewatsky and Orlandi are employees of Lantheus Medical Imaging.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received December 12, 2019.
- Revision received April 28, 2020.
- Accepted May 26, 2020.
- 2020 American College of Cardiology Foundation
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