Abstract
Background: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies. Objectives: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging. Methods: Two international, single-vendor, phase 3 clinical trials of near identical design, “GadaCAD1” and “GadaCAD2,” were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD. Results: Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2. Conclusions: Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1536-1547 |
| Number of pages | 12 |
| Journal | Journal of the American College of Cardiology |
| Volume | 76 |
| Issue number | 13 |
| DOIs | |
| State | Published - Sep 29 2020 |
Funding
Funding was provided by Bayer AG, Siemens Healthineers, and in part by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. Dr. Arai has a Cooperative Research and Development Agreement (CRADA) with Bayer, Siemens, and Circle CVI Inc.; and has patents and invention reports related to perfusion quantification and cine MRI. Dr. Schulz-Menger has served as an advisor for Bayer. Dr. Berman has served as a consultant for Bayer. Dr. Han has received research grants from Gilead Sciences and General Electric; has served as a consultant for Acceleron, Bracco, and Complexa; and has served on the Speakers Bureau of General Electric, all unrelated to this work. Dr. Gutberlet has received speaker honorarium from Bayer, Bracco, Circle CVI, Philips, and Siemens. Dr. Woodard has received research support from Bayer, Lilly, and Roche; has a research agreement with Siemens; and has served as a consultant for Medtronic. Dr. Schoepf has received research support from and/or served as a consultant for Bayer, Bracco, Elucid BioImaging, GE, Guerbet, HeartFlow, and Siemens. Dr. Friedrich has received grants and personal fees from Circle Cardiovascular Imaging Inc., outside of the submitted work. Drs. Haverstock, Liu, Brueggenwerth, Bacher-Stier, and Santiuste are employees of Bayer. Dr. Pennell has received research support from Siemens, ApoPharma Apotex, La Jolla, and Bayer; and has served as a consultant for Apotex, La Jolla, and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Raymond Y. Kwong, MD, MPH, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, served as Guest Editor-in-Chief for this paper.
Keywords
- CMR
- coronary artery disease
- gadobutrol
- myocardial infarction
- myocardial perfusion
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
