Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging for Detection of Coronary Artery Disease
Andrew E. Arai, Jeanette Schulz‐Menger, Daniel S. Berman, Heiko Mahrholdt, Yuchi Han, W. Patricia Bandettini, Matthias Gutberlet, Arun Abraham, Pamela K. Woodard, Joseph B. Selvanayagam, Gerry P McCann, Christian Hamilton‐Craig, U. Joseph Schoepf, Ru‐San Tan, Christopher M. Kramer, Matthias G. Friedrich, Daniel Haverstock, Zheyu Liu, Guenther Brueggenwerth, Claudia Bacher-Stier, Marta Santiuste, Dudley J. Pennell, Dudley J. Pennell, Jeanette Schulz‐Menger, Heiko Mahrholdt, Matthias Gutberlet, Ulrich Krämer, Giso von der Recke, Kai Naßenstein, Christoph Tillmanns, Matthias Taupitz, Gregor Pache, Oliver K. Mohrs, Joachim Lotz, Sung-Min Ko, Ki Seok Choo, Yon Mi Sung, Joon‐Won Kang, Stefano Muzzarelli, Uma Valeti, Gerry P McCann, Sukumaran Binukrishnam, Pierre Croisille, Alexis Jacquier, Brett R. Cowan, Andrew E. Arai, Daniel Berman, Dipan J. Shah, W. Patricia Bandettini, Yuchi Han, Pamela K. Woodard, Ryan Avery, Joseph Schoepf, James Carr, Christopher M. Kramer, Scott D. Flamm, Mukesh Harsinghani, Stamitios Lerakis, Raymond G. Kim, Subha V. Raman, François Marcotte, Ali Islam, Matthias G. Friedrich, Arun Abraham, Joseph B. Selvanayagam, Christian Hamilton‐Craig, Woon Kit Chong, Lynette Teo, Ru‐San Tan
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.