Efficacy and Safety of Half-Dose Gadopiclenol versus Full-Dose Gadobutrol for Contrast-enhanced Body MRI.

Background Gadopiclenol is a macrocyclic gadolinium-based contrast agent (GBCA) with higher relaxivity compared with standard GBCAs, potentially allowing gadolinium dose reduction without decreasing efficacy. Purpose To investigate whether gadopiclenol at 0.05 mmol/kg is noninferior to gadobutrol at 0.1 mmol/kg for lesion visualization in body MRI. Materials and Methods A randomized, double-blind, crossover, phase 3 study was conducted between August 2019 and December 2020 at 33 centers in 11 countries. Adults with at least one suspected focal lesion in one of three different body regions (head and neck; breast, thorax, abdomen, or pelvis; or musculoskeletal system) underwent two contrast-enhanced MRI examinations, randomized to start with either gadopiclenol or gadobutrol. MRI examinations were read by three blinded expert readers for each respective body region. Readers rated border delineation, internal morphologic characteristics, and visual contrast enhancement. Three additional blinded readers assessed reader preference. For safety analysis, adverse events were recorded. The differences between gadopiclenol- and gadobutrol-enhanced MRI in terms of lesion visualization were analyzed with a generalized linear mixed model using a two-sided paired t test. Results Among 273 participants (mean age, 57 years ± 13 [SD]; 162 women) who underwent both gadopiclenol- and gadobutrol-enhanced MRI and had at least one correlating lesion, 260 participants without major protocol deviations were analyzed for noninferiority. Gadopiclenol was noninferior to gadobutrol for all qualitative visualization parameters and for all readers (lower limit 95% CI of the difference of at least -0.10, which was above the noninferiority margin [-0.35]; P < .001). For most participants (75%-83% [206-228 of 276]), readers reported no preference between gadopiclenol- and gadobutrol-enhanced images. Adverse events did not differ in frequency, intensity, type, or association with GBCA injection (12 of 288 participants receiving gadopiclenol and 16 of 290 receiving gadobutrol). Conclusion Gadopiclenol at 0.05 mmol/kg was comparable with gadobutrol at 0.1 mmol/kg for lesion evaluation at contrast-enhanced body MRI and had a similar safety profile. Clinical trial registration no. NCT03986138 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Bashir and Thomas in this issue.

Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for use.

Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field.

Nonstenotic bicuspid aortic valve is associated with elevated plasma asymmetric dimethylarginine.

BACKGROUND: Recently, it has been reported that nonstenotic bicuspid aortic valve (BAV) with dilated proximal aorta is linked with increased matrix metalloproteinase-2 (MMP-2) and endothelial dysfunction. OBJECTIVE: We wondered whether asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, might be altered and associated with MMP-2 in BAV patients. We assessed the relation between ADMA levels and aortic diameters and hypothesized that elevated ADMA might be an independent predictor of progressive aortic dilatation in BAV patients. METHODS: We studied 20 patients with nonstenotic BAV (17 men and 3 women, median age 27, range 24-33 years). Twenty age-matched patients with tricuspid aortic valves served as controls. Plasma levels of ADMA, symmetric dimethylarginine (SDMA), L-arginine, serum MMP-2, MMP-9, and plasma total homocysteine (tHcy), together with parameters of aortic elasticity, were measured. RESULTS: ADMA and MMP-2 levels were higher in the BAV group compared with controls (medians, 0.55 vs. 0.43 µmol/l, P < 0.001 and 1.25 vs. 1.00 µmol/l, P < 0.001, respectively). The BAV patients also had higher SDMA and tHcy levels than controls (0.39 vs. 0.35 µmol/l, P < 0.001 and 11.5 vs. 9.7 µmol/l, P = 0.006). ADMA levels in BAV patients correlated with aortic annulus (r = 0.4, P = 0.043), peak aortic velocity (r = 0.6, P = 0.001), aortic distensibility (r = 0.6, P = 0.004), aortic stiffness index (r = 0.7, P < 0.001), and aortic strain (r = 0.7, P < 0.001) as well as with MMP-2 (r = 0.6, P = 0.002) and tHcy (r = 0.4, P = 0.042). CONCLUSIONS: This study is the first to show that circulating ADMA together with MMP-2 is a marker of proximal ascending aortic dilatation and impaired aortic elastic properties in nonstenotic BAV patients. It might be speculated that plasma ADMA could be helpful in identifying BAV patients at a higher risk of aortic aneurysm.