A case report in cardiovascular magnetic resonance: the contrast agent matters in amyloid
© The Author(s). 2017
Received: 13 July 2016
Accepted: 21 December 2016
Published: 7 January 2017
Cardiac amyloidosis is a progressive but underdiagnosed and underappreciated cause of heart failure. In the last few years, cardiovascular magnetic resonance (CMR) has become the gold standard for non invasive diagnosis of cardiac amyloidosis with the characteristic subendocardial late gadolinium enhancement.
We describe a case of a patient who, in the process of aligning protocols for a trial between different centers, had a paired study with two different contrast agents, Dotarem® and MultiHance®. MultiHance® surprisingly failed to demonstrate the characteristic imaging pattern, showing only non specific late gadolinium enhancement at the inferior right ventricular insertion point and different myocardial extracellular volume fraction compared to the one obtained with Dotarem®. MultiHance® is used by many centres, because its partial blood protein binding is a strength for MR angiography, but late gadolinium enhancement, particularly non-ischemic, appears to be compromised.
This case report suggests that contrast agents should be selected with caution, especially with new therapies lining up for amyloid and CMR being used as exploratory end point in clinical trials.
KeywordsCase report Amyloidosis CMR Contrast
In the last decade, cardiovascular magnetic resonance (CMR) has grown dramatically and in amyloidosis has become the gold standard for non invasive diagnosis of cardiac involvement with the characteristic subendocardial late gadolinium enhancement (LGE) . The number of new referrals for cardiac amyloidosis has significantly increased in the last few years, with the diagnosis being based on CMR and the characteristic LGE. New contrast agents favoured for their high relaxivity related to blood protein binding,  have become available but no one has ever tested the diagnostic performance of these new agents in infiltrative disease.
Gd-BOPTA (MultiHance®) is an ionic linear chelate favoured for its high relaxivity related to blood protein binding,  which also makes it a partially “intra-vascular” contrast agent. Here, paired scanning performed serendipitously for a clinical trial failed to demonstrate the characteristic pattern of myocardial amyloidosis, and performed poorly compared to gadoterate meglumine. MultiHance® is widely used for CMR. This effect was unexpected – but theoretical concerns had been raised for ECV mapping with protein bound contrast agents . Due to difference in relaxivity between the contrast agents, some Authors proposed the use of a lower dose of Gd-BOPTA for reaching similar T1 and ECV values. In this case the same dose was used for both contrasts and this could explain in part the differences observed. In this case, the use of MultiHance® did not affect the diagnosis, but reporting the MultiHance® CMR in isolation without the previous work-up by the National Amyloid Centre could have conceivably led to a misdiagnosis.
We suggest that protein bound agents for interstitial enhancement of non-ischaemic cardiomyopathy (myocardium, ECV measurement) should be used with caution whilst further work is undertaken as the diagnostic performance may not be the same as non-protein bound variants.
Cardiovascular magnetic resonance
Late gadolinium enhancement
Phase Sensitive Inversion Recovery
Shortened Modified Look-Locker Inversion recovery
Availability of data and materials
If asked, I will provide or fully cooperate in obtaining and providing the original data on which the manuscript is based so the editors or their designates can examine it.
MF and JCM have made substantial contributions to conception and design of the case, have been involved in drafting the manuscript and revising it critically for important intellectual content and have given final approval of the version to be published. TAT, AMN, RYK, JDG and PNH have made substantial contributions to conception and design of the case, have been involved in revising the manuscript critically for important intellectual content and have given final approval of the version to be published. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors do hereby declare that all illustrations and figures in the manuscript are entirely original and do not require reprint permission.
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- Maceira AM, Joshi J, Prasad SK, Moon JC, Perugini E, Harding I, Sheppard MN, Poole-Wilson PA, Hawkins PN, Pennell DJ. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2005;111(2):186–93.View ArticlePubMedGoogle Scholar
- Pintaske J, Martirosian P, Graf H, Erb G, Lodemann KP, Claussen CD, Schick F. Relaxivity of Gadopentetate Dimeglumine (Magnevist), Gadobutrol (Gadovist), and Gadobenate Dimeglumine (MultiHance) in human blood plasma at 0.2, 1.5, and 3 Tesla. Investig Radiol. 2006;41(3):213–21.View ArticleGoogle Scholar
- Fontana M, White SK, Banypersad SM, Sado DM, Maestrini V, Flett AS, Piechnik SK, Neubauer S, Roberts N, Moon JC. Comparison of T1 mapping techniques for ECV quantification. Histological validation and reproducibility of ShMOLLI versus multibreath-hold T1 quantification equilibrium contrast CMR. J Cardiovasc Magn Reson. 2012;14:88.View ArticlePubMedPubMed CentralGoogle Scholar
- Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M, Gatehouse PD, Arai AE, Friedrich MG, Neubauer S, et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson. 2013;15:92.View ArticlePubMedPubMed CentralGoogle Scholar