GBCA-related allergic reactions rare in cardiac MRI

CHICAGO - With the ongoing debate over the safety of gadolinium-based contrast agents (GBCAs), German researchers are offering evidence that GBCAs are safe to use in cardiac MRI applications, according to a study presented on Tuesday at RSNA 2017.

Based on data from the European Society of Cardiovascular Radiology (ESCR) MR/CT Registry, the frequency of acute adverse and severe events attributed to six GBCAs was less than 0.4%. Perhaps most importantly, the rate of allergic reactions varied slightly depending on the type of GBCA and pharmacological stressor used, even after researchers accounted for potential confounders.

"Certain combinations of GBCA and pharmacological stressors seem to further increase the risk of acute adverse events," said study co-author Dr. Johannes Uhlig from University Medical Center Göttingen.

Growing research

There has been considerable research in recent years into adverse events linked to GBCAs.

Behzadi et al recently performed a meta-analysis that included 716,978 administrations of linear, macrocyclic, ionic, and nonionic GBCAs. They found 662 immediate allergic reactions, representing an incidence rate of 0.52 per 10,000 injections. Of those adverse events, 539 (81%) were deemed mild, 86 (18%) were moderate, and 37 (6%) were severe. There were two deaths, for a rate of 2.8 deaths per 1 million administrations.

With cardiac MRI scans, GBCAs and pharmacological stressors often are combined to achieve superior image quality and diagnostic results, Uhlig explained.

"Still, there is inadequate literature that explicitly evaluates the potential interaction of these drug classes," he said. "Promoting patient safety is of utmost importance in the healthcare system, particularly in the case of cardiac examinations with patients that often have relevant comorbidities."

Uhlig and co-author Dr. Matthias Gutberlet, PhD, from Heart Center Leipzig explored the ESCR MR/CT Registry, which stores more than 180,000 exams from 1,124 users at 272 institutions in 32 countries. The database allows cardiac radiologists to upload their cases and exam results anonymously. At the same time, they can review cases from other registered clinicians and institutions.

"The number of contributors and cardiac MRI studies in the ESCR MR/CT Registry has increased significantly over the past 12 months," Uhlig said. "This growing database allows us to follow-up on our initial results and to evaluate potential changes in GBCA administration patterns and associated adverse events."

Allergic reactions

Using the registry, the researchers reviewed 72,839 GBCA-enhanced cardiac MRI scans performed between 2009 and 2016. There were 260 acute adverse events, for a frequency rate of 0.36%. The group reported 140 (0.19%) mild events, 132 (0.18%) moderate events, and 24 (0.033%) severe events.

By far, the most common allergic reactions were dyspnea (88 cases, 0.12%) and hypersensitivity (61 events, 0.084%) to a GBCA. There were no late-onset adverse events.

In addition, the linear GBCA gadodiamide had the lowest percentage (0.13%) of adverse events but also the fewest number of administrations (2,252). The macrocyclic GBCA gadoteric acid had the second-lowest rate of allergic reactions (0.25%) and the second-greatest number of administrations (14,257) in the study.

Pharmacological factors

The researchers also counted 54,285 patients who did not undergo pharmacological stress imaging. That group had 120 acute adverse events, for a frequency rate of 0.22%. In comparison, the remaining 18,554 patients who received pharmacological stress imaging had 140 occurrences (0.75%). The highest acute adverse event rate was reported for regadenoson (34 of 1,151 cases; 2.95%), with the most common allergic reaction being dyspnea (29 cases).

Uhlig and colleagues also considered other factors for how patients reacted to GBCAs. In a comparison of patients with known coronary artery disease, individuals with suspected or known cardiomyopathy (odds ratio [OR] = 0.5, p = 0.006), myocarditis (OR = 0.39, p < 0.001), and imaging indications classified as "other" (OR = 0.5, p = 0.005) were significantly less likely to experience an acute adverse event.

In addition, the volume of GBCA administered and its concentration, molecular structure, and thermodynamic stability showed no correlation with adverse events.

With this additional information on patients' reactions to GBCA-enhanced cardiac MRI scans, Uhlig said he and his fellow clinicians can adjust their protocols accordingly.

"At our institutions, patient populations receiving certain combinations of gadolinium-based contrast media and pharmacological stressor are under close surveillance during imaging," he added. "Should further prospective data support our findings on the increased likelihood of an adverse event for specific GBCAs and drug combinations, imaging protocols will be adapted accordingly."