While recently published research suggested an increase in severe allergic reactions associated with ultrasound-enhancing agents (UAEs), a new nationwide study involving over 11 million patients found that UAE use for transthoracic (TTE) or stress echocardiography (SE) was linked to lower rates of death.
For the retrospective study, recently published in the Journal of the American Heart Association, researchers reviewed data from a nationwide claims database for 11,421,463 individuals (mean age of 57.5) who had TTE or SE. According to the study, UEAs were utilized for 500,073 patients (4.4 percent of the total cohort).
The study authors found that the overall all-cause death rate was lower with UEA use in comparison to no UEA use in the cohort (0.02 percent vs. 0.14 percent). After propensity matching, the all-cause death rate declined to 0.07 percent for patients who did have UEAs for TTE or SE exams.
The researchers also noted comparable rates of adverse events between UEA use and no UEA use for patients undergoing TTE or SE. In addition to an equivalent rate of anaphylaxis (0.01 percent), the study authors pointed out no statistically significant differences in the between the groups in the propensity-matched cohort with respect to rates of myocardial infraction (1.97 percent for UEA use vs. 1.67 percent for no UEA use), ventricular tachycardia (0.99 percent vs. 0.8 percent) and cardiac arrest (0.12 percent vs. 0.26 percent).
“These results overall underscore the continued safety of UEAs in nationwide practice and suggest observed differences across agents may be due in part to the settings in which these agents are used and patient comorbidities,” wrote lead author Jordan B. Strom, M.D., MSc, who is affiliated with the Department of Medicine and the Cardiovascular Division at the Beth Israel Deaconess Medical Center in Boston, and colleagues.
In the cohort with propensity score marching, the study authors noted no significant differences between the three UEA agents included in the study with respect to odds of death, citing 0.02 percent for Definity (Lantheus), 0.03 percent for Lumason (Bracco Diagnostics) and 0.01 percent for Optison (GE HealthCare). The researchers added that rates of other adverse outcomes were similar across these agents and those not receiving UEAs.
Three Key Takeaways
1. UEA use linked to lower odds of death. In a nationwide cohort of over 11 million patients undergoing transthoracic or stress echocardiography, the use of ultrasound-enhancing agents (UEAs) was associated with lower all-cause mortality compared to those who did not receive UEAs.
2. Comparable safety profile. The incidence of adverse events —including anaphylaxis, myocardial infarction, ventricular tachycardia, and cardiac arrest — was similar between patients who received UEAs and those who did not, reinforcing the overall safety of UEAs in clinical practice.
3. Setting and comorbidities may influence UEA use. UEA use was more common in emergency settings and among patients with recent anticoagulation therapy, while it was less frequently used in patients with cerebrovascular disease or recent acute myocardial infarction, suggesting that patient characteristics and clinical context may influence both the choice and outcomes of UEA use.
The study authors pointed out that UEA use was more common for patients who had an index TTE or SE in an emergency department setting (12.6 percent vs. 4.5 percent) and in those who had anticoagulation therapy within a month prior to index TTE or SE (8.6 percent vs. 5.8 percent). The use of UEAs occurred less in patients with cerebrovascular disease, recent coronary angiography, or a recent acute myocardial infarction, according to the researchers.
(“The findings) suggest that safety differences between agents should be contextualized by the setting of administration, the comorbidities of those receiving UEAs, and the route/manner of administration. Given the plurality of benefits associated with UEA receipt and underuse relative to need, these data support the continued use of UEAs for diagnostic evaluation,” added Strom and colleagues.
(Editor’s note: For related content, see “FDA Expands Approval of Cardiac Ultrasound Imaging Agent for Pediatric Patients,” “FDA Clears AI-Enabled Software for Cardiac Ultrasound” and “What New Research Reveals About Novice Use of AI-Guided Cardiac Ultrasound.”)
In regard to study limitations, the authors acknowledged the possibility of unmeasured variables that may have affected assessments of the UEAs reviewed in the study. They conceded a lack of death date information in the data set and noted that serial exposure to UEAs was not assessed in the study.
