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. 2025 May 20;14(10):e039480.
doi: 10.1161/JAHA.124.039480. Epub 2025 May 14.

Contemporary Safety of Ultrasound Enhancing Agents in a Nationwide Analysis

Jordan B Strom  1   2   3 , Sharon L Mulvagh  4 , Thomas R Porter  5 , Kevin Wei  6 , Jessica L Stout  1   3 , Michael L Main  7
Affiliations

Contemporary Safety of Ultrasound Enhancing Agents in a Nationwide Analysis

Jordan B Strom et al. J Am Heart Assoc. .

Abstract

Background: Ultrasound enhancing agents (UEAs) are an important diagnostic tool for transthoracic or stress echocardiography (TTE/SE) but recent concerns have been raised about their safety in reports from individual health systems. As such, we aimed to identify if UEAs for TTE/SE are associated with serious adverse events within 2 days of administration.

Methods and results: All-payor nationwide claims from 11.4 million insured individuals across the United States, 2018 to 2022 were used to evaluate rates of death, anaphylaxis, myocardial infarction, ventricular tachycardia, or cardiac arrest within 2 days of TTE/SE among adults receiving and not receiving UEAs. Of the 11 421 463 individuals included (mean age 57.5±16.2, 54.0% female, 46.2% White), a total of 500 073 (4.4%) received TTE/SE with UEAs. After propensity score matching, the odds of death were lower in those receiving UEAs (receipt versus nonreceipt, 0.02% versus 0.14%, odds ratio [OR], 0.23 [95% CI, 0.19-0.28], P<0.001) and were not different across agents (Definity: 0.02%, OR, 0.22 [95% CI, 0.18-0.28]; Lumason: 0.03%, OR, 0.33 [95% CI, 0.20-0.57]; Optison: 0.01%, OR, 0.17 [95% CI, 0.08-0.38]; all P < 0.001). Rates of nondeath outcomes were similar to those observed in individuals not receiving UEAs, overall, and across specific agents. Rates of all outcomes were stable across years, including considering pre- and post-COVID periods.

Conclusions: In this large nationwide claims analysis from 2018 to 2022, serious adverse events associated with UEAs for TTE/SE were uncommon and overall consistent across agents and years of study. Compared with nonreceipt, receipt of UEAs was associated with a lower odds of death within 2 days of TTE/SE.

Keywords: adverse events; claims; echocardiography; safety; ultrasound enhancing agents.

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Conflict of interest statement

Jordan B. Strom additionally reports grant funding from the National Institutes of Health (1R01HL169517, 1R01HL173998, 1R01AG063937), Anumana, EVERSANA Lifesciences, Bracco Diagnostics, and Philips Healthcare, consulting for Bracco Diagnostics, Edwards Lifesciences, GE Healthcare, Philips Healthcare, and EVERSANA Lifesciences. Jordan B. Strom additionally reports scientific advisory board roles for Ultromics, HeartSciences, Bristol Myers Squibb, Alnyam, Ultrasight, and EchoIQ and is on a clinical end point committee for Pfizer. The remaining authors have no disclosures to report.

Figures

Figure 1
Figure 1. Study flow chart.
Shown is a flow chart demonstrating study inclusion and exclusion criteria. The numbers of individuals excluded for each reason are not mutually exclusive. NDC indicates National Drug Code; PS, propensity score; TTE/SE, transthoracic echocardiography or stress echocardiography; and UEA, ultrasound enhancing agents.
Figure 2
Figure 2. Love plot demonstrating imbalances between groups before and after propensity score matching.
Shown are the standardized mean differences in baseline covariates between groups receiving and not receiving ultrasound enhancing agents both before propensity score matching (crude; white diamond) and after (matched; black circle). Vertical hashed lines indicate the standardized mean difference thresholds above and below which a group is considered to be imbalanced. In general, the plot results indicate that the groups are well balanced after matching. CABG indicates coronary artery bypass grafting; CCI, Charlson Comorbidity Index; ED, emergency department; Ins., insurance; MI, myocardial infarction; PCI, percutaneous coronary intervention; and SOC, setting of care.
See this image and copyright information in PMC

Comment in

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