Contemporary Safety of Ultrasound Enhancing Agents in a Nationwide Analysis
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".