Ultrasound enhancing agents modify the effect of suboptimal image quality on mortality

Abstract Background Suboptimal image quality (SIQ) on transthoracic echocardiography (TTE) is independently associated with a higher risk for mortality. Ultrasound enhancing agents (UEAs) are indicated to enhance endocardial border definition in these settings, but it remains uncertain if the use of UEAs modifies risk of mortality or changes the prognostic association of key TTE variables such as LVEF on mortality among those with SIQ. Methods We evaluated the relationship of SIQ, UEA receipt, and mortality using structured reports from clinically-indicated TTEs, 2018-2024, across a single large US-based multicenter community and academic healthcare network linked to state mortality registries (N = 79,412; mean age 65.6 ± 17.1 years, 49.5% female). We repeated the analysis in a separate TTE report dataset linked to Medicare claims and vital status information, 2003-2017 (N = 48,778; mean age 70.3 ± 13.2 50.5% female). Results A total of 14,526 (18.2%) individuals had SIQ, of which 28.1% received UEAs vs. 7.7% of those with adequate quality (p 0.001). Over a median follow-up of 0.67 years (Q1: 0.1, Q3: 2.14), 21.1% died (32.1% with SIQ vs. 18.6% without, HR 1.87, 95% CI 1.81-1.93, p 0.001). As an effect modifier, UEA use attenuated the relationship between SIQ and mortality (UEA+: SIQ vs. adequate quality, HR 1.21, 95% CI 1.12-1.31, p 0001; UEA-: SIQ vs. adequate quality, HR 1.91, 95% CI 1.84-1.98, p 0.001; interaction p 0.001). In individuals with SIQ, the inverse association of LVEF with mortality was stronger in those receiving UEAs vs. not (Table; p-value for 3-way interaction between UEA, SIQ, and LVEF on mortality = 0.037). Findings were similar in the separate Medicare-linked dataset, where a relationship between SIQ and mortality was observed only in those who did not receive UEAs (UEA+: SIQ vs. adequate quality, HR 1.00, 95% CI 0.83-1.20, p = 0.99; UEA-: SIQ vs. adequate quality, HR 1.53, 95% CI 1.48-1.58, p 0.001; interaction p 0.001). Conclusion While SIQ is associated with increased mortality, this hazard rate is lower in those receiving UEAs. In individuals with SIQ, the inverse association of LVEF and mortality was greater in individuals receiving UEAs vs. those not receiving UEAs. Further studies are needed to evaluate the unbiased effect of UEAs on mortality.