Abstract Body (Do not enter title and authors here): Background:
Distinguishing dense spontaneous echo contrast (SEC) from true thrombus in the left atrial appendage (LAA) remains a major diagnostic challenge in atrial fibrillation (AF), often resulting in delays in cardioversion or left atrial appendage closure (LAAC). Low-dose isoproterenol (ISP), a β-adrenergic agonist, may enhance LAA contractility and washout, facilitating SEC resolution and revealing underlying thrombus. We conducted the first meta-analysis to evaluate the diagnostic yield, physiological impact, and safety of ISP infusion during transesophageal echocardiography (TEE).
Methods:
A systematic search of PubMed, Embase, Scopus, Cochrane, and Google Scholar was conducted through April 2025 for studies evaluating ISP use during TEE in AF patients with dense SEC or sludge. Eight studies (n=174) were included. Primary outcomes were change in LAA emptying and filling velocities (cm/s), and SEC or sludge resolution. Secondary outcomes included unmasking of thrombus, changes in heart rate (HR) and systolic blood pressure (SBP), and adverse events. Subgroup analysis was performed based on SEC density. Continuous variables were pooled using random-effects models with 95% confidence intervals (CI) and heterogeneity (I2); binary outcomes were descriptively summarized.
Results:
ISP increased LAA emptying velocity by +45.3 cm/s (95% CI: 37.4–53.3; I2=64.9%) and filling velocity by +43.7 cm/s (95% CI: 27.8–59.5; I2=92.7%). HR rose by +34.4 bpm (95% CI: 13.0–55.7), and SBP decreased by –8.8 mmHg (95% CI: –13.9 to –3.6). SEC or sludge resolved in 152 of 170 cases (89.4%). Among 110 patients with pre- and post-infusion SEC grading, 74 (67.3%) showed improvement. ISP unmasked thrombus in 2 patients (1 surgical confirmation), with 4 additional suspected cases. Adverse events included palpitations (27.8%) and PVCs or hypotension (4.8%), with no procedural strokes or sustained arrhythmias reported. In subgroup analysis, LAA velocity increased by +37.5 cm/s (95% CI: 30.8–44.2; I2=20.3%) in dense SEC and by +62.3 cm/s (95% CI: 48.3–76.2; I2=0%) in sludge (p < 0.01 for subgroup difference).
Conclusions:
Low-dose ISP during TEE improves LAA flow and enhances diagnostic clarity in AF patients with dense SEC. Nearly 90% of cases showed SEC resolution, and clinically relevant thrombus was identified in select cases. ISP-guided TEE may be a valuable adjunct in decision-making for rhythm control or LAAC when thrombus cannot be excluded.