Sonothrombolysis as an adjunct to primary percutaneous coronary intervention in ST-elevation myocardial infarction patients: a systematic review and meta-analysis

Background/Introduction Despite advances in interventional techniques and medical therapy, microvascular obstruction (MVO) and suboptimal myocardial reperfusion remain major challenges even after successful primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Sonothrombolysis, which combines high mechanical index ultrasound energy with microbubbles, has emerged as a promising adjunct to enhance thrombus dissolution and microvascular flow. Aims We aimed to evaluate the efficacy of sonothrombolysis as an adjunct to primary PCI in patients with ST-elevation myocardial infarction. Methods We systematically searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to 15 September 2025, to identify studies comparing sonothrombolysis plus PCI vs. PCI alone. Pooled analyses were performed 9 outcomes including left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS), left ventricular mass (LVM), wall motion score index (WMSI), infarct size (IS), relative infarct size, and microvascular obstruction (MVO) using standardised mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI), and heterogeneity was assessed using the I2 statistic. All analyses were done using Review Manager version 5.4. Results Five studies, including 699 patients, were analysed, with 377 patients in the sonothrombolysis group and 322 patients in the control group. Sonothrombolysis significantly improved LVEF (SMD = 0.31, 95% CI [0.15, 0.48], P = 0.0002; I2 = 36%) and LV-GLS (SMD = 0.69, 95% CI [0.35, 1.03], P < 0.0001; I² = 40%) compared to the control group. WMSI was significantly better in the sonothrombolysis group (MD = −0.16, 95% CI [−0.21, −0.11], P < 0.00001; I2 = 0%). Infarct size was reduced (MD = −5.78, 95% CI [−11, −0.56], P = 0.03; I2 = 56%), and relative infarct size also decreased (MD = −3.94, 95% CI [−5.79, −2.09], P < 0.0001; I2 = 23%). Analysis of MVO showed statistically significant difference favouring the sonothrombolysis group (SMD = −0.49, 95% CI [−0.87, −0.12], P = 0.01; I2 = 0%). Left ventricular mass (LVM) analysis showed non statistically significant differences between the two groups (MD = −0.65, 95% CI [−10.38, 9.08], P = 0.9; I2 = 18%). Conclusions Sonothrombolysis significantly improves early myocardial recovery, reduces infarct size, and mitigates microvascular obstruction when used as an adjunct to primary PCI in STEMI. By enhancing both global systolic function (LVEF) and myocardial deformation (LV-GLS), this intervention offers a promising strategy for improving post-infarct prognosis. Future large-scale multicenter trials with standardised protocols are warranted to validate long-term clinical outcomes and optimise treatment delivery.