Efficacy of sonothrombolysis as an adjunct to PCI in STEMI: a meta-analysis of randomized controlled trials

Abstract Background Primary percutaneous coronary intervention (PCI) has revolutionized the management of ST-elevation myocardial infarction (STEMI). However, optimal microvascular reperfusion — which is linked to improved clinical outcomes — remains a significant challenge with current therapies. Sonothrombolysis has emerged as a potential adjunct to PCI to enhance myocardial reperfusion in STEMI. Despite promising mechanistic insights, its clinical impact on myocardial reperfusion and subsequent cardiac function is uncertain. Purpose To systematically evaluate the effects of sonothrombolysis on myocardial reperfusion, cardiac mechanical function, as well as clinical and laboratory outcomes in patients with STEMI undergoing PCI. Methods We searched MEDLINE, Embase, and Cochrane databases for randomized clinical trials (RCTs) that assessed the effectiveness of sonothrombolysis associated with percutaneous coronary intervention in patients presenting with STEMI from inception to November 2024. Following PRISMA protocol, 184 articles were screened. Binary outcomes were analyzed using the Mantel-Haenszel random-effects model, with OR and 95%CI as effect size metrics. Mean differences (MD) were utilized to pool continuous endpoints. Heterogeneity variance (I²) was calculated by restricted maximum likelihood estimator and heterogeneity was computed with Cochrane’s Q statistic and Higgins and Thompson’s I² statistic. All calculations and graphic representations were executed using R version 4.4.2. Results After duplicate removal and exclusion by title and abstract, 36 studies were thoroughly read. A total of 5 RCTs with 294 patients were included out of which 150 (51,02%) were allocated to sonothrombolysis and 144 (48,97%) underwent PCI only. The mean age was 59.8 years and 79% were male patients. A significant difference in left ventricular ejection fraction (ECO LVEF) at 3 days post-procedure was observed in the intervention group compared to the control group (MD = 4.24%; 95%CI: 1.22 to 7.27; p = 0.006). Additionally, the intervention group showed a reduction in infarct size (g) at 3 days post-procedure compared to the control group (MD = -9.80 g; 95%CI: -13.63 to -5.98; p < 0.001). The presence of low heterogeneity among these analyses (I² ≤ 25%) reinforces the consistency of the findings. In other analyses involving several of the explored variables, a general trend toward better outcomes from sonothrombolysis compared to PCI-only was also observed. Conclusion These results suggest that sonothrombolysis contributes to better cardiac mechanical function and myocardial reperfusion following a cardiac ischemic event, potentially improving long-term clinical outcomes. Despite these promising findings, the current evidence remains limited. Therefore, further large-scale clinical trials are required to confirm its clinical applicability.LVEF at 3 days  Infarct size at 3 days