Sonothrombolysis after percutaneous coronary intervention in STEMI patients with increased risk for microvascular obstruction: a multicenter randomized controlled trial

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Lantheus. Introduction Despite successful recanalization with percutaneous coronary intervention (PCI), approximately 50% of patients with ST-elevation myocardial infarction (STEMI) suffer from ongoing infarction due to microvascular obstruction (MVO) (1). The use of intravascular microbubbles with concomittant intermittent high mechanical index (HMI) ultrasound impulses has been shown to dissolve thrombi and augment microvascular perfusion through vasodilative pathways (2). This technique, also termed sonothrombolysis, could be used in STEMI patients at high risk of developing MVO, to enhance reperfusion and limit infarct size. Methods In this multi-center, prospective, randomized controlled trial, 118 STEMI patients with increased risk for MVO (defined as occlusion of the LAD artery [center 1] or incomplete ST-resolution (≤70%) on the ECG after PCI irrespective of culprit artery [center 2]) will be randomized to sonothrombolysis or control. Sonothrombolysis treatment consists of a 3% infusion of lipid-coated microspheres with 40–80 transthoracic intermittent HMI ultrasound flashes. Control cases receive a 3% lipid-coated microspheres infusion with low mechanical index ultrasound and no more than 6 HMI flashes for perfusion imaging. Primary endpoints are infarct size (% of LV mass) and left ventricular ejection fraction (LVEF %) as assessed on cardiac magnetic resonance (CMR) imaging two months after inclusion. Secondary endpoints include changes in infarct size and LVEF on CMR (CMR < 1 week vs CMR at 2 months), ST-resolution, and clinical outcome at six months after inclusion. Results To date, 100 patients have been included. Mean age was 62 (± 12) and 82 patients (82%) were male. Culprit artery in patients included in center 2 was LAD in 38 patients (72%),RCA in 11 patients (21%) and LCX in 4 patients (7%). Time to first medical contact was 97 (IQR: 48–174) and 105 (IQR: 55–228) minutes and time from diagnosis to PCI was 45 (IQR: 36–63) and 49 (IQR: 40–59) minutes in the sonothrombolysis group and in the control group respectively. Summed ST-elevation on ECG before and after PCI (before randomization) was not statistically different: 11.5 mm (6.5 – 16.1) and 11.2 mm (5.9–16.9) (p = 0.81) before PCI and 8.4 mm (4.3 – 13.0) and 9.7 mm (4.1–16.4) (p = 0.39) after PCI, in the sonothrombolysis and control group. No differences between the groups were observed in medical history and drug use before admission. Conclusions STEMI patients with LAD occlusion and patients with incomplete ST-resolution on ECG after PCI are at increased risk of MVO and have worse clinical prognosis (3). This clinical trial aims to assess efficacy of post-PCI sonothrombolysis in this patient population to limit final infarct size and salvage myocardial function. Currently, 100 patients have been included with overall similar baseline characteristics. Inclusion, blinded assessment of primary and secondary endpoints and clinical follow up is expected to be completed in 2023.