Sonothrombolysis with microbolus administration of perfluoropropane as point of care therapy for STEMI patients

Abstract

Abstract Introduction There are still major obstacles to timely revascularisation of STEMI patients even on arrival to PCI capable centers. Delivery of intermittent high mechanical index(MI) pulses during contrast infusion(Sonothrombolysis) has been shown to improve culprit vessel recanalization rates, reduce infarct size and improve myocardial hemodynamics. Purpose Our objective was to see if sonothrombolysis administered with a low dose of echo contrast(2mL) given as successive microboluses resulted in angiographic recanalisation. This is pertinent in our resource limited setup as continuous infusion needs specialised pumps and cost of echo contrast is high. Methods This was a randomised control trial on 100 patients presenting with first STEMI (within a window period of 12 hours, Killips stage I or II) to the Chest Pain Unit(CPU) of our institution. The intervention was sonothrombolysis during successive microboluses of perfluoropropane followed by PPCI. Technique of Sonothombolysis: 1 vial of perfluoropropane(2mL) is agitated and diluted in 20ML normal saline(0.1%w/v). Using a 3 way stop cock, 2mL solution is given while performing echocardiography in standard views. This leads to good chamber opacification for 40-60 beats. Once chamber opacification is adequately achieved (usually within 10 beats), high MI pulses (>1.1 MI) were given repeatedly after low MI imaging shows replenishment of microbubbles in the myocardial segment. Once opacification wanes, then another bolus of 2mL is given and steps repeated. The control group underwent low MI imaging with 0.2mL of perfluoropropane followed by PPCI. Results The trial was halted after recruitment of 57 patients following an interim analysis which showed no significant benefit with sonothrombolysis. Angiographic recanalization of culprit vessel occured in 28% of cases (8vs6, p=0.589). Baseline characteristics were similar across both groups. The time from first medical contact(FMC) to balloon time were similar. The use of Gp IIb/IIIa inhibitors or thrombus aspiration catheters did not differ. Discussion Sonothrombolysis with successive microboluses of perflouropropane is not effective in producing angiographic recanalization in STEMI patients. Our results vary from that of Mathias et al which showed a 48% angiographic recanalization rate. The protocol of giving microboluses as against continuous infusion could have contributed though we looked specifically for microbubble replenishment in myocardial segments before delivering high MI pulses. Secondly the higher prevalence of diabetes, dyslipidemia and multivessel CAD in our population could have contributed to the lack of efficacy. Thirdly the mean window period (time between onset of symptoms to arrival at CPU) was 7±2.31hrs which could have contributed to thrombus organization and resistance to shearing forces produced by microbubble cavitation. Further randomized studies are needed to see the efficacy of sonothrombolysis in other populations.Table 1.Baseline CharacteristicsTable 2.Results