A Clinical Study Of Selective Intracoronary Hypothermia Treatment In Primary Percutaneous Coronary Intervention

Objectives:Acute myocardial infarction,especially ST-segment elevation myocardial infarction(STEMI)is one of the main causes of death and disability worldwide.Primary percutaneous coronary intervention(PPCI)is one of the fastest and most effective methods to achieve myocardial reperfusion.Involving the mechanisms of ischemia and reperfusion injury,PPCI may contribute to secondary damage to the myocardium.Therapeutic hypothermia(TH),which was induced by cooling the jeopardized myocardium to 33℃by means of systemic hypothermia intervention or intracoronary hypothermia method,may attenuate this reperfusion injury.Intracoronary hypothermia,the feasibility and safety of which has been validated in humans,induced by selectively trans-coronary infusion of saline at different temperatures can reduce infarct size(IS)prior to reperfusion in animal models of STEMI.However,no data to date about the outcomes of this cooling method on infarct size and prognostic results have been reported.We aimed to assess the effect of this selective intracoronary hypothermia on outcomes in patients with STEMI undergoing PPCI.Methods:We screened STEMI patients,aged≧18 years,diagnosed with ST-segment elevation voltage of≧0.2 mV in at least 2 contiguous leads,and a duration of onset of symptoms within 6 hours,who were intended to PPCI.Sixty STEMI patients presenting with thrombolysis in myocardial infarction(TIMI)flow grade 0/1 were randomized after coronary artery angiography.Intracoronary hypothermia was induced by selective trans-coronary infusion of saline at 4℃to the endangered myocardium via the DIVER aspiration catheter in the 30 patients.The target distal coronary temperature,stable 6℃below the body temperature,was set on console and was induced by infusion with the cold saline at varying rate in the infarct-related artery.The time from onset of symptoms to randomization,door-to-flow restoration time,procedure duration,defibrillation,transient conduction block and the dosage of contrast used were record.High sensitive(Hs)-troponin T were measured before randomization and at 6 and 12 hours post-PCI.The primary endpoint,absolute IS expressed as IS/myocardium at risk(MaR),was assessed by cardiac magnetic resonance imaging at day 7 post-PPCI in 50 patients.Clinical follow-up was undertaken at day 30 after procedure.Results:Intracoronary hypothermia was successfully performed in hypothermia group,without increase in arrhythmia or hemodynamic instability.The difference of mean times from onset of symptoms to randomization(277±91 versus 272±94minutes,hypothermia versus control,P=0.84),door-to-flow restoration times(96±24versus 83±32 minutes,hypothermia versus control,P=0.07)and PPCI duration times(61±19 versus 54±18 minutes,hypothermia versus control,P=0.48)did not reach statistical significance.The mean temperature reduction of 5.8±1.1℃in distal coronary artery was achieved before reperfusion.The rate of no/slow flow did not show a statistical difference between the hypothermia and control group(7%versus17%,P=0.15).We found the significant reduction of median Hs-troponin T in the hypothermia group at 6 hours and 12 hours after PPCI in comparison with the control group[1626.00(1071.00-4033.00)ng/L versus 6399.00(3343.00-10000.00)ng/L,P<0.001;1643.00(1021.40-2960.50)ng/L versus 5999.00(3119.00-8198.50)ng/L,P<0.001,respectively].Although no statistical differences of mean IS normalized to BSA was found between the two groups(16.65±6.91 g/m~2 versus 21.11±9.33 g/m~2,P=0.061),mean IS/MaR was predominantly reduced in the hypothermia group(44.85±5.89%vs.50.69±10.75%,P=0.022),especially in the anterior STEMI subgroup(46.12±7.54%vs.55.27±11.175%,P=0.023).The clinical events,including cardiac death,stroke,major bleeding,heart failure,re-infarction,stent thrombosis,target vessel revascularization,cardiogenic shock and repeat PCI,appeared no statistical difference between the two groups at the 30-day follow-up.Conclusion:The statistical difference in IS/MaR by intracoronary hypothermia as adjunctive therapy to PPCI is an important observation and warrants a larger pivotal trial fully powered for efficacy.