TRANSCORONARY COOLING AND DILUTION FOR CARDIOPROTECTION DURING REVASCULARISATION FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: THE STEMI-COOL PILOT STUDY.

Background: The effectiveness of primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) is limited by reperfusion injury (RI), for which no therapy has yet proven beneficial. Transcoronary hypothermia has shown good tolerability and safety but with a neutral effect on outcomes in previous clinical trials. Potential reasons include complex protocols that prolong ischaemia and transient reperfusion prior to cardioprotection. Transcoronary haemodilution may also reduce RI by effectively slowing reperfusion. We developed a novel, simple method combining transcoronary cooling and dilution (TCCD) to reduce RI during pPCI. Methods: STEMI-Cool is a pragmatic, registry-based randomised pilot assessing recruitment, feasibility, and safety of a simplified TCCD strategy for cardioprotection. Sixty STEMI patients (1 drop out) presenting within 12 h of symptom onset, regardless of infarct territory, were randomised 1:1 to standard of care (SOC) pPCI or pPCI with TCCD. Patients in cardiogenic shock or resuscitated after cardiac arrest were also included. Up to 750 mL of room temperature normal saline (NS) was infused through the guiding catheter in the culprit vessel using a pressure bag, starting before crossing the occlusion, with pressure adjusted to reduce proximal coronary temperature by 6-8°C. A pressure/thermistor wire was used as a guidewire or placed proximally for monitoring. Post-procedure index of microvascular resistance (IMR) was measured. A subgroup underwent cardiac magnetic resonance (CMR) at 1-7 days. Clinical follow-up was at 6 weeks (completed) and 1 year (ongoing). Continuous variables were compared using the Student’s t-test or Mann–Whitney U test, as appropriate. Categorical data were analysed using the chi-square test or Fisher’s exact test. Results: An average of 549±229 mL of room temperature NS was infused at a rate of 61±29 mL/min, achieving a coronary temperature reduction of 6.37±1.22°C. Steady-state recruitment rate was ~5 patients/month at a single centre. Establishing TCCD protection before crossing the occlusion was feasible in 24/30 (80%) cases. The following data are presented as treatment vs SOC arms: there was no periprocedural mortality, while there were 2 vs 4 postprocedural deaths (p=0.37). There was an increase in ventricular fibrillation (VF): 10 vs 2, p=0.01, mainly occurring on reperfusion, however all patients were successfully defibrillated. CMR area at risk was similar: 23.69±11.01% vs 22.70±14.79%, p=0.87, with a trend towards infarct size reduction: 11.73±10.40% vs 17.74±12.39%, p=0.24. Further favourable trends in mechanistic outcomes are summarised in the table. We built a linear regression model linking diastolic blood pressure (DBP) to pressure required in the infusion bag to achieve target temperature (=DBP×4–100 mmHg). Conclusions: Preliminary results from STEMI-Cool suggest good recruitability and feasibility of the combined cooling and dilution cardioprotective strategy. There was an increased incidence of reperfusion arrhythmia in the intervention arm with no associated difference in clinical outcomes. NS was chosen for its reported safety in other studies, but the high incidence of VF may be related to lack of physiological plasma electrolytes. Harmann’s solution was safe in our previous proof-of-concept study and might be preferred for future investigation. We demonstrated a relationship linking DBP to infusion pressure that may eliminate the need for a thermistor wire facilitating widespread adoption of this therapy if effective. The encouraging trends in mechanistic outcomes suggest the need for a multicentre, efficacy-powered trial to detect infarct size reduction.