Cardioprotection with transcoronary saline infusion during primary angioplasty for ST-elevation myocardial infarction: design and rationale of the STEMI-Cool pilot study

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Abstract Background Prompt restoration of blood flow in ST-segment elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (pPCI) improves outcomes, but is associated with myocardial stunning, increased infarct size, and microvascular dysfunction. To date, there is no effective therapy to reduce this ischaemia-reperfusion injury (IRI). Mild systemic hypothermia has demonstrated potential but is difficult to achieve and poorly tolerated. Transcoronary hypothermia delivers rapid and effective myocardial cooling, is well tolerated, but not effective when commenced after flow restoration. Coronary haemodilution during reperfusion has shown cardioprotective effects in preclinical studies but has not been fully assessed. Purpose STEMI-Cool is a pragmatic, registry-based randomised clinical trial to assess recruitment rate, feasibility, and safety of a simple protocol which we have reported in a proof-of-concept study. The study has commenced recruitment and aims to overcome the limitations of previous negative studies by combining the beneficial effects of transcoronary cooling and dilution, initiating the infusion prior to wire insertion - therefore avoiding initial unprotected reperfusion (likely to be the critical time for IRI), and avoiding significant delays in reperfusion. Moreover, we will explore mechanistic endpoints and an original method to quantify the intracoronary dilution (with a thermodilution-derived "haemodilution constant ratio"). Lastly, we will investigate ways to "engineer out" the thermistor wire so that the method could be applied to routine pPCI with conventional equipment. Methods Pragmatic broad eligibility criteria allow potential recruitment of all STEMI cases clinically eligible for pPCI. Sixty patients will be randomised 1:1 to standard of care or protected reperfusion with continuous infusion of room temperature saline through the guiding catheter, to achieve intracoronary temperature reduction of 6-8°C. The infusion commences prior to crossing the occlusion with a thermistor wire, which is used as guidewire, and continues for 10 minutes after flow restoration (i.e., TIMI flow≥2). Invasive coronary physiology studies are undertaken after pPCI. Novel and established biomarkers of myocardial damage and inflammation (including dipeptidyl peptidase 3, tumor necrosis factor α, and interleukins 1β, 6, 10) are measured in the preprocedural arterial blood. Cardiac imaging and clinical outcomes are assessed at 48h and 6-12 months. Nesting STEMI-Cool in our local registry Heart-ACS facilitates blood sampling and follow-up. Conclusions STEMI-Cool will primarily investigate recruitment rate, feasibility and safety of an innovative, simple cooling and diluting strategy for cardioprotection during pPCI. Mechanistic outcomes will explore inflammatory, microvascular, structural and functional changes. Finally, we will aim to simplify further the protocol for future research and potential clinical use.STEMI-Cool method schematicSTEMI-Cool protocol timeline