Heart Attack Blood Oxygen Therapy Trial

This study is an academic, investigator-initiated clinical trial.

The design involves prospective enrolment of patients with a diagnosis of acute, anterior ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom and undergoing primary PCI with radial artery acess. The protocol begins after standard, primary percutaneous coronary intervention (PCI). The timepoint for randomization (time zero) is at the end of successful primary PCI. Eligibility criteria include successful completion of primary PCI, defined as TIMI flow grade 2-3 in the left anterior descending coronary artery.

Given that the initial point of urgent/emergency care is in the catheter laboratory, the consent process will involve an initial witnessed verbal informed consent followed by randomization. This approach is in line with prior research in our hospital, contemporary evidence, feedback from experts with lived experience and international practice guidelines [PMID: 37622654 PMID: 32143733]. The Patient Information Sheet and Consent form will be provided to patients and carers on the ward after the angiogram. If the patient agrees to continue in the study then written informed consent will be obtained on the ward.

The study assessments will involve a blood sample, coronary angiography, coronary physiology, cardiovascular magnetic resonance (CMR) imaging scans, health status questionnaires, and electronic case record linkage. If the patient is eligible to participate and agrees to have electronic health record linkage follow-up but no other assessments or procedures, then consent will be invited for electronic health record follow-up only (no visits).

Informed consent will initially be obtained following arrival in the catheter laboratory. Blood samples would be obtained following arterial sheath insertion before PCI (since hemodilution due to the volume of radiographic contrast media may confound the analysis) study begins at the end of standard care primary PCI. Patients who fulfil the eligibility criteria and who have given written witnessed informed assent will be randomly assigned (2:1) to the intervention group or the control group.

Coronary microvascular function will be assessed in all patients at the end of the standard care primary PCI. The diagnostic guidewire should be positioned in the left anterior descending coronary artery using X-ray fluoroscopy. This will be repeated at the end of the intervention / control procedure.

Intervention group SSO2 therapy involves withdrawal of arterial blood, extra-corporeal hyper-oxygenation (ZOLL Circulation Inc console), and infusion of the hyper oxygenated blood into the PCI-treated left anterior descending coronary artery. The hyper oxygenated blood is returned using a standard catheter positioned in the left main coronary artery, via radial artery access. Therefore, temporary radial artery access using one or both radial arteries is needed for the one-hour duration of the SSO2 therapy in the cardiac catheter laboratory. Blinding measures will be implemented, including after returning to the coronary care unit until the end of the study.

Control group To minimize bias, patients assigned to the control group would follow the same schedule as if they were assigned to the intervention group. A control procedure will be undertaken. This procedure will mimic the actual procedure but without additional artery access i.e. no oxygen catheter therapy. The control procedure will involve conscious sedation, local anesthetic given in the usual way in the radial area, manual pressure, activation of the ZOLL Circulation Inc console (without the blood circuit), and then application of the radial closure device. The patient will be cared for by the clinical team in the usual way. The patient will remain blind to treatment group allocation, including after returning to the coronary care unit until the end of the study. Blinding to treatment group assignment will be prospectively documented.

Participants will be followed up with in person contacts up to 1-year post enrolment. Electronic health records may be checked without participant contact into the longer term.

Inclusion criteria

• Age ≥18 years.
• Ischemic time ≤6 hours from symptom onset
• Acute anterior ST-segment elevation myocardial infarction
• Infarct-related left anterior descending coronary artery TIMI flow grade 2-3 at the end of PCI
• Radial artery access
• Partial pressure of oxygen (PaO2) >80 mmHg (10.7 kPa)

Exclusion criteria

• Proximal coronary artery stenosis that restricts blood flow with the SSO2 catheter in place
• Post-PCI non-stented dissection or perforation.
• Moderate - severe heart valve stenosis, insufficiency, pericardial disease, or non-ischaemic cardiomyopathy
• Known pregnancy.
• Cardiogenic shock
• Contra-indication to anticoagulation
• Acute mechanical complication e.g., ventricular septal rupture, pseudoaneurysm, mitral regurgitation
• Hemoglobin <10 g/dL
• Major bleeding or major surgery within the past two months
• Contra-indication to cardiovascular magnetic resonance (CMR) imaging e.g., severe claustrophobia, metallic foreign body.
• Lack of witness verbal consent.