Safety and Effectiveness of Intra-coronary Nitrite in Acute Myocardial Infarction

Coronary heart disease is still the commonest cause of death in the UK (in the main as a consequence of acute myocardial infarction (AMI)). Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF), and improving the clinical outcomes in such patients. However, substantial mortality and morbidity rates still persist with respect to longer term outcome. One of the main determinants of prognosis after AMI is the size of the infarct. Thus, identification of additional strategies that might decrease infarct size is desirable.

Evidence from pre-clinical studies suggests that inorganic nitrite administration reduces infarct size in animal models of AMI. In this study we aim to translate these findings into man. We will test the hypothesis that in patients with STEMI undergoing PPCI, an intra-coronary injection of nitrite, initiated prior to establishment of full reperfusion reduces infarct size through prevention of ischemia-reperfusion injury.

Inclusion criteria

• Patients aged at least 18 years
• Acute STEMI with ECG showing ST-segment elevation of 1mm or more in two adjacent limb leads or 2mm or more in at least two contiguous precordial leads or new left bundle branch block;
• Haemodynamically stable
• Estimated symptom to balloon or aspiration time < 6 hours
• Angiographically i) PPCI indicated for revascularisation ii) Single epicardial artery to be treated iii) Expected ability to use over the wire balloon

Exclusion criteria

• Patients on organic nitrate treatment (Nicorandil, isosorbide mononitrate)
• Previous history of AMI, systolic dysfunction or CABG
• Subjects presenting with cardiogenic shock (systolic blood pressure <80 mmHg for > 30 minutes, or requiring inotropes/emergency intra aortic balloon pump or cardiopulmonary resuscitation
• Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer.
• Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
• Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
• Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject's unwillingness to comply with all study-related procedures).
• Severe acute infection, or significant trauma (burns, fractures).
• Pregnancy.
• Contra-indications to CMR scanning i) Pacemakers, intracranial clips or other metal implants ii) Claustrophobia iii) Renal failure (eGFR < 30mls/min)
• History of alcohol or drug abuse within the past 6 months.
• History of congenital methaemoglobinaemia.
• Angiographically severe vessel tortuosity, diffuse disease or severe calcification which may impede successful delivery of the the over the wire balloon.