Risk Characterization of Non-culprit Vessels in Patients Undergoing Primary PCI for ST-elevation MI in Multivessel Disease

Approximately 50% of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (CAD). Five randomized studies have shown that complete revascularization, either at the time of primary percutaneous coronary intervention (PPCI) or within 45 days of the index admission, is safe and reduces the risk of repeat coronary revascularization and myocardial infarction (MI), particularly in the non-infarct related artery (NIRA). Despite these improvements in clinical outcomes, no study to date has provided a mechanistic insight as to how complete revascularization of chronic bystander disease may lead to the observed benefit. Indeed, the randomized studies, through the variable nature of their results (reduction in MI versus revascularization etc), have suggested the possibility that there are differing mechanisms for the observed benefit. The data would also be consistent with the concept that not all patients undergoing primary PCI with bystander disease require or benefit from complete revascularisation. This is an important possibility with important potential implications for resource utilisation and patient experience.

The investigators hypothesize that the susceptibility of non-culprit disease to ischaemic events after primary PCI is variable between individuals, and possibly even between their coronary vessels and lesions. Specifically, the investigators postulate that this susceptibility may be related to multiple factors including their anatomical and physiological vulnerability, and their local vascular inflammatory status. In order to test this hypothesis, the investigators will systematically examine the following parameters in each bystander coronary vessel in patients who present with STEMI and are undergoing primary PCI of the culprit vessel:

• markers of systemic inflammatory status
• plaque anatomy including lesion severity and markers of lesion vulnerability on CTCA
• assessment of individual coronary vessel inflammation using CT-derived fat attenuation index
• vessel physiology using FFRCT (fractional flow reserve from computed tomography) incorporating wall shear stress and axial plaque stress.

Aims

The aims of this study are to address the following research questions:

• What are the anatomical, physiological & inflammatory features of lesions in the NIRA(s) of patients presenting with STEMI who are treated with a strategy of culprit-only PPCI?
• Is there an association between these anatomical, physiological & inflammatory features and the risk of non-culprit lesions causing adverse events in STEMI patients with significant bystander disease in the NIRA(s)?

Inclusion criteria

• Ability to provide written informed consent (post PPCI)
• Age 18 years to 85 years
• Presentation of acute STEMI within 12 hours of symptom on-set
• Culprit artery PPCI
• Coronary stenosis of > 50% diameter stenosis by visual estimation in NIRA with a minimum diameter of 2.5mm

Exclusion criteria

• Cardiogenic shock
• Decompensated heart failure requiring intubation, inotropes, or intra-aortic balloon counter pulsation
• Refractory ventricular arrhythmia
• Previous coronary artery bypass surgery (CABG)
• Stent thrombosis and in stent restenosis
• An intention before inclusion into the study to revascularize a non-culprit lesion
• Active malignancy or inflammatory disorders such as rheumatoid arthritis or inflammatory bowel disease
• Severe valvular heart disease requiring surgery
• Planned surgical revascularisation
• Active participation in another study/trial
• < 12 months life expectancy
• Contraindication to CTCA

• Presence of internal defibrillator
• Known allergy to iodinated contrast
• Pregnancy
• Contraindication to intravenous beta blockade
• Contraindication to acute sublingual nitrate administration
• Mechanical prosthetic heart valve
• Advanced renal impairment (creatinine >200)
• Significant valve disease (sever aortic stenosis or regurgitation; severe mitral regurgitation)

Angiographic exclusion criteria

• NIRA stenosis of 50% or more in the left main stem or the ostia of both the left anterior descending and circumflex arteries
• < TIMI (thrombolysis in myocardial infarction) flow grade 3 in the NIRA,
• Evidence of thrombus in the NIRA.