Clinical trial NCT06506448: Risk Characterization of Non-culprit Vessels in Patients Undergoing Primary PCI for ST-elevation MI in Multivessel Disease
Official title: Anatomical, Physiological and Inflammatory Characterization of the Non-Culprit Vessels in Patients Undergoing Primary PCI for ST-Elevation Myocardial Infarction in the Presence of Multivessel Disease Toward a Personalised Approach to Complete Revascularisation After Primary PCI
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: ST Elevation Myocardial Infarction
Keywords: Primary percutaneous coronary intervention
Infarct related artery
Non-infarct related artery
Computerised Tomography Coronary Angiography CTCA
Fractional Flow Reserve from CT (FFRct)
Fat Attenuation Index (FAI)
Inflammation
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
name: HeartFlow, Inc.
name: Wessex Heartbeat
name: Caristo
First posted: 2024-07-17
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting with ST elevation myocardial infarction who are found to have significant stenoses in the non-infarct related artery(s) defined as coronary stenosis \>50% by visual estimation

Brief summary: Most heart attacks occur because a clot forms in a coronary artery blocking blood flow. Without blood heart muscle dies. Untreated, clots can cause a specific type of heart attack -ST-elevation myocardial infarction (STEMI). STEMI patients are treated immediately by finding the blocked artery ("culprit" lesion) using a dye injected into the coronary arteries and then by unblocking the artery using balloons and stents. This procedure - primary angioplasty - is offered 24/7 and limits the size of heart attacks and saves lives.

Cardiologists know how to treat STEMI patients but it's less clear what to do about narrowings in other coronary arteries ("bystander" disease). This is important - if they're left alone some bystander lesions can cause future events including heart attacks or angina. Recent trials compared stenting ALL the bystander narrowings after primary angioplasty, with stenting none and showed some benefit from stenting all of them ("complete revascularisation").

However, complete revascularisation carries extra risk, putting patients through more complicated procedures and using up resource. A blanket strategy of complete revascularisation of ALL bystander narrowings in ALL STEMI patients is unlikely to be the correct answer as only a small minority of these patients have further events.

In PICNIC the investigators want to identify bystander narrowings most likely to cause a future event, and those unlikely to do so. The study can then test the hypothesis that only the high-risk bystander narrowings need stenting, and the others can be treated with tablets only. Investigators will study patients using specialised imaging techniques from coronary artery CT scans and levels of inflammation to see which narrowings cause future events and which do not. If this can be done, a case can be made to test complete revascularisation only in bystander narrowings that look high risk.

Detailed description: 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:

1. markers of systemic inflammatory status
2. plaque anatomy including lesion severity and markers of lesion vulnerability on CTCA
3. assessment of individual coronary vessel inflammation using CT-derived fat attenuation index
4. 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:

1. 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?
2. 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)?

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Cardiogenic shock
2. Decompensated heart failure requiring intubation, inotropes, or intra-aortic balloon counter pulsation
3. Refractory ventricular arrhythmia
4. Previous coronary artery bypass surgery (CABG)
5. Stent thrombosis and in stent restenosis
6. An intention before inclusion into the study to revascularize a non-culprit lesion
7. Active malignancy or inflammatory disorders such as rheumatoid arthritis or inflammatory bowel disease
8. Severe valvular heart disease requiring surgery
9. Planned surgical revascularisation
10. Active participation in another study/trial
11. \< 12 months life expectancy
12. 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

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

Primary outcomes:
measure: Correlation between major adverse cardiac & cerebrovascular events (MACCE) and CTCA-derived anatomical, physiological, plaque & inflammatory characteristics and serum inflammatory markers at 2 years
timeFrame: 2 years
Secondary outcomes:
measure: Correlation between major adverse cardiac & cerebrovascular events (MACCE) and components of CTCA-derived anatomical, physiological, plaque & inflammatory characteristics and serum inflammatory markers at 1 year
timeFrame: 1 year
measure: Correlation between anatomical, physiological & serum inflammatory markers and future adverse events at 3 years
timeFrame: 3 years
measure: Development of a risk score to predict clinical events based upon individual-, vessel- & lesion-specific factors
timeFrame: 1 year
measure: Development of a risk score to predict clinical events based upon individual-, vessel- & lesion-specific factors
timeFrame: 3 years
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: University Hospitals Dorset NHS Foundation Trust
state: Dorset
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Nick Curzen, PhD
role: PRINCIPAL_INVESTIGATOR
References: