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

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

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.

Study Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Diagnostic test: CT Coronary Angiography

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)?

• Study Type: Observational
• Enrollment (Estimated): 320

Contacts and Locations

• Study Contact: Name: Zoe Nicholas; Phone Number: 02381208538; Email: zoe.nicholas@uhs.nhs.uk

Study Locations

• United Kingdom
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH15 2JB
      • Recruiting
      • University Hospitals Dorset NHS Foundation Trust
      • Contact: Jonathan Hinton, MD; Phone Number: 01202303626; Email: jonathan.hinton@uhd.nhs.uk
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • University Hospital Southampton NHS Foundation Trust
      • Principal Investigator: Nick Curzen, BM(Hons) PhD FRCP
      • Contact: Nick Curzen, BM (Hons) PhD FRCP; Email: nick.curzen@uhs.nhs.uk
      • Sub-Investigator: Michael Mahmoudi, PhD
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • Recruiting
      • Royal Stoke University Hospital
      • Contact: Mamas Mamas; Phone Number: 01782 715444; Email: mamasmamas1@yahoo.co.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
STEMI patients with multivessel disease; 320 patients undergoing primary angioplasty for ST-elevation myocardial infarction (STEMI) who have bystander disease in a main coronary artery with at least one stenosis of 50% or more	Diagnostic test: CT Coronary Angiography; CTCA for anatomical, physiological, plaque composition and inflammatory assessment of coronary arteries; Other Names: FFRCT and plaque analysis (HeartFlow) and Fat Attenuation Index (Caristo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between major adverse cardiac & cerebrovascular events (MACCE) and CTCA-derived anatomical, physiological, plaque & inflammatory characteristics and serum inflammatory markers at 2 years	Correlation between: major adverse cardiac & cerebrovascular events (MACCE) defined as the composite of all-cause mortality, cardiovascular death, cardiac arrest, acute coronary syndrome (unstable angina, NSTEMI, or STEMI), additional revascularization by CABG or PCI, rehospitalisation for angina, heart failure, stroke, ventricular or atrial fibrillation or tachyarrhythmia at 2 years &:; Anatomical & physiological characteristics of coronary vessels/lesions in the NIRA(s) as assessed by CTCA parameters (FFRCT + FAI + plaque characteristics)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Correlation between: major adverse cardiac & cerebrovascular events (MACCE) defined as the composite of all-cause mortality, cardiovascular death, cardiac arrest, acute coronary syndrome (unstable angina, NSTEMI, or STEMI), additional revascularization by CABG or PCI, rehospitalisation for angina, heart failure, stroke, ventricular or atrial fibrillation or tachyarrhythmia at 1 year &:; Anatomical & physiological characteristics of coronary vessels/lesions in the NIRA(s) as assessed by CTCA/FFRCT/FAI parameters between individual components of MACCE	1 year
Correlation between anatomical, physiological & serum inflammatory markers and future adverse events at 3 years	Correlation between: major adverse cardiac & cerebrovascular events (MACCE) defined as the composite of all-cause mortality, cardiovascular death, cardiac arrest, acute coronary syndrome (unstable angina, NSTEMI, or STEMI), additional revascularization by CABG or PCI, rehospitalisation for angina, heart failure, stroke, ventricular or atrial fibrillation or tachyarrhythmia at 3 years &:; Anatomical & physiological characteristics of coronary vessels/lesions in the NIRA(s) as assessed by CTCA/FFRCT/FAI parameters between individual components of MACCE	3 years
Development of a risk score to predict clinical events based upon individual-, vessel- & lesion-specific factors	To build a multidimensional AI-mediated deep learning model that uses the following data inputs (a) blood biomarkers, (b) CTCA lesion severity, (c) CTCA conventional plaque characteristics (e.g. spotty calcification etc); (d) FFRCT-derived plaque characteristic (ie adverse plaque and haemodynamic characteristics); (d) FAI-derived output; (e) clinical characteristics in order to correlate them with clinical events. The model will then be used to develop a risk score	1 year
Development of a risk score to predict clinical events based upon individual-, vessel- & lesion-specific factors	To build a multidimensional AI-mediated deep learning model that uses the following data inputs (a) blood biomarkers, (b) CTCA lesion severity, (c) CTCA conventional plaque characteristics (e.g. spotty calcification etc); (d) FFRCT-derived plaque characteristic (ie adverse plaque and haemodynamic characteristics); (d) FAI-derived output; (e) clinical characteristics in order to correlate them with clinical events. The model will then be used to develop a risk score	3 years

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust
• Collaborators: Boston Scientific Corporation; HeartFlow, Inc.; Wessex Heartbeat; Caristo
• Investigators: Principal Investigator: Nick Curzen, PhD, University Hospital Southampton NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: May 22, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 17, 2024

Study Record Updates

• Last Update Posted (Estimated): September 23, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; 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)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Pathological Conditions, Signs and Symptoms; ST Elevation Myocardial Infarction; Inflammation
• Other Study ID Numbers: RHMCAR0647

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not applicable. There will be no individual participant data available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No