Despite all advances in diagnostic and therapeutic methods over the past century, ischemic heart disease (IHD) remains a leading cause of mortality and morbidity worldwide. IHD develops as a result of reversible or irreversible impairment of myocardial perfusion in acute or chronic settings. This perfusion abnormality most commonly arises from compromise of epicardial coronary artery patency due to stenosis, occlusion, or vasomotor abnormalities. Structural and/or functional alterations in the microcirculation may also contribute to impaired myocardial perfusion.

Conditions in which myocardial perfusion is acutely compromised are classified as acute coronary syndromes (ACS), whereas reversible ischemia developing on a chronic basis is evaluated under the umbrella of chronic coronary syndromes (CCS). In the assessment of epicardial (macrovascular) or microvascular pathologies leading to ischemia in CCS, angiography, a macroscopic lumenographic method, is often insufficient. Intracoronary pressure and flow measurements are required to determine the impact of angiographically detected epicardial lesions on coronary blood flow, perfusion pressure, and consequently myocardial perfusion. These measurements are referred to as invasive intracoronary physiology (IIP).

Current guidelines recommend that decisions regarding revascularization of intermediate epicardial lesions should be based on IIP. Revascularization guided by IIP is associated with reduced mortality and morbidity, along with a lower stent burden. IIP can be performed using pressure-based, flow-based, or combined strategies. Recent multinational studies indicate that strategies integrating both flow and pressure parameters achieve better clinical outcomes with fewer interventions and reduced stent implantation compared to pressure-only approaches. Indeed, in cases where coronary flow and flow reserve are preserved, abnormalities in pressure parameters alone may not justify revascularization.

Nevertheless, lesions deemed not to be associated with reversible ischemia based on IIP may still pose a risk due to plaque erosion/rupture and subsequent thrombotic cascades that can acutely compromise the lumen. Many acute coronary syndromes arise from lesions that are hemodynamically insignificant (i.e., do not affect flow) and unrelated to reversible ischemia in the CCS setting, but which undergo sudden near-total or total occlusion.

The histopathological characteristics of any coronary lesion can be evaluated using intracoronary imaging techniques. Intracoronary Optical Coherence Tomography (IC-OCT) is a high-resolution, real-time imaging modality that quantitatively assesses lipid-rich plaque content, evaluates the thickness and stability of the fibrous cap separating this content from the lumen, and provides detailed information regarding minimal lumen area, lesion morphology, surface characteristics, presence of erosion, and plaque vulnerability to rupture. IC-OCT can identify lesions that are hemodynamically insignificant yet may benefit from revascularization and have the potential to cause ACS.

Combined evaluation using IC-OCT and IIP enables an integrated assessment of both the relationship with chronic reversible perfusion impairment and the risk of precipitating ACS for each lesion and coronary segment, thereby facilitating optimal revascularization strategies. Despite the available evidence and guideline recommendations in CCS, the use of IC-OCT and IIP in the context of ACS remains limited due to procedural challenges and variability in practical application. These methods are not routinely recommended in guidelines and, in some cases, are even discouraged.

However, the optimal strategy for revascularization of non-culprit lesions in ACS remains uncertain, and no consensus has yet been established. Patients with ACS are at increased risk for recurrent events arising from all coronary lesions. Therefore, accurate evaluation and preventive revascularization strategies for these lesions are expected to provide substantial benefit. Our study aims to reclassify and characterize non-culprit lesions in patients with ACS using combined IC-OCT and IIP assessment.

Inclusion Criteria:

• Presenting to the clinic with a diagnosis of Acute Coronary Syndrome.
• Having a significant (total or subtotal) culprit lesion detected during the index angiography procedure and having successfully undergone percutaneous coronary intervention (PCI) for this lesion.
• Having at least one distant non-culprit lesion with moderate stenosis (between 50% and 90%) according to visual angiographic evaluation in coronary arteries (or side branches with a diameter >2.5 mm) that are not major epicardial and not major left main coronary arteries.
• Having TIMI III flow in the vessel containing the non-culprit lesion to be evaluated.
• The patient being able to understand the nature of the study and signing the written informed consent form.
• Patients for whom intracoronary hemodynamic evaluation is planned for treatment planning of the non-culprit lesion after the index procedure.

Exclusion Criteria:

Clinical Exclusion Criteria:

• Advanced renal insufficiency to the extent that the patient cannot tolerate the additional contrast load required for intracoronary imaging (IC-OCT) (e.g., eGFR < 30 mL/min/1.73 m²).
• Known serious allergy or absolute contraindication to the hyperemic agents to be used (e.g., adenosine, papaverine), iodinated contrast agents, or mandatory antiplatelet/anticoagulant therapy.
• Patients presenting to the hospital due to heart failure and cardiogenic shock.
• Additional investigation required due to in-stent restenosis of a non-culprit vessel.
• Patients with blood disorders, bleeding disorders, cancer, end-stage liver or kidney failure, patients with active bleeding, and pregnant women.

Angiographic and Procedural Exclusion Criteria:

• Presence of significant stenosis in the left main coronary artery (LMCA) or the patient having previously undergone coronary artery bypass graft (CABG) surgery.
• Failure of PCI on the culprit lesion in the index procedure, no-reflow, etc. The vessel containing the non-culprit lesion has technical impediments that prevent safe passage of the IC-OCT catheter or pressure/flow wire (e.g., excessive tortuosity, advanced angulation, very dense calcification, or chronic total occlusion [CTO]).

Patients presented with acute coronary syndrome undergoing successful PCI for the culprit vessel and at least one additional non-culprit vessel were enrolled form the Mehmet Akif Ersoy Hospital Emergency Department