Description

AIM Primary aim The present study aims to assess whether the composition of thrombus-aspirated material differs in samples retrieved from patients with OCT-described plaque rupture, erosion, or calcified nodules. In particular, the specific aim is to assess the presence of plaque components (atheromatous material, consisting of cholesterol clefts, foam cells, iron-loaded macrophages, cap fragments, and calcifications) in plaques described at OCT as RFC, IFC, and CN. The working hypothesis is that the pre-PCI aspirated material from plaque rupture should contain plaque components, while aspirated material from plaque erosion, should only contain thrombotic material. The pathology study was planned to be performed blindly to imaging data, and report independent descriptors of the pathology features.

Secondary aims

1. A secondary aim addresses pathophysiology mechanisms, potentially related to features promoting plaque rupture. Given the proposed major role of macrophages in the context of plaque inflammation commonly observed in vulnerable plaque prone to rupture, we aimed to investigate the presence of M1 (pro-inflammatory, pro-rupture effect) and M2 (anti-inflammatory, anti-rupture effect) macrophages in samples containing plaque material.
2. A further secondary aim is the assessment of short- and long-term outcomes in patients with OCT-diagnosed plaque complications, as identified by imaging and confirmed by pathology.

STUDI ELIGIBILITY CRITERIA Inclusion criteria

1. Patients aged ≥20 years;
2. diagnosis of ACS, both ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI);
3. Culprit plaque affecting native coronary arteries;
4. Optical coherence tomography (OCT) with sufficient quality before PCI;
5. Successful thrombus aspiration with enough amount of thrombus. Recent guidelines and consensus documents indicated that routine thrombus aspiration is not recommended; exceptions include large thrombus burden, when thrombus aspiration may be considered. Therefore, athero-thrombotic aspiration was selectively performed in patients fulfilling the aspiration procedure indications due to the large thrombus burden.

Exclusion criteria

1. patients with cardiogenic shock,
2. patients with coronary bypass grafting (CABG),
3. patients with contraindications to anticoagulation and anti-platelet therapy,
4. lesions located in tortuous vessels, ostial segments, and the left main coronary trunk, due to the difficulty in performing high-quality intracoronary imaging.

SAMPLE SIZE Due to the unprecedented similar in vivo studies and the non-routine possibility of performing pre-PCI thrombus aspiration according to guidelines, it was not possible to precisely calculate the sample size.

Based on the probability of plaque rupture in ACS (75% in consecutive ACS) and erosion (25% in consecutive series), a minimum number of 100 cases was considered necessary for the study scope.

PATIENT RECRUITMENT The study is conducted at the Fujita Health University Hospital, Okazaki Medical Center, and Nagoya First Red Cross Hospital. The study was approved by local ethics committees (HM 16019) and was carried out according to the guidelines of the Declaration of Helsinki. Written informed consent was obtained from all patients before index PCI.

PATHOLOGICAL ANALYSIS The pathologic study was planned to be performed at the IRCCS, Policlinico San Matteo, Pavia, Italy, where samples had to be blindly analyzed after routinely processing for histopathology.

Pathological plaque rupture (PATHO-PR) was defined as the presence within the retrieved samples of atheromatous material, consisting of cholesterol clefts, foam cells, iron-loaded macrophages, cap fragments/fibrous tissue, and calcifications.

Serial sections for each case were stained (H&E, MOVAT, Perls', Von Kossa). The immuno-characterization of the macrophage populations was performed by immunostaining sample sections with antibodies to the pan-macrophage CD68, and M1 (CD80, CD86, IL-6) and M2 (CD163, CD206, TGF-β) polarized macrophage.

Samples with plaque material were classified as RFC-derived, while thrombus-only samples were unsuitable for plaque analysis.

CLINICAL EVALUATION Clinical outcomes were planned at 100 days and 5 years. Major adverse cardiac events (MACE) included cardiac death, non-fatal ACS, ischemia-driven revascularization, cardiogenic shock, and heart failure requiring hospitalization.