Thrombus Aspiration and Pathology and OCT Study

NCT ID: NCT07151976

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-07-01
• Study Completion Date: 2027-12-31

Brief Summary

Most acute coronary syndromes (ACS) are caused by plaque complications triggering thrombotic events in the culprit plaques. Plaque complications include plaque rupture (Ruptured Fibrous Cap-RFC) with exposure of highly thrombogenic substrate to the flow and plaque erosion (Intact Fibrous Cap-IFC) a condition characterized by endothelial/intimal damage occurring over non-ruptured plaques. Far less commonly (<5%), calcified nodules (CN) may trigger acute coronary thrombosis. Plaque rupture accounts for 75% of fatal AMI in autopsy series, while erosion is found in about 25% of cases. These proportions have been supported by in vivo invasive studies (OCT) and OCT-pathology correlation studies. However, it remains unclear whether OCT findings consistently align with in vivo pathology-based evidence of RFC in ACS. Guidelines addressing treatments of ACS unanimously indicate percutaneous coronary intervention (PCI) to restore the coronary flow. Pre-PCI thrombus aspiration is not currently indicated by most guidelines, with the exception of cases with very high thrombus burden. The samples retrieved from thrombus aspiration can be suitable for pathology investigation and aim to evaluate the presence of plaque components in the context of the thrombotic material, a finding that demonstrates plaque rupture as the substrate for the acute coronary event. These studies are uniquely qualified to provide information on the correct OCT-based interpretation of plaque complications in ACS and require OCT imaging quality suitable to classify RFC, IFC, and CN.

Therefore, a prospective OCT-pathology study was designed using the pre-PCI aspirated material from patients with high thrombus burden, to explore the contribution of pathology study in OCT-based classification of plaque complications.

Detailed 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.

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.

Conditions

Acute Coronary Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

PCI

PCI with athero-thrombotic aspiration and subsequent pathological analysis: Pathologic Characteristics of Athero-Thrombotic AsPirated Material of OCT-Verified Culprit Lesion in Acute Coronary Syndrome

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Patients with ACS showing ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) are studied.

2. Only native coronary artery lesions are included in the study.

3. Optical coherence tomography (OCT) was performed prospectively to compare OCT culprit lesions characteristics with histological analysis of athero-thrombotic aspirated material of the culprit lesion. For this purpose, only lesions with both athero-thrombotic aspirated material and OCT observations are included in the study.

4. All patients provided written informed consent for the index procedure, follow-up, and anonymous data management.

Exclusion Criteria

1. Patients are excluded from the study when they had cardiogenic shock and contraindications to anticoagulation and anti-platelet therapy.

2. Lesions located in tortuous vessels, in ostial segment and in the left main stem are excluded from the study due to the difficulty in performing high-quality intracoronary imaging.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: collaborator

Fujita Health University

OTHER

Sponsor Role: lead

Responsible Party

Yukio Ozaki

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

YUKIO OZAKI, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fujita Health University, Aichi, Japan

Eloisa Arbustini, MD

Role: STUDY_CHAIR

IRCCS Foundation Policlinico San Matteo, Pavia, Italy

Locations

Fujita Health University

Toyoake, Aichi-ken, Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Yukio Ozaki, MD, PhD

Role: CONTACT

ozakiyuk@fujita-hu.ac.jp

+1 9492996512

Reina Ozaki, MD

Role: CONTACT

yukio.ozaki7@gmail.com

+1 9492996512

Facility Contacts

YUKIO OZAKI, MD, PhD

Role: primary

ozakiyuk@fujita-hu.ac.jp

+1 9492996512

YUKIO OZAKI, MD, PhD

Role: backup

yukio.ozaki7@gmail.com

+1 9492996512

Other Identifiers

HM22-157

Identifier Type: -

Identifier Source: org_study_id