Interventional Cardiology. Группа авторов

along the entire acquisition segment, or within the 4 mm segment of highest accumulation (LCBI4mm). Commercially available systems allow the simultaneous acquisition of IVUS and NIRS signals, providing the assessment of lipid content, lumen stenosis severity and plaque burden. Four non‐randomized studies, the two largest ATHEROREMO‐NIRS and Spectrum NIRS‐IVUS registry enrolling more than 400 patients, demonstrated that an increased LCBI is associated with the development of subsequent MACE. In the LRP study, NIRS‐IVUS imaging was performed in non‐culprit arteries in 1563 patients with coronary artery disease (46.3% stable angina) who underwent PCI for an index event. Patient‐ and plaque‐level events were followed for two years among those with at least one maxLCBI4mm segment ≥ 250 and a randomly selected 50% of patients with all maxLCBI4mm segments < 250. A representative example is presented in Figure 9.8. The adjusted patient‐level analysis showed that for each 100 unit increase of maxLCBI4mm the risk of non‐culprit MACE increased by 18% and patient with maxLCBI4mm greater than 400 is at 87% higher risk of non‐culprit MACE. Also, the plaque‐level analysis demonstrated a 45% higher risk of events within 24 months with each 100‐unit increase in maxLCBI4mm in a coronary segment, with MACE rates of 3.7% versus 0.8% for plaques with maxLCBI4mm ≥ 400 and < 400, respectively. The results of this trial show that NIRS is a safe and feasible technique able to identify vulnerable plaque and vulnerable patients in whom strategies of tailored secondary prevention could be focused [128].

Figure 9.8 _{Angiography at baseline without significant stenosis (a). Angiography at one year follow‐up with a stenotic lesion at the region of MaxLCBI4mm from baseline assessment (b). Chemogram (c) from baseline near‐infrared spectroscopy (NIRS) with MaxLCBI4mm = 472 at the site of a future event at one year post index procedure.}

      The recent IBIS‐3 trial demonstrated that high‐intensity rosuvastatin therapy during one year resulted in a neutral effect on NC and LCBI within non‐stenotic, non‐culprit coronary segments with a relatively low atheroma burden (The Netherlands Trial Register n. 2872).

      Prevention of peri‐procedural myocardial infarction and optimizing interventions

      Peri‐procedural myocardial infarction can be related to distal embolization of LCP component, contents, and/or intracoronary thrombus. In a sub‐study of COLOR (Chemometric Observation of Lipid Core Plaques of Interest in Native Coronary Arteries) registry, the cardiac biomarkers in 62 stable patients undergoing stenting were evaluated. Findings revealed that 7 out of 14 (50%) patients with a maxLCBI_4mm ≥500 developed peri‐procedural myocardial infarction in comparison with the occurrence of this in only 2 out of 48 (4.2%) patients with a < maxLCBI_4mm [129]. In a study by Raghunathan et al. [130], in which a creatinine kinase‐MB increase >3 times the upper normal limit was observed in 27% of patients with a ≥1 yellow block as opposed to none of the patients without a yellow block within the stented lesion. Similarly, in the CANARY (Coronary Assessment by Near‐infrared of Atherosclerotic Rupture‐prone Yellow) trial, patients with periinterventional myocardial infarction had higher maxLCBI_4mm than patients without MI [131]. However, preventive measures for this situation remain uncertain. The use of a distal emboli protection device frequently resulted in embolized material retrieval during intervention in a small group of patients with LCP [132]; however, there was no benefit of this adjunctive treatment in the randomized CANARY trial.

      A prospective use of NIRS in catheterization laboratories is in stent sizing to ensure adequate lesion coverage. Visual evaluation of lesions by angiography occasionally lack accuracy and using NIRS, Dixon et al. [133] demonstrated that in 16% of the lesions assessed in their study, the LCP extended beyond the angiographic margins of the initial target lesion. Therefore, together with the information provided by IVUS, NIRS data can be used for determining the size and length of the artery to be stented.

       Guiding the effects of treatment

      The effects of current or novel agents that modify plaque composition can be evaluated using NIRS, because it is able to assess the lipid content over time. The YELLOW trial recruited patients with multivessel CAD undergoing PCI. After NIRS and IVUS baseline assessment, patients were randomized to either rosuvastatin 40 mg/day vs the standard of care lipid‐lowering therapy. After seven weeks of short‐term intensive statin therapy, a significant reduction in the lipid content was found when measured via max LCBI_4mm [134].

      Ongoing trial

      The prospective multicenter PROSPECT II trial aims to collect the post‐PCI NIRS/IVUS data of patients with ACS and evaluate the prognostic value of LCBI >400 to evaluate in the two year follow‐up.

Near‐infrared fluorescence molecular imaging

      Current intravascular imaging approaches such as OCT or IVUS are inable to assess specific biologic processes in the coronary arteries in vivo. Molecular imaging is a relatively new field that aims to image specific molecules and cells involved in the pathogenesis of vascular disease, including macrophages, endothelial cell adhesion molecules, fibrin, and coagulation factor XIII activity [136,137]. Molecular imaging requires injectable targeted imaging agents that bind a specific molecular or internalized within a cell. These agents can then be detected by an appropriate hardware imaging system, including positron‐emission tomography (PET), magnetic resonance imaging (MRI), single‐photon emission tomography (SPECT), ultrasound and, more recently, fluorescence imaging systems.

      While PET and MRI molecular imaging approaches appear promising for large arterial beds (e.g. carotids, peripheral arteries), the smaller size of the coronary arteries dictates an intravascular‐based imaging approach to achieve sufficient sensitivity and resolution. To meet this need, optical‐based imaging using near‐infrared fluorescence (NIRF) has evolved to serve as a promising coronary artery‐targeted intravascular imaging platform. The NIR window (650–900 nm) is advantageous for fluorescence imaging as this window exhibits reduced blood absorption and scattering, and reduced background tissue autofluorescence, which serves to increase the ability to detect NIRF molecular imaging agents in vivo.

In the last decade, several intravascular NIRF systems have been engineered, including a one‐dimensional wire spectroscopic‐based system, a standalone two‐dimensional imaging system, and most recently, a combined NIRF‐OCT imaging system [138,139].(Figure 9.9). Several preclinical investigations have provided the first clinical‐type demonstrations of imaging inflammatory protease activity and endothelial leakage in atheroma [138–142], fibrin deposition and inflammation on stents[143,144], and imaging the plaque response to paclitaxel drug‐coated balloons [145]. Imaging occurred in vivo in human coronary‐sized arteries of rabbits and pigs, suggesting the potential for clinical translation. The most recent NIRF‐OCT system has the further advantage of providing simultaneous anatomic information that is precisely co‐registered with NIRF molecular information, which further allows quantitative NIRF imaging (Figure 9.8). Similarly to NIRF‐OCT, a NIRF‐IVUS catheter has been developed and is undergoing clinical translation [146].

Figure 9.9 Intravascular near‐infrared fluorescence molecular imaging of plaque inflammation integrated with exactly co‐registered OCT. A dual‐modal near‐infrared fluorescence