Author + information
- Ik-Kyung Jang, MD, PhD⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Ik-Kyung Jang, Cardiology Division, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114
- intravascular ultrasound
- optical coherence tomography (OCT)
- plaque burden
- thin capped fibroatheroma (TCFA)
Intravascular ultrasound (IVUS) has been an important modality in understanding the in vivo pathophysiology of coronary artery disease and in predicting outcome of percutaneous coronary intervention (PCI). The IVUS features associated with acute coronary syndromes include positive remodeling, large plaque burden, ruptured plaque, and intracoronary thrombus. Plaque burden, lesion site calcium, and positive remodeling have been reported to be associated with no-reflow phenomenon and periprocedural myocardial necrosis after PCI (1,2). Attempts to characterize coronary plaques using IVUS were less successful. Although some studies showed that lipid pool-like hypoechoic plaques on IVUS may be associated with periprocedural myocardial infarction, conflicting studies have been reported. It was generally accepted that IVUS is not an ideal tool to detect lipid-rich plaque. However, recent studies reported that echo-attenuated plaque on gray scale IVUS was associated with no-reflow and/or elevated creatine kinase-myocardial band (CK-MB) after PCI, which indicates that this type of plaque contains vasoactive substances, thrombogenic substrates, or rigid material including cholesterol crystal that does not go through the capillary system, causing distal embolization with resultant myocardial necrosis (3,4).
The difference between the previously reported hypoechoic plaque and echo-attenuated plaque is that attenuated plaque has deep ultrasound attenuation (hypoechoic area) without calcification or very dense fibrous plaque. An important methodological difference is that, in the previous studies, low-resolution IVUS (25 or 30 MHz) probes were used, whereas only higher-resolution 40-MHz probes were exclusively used in recent studies. Pathological studies and the atherectomy study showed that the nature of attenuation was lipid core, microcalcification, fibrofatty tissue with necrotic core, thrombus, cholesterol crystal, or hyalinization with scattered, small calcified areas (5,6). An animal experiment showed that microcalcification and thrombus with underlying advanced atherosclerosis were responsible for echo attenuation.
In the study by Lee et al. (7) in this issue of JACC: Cardiovascular Interventions, echo-attenuated plaque was found in 34.8% of patients and was associated with optical coherence tomography (OCT)-derived thin capped fibroatheroma (TCFA) and greater lipid content. Of note, most patients (107 of 135; 79%) had stable angina. Interestingly, a previous study showed 0% echo-attenuated plaque in stable patients and 25.5% in acute coronary syndrome patients (4). Although intraobserver and interobserver variability were excellent in this study (kappa = 0.91 and 0.85, respectively), the discrepancy between the 2 studies indicates the intrinsic problem of subjective interpretation and the absence of standard definition.
The new information from this study is the OCT findings of echo-attenuated plaques. A little more than one-half (51.1%) of the echo-attenuated plaques had OCT-derived TCFA (vs. 21.6% in the nonattenuated group). The question is, “What do the other one-half (48.9%) of the attenuated plaques have?” Because the thin fibrous cap is below the resolution of IVUS (the difference in fibrous cap thickness between the groups was only 25 μm), echo attenuation might have been due to lipid core. Indeed, lipid-rich plaque was found in 89.4% of the attenuated plaques. However, lipid-rich plaque was also found in 55.7% of the nonattenuated plaques. The incidence of thrombus between the groups was not different. These data indicate that structural differences between attenuated plaques and nonattenuated plaques could not be discerned by OCT. It is unclear what the real nature of echo attenuation is. Despite the high prevalence of lipid-rich plaque, less than one-half of patients with attenuated plaque had post-PCI CK-MB elevation. Although co-registration is always an issue when 2 different intravascular imaging modalities are used to study a plaque, it is unclear whether the findings in this study can be explained by this technical registration problem.
Multivariable logistic regression analysis showed 2 predictors for post-PCI CK-MB elevation: attenuated plaque by IVUS and ruptured plaque by OCT. A question remains with regard to whether IVUS or OCT would better predict the post-procedural CK-MB elevation. The odds ratio was higher with attenuated plaque than with ruptured plaque. Neither OCT-derived lipid-rich plaque nor TCFA were identified as a predictor for post-procedural myocardial necrosis.
Since most components of a coronary plaque are below the resolution of noninvasive imaging tests such as multislice computed tomography or cardiac magnetic resonance, intravascular modalities have been the focus of the investigation to characterize coronary plaques and to detect vulnerable plaques (8). Among those, IVUS and OCT have been the most extensively studied (Table 1). Until the second- generation frequency domain C7 OCT system was developed, OCT remained a research tool despite its higher resolution, mainly due to 2 reasons. First, a blood-free zone has to be created. Among the different techniques used to displace red blood cells, proximal occluding balloon with saline infusion was most widely used. This approach requires multiple wire and catheter exchanges and obstruction of blood flow during imaging. All these steps required time and posed potential risk. Second, the image depth was shallow. It was often difficult to visualize coronary arteries with a diameter >3 mm. Now, with the introduction of the C7 system these 2 problems have been basically solved. The only difference in use between OCT and IVUS is that clear solution (contrast or Dextran [Hospira Inc., Lake Forest, Illinois]) should be injected through the guiding catheter during OCT imaging. It can be done by a power injector using contrast or Dextran (14 ml at 4 ml/s) or by hand injection using a 20 ml syringe. This step (connecting a manifold to an injector and delivering solution) usually takes less than a few minutes. Since pullback time is much shorter with OCT (3 to 4 s), the total time required for imaging is comparable between the 2 techniques. The scan depth has also improved with the new C7 system. Vessels with a diameter up to 3.5 mm can easily be visualized. Large vessels such as vein graft or left main, and ostial lesions remain a challenge for OCT.
The most striking difference between the 2 modalities is the resolution (12 to 15 µm in OCT vs. 150 µm in IVUS). One of the reasons why IVUS has not been widely used in the United States is that it requires a learning period and some experience to be able to interpret images. Even after some experience it is not always easy to interpret certain images such as thrombus and tissue prolapse. On the other hand, the learning curve of OCT is such that one does not need much experience to interpret images. A new problem, however, is that we see so many details that we have never seen before such as plaque disruption, microdissection, thrombus, tissue prolapse/protrusion, tissue covering previous stent strut surface, macrophage, and cholesterol crystals. Following stent placement malapposition is a frequent finding on OCT images. Recently, a new analysis system was developed to objectively analyze the optical property of tissue, which can be used to study changes in the optical properties of neointima inside previous stents over time. Clinical significance of these findings is unknown at present. Long-term follow up of a large number of patients would be required to understand the importance of this novel information and to know if treatment should be employed. The main question is which modality we should choose, if we were to use one. For better understanding of vascular biology, OCT would be far superior to IVUS. For the majority of PCI cases, I believe frequency domain OCT can now replace IVUS. For large vessels (diameter >4.0 mm), ostial lesions, or very tight lesions, IVUS would provide more information. There is no significant difference in safety. In our institution we have over 10 years of experience with OCT, but there have been no OCT-related complications such as major dissection, ventricular tachyarrhythmia, or acute renal failure.
In this study, 4% (6 of 135) of patients had post-procedural CK-MB elevation more than 3 times the upper limit and 26% (36 of 135) of patients had CK-MB elevation between 1 and 3 times the upper limit. The question is whether we should try to prevent or reduce periprocedural myocardial necrosis and, if so, when and how. Should we target 4% or 26% of patients? What should be used: pharmacological therapy such as vasodilators or more effective antithrombotic agents or protection devices? Many studies can be designed to answer these questions. However, before we try to focus on prevention or treatment, we should first find better predictors for post-PCI myocardial necrosis.
Dr. Jang has received research grants and consulting fees from LightLab Imaging/St. Jude, and research grants from Medtronic, Abbott Vascular, and Johnson & Johnson.
↵⁎ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
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