Discussion
This observational study evaluated the diagnostic performance of HD-IVUS of OFDI-derived calcium modification and fracture. The main findings were as follows: 1) As a result of aggressive plaque modification by atherectomy and ballooning, calcium modification and fracture were frequently observed by both OFDI and HD-IVUS. 2) Regarding the detection of calcium modification, HD-IVUS had high specificity, PPV and NPV, while having modest sensitivity. 3) Diagnostic performance of HD-IVUS for the detection of calcium fracture, sensitivity, specificity and NPV was high, although it was only modest for PPV. 4) For the assessment of HD-IVUS images, lesion morphologies and guide wire artifact were potentially related to the misdiagnosis of calcium modification and fracture. These results demonstrate both the capabilities and limitations of HD-IVUS for the treatment of heavily calcified lesions requiring atherectomy.
While IVUS has an excellent detection performance for coronary calcium, it is impossible for IVUS to quantify calcium thickness due to the acoustic shadow [8, 17]. Therefore, a newly developed reverberation behind post-atherectomy calcium has been considered to be a useful marker of calcium modification [15]. However, our study revealed that more than 40% of the calcium modifications were undetectable by HD-IVUS. One of the potential reasons for this might be that when using IVUS, the calcified plaque sometimes has signal attenuation behind the coronary calcium. According to pathological reports, when using IVUS, some of the calcified plaques, which include the necrotic core or calcified nodule, potentially have strong signal attenuation [13, 18, 19]. In addition, our study demonstrated that the echo-lucent area behind the layered calcium or calcified nodule did not always have a reverberation echo, despite OFDI confirmation of the calcium modification. Thus, this suggests that signal attenuation behind heterogeneous calcium decreases the diagnostic accuracy of HD-IVUS when assessing calcium modification. In other words, HD-IVUS assessment of calcium modification might be useful only for the calcified fibrous plaque. As shown by the representative images, another reason for the discordance of the calcium modification detection is that the guide wire artifact can sometimes hide the narrow-angle reverberation caused by atherectomy. Therefore, when using HD-IVUS to confirm the occurrence of calcium modification, careful reviews around the guide wire artifact will need to be performed.
The present study also showed that the separate calcium determined by HD-IVUS sometimes mimicked a calcium fracture. With regard to the detection of coronary calcium, both IVUS and OFDI had a similar diagnostic performance [8, 20]. However, when using IVUS, the calcium border is sometimes found to be non-continuous due to non-fibro-dense calcium [19]. Furthermore, since axial resolution of HD-IVUS as compared to OFDI is relatively low (15-20 μm versus 20-40 μm) [8]. the originally separated calcium and calcium fracture with the small piece of calcium might be difficult to differentiate when using HD-IVUS. Indeed, the PPV of the calcified segments without small (≤180 degrees) calcium in the present study was relatively high as compared to the overall calcified segments. Considering the difference in the image reconstruction method and resolution between HD-IVUS and OFDI, it might be unavoidable with regard to making an over- and under-diagnosis of the calcium fracture by HD-IVUS. When performing a quick review of HD-IVUS images in the catheter laboratory, it is potentially easy to make a misdiagnosis for the calcium fracture due to the guide wire artifact that crosses the coronary calcium. If an operator implants a stent in the lesion with thick and large coronary calcium based on this misdiagnosis by the HD-IVUS, this may subsequently be associated with stent underexpansion. In fact, a recent single-center retrospective observational study demonstrated that OFDI-guided RA for calcified coronary lesions resulted in larger stent expansions as compared to the IVUS-guided RA [21]. During HD-IVUS guided PCI for a heavily calcified lesion, it might be important to perform an additive confirmation of full balloon expansion via fluoroscopy to avoid stent underexpansion. In contrast, this study demonstrated that the negative predictive value for detecting the calcium fracture was about 95%, regardless of the size of the coronary calcium. This indicates that HD-IVUS can be used to evaluate ineffective calcified plaque modification.
During the atherectomy procedure, intravascular imaging is helpful for determining the need for additional atherectomy and completion of atherectomy [7]. In particular, as the rotating speed is never displayed during an OA procedure, evaluation of the presence or absence of calcium modification is important for evaluating the efficacy of OA [22]. Therefore, during the OA procedure, OFDI could potentially be very useful for determining the calcium modification. For a heavily calcified lesion, calcium fracture is required to avoid stent underexpansion, and thus, confirmation of the fracture by intravascular imaging could warrant favorable stent expansion [4, 5]. Recently, intravascular lithotripsy (IVL) has been developed for the treatment of a heavily calcified lesion, thereby making it possible to cause a calcium fracture through the use of shock waves [23]. If IVL becomes the first therapeutic option for the treatment of a heavily calcified lesion, then it is likely that OFDI (or OCT) will be used to a greater extent than HD-IVUS due to the high diagnostic accuracy for assessing calcium fracture, as was shown in the present study.
OFDI has an excellent diagnostic performance for calcium modification and fracture. However, it is often unable to obtain an image for severe stenotic lesions due to blood clearance difficulties [8]. Although it is impossible to evaluate the thickness of calcium, IVUS as well as OFDI can determine the degree of the calcium angle [17]. Thus, HD-IVUS is an appropriate imaging modality that can be used to evaluate the need for atherectomy [7, 8]. Depending on both the situation and the procedural steps, either HD-IVUS or OFDI might be needed for the treatment of a heavily calcified lesion in a single case. To address this, novel hybrid IVUS and OFDI catheter systems have recently been developed by several companies [24]. When these hybrid imaging systems are widely available in daily practice, results of our study will be helpful in determining the effective utilization of these hybrid systems.
Study limitations
There were several limitations for the present study. First, although more than 1,000 OFDI-matched HD-IVUS images were analyzed, the number of enrolled subjects was relatively small. Second, because both the indication and the atherectomy procedure technique vary between physicians or institutes, selection bias could not be avoided. Third, since there was no head-to-head comparison between OFDI and the other HD-IVUS systems, our findings might not be generalizable for the other HD-IVUS systems. Fourth, the clinical impact of the misdiagnosis of calcium modification and fracture on stent expansion and clinical outcomes has yet to be established. A larger clinical study using multi-modalities will need to be conducted to establish the capability of HD-IVUS.