Intravascular ultrasound (IVUS) has a long history of use in the management of coronary artery disease. Historically, application of the technology was often limited to its use as a research tool; thus, the use of IVUS was restricted to cardiac centres engaged in clinical studies. These early studies generally aimed to demonstrate the safety and efficacy of short-term stent results as new devices were introduced into clinical practice. The publication of the MUSIC study in 1998 introduced the concept of a protocol-driven approach to stent implantation.1 Subsequently, there has been an extensive accumulation of published knowledge consistently demonstrating that IVUS-optimised percutaneous coronary intervention (PCI) is superior to angiography-guided PCI. Although beyond the scope of this paper, recently published and contemporary reviews of this evidence are available elsewhere.2,3
There are now numerous randomised controlled trials, which have enrolled thousands of patients, confirming the benefits of IVUS-guided PCI over angiographic guidance in the longer term (up to 5 years).4–6 Additional large randomised studies continue to recruit patients today and will continue to inform best practice. An overview of outcomes of the application of IVUS in clinical practice demonstrates a reduction in the composite of major adverse cardiovascular events by 30–50% at any given time point.4–6 This is principally driven by a decrease in target lesion revascularisation or target vessel failure when a protocol-driven practice is followed. Yet, limitations remain, with the application of these approaches only leading to an optimal IVUS result in approximately 50% of procedures within most imaging studies.4–6 Therefore, thoughtful interpretation and application of image optimisation is also needed to maximise the benefits of this approach, while minimising procedural complications.
Despite this large body of evidence, adoption of imaging during PCI (with either IVUS or optical coherence tomography) is low across most healthcare systems.2,3 Education on the appropriate application of this technology remains a major, addressable barrier.2 Our aim within this paper is to aid the generalisability of IVUS during PCI by providing a pragmatic and simple workflow that forms a foundation for image-optimised PCI. This expert review and consensus document suggests a workflow that provides a framework to standardise patient care. The ultimate aim of this workflow is to shorten the learning curve with IVUS-guided PCI and to facilitate its adoption.
Intravascular Ultrasound Fundamentals
IVUS is an adjunctive imaging modality that augments coronary angiography, with results interpreted within the clinical context. This additional information requires appropriate interpretation to add value. Advances in technology have resulted in higher-resolution rotational IVUS, with newer-generation devices operating at 60 MHz. The images and approaches described within this paper were obtained using a 60MHz IVUS system (Boston Scientific) with an axial resolution of 22 µm (Supplementary Figure 1 ). In addition, they were captured by the systematic use of a mechanised pull-back sled (at 0.5–1 mm/s). This allows longitudinal measurement of the segments that are being assessed, meaning lesion length can be calculated, which would not be available from manual pull-back runs. The principles of the IVUS 123 methodology can be applied to any IVUS system that uses a mechanised pull-back for length measurement. However, image interpretation may be hampered by lower-resolution systems and length measurements cannot be derived from manual pull-backs.
Ideally, imaging runs should begin in a disease-free area of the vessel a few millimetres distal to the target lesion (Supplementary Figure 2). The vessel should be interrogated from here to the ostium. Intracoronary nitroglycerine is also required prior to each IVUS run to avoid undermeasurement, due to vessel spasm, assuming clinical circumstances allow.
Effective coregistration can be understood from storing a fluoroscopic image that highlights where the IVUS run begins (Supplementary Figure 2). Side branches that are also evident on the angiogram can be correlated with the IVUS images that are obtained to increase the accuracy of this coregistration. Areas of interest can be bookmarked live as they are noted, and a fluoroscopy image stored to note where these are sited.
Understanding the Context of IVUS 123
This paper is foundational and not intended as a comprehensive guide to all clinical circumstances. There are many nuances around the management of calcium, left main disease, bifurcations and total occlusions that require additional education, thought and evidence. In addition, it should be noted that this paper represents an expert consensus that has not been prospectively validated at the time of publication. Ongoing validation is under way in the CYCLOPES clinical study (NCT06678594).
Intravascular Ultrasound Considerations Before Stent Implantation
A foundational principle of image-optimised PCI is that lesions should be fully assessed prior to the decision to implant a stent. Coronary angiography has significant limitations in lesion assessment if not augmented by IVUS, which may introduce errors; these errors include underestimation of vessel diameter and underestimation of the extent of plaque.3,7 Both these errors may lead to stent deployment in areas of significant plaque burden, which is also referred to as geographic miss, a risk factor for target vessel failure.8–11
Deciding on the Length of Disease to Be Treated
To avoid geographic miss, the diseased segment should be treated from a healthy area distally (i.e. an area that has minimal or no plaque burden) to a proximal landing zone that is also healthy. However, this comes with the caveat that stent lengths should not be extended across areas of minor plaque burden to land in a truly normal area of the vessel. Sensible clinical judgement is still needed to find a balance between an acceptable landing zone (defined as a plaque burden on IVUS of ≤50%) and seeking an overly distant non-diseased segment. If it proves necessary to land a stent in a plaque, areas of lipid-rich disease or thin-cap fibroatheroma should be avoided.
Understanding Plaque Morphology
A second crucial factor in lesion assessment is understanding the nature of the plaque that requires treatment. The presence of angiographically detected moderate or severe calcification has long been associated with adverse clinical outcomes. However, the angiogram itself is a poor tool for predicting patterns and distribution of calcium.3 Calcium is much more accurately assessed by IVUS, where scoring systems may aid the decision to proceed to more targeted calcium modification, with the goal of an optimised stent outcome and improved PCI durability.12 It is of note that increasingly calcific segments of constraint leading to smaller minimal stent areas (MSAs) were associated with an increase in adverse events in the NOBLE study.13
Assessing Vessel Size
The goal of the procedure is to restore normal vessel physiology by ensuring the stent implant reflects the size of the inflow (proximal landing zone) and outflow (distal landing zone). The stent diameter between these segments should provide a smooth tubular conduit for laminar blood flow, where the areas are appropriately matched across the length of the device. There are two key questions at the outset: first, which stent diameter will facilitate an implant and not cause a dissection at the distal edge; and second, which post-dilation balloons are appropriate to maximise the MSA and obtain an indicated expansion index, without risking vessel perforation?
A misunderstood nuance of device selection is correct vessel sizing; should this be assessed by measuring the lumen–lumen border or the external elastic lamina (EEL) of the vessel? Provided there is no negative remodelling (Figures 1A–1C) elsewhere in the segment, some basic principles can be applied. A suggested algorithm for appropriate initial device diameter selection is provided in Figure 1D.
For the distal landing zone, sizing the stent to the lumen–lumen dimension will minimise the risk of edge dissection. Post-dilation balloons can then be used to maximise expansion using the EEL–EEL measurements as a foundation.
As plaque develops, a vessel will initially remodel outwardly, with continued plaque enlargement eventually resulting in the lumen being impinged and blood flow obstructed (Glagov phenomenon; Figure 1A–C).14 Therefore, caution must be applied if EEL–EEL measurements are taken in the presence of plaque. In such cases, post-dilation can be performed with the aim of balancing maximum stent expansion while minimising the risk of perforation. The EEL–EEL dimension is a safe reference measurement in healthy or minimally diseased segments. A pragmatic goal of the EEL–EEL diameter minus 0.5 mm is reasonable in moderate plaque. Alternatively, a diameter approximately halfway between the lumen–lumen dimension and EEL–EEL dimension is also a reasonable target (Figure 1D). It should be noted that the ultimate indication for a successful implant will come from post-stent measurements. Additional post-dilation can always occur if these indices are suboptimal, as long as appropriate plaque modification has been performed before stent implantation.
Finally, heavily diseased segments with extensive plaque burden are not appropriate for stent landing zones. EEL–EEL measurements in these segments (ahead of stent implantation) also risk overestimating vessel size due to positive remodelling.
IVUS 123 Steps: Vessel Preparation, Stenting and Post-dilation
The three key questions prior to stent implantation are outlined in Figure 2:
- How much plaque should be covered (lesion length)?
- What is the nature of the disease (plaque morphology)?
- What is an appropriate size for the segment after the intervention (vessel diameter/area)?
This should then lead to three actions (Figure 2):
- identifying the landing zones for the stent (ideally healthy areas with no or minimal plaque);
- assessing plaque morphology within the target segment; and
- measuring the lesion length and the appropriate proximal and distal stent diameters (Figure 3).
When these questions are asked, assessments made and appropriate decisions taken, a PCI road map is provided. The information provided by IVUS leads to actionable outcomes. Tools for plaque modification can be selected, if required. Predilation balloons can be used according to the script provided. The stent length and diameter (best matched to the distal/smaller measurement) are accurately clarified. Post-dilation is also predetermined. This will improve procedure efficiency by reducing the likelihood of equipment changes or the addition of procedural steps while ensuring the best possible stent result.
By matching the implanted stent diameter to the distal reference measurement, edge dissections are prevented and the risk of perforation is minimised. Options for further overexpansion of the stent to match the larger proximal vessel (in the case of tapering) are retained.
Intravascular Ultrasound Considerations After Stent Implantation and Optimisation
Assessment of Stent Edges
Numerous features are known to compromise the acute and longer-term results of PCI. Acutely, the presence of a significant dissection (Figure 4) may lead to abrupt closure of the target vessel and adverse patient outcomes. In RENOVATE, this was defined as “no major edge dissection extended to media layer with potential to provoke flow disturbances (defined as ≥60° of the circumference of the vessel at site of dissection and/or ≥3 mm in length of dissection flap)”.6
This is critical, not just in avoiding short-term major adverse cardiovascular events but also in facilitating safe, same-day-discharge PCI. In addition, avoiding geographic miss is key to reduce target vessel failure. Ensuring accurate stent placement and avoiding extensive plaque burden at either edge is critical in ensuring stent durability.
Understanding and Treating Malapposition
Malapposition refers to areas where a stent is not fully in contact with the vessel wall; this should not be confused with stent struts that sit across the origin of side-branches (Figure 4B). Although malapposition within a stented segment has not been associated with restenosis or repeat revascularisation, gross malapposition is often noted in association with stent thrombosis and subsequent acute, emergency presentations with acute coronary syndromes. Malapposed segments of stents can also contribute to acute procedural complications. For example, stent deformation may occur if equipment interacts with malapposed struts at the proximal stent edge. In bifurcation procedures, a second wire can potentially be introduced while passing behind the malapposed stent struts. Abluminal wiring in these circumstances can lead to deformation of the initial stent and adverse outcomes.
Any struts ≥400 µm off the wall of the vessel, particularly over longer lengths (≥0.5 mm) should be corrected with further post-dilation. Malapposition is most commonly seen at the proximal end of a stent that is matched to the distal reference diameter in a tapered vessel. This is best resolved with a balloon sized 1 : 1 with the proximal reference measurement. Semicompliant balloons may cross proximally non-opposed struts with a lower likelihood of causing deformation. When the aim is simply to appose a stent to the wall (without needing to expand resistant plaque), higher-pressure non-compliant inflations are not necessary and may simply promote edge dissection.
Understanding Optimised Stent Expansion Parameters
Stent underexpansion is the biggest mechanical predictor of subsequent stent failure.2,3 An imperative is to ensure that stents are appropriately sized and adequately expanded. Therefore, post-stent assessments require careful and nuanced interpretation. In addition, longer stents that cross large bifurcations or that extend over significant vessel tapering must be capable of overexpansion to an adequate diameter to match the more proximal segments. The stent should be selected to ensure that the overexpansion limit is not exceeded for the proximal portion of the device.15 For post-dilation, three different balloons may be appropriate where large bifurcations are crossed. For example, within a single stented segment, the mid-left anterior descending vessel may be 3.5 mm beyond the first diagonal, 4 mm in the proximal vessel and then 5 mm in the left main.
The protocols applied from the MUSIC study through to the larger randomised controlled trials that define an optimal outcome vary between studies and populations. Although early studies examining the utility of IVUS to optimise PCI were performed in an era when very short bare-metal stents were implanted, some basic principles can still be applied. First, MSAs should be compared to the distal and proximal reference lumen area as a primary ratio (Figure 5). The EEL, especially in the presence of a significant disease burden, should not represent the denominator for the stent expansion assessment. The aim of achieving MSAs that are ≥90% of the distal lumen reference area is a concept that has been prospectively validated in a large contemporary randomised controlled trial.16 This is an easier calculation when stent segments are shorter.
Historically, the proximal and distal reference assessments were made within 5 mm of either stent edge. However, in today’s practice, much longer segments are commonly treated. Under these circumstances, a more detailed assessment is needed. One approach is to consider an MSA that is 80% of the average of the proximal and distal lumen reference areas.6,17 Another is to divide the stented segments into halves and to assess the MSA in each half of the segment, as applied in the ILLUMIEN IV study, and to then compare the MSA of each to the corresponding reference measurement.18,19 A third approach is to consider using an ‘indexed’ measurement of the MSA versus the vessel size.20 Although the latter has not been prospectively validated in large trials, these recommendations may change. At present, most clinicians will take a series of measurements throughout a longer stent length and apply judgement to ensure an adequate MSA is achieved, while also making allowances for increases in vessel diameter as the artery tapers up in size more proximally and/or significant bifurcations are crossed.
Finally, it is important that a degree of pragmatism is also applied. In the presence of severe calcification or tortuosity, operators must be cautious and accept stent areas that are reasonable for the patient. Multiple studies have reported that the threshold for the risk of restenosis with modern drug-eluting stents correlates to an MSA of approximately 5 mm2.21–25 If there is a measure of underexpansion or eccentric stent expansion with an acceptable MSA, pursuit of a 90% expansion parameter may be counter-productive and risk adverse outcomes. This is especially pertinent in larger vessels, if the MSA already significantly exceeds 5 mm2. Under these circumstances, a risk–benefit calculation should always be made, with patient safety being the primary consideration.
Finally, EEL–EEL measurements within the stented segment should not be used to guide any subsequent post-dilation. These judgements are best made from the pre-stent images.
IVUS 123 Steps After Vessel Preparation, Stenting and Post-dilation
A systematic and step-by-step workflow for post-stent optimisation with IVUS is shown in Figures 4 and 5. To ensure an optimised stent implant has been obtained, it is important that operators follow a step-by-step process as the final assessment.
Working through these steps will ensure that the stent edges are free of significant dissection and that an appropriate landing zone has been achieved proximally and distally. Ensuring the stent is apposed throughout will reduce the risk of stent thrombosis. Finally, ensuring adequate stent expansion and appropriate MSAs will help guarantee the durability of the PCI. It is important that physicians remember that when IVUS optimisation parameters are achieved, adverse events are minimised. However, ‘IVUS endorsement’ without careful optimisation will under-realise the benefit of IVUS guidance.5,26
Conclusion
Standardisation of patient care is likely to lead to enhanced acute and long-term results from PCI procedures. It is clear from numerous trials that image optimisation plays a key role in this regard. We introduce the IVUS 123 essentials framework as a means of supporting a standardised workflow for the application of intravascular ultrasound during PCI. The aim of this paper is to encourage a consistent approach for these procedures to promote both acute procedural safety and long-term durability.