Introduction

In the three decades since the first in vivo use of intravascular ultrasound (IVUS) for coronary imaging, IVUS has evolved from a niche investigational technique to an integral adjunct to a conventional angiography [1]. Over this period, IVUS catheters have been miniaturized, imaging resolution improved, the user interface simplified, and the root technology expanded to include several useful adjunctive imaging modalities, detailed below. While conventional angiography is still regarded as the de facto standard for the assessment of coronary artery disease (CAD), acknowledged limitations in angiographic technique and the method of image acquisition can result in underappreciation of coronary disease extent, severity, and composition. Intravascular ultrasound has long been recognized as a reliable and objective methodology for addressing the shortcomings of angiography and yet, IVUS is still only utilized in the small minority of coronary angiograms or percutaneous coronary intervention (PCI) procedures performed in the USA today [1]. This review summarizes the clinical scenarios in which coronary IVUS imaging may provide meaningful, incremental information and should therefore be considered in addition to angiography for the purposes of aiding in clinical decision-making and/or optimization of patient outcomes.

Overview of IVUS Technology

Intravascular ultrasound (IVUS) utilizes reflected acoustic energy to generate high-resolution tomographic images of vascular structures in vivo. Most IVUS systems currently in use emit transducer frequencies in the range of 20 to 45 MHz, requisite to ensure high near-field image resolution. Axial resolution, defined as the capacity to differentiate closely adjacent structures along the axis of the ultrasound beam (projecting radially outward from the imaging element of the catheter) typically ranges between 100 and 150 μm for 20- to 40-MHz probes. Lateral resolution, defined as the ability to distinguish adjacent structures along the circumferential sweep of the ultrasound beam, ranges between 200 and 250 μm [2, 3]. The two imaging approaches currently used in IVUS systems are mechanical rotational, single-element scanning, and solid-state multi-element scanning with each of these technologies demonstrating specific advantages and disadvantages.

IVUS imaging is potentially subject to various technical limitations—including reduced image quality due to inadequate catheter preparation, acoustic guide wire artifact, nonuniform rotational distortion (NURD; only occurring with rotational IVUS systems) due to drive cable friction in tortuous vessels, and ring-down artifact (occurring only with non-rotational, phased-array IVUS catheters) where the ring of imaging closest to the catheter is distorted and must be digitally subtracted from the imaging field upon introduction of the catheter into the vessel.

Grayscale imaging, the foundational IVUS processing modality, enables visualization of the vessel lumen and delineation of the vessel wall which normally appears tri-layered, comprising the intima (with which atherosclerotic plaque is confluent), the echolucent, the muscular media, and the highly echoreflective adventitia [2, 3]. Lesion severity, plaque burden, intimal thickness, gross plaque characteristics, and numerous topographic features can all be assessed with this technique. The addition of non-directional color flow imaging (ChromaFlo ®, Volcano Corporation, San Diego, CA) allows for luminal blood flow to be tracked in real time, which may assist in visualization of dissections, perforations and side branches, delineation of thrombus or soft plaque from blood speckle, and identification of stent malapposition. Other post-processing applications allow for a more detailed plaque characterization with in vivo tissue typing.

Virtual Histology (VH) IVUS (Philips Volcano) applies a validated autoregressive algorithm to gathered radiofrequency data to facilitate categorization of IVUS-visualized plaque into four groups: fibrous, fibrofatty, dense calcium, and necrotic core. The iMAP application found on Boston Scientific (Natick, MA) IVUS systems applies fast Fourier transformation to acoustic backscatter to produce a plaque composition analysis [2, 3].

Newer generation IVUS catheters have sought to increase spatial resolution while simultaneously improving user interface. One recently commercialized high-definition IVUS system (Kodama HD IVUS catheter, Acist Medical Systems, Inc., Eden Prairie, MN) utilizes a rotational transducer which may be operated in a 60 MHz high-definition imaging mode with significantly improved axial resolution (< 40 μm) as compared with conventional IVUS catheters (typically > 100 μm), or a standard 40 MHz frequency for increased tissue penetration. Several other novel and late-stage investigational devices seek to expand the imaging capabilities and ultimately, clinical applications, of IVUS [4].

Use of IVUS in the Assessment of Atherosclerotic Disease

Detection of Angiographically Occult Disease

Conventional coronary angiography is most often utilized as a freestanding test for atherosclerosis detection; however, it is limited in its ability to assess early evidence of atherogenesis and furthermore, offers no capacity whatsoever for quantification of plaque burden or the extent of compensatory arterial remodeling. The first diagnostic coronary angiogram was performed in 1958 by Dr. Mason Sones and was widely acknowledged as a breakthrough in CAD assessment but within just a few years, questions began to arise regarding the veracity and reproducibility of the data obtained using this technique [5]. Indeed, it has been recognized for over a half century that coronary angiography, in relying on relative differences in luminal silhouette to identify and quantify atherosclerotic disease, can often lead to systematic underestimation of disease burden in many commonly encountered clinical settings—including those of diffuse disease, lesion eccentricity, coronary ectasia, and positive arterial remodeling. The latter phenomenon, first described by Glagov et al., predicts that characteristically eccentric, outward vascular remodeling offsets luminal attrition until plaque burden has reached approximately 40% of the internal elastic lamina area within a diseased segment [6]. Thus, without the cross-sectional vessel view afforded by IVUS and other tomographic imaging technologies, identification of early stage atherosclerosis is nearly impossible with coronary angiography alone [2, 7].

While the clinical significance of angiographically occult CAD remains controversial, there is a growing evidence that its detection may offer both mechanistic insights and prognostic value. Over 20 years ago, the association between atherosclerosis and disrupted coronary vasomotor tone was made with IVUS in angiographically normal or mildly diseased coronary segments of patients presenting with chest pain and provokable coronary vasospasm [8] . Similarly, St. Goar et al. described IVUS evidence of angiographically invisible, pathologic intimal thickening of the coronary arteries in the majority of heart transplant recipients who were at least 1 year post-transplantation [9]. More recently, the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study evaluated 697 patients with acute coronary syndromes enrolled post-PCI using three-vessel coronary angiography with grayscale and radiofrequency IVUS (VH-IVUS). At a median follow-up of 3.4 years, it was observed that 20.4% of patients in this cohort suffered major adverse cardiac events (MACE), of which 11.6% were attributable to lesions deemed nonculprit by initial angiography [10••]. Furthermore, it was noted that the majority of nonculprit lesions responsible for future cardiovascular events were angiographically mild at baseline (visually estimated mean [±SD] diameter stenosis, 32.3 ± 20.6%). Multivariate analysis of the IVUS data found, however, that nonculprit lesions associated with recurrent MACE were more likely than those not associated with recurrent events to have a plaque burden of 70% or greater (hazard ratio, 5.03; 95% confidence interval [CI], 2.51 to 10.11; p < 0.001) or a minimal luminal area of 4.0 mm2 or less (hazard ratio, 3.21; 95% CI, 1.61 to 6.42; p = 0.001), or to be classified on the basis of VH-IVUS as thin-cap fibroatheromas (hazard ratio, 3.35; 95% CI, 1.77 to 6.36; p < 0.001). These results underscore the discriminatory and predictive capabilities of IVUS in angiographically insignificant disease and highlight the significance of lesion composition in assessing the clinical relevance of atherosclerosis.

Assessment of Lesion Significance

Conventional angiography is susceptible to significant intra- and inter-observer variability, rendering accurate assessment of lesion severity challenging in general, but especially so in the settings of intermediate disease (visually estimated 40–70% diameter stenoses), small vessels, lesions at vessel ostia, in bifurcation/trifurcation disease, in diffusely diseased vessels, and when imaging the left main coronary artery (LMCA) or other anatomically complex structures [5, 7]. Measurement of minimal luminal area (MLA) and plaque burden (PB) using IVUS can provide helpful quantitative data regarding disease burden [2]. Minimal luminal area is measured at the region of greatest angiographic stenosis and compared to the area obtained in adjacent angiographically normal segment(s) (reference luminal area; RLA). While functionally significant coronary MLA cutoff values have been described in the literature and are frequently invoked for therapy guidance, stand-alone IVUS MLA measurements should be interpreted with great caution for the following reasons: Firstly, a wide range of MLA values (4.5–6.0 mm2 for the left main coronary artery, 1.6–3.2 mm2 for non-left main coronary arteries) have been correlated with functionally significant fractional flow reserve (FFR) values (0.75–0.80), varying with anatomic variables such as specific vessel being evaluated, location of the lesion within the vessel, and reference vessel caliber, etc. [11,12,13]. Secondly, lesion MLA represents only one aspect of coronary flow dynamics and relying solely on this measurement discounts the impact of other contributors such as diffuse disease, lesions in tandem, and dynamic vasomotor tone. Finally, the total amount of myocardium subtended by the lesion of interest and the presence of collaterals (either originating from or partially supplying the territory being studied) are important considerations which have yet to be characterized in studies addressing this issue. While it was mentioned previously that MLA ≤ 4 mm2 was one of the IVUS-derived variables correlated with future incidence of MACE in the PROSPECT trial, it should be noted that MLA measurements < 4mm2 do not consistently correlate with objective ischemia and furthermore, it remains unknown on what proportion of these lesions will eventually progress and/or result in MACE in stable or unstable CAD populations [10••, 13]. Overall, only modest agreement has been found between IVUS MLA threshold values and FFR significance, highlighting a fundamental disparity between biological structure and function [13, 14, 15•]. One recent analysis utilized receiver-operating characteristic (ROC) curve analysis to identify MLA < 2.8 mm2 (sensitivity 79.7%, specificity 80.3%) as the optimal threshold value for FFR < 0.75 and MLA < 3.2 mm2 for FFR < 0.80 (sensitivity 69.2%, specificity 68.3%) [15•]. In summary, when assessing intermediate lesions using IVUS, higher MLA values may be considered as a tool to rule out functionally significant stenosis (especially when evaluating isolated ostial or mid-shaft left main lesions), while lower MLA values should trigger evaluation of physiologic lesion significance using FFR, instantaneous wave-free interval ratio (iFR) or noninvasive stress testing [14].

Evaluation of Plaque Characteristics and Detection of Vulnerable Plaque

As mentioned previously, radiofrequency plaque analysis with VH-IVUS provides a powerful tool to classify atherosclerotic lesions, aiding in determination of risk and vulnerability. Thin-cap fibroatheromas (TCFA), characterized by a lipid-rich necrotic core with an overlying thin cap filled with abundant infiltrating macrophages, are believed to be the most common phenotype of high-risk atherosclerotic plaque [16]. A strong association between the presence of TCFAs and future development of MACE has been demonstrated [16, 17]. A TCFA with large plaque burden (70% or greater) further increased the risk of MACE in the PROSPECT study [18]. As coronary angiography fundamentally lacks the ability to distinguish lesion morphology and/or determine plaque burden, adjunctive-imaging techniques aimed at capturing histopathological plaque features associated with plaque vulnerability may aid in risk assessment, prognostication, and guidance of therapeutic strategy. VH-IVUS has been validated for the detection of calcified and non-calcified TCFA and has demonstrated predictive capabilities for plaque progression and rupture [10••, 17, 19]. Sensitivity of IVUS for identifying autopsy-confirmed TCFA was found to be 63.6% with a specificity of 78.1% and was reportedly comparable to the sensitivity and specificity of optical coherence tomography (OCT) [20]. Figure 1 demonstrates a potential clinical application for use of VH-IVUS in conjunction with angiography to guide PCI of unstable atherosclerotic disease.

Fig. 1
figure 1

VH-IVUS pullback of a mid-LAD segment in a patient presenting with NSTEMI. While the angiogram reveals a focal “culprit” lesion, selected Virtual Histology (Volcano Corporation, San Diego, CA) cuts taken through the entire diseased segment of LAD reveal significant differences in plaque burden and composition in closely adjacent segments as well as disparities between IVUS-derived MLA versus apparent angiographic stenoses along the course of the vessel. The VH-IVUS colorized tissue map corresponds to four tissue types: necrotic core (red), dense calcium (white), fibrous (dark green), and fibrofatty (light green)

Full size image

Stone et al. found in the PROSPECT study that the presence of TCFA identified with IVUS-VH in patients treated for ACS was an independent predictor of future MACE attributable to nonculprit lesions [10••]. Fifty-one percent of recurrent events related to nonculprit lesions were associated with TCFA, and the authors suggest that a portion of the remainder of lesions may have involved undetected TCFA due to technology limitations or evolved over time to meet criteria for TCFA. As the prognostic value of IVUS TCFA becomes evident, early identification becomes a crucial step toward ensuring that therapies are directed toward target lesions with the highest likelihood of plaque rupture. It should be noted however, that no large-scale data currently exist to assess the impact of catheter-based intervention on the natural history of this type of subclinical atherosclerotic disease [21].

IVUS-Guidance in Percutaneous Coronary Intervention

Improvement in Percutaneous Coronary Intervention (PCI) Outcomes

Adjunctive IVUS during PCI can offer a wealth of information to complement available angiographic and physiologic data. Specifically, details relating to vessel size and structure, plaque morphology and composition, and the extent of disease may influence lesion preparation strategy and device selection. IVUS-derived parameters relevant to coronary stent optimization include metrics of stent sizing, confirmation of stent expansion and apposition, avoidance of “geographic miss” at the location of implant, and detection of edge dissections which may require additional therapies. (Fig. 2).

Fig. 2
figure 2

Use of grayscale IVUS and adjunctive color flow imaging with ChromaFlo ® (Volcano Corporation, San Diego, CA) for stent optimization. ChromaFlo ® imaging, which is based on Doppler shift principles, performs rapid comparisons of sequential axial IVUS images in order to determine differences in the position of echogenic blood particles between successive images. The software then depicts areas of active blood flow with a red (nondirectional) color scheme. A Reveals a well-expanded and well-apposed 4.0 mm DES. B Demonstrates complete stent expansion (per manufacturer’s labeling) but significant malapposition with abluminal blood flow (arrows) resulting from visually guided stent undersizing. C, D Demonstrate an apposed but underexpanded DES. Note the absence of abluminal blood flow in C, but comparison of the stented area (green) with the area of the immediately distal, normal reference segment (blue) highlights the discrepancy in expansion

Full size image

A pre-specified subgroup analysis of the prospective, multi-center Assessment of Dual AntiPlatelet Therapy with Drug Eluting Stents (ADAPT-DES) study (n = 3349 of 8583 consecutive patients enrolled in the main trial) comprised, at the time of publication, the single largest published experience with IVUS guidance of PCI. A significant reduction in rates of stent thrombosis (0.6% versus 1.0%; aHR 0.40 [0.21–0.73]; p = 0.003), myocardial infarction (2.5% versus 3.7%; aHR 0.66 [0.49–0.88]; p = 0.004), and composite MACE (3.1 vs 4.7%; aHR 0.70 [0.55–0.88]; p = 0.002) at 1-year post-PCI was seen in patients with IVUS-guided procedures versus angiography alone [22••]. The greatest absolute benefit was noted in patients who presented with acute coronary syndromes (particularly STEMI) and in patients with complex coronary anatomy. While use of IVUS in ADAPT-DES was at operator discretion and not a randomized procedural variable, IVUS data influenced PCI strategy in 74% of the cases in which it was utilized: In 38% of cases, operators utilized a larger stent or balloon and in 23% of cases, higher inflation pressures were used. Incomplete expansion of stents or stent malapposition detected by IVUS led to stent post-dilatation in 13 and 7% of patients, respectively.

In patients with stable coronary disease and significant angiographic stenosis, the value of PCI in addition to optimal medical therapy has been a source of considerable debate for the past decade. It has been suggested that IVUS-guided intervention in this population may offer differential benefit over conventional angiographically-guided PCI. The results of the North America-based Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial suggested that while PCI in patients with stable coronary disease as an initial management strategy improved anginal symptoms, it did not significantly improve mortality or risk of myocardial infarction over optimal medical therapy alone [23]. In contrast, the Japanese Stable Angina Pectoris (JSAP) trial, demonstrated a reduction in the incidence of acute coronary syndromes with the addition of PCI to optimal medical therapy in patients with a stable disease [24]. Notably, all PCI in the JSAP trial was performed with IVUS guidance while this was much less common in the COURAGE trial. It stands to reason that this may have contributed to the higher initial success rate of PCI per vessel in JSAP (99.5%) versus what was observed in COURAGE (93%) and further, may have impacted the durability of the post-PCI outcomes [24].

Several meta-analyses to date have evaluated the impact of IVUS-guidance on post-PCI outcomes [25•, 26, 27•, 28, 29]. Two recent, large meta-analyses summarize the majority of evidence available at the time of writing on this issue. A meta-analysis by Ahn et al. of 26,503 patients including three randomized trials and 14 observational studies found a significantly lower risk of death (OR 0.61 [0.48–0.79]; p < 0.001), MI (OR 0.57 [0.44–0.75]; p < 0.001), stent thrombosis (OR 0.59 [0.47–0.75]; p < 0.001), and target vessel revascularization (OR 0.81 [0.66–1.00]; p = 0.046) in patients with IVUS-guided DES implantation versus those with angiography-guided implantation [27•]. While IVUS guidance has previously been shown to reduce restenosis in patients with bare metal stents, this difference was not demonstrated in this DES population, presumably due to lower baseline rates of restenosis with DES. IVUS-guided procedures in this meta-analysis were more likely to utilize larger and longer stents, with a mean difference in stent size of 0.33 mm (p < 0.001) and a mean difference in stent length of 0.18 mm (p < 0.001). A greater number of stents were also utilized in the IVUS-guided group, with a mean difference of 0.27 (p < 0.001). Zhang et al. similarly found in a meta-analysis of 20 studies including 29,068 patients (13,552 (46.6%) with IVUS-guided DES implantation and 15,516 (53.4%) with angiography-guided DES implantation) that IVUS-guided DES placement was associated with decreased MACE (OR 0.77 [0.71–0.83]; p < 0.001), death (OR 0.62 [0.54–0.71]; p < 0.001), and stent thrombosis (OR 0.59 [0.47–0.73]; p < 0.001) compared to angiographically guided DES placement [25•]. Of note, in a meta-regression subanalysis of the 6393 patients with complex lesions or ACS, the authors found that the benefits of IVUS guidance were even more pronounced than in patients with mixed lesions or stable presentations.

Use of IVUS Guidance in PCI for Complex Patient and Lesion Subsets

As mentioned, several publications have hinted at the differential value of IVUS-guided stent implantation in patients with complex (versus straightforward) coronary disease. The issue was again addressed by a recent meta-analysis focusing on patients receiving newer generation drug-eluting stents for long lesions or chronic total occlusions. In this analysis, IVUS-guided stent implantation was associated with significantly lower rates of MACE than angiographically guided procedures (0.4 vs 1.2%; HR 0.35 [0.13–0.99]; p = 0.040) [30]. Similarly, in the Impact of IntraVascular UltraSound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) trial, 1400 patients with long lesions requiring stents greater than or equal to 28 mm were randomized to receive IVUS-guided versus angiographically guided second-generation DES implantation [31]. The incidence of MACE at 1 year was significantly lower in patients who received IVUS-guided DES (2.9% v 5.8%; HR 0.48 [0.28–0.83]; p = 0.007).

Percutaneous treatment of unprotected LMCA disease is another area where IVUS guidance appears to confer consistent benefit over angiographic guidance alone. In the Korean MAIN-COMPARE registry, propensity-matched comparisons of patients undergoing elective stenting of an unprotected LMCA with or without IVUS-guidance found that 3-year mortality was lower in patients who received IVUS-guided drug-eluting stents as compared to angiographically guided procedures (4.7% versus 16.0%, log-rank p = 0.048) [32]. No mortality difference was noted, however, in patients who received bare metal stents (8.6% versus 10.8%, log rank p = 0.35). These observations were echoed by a recent meta-analysis of IVUS-guided DES for LMCA disease. In 4592 patients sourced from seven observational studies and one randomized clinical trial, IVUS-guided stenting was associated with significantly lower MACE (RR 0.61 [0.53–0.70]; p < 0.001), including stent thrombosis (RR 0.48 [0.27–0.84]; p = 0.01) and myocardial infarction (RR 0.66 [0.55–0.80]; p < 0.001) [33]. The specific IVUS-derived measurement thresholds which impact clinical outcomes following LMCA PCI were investigated in a study by Kang et al. who evaluated post-stenting IVUS minimal stent area (MSA) in 4 LMCA segments [ostial left anterior descending (LAD), ostial left circumflex (LCX) polygon of confluence (POC, confluence zone of LAD, and LCX), and proximal LM above the POC] [34•]. In 403 patients with unprotected LMCA disease treated with single- or 2-stent PCI strategies, it was found that the IVUS MSA cutoffs that optimally predicted in-stent restenosis (ISR) on a segmental level, were 5.0 mm2 (ostial LCX ISR), 6.3 mm2 (ostial LAD ISR), 7.2 mm2 (ISR within the POC), and 8.2 mm2 (ISR in the LM above the POC). Utilizing these threshold values, it was noted that 33.8% (133) of patients evidenced DES underexpansion of at least one LMCA segment and 2-year MACE-free survival rate was significantly lower in patients with underexpansion of ≥ 1 segments versus lesions with no underexpansion (90 ± 3% versus 98 ± 1%, log-rank p < 0.001). Regression analysis found IVUS-assessed LMCA DES underexpansion to be an independent predictor for MACE (adjusted hazard ratio, 5.56; 95% confidence interval, 1.99–15.49; p = 0.001). Figures 3 and 4 provide step-by-step detail of IVUS guidance in PCI of an unprotected LMCA and confluent LAD disease).

Fig. 3
figure 3

IVUS-guided stenting of proximal-mid LAD and unprotected LMCA from a right radial approach. A Demonstrates high-grade disease in the LMCA with confluent disease in the proximal to mid LAD. Following IVUS-guided vessel sizing, overlapping B 3.0 × 30 mm and C 3.5 × 30 mm DES were deployed at rated burst pressures. D IVUS assessment of the entire stented segment was performed confirming excellent apposition but modest under-sizing. E High-pressure post-dilatation was performed using 3.5 mm and 4.0 mm non-compliant balloons along the entire stented segment. F Reveals excellent angiographic results with IVUS images corresponding to each vessel segment, shown in Fig. 4

Full size image
Fig. 4
figure 4

Post-stenting IVUS images of the PCI case detailed in Fig. 3. Clockwise from top left, appropriate expansion and complete stent apposition at the ostial LMCA, mid-shaft LMCA, the polygon of confluence (LCx ostium labeled), and proximal LAD with the undiseased LAD segment shown for reference

Full size image

Thus, an abundance of data currently exists to support the routine use of IVUS guidance in patients with LMCA lesions of indeterminate severity or extent and in PCI, especially for complex lesions, ACS presentation, and unprotected LMCA disease. The 2011 American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography (ACC/AHA/SCAI) guidelines for PCI offer class IIa recommendations for the use of adjunctive IVUS in evaluation of angiographically indeterminate LMCA disease (level of evidence B) and for determining the mechanism of restenosis (level of evidence C) [35]. A class IIb recommendation is offered for IVUS guidance in coronary stent implantation, especially in LMCA PCI (level of evidence B), and in the assessment of non-LMCA coronary arteries with angiographically indeterminate stenosis (level of evidence B) [35].

Evaluation and Management of Stent Thrombosis

While newer generation drug-eluting stents have posted lower rates of stent thrombosis (ST) than their predecessors, DES ST remains an ongoing concern. Data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) found that 1.3% of patients with second-generation DES placed for acute myocardial infarction developed stent thrombosis over a 3-year follow-up period [36]. IVUS has long been utilized to elucidate the primary mechanism of stent thrombosis and to guide therapeutic options [37,38,39]. Common morphologic abnormalities found in patients with acute to subacute stent thrombosis include stent malapposition (also referred to as incomplete stent apposition) and stent underexpansion [40]. Stent malapposition, characterized by the visible separation of one or more struts from the intimal surface with evidence of blood speckle posterior to the strut and without the presence of side branches, can occur at the time of initial stent placement or can develop over time [41, 42]. Initial malapposition can occur when DES are under sized or inflated at low pressures while the latter may be a reflection of positive vessel remodeling on the backdrop of incomplete DES endothelialization [37, 38]. Malapposition is reportedly more common with DES than BMS, with an estimated incidence as high as 10–25% [41, 42]. Ectatic vessels may increase the likelihood of malapposition. IVUS-guided DES post-dilation can help minimize or eliminate abluminal space behind the stent, decreasing future thrombotic risk.

Stent underexpansion differs from malapposition in that in the former scenario, contact with the diseased intima may exist in the majority of stented segments. However, the finished dimensions of the stent are smaller than predicted by the inflation chart and/or with respect to reference vessel dimensions. Stent underexpansion is believed to be a major contributor to both restenosis as well as thrombosis of the target vessel and can result from a number of factors—including inadequate lesion preparation (especially in the setting of unrecognized fibrocalcific disease), low-inflation pressure, and failure to post-dilate the stent. IVUS can be employed to assess the need for lesion preparation pre-DES and the adequacy of stent expansion post-DES and may be utilized iteratively to guide balloon post-dilation [43]. In a prospective study of 48 patients with DES placement and routine post-dilation, IVUS evaluation of cross-sectional area revealed that adequate stent deployment was only achieved in 54% of patients despite the post-dilation [44]. When IVUS was used to guide further post-dilation, optimal stent deployment was able to be attained in 81% of cases.

Edge dissections may also contribute to stent thrombosis by affecting target segment inflow and outflow [45]. In 887 patients undergoing DES implantation with IVUS guidance, the incidence of edge dissections as assessed by IVUS was 9.2% per patient and 8.4% per artery [46]. Edge dissections were found to be more common in patients with bare metal stents who developed stent thrombosis than in those who did not [47]. Use of IVUS to detect uncovered dissections at the very least allows for a more sensitive evaluation of the issue than permitted by angiography and may guide additional therapies with an attendant decrease in the risk of future stent thrombosis.

Assessment of Cardiac Allograft Vasculopathy Using IVUS

In addition to the myriad applications of IVUS in native coronary artery disease, IVUS also plays a vital role in the evaluation of cardiac allograft vasculopathy (CAV) in heart transplant recipients [9]. Cardiac allograft vasculopathy is an accelerated and at times, rapidly progressive form of vascular disease characterized by the progression of concentric fibrous intimal hyperplasia throughout the transplanted coronary vessels. This syndrome is recognized as a major contributor to post-transplant morbidity and mortality, with an incidence of approximately 10% at 1 year post-transplant and over 50% at 10 years [48]. Measurement of maximal intimal thickening (MIT) with IVUS provides an early measure of developing CAV. Progression of MIT ≥ 0.5 mm over the first year after transplant is strongly associated with higher 5-year mortality or graft loss (20.8% vs. 5.9%; p = 0.007) [49]. This is often evident well before the development of angiographically discernable disease [50]. The attenuated-signal plaque (ASP) score has also been utilized in the evaluation of CAV as a surrogate for plaque instability. In 105 heart transplant patients, IVUS-guided assessment of ASP at baseline and 1 year post-transplant found that ASP progression was associated with a higher incidence of acute cellular rejection (p = 0.006) and all-cause death or re-transplantation (p = 0.0005) [51]. Serial IVUS examinations are a key component of identification of high-risk patients. Early identification of CAV allows for implementation of aggressive medical therapies, including augmented anti-atherosclerotic and/or immunosuppressive treatment [50]. IVUS has been utilized to monitor progression of CAV and assess the impact of interventions such as mTOR inhibitors and statins [52, 53]. In the 2011 ACC/AHA/SCAI PCI guidelines, use of IVUS in conjunction with coronary angiography at 4–6 weeks and 1 year after cardiac transplantation to exclude donor CAD, detect rapidly progressive CAV and provide prognostic information, garners a class IIa recommendation (level of evidence B) [35].

Conclusions

Intravascular ultrasound is an indispensable, if underutilized, tool for the assessment of patients with atherosclerotic and non-atherosclerotic native coronary disease as well as for detection and surveillance of cardiac allograft vasculopathy. Recent investigations have highlighted the value of IVUS in identifying high-risk (vulnerable) lesions, guiding interventional strategies, and optimizing PCI outcomes. The use of IVUS guidance in PCI has been associated, in numerous individual studies and meta-analyses, with lower incidence of MACE, stent thrombosis, and repeat revascularization, as compared with angiographically guided PCI. The benefits of IVUS-guided PCI are especially pronounced in patients with complex coronary anatomy (i.e., long lesions, fibrocalcific disease, and chronically occluded vessels), high presentation acuity (ACS/STEMI), and in unprotected LMCA disease. While IVUS sizing of coronary vessels often complements angiographic and physiologic data, use of standalone IVUS measurements for determination of lesion significance is discouraged, as coronary cross-sectional area is but one of many determinants of coronary flow dynamics. Post-processing applications such as Virtual Histology and iMAP offer the promise of in vivo plaque compositional analysis with prognostic implications therein, but the full potential and application of these and related technologies are as yet, unrealized. In conclusion, grayscale IVUS is a vital tool for the comprehensive evaluation of vascular disease and for the optimal performance of PCI. The performance and accurate, real-time interpretation of IVUS should be regarded as requisite skills for all interventional operators, especially those engaged in complex PCI procedures.