and attenuated plaques are considered to be unstable and have been identified in both culprit and non‐culprit lesions of patients with (STEMI) [4–5]. Histopathologically, the vast majority of attenuated plaques correspond to either a fibroatheroma with a necrotic core or pathologic intimal thickening with a lipid pool; almost all segments with superficial echo attenuation indicated the presence of an fibroatheroma with an advanced necrotic core [19]. Most importantly, attenuated plaque has been associated with the occurrence of microvascular obstruction after primary PCI no‐reflow phenomenon, and with late acquired stent malapposition in patients with STEMI [4–6,20,21].
Detection of Vunerable Plaque
PROSPECT and VIVA were the first prospective studies that used three‐vessel IVUS imaging to examine it is efficacy in detecting nonculprit lesions that are likely to progress and cause cardiovascular ischemi events [5] In PROSPECT [22], a minimum lumen area≤4mm2, plaque burden ≥ 70%, and the presence of a TCFA phenotype, derived by virtual histology (VH)‐IVUS, were predictors of subsequent non‐culprit MACE. Lesions with these high risk plaque characteristics were eleven times more likely to cause events within a 3.4‐year follow‐up than simple lesions [hazard ratio (HR): 11.05, P < 0.001]; however, the positive predictive value of these three high‐risk plaque features for subsequent events was low (18.2%). In the light of IVUS limitations in detecting vulnerable plaque [22–25] other imaging modalities including NIR and OCT has the potential value of vulnerable plaque detection (e.g. COMBINE OCT‐FFR; PROSPECT II [26,27] and plaque sealing are promising (PROSPECT II ABSORB; PREVENT Trial NCT02316886 [28].
Role of intravascular imaging for assessment of lesion severity
Coronary angiography may underestimate stenosis severity most markedly in arteries with a 50–75% plaque burden and in patients with multivessel disease [6]. In patients with stable coronary artery disease, fractional flow reserve (FFR) or instantaneous flow reserve (iFR) is the well‐established physiologic index to assess the functional significance of a coronary stenosis. Studies have used FFR ≤0.80 as the optimal cut‐off point to guide revascularization [29,30], and have reported correlation between FFR values and anatomic parameters (especially minimum lumen area; MLA) derived from IVUS or optical coherence tomography (OCT) [31]. Of the IVUS‐derived measurements, MLA cut‐off values to predict FFR had been widely reported. The correlation between MLA cut‐off points and ischemic FFR threshold ranged from 2.0 to 3.9 mm2 in non‐left main coronary artery (LMCA) intermediate stenosis and from 4.5 to 5.9 mm2 in LMCA stenosis [4–5,32]. The FIRST (Fractional Flow Reserve and Intravascular Ultrasound Relationship) study, based on a multicenter, prospective registry in the USA and Europe proposed 3.07 mm2 as a best cut‐off value to define the presence of myocardial ischemia [33]. In the largest sample‐size and international multicenter study with 822 patients (881 lesions), Han et al. [31] found that best cut‐off value of IVUS‐MLA to define the functional significance (FFR <0.8) to be 2.75 mm2. A meta‐analysis of 11 studies comparing IVUS‐MLA with FFR for assessment of intermediate lesions showed that the weighted overall mean MLA cut‐off was 2.61 mm2 in non‐LMCA and 5.35 mm2 in LMCA to predict a functional stenosis [34].
Atherosclerotic obstruction of the LMCA is present in approximately 4% of all coronary angiograms [35] and is often underestimated by coronary angiography. The main reasons for the discrepancy between angiography and IVUS are the following: (i) diffuse atherosclerotic plaque involvement may lead to a lack of a “true normal” reference segment, (ii) a short LMCA makes identification of a normal reference segment difficult, (iii) the presence of arterial remodeling, (iv) the correlation between angiography and necropsy or IVUS appears to be better in non‐LMCA lesions possibly because of unique geometric and angulation issues in the LMCA [66], and (v) significant inter‐ and intraobserver variability in the angiographic assessment of LMCA disease, especially in ostium location [4–6]. Hence, comparable to LMCA limitations of FFR, IVUS interrogation of the LMCA has multiple shortcomings. Imaging pullback from 2 directions (i.e. from each of its 2 branch arteries) can be helpful.
Other unusual lesion morphology
During coronary angiography it is common to encounter unusual appearing lesions that elude accurate characterization despite thorough examination using multiple radiographic projections. The use of IVUS allows accurate characterization of unusual morphology: filling defects, aneurysms, and spontaneous dissections. While most filling defects are true thrombi, a small percentage are highly calcified plaque (Figures 8.8 and 8.9) or even calcified nodules, an unusual form of vulnerable plaque.
Figure 8.9 This patient underwent a previous PCI with DES implantation of a lesion, in the diagonal artery, during which the artery was dissected. Follow‐up catheterization showed both restenosis and a large aneurysm on angiography. The IVUS shows from proximal to distal (a to h) the body of the aneurism (asterix in the longitudinal view and c to h) and the eccentric proximal restenotic lesion (b). Notice that the adventitia stops at the point of transition from the vessel to the aneurysm (c and d), indicating loss of vessel wall integrity and making this, in fact, a pseudoaneurysm. Notice the double lumen from e to g; and normal vessel with three‐layer aspect in h.
In an IVUS analysis of 77 angiographically diagnosed aneurysms, 27% were true aneurysms (Figure 8.10), 4% were pseudoaneurysms (Figure 8.10), 16% were complex plaques, and 53% were normal arterial segments adjacent to stenoses [6]. In‐stent neoatherosclerosis has been recently described as an important mechanism of late stent failure (i.e. restenosis and stent thrombosis).
Figure 8.10 This young, female patient presented with STEMI and type 4 SCAD by angiography in the mLAD. IVUS showed a normal three‐layer aspect to the proximal vessel (a and magnified image in b). Notice the crescent aspect of the hyperechoic hematoma comprising the true lumen from c to h (arrows in e). FL indicates false lumen and TL true lumen; note a septal branch within the FL in panel F.
Courtesy of Dr. José Mariani Jr.
Spontaneous coronary artery dissection (SCAD)
Both IVUS and OCT can be used to diagnosis of SCAD, and both modalities have strengths and weaknesses). IVUS can be preferred where there in evidence of false lumen (Type 1), and in small calibre and tortuous vessels, where the imaging probe risks being occlusive; and proximal vessel dissections, where the false lumen stretches the external elastic lamina, increasing the vessel size. However, IVUS resolution can be insufficient for the detection of intima‐media complex fenestrations as seen in OCT [5]. By IVUS, a spontaneous coronary artery dissection appears as a medial dissection with an intramural hematoma occupying some or all of the dissected false lumen without identifiable intimal tears and without a communication between the true and false lumens, typically in a non‐atherosclerotic artery (Figure 8.11).
