In patients with acute coronary syndrome (ACS) and no obvious angiographic culprit lesion, intravascular imaging can define potential coronary atherothrombotic causes, such as plaque rupture, non-obstructive erosions, calcified nodules, or napkin-ring lesions [9]. These diagnoses carry implications for therapy as continuation of antithrombotic and antiplatelet agents may be desirable in these settings. There are no randomized studies to determine the benefit of PCI in non-critical obstructive disease, thus the justification to proceed with revascularization must be made on clinical grounds, considering procedural risks related to lesion location (distal or bifurcation disease) and calcification, as well as vessel tortuosity and diameter. In patients already undergoing PCI, intravascular imaging may be useful to characterize intraprocedural ambiguous angiographic findings, such as haziness or luminal narrowing post-stent deployment or at the edges of the stent, which usually may be signs of unrecognized edge or vessel dissection, residual thrombus, or stent under-expansion.

Intracoronary imaging may be necessary to diagnose spontaneous coronary artery dissection (SCAD) when there is angiographic uncertainty [10]. However, it should be carefully considered given the high risk of propagating the dissection due to instrumentation into the false lumen. While there are no randomized studies that guide management of SCAD, most observational studies and expert consensus documents support a conservative approach [11]. If SCAD is strongly suspected by angiography and conservative therapy has been chosen, there is no indication to perform further intravascular imaging.

Some studies collectively highlight the role of IVUS and OCT in assessing intermediate coronary stenoses (40–70% occlusion by visual estimation on coronary angiography) for aiding in the decision to proceed with PCI. Koo et al. [12] and Waksman et al. [13] determined that there was only a modest correlation between minimal-lumen area (MLA) and plaque burden by IVUS and fractional flow reserve (FFR) values. The MLA thresholds that correlated with ischemia varied by location of the lesion. In both studies, an MLA ≤ 3.0 mm2 in the LAD and ≤ 2.4 mm2 in non-LAD arteries correlated with ischemia by FFR. Vergallo et al. [14] performed a multicenter, international, pooled analysis of individual patient-level data from published studies assessing FFR and OCT on the same vessel. In their study, an MLA < 2.0 mm2 and an area stenosis > 73% were effective predictors of an FFR ≤ 0.80. For proximal coronary segments, the optimal OCT thresholds that correlated with an FFR ≤ 0.80 were MLA < 3.1 mm2 and area stenosis > 61%. Although these studies point in general to some correlation between imaging findings and a threshold FFR, their findings were not perfectly aligned, suggesting that IVUS and OCT alone may not fully replace FFR for physiologic assessment and that if used as surrogates for this purpose, ample consideration should be made to the clinical context.

The benefit of intravascular imaging to support and optimize PCI results and improve patient outcomes is now well established, yet use of these modalities remains low. Fazel et al. [15] recently reported that among Medicare beneficiaries undergoing PCI, use of intravascular imaging increased over a span of 6 years from 9.4% to 15.4%. In this population, use of intravascular imaging to guide PCI was associated with lower rates of major adverse cardiovascular events (MACE) (26% risk reduction), including all-cause mortality, compared to angiography-guided PCI. Similarly, Malik et al. [16] reported that the median use of intravascular imaging to guide PCI in the US had increased from 2.7% in 2016 to just 6.3% in 2020, despite imaging being available in 86% of hospitals. Although studies like these consistently show an increase in utilization of imaging, adoption continues to lag behind a growing body of evidence.

The IVUS-XPL Trial [17, 18] randomized patients to IVUS-guided versus angiography-guided drug-eluting stent implantation in long coronary lesions. IVUS guidance significantly reduced the rate of MACE, mainly by lowering target lesion revascularization (TLR)(2.5% vs 5.0% in the angiography-guided group, HR, 0.51 [95% CI, 0.28 to 0.91], P = 0.02). This benefit was sustained at 5 years with lower rates of MACE (5.6% vs 10.7%, HR: 0.50; 95% confidence interval: 0.34 to 0.75; p = 0.001) and TLR in the IVUS group (4.8% vs 8.4%, HR: 0.54; 95% CI: 0.33 to 0.89; p = 0.007). The ULTIMATE Trial [19, 20] was a large scale, all-comers trial comparing IVUS-guided and angiography-guided PCI using drug-eluting stents. IVUS guidance resulted in a significantly lower rate of target vessel failure (TVF) at 3 years (6.6% vs 10.7%, p = 0.01), primarily due to reduced Target Vessel Revascularization (TVR) (4.5% vs 6.9%, p = 0.05) and definite/probable stent thrombosis (0.1% vs 1.1%, p = 0.02). These studies consistently demonstrate that IVUS-guided PCI improves long-term clinical outcomes compared to angiography guidance alone.

The CLI-OPCI II multicenter registry [21] and a subsequent review of the major studies evaluating the clinical impact of OCT findings during PCI [22], revealed that in-stent MLA < 4.5 mm2, major distal edge dissections (> 200 μm in depth or > 60° and/or > 3 mm in length), and reference lumen narrowing < 4.5 mm2, were independent predictors of MACE. Suboptimal stent implantation utilizing these and other criteria occurred in 31%−58% of cases. Their findings underscored the value of OCT in detecting suboptimal stent deployment, which is linked to adverse clinical outcomes during follow-up. The DOCTORS Study [23] assessed the impact of OCT guidance in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and reported that OCT-guided PCI led to larger final minimal stent area (MSA) and greater post-PCI FFR compared to angiography-guided PCI. ILUMIEN III [24] compared OCT-guided, IVUS-guided, and angiography-guided PCI and found that OCT guidance resulted in a similar MSA compared to IVUS and was superior to angiography in detecting suboptimal stent implantation. However, there was no significant difference in clinical outcomes between the imaging modalities at one year [25]. Its follow-up study, ILUMIEN IV [26] compared OCT-guided vs. angiography-guided PCI in patients receiving drug-eluting stents. Although OCT guidance led to larger stent dimensions, reduced residual stenosis, and significantly lower incidence of definite/probable stent thrombosis vs angiography guidance (0.5% vs. 1.4%; HR 0.36; 95% CI, 0.14–0.91; P = 0.02), there was no significant difference in the rate of the primary efficacy endpoint of target-vessel failure (death from cardiac causes, target-vessel myocardial infarction (MI), or ischemia-driven TVR). In the OCTOBER trial [27], OCT-guided PCI in patients with complex coronary bifurcation lesions was associated with a lower risk of a composite of death from a cardiac cause, target-lesion MI, or ischemia-driven TLR at 2 years than angiography-guided PCI (10.1% vs. 14.1%; HR 0.70; 95% CI, 0.50–0.98; P = 0.035). The collective findings of all these studies suggest that OCT guidance during PCI can generally improve procedural results and in certain patient populations improve long term outcomes compared to angiography guidance alone.

A few studies have performed head-to-head comparisons of IVUS and OCT for PCI guidance. In the OPINION Trial [28], use of both imaging techniques led to similar 1-year clinical outcomes with very low rates of 8-month angiographic binary in-segment restenosis (6.2% and 6.0%) and 12-month TVF (5.2% and 4.9%) for OCT and IVUS, respectively. Similarly, the OCTIVUS trial [29] reported that OCT-guided PCI was noninferior to IVUS-guided PCI with respect to the incidence of a composite of death from cardiac causes, target vessel–related myocardial infarction, or ischemia-driven TVR at 1 year. The RENOVATE-COMPLEX-PCI trial [30] demonstrated that either IVUS or OCT-guided PCI significantly reduced MACE compared to angiography-guided PCI in patients with complex coronary artery lesions. Over a 2.1-year follow-up, the imaging-guided group had a lower incidence of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization (7.7% vs. 12.3%; HR 0.64; P = 0.008). Several recent meta-analyses and observational studies [31,32,33,34] have reported that both IVUS and OCT outperform angiography alone in PCI guidance by reducing stent-related complications and improving procedural outcomes. Although OCT may be superior for procedural optimization (stent expansion, malapposition detection), the current evidence for reducing long-term adverse events (stent thrombosis, restenosis) may be stronger for IVUS. There are no studies utilizing NIRS for optimization of PCI. Regardless of the individual choice in imaging, the preponderance of evidence supports using adjunct intravascular imaging with either IVUS or OCT over angiography-guidance alone as a superior strategy for optimizing stent implantation and improving long-term PCI outcomes, mainly lower rates of restenosis, target lesion failure (TLF), and stent thrombosis.

Detection of vulnerable plaque to prevent future ACS and sudden death remains the holy grail of intravascular imaging. All three commercially available imaging technologies—IVUS, OCT, and NIRS, can detect at-risk plaques which are defined differently and correlated with different histopathologic findings. The PROSPECT trial [5] reported that the IVUS findings of plaque burden ≥ 70%, a luminal area ≤ 4mm2, and the presence of a virtual histology thin-cap-fibroatheroma (VH-TCFA) in non-culprit lesions were independent predictors of MACE (HR 5.03, 95% CI 2.51–10.11,P < 0.001, for plaque burden; HR 3.21, 95% CI 1.61–6.42, P = 0.001, for MLA; and HR 3.35, 95% CI 1.77–6.36, P < 0.001 for VH-TCFA). The presence of all three findings in a non-culprit lesion was associated with a 18.2% 3-year MACE rate compared to 1.9% without these characteristics (lesion HR 11.05, CI 4.39–27.82, p < 0.001). However, the main driver of MACE was rehospitalization for angina and not necessarily MI or death. ​ ​The LRP study [35] investigated the use of NIRS-IVUS to identify patients and plaques vulnerable to future coronary events. In this prospective cohort study, imaging of non-culprit segments was performed in patients undergoing cardiac catheterization for possible percutaneous coronary intervention. Over a two-year follow-up, the cumulative incidence of non-culprit MACE was 9%. The study found that for each 100-unit increase in the maximum lipid core burden index over a 4 mm segment (maxLCBI₄ₘₘ), there was an 18% increase in the risk of non-culprit MACE at the patient level, and a 45% increase at the plaque level. Patients with a maxLCBI₄ₘₘ greater than 400 had a significantly higher risk of non-culprit MACE compared to those with lower values (adjusted HR 3·39, CI 1·85–6·20, p < 0·0001). PROSPECT II [36] also used combination NIRS-IVUS to identify non-obstructive coronary plaques at risk of causing future adverse cardiac events. Over a median follow-up of 3.7 years, lesions with high lipid content detected by NIRS and large plaque burden identified by IVUS were found to be independent predictors of MACE. Specifically, lesions exhibiting both characteristics had a 4-year MACE rate of 7.0% (95% CI 4·0–10·0), and patients with at least one such lesion had a 13.2% MACE rate (95% CI 9·4–17·6). These findings suggest that combined NIRS-IVUS imaging can effectively detect vulnerable plaques and patients at increased risk for future cardiac events.

The CLIMA study [37] investigated the relationship between specific plaque characteristics in the proximal left anterior descending artery, as identified by OCT, and the occurrence of MACE over a 12-month period. The study found that the independent or simultaneous presence of four high-risk OCT features—MLA < 3.5 mm2, fibrous cap thickness (FCT) < 75 µm, lipid arc circumferential extension > 180°, and OCT-detected macrophages—was significantly associated with an increased risk of MACE. Patients exhibiting all four features had a hazard ratio of 7.54 (95% CI 3.1–18.6) for experiencing events such as cardiac death or target segment myocardial infarction, underscoring the prognostic value of OCT in detecting vulnerable plaques and stratifying patient risk.

The findings from these studies collectively suggest that NIRS, IVUS, and OCT imaging is a safe and effective tool for identifying vulnerable patients and plaques. The next question is whether identification of these lesions can be used to potentially guide preventive strategies in clinical practice. In a sub study of the PROSPECT Trial, Stone et al. [38] explored the concept of PCI for treating vulnerable coronary atherosclerotic non-obstructive plaques identified by IVUS-NIRS with a bioabsorbable scaffold (BVS). Their findings demonstrated that lesions treated with BVS had a statistically significantly larger follow-up MLA, their primary endpoint, compared to those managed with guideline directed medical therapy alone. Although TLF rates at 24 months were similar between the groups, the study was not powered to detect differences in clinical events. Their results suggested that PCI of angiographically mild lesions deemed to be vulnerable is safe, and highlighted the need for larger trials to assess the clinical efficacy of preemptive PCI in vulnerable plaques.​ The PREVENT trial [39] evaluated whether preventive PCI of non-flow-limiting vulnerable plaques, identified via intracoronary imaging, could improve clinical outcomes compared to optimal medical therapy (OMT) alone. At the 2-year mark, the primary composite endpoint of cardiac death, target-vessel myocardial infarction, ischemia-driven TVR, or hospitalization for unstable or progressive angina, occurred in 0.4% of the PCI group versus 3.4% of the OMT group (absolute difference: −3.0 percentage points; p = 0.0003). These findings suggest that in patients with non-flow-limiting vulnerable plaques, preventive PCI in addition to OMT may reduce major adverse cardiac events compared to OMT alone. Important to note that in this study, operators employed IVUS, OCT, or NIRS based on their expertise and discretion to identify vulnerable lesions. A plaque was classified as vulnerable if it met at least two of the following criteria: MLA ≤ 4.0 mm2 by IVUS or OCT, plaque burden > 70% by IVUS, maxLCBI₄ₘ > 315 identified through NIRS, and the presence of a TCFA detected by OCT or VH-IVUS. This was the first large trial to show the potential effect of the focal treatment for vulnerable plaques identified by intravascular imaging and gives further support to the paradigm of prevention through early detection and treatment of non-flow-limiting, high-risk vulnerable plaques.

In heart transplant recipients, IVUS remains the gold standard for detecting diffuse intimal thickening and cardiac allograft vasculopathy (CAV) [40]. There are robust data that IVUS-based findings of intimal thickening are associated with clinical outcomes in heart transplant patients and have important prognostic implications. Besides several studies demonstrating an association between high-grade acute cellular rejection and abnormal OCT findings, hard outcome data validating the prognostic impact of OCT plaque parameters in the heart transplant population continue to emerge [41]. A recent study has utilized OCT for this purpose in a pediatric heart transplant population with promising results [42]. The totality of data have led to an updated recommendation in 2023 for use of OCT as an alternative to IVUS to detect CAD.

IVUS guidance during PCI of chronic total occlusions has been associated with higher procedural success and improved long-term outcomes compared with angiography alone. In a study by Tian et al. [43], in-stent late-luminal loss in the IVUS-guided group was significantly lower compared to the angiography-guided group at one-year follow-up (0.28 ± 0.48 mm vs. 0.46 ± 0.68 mm, p = 0.025), with a significant difference in restenosis of the “in-true-lumen” stent between the two groups (3.9% vs.13.7%, p = 0.021). Kim et al. [44] reported that the major MACE rates (composite of cardiac death, MI, and TVR) were significantly lower in the IVUS-guided group than that in the angiography-guided group (2.6% versus 7.1%; P = 0.035; HR 0.35; 95% confidence interval, 0.13–0.97). However, the rate of cardiac death or TVR was not significantly different between the groups.