Inside the Artery: Landmark Trials Redefine When Imaging Improves Stent Outcomes

For decades, interventional cardiologists have opened blocked coronary arteries largely by feel and by fluoroscopy, relying on the shadowy two-dimensional silhouette that coronary angiography casts of the vessel lumen. Yet the artery itself is a three-dimensional, living structure, and the plaque within it can be soft, fibrotic, or calcified in ways no angiographic projection can reveal. A comprehensive review published in Nature Reviews Cardiology by Flavio Giuseppe Biccirè, Lorenz Räber and colleagues now synthesizes the evidence from eight large randomized trials — ILUMIEN IV, IVUS-ACS, IVUS-CHIP, IVUS-XPL, OCCUPI, OCTOBER, RENOVATE-COMPLEX-PCI and ULTIMATE — each enrolling more than 1,000 patients, to answer a deceptively simple question: when does looking inside the artery with intracoronary imaging actually save lives, and when is it merely an expensive addition to procedure time?

The two dominant technologies at the heart of this debate are intravascular ultrasonography (IVUS) and optical coherence tomography (OCT). IVUS uses a miniaturized ultrasound transducer mounted on a catheter to generate cross-sectional images of the vessel wall, penetrating deeply enough to visualize the full plaque burden and the external elastic lamina. OCT, by contrast, employs near-infrared light to achieve resolution roughly ten times finer than ultrasound — on the order of 10 to 20 micrometers — allowing clinicians to identify thin-cap fibroatheromas, macrophage infiltration, microchannels, calcium thickness, and dissection planes with unprecedented detail. The trade-off is penetration depth: OCT light struggles to see beyond roughly 1 to 2 millimeters of tissue, whereas ultrasound reaches the adventitia. Together they offer complementary windows onto the pathology that angiography misses.

The cumulative randomized evidence now indicates that imaging-guided percutaneous coronary intervention (PCI) delivers measurable prognostic benefit over angiography guidance alone, but with important heterogeneity. The Korean IVUS-XPL and ULTIMATE trials showed reduced major adverse cardiac events with IVUS guidance in long lesions and in mixed populations. RENOVATE-COMPLEX-PCI and IVUS-ACS extended this signal to complex lesions and acute coronary syndromes. On the OCT side, OCCUPI demonstrated fewer device-oriented composite endpoints in complex lesions, and OCTOBER showed that OCT guidance dramatically improved outcomes in true bifurcation stenting, reducing target-vessel failure by roughly a third compared with angiography. Notably, ILUMIEN IV in North America and IVUS-CHIP in Europe failed to reach their primary endpoints, underscoring that trial design, protocol intensity, operator expertise and patient mix all shape whether imaging’s theoretical advantages translate into clinical gains.

One of the most consistent findings across the pooled datasets is that the benefit of imaging scales with lesion complexity. Simple, short, non-calcified lesions in large vessels rarely benefit measurably — the angiogram usually suffices. But in left main coronary interventions, true bifurcations, long diffuse disease, chronic total occlusions, and heavily calcified plaques, imaging changes management decisions in a substantial fraction of cases: stents are sized larger, placed longer, and dilated more aggressively. In the OCTOBER bifurcation population, for example, OCT uncovered extensive unintended stent deformation after side-branch techniques, deformities invisible on the angiogram that imaging-guided optimization could correct. Meta-analyses, including network meta-analyses by Stone and colleagues and by Giacoppo and colleagues, converge on the conclusion that both OCT and IVUS guidance reduce cardiac mortality, stent thrombosis and repeat revascularization relative to angiography alone, without meaningful differences between the two modalities in head-to-head comparisons such as OCTIVUS and OPINION.

The mechanistic explanation for the survival benefit is procedural. Imaging-guided PCI consistently results in larger post-dilatation balloons, larger and longer stents, greater minimal stent area, and more complete coverage of the diseased segment. Registry data going back to the HORIZONS-AMI substudies and the seminal work of Fujii have linked stent underexpansion and residual reference stenosis to acute and late stent thrombosis — the most feared complication of PCI, carrying high mortality. Imaging makes these failure modes visible before the patient leaves the catheterization laboratory. Achieving prespecified optimization criteria — typically a minimal stent area of 5.0 square millimeters by OCT or 5.5 square millimeters by IVUS in distal references, plus full lesion coverage — has been repeatedly associated with improved long-term outcomes, although the review’s authors stress that pursuing these numeric thresholds must never come at the cost of procedural safety, for instance by forcing oversized balloons into vessels at risk of rupture.

Patient subgroups add further nuance. In acute coronary syndromes, imaging characterizes the culprit plaque, identifies plaque rupture and erosion, detects residual thrombus, and helps distinguish which lesions truly warrant stenting — particularly valuable when multiple lesions compete for attention. Patients with diabetes mellitus, whose plaques tend to be diffuse and negatively remodeled, and those with chronic kidney disease, who face elevated event rates after PCI, appear to derive particular prognostic benefit from imaging-guided optimization in complex anatomy, as shown in analyses from ULTIMATE and from the JAMA Network Open cohort of Kwon and colleagues. Conversely, in straightforward lesions, the added contrast injections, catheter exchanges, cost, and procedural time may not be justified. Current guidelines reflect this gradient: the 2024 European Society of Cardiology chronic coronary syndrome guidelines give imaging a class IIa recommendation for stent sizing and optimization, while the 2025 American ACC/AHA acute coronary syndrome guideline similarly endorses imaging use in selected settings.

The barriers to wider adoption are less scientific than economic and cultural. Surveys by the European Association of Percutaneous Cardiovascular Interventions and the Japanese association CVIT documented persistent underuse outside East Asia, where imaging guidance in complex PCI has become routine. A white paper by Escané and colleagues catalogued the reasons: reimbursement gaps, longer procedure times, unfamiliarity with image interpretation, and organizational inertia. Health-economic analyses complicate the picture in imaging’s favor — the RENOVATE-COMPLEX-PCI cost-effectiveness analysis suggested that, despite upfront device costs, avoided repeat revascularizations and reduced infarctions can offset expenditures, particularly in complex anatomy where the event-rate reduction is largest.

The review also charts where the field is heading. Hybrid catheters combining IVUS and near-infrared spectroscopy can map lipid-rich, potentially vulnerable plaques, and the PROSPECT II natural-history study showed that such non-culprit lipid-rich plaques predict future events, opening the door to preventive local therapy. Computational advances promise to shrink the learning curve: artificial-intelligence algorithms now perform automated lumen and external elastic membrane contouring, stent-apposition analysis, calcium scoring, and even OCT-derived fractional flow reserve, validated in trials such as FLASH and FUSION. Combining optical flow ratio with post-stent physiology assessment may eventually let one imaging pull-through yield both anatomical and functional verdicts on the result, reducing contrast load and procedure time simultaneously.

For clinicians, the practical message distilled by Biccirè and colleagues can be organized around four questions: why, when, how and which. Why: because imaging converts an educated guess into measurement, and the randomized evidence shows this conversion lowers cardiac death, stent thrombosis and repeat procedures in the right patients. When: preferentially in left main, bifurcation, long, calcified and chronic total occlusion lesions, in acute coronary syndromes with ambiguous culprits, and in patients with diabetes or chronic kidney disease undergoing complex PCI. How: with disciplined pre-implantation sizing, deliberate post-dilatation, and verification against validated optimization thresholds, without compromising safety. Which: either OCT or IVUS produces comparable outcomes in most settings, so the choice can follow availability, operator expertise and specific needs — OCT’s superior resolution for bifurcation morphology and plaque characterization, IVUS’s deeper penetration for sizing large vessels such as the left main. What began as a technology searching for proof now stands, for complex interventions, on one of the firmer evidentiary foundations in interventional cardiology.

Subject of Research: Use of intracoronary imaging to guide percutaneous coronary intervention in randomized clinical trials

Article Title: Intracoronary imaging in percutaneous coronary intervention: why, when, how and which from large, randomized trials

Article References: Biccirè, F. G., Gonzalo, N., Hahn, J.-Y., Jang, I.-K., & Räber, L. (2026). Intracoronary imaging in percutaneous coronary intervention: why, when, how and which from large, randomized trials. Nature Reviews Cardiology. https://doi.org/10.1038/s41569-026-01342-3

Image Credits: AI Generated

DOI: 10.1038/s41569-026-01342-3

Keywords: intracoronary imaging, percutaneous coronary intervention, optical coherence tomography, intravascular ultrasound, stent optimization, randomized trials, bifurcation lesions, acute coronary syndrome, stent thrombosis, left main PCI, coronary artery disease, interventional cardiology