Researchers led by Annemieke C. Ziedses des Plantes and Joost Daemen of Erasmus University Medical Center in Rotterdam screened 1,945 studies to find trials and cohort studies in which patients received a drug-eluting stent, then had FFR measured both before and after a deliberate optimization procedure — either inflating a balloon inside the existing stent, known as post-dilatation, or implanting an additional stent. Eleven studies met the criteria, and usable patient-level data were obtained from eight of them, yielding 314 patients in whom the complete before-and-after physiological picture could be reconstructed and analyzed with mixed-effects regression models that account for differences between studies.

The headline result is that optimization works, at least physiologically. Median FFR rose from 0.81 to 0.86, a statistically significant improvement, with the magnitude of the gain depending heavily on which technique was used. Post-dilatation alone added an average of 0.03 FFR points, while placing an additional stent produced an average increase of 0.08 points. The proportion of patients left with an ischemic FFR value of 0.80 or below dropped from 49 percent to 21 percent after the optimization procedure — a meaningful shift in a measurement where each hundredth of a point reflects improved perfusion across the treated segment.

Yet the number of patients who actually reached the conventional optimum of FFR at or above 0.90 was just 23.2 percent. In other words, fewer than one in four patients with a suboptimal result could be pushed into the ideal physiological range, even with a second intervention inside the vessel. This is a crucial nuance for a field that has been moving toward routine physiological verification of stent results: the tools available to correct a lingering pressure drop are limited, and the residual disease that produces a low post-stent FFR is often not something a balloon inflation can easily eliminate.

The multivariable analysis revealed which patients stood to gain the most. When the initial post-PCI FFR was low, adding a stent yielded substantially larger improvements than post-dilatation, but this advantage steadily shrank as the starting FFR rose — a statistical interaction that makes physiological sense, since a very low FFR usually signals residual disease beyond the stent edges or incomplete coverage of the lesion, problems that additional stenting directly addresses. Conversely, when the pressure wire shows an FFR close to 0.90 already, there is little residual obstruction left for another stent to relieve.

Location mattered as well. Lesions in the left anterior descending artery, the vessel that supplies the largest mass of heart muscle, showed smaller absolute FFR gains after optimization than lesions elsewhere, even after adjusting for the starting FFR value. The authors attribute this to the larger subtended myocardium and hydrostatic pressure effects along the long LAD, which depress FFR readings for reasons that no stent can correct. The finding supports a growing argument in the interventional cardiology literature that post-procedure FFR thresholds may need to be vessel-specific rather than uniform across the coronary tree.

Perhaps the most consequential negative result concerns clinical outcomes. With follow-up data available for 267 patients over a median of three years, the composite of target vessel revascularization or target vessel myocardial infarction occurred in about 11.7 percent of patients. Neither the final FFR achieved nor the size of the FFR improvement predicted who had events. Patients whose final FFR was at or above the median of 0.85 fared no better numerically than those below it — 8.9 percent versus 15.8 percent cumulative incidence, a difference that did not reach statistical significance — and the same held true when comparing large and small FFR gains.

The authors caution that this analysis was likely underpowered rather than proof that physiology-driven optimization is clinically useless. The patient group was selected precisely because of suboptimal starting values, creating a comparatively high-risk cohort in which the most dangerous anatomical problems may already have been corrected during the optimization itself. Only a minority of patients had FFR pullback data or intracoronary imaging available, preventing the researchers from mapping exactly where residual disease lurked. And the included studies used wildly different optimization protocols and FFR cut-offs, introducing heterogeneity that random-effects modeling can dampen but not eliminate.

Context from the broader literature sharpens the interpretation. Previous work has established that suboptimal post-stent FFR values appear in roughly 30 to 70 percent of angiographically successful procedures, and that they carry prognostic weight. The FFR REACT trial showed that guiding optimization with intravascular ultrasound in patients with post-PCI FFR below 0.90 reduced target vessel revascularization over three years, with a trend toward fewer target vessel failures. But this new meta-analysis found no advantage for imaging-guided protocols over operator discretion once the starting FFR was accounted for — a result the authors suggest may partly reflect the fact that imaging-guided procedures catch subtle problems earlier, leaving less room for improvement by the time a low FFR triggers optimization.

Two ongoing randomized trials, DEFINE GPS and INSIGHTFUL-FFR, are expected to clarify whether physiology-guided stent optimization can translate into fewer heart attacks and repeat procedures. Until those results arrive, this meta-analysis offers interventional cardiologists a practical algorithm: if the post-stent FFR is markedly low, especially outside the LAD and particularly when residual disease is suspected, additional stenting offers the best chance of physiological rescue; if the value hovers just below 0.90, the achievable gain is modest and the clinical payoff unproven. The pressure wire, it turns out, is excellent at telling operators when something is wrong — but far less reliable at predicting whether fixing it will change the patient’s story.

Subject of Research: Effectiveness of fractional flow reserve-guided optimization after coronary stenting

Article Title: Effectiveness and clinical impact of functional post-PCI optimization—a systematic review and individual patient-data meta-analysis

Article References: Ziedses des Plantes, A. C., Neleman, T., Hakeem, A., Uretsky, B. F., Agarwal, S. K., Miller, K., Collison, D., Oldroyd, K., Wijns, W., Leone, A. M., Burzotta, F., Trani, C., Galante, D., Leesar, M. A., Hoeks, S. E., Van Mieghem, N. M., & Daemen, J. (2026). Effectiveness and clinical impact of functional post-PCI optimization—a systematic review and individual patient-data meta-analysis. Clinical Research in Cardiology. https://doi.org/10.1007/s00392-026-03009-y

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03009-y

Keywords: fractional flow reserve, PCI optimization, percutaneous coronary intervention, drug-eluting stent, meta-analysis, cardiology, intravascular ultrasound, post-dilatation, LAD artery, target vessel revascularization, FFR-REACT, coronary physiology

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