NEW ORLEANS — Intravascular ultrasound (IVUS) is already guideline recommended for complex percutaneous coronary interventions (PCIs), so when IVUS failed to outperform angiography in two new randomized trials, the surprise triggered discussion about how the results should be interpreted.

One of the randomized trials, called OPTIMAL, showed no significant benefits for IVUS over angiography for guiding PCI in repair of left main stenosis. The other, IVUS-CHIP, was a larger trial enrolling patients with a broader range of complex lesions, and it also gave no advantage to IVUS-guided PCI on the key endpoints.

Both were presented during a late breaking clinical trial session at the American College of Cardiology (ACC) Scientific Session 2026 and published simultaneously in The New England Journal of Medicine.

Sending the Wrong Message?

Experts invited to discuss the trials at ACC worried the results will send the wrong message. In his interpretation of OPTIMAL, Juan F. Granada, MD, president and CEO of the Cardiovascular Research Foundation in New York City, expressed an opinion that could be applied to either trial.

“The data goes against what we propose is best clinical practice,” Granada said. He emphasized that the study and its results are important, but he hastened to add that the design was “very unique” and might not be broadly applicable because the procedures were performed at high-volume centers with very experienced operators.

For those with significant IVUS experience, the ability to achieve comparable results with either imaging guidance “is one thing, but the generalization to operators in a regular-volume center is another,” he said.

Both trials, conducted in Europe, hypothesized that IVUS would be superior to angiography in guiding PCI. A substantial body of data predicted an advantage for IVUS-guided PCI in both left main disease and unselected complex lesions, according to the lead investigators. However, the trials yielded opposite results.

In OPTIMAL, 806 patients with left main disease scheduled for PCI were randomly assigned to either IVUS-guided or angiography-guided PCI. The primary outcome was a composite endpoint of myocardial infarction, stroke, revascularization, or death from any cause.

After a median of 2.9 years of follow-up, the primary endpoint occurred in 33.7% of those who had undergone IVUS-guided PCI and 30.9% of those who had undergone angiography-guided PCI. The slightly higher hazard ratio (HR) for an adverse outcome in the IVUS-guided PCI arm was not statistically significant (HR, 1.11; P = .40).

There were no significant between-group differences in the secondary endpoints, which included the individual components of the primary endpoint along with stent thrombosis, procedure- vs non-procedure-related myocardial infarction, and death from a cardiovascular cause.

“The percentages of patients with procedure-related and overall safety events also appeared to be similar in the two groups,” reported the OPTIMAL investigators, led by Luca Testa, MD, PhD, head of the Coronary Revascularization Unit at IRCCS Policlinico San Donato in Milan, Italy.

Results Relevant Only to Experienced Operators

Testa readily conceded that although IVUS did not reduce risk for events, the conclusion should be restricted to procedures performed by expert IVUS operators. He further agreed with Granada that IVUS leads to PCI skills that can be applied when using angiography.

“Obviously, it is related to years and years of experience to reach a certain level of confidence,” Testa said. Further echoing Granada’s interpretation, he added that he considers expertise with IVUS is essential for these results to be replicated. Otherwise, the OPTIMAL trial is not applicable, he said.

In an accompanying NEJM editorial by Frederick Welt, MD, director of the Cardiac Catheterization Laboratory at the University of Utah Health Sciences Center in Salt Lake City, this same point was echoed.

Based on the low rate at which IVUS data influenced procedural changes in OPTIMAL (29.3%), he speculated that results are likely explained by IVUS training leading to better outcomes when performing angiography-guided PCI.

In his editorial, he expressed doubt that OPTIMAL results will lead to substantial practice change for handling left main disease given prior evidence that IVUS guidance improves outcomes, a conclusion most relevant to inexperienced interventionalists.

In IVUS-CHIP, 2020 patients with complex coronary artery lesions were also randomized to IVUS-guided or angiography-guided PCI. Complex lesions were defined as ostial, at bifurcations involving side branches > 2.5 mm. They involved the left main artery, characterized by chronic total occlusion or in-stent restenosis or being of long length (stent > 28 mm) or heavily calcified.

The primary target vessel failure outcome was a composite target vessel myocardial infarction, clinically indicated target vessel revascularization, and cardiac death.

Unfavorable Trend With IVUS Guidance

After a median 19 months of follow-up, the primary endpoint had occurred in 13.9% of those in the IVUS-guided PCI group and 11.1% of the angiography-guided PCI group, producing a trend for a worse outcome in the IVUS-guided PCI group (HR, 1.25; P = .08).

IVUS-guided PCI was also at a disadvantage for each of the primary endpoint components, ranging from 13% for target vessel myocardial infarction (HR, 1.13; 95% CI, 0.80-1.61) to 24% for cardiac death (HR,1.24; 95% CI, 0.75-2.05), although none of these findings reached statistical significance.

The exception was the rate of definite or probable stent thrombosis, which was significantly lower in the IVUS-guided PCI group (HR, 0.33; 95% CI, 0.12-0.90).

According to the authors of IVUS-CHIP, led by Roberto Diletti, MD, PhD, an interventional cardiologist at the Thoraxcenter of Erasmus MC in Rotterdam, Netherlands, the results differ markedly from recent trials and meta-analyses.

For example, the risk of reaching a composite hard endpoint was reduced 36% in the IVUS-guided vs the angiographic-guided PCI arm of the 1623-patient RENOVATE-COMPLEX-PCI trial published in 2023. In a 2024 22-study systematic review, IVUS vs angiographic guidance was associated with a 29% (P < .0001) reduction in risk for a composite target lesion failure endpoint following complex PCI.

Diletti offered several explanations for the discrepancy between IVUS-CHIP and these prior trials. But the high level of experience of all interventionalists participating in IVUS-CHIP was also significant discussion point.

“One criterion for selecting sites in this study was experience with IVUS, so one thing to consider is that these operators have learned a lot with IVUS and they might be applying what they learned in the angiography arm,” Diletti said.

Deepak Bhatt, MD, MPH, who served as a discussant for the trial at ACC, also emphasized that he believes IVUS improves the skills of interventionalists. Previous data have consistently favored IVUS-guided PCI with outcomes that, in one meta-analysis, included a reduction in cardiac mortality, he said.

Bhatt, the director of the Mount Sinai Fuster Heart Hospital in New York City, also focused on the disconnect between a numerical disadvantage for IVUS-guided PCI despite a significant advantage for the outcome of stent thrombosis. Although he acknowledged stent thrombosis was a secondary outcome, he said that improved stent placement would be expected to lead to better outcomes.

IVUS Did Reduce Risk for Stent Underexpansion

Diletti acknowledged that IVUS guidance was associated with a reduced rate of stent underexpansion, which he admitted is a major predictor of stent thrombosis even if this did not translate into an outcome advantage in this trial. Further, he accepted the premise set forth by Bhatt that experience with IVUS improves PCI skills, likely allowing experienced interventionalists to achieve good results with any type of imaging.

“IVUS is very important for us to understand better what we are doing,” Diletti said, noting its potential benefits in PCI training. “I would suggest that it is very important to learn to perform PCI with angiography and IVUS support. IVUS can inform us much more than angiography.”

“Once we are very skilled in PCI, probably we can use IVUS just in a selected proportion of our patients,” he added.

Bhatt was surprised by the results and believes IVUS is “adding value” when performing PCI in complex lesions. He said he does not believe the results of either OPTIMAL or IVUS-CHIP should alter guidelines.

In the 2024 European Society of Cardiology guidelines, IVUS guidance was awarded a class 1A recommendation for complex coronary lesions. The question that IVUS-CHIP raises is whether it is needed in every case, according to Diletti.

This point was taken up in an NEJM editorial that accompanied publication of IVUS-CHIP. Author Adnan Kastrati, MD, a professor of cardiology at the Technical University of Munich in Munich, Germany, wrote that IVUS-CHIP does not fully resolve when and under what circumstances it is safe to forego IVUS-guided imaging in PCI. However, he suggested increased cost might be a reason to opt against IVUS when it is not expected to improve results.

In IVUS-CHIP, “use of IVUS increased the procedural time by 34%,” Kastrati observed. To compensate for the extra time and cost, he called for more attention to the role of IVUS guidance in preparing, not just guiding, PCI to better reap its advantages.

IVUS Advantages Not Yet Fully Realized

“We have yet to fully establish how to leverage the unique information provided by intravascular imaging to guide both the indications for and the execution of PCI in a way that justifies the associated increase in procedural complexity and cost,” Kastrati wrote in his editorial.

Rather than showing superiority, IVUS-guided PCI was associated with numerically higher rates of most adverse outcomes in both OPTIMAL and IVUS-CHIP, and the potential explanations for this were not explored in detail. Given the greater inherent limitations of angiography relative to IVUS, both Testa and Diletti speculated that operators might have exercised greater diligence when performing PCI with angiographic guidance.

In essence, none of those involved in these studies, nor any of the discussants, interpreted the data from these two trials as suggesting that IVUS guidance and angiographic guidance for PCI in complex coronary lesions can be considered interchangeable.

In his comments on the trials, Granada compared IVUS to a car’s seatbelt: Each offers a potential safety advantage, but it is only realized intermittently. Just as there is less opportunity for a seatbelt to demonstrate an advantage over no seatbelt among experienced drivers acting prudently, the advantage of IVUS-guided PCI over angiographic-guided PCI is more difficult to demonstrate when operators are already highly experienced.

“The bottom line is that imaging is extremely valuable in evolving one’s PCI practice, but the incremental benefit of imaging becomes harder to show for great operators,” said Ajay J. Kirtane, MD, director of Columbia interventional cardiovascular care and a professor of medicine at Columbia University Irving Medical Center in New York City.

Kirtane also used the seatbelt analogy to explain the difficulty of showing an advantage for IVUS over angiographic guidance in complex PCI. He told Medscape Medical News that the sample size to show a reduction in events for IVUS guidance among highly skilled operators would be untenable.

“I am not surprised that these individual studies had a hard time proving a safety margin,” said Kirtane, who was not involved in either trial.

Kirtane emphasized the importance of not losing sight of the fact that IVUS and other advanced forms of imaging, such as optical coherence tomography, are diagnostic and not therapeutic. And so the skills learned with these tools, more than the tools themselves, are what drive outcomes.

“If the treatment strategies are similar in both arms as practiced by experienced operators trained to size by imaging, it is very hard to discern an additional benefit” whether they are using imaging or not, Kirtane said.

Recounting his experience moving to a center where imaging was routinely employed after a training where access was limited, the value of this tool became immediately apparent. For example, he realized the need to size stents in larger diameters relative to his practice before his exposure to IVUS. He now uses advanced imaging in “virtually all cases.”

Granada reported having no potential conflicts of interest. Testa reported having financial relationships with Abbott, Boston Scientific, JenaValve, Medtronic, and Meril. Welt reported having no potential conflicts of interest. Diletti reported having financial relationships with Abbott, ACIST Medical Systems, Biotronik, Boston Scientific, and Medtronic. Bhatt reported having financial relationships with more than 40 pharmaceutical and device companies. Kastrati reported having no potential conflicts of interest. Kirtane reported having financial relationships with Abiomed, Boston Scientific, Medtronic, and St. Jude Medical.