SAN FRANCISCO, CA—Among patients with anatomically high-risk chronic total occlusion (CTO) lesions, a two-part staged intervention consisting of an initial modification and a secondary completion procedure may improve procedural success and safety outcomes, according to the INVEST-CTO study.

The “investment” procedure, which resulted in 86.7% procedural success with no in-hospital MACE, starts with a planned modification of the proximal cap, occlusive segment, and distal cap with a noncompliant balloon, with no attempt at reentry or retrograde wiring. Patients return 8 to 12 weeks later for the “completion” CTO PCI.

“The success rate has been too low and complication rates are too high in complex CTOs,” said Anja Øksnes, MD (Haukeland University Hospital, Bergen, Norway), who presented the findings last week at TCT 2025. “As a consequence, operators have been less likely to offer PCI as a therapeutic option. A planned two-stage intervention provides safe and effective treatment in anatomically complex occlusions. Investment should be considered as an initial or early strategy in the treatment of high-risk CTOs.”

Commenting during a press conference, Evelyn Regar, MD, PhD (LMU Klinikum, Munich, Germany), agreed procedural success can be optimized for CTO PCI, and that the investment strategy “opens the field and the accessibility for the patients.” Many PCI operators with limited CTO experience “would feel comfortable doing that, and in case you need the second procedure, you then can bring the patients to specialized CTO operators,” she said. As a bonus, this method might even lower “the burden on the specialized CTO operators.”

Øksnes added: “This is going to be a really good stepping stone for people to increase their experience and take on patients.”

Also during the press conference, Subhash Banerjee, MD (Baylor Scott & White Health, Dallas, TX), cautioned against interpreting the data in this manner, as INVEST-CTO did not assess the experience level of the operators who took part. Rather, he said, “I think it should be interpreted as an expert CTO operator doing a predetermined first stage in highly complex CTOs and where they are invested in the investment procedure so they can come back and complete the initial investment.”

Noninferiority Met

For INVEST-CTO, researchers enrolled 153 patients (mean age 66 years; 85% male) with high-risk anatomy to undergo a two-step investment procedure at one of five study sites in the United Kingdom, United States, and Norway. The median J-CTO score was 4, and most patients (92.8%) presented with stable CAD. Just over half of patients (55.6%) had had prior PCI, and 26.8% had prior CABG.

Two-thirds of lesions were in the right coronary artery, and moderate or severe angiographic calcium was present in 88.2%. CTO length was greater than 20 mm in 81.7% of patients, and 80.4% had an ambiguous proximal cap. Tortuosity was greater than 45 degrees in 77%, and 61.4% of patients did not have collaterals that could be used for retrograde access.

Most patients (89.6%) received only radial access for the investment procedure, in which the median doses of radiation and contrast used were 550 mGy and 100 mL, respectively. These procedures lasted a median of 61 minutes.

Among the 131 patients who returned for the completion procedure, the median duration was 124 minutes and 74.1% received only radial access. Antegrade wiring was most often used as the final crossing strategy (65%) and retrograde was used in 30%.

The high rate of procedural success drove the study to meet its noninferiority endpoint for investment compared with an estimated 75% procedural success rate in similar populations. Additionally, procedural success after the second attempt remained high at 93.4%. The composite safety endpoint rate at 30 days was 4.6%.

Angina, as defined by the Canadian Cardiovascular Society scale, went down with the intervention. At baseline, 85% of patients scored 2 or higher, with that proportion declining to 62.6% after the first procedure and 19.9% after completion.

Several Limitations

Øksnes acknowledged several limitations of the study, including its single-arm design, the use of an estimated comparator based on registry and RCT data, and differing levels of operator experience. Still, she told TCTMD, investment is now a part of her practice, and it has “been for a while. I know that it’s already starting to be adopted by the community in some of these patients.”

Lingering questions over increased radiation and contrast with two staged procedures should hopefully be put to rest with these new data, Øksnes added.

Lead discussant Ashish Pershad, MD (Chandler Regional Medical Center, AZ), said in the late-breaking session that the lack of a sham arm and the high screen fail rate in the study create bias. He likened the investment procedure to a “measure twice, cut once” approach that led to good procedural success and “impressive” safety.

“However, I don’t think I’m convinced that these results can all be attributed to the investment versus the advanced skill set of the operators involved,” Pershad said. In the future, he would like to see a CTO PCI trial comparing the deferred investment strategy to a single procedure.