To our knowledge, this is the first study evaluating stent expansion criteria specifically in calcified coronary lesions. We assessed multiple stent expansion indices to determine their predictive value for clinical outcomes.

The major findings of this study were: first, achieving an MSA > 100% of the distal reference lumen area was associated with a lower incidence of TLF; second achieving an MSA > 90% of the distal reference lumen area was associated with a lower incidence of TLF and third, meeting the criterion of MSA > 5.0 mm2 or > 90% of the distal reference lumen area was similarly associated with reduced TLF rates.

In this cohort, the optimal cutoff for MSA/distal reference lumen area was determined to be 96.5% (Sensitivity = 80.5%, Specificity = 44.4%) (Supplementary Fig. 2).

According to our results, stent expansion should also be assessed relative to the distal reference lumen area. A small MSA may be acceptable if the distal reference is also small, whereas even adequate MSA (> 5.5 mm2) may be insufficient if it does not reach 100% of the distal reference lumen area. Representative cases for MSA/Distal reference area are shown in Fig. 4.

Representative cases with different patterns of MSA/Distal reference vessel area. (A) Both OCT and IVUS images show a small MSA. However, the distal reference lumen area is also small, resulting in an MSA > 100% of the distal reference lumen area. (B) The MSA is small, but the distal reference lumen area is large, leading to an MSA < 100% of the distal reference lumen area. (C) An adequate MSA but with a larger distal reference lumen area resulting in an MSA < 100% of the distal reference lumen area. IVUS = Intravascular ultrasound; MSA = Minimum stent area; OCT = Optical coherence tomography

Although achieving complete stent expansion is limited by vessel size, the MSA has been widely recognized in numerous studies as the strongest predictor of clinical events. Reported cutoff values for predicting stent failure as assessed by IVUS typically range between 5 and 5.5 mm2 for non-left main lesions while for OCT the optimal cut-off value is 4.5 mm2 [9,10,11, 13, 24].

The median MSA in the current cohort was 6 mm2 (IQR 4.9–7.7 mm2) suggesting that the lack of a significant association between MSA and clinical events can be attributed to appropriate stent expansion.

A sub-study from the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) registry found that relative stent expansion criteria were not predictive of clinical events. Instead, clinical outcomes were best predicted by the ratio of MSA to vessel area at the site of the MSA [18]. In this cohort, acoustic shadowing from coronary calcium hindered the visualization of the region behind the calcium by IVUS, which limited the ability to measure the vessel area at the MSA site to 152 out of 280 lesions (54.3%), thus making this criterion challenging to apply in routine clinical practice. This relatively small sample size may explain the lack of a significant association between MSA/vessel area at the MSA site and TLF.

In previous studies, including the original MUSIC (Multicenter Ultrasound Stenting in Coronaries) study [25] and the SYNTAX II trial [14], which utilized modified MUSIC criteria, optimal stent expansion was based on the MSA. Specifically, this has been measured as a percentage relative to either the average lumen area of the proximal and distal reference segments (ranging from 80 to 90%) or the distal reference lumen area alone (ranging from 90 to 100%).

Criteria like these were also used in the optimization protocol of randomized trials comparing imaging guided (OCT or IVUS) and angiography guided PCI (such as IVUS-XPL, ULTIMATE and ILUMIENIV) [3, 4, 23]. In the IVUS-XPL and ULTIMATE trials, patients who achieved the stent expansion criteria during IVUS guided PCI experienced better clinical outcomes than those who did not.

Moreover, in a pooled data analysis of IVUS-XPL and ULTIMATE, conventional stent expansion was not associated with the three-year clinical outcomes [26] while a pooled analysis with IVUS-XPL and RESET trials reported that conventional stent expansion was a good predictor of clinical outcomes [9, 27].

In line with most previous studies, our study found that conventional stent expansion and MSA of the proximal segment ≥ 90% of proximal reference lumen area and MSA of the distal segment ≥ 90% of distal reference lumen area criteria were not strong predictors of clinical outcomes.

The previously mentioned pooled analysis from the IVUS-XPL and ULTIMATE trials concluded that achieving optimal stent expansion—defined as MSA > 5.5 mm2, MSA > 5.0 mm2, or MSA/distal reference lumen area > 90%—was associated with improved long-term hard clinical outcomes [26]. Another study utilizing post-stent OCT to assess the impact of different stent expansion indices found that an MSA < 5.0 mm2 and an MSA/distal reference lumen area < 90% were independently linked to an increased risk of device-oriented clinical endpoints following the implantation of new-generation DES [16].

However, none of these trials specifically focused on calcified lesions. In our study, meeting MSA > 100% of distal reference lumen area, MSA > 90% of distal reference lumen area or MSA > 5.0 mm2 or > 90% of distal reference lumen area criteria was associated with improved long-term clinical outcomes. Particularly in patients with severe coronary artery calcification, MSA > 100% of distal reference lumen area criterion played a more significant role in predicting outcomes (Fig. 3).

Therefore, in cases of severe calcification where the MSA is smaller than the distal reference lumen area, additional high-pressure post-dilation with a properly sized non-compliant balloon or a super high pressure non-compliant balloon (OPN) should be considered to further modify the calcium and enhance stent expansion. While not formally recommended, intravascular lithotripsy may also be used as a bail-out strategy.

Nevertheless, achieving optimal stent expansion in severely calcified lesions remains challenging and is often not attainable despite adequate lesion preparation. In the PREPARE-CALC trial (Comparison of Strategies to Prepare Severely Calcified Coronary Lesions), mean stent expansion was 73.5 ± 13.3% in the modified balloon group and 73.1 ± 12.2% in the rotational atherectomy group, despite the use of specialized preparation techniques [28]. In the ISAR-CALC trial (Super High-Pressure Balloon versus Scoring Balloon to Prepare Severely Calcified Coronary Lesions), mean stent expansion was 72 ± 12% in the super high-pressure balloon group and 68 ± 13% in the scoring balloon group [29]. Similarly, in our cohort, the median conventional stent expansion for the severely calcified group was 74.1% (IQR 63.6–83.8%), with 63% of lesions failing to reach the > 80% threshold currently recommended by intracoronary imaging consensus documents [30].

Taken together, these findings highlight that the currently recommended expansion cut-offs may be difficult to achieve in this lesion subset and suggest that clinically relevant stent expansion indices in severely calcified lesions warrant further investigation.

Although our study did not find a significant association between some widely used stent expansion indices and clinical outcomes, this does not imply that these metrics are without value. Rather, it suggests that other indices such as MSA relative to the distal reference lumen area may offer additional insights that should be explored in future research. Larger, prospective studies are needed to validate these findings and determine the optimal criteria for stent expansion assessment in calcified coronary artery disease.