Key Points
Question
Is optical coherence tomography (OCT) imaging superior to angiography when guiding percutaneous coronary intervention (PCI) procedures in calcified coronary lesions?
Findings
In this randomized clinical trial, an OCT-based strategy (including lesion analysis and standardized plaque preparation according to predefined algorithms) resulted in better stent implantation results (stent expansion and apposition) than angiography guidance, without any additional safety concern.
Meaning
Considering the high incidence of calcified stenoses among patients with stable coronary artery disease and the poorer prognosis of PCI in this situation, use of this OCT-based strategy could improve the clinical outcome of these patients by improving the quality of stent implantation.
Abstract
Importance
The use of intravascular imaging for calcified plaque characterization and preparation has been advocated over conventional methods to improve percutaneous coronary intervention (PCI) outcomes, but this approach has never been evaluated.
Objective
To determine if optical coherence tomography (OCT) is superior to angiography for calcified lesions PCI guidance.
Design, Setting, and Participants
The CALIPSO (Calcified Lesion Intervention Planning Steered by OCT) trial was a prospective, multicenter, open-label, randomized clinical trial that included patients with stable moderate to severe calcified coronary lesions on coronary angiography scheduled for PCI. The trial was conducted at 12 sites in France between December 2021 and June 2023, and data were analyzed from December 2023 to April 2024.
Intervention
After diagnostic coronary angiography, eligible patients were randomly assigned in a 1:1 ratio to receive OCT-guided PCI or angiography-guided PCI. In the OCT group, the procedures were guided by OCT analysis and predefined standardized management algorithms. Patients from both arms had control post-PCI OCT analysis after procedure completion for primary end point measurement.
Main Outcomes and Measures
The primary end point was the minimal stent area (MSA) measured by OCT in both groups. Secondary key safety end points included periprocedural myocardial infarction, radiation dose, contrast medium volume, and procedure duration.
Results
A total of 143 patients were randomized, and 134 were included in the final analysis (65 in the OCT group and 69 in the angiography group). Median (IQR) patient age was 73.0 (66.0-78.0) years, and 25 patients (18.7%) were female. The baseline characteristics of the groups were comparable, but the use of intravascular lithotripsy was more frequent in the OCT arm (30 patients [46%] vs 8 patients [12%]; P < .001). The final median (IQR) MSA was larger in the OCT group than in the angiography group (6.5 [5.5-8.1] mm2 vs 5.0 [4.1-6.1] mm2; P < .001). There was no difference in periprocedural complications incidence, contrast medium volume, or procedure duration between groups.
Conclusions and Relevance
The CALIPSO randomized clinical trial showed that OCT guidance associated with predefined algorithmic management achieved better stent implantation results than angiography guidance in patients with calcified lesions PCI, without any additional safety concern.
Trial Registration
ClinicalTrials.gov Identifier: NCT05301218
This randomized clinical trial determines if optical coherence tomography (OCT) is superior to angiography for calcified lesions percutaneous coronary intervention guidance.
Introduction
The management of calcified coronary lesions represents a daily challenge for interventional cardiologists.1 The prevalence of calcified lesions is estimated at roughly 40% of all coronary lesions by angiography.1,2 However, intracoronary imaging analyses report that calcium deposits might be identified in 76% to 83% of lesions.2,3 Calcified lesions are associated with increased periprocedural complications (eg, coronary perforations, acute stent thrombosis, and stent underexpansion) and poorer clinical outcomes (eg, stent failure and need for repeat revascularization).4,5
Although several devices, such as rotational atherectomy (RA), intravascular lithotripsy (IVL), or scoring balloons, have been proposed to prepare calcified lesions before stent implantation, the optimal indications of these tools remain debated. The recent European Association of Percutaneous Cardiovascular Interventions (EAPCI) and Society for Cardiovascular Angiography & Interventions (SCAI) consensus papers highlight the need for lesion preparation before stent implantation to improve short- and long-term clinical results1,6 and advocate the use of intravascular imaging to guide percutaneous cardiovascular intervention (PCI) strategies according to predefined algorithms.1,6,7,8 Optical coherence tomography (OCT) is a valuable option for this task because of its excellent spatial resolution and ability to measure calcification thickness.9 Furthermore, OCT allows an accurate assessment of post-PCI results, including the minimal stent area (MSA), which predicts future adverse clinical events.10,11 However, OCT guidance was never evaluated comparatively to conventional angiography guidance when it comes to management of calcified lesions PCI, and clinical data remain scarce. The CALIPSO (Calcified Lesion Intervention Planning Steered by OCT) randomized clinical trial aimed to compare both approaches. We hypothesized that a PCI strategy based on OCT guidance and standardized algorithms for lesion preparation, stent sizing, and procedure optimization could provide a larger final MSA than a classical angiography-based strategy, without impacting the safety of the patient.
Methods
Study Design and Population
The CALIPSO trial was a prospective, multicenter, superiority randomized clinical trial that compared OCT-based and angiography-based PCI strategies for calcified lesions management. The study was sponsored by Fonds Montsouris and was supported by an investigator-initiated grant from Abbott. This study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines. Patients were eligible for inclusion if they met the following criteria: (1) patient with chronic coronary syndrome; (2) angiographically moderately to severely calcified target lesion (type B or C by Mintz classification2,12); and (3) anticipated possibility to cross the target lesion with OCT catheter.
Exclusion criteria were cardiogenic shock, acute coronary syndrome related to target lesion, severe kidney failure (creatinine clearance <29.94 mL/min/1.73 m2 [to convert creatinine clearance from mL/min/1.73 m2 to mL/s/m2, multiply by 0.0167]), impossibility to cross target lesion with OCT catheter and balloons requiring RA as first line therapy, ostial left main artery lesion, pregnancy, age younger than 18 years, and denial of consent.
Patient characteristics, including medical history and clinical and biological parameters, were prospectively collected on a predefined standardized electronic case report form. The study was conducted in accordance with the principles of the Declaration of Helsinki. All patients received appropriate information and provided written informed consent prior to inclusion. The study protocol was approved by the CHU Tours ethics committee and is available in Supplement 1. The CALIPSO trial was registered on the ClinicalTrials.gov database (NCT05301218).
Protocol Overview and PCI Planning
The global overview of the trial design is provided in Figure 1A. Patients included in the study were randomized after the initial coronary angiography between the OCT guidance group (OCT group) and the control group (angiography [angio] group) in a 1:1 ratio with a secure web-based system.
Figure 1. Design and Calcium Preparation Algorithm of the CALIPSO Trial.
A, Global design of the trial. B, The CALIPSO optical coherence tomography (OCT)-based algorithm is based on the maximal calcium arc extension for choice of the plaque preparation modality. F indicates balloon expansion failure; IVL, intravascular lithotripsy; max, maximum; MSA, minimal stent area; NC, noncompliant; OPN, high-pressure noncompliant balloon; PCI, percutaneous coronary intervention; S, balloon expansion success.
Angiography-Guided Group
Lesion preparation, stent sizing, and postimplantation optimization were performed at the discretion of the operator. Procedural success was defined as combination of residual stenosis less than 30% of reference proximal diameter and Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the target vessel. When best of care angiographic results were obtained, a qualifying OCT run was acquired for primary end point assessment (MSA). When operators felt that the OCT result was unsatisfactory (significant underexpansion, malapposition, or dissection), further correction was performed (this step was specifically requested by the ethics committee), followed or not by subsequent imaging at the discretion of the physician. In the latter case, the final MSA was not used for primary end point assessment.13
OCT-Guided Group
Predilation with 1.5- to 2.0-mm balloon was accepted to facilitate OCT catheter delivery through the target lesion. An initial OCT run was acquired, and the plaque preparation was guided by a predefined algorithm (Figure 1B).
A dedicated lesion preparation was decided in case of calcium OCT scores of 2 or higher.14 The lesion preparation strategy could use RA, IVL, or noncompliant balloons as the first-line strategy. The efficiency of preparation was assessed by noncompliant balloon expansion analysis on 2 orthogonal angiography views. Inadequate preparation was defined as a persistent imprint and/or suboptimal balloon expansion (>30% residual stenosis on expanded balloon; Figure 1B). Plaque preparation analysis by OCT was performed at the discretion of the operators.
The stent sizing (diameter and length) was defined according to the ILUMIEN IV trial methodology (eTable 1 in Supplement 2).15
Post-PCI results were assessed by control OCT, and potential optimization steps were proposed according to predefined success criteria in terms of stent expansion, struts apposition, and presence of dissection based on the EAPCI consensus document.16 In case of underexpansion (defined as MSA <4.5 mm2), the ILUMIEN IV postdilation strategy was used, and a control OCT run was acquired.17 Procedural success was defined as combination of residual stenosis less than 30% of reference proximal diameter, TIMI grade 3 flow in the target vessel, MSA greater than 4.5 mm2, and absence of major dissection.16 The OCT run performed at the end of the procedure was the qualifying run used for primary end point measurement. An example of an OCT-guided procedure is displayed in eFigures 1 and 2 in Supplement 2.
In both groups, the use of a second-line plaque modification device was possible before stent implantation but was identified as a bailout strategy.
OCT Acquisition and Analysis
Extensive description of the methods used for OCT data acquisition and analysis are provided in the eMethods in Supplement 2. Struts apposition and edge dissections were analyzed according to the latest EAPCI consensus document.16 The stent area was measured along the stent on the target lesion to identify the MSA and mean stent area. Stent expansion was assessed by the crude MSA (mm2) or geometrical expansion (percentage) according to the DOCTORS criteria (for nonleft main artery lesions) and LEMON criteria (for lesions involving the left main bifurcation).18,19 The stent eccentricity was defined as the ratio between maximal and minimal diameter.
Coronary Angiography Data
Extensive description of the methods used for coronary angiography analysis are provided in the eMethods in Supplement 2.
Clinical Follow-Up and End Points
Patients were prospectively followed up by clinic visits and/or through telephone contact at 1 and 12 months after hospital discharge following initial PCI treatment.
The primary end point of the CALIPSO trial was the MSA on the qualifying OCT run. Secondary efficacy end points included successful geometrical stent expansion according to the DOCTORS or LEMON criteria, residual major struts malapposition (incidence, maximal malapposition distance, and length of malapposed stent), stent eccentricity (maximal and average), and residual post-PCI stenosis on angiography.
Secondary safety end points included periprocedural myocardial infarction (MI) according to the SCAI definition,20 coronary artery perforation (according to Ellis classification21), radiation dose, contrast medium volume, procedure duration, and major adverse clinical events (MACE, composite of cardiovascular death, any myocardial infarction, or need for clinically driven reintervention on the target lesion) incidence at 30 days and 1 year.
The present article presents the primary end point, secondary imaging and safety end points, and 30 days’ clinical follow-up.
Statistical Analysis
Sample size calculation data are provided in the eMethods in Supplement 2. The primary analyses were performed in all randomly allocated participants who had primary outcome data. Statistical analyses were performed with SPSS version 28.0 software (IBM). Qualitative data are expressed in percentages, and continuous data are medians with interquartile ranges. Continuous variables’ normal distribution was tested by the Kolmogorov-Smirnov test. The differences between the variables were compared by the χ2 or Fischer test for qualitative variables and the Welch, Mann-Whitney U, or paired t test for continuous variables. The relationships between baseline or procedural characteristics and presence of significant stent underexpansion in the trial population were studied using a binary logistic regression analysis, including in the initial model all variables associated with target vessel failure with P < .10 in the univariable analysis. All tests were 2-sided, and P < .05 was considered statistically significant.
Results
Baseline Characteristics
The study workflow chart is shown in eFigure 3 in Supplement 2. From December 2021 to June 2023, 161 patients were screened for inclusion, and 143 were included and randomized in 12 French centers. Finally, 134 patients were included in the primary end point analysis (OCT group: 65 patients; angio group: 69 patients). There was no crossover between groups. The population baseline characteristics are given in Table 1. Median (IQR) patient age was 73 (66-78) years, and 25 patients (18.7%) were female.
Table 1. Clinical and Angiographic Baseline Characteristics.
| Characteristic | No. (%) | ||
|---|---|---|---|
| Overall (N = 134) | OCT guidance group (n = 65) | Angio guidance group (n = 69) | |
| Age, median (IQR), y | 73.0 (66.0-78.0) | 72.0 (65.0-76.5) | 74 (68.5-79.0) |
| Sex | |||
| Female | 25 (19) | 13 (20) | 12 (17) |
| Male | 109 (81) | 52 (80) | 57 (83) |
| Cardiovascular risk factors | |||
| HBP | 89 (66) | 46 (71) | 43 (62) |
| Active smoking | 18 (13) | 8 (12) | 10 (15) |
| Dyslipidemia | 117 (87) | 56 (86) | 61 (88) |
| Diabetes | 51 (38) | 24 (37) | 27 (39) |
| Body mass index, median (IQR)a | 26.6 (24.3-29.1) | 26.8 (24.6-28.9) | 26.0 (24.0-29.1) |
| Previous PCI | 43 (32) | 18 (28) | 25 (37) |
| Previous CABG | 2 (1) | 2 (2) | 0 |
| Significant AV stenosis | 9 (7) | 4 (6) | 5 (7) |
| Previous valvular surgery | 3 (2) | 1 (2) | 2 (3) |
| Kidney failureb | 6 (5) | 4 (6) | 2 (3) |
| Peripheral arterial disease | 21 (16) | 10 (15) | 11 (16) |
| LVEF, median (IQR), % | 60 (50-65) | 60 (50-65) | 60 (50-64) |
| Culprit vessel | |||
| Distal left main artery | 9 (7) | 4 (6) | 5 (7) |
| Left anterior descending | 92 (69) | 47 (72) | 45 (65) |
| Circumflex | 5 (4) | 2 (3) | 3 (4) |
| Right coronary artery | 28 (21) | 12 (19) | 16 (23) |
| QCA analysis | |||
| Lesion length, median (IQR), mm | 35.0 (25.0-43.0) | 35.0 (25.0-44.0) | 35.0 (24.0-43.0) |
| Reference vessel diameter, median (IQR), mm | 2.9 (2.6-3.2) | 2.9 (2.5-3.3) | 3.0 (2.7-3.3) |
| Pre-PCI stenosis, median (IQR), % | 61 (48-72) | 60 (47-74) | 61 (50-72) |
| Moderate calcification | 59 (44) | 29 (45) | 30 (44) |
| Severe calcification | 75 (56) | 36 (55) | 39 (56) |
Abbreviations: angio, angiography; AV, aortic valve; CABG, coronary artery bypass graft; HBP, high blood pressure, LVEF, left ventricular ejection fraction; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; QCA, quantitative coronary angiography.
SI conversion factor: To convert creatinine clearance from mL/min/1.73 m2 to mL/s/m2, multiply by 0.0167.
Calculated as weight in kilograms divided by height in meters squared.
Patients with kidney failure are defined by creatinine clearance ranging from 29.94 to 59.88 mL/min/1.73 m2.
Procedural Characteristics
The procedural features are displayed in Table 2. The plaque preparation modalities differed significantly between the 2 groups. Lesion predilation with noncompliant balloon was the most frequent first-line option in the angio group (42 of 69 patients [61%] vs 23 of 65 patients [35%]; P = .003). In the OCT group, IVL or RA were used as first-line strategy in 63% of cases, with a most-liked selection of IVL (30 patients [46%] vs 8 patients [12%] in the angio group; P < .001). In addition, a bailout strategy was applied more frequently in the angio group compared to the OCT group (14 patients [20%] vs 4 patients [6%]; P = .02). The different strategies used in the OCT arm are provided in eFigure 4 in Supplement 2.
Table 2. Procedural Characteristics.
| Characteristic | No. (%) | P value | ||
|---|---|---|---|---|
| Overall (N = 134) | OCT guidance group (n = 65) | Angio guidance group (n = 69) | ||
| Up-front lesion preparation device | ||||
| NC balloon | 68 (51) | 23 (35) | 42 (61) | .006 |
| High-pressure NC balloon | 1 (1) | 0 | 1 (1) | >.99 |
| Rotational atherectomy | 28 (21) | 12 (19) | 18 (26) | .29 |
| Intravascular lithotripsy | 38 (28) | 30 (46) | 8 (12) | <.001 |
| Bailout strategy | 18 (13) | 4 (6) | 14 (20) | .02 |
| Scoring balloon | 0 | 0 | 0 | >.99 |
| Rotational atherectomy | 3 (2) | 1 (1) | 2 (3) | .62 |
| Intravascular lithotripsy | 15 (11) | 3 (5) | 12 (17) | .03 |
| High-pressure NC balloon | 0 | 0 | 0 | >.99 |
| Stent, median (IQR) | ||||
| Stent No. | 1.0 (1.0-2.0) | 1.0 (1.0-2.0) | 1.0 (1.0-2.0) | .31 |
| Stent length, mm | 40 (28-51) | 40 (27-51) | 40 (28-56) | .74 |
| Maximal stent diameter, mm | 3.5 (3.0-3.5) | 3.5 (3.0-3.5) | 3.0 (3.0-3.5) | .20 |
| Postdilation, median (IQR) | ||||
| NC balloons, No. | 1 (1-2) | 1 (1-2) | 1 (1-2) | .66 |
| NC balloon maximal diameter, mm | 3.5 (3.5-4.0) | 3.5 (3.5-4.0) | 3.5 (3.5-4.0) | .46 |
| NC balloon length, mm | 15 (12-20) | 15 (12-20) | 15 (10-16) | .34 |
| Maximal pressure, atm | 16 (14-20) | 16 (14-18) | 18 (16-20) | .02 |
| Complications | ||||
| Significant dissection | 6 (4) | 2 (3) | 4 (6) | .68 |
| Coronary perforation (all) | 1 (1) | 1 (1) | 0 | .48 |
| Ellis class I perforation | 1 (1) | 1 (1) | 0 | .48 |
| Ellis class II perforation | 0 | 0 | 0 | >.99 |
| Ellis class III/III-CS perforation | 0 | 0 | 0 | >.99 |
| Procedure duration, median (IQR), min | 64 (48-84) | 63 (51-87) | 64 (46-82) | .22 |
| Fluoroscopy duration, median (IQR), min | 17 (11-24) | 17 (11-21) | 17 (12-27) | .95 |
| Total radiation dose, median (IQR), cGy/cm2 | 4219 (2635-7270) | 4148 (2550-7155) | 4403 (2630-7333) | .65 |
| Contrast medium volume, median (IQR), mL | 182 (145-223) | 180 (140-233) | 184 (150-219) | .88 |
Abbreviations: angio, angiography; CS, cavity spilling; NC, noncompliant; OCT, optical coherence tomography.
The number of stents, total stent length, and maximal stent diameter did not significantly differ between groups. There was no difference in the final median (IQR) stenosis degree analyzed by quantitative coronary angiography (QCA) (OCT: 12% [6%-18%] vs angio: 12% [4%-22%]; P = .44). Interestingly, we did not observe significant differences between groups regarding procedure and fluoroscopy duration, radiation dose, contrast medium volume, or complications, yet a trend toward a higher incidence of major dissections (identified by OCT) was observed in the angio guidance group (Table 2 and Table 3).
Table 3. Optical Coherence Tomography (OCT) Baseline Characteristics and Results.
| Measure | Median (IQR) | P value | |
|---|---|---|---|
| OCT guidance group (n = 65) | Angio guidance group (n = 69) | ||
| Pre-PCI analysis | |||
| Lesion length, mm | 30.0 (22.0-38.0) | NA | NA |
| Maximal continuous calcium radial extent, degrees | 360 (270-360) | NA | NA |
| Mean calcium radial extent, degrees/mm | 168 (133-220) | NA | NA |
| Max calcium radial extent, No. (%), degrees | |||
| <180 | 13 (20) | NA | NA |
| 180-270 | 11 (17) | NA | NA |
| >270-360 | 41 (63) | NA | NA |
| 360 | 37 (57) | NA | NA |
| Maximal calcium thickness, μm | 1300 (1100-1495) | NA | NA |
| Lumen area at the site of max calcification, mm2 | 3.4 (2.3-4.6) | NA | NA |
| Minimal calcium thickness, μm | 410 (320-520) | NA | NA |
| Calcium length, mm | 20.0 (14.0-28.0) | NA | NA |
| Calcium volume index | 4 (4-4) | NA | NA |
| Minimal lumen area, mm2 | 2.0 (1.3-3.1) | NA | NA |
| Area stenosis, % | 72 (65-84) | NA | NA |
| Calcium radial extent at the site of MLA, degrees | 180 (145-300) | NA | NA |
| Calcium thickness at the site of MLA, μm | 915 (623-1103) | NA | NA |
| Mean lumen area, mm2 | 4.9 (3.8-6.4) | NA | NA |
| Mixed plaque (calcium + lipid), No. (%) | 51 (79) | NA | NA |
| Calcified nodule, No. (%) | 17 (27) | NA | NA |
| Final post-PCI analysis | |||
| Stent length, mm | 33.0 (24.0-48.0) | 38.0 (25.0-48.0) | .35 |
| Minimal stent area, mm2 | 6.5 (5.5-8.1) | 5.0 (4.1-6.1) | <.001 |
| Minimal stent area ≤4.5 mm2, No. (%) | 5 (8) | 25 (36) | <.001 |
| Mean stent area, mm2 | 8.4 (7.0-10.3) | 7.4 (6.4-8.6) | .01 |
| Proximal reference area, mm2 | 8.8 (7.5-12.1) | 9.3 (7.2-11.7) | .84 |
| Distal reference area, mm2 | 6.3 (5.1-7.5) | 5.5 (4.3-6.9) | .06 |
| Geometrical expansion, % | 86.6 (75.2-95.0) | 69.9 (59.1-77.6) | <.001 |
| Successful geometrical expansion, No. (%) | 49 (75) | 20 (31) | <.001 |
| Successful expansion via LEMON criteria, patient No./total No. (%) | 10/12 (83) | 4/12 (33) | .02 |
| Successful expansion via DOCTORS criteria, patient No./total No. (%) | 39/53 (74) | 16/57 (28) | <.001 |
| Stent area at the site of max calcification, mm2 | 8.5 (7.1-9.7) | NA | |
| Major malapposition, No. (%) | 23 (35) | 34 (49) | .10 |
| Malapposition max distance, μm | 535 (352-700) | 570 (330-790) | .13 |
| Mean malapposition distance, μm | 327 (248-429) | 354 (254-506) | .28 |
| Major malapposition length, mm | 0 (0-2) | 0 (0-4) | .03 |
| Malapposed stent percentage, % | 0 (0-8.3) | 0 (0-14.5) | .02 |
| Mean stent eccentricity | 1.21 (1.16-1.25) | 1.19 (1.17-1.24) | .87 |
| Max stent eccentricity | 1.43 (1.35-1.55) | 1.51 (1.36-1.60) | .47 |
| Major dissection, No. (%) | 7 (11) | 13 (19) | .19 |
| Minor dissection, No. (%) | 9 (14) | 15 (22) | .23 |
Abbreviations: angio, angiography; max, maximal; MLA, minimal lumen area; NA, not available; PCI, percutaneous coronary intervention.
OCT Results and Impact on Procedure Flow
The procedural success rates were 81.5% and 91.3% in the OCT and angio groups, respectively, according to the prespecified criteria. The OCT analyses results are provided in Table 3 and in eTable 2 in Supplement 2.
The final median (IQR) post-PCI minimum stent area (primary end point) was 6.5 mm2 (5.5-8.1) in the OCT group and 5.0 mm2 (4.1-6.1) in the angio group (P < .001; Figure 2). A total of 25 patients (36%) from the angio group had MSA of 4.5 mm2 or less (vs 5 patients [8%] in the OCT group; P < .001). A significantly higher median (IQR) mean stent area (8.4 mm2 [7.0-10.3] vs 7.4 mm2 [6.4-8.6]; P < .001) was observed in patients in the OCT group compared to the others. In addition, the geometric stent expansion was better in the patients treated with OCT guidance compared to the others. Although the prevalence of major struts malapposition was similar among groups, the total major malapposition length was longer among patients from the angio group (Table 3). There was no difference among groups regarding the incidence of dissections and stent eccentricity degree.
Figure 2. Primary End Point Results.
The dashed line represents the 4.5-mm2 cutoff value for minimal stent area (MSA). For optical coherence tomography (OCT) guidance, mean (SD) MSA was 6.9 (1.9) mm2, and median (IQR) MSA was 6.5 (5.5-8.1) mm2. For angiography guidance, mean (SD) MSA was 5.3 (1.7) mm2, and median (IQR) MSA was 5.0 (4.1-6.1) mm2. Angio indicates angiography.
The impact of OCT findings on procedure flow is provided in eFigure 5 in Supplement 2. In the OCT group, the initial post-PCI OCT analysis led to further optimization in 43% of cases. In this subgroup of 28 patients, the median (IQR) MSA significantly increased from 5.9 mm2 (4.7-7.4) to 7.2 mm2 (5.4-8.4) (P < .001, paired t test). In the angio group, a complementary correction was provided in 29% of cases according to the qualifying OCT run results analysis.
To clarify the impact of OCT-guided post-PCI optimization on the primary end point, we compared the MSA value measured on the first control OCT run among patients from the OCT group (MSA 1, or intermediate MSA, measured before optimization) to the MSA measured on the qualifying run in the angio group. This comparison takes directly into consideration the impact of the plaque preparation quality and device sizing in each group, without the bias of OCT guidance postdilatation. We observed that this MSA before any optimization was higher than the final MSA in the angio group (median [IQR], 6.3 mm2 [5-8.1] vs median [IQR], 5.0 mm2 [4.1-6.1]; P < .001).
Furthermore, we observed similar findings in patients with moderate and severe calcifications on baseline angiography (eTables 2-4 and eFigure 6 in Supplement 2) and in patients with Ca2+ arc extension below or over 180° (eFigure 7 in Supplement 2).
Predictors of Inadequate Stent Expansion
To analyze the factors associated with significant stent underexpansion (MSA ≤4.5 mm2), a multivariable logistic regression analysis was performed. We observed that OCT guidance, larger reference vessel diameter, and shorter lesion length were independently associated with lower risk of stent underexpansion, whereas IVL up-front use was not (eTable 5 in Supplement 2).
Clinical End Points
Clinical follow-up was completed by all patients included in the analysis. The incidence of periprocedural MI was 8.1% and 8.8% in the OCT and angio groups, respectively (P > .99, Fisher test). There was no other MACE recorded during the first 30 days following PCI in both groups.
Discussion
To our knowledge, the CALIPSO study is the first randomized clinical trial to compare OCT- and angiography-based PCI strategies for moderate to severe calcified lesions, using a predefined algorithm for plaque preparation, stent sizing, and optimization. Post-PCI minimum stent area achieved in the OCT group was superior to that achieved with angio guidance, meeting the primary end point of the trial. In addition, OCT-guided PCI resulted in significantly greater average stent expansion and lower malappositon than angiography-guided PCI, without any concern regarding procedural safety.
Despite recent improvements in plaque preparation strategies, the results of calcified lesions PCI frequently remain suboptimal, with a higher risk of underexpansion or severe malapposition14,22,23,24 that could trigger adverse outcomes.1 The most recent consensus documents promote the use of intracoronary imaging to guide coronary calcified lesion management, which includes evaluation of the global calcium burden, choice of an appropriate adjunctive device, stent sizing, early results assessment, and potential results optimization.1,6 In this perspective, OCT imaging is an appealing option because of the limited reflection and attenuation of low coherence light across calcified tissue that allows for better calcium detection and quantification compared to intravascular ultrasound.1 However, there are scarce data supporting this approach, and most of the dedicated calcification management algorithms remain expert consensus. Although intracoronary imaging–guided PCI has showed its superiority over angio guidance in various situations,25 no study has specifically focused on calcified lesions, yet a 2024 meta-analysis suggested benefits.26 Hence, in the RENOVATE-COMPLEX PCI, ILUMIEN IV, and OCCUPI trials, the percentage of severe calcified lesions ranged between 9% and 14%, and the strategies for plaque preparation were left at the discretion of the operator.27,28,29,30 The CALIPSO randomized clinical trial is the first study to include only patients with significant calcifications, and this study aimed to validate prospectively a prespecified OCT-guided management. From this perspective, our study differs from the previously published trials. We observed that this OCT-guided strategy was associated with a larger MSA compared to the conventional approach, irrespective of the angiographic baseline calcification degree. In addition, patients treated in the OCT arm also displayed better results in average stent area, geometrical expansion, and major struts malapposition length. These results confirm previous observations from noncalcified and complex lesions28 and are also in line with the data from the OCT subgroup of the ECLIPSE trial31 and the results of the ILUMIEN IV trial calcified lesions subanalysis32 presented at the TCT 2024 conference. This larger MSA we observed could be potentially related to 3 factors: (1) better plaque preparation; (2) more appropriate stent sizing; and (3) post-PCI optimization steps. Although the PCI optimization steps may have contributed to the benefits, it is likely, in view of our analyses of intermediate MSA, that the quality of lesion preparation largely drove these results. The use of higher-pressure postdilation with noncompliant balloons in the conventional group did not overcome the lower stent expansion, suggesting that this approach could present limitations. Finally, although the stents’ dimensions did not statically differ between groups in the current analysis, we believe that the modest sample size potentially prevented us from demonstrating the significant difference in stent diameter and length between the OCT- and angio-guided patients that is classically observed in other intracoronary imaging studies.27,28,29
We observed that the pre-PCI OCT analysis significantly influenced the plaque preparation strategy among operators. Hence, IVL was used significantly more frequently as a first-line option in this group. This could be explained by the high prevalence of maximal calcium arc greater than 180° among most patients (80%), irrespective of baseline angiography calcification degree. These data are in line with previous reports illustrating the poor predictive value of coronary angiography for accurate evaluation of calcium burden compared to intracoronary imaging.2,3 Our results therefore suggest that OCT analysis of calcified lesions prior to PCI confers an advantage by enabling a more accurate assessment of lesion complexity and global calcium burden, which in turn enables proposal of a more appropriate management strategy. However, it is important to bear in mind that these results do not prove the superiority of one tool over another—the trial was not designed for this purpose, and several ongoing studies will focus specifically on this issue.6
The OCT guidance strategy was safe and did not cause increased adverse periprocedural events. Interestingly, we did not observe any significant difference in contrast medium volume and procedure duration between groups. These results contrast with previously published data28,33 but may be explained by the nature of the procedures. Indeed, calcified lesions PCIs are more complex and time-consuming than simpler lesions angioplasties. In addition, bailout strategies were used more frequently in the angio group than in the OCT group, and postimplantation stent optimization procedures were frequent, which may have lengthened the procedure time and involved greater use of contrast media. Thus, in this context, the initial investment in time and contrast medium for OCT analysis seems to be balanced by better immediate results and a lower risk of continuing the procedure. Finally, all the patients from the angio group also underwent a final OCT run (as part of the protocol), which might also have increased the contrast medium volume.
Limitations
The CALIPSO trial sample size is limited, since the trial was not designed or powered to prove any clinical superiority of OCT-guided strategy and mostly focused on imaging end points. The choice of MSA as the primary end point could be debated but is justified by previous trials reports that identified MSA as a predictor of stent failure and subsequent clinical events.10,11,34 Thus, MSA can be considered a surrogate end point. Several patients (6.3%) were excluded from the analysis because of the impossibility to cross the most severe lesions with the OCT catheter or the poor quality of the images. This number is within the prespecified expected range but could have impacted the results. In addition, patients with anticipated uncrossable lesion and indication for up-front RA1 were not included in the study. This type of lesion was not suitable for the validation of the algorithm, since pre-PCI OCT runs could have been affected by the initial preparation steps. However, OCT guidance still has some great interest in this situation. The CALIPSO algorithm did not include orbital atherectomy among the potential options, since this tool was not available in all the French catheterization laboratories at the time the protocol was designed. In addition, we did not propose specific strategy for management of calcified nodules.35 The algorithm might thus be updated in the future according to ongoing trials results.6 In the angio group, an optional post-PCI optimization step, according to the qualifying OCT run results, was proposed by the ethics committee during protocol review. This step was left at the discretion of the operators and was applied in 29% of cases. This might have affected the clinical outcomes, but not the primary and secondary imaging end points results. Finally, the OCT data reported in the manuscript are based on the core laboratory analyses, whereas the patients’ PCI strategy relied on the local operators’ interpretation.
Conclusions
In conclusion, the CALIPSO randomized clinical trial showed that a strategy of OCT-guided PCI according to a prespecified algorithm conferred better stent expansion compared to conventional angiography guidance in patients with moderate to severe calcified lesions. Whether this superiority in terms of imaging end points will translate into clinical benefit should be assessed in the future.32
Trial Protocol
eMethods. OCT Acquisition and Analysis, Coronary Angiography Analysis, Sample Size Calculation
eTable 1. Stent and POT Balloon Sizing Methodology
eTable 2. Pre-PCI OCT Results According to Calcification Degree on Baseline Angiography in the OCT-Guidance Group
eTable 3. Plaque Preparation and Main OCT Results in Patients With Moderate Calcifications on Baseline Angiography
eTable 4. Plaque Preparation and Main OCT Results in Patients With Severe Calcifications on Baseline Angiography
eTable 5. Predictors of Inadequate Stent Expansion in the CALIPSO Study Population
eFigure 1. A Case From the CALIPSO Trial / OCT Arm: Pre PCI Analysis
eFigure 2. A Case From the CALIPSO Trial / OCT Arm: PCI Strategy and OCT Analysis
eFigure 3. Global CONSORT Workflow of the CALIPSO Trial
eFigure 4. Plaque Preparation Modalities According to the Baseline Maximal Calcium Arc Extent in the OCT Group
eFigure 5. PCI Optimization Strategies Among OCT-Guidance and Angio-Guidance Groups
eFigure 6. Post-PCI MSA Values in Patients From the OCT & Angio Groups According to Their Baseline Calcification Degree on Angiography
eFigure 7. Post-PCI MSA Values in Patients From the OCT Group According to Their Baseline Maximal Calcium Radial Extent Compared to Patients From the Angio Group
eReferences.
Data Sharing Statement
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial Protocol
eMethods. OCT Acquisition and Analysis, Coronary Angiography Analysis, Sample Size Calculation
eTable 1. Stent and POT Balloon Sizing Methodology
eTable 2. Pre-PCI OCT Results According to Calcification Degree on Baseline Angiography in the OCT-Guidance Group
eTable 3. Plaque Preparation and Main OCT Results in Patients With Moderate Calcifications on Baseline Angiography
eTable 4. Plaque Preparation and Main OCT Results in Patients With Severe Calcifications on Baseline Angiography
eTable 5. Predictors of Inadequate Stent Expansion in the CALIPSO Study Population
eFigure 1. A Case From the CALIPSO Trial / OCT Arm: Pre PCI Analysis
eFigure 2. A Case From the CALIPSO Trial / OCT Arm: PCI Strategy and OCT Analysis
eFigure 3. Global CONSORT Workflow of the CALIPSO Trial
eFigure 4. Plaque Preparation Modalities According to the Baseline Maximal Calcium Arc Extent in the OCT Group
eFigure 5. PCI Optimization Strategies Among OCT-Guidance and Angio-Guidance Groups
eFigure 6. Post-PCI MSA Values in Patients From the OCT & Angio Groups According to Their Baseline Calcification Degree on Angiography
eFigure 7. Post-PCI MSA Values in Patients From the OCT Group According to Their Baseline Maximal Calcium Radial Extent Compared to Patients From the Angio Group
eReferences.
Data Sharing Statement
