We evaluated 3-year clinical outcomes after contemporary left main percutaneous coronary intervention in patients with and without acute coronary syndrome (ACS) in a real-world cohort, in which intracoronary imaging guidance was routinely used. Among 758 consecutive patients undergoing left main percutaneous coronary intervention for unprotected de novo lesions, 97.6% received imaging guidance. Patients were categorized by presenting ACS (n = 241) or without ACS (n = 516). Three-year major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause mortality, clinically driven revascularization, myocardial infarction, and cerebrovascular events were analyzed. Patients with ACS presented more true bifurcation lesions (31.9% vs 24.2%), cardiogenic shock (18.3% vs 0.2%), and increased mechanical circulatory support use (40.2% vs 5.6%). They had significantly higher MACCE (40.7% vs 28.5%; hazard ratio [HR] 1.81) and mortality rates (25.8% vs 10.2%; HR 3.09), primarily due to higher mortality within 30 days (HR 9.05), while revascularization rates were similar (13.4% vs 15.8%). MACCE predictors in ACS included male (HR 2.62), mechanical circulatory support (HR 2.44), and radial access (HR 0.42). In patients without ACS, left ventricular ejection fraction <40% (HR 2.27), severe calcification requiring coronary atherectomy (HR 1.86), two-stent implantation (HR 1.99), and radial access (HR 0.59) were predictive. In this cohort with extensive use of intracoronary imaging, rates of two-stent implantation (8.9%), target lesion revascularization (4.0%), myocardial infarction (3.0%), and stent thrombosis (0.3%) were low. In conclusion, in contemporary left main percutaneous coronary intervention practice, patients presenting with ACS experienced worse 3-year outcomes, largely attributable to early mortality. After the early phase, longer-term outcomes, including revascularization, were comparable between ACS and non-ACS presentations.
Intracoronary imaging guidance during percutaneous coronary intervention (PCI) in complex coronary lesions is strongly recommended by the recently revised European Society of Cardiology guidelines (Class IA). A meta-analysis of 22 trials involving 15,964 patients demonstrated that intracoronary imaging guidance reduced target lesion failure, comprising death, target lesion revascularization, myocardial infarction, and stent thrombosis, by 29% compared to angiography-guided PCI. In a British nationwide survey, 41.2% of left main (LM) PCI cases were guided by intracoronary imaging and demonstrated a significant reduction in major adverse cardiovascular and cerebrovascular events (MACCEs) and mortality, with an odds ratio < 0.5. However, real-world registry studies have primarily included complex cases for imaging-guided PCI (25%–41% of enrolled patients), ,, leaving the efficacy of routine imaging guidance for all LM-PCI cases in daily practice unclear. Furthermore, imaging guidance was likely underutilized in patients with hemodynamic collapse (15%–22%), , and the differences in the benefits between acute coronary syndrome (ACS) and stable chronic coronary syndrome remains to be elucidated. We aimed to investigate the clinical outcomes of patients with ACS and chronic syndromes among consecutive LM-PCI cases in the Japanese National Hospital Organization group, where intracoronary imaging guidance is routinely employed as contemporary guideline recommended.
Methods
Study population and design
LM-PCI cases in the Japanese National Hospital Organization is a multicenter, retrospective, observational registry study. We enrolled 806 consecutive patients who underwent LM-PCI with drug-eluting stents between January 2016 and December 2020 at 19 Japanese National Hospital Organization institutions.
The inclusion criteria were as follows: (1) de novo LM lesions, including significant stenosis in the LM (≥50%) and/or daughter branches (≥75%) within 5 mm of the carina, treated with drug-eluting stent implantation in LM or crossover from LM to daughter branches; (2) suitable lesion for drug-eluting stent implantation in the LM; (3) patient age > 20 years; and (4) toleration of dual antiplatelet therapy for >6 months. The exclusion criteria were as follows: (1) in-stent restenosis lesions; (2) chronic total occlusion in the LM or adjusting branches; (3) left anterior descending artery and/or left circumflex artery (LCX) protected by prior coronary artery bypass grafting (CABG); (4) possible or definite pregnancy in female participants; (5) patients deemed unsuitable by the responsible physician; and (6) refusal to provide personal information for the study after receiving the study information, in accordance with the opt-out system.
After excluding 29 patients (28 for unmet inclusion criteria, one by physician’s discretion) and 19 patients with incomplete 3-year follow-up data, 758 patients were included in the study ( Figure 1 ). The study protocol was approved by the Institutional Review Board of the Japanese National Hospital Organization and each attending hospital. The approved protocol included the use of the opt-out consent process, and the requirement for written informed consent was waived. The study protocol was developed in accordance with the Declaration of Helsinki and registered in the University Hospital Medical Information Network (ID: UMIN 000037332) prior to the initiation of enrollment.
Study flow of the extraction of the analyzed patients. ACS = acute coronary syndrome.
PCI protocol
All patients received periprocedural heparin and dual antiplatelet therapy (aspirin 100 mg plus clopidogrel 50–75 mg or prasugrel 3.75 mg for at least 6 months) according to the Japanese guidelines. Loading doses (aspirin, 200 mg; clopidogrel, 300 mg; or prasugrel, 20 mg) were administered if necessary. Intracoronary imaging, using intravascular ultrasound (IVUS) or optical coherence tomography (OCT)/optical frequency domain imaging, was recommended both before and after PCI for lesion assessment and optimization. Operators performed additional treatments if imaging detected stent malapposition (>400 μm), inadequate expansion (<80% of mean reference), or significant dissection. The proximal optimization technique was advised but remained operator-dependent. Side-branch dilation strategies, including kissing balloon inflation and side-branch dilation alone, were also performed at the operator’s discretion.
Data collection
Patient background, lesion characteristics, PCI procedures, and clinical outcomes were recorded using the REDCap system hosted by the Osaka Metropolitan University.
End points
The primary end point was MACCE at 3 years: all-cause death, clinically driven revascularization, myocardial infarction, and cerebrovascular events. The secondary end points included target lesion revascularization, target vessel revascularization, and cardiac death.
In this study, ACS was defined as any acute presentation of coronary artery disease, including unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction. Cardiac death was defined as death caused by cardiac diseases, including heart failure, fatal arrhythmia, and sudden death. TLR was defined as any revascularization using PCI or CABG in the treated LM and adjusting proximal left anterior descending artery and LCX within 5 mm from the branch ostium. TVR was defined as the revascularization of the LM, left anterior descending artery, or LCX. Clinically driven revascularization included TVR and non-TVR, which was prompted by symptoms or objective evidence of ischemia in the presence of ≥50% stenosis of the vessel. Stent thrombosis included definite and probable stent thrombosis as defined by the Academic Research Consortium. Cerebrovascular disorders included stroke with any new-onset neurological deficit caused by cerebrovascular artery occlusion and cerebrovascular hemorrhage, except for traumatic hemorrhage. Successful PCI was defined as the achievement of thrombolysis in myocardial infarction flow grade III with residual stenosis of ≤25% in the target lesion.
Statistical analyses
Continuous variables are presented as mean ± SD and compared using Student’s t test. Categorical variables are expressed as percentages and compared using the chi-square test. The Kaplan–Meier method with log-rank tests was used to evaluate the cumulative incidences of MACCE and all-cause death. Cox proportional hazard models were used to assess risk factors for the MACCE and all-cause death. For the multivariable Cox regression analyses, the following variables were included as covariates: age > 65 gt; 65 years, male sex, left ventricular ejection fraction (LVEF) < 40%, dyslipidemia, Canadian Cardiovascular Society (CCS) class IV angina, radial access, mechanical circulatory support (MCS), LM stent size ≥ 3.5mm, and two-stent implantation. In the analysis with clinically driven revascularization, myocardial infarction, cerebrovascular events, TLR, TVR, and cardiac death as end points, a competing risk approach was used because all-cause death was considered to be a competing risk. The cumulative incidence function was estimated for each end point, and the Fine–Gray model was used to obtain the sub-distribution hazard ratio (HR). Analyses were performed using the R software (version 4.2.2) (R Foundation for Statistical Computing, Vienna, Austria).
Results
Baseline characteristics
Baseline patient characteristics are summarized in Table 1 . Patients with ACS had a lower prevalence of recognized comorbidities than that in patients without ACS, including hypertension (66.8% vs 78.9%; p < 0.001), dyslipidaemia (63.9% vs 73.6%; p = 0.006), peripheral artery disease (7.5% vs 13.2%; p = 0.02), previous myocardial infarction (17.0% vs 29.7%; p < 0.001), and prior PCI or failed CABG (23.7% vs 52.5%; p < 0.001). However, patients with ACS presented more CCS class IV angina (67.7% vs 6.8%; p < 0.001) and lower LVEF (52±15% vs 58±14%; p < 0.001). They also presented more severe clinical states, including cardiogenic shock (18.3% vs 0.2%; p < 0.001), cardiopulmonary arrest (7.5% vs 0%; p < 0.001), and pulmonary edema (13.7% vs 2.7%; p < 0.001). Moreover, patients with ACS exhibited a tendency of a lower systolic blood pressure (123 ± 31 vs 129 ± 22 mm Hg; p = 0.072) and higher diastolic pressure (72 ± 19 vs 70 ± 14 mm Hg; p = 0.008) and pulse rate (82 ± 21 vs 69 ± 13 beats/min; p < 0.001), with more significant electrocardiogram (ECG) ischemic change (86.3% vs 36.6%, p < 0.001), than those in their counterparts.
Table 1
Clinical characteristics and lesion background
| Whole | Without ACS | ACS | p Value | ||
|---|---|---|---|---|---|
| Patients | 758 | 516 | 241 | ||
| Patient background | |||||
| Age | years old | 73.1 ± 10.0 | 73.3 ± 9.2 | 72.9 ± 11.6 | 0.96 |
| Male | n (%) | 596 (78.6) | 409 (79.3) | 186 (77.2) | 0.52 |
| Body mass index | kg/m 2 | 24.5 ± 7.2 | 24.1 ± 3.6 | 25.4 ± 11.6 | 0.35 |
| Hypertension | n (%) | 569 (75.1) | 407 (78.9) | 161 (66.8) | <0.001 |
| Dyslipidemia | n (%) | 534 (70.4) | 380 (73.6) | 154 (63.9) | 0.006 |
| Diabetes | n (%) | 374 (49.3) | 260 (50.4) | 114 (47.3) | 0.43 |
| Smoking | n (%) | 244 (32.2) | 163 (31.6) | 81 (33.6) | 0.58 |
| Hemodialysis | n (%) | 34 (4.5) | 28 (5.4) | 6 (2.5) | 0.07 |
| COPD | n (%) | 17 (2.2) | 11 (2.1) | 6 (2.5) | 0.76 |
| Peripheral artery disease | n (%) | 86 (11.3) | 68 (13.2) | 18 (7.5) | 0.02 |
| Prior myocardial infarction | n (%) | 194 (25.6) | 153 (29.7) | 41 (17.0) | <0.001 |
| Prior PCI/CABG | n (%) | 328 (43.3) | 271 (52.5) | 57 (23.7) | <0.001 |
| Family history | n (%) | 97 (12.8) | 72 (14.0) | 25 (10.4) | 0.17 |
| Left ventricular ejection fraction | % | 56±15 | 58±14 | 52±15 | <0.001 |
| Clinical presentation | |||||
| Stable angina | n (%) | 297 (39.2) | 297 (57.6) | 0 (0) | <0.001 |
| Old myocardial infarction | n (%) | 39 (5.2) | 39 (7.6) | 0 (0) | |
| Silent myocardial ischemia | n (%) | 144 (19.0) | 144 (27.9) | 0 (0) | |
| Other heart disease without angina | n (%) | 26 (3.4) | 26 (5.0) | 0 (0) | |
| Acute coronary syndrome | n (%) | 241 (31.8) | 0 (0) | 241 (100.0) | |
| Cardiogenic shock | n (%) | 45 (5.9) | 1 (0.2) | 44 (18.3) | <0.001 |
| Cardiopulmonary arrest | n (%) | 18 (2.4) | 0 (0) | 18 (7.5) | <0.001 |
| Pulmonary edema | n (%) | 47 (6.2) | 14 (2.7) | 33 (13.7) | <0.001 |
| CCS classification | |||||
| I | n (%) | 288 (38.5) | 271 (52.9) | 17 (7.2) | <0.001 |
| II | n (%) | 161 (21.5) | 144 (28.1) | 16 (6.8) | |
| III | n (%) | 105 (14.0) | 62 (12.1) | 43 (18.3) | |
| IV | n (%) | 194 (25.9) | 35 (6.8) | 159 (67.7) | |
| Hemodynamics | |||||
| Systolic blood pressure | mm Hg | 127±25 | 129±22 | 123±31 | 0.072 |
| Diastolic blood pressure | mm Hg | 70±16 | 70±14 | 72±19 | 0.008 |
| Pulse rate | beats/min | 73±17 | 69±13 | 82±21 | <0.001 |
| ECG ischemic change | 380 (51.9) | 185 (36.6) | 195 (86.3) | <0.001 | |
| Pre-PCI | |||||
| Total cholesterol | mg/dl | 169.1 ± 42.4 | 165.3 ± 37.5 | 180.4 ± 52.7 | <0.001 |
| Trigriceride | mg/dl | 130.4 ± 82.0 | 136.6 ± 81.4 | 115.0 ± 81.8 | <0.001 |
| High density lipoprotein cholesterol | mg/dl | 49.0 ± 13.6 | 49.7 ± 13.7 | 47.0 ± 13.3 | 0.029 |
| Low density lipoprotein cholesterol | mg/dl | 98.6 ± 36.8 | 92.6 ± 30.8 | 113.9 ± 45.4 | <0.001 |
| Hemoglobin A1c | % | 6.6 ± 1.2 | 6.6 ± 1.1 | 6.6 ± 1.3 | 0.23 |
| Serum creatinine | mg/dl | 1.26±1.37 | 1.29±1.45 | 1.22±1.17 | 0.61 |
| eGFR | ml/min/1.73m2 | 58±23 | 58±23 | 58±24 | 0.57 |
| Lesion background | |||||
| Bifurcation lesion | n (%) | 587 (78.5) | 402 (78.5) | 184 (78.3) | >0.9 |
| Medina 1-0-0 | n (%) | 55 (9.4) | 54 (9.4) | 54 (9.4) | 0.033 |
| Medina 1-1-0 | n (%) | 180 (30.7) | 134 (33.3) | 46 (25.0) | |
| Medina 1-1-1 | n (%) | 143 (24.4) | 84 (20.9) | 58 (31.5) | |
| Medina 1-0-1 | n (%) | 31 (5.3) | 22 (5.5) | 9 (4.9) | |
| Medina 0-1-0 | n (%) | 137 (23.3) | 102 (25.4) | 35 (19.0) | |
| Medina 0-1-1 | n (%) | 29 (4.9) | 19 (4.7) | 10 (5.4) | |
| Medina 0-0-1 | n (%) | 12 (2.0) | 6 (1.5) | 6 (3.3) | |
| True bifurcation lesion | n (%) | 203 (34.6) | 125 (31.1) | 77 (41.8) | 0.012 |
| Medina 0-x-x | n (%) | 178 (30.3) | 127 (31.5) | 51 (27.7) | 0.38 |
Values are n (%) or mean ± SD.
ACS = acute coronary syndrome; COPD = chronic obstructive pulmonary disease; eGFR = estimated glomerular filtration ratio; PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting.
Lesion background
The backgrounds of the lesions are shown in Table 1 . Although LM bifurcation lesions were similarly included in 78% to 79%, patients with ACS had more true bifurcation lesions (41.8% vs 31.1%; p = 0.012). Angiographically nonsignificant LM lesions (Medina 0-x-x) were similarly included in 27% to 32%, because of the identification of continuous plaque from the LM to daughter branches on intracoronary imaging.
PCI procedures
The details of the PCI procedures are presented in Table 2 . In patients with ACS, PCI was performed with less frequent radial access (63.5% vs 73.8%; p = 0.013) and with more frequent use of a 6-Fr guiding system (62.7% vs 47.7%; p = 0.001). Imaging guidance was performed in over 97% of cases, although IVUS was more commonly used in patients with ACS (94.2% vs 82.9%; p < 0.001). Two-stent implantation for LM bifurcation occurred more frequently (12.0% vs 7.4%; p = 0.040). However, the proximal optimization technique (46.0% vs 53.8%; p = 0.055) and side-branch dilation during single-stent implantation (64.0% vs 79.6%; p < 0.001) were less commonly performed. MCS was used more often in patients with ACS (40.2% vs 5.6%; p < 0.001), while lesion modification with rotational or orbital atherectomy was less common (5.4% vs 11.1%; p = 0.018). Stent type, size, and length did not differ significantly between groups. PCI success rates remained high in both cohorts, although they were slightly lower in patients with ACS (97.1% vs 99.4%; p = 0.009).
Table 2
Procedural characteristics
| Whole | Without ACS | ACS | p Value | ||
|---|---|---|---|---|---|
| Access | |||||
| Radial | n (%) | 534 (70.4) | 381 (73.8) | 153 (63.5) | 0.013 |
| Femoral | n (%) | 201 (26.5) | 122 (23.6) | 78 (32.4) | |
| Brachial | n (%) | 23 (3.0) | 13 (2.5) | 10 (4.1) | |
| System | |||||
| 6 Fr | n (%) | 397 (52.4) | 246 (47.7) | 151 (62.7) | 0.001 |
| 7 Fr | n (%) | 310 (40.9) | 232 (45.0) | 78 (32.4) | |
| 8 Fr | n (%) | 49 (6.5) | 37 (7.2) | 11 (4.6) | |
| Imaging guide | n (%) | 740 (97.6) | 505 (97.9) | 234 (97.1) | 0.50 |
| IVUS | n (%) | 656 (86.5) | 428 (82.9) | 227 (94.2) | <0.001 |
| OCT | n (%) | 91 (12.0) | 83 (16.1) | 8 (3.3) | <0.001 |
| Drug-eluting stent | |||||
| First generation | n (%) | 0 (0) | 0 (0) | 0 (0) | |
| Current generation | n (%) | 742 (99.9) | 515 (99.9) | 241 (100.0) | >0.9 |
| Two-stent | n (%) | 67 (8.9) | 38 (7.4) | 29 (12.0) | 0.040 |
| Elective | n (%) | 53 (79.1) | 29 (76.3) | 24 (82.8) | 0.50 |
| Culotte | n (%) | 28 (41.8) | 15 (39.5) | 13 (44.8) | >0.9 |
| Crush | n (%) | 16 (23.9) | 10 (26.3) | 6 (20.7) | |
| T-stenting | n (%) | 21 (31.3) | 12 (31.6) | 9 (31.0) | |
| Proximal optimization technique | n (%) | 361 (51.2) | 258 (53.8) | 103 (46.0) | 0.055 |
| Side-branch dilation in one-stent | n (%) | 479 (74.8) | 352 (79.6) | 126 (64.0) | <0.001 |
| Kissing balloon inflation | n (%) | 396 (61.9) | 290 (65.6) | 105 (53.3) | <0.001 |
| Side-branch dilation alone | n (%) | 83 (13.0) | 62 (14.0) | 21 (10.7) | 0.89 |
| Support device | n (%) | 126 (16.6) | 29 (5.6) | 97 (40.2) | <0.001 |
| IABP | n (%) | 122 (16.1) | 29 (5.6) | 93 (38.6) | <0.001 |
| ECMO | n (%) | 20 (2.6) | 2 (0.4) | 18 (7.5) | <0.001 |
| Lesion modification | |||||
| Rotational/orbital atherectomy | n (%) | 70 (9.2) | 57 (11.1%) | 13 (5.4%) | 0.018 |
| Directional atherectomy | n (%) | 10 (1.3) | 9 (1.7) | 0 (0.0) | 0.039 |
| Scoring balloon | n (%) | 145 (19.1) | 105 (20.3) | 39 (16.2) | 0.20 |
| Main vessel stent | |||||
| Size: ≥4.0 mm | n (%) | 120 (16.2) | 91 (18.0) | 29 (12.3) | 0.12 |
| 3.5–4.0 mm | n (%) | 391 (52.7) | 270 (53.5) | 120 (50.8) | |
| 3.0–3.5 mm | n (%) | 193 (26.0) | 118 (23.4) | 75 (31.7) | |
| 2.5–3.0 mm | n (%) | 33 (4.5) | 24 (4.8) | 9 (3.8) | |
| <2.5 mm | n (%) | 5 (0.7) | 2 (0.4) | 3 (1.3) | |
| Length | mm | 22.9 ± 8.6 | 22.9 ± 8.5 | 22.9 ± 8.6 | 0.80 |
| Product | |||||
| Xience | n (%) | 370 (49.9) | 242 (47.9) | 128 (54.2) | 0.60 |
| Synergy/Promus | n (%) | 130 (17.5) | 95 (18.8) | 35 (14.8) | |
| Resolute Integrity/Onyx | n (%) | 82 (11.1) | 57 (11.3) | 24 (10.2) | |
| Ulitimaster | n (%) | 107 (14.4) | 73 (14.5) | 34 (14.4) | |
| Nobori/BioFreedom | n (%) | 38 (5.2) | 29 (5.7) | 9 (3.8) | |
| Orsilo | n (%) | 14 (1.9) | 8 (1.6) | 6 (2.5) | |
| Bare metal stent | n (%) | 1 (0.1) | 1 (0.2) | 0 (0.0) | |
| Side branch | |||||
| Size: ≥4.0 mm | n (%) | 4 (4.7) | 1 (2.1) | 3 (8.1) | 0.40 |
| 3.5–4.0 mm | n (%) | 8 (9.4) | 4 (8.3) | 4 (10.8) | |
| 3.0–3.5 mm | n (%) | 35 (41.2) | 24 (50.0) | 11 (29.7) | |
| 2.5–3.0 mm | n (%) | 29 (34.9) | 15 (31.2) | 14 (37.8) | |
| <2.5 mm | n (%) | 9 (10.6) | 4 (8.3) | 5 (13.5) | |
| Length | mm | 21.5 ± 7.8 | 21.4 ± 8.0 | 21.5 ± 7.5 | >0.9 |
| Product | |||||
| Xience | n (%) | 34 (40.0) | 19 (39.6) | 15 (40.5) | 0.80 |
| Synergy/Promus | n (%) | 17 (20.0) | 8 (16.7) | 9 (24.3) | |
| Resolute Integrity/Onyx | n (%) | 13 (15.3) | 9 (18.8) | 4 (10.8) | |
| Ulitimaster | n (%) | 18 (21.2) | 10 (20.8) | 8 (21.6) | |
| Nobori/BioFreedom | n (%) | 1 (1.2) | 1 (2.1) | 0 (0.0) | |
| Orsiro | n (%) | 2 (2.4) | 1 (2.1) | 1 (2.7) | |
| Bare metal stent | n (%) | 0 (0.0) | 0 (0) | 0 (0) | |
| PCI success | n (%) | 748 (98.7) | 513 (99.4) | 234 (97.1) | 0.009 |
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