Highlights
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The current study exclusively evaluated the prognostic impact of intravascular imaging-guided percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients with high thrombus burden using nationwide, multicenter, prospective registries.
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Intravascular imaging-guided PCI was associated with a lower risk of major adverse cardiovascular event and cardiac death without increased risk of stroke than angiography-guided PCI in AMI patients with high thrombus burden.
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Intravascular imaging-guided PCI could be considered for optimal revascularization in AMI patients with high thrombus burden due to its potential survival benefit.
Despite the established clinical efficacy following intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) than angiography-guided PCI, evidence regarding prognostic benefits of IVI-guided PCI in acute myocardial infarction (AMI) patients with high thrombus burden remains limited. Using the nationwide registries of KAMIR-NIH and KAMIR-V, we evaluated the prognostic impact of IVI-guided PCI in AMI patients with high thrombus burden. A total of 4,074 patients with AMI and TIMI thrombus grades 4 or 5 who underwent aspiration thrombectomy were selected, of whom 892 patients (21.9%) received IVI-guided PCI and 3,182 patients (78.1%) received angiography-guided PCI. Primary outcome was major adverse cardiovascular event (MACE, a composite of all-cause death, MI, repeat revascularization, and stent thrombosis). Major secondary efficacy outcome was cardiac death and safety outcome was stroke at 3 years. During the median 3 years of follow-up, the risk of MACE was significantly lower in the IVI-guided PCI group than in the angiography-guided PCI group (12.9% vs 16.3%; adjusted HR, 0.80; 95% CI, 0.65 to 0.98; p = 0.035), mainly driven by a lower risk of all-cause death (5.7% vs 10.0%; adjusted HR, 0.65; 95% CI, 0.48 to 0.89; p = 0.007). IVI-guided PCI also showed lower risk of cardiac death compared with angiography-guided PCI (3.8% vs 7.0%; adjusted HR, 0.65; 95% CI, 0.44 to 0.95; p = 0.025). There was no significant difference in the risk of stroke between the groups. In this hypothesis generating study, IVI-guided PCI was associated with a lower risk of MACE and cardiac death than angiography-guided PCI in AMI patients with high thrombus burden.
Acute myocardial infarction (AMI) with high thrombus burden has been a significant challenge to clinicians. The presence of a large amount of thrombus in the infarct-related artery is associated with a higher incidence of distal embolization and microvascular obstruction, which is an established predictor for larger infarct size. Despite the theoretical basis for thrombus aspiration in improving myocardial perfusion by reducing thrombus burden, routine thrombus aspiration , or deferred stenting , have failed to demonstrate a clinical benefit in randomized clinical trials. As recent clinical data have suggested that the superiority of intravascular imaging (IVI)-guided PCI could be extended to patients with AMI, there has been increased use of intravascular imaging modalities for optimal revascularization in these patients. ,,, However, despite the established clinical efficacy of IVI-guided PCI, evidence regarding prognostic benefit of IVI-guided PCI in AMI patients with high thrombus burden remains limited. Therefore, we sought to evaluate the prognostic impact of IVI-guided PCI in AMI patients with high thrombus burden, using the nationwide, multicenter, prospective KAMIR (Korea Acute Myocardial Infarction Registry) registries.
Methods
Study protocols and patient selection
This current study is an individual patient level pooled data analysis of 2 independent registries specifically designed for patients with AMI: the KAMIR-NIH (Korea Acute Myocardial Infarction Registry-National Institutes of Health) and the KAMIR-Ⅴ (Korea Acute Myocardial Infarction Registry-Ⅴ). The KAMIR-NIH registry prospectively enrolled patients with AMI at 20 tertiary university hospitals in Korea from November 2011 to December 2015. Similarly, the KAMIR-Ⅴ registry prospectively enrolled patients with AMI at 43 cardiovascular centers in Korea from January 2016 to June 2020. The detailed study protocols of both registries have been previously published. ,, The individual ethics committee at each participating center approved the protocol of the KAMIR-NIH and KAMIR-Ⅴ registries and all patients provided written informed consent. The study protocol was conducted in accordance with the principles of the Declaration of Helsinki.
Among a total of 29,625 patients in the KAMIR-NIH and KAMIR-Ⅴ registries, AMI patients with high thrombus burden were selected. STEMI was defined as new ST-segment elevation in 2 or more contiguous leads measuring ≥0.1 mV, or a new left bundle branch block on 12-lead electrocardiography, with a concomitant rise in cardiac biomarker levels above the upper limit of normal. NSTEMI was defined as AMI without the abovementioned criteria of new ST-segment elevation. High thrombus burden was defined as Thrombolysis In Myocardial Infarction (TIMI) thrombus grades 4 or 5 in patients who underwent aspiration thrombectomy. Patients with unavailable follow-up data including use of intravascular imaging devices were excluded. Consequently, 4,074 patients were selected for the current study and classified according to use of intravascular imaging devices such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT) ( Figure 1 ).
Study flow. The study population was derived from the nationwide, multicenter, prospective KAMIR-NIH (Korea Acute Myocardial Infarction Registry-National Institute of Health) and KAMIR-V (Korea Acute Myocardial Infarction Registry-V) registries. IVI = intravascular imaging; MI = myocardial infarction; PCI = percutaneous coronary intervention; TIMI = thrombolysis in myocardial infarction.
Patient management
The management of AMI was performed in accordance with contemporary guidelines. Regarding antiplatelet therapy, a loading dose of aspirin 300 mg was given before PCI, unless patients had been on aspirin therapy for at least 7 days. Additionally, a loading dose of P2Y 12 inhibitor (clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg) was given before PCI, unless patients had been on P2Y 12 inhibitor therapy for at least 7 days. Dual antiplatelet therapy comprising aspirin and a P2Y 12 inhibitor was recommended for at least 12 months following the index procedure unless there was an undisputed reason for discontinuing antiplatelet agents. Decisions regarding treatment strategies, including the intervention techniques, type of stents, adjunctive drug therapy (e.g., GPIIbIIIa inhibitor), thrombus aspiration, and the use of intravascular imaging device, and hemodynamic support devices were left to the operator’s discretion. Although there was no mandated protocol regarding the timing of intravascular imaging, intravascular imaging was performed after acquiring at least TIMI 2 flow using aspiration thrombectomy or balloon angioplasty according to standard clinical practice.
Data collection and follow-up
Baseline demographics and cardiovascular risk factors were collected through patient or guardian interviews, or review of electronic medical records. The collection of admission data, such as clinical presentation, initial vital signs, electrocardiographic, and laboratory findings, were conducted at the emergency department. Information about coronary angiography, procedural characteristics and complications, and discharge medications were systematically collected during hospitalization. After discharge, patients were monitored at 6, 12, 24, and 36 months via outpatient visit or telephone contact. All data were collected by independent clinical research coordinators, using a web-based case report form on the internet-based Clinical Research and Trial management system (iCReaT). An independent event adjudication committee evaluated clinical events.
Study outcomes
The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), repeat revascularization, and definite stent thrombosis at 3 years of follow-up. The major secondary efficacy outcome was cardiac death, and safety outcome was stroke at 3 years. Other secondary outcomes were the individual components of MACE, and Bleeding Academic Research Consortium (BARC) type 2 or greater bleeding at 3 years. Complications during index hospitalization were also analyzed as secondary outcomes. Cardiac death was defined according to the definitions of the Academic Research Consortiums (ARC). Recurrent MI was defined as the recurrence of symptoms or the presence of electrocardiographic changes with a rise in cardiac biomarker levels above the upper limit of normal range. Repeat revascularization was defined as clinically-driven unplanned revascularization. Planned staged PCI was coded separately and was not included as a clinical event. Definite stent thrombosis was defined according to the ARC definitions.
Statistical analysis
Categorical variables are expressed as numbers and frequencies with percentages, and continuous variables were presented as mean ± standard deviation or median (interquartile range) depending on their distribution. Differences in baseline characteristics between the groups were analyzed using the Chi-square test for categorical variables and either Student’s t-test or Mann-Whitney U test for continuous variables according to their distribution. Kaplan-Meier estimates were used to calculate cumulative event rates, and comparisons of clinical outcomes between the groups were made using the log-rank test.
Multiple sensitivity analyses were performed using multivariable Cox regression model, propensity scorematching (PSM) and inverse probability treatment of weighting (IPTW) analysis to adjust the confounders. Covariables in the multivariable Cox regression model were selected for variables with clinical relevance, while considering multicollinearity and model overfitting ( Supplementary Table 1 ). Adjusted variables included age, sex, presented with STEMI or NSTEMI, anterior MI, previous MI, previous cerebrovascular accident, heart failure, atrial fibrillation, diabetes mellitus, hypertension, estimated glomerular filtration rate <60 mL/min/1.73m2 at admission, current smoking, multivessel disease, use of aspirin and potent P2Y 12 inhibitor, and use of venoarterial extracorporeal membrane oxygenation or intra-aortic balloon pump. The assumption of proportionality was assessed using the log-minus-log plot and Cox proportional hazard models for all clinical outcomes satisfied the proportional hazards assumption. For PSM and IPTW analysis, the logistic regression model for use of intravascular imaging device was used to calculate propensity scores. Patients receiving angiography-guided PCI were matched 3:1 with patients receiving IVI-guided PCI by “nearest-neighbor matching” (a greedy match) without replacement. PSM yielded 2,456 patients in the angiography-guided PCI group and 869 patients in the IVI-guided PCI group. Residual differences between the groups after PSM or IPTW adjustment were assessed by calculating absolute standardized mean differences. Absolute standardized mean differences were <0.1 across all matched covariates (age, sex, presented with STEMI or NSTEMI, anterior MI, previous MI, previous cerebrovascular accident, heart failure, atrial fibrillation, diabetes mellitus, hypertension, estimated glomerular filtration rate <60 mL/min/1.73m 2 at admission, current smoking, multivessel disease, use of aspirin and potent P2Y 12 inhibitor, and oral anticoagulant, and use of venoarterial extracorporeal membrane oxygenation or intra-aortic balloon pump), indicating successful balance achievement between the groups ( Supplementary Figure 1 and Supplementary Table 2 ). Subgroup analysis of primary and major secondary efficacy outcomes was performed according to clinical and procedural factors of interest between the groups. The interaction between treatment effects and the covariables was evaluated by a Cox proportional hazard regression model.
All probability values were 2-sided, and p values <0.05 were considered statistically significant. Statistical analyses were performed using R version 4.4.2 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Baseline characteristics
Baseline clinical and procedural characteristics are summarized in Table 1 and Table 2 . The median follow-up period was 3.0 years (interquartile range, 2.9 to 3.1 years). Among a total of 4,074 patients (mean age, 61.9 ± 12.9 years; 3,239 males [79.5%]), 892 patients (21.9%) received IVI-guided PCI, and 3,182 patients (78.1%) received angiography-guided PCI. A greater proportion of patients in the IVI-guided PCI group presented with anterior MI and had complex culprit lesion according to the American College of Cardiology/American Heart Association (ACC/AHA) classification than in the angiography-guided PCI group. During the procedure, the use of radial access and drug-eluting stents was comparable between the groups. However, glycoprotein IIb/IIIa inhibitor was more frequently used in the IVI-guided PCI group compared with the angiography-guided PCI group (38.5% vs 28.2%; p < 0.001). In the characteristics of stents used in culprit lesion, IVI-guided PCI resulted in the use of a higher number of stents, with longer total length and greater mean diameter, than angiography-guided PCI. There was no significant difference in the rates of complete revascularization during index hospitalization between the IVI-guided PCI group and the angiography-guided PCI group (68.5% vs 69.7%; p = 0.504).
Table 1
Baseline clinical characteristics of AMI patients with high thrombus burden according to use of intravascular imaging device
| Characteristics | Total | IVI-guided PCI | Angio-guided PCI | p value |
|---|---|---|---|---|
| (n = 4,074) | (n = 892) | (n = 3,182) | ||
| Demographics | ||||
| Age, years | 61.9 ± 12.9 | 60.5 ± 12.7 | 62.3 ± 12.9 | <0.001 |
| Male, no. (%) | 3,239 (79.5) | 741 (83.1) | 2,498 (78.5) | 0.003 |
| Body mass index, kg/m 2 | 24.5 ± 3.3 | 24.7 ± 3.3 | 24.4 ± 3.3 | 0.024 |
| Initial presentation, no. (%) | ||||
| ST-segment elevation MI | 3,179 (78.0) | 687 (77.0) | 2,492 (78.3) | 0.435 |
| Non-ST-segment elevation MI | 895 (22.0) | 205 (23.0) | 690 (21.7) | 0.435 |
| Anterior MI | 1,595 (39.2) | 391 (43.8) | 1,204 (37.8) | 0.001 |
| Inferior MI | 1,962 (48.2) | 395 (44.3) | 1,567 (49.2) | 0.010 |
| Hemodynamic data | ||||
| Systolic blood pressure, mm Hg | 125.0 ± 29.2 | 126.1 ± 28.1 | 124.7 ± 29.5 | 0.214 |
| Diastolic blood pressure, mm Hg | 76.7 ± 18.6 | 77.6 ± 17.8 | 76.5 ± 18.8 | 0.133 |
| Heart rate, beats/min | 75.1 ± 19.6 | 75.2 ± 19.2 | 75.1 ± 19.7 | 0.920 |
| Killip class 3 or 4, no. (%) | 490 (12.3) | 121 (13.6) | 369 (11.9) | 0.172 |
| Medical history, no. (%) | ||||
| Hypertension | 1,779 (43.7) | 359 (40.2) | 1,420 (44.6) | 0.022 |
| Diabetes mellitus | 912 (22.4) | 186 (20.9) | 726 (22.8) | 0.231 |
| Dyslipidemia | 464 (11.4) | 103 (11.5) | 361 (11.3) | 0.914 |
| Current smoking | 1,757 (44.3) | 414 (47.3) | 1,343 (43.5) | 0.049 |
| Cerebrovascular accident | 206 (5.1) | 35 (3.9) | 171 (5.4) | 0.095 |
| Heart failure | 40 (1.0) | 10 (1.1) | 30 (0.9) | 0.780 |
| Previous MI | 253 (6.2) | 61 (6.8) | 192 (6.0) | 0.423 |
| Atrial fibrillation | 243 (6.0) | 52 (5.8) | 191 (6.0) | 0.906 |
| LVEF, % | 50.4 ± 9.9 | 51.2 ± 9.6 | 50.1 ± 10.0 | 0.007 |
| Left main disease, no. (%) | 106 (2.6) | 30 (3.4) | 76 (2.4) | 0.134 |
| Arteries with stenosis, no. (%) | ||||
| 1 | 2,263 (55.5) | 479 (53.7) | 1,784 (56.1) | 0.223 |
| 2 | 1,162 (28.5) | 268 (30.0) | 894 (28.1) | 0.272 |
| 3 | 649 (15.9) | 145 (16.3) | 504 (15.8) | 0.804 |
| ACC/AHA type C of culprit lesion, no. (%) | 2,467 (61.5) | 617 (70.0) | 1,850 (59.1) | <0.001 |
| Laboratory data | ||||
| Hemoglobin, g/dL | 14.1 ± 1.9 | 14.3 ± 1.9 | 14.1 ± 2.0 | 0.071 |
| Cr, mg/dL | 1.0 ± 0.7 | 1.0 ± 0.8 | 1.0 ± 0.7 | 0.702 |
| eGFR (mL/min/1.73m 2) | 81.8 ± 35.3 | 82.3 ± 29.1 | 81.7 ± 36.9 | 0.630 |
| Glycated hemoglobin, % | 6.4 ± 1.4 | 6.3 ± 1.3 | 6.4 ± 1.5 | 0.258 |
| Total cholesterol, mg/dL | 180.5 ± 44.9 | 182.8 ± 44.8 | 179.8 ± 44.9 | 0.097 |
| HDL-cholesterol, mg/dL | 85.9 ± 46.6 | 82.6 ± 47.6 | 86.9 ± 46.3 | 0.019 |
| LDL-cholesterol, mg/dL | 70.9 ± 43.5 | 78.9 ± 46.7 | 68.6 ± 42.3 | <0.001 |
| Discharge medication, no. (%) | ||||
| Aspirin | 4,057 (99.6) | 892 (100.0) | 3,165 (99.5) | 0.058 |
| P2Y 12 inhibitors | 4,050 (99.4) | 891 (99.9) | 3,159 (99.3) | 0.063 |
| Potent P2Y 12 inhibitors | 1,955 (48.0) | 491 (55.0) | 1,464 (46.0) | <0.001 |
| RASi | 3,068 (75.3) | 650 (72.9) | 2,418 (76.0) | 0.062 |
| Beta blocker | 3,246 (79.7) | 703 (78.8) | 2,543 (79.9) | 0.497 |
| Calcium channel blocker | 131 (3.2) | 32 (3.6) | 99 (3.1) | 0.545 |
| Oral anticoagulants | 197 (4.8) | 42 (4.7) | 155 (4.9) | 0.911 |
| Statin | 3,783 (92.9) | 844 (94.6) | 2,939 (92.4) | 0.025 |
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