Optimal timing of revascularization for patients with non-ST segment elevation myocardial infarction and severe left ventricular dysfunction.

Optimal timing of revascularization for patients who presented with non-ST segment elevation myocardial infarction (NSTEMI) and severe left ventricular (LV) dysfunction is unclear. A total of 386 NSTEMI patients with severe LV dysfunction from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction Registry V (KAMIR-V) were enrolled. Severe LV dysfunction was defined as LV ejection fraction ≤ 35%. Patients with cardiogenic shock were excluded. Patients were stratified into two groups: PCI within 24 hours (early invasive group) and PCI over 24 hours (selective invasive group). Primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, non-fatal MI, repeat revascularization, and stroke at 12 months after index procedure. Early invasive group showed higher incidence of in-hospital death (9.4% vs 3.3%, P = .036) and cardiogenic shock (11.5% vs 4.6%, P = .030) after PCI. Early invasive group also showed higher maximum troponin I level during admission (27.7 ±â€…44.8 ng/mL vs 14.9 ±â€…24.6 ng/mL, P = .001), compared with the selective invasive group. Early invasive group had an increased risk of 12-month MACCE, compared with selective invasive group (25.6% vs 17.1%; adjusted HR = 2.10, 95% CI 1.17-3.77, P = .006). Among NSTEMI patients with severe LV dysfunction, the early invasive strategy did not improve the clinical outcomes. This data supports that an individualized approach may benefit high-risk NSTEMI patients rather than a routine invasive approach.

First-in-Human Evaluation of a Polymer-Free Everolimus-Eluting Stent Using a Titanium Dioxide Film.

BACKGROUND: In patients with coronary artery disease treated with permanent polymer-coated drug-eluting stents (DES), the persistent presence of a less biocompatible polymer might delay arterial healing. Thin strut polymer-free DES have the potential to improve clinical outcomes and reduce the duration of dual antiplatelet therapy (DAPT). The purpose of this first-in-human study was to assess the safety and effectiveness of a novel polymer-free DES in patients with de novo coronary lesions. The TIGERevolutioN® stent (CG Bio Co., Ltd., Seoul, Korea) consists of a cobalt chromium platform with a strut thickness of 70 µm and a surface treated with titanium dioxide onto which everolimus-eluting stent (EES) is applied abluminally (6 µg/mm of stent length) without utilization of a polymer. METHODS: A total of 20 patients were enrolled, with de novo coronary lesions (stable or unstable angina) and > 50% diameter stenosis in a vessel 2.25 to 4.00 mm in diameter and ≤ 40 mm in length for angiographic, optical coherence tomography (OCT), and clinical assessment at 8 months. All patients received DAPT after stent implantation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at 8 months. RESULTS: Twenty patients with 20 lesions were treated with TIGERevolutioN®. At 8 months, in-stent LLL was 0.7 ± 0.4 mm. On OCT, percent area stenosis was 29.2 ± 9.4% and stent strut coverage was complete in all lesions. No adverse cardiovascular event occurred at 8 months. CONCLUSION: The new polymer-free EES was safe and effective with low LLL and excellent strut coverage at 8 months of follow-up. TRIAL REGISTRATION: Trial Registration: Clinical Research Information Service Identifier: KCT0005699.

Pre-Hospital Delay and Outcomes in Myocardial Infarction With Nonobstructive Coronary Arteries.

BACKGROUND AND OBJECTIVES: Real-world evidence on the relationship between delayed hospitalization and outcomes in myocardial infarction with nonobstructive coronary arteries (MINOCA) is lacking. Hence, we aimed to evaluate the clinical characteristics of patients with MINOCA and the 2-year mortality outcomes in this patient population according to the symptom-to-door time (SDT). METHODS: Overall, 861 patients with MINOCA from 2 Korean nationwide observational registries (2011-2020) were included and categorized as early or late presenters. Late presentation was defined as SDT ≥12 hours in patients with ST-segment elevation myocardial infarction (STEMI) and SDT ≥24 hours in patients with non-STEMI. The primary outcome was 2-year all-cause mortality. Propensity score matching (PSM) and age-sex adjusted analysis were used to determine whether late presentation independently affected mortality. Multivariate logistic regression analysis was used to examine the independent factors correlated with late presentation. RESULTS: In unadjusted data, late presenters had a notably higher risk of 2-year all-cause mortality than early presenters (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.47-4.08). This trend persisted in age-sex adjusted analysis (adjusted HR, 2.29; 95% CI, 1.36-3.84) and PSM-adjusted analysis (adjusted HR, 2.18; 95% CI, 1.05-4.53). The positive independent factors for late presentation included female sex, no emergency medical service use and high creatinine level, whereas the negative independent factor was a dyslipidemia. CONCLUSIONS: Late presentation is associated with higher mortality in patients with MINOCA. Multidisciplinary efforts are needed to reduce pre-hospital delay, thereby improving the clinical outcomes in these patients.

Clinical outcomes of adjusted-dose versus standard-dose prasugrel in East Asian patients with acute myocardial infarction.

BACKGROUND: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI. METHODS: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups. RESULTS: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000). CONCLUSIONS: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE.

Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model.

BACKGROUND: A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests. METHODS: Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC). The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks. RESULTS: SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES). CONCLUSION: Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.

Optimal timing of percutaneous coronary intervention for non-ST elevated myocardial infarction with congestive heart failure.

OBJECTIVES: This study investigated the optimal timing for percutaneous coronary intervention (PCI) in patients with NSTEMI complicated by heart failure (HF). METHODS: In total, 762 patients with NSTEMI and HF in a multicenter, prospective registry in South Korea were classified according to the Killip classification (Killip class 2, n = 414 and Killip class 3, n = 348) and underwent early (within 24 h) and delayed (after 24 h) PCI. The primary outcome was all-cause mortality which was further analyzed with landmark analysis with two months as a cut-off. Secondary outcomes were cardiovascular death, in-hospital cardiogenic shock (CS), readmission due to HF, and acute myocardial infarction during follow-up. RESULTS: Delayed PCI was associated with lower rates of 2-month mortality (6.1 % vs. 15.8 %, p = 0.007) and in-hospital CS (4.3 % vs. 14.1 %, p = 0.003), along with lower risks of 2-month mortality (hazard ratio [HR] = 0.38, 95 % confidence interval [CI] = 0.18-0.83, p = 0.014), in-hospital CS (HR = 0.29, 95 % CI = 0.12-0.71, p = 0.006) in multivariate Cox models of Killip class 3 patients. There was no statistical difference of incidence and risk of all predefined outcomes according to varying timing of PCI in Killip 2 patients. CONCLUSIONS: Based on these results, the timing of PCI in patients with NSTEMI complicated by HF should be determined based on HF severity. Delayed PCI should be considered in patients with NSTEMI and more severe HF.

Timing of fractional flow reserve-guided complete revascularization in patients with ST-segment elevation myocardial infarction with multivessel disease: Rationale and design of the OPTION-STEMI trial.

BACKGROUND: Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA. METHODS: The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least 1 non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into 2 groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50%-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis was revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025. CONCLUSIONS: The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457.

Clinical Outcome after Everolimus-Eluting Stent Implantation for Small Vessel Coronary Artery Disease: XIENCE Asia Small Vessel Study.

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270). Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.

Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model.

BACKGROUND: Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models. METHODS: The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The in-vitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig's coronary artery. RESULTS: Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 µm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP: 118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGA-EES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGA-EES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced re-endothelialization. CONCLUSION: Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.

Time to presentation and mortality outcomes among patients with diabetes and acute myocardial infarction.

BACKGROUND/AIMS: Due to limited real-world evidence on the association between time to presentation (T2P) and outcomes following acute myocardial infarction and diabetes (AMI-DM), we investigated the characteristics of patients with AMI-DM and their outcomes based on their T2P. METHODS: 4,455 patients with AMI-DM from a Korean nationwide observational cohort (2011-2015) were divided into early and late presenters according to symptom-to-door time. The effects of T2P on three-year all-cause mortality were estimated using inverse probability of treatment weighting (IPTW) and survival analysis. RESULTS: The incidence of all-cause mortality was consistently higher in late presenters than in early presenters (11.4 vs. 17.2%; p < 0.001). In the IPTW-adjusted dataset, the incidence of all-cause mortality was numerically higher in late presenters than in early presenters (9.1 vs. 12.4%; p = 0.072). In the survival analysis, the cumulative incidence of all-cause mortality was significantly higher in late presenters than in early presenters before and after IPTW. In the subgroup with ST-elevation myocardial infarction, late presenters had a higher incidence of cardiac death than early presenters before (4.8 vs. 10.5%; p < 0.001) and after IPTW (4.2 vs. 9.7%; p = 0.034). In the initial glycated hemoglobin (HbA1c)-stratified analysis, these effects were attenuated in patients with HbA1c ≥ 9.0% before (adjusted hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 0.80-2.64) and after IPTW (adjusted HR: 0.82, 95% CI: 0.40-1.67). CONCLUSION: Late presentation was associated with higher mortality in patients with AMI-DM; therefore, multifaceted and systematic interventions are needed to decrease pre-hospital delays.

Early Left Ventricular Unloading or Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation: The EARLY-UNLOAD Randomized Clinical Trial.

BACKGROUND: Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) is beneficial for the treatment of profound cardiogenic shock, peripheral VA-ECMO cannulation can increase left ventricular afterload, thus compromising myocardial recovery. We investigated whether early routine left ventricular unloading can reduce 30-day mortality compared with the conventional approach in patients with cardiogenic shock undergoing VA-ECMO. METHODS: This randomized clinical trial involved 116 patients with cardiogenic shock undergoing VA-ECMO from March 2021 to September 2022 at Chonnam National University Hospital, Gwangju, South Korea. The patients were randomly assigned to undergo either early routine left ventricular unloading with transseptal left atrial cannulation within 12 hours after randomization (n=58) or the conventional approach, which permitted rescue transseptal left atrial cannulation in case of an increased left ventricular afterload (n=58). The primary outcome was all-cause mortality within 30 days. RESULTS: All 116 randomized patients (mean age, 67.6±13.5 years; 34 [29.3%] women) completed the trial. At 30 days, all-cause death had occurred in 27 (46.6%) patients in the early group and 26 (44.8%) patients in the conventional group (hazard ratio, 1.02 [95% CI, 0.59-1.74]; P=0.942). Crossover to rescue transseptal left atrial cannulation occurred in 29 patients (50%) in the conventional group according to a clear indication. Time to rescue transseptal cannulation in the conventional group was a median of 21.8 (interquartile range, 12.4-52.2) hours after randomization. There were no significant differences in other secondary outcomes between the 2 groups except for a shorter time to disappearance of pulmonary congestion in the early group (median, 3 [interquartile range, 2-6] versus 5 [interquartile range, 3-7] days; P=0.027). CONCLUSIONS: Among patients with cardiogenic shock undergoing VA-ECMO, early routine left ventricular unloading with transseptal left atrial cannulation did not reduce 30-day mortality compared with the conventional strategy, which permitted rescue transseptal left atrial cannulation. These findings should be cautiously interpreted until the results of multicenter trials using other unloading modalities become available. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04775472.

Impact of sex difference on clinical outcomes in acute myocardial infarction patients with single-vessel and multi-vessel disease: based on Korea Acute Myocardial Infarction Registry-National Institute of Health.

Background: Several studies have compared clinical outcomes according to sex in patients with acute myocardial infarction (AMI). However, studies evaluating sex differences in clinical outcomes of single-vessel disease (SVD) and multi-vessel disease (MVD) in Korean patients with AMI are lacking. Therefore, this study aimed to analyze sex differences in the clinical characteristics of patients with AMI with SVD and MVD and to evaluate the impact of sex differences on the clinical outcomes in patients with AMI with SVD and MVD. Methods: A total of 11,002 AMI patients from November 2011 to June 2015 in the Korea AMI Registry, National Institute of Health, were enrolled. The current study was retrospective observational study. Patients were divided into SVD (n=5,644) and MVD (n=5,358) groups, and clinical impact of sex difference were analyzed by propensity score matching analysis and Cox proportional hazard regression model. Results: Women were older and had poor baseline clinical characteristics than men. Propensity score-matched analysis of men and women with SVD and MVD revealed that the adjusted 3-year risk of major adverse cardiac event (MACE) (15.0% vs. 9.4%; hazard ratio, 1.86; 95% confidence interval, 1.10-3.13; P=0.020) was higher in women with SVD aged <65 years. However, the incidence and risk of MACE were similar for men and women with MVD, and those with SVD aged ≥65 years. Conclusions: In the present study of Korean patients with AMI, women were older and exhibited a higher prevalence of comorbidities than men. Women with SVD aged <65 years had a significantly higher risk of MACE.

De-escalation from ticagrelor to clopidogrel in patients with acute myocardial infarction: the TALOS-AMI HBR substudy.

BACKGROUND: The benefits of de-escalation of P2Y12 inhibition after percutaneous coronary intervention (PCI) may differ by high bleeding risk (HBR) status. AIMS: We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status. METHODS: This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspirin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria. RESULTS: A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84). CONCLUSIONS: In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y12 inhibition on reducing haemorrhagic events was greater in patients with HBR.

Early left ventricular unloading after extracorporeal membrane oxygenation: rationale and design of EARLY-UNLOAD trial.

AIMS: The clinical benefits of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for profound cardiogenic shock are well known. However, peripheral VA-ECMO increases the left ventricular afterload, thus compromising myocardial recovery. Recent studies have revealed the benefit of left ventricular unloading using various methods applied at different times. The EARLY-UNLOAD trial compares the clinical outcomes of early left ventricular unloading and conventional approach after VA-ECMO. METHODS AND RESULTS: The EARLY-UNLOAD trial is a single-centre, open-label, randomized trial that recruited 116 patients with cardiogenic shock undergoing VA-ECMO. Patients meeting the inclusion criteria were randomized in a 1:1 ratio to two groups: routine left ventricular unloading via intracardiac echocardiography-guided transseptal left atrial cannulation within 12 h of VA-ECMO initiation or conventional approach that indicates rescue left ventricular unloading if clinical signs of an increased left ventricular afterload are present. The primary endpoint is the cumulative incidence of all-cause death within 30 days, and patients will be followed-up for 12 months. A key secondary endpoint is a composite measure of all-cause death and rescue transseptal left atrial cannulation in the conventional group (suggestive of VA-ECMO treatment failure) within 30 days. The enrolment of patients was finished in September 2022. CONCLUSIONS: The EARLY-UNLOAD trial is the first randomized controlled trial to compare early left ventricular unloading and conventional approach after VA-ECMO using the same unloading modality. The results could impact clinical practice to overcome the haemodynamic issues associated with VA-ECMO.

Culprit lesion plaque characteristics and angiopoietin like 4 in acute coronary syndrome: A virtual histology-intravascular ultrasound analysis.

BACKGROUND: Thin-cap fibroatheroma is a rupture-prone vulnerable plaque that leads to acute coronary syndrome (ACS). However, its underlying mechanisms are not fully understood. Several studies have investigated the clinical association between angiopoietin-like protein 4 (ANGPTL4) and coronary artery disease. Therefore, this study aimed to investigate the correlation of plasma ANGPTL4 in culprit lesion of ACS patients using intravascular ultrasound (IVUS) and virtual-histology IVUS (VH-IVUS). METHODS: Fifty patients newly diagnosed with ACS between March to September 2021 were selected. Blood samples for baseline laboratory tests, including ANGPTL4, were collected before percutaneous coronary intervention (PCI), and all pre- and post-PCI IVUS examinations were performed of the culprit lesions. RESULTS: Linear regression analysis between plasma ANGPTL4 and grayscale IVUS/VH-IVUS parameters revealed that plasma ANGPTL4 was strongly correlated with the necrotic core (NC) of the minimal lumen site (r = -0.666, p = 0.003) and largest NC site (r = -0.687, p < 0.001), and patients with lower plasma ANGPTL4 levels showed a significantly higher proportion of TFCA. CONCLUSION: The present study further demonstrated the protective role of ANGPTL4 in the spectrum of atherosclerotic development in patients with ACS by culprit lesion morphology analysis using IVUS and VH-IVUS.

Incidence, Relevant Patient Factors, and Clinical Outcomes of the Misdiagnosis of ST-Segment-Elevation Myocardial Infarction: Results From the Korea Acute Myocardial Infarction Registry.

Background Data on the incidence, relevant patient factors, and clinical outcomes of the misdiagnosis of ST-segment-elevation myocardial infarction (STEMI) in the modern era of percutaneous coronary intervention are limited. Methods and Results Data from KAMIR (Korea Acute Myocardial Infarction Registry) between November 2011 and June 2020 were analyzed. Out of 28 470 patients with acute myocardial infarction, 11 796 were eventually diagnosed with STEMI following a coronary angiogram. They were classified into 2 groups: patients with an initial working diagnosis of STEMI before starting the initial treatment and patients with an initial working diagnosis of non-STEMI (misdiagnosed group). Out of 11 796 patients with a final diagnosis of STEMI, 165 (1.4%) were misdiagnosed. The door-to-angiography time in the misdiagnosed group was 5 times longer than that in the timely diagnosed group (median 220 [interquartile range {IQR}, 66-1177] versus 43 [IQR, 31-58] minutes; P<0.001). In a multivariable adjustments model, patients with a history of heart failure, atypical chest pain, anemia, or symptom-to-door time ≥4 hours had significantly higher odds, whereas those with systolic blood pressure <100 mm Hg or anterior ST elevation or left bundle-branch block on ECG had lower odds of STEMI misdiagnosis. For patients with culprit lesions in the left anterior descending artery (n=5838), the adjusted 1-year mortality risk for STEMI misdiagnosis was 1.84 (95% CI, 1.01-3.38). Conclusions Misdiagnosis of STEMI is not rare and is associated with a significant delay in coronary angiography, resulting in increased 1-year mortality for patients with culprit lesions in the left anterior descending artery.

Renin-Angiotensin-Aldosterone System Inhibitions and Cardiovascular Outcomes in Acute Myocardial Infarction With Renal Impairment.

OBJECTIVE: To compare the clinical outcomes of patients with acute myocardial infarction with renal impairment (AMI-RI) treated with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in real-world clinical settings. PATIENTS AND METHODS: A total of 4790 consecutive patients with AMI-RI between November 1, 2011, and December 31, 2015, were subdivided into ACEI (n=2845) and ARB (n=1945) treatment groups. The primary end points were major adverse cardiac and cerebrovascular events, including all-cause mortality, nonfatal myocardial infarction, any revascularization, cerebrovascular accident, rehospitalization, and stent thrombosis. Propensity score matching (PSM) was used to adjust for group differences. RESULTS: The ARB group had a significantly higher incidence of major adverse cardiac and cerebrovascular events (at 3-year follow-up) than the ACEI group according to the unadjusted analysis (3-year hazard ratio [HR], 1.60; 95% CI, 1.43 to 1.78) and the PSM-adjusted analysis (3-year HR, 1.34; 95% CI, 1.15 to 1.56). However, any revascularization (3-year HR, 1.21; 95% CI, 0.95 to 1.54) and rehospitalization (3-year HR, 1.21; 95% CI, 0.88 to 1.67) were not significantly different between groups in the PSM-adjusted analysis. Compared with the ARB group, the ACEI group had lower rates of all-cause mortality at estimated glomerular filtration rates of at least 15 or less than 90 mL/min/1.73 m2 in the unadjusted data and at least 60 or less than 90 mL/min/1.73 m2 in the PSM-adjusted analysis. CONCLUSION: Treatment with ACEIs seemed to be more beneficial than treatment with ARBs for patients with AMI-RI; further prospective studies are required to confirm these results.

Baseline Lipoprotein(a) Levels and Long-Term Cardiovascular Outcomes After Acute Myocardial Infarction.

BACKGROUND: Lipoprotein(a) is a known independent risk factor for atherosclerotic cardiovascular disease. However, the prognostic impact of the baseline lipoprotein(a) levels on long-term clinical outcomes among patients with acute myocardial infarction remain unclear. METHODS: We analyzed 1,908 patients with acute myocardial infarction from November 2011 to October 2015 from a single center in Korea. They were divided into 3 groups according to their baseline lipoprotein(a) levels: groups I (< 30 mg/dL, n = 1,388), II (30-49 mg/dL, n = 263), and III (≥50 mg/dL, n = 257). Three-point major adverse cardiovascular events (a composite of nonfatal myocardial infarction, nonfatal stroke, and cardiac death) at 3 years were compared among the 3 groups. RESULTS: The patients were followed for 1094.0 (interquartile range, 1,033.8-1,095.0) days, during which a total of 326 (17.1%) three-point major adverse cardiovascular events occurred. Group III had higher rates of three-point major adverse cardiovascular events compared with Group I (23.0% vs. 15.7%; log-rank P = 0.009). In the subgroup analysis, group III had higher rates of three-point major adverse cardiovascular events compared with group I in patients with non-ST-segment elevation myocardial infarction (27.0% vs. 17.1%; log-rank P = 0.006), but not in patients with ST-segment elevation myocardial infarction (14.4% vs. 13.3%; log-rank P = 0.597). However, in multivariable Cox time-to-event models, baseline lipoprotein(a) levels were not associated with an increased incidence of three-point major adverse cardiovascular events, regardless of the type of acute myocardial infarction. Sensitivity analyses in diverse subgroups showed similar findings to those of the main analysis. CONCLUSION: Baseline lipoprotein(a) levels in Korean patients with acute myocardial infarction were not independently associated with increased major adverse cardiovascular events at 3 years.

Preclinical Evaluation of an Everolimus-Eluting Bioresorbable Vascular Scaffold Via a Long-Term Rabbit Iliac Artery Model.

BACKGROUND: Biodegradable poly (l-lactic acid) (PLLA), a bio safe polymer with a large elastic modulus, is widely used in biodegradable medical devices. However, because of its poor mechanical properties, a PLLA strut must be made twice as thick as a metal strut for adequate blood vessel support. Therefore, the mechanical properties of a drug-eluting metal-based stents (MBS) and a bioresorbable vascular scaffolds (BVS) were evaluated and their safety and efficacy were examined via a long-term rabbit iliac artery model. METHODS: The surface morphologies of the MBSs and BVSs were investigated via optical and scanning electron microscopy. An everolimus-eluting (EE) BVS or an EE-MBS was implanted into rabbit iliac arteries at a 1.1:1 stent-to-artery ratio. Twelve months afterward, stented iliac arteries from each group were analyzed via X-ray angiography, optical coherence tomography (OCT), and histopathologic evaluation. RESULTS: Surface morphology analysis of the EE coating on the MBS confirmed that it was uniform and very thin (4.7 µm). Comparison of the mechanical properties of the EE-MBS and EE-BVS showed that the latter outperformed the former in all aspects (radial force (2.75 vs. 0.162 N/mm), foreshortening (0.24% vs. 1.9%), flexibility (0.52 vs. 0.19 N), and recoil (3.2% vs. 6.3%). At all time points, the percent area restenosis was increased in the EE-BVS group compared to the EE-MBS group. The OCT and histopathological analyses indicate no significant changes in strut thickness. CONCLUSION: BVSs with thinner struts and shorter resorption times should be developed. A comparable long-term safety/efficacy evaluation after complete absorption of BVSs should be conducted.