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.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Intravascular imaging-guided percutaneous coronary intervention in patients with acute myocardial infarction and cardiogenic shock.

INTRODUCTION AND OBJECTIVES: There are no clinical data on the efficacy of intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI in patients with acute myocardial infarction (AMI) and cardiogenic shock. The current study sought to evaluate the impact of intravascular imaging-guided PCI in patients with AMI and cardiogenic shock. METHODS: Among a total of 28 732 patients from the nationwide pooled registry of KAMIR-NIH (November, 2011 to December, 2015) and KAMIR-V (January, 2016 to June, 2020), we selected a total of 1833 patients (6.4%) with AMI and cardiogenic shock who underwent PCI of the culprit vessel. The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, a composite of cardiac death, myocardial infarction, repeat revascularization, and definite or probable stent thrombosis. RESULTS: Among the study population, 375 patients (20.5%) underwent intravascular imaging-guided PCI and 1458 patients (79.5%) underwent angiography-guided PCI. Intravascular imaging-guided PCI was associated with a significantly lower risk of 1-year MACE than angiography-guided PCI (19.5% vs 28.2%; HR, 0.59; 95%CI, 0.45-0.77; P<.001), mainly driven by a lower risk of cardiac death (13.7% vs 24.0%; adjusted HR, 0.53; 95%CI, 0.39-0.72; P<.001). These results were consistent in propensity score matching (HR, 0.68; 95%CI, 0.46-0.99), inverse probability weighting (HR, 0.61; 95%CI, 0.45-0.83), and Bayesian analysis (Odds ratio, 0.66, 95% credible interval, 0.49-0.88). CONCLUSIONS: In AMI patients with cardiogenic shock, intravascular imaging-guided PCI was associated with a lower risk of MACE at 1-year than angiography-guided PCI, mainly driven by the lower risk of cardiac death.

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.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Non-ST-Elevation Myocardial Infarction.

BACKGROUND: Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI).Methods and Results: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. CONCLUSIONS: In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

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.

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.

Gallic Acid Inhibits Proliferation and Migration of Smooth Muscle Cells in a Pig In-Stent Restenosis Model.

In-stent restenosis (ISR) develops primarily due to neointimal hyperplasia. Gallic acid (GA) has anti-inflammatory, antioxidant, and cardioprotective effects. This study sought to investigate the effects of GA on neointimal hyperplasia and proliferation and migration of vascular smooth muscle cells (VSMCs) in a pig ISR model. In vitro proliferation and migration experiments were confirmed, after VSMCs were treated with platelet-derived growth factor (PDGF-BB) and GA (100 µM) using a 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay and a scratch wound assay for 24 hours and 48 hours. A bare metal stent (BMS) was implanted in the pig coronary artery to induce ISR with overdilation (1.1-1.2:1), and GA (10 mg/kg/day) was administered for 4 weeks. At the 4-week follow-up, optical coherence tomography (OCT) and histopathological analyses were performed. GA decreased the proliferation of VSMCs by PDGF-BB for 24 hours (89.24±24.56% vs. 170.04±19.98%, p<0.001) and 48 hours (124.87±7.35% vs. 187.64±4.83%, p<0.001). GA inhibited the migration of VSMCs induced by PDGF-BB for 24 hours (26.73±2.38% vs. 65.38±9.73%, p<0.001) and 48 hours (32.96±3.04% vs. 77.04±10.07%, p<0.001). Using OCT, % neointimal hyperplasia was shown to have significantly decreased in the GA group compared with control vehicle group (28.25±10.07% vs. 37.60±10.84%, p<0.001). GA effectively reduced neointimal hyperplasia by inhibiting the proliferation and migration of VSMCs in a pig ISR model. GA could be a potential treatment strategy for reducing ISR after stent implantation.

Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial.

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.

Cost-Effectiveness of Fractional Flow Reserve-Guided Treatment for Acute Myocardial Infarction and Multivessel Disease: A Prespecified Analysis of the FRAME-AMI Randomized Clinical Trial.

Importance: Complete revascularization by non-infarct-related artery (IRA) percutaneous coronary intervention (PCI) in patients with acute myocardial infarction is standard practice to improve patient prognosis. However, it is unclear whether a fractional flow reserve (FFR)-guided or angiography-guided treatment strategy for non-IRA PCI would be more cost-effective. Objective: To evaluate the cost-effectiveness of FFR-guided compared with angiography-guided PCI in patients with acute myocardial infarction and multivessel disease. Design, Setting, and Participants: In this prespecified cost-effectiveness analysis of the FRAME-AMI randomized clinical trial, patients were randomly allocated to either FFR-guided or angiography-guided PCI for non-IRA lesions between August 19, 2016, and December 24, 2020. Patients were aged 19 years or older, had ST-segment elevation myocardial infarction (STEMI) or non-STEMI and underwent successful primary or urgent PCI, and had at least 1 non-IRA lesion (diameter stenosis >50% in a major epicardial coronary artery or major side branch with a vessel diameter of ≥2.0 mm). Data analysis was performed on August 27, 2023. Intervention: Fractional flow reserve-guided vs angiography-guided PCI for non-IRA lesions. Main Outcomes and Measures: The model simulated death, myocardial infarction, and repeat revascularization. Future medical costs and benefits were discounted by 4.5% per year. The main outcomes were quality-adjusted life-years (QALYs), direct medical costs, incremental cost-effectiveness ratio (ICER), and incremental net monetary benefit (INB) of FFR-guided PCI compared with angiography-guided PCI. State-transition Markov models were applied to the Korean, US, and European health care systems using medical cost (presented in US dollars), utilities data, and transition probabilities from meta-analysis of previous trials. Results: The FRAME-AMI trial randomized 562 patients, with a mean (SD) age of 63.3 (11.4) years. Most patients were men (474 [84.3%]). Fractional flow reserve-guided PCI increased QALYs by 0.06 compared with angiography-guided PCI. The total cumulative cost per patient was estimated as $1208 less for FFR-guided compared with angiography-guided PCI. The ICER was -$19 484 and the INB was $3378, indicating that FFR-guided PCI was more cost-effective for patients with acute myocardial infarction and multivessel disease. Probabilistic sensitivity analysis showed consistent results and the likelihood iteration of cost-effectiveness in FFR-guided PCI was 97%. When transition probabilities from the pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials were used, FFR-guided PCI was more cost-effective than angiography-guided PCI in the Korean, US, and European health care systems, with an INB of $3910, $8557, and $2210, respectively. In probabilistic sensitivity analysis, the likelihood iteration of cost-effectiveness with FFR-guided PCI was 85%, 82%, and 31% for the Korean, US, and European health care systems, respectively. Conclusions and Relevance: This cost-effectiveness analysis suggests that FFR-guided PCI for non-IRA lesions saved medical costs and increased quality of life better than angiography-guided PCI for patients with acute myocardial infarction and multivessel disease. Fractional flow reserve-guided PCI should be considered in determining the treatment strategy for non-IRA stenoses in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02715518.

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.

Angiographic Severity of the Nonculprit Lesion and the Efficacy of Fractional Flow Reserve-Guided Complete Revascularization in Patients With AMI: FRAME-AMI Substudy.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for noninfarct-related artery (IRA) lesions with angiographically severe stenosis in patients with acute myocardial infarction is unclear. METHODS: Among 562 patients from the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infraction Related Artery Stenosis in Patients With Acute Myocardial Infarction) who were randomly allocated into either FFR-guided or angiography-guided PCI for non-IRA lesions, the current study evaluated the relationship between non-IRA stenosis measured by quantitative coronary angiography (QCA) and the efficacy of FFR-guided PCI. The incidence of the primary end point (death, myocardial infarction, or repeat revascularization) was compared between FFR- and angiography-guided PCI according to non-IRA stenosis severity (QCA stenosis ≥70% or <70%). RESULTS: A total of 562 patients were assigned to FFR-guided (n=284) versus angiography-guided PCI (n=278). At a median follow-up of 3.5 years, the primary end point occurred in 14 of 181 patients with FFR-guided PCI and 31 of 197 patients with angiography-guided PCI among patients with QCA stenosis ≥70% (8.5% versus 19.2%; hazard ratio, 0.41 [95% CI, 0.22-0.80]; P=0.008), while occurred in 4 of 103 patients with FFR-guided PCI and 9 of 81 patients with angiography-guided PCI among those with QCA stenosis <70% (3.9% versus 11.1%; P=0.315). There was no significant interaction between treatment strategy and non-IRA stenosis severity (P for interaction=0.636). FFR-guided PCI was associated with the reduction of death and myocardial infarction in both patients with QCA stenosis ≥70% (6.7% versus 15.1%; P=0.008) and those with QCA stenosis <70% (1.0% versus 9.6%; P=0.042) compared with angiography-guided PCI. CONCLUSIONS: In patients with acute myocardial infarction and multivessel disease, FFR-guided PCI tended to have a lower risk of primary end point than angiography-guided PCI regardless of non-IRA stenosis severity without significant interaction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

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.

Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound.

BACKGROUND: Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have shown comparable outcomes in guiding percutaneous coronary intervention (PCI). However, their comparative effectiveness in complex coronary artery lesions remains unclear. OBJECTIVES: This study compared the effectiveness and safety of OCT-guided vs IVUS-guided PCI for complex coronary artery lesions. METHODS: This was a prespecified, main subgroup analysis of complex coronary artery lesions in the OCTIVUS (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention) trial, which included unprotected left main disease, bifurcation disease, an aorto-ostial lesion, a chronic total occlusion, a severely calcified lesion, an in-stent restenotic lesion, a diffuse long lesion, or multivessel PCI. The primary endpoint was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization. RESULTS: In 2,008 randomized patients, 1,475 (73.5%) underwent imaging-guided PCI for complex coronary artery lesions; 719 (48.7%) received OCT-guided and 756 (51.3%) IVUS-guided PCI. At a median follow-up of 2.0 years, primary endpoint event had occurred in 47 patients (6.5%) in the OCT-guided group and in 56 patients (7.4%) in the IVUS-guided group (HR: 0.87; 95% CI: 0.59-1.29; P = 0.50). These findings were consistent in adjusted analyses. The incidence of contrast-induced nephropathy was similar between the 2 groups (1.9% vs 1.5%; P = 0.46). The incidence of major procedural complications was lower in the OCT-guided group than in the IVUS-guided group (1.7% vs 3.4%; P = 0.03). CONCLUSIONS: Among patients with complex coronary artery lesions, OCT-guided PCI showed a similar risk of primary composite event of death from cardiac causes, target vessel-related myocardial infarction, or target vessel revascularization as compared with IVUS-guided PCI. (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention [OCTIVUS]; NCT03394079).

Significant Gap Between Guidelines and Practice in the Management of LDL Cholesterol: Insight From the Survey of the Korean Society of Myocardial Infarction.

The Guidelines of the 2019 European Society of Cardiology (ESC) and the 5th Society of Lipid and Atherosclerosis (KSoLA) for the Management of Dyslipidemia advocate a more intensive lipid-lowering strategy. However, there is a lack of evidence regarding the current status of lipid management in Korean patients in real-world practice. The Korean Society of Myocardial Infarction conducted a survey among its members of the Korean Society of Cardiology on the new lipid guidelines. Although most participants were aware of the changes in the ESC and the KSoLA guidelines, more than half of them did not agree with lowering the low-density lipoprotein cholesterol levels to < 55 mg/dL, because its safety and efficacy have not yet been proven in Koreans. A substantial disparity exists between lipid management guidelines and current clinical practices, highlighting the necessity for clinical research that specifically targets East Asians and Koreans to bridge this gap.

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

Remote epitaxial interaction through graphene.

The concept of remote epitaxy involves a two-dimensional van der Waals layer covering the substrate surface, which still enable adatoms to follow the atomic motif of the underlying substrate. The mode of growth must be carefully defined as defects, e.g., pinholes, in two-dimensional materials can allow direct epitaxy from the substrate, which, in combination with lateral epitaxial overgrowth, could also form an epilayer. Here, we show several unique cases that can only be observed for remote epitaxy, distinguishable from other two-dimensional material-based epitaxy mechanisms. We first grow BaTiO3 on patterned graphene to establish a condition for minimizing epitaxial lateral overgrowth. By observing entire nanometer-scale nuclei grown aligned to the substrate on pinhole-free graphene confirmed by high-resolution scanning transmission electron microscopy, we visually confirm that remote epitaxy is operative at the atomic scale. Macroscopically, we also show variations in the density of GaN microcrystal arrays that depend on the ionicity of substrates and the number of graphene layers.

QFR Assessment and Prognosis After Nonculprit PCI in Patients With Acute Myocardial Infarction.

BACKGROUND: Complete revascularization using either angiography-guided or fractional flow reserve (FFR)-guided strategy can improve clinical outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, there is concern that angiography-guided percutaneous coronary intervention (PCI) may result in un-necessary PCI of the non-infarct-related artery (non-IRA), and its long-term prognosis is still unclear. OBJECTIVES: This study sought to evaluate clinical outcomes after non-IRA PCI according to the quantitative flow ratio (QFR). METHODS: We performed post hoc QFR analysis of non-IRA lesions of AMI patients enrolled in the FRAME-AMI (FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease) trial, which randomly allocated 562 patients into either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis >50%) for non-IRA lesions. Patients were classified by non-IRA QFR values into the QFR ≤0.80 and QFR >0.80 groups. The primary outcome was a major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, and repeat revascularization. RESULTS: A total of 443 patients (552 lesions) were eligible for QFR analysis. Of 209 patients in the angiography-guided PCI group, 30.0% (n = 60) underwent non-IRA PCI despite having QFR >0.80 in the non-IRA. Conversely, only 2.7% (n = 4) among 209 patients in the FFR-guided PCI group had QFR >0.80 in the non-IRA. At a median follow-up of 3.5 years, the rate of MACEs was significantly higher among patients with non-IRA PCI despite QFR >0.80 than in patients with deferred PCI for non-IRA lesions (12.9% vs 3.1%; HR: 4.13; 95% CI: 1.10-15.57; P = 0.036). Non-IRA PCI despite QFR >0.80 was associated with a higher risk of non-IRA MACEs than patients with deferred PCI for non-IRA lesions (12.9% vs 2.1%; HR: 5.44; 95% CI: 1.13-26.19; P = 0.035). CONCLUSIONS: In AMI patients with multivessel disease, 30.0% of angiography-guided PCI resulted in un-necessary PCI for the non-IRA with QFR >0.80, which was significantly associated with an increased risk of MACEs than in those with deferred PCI for non-IRA lesions. (FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease [FRAME-AMI] ClinicalTrials.gov number; NCT02715518).