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Aims Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS. Methods and results Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints. Conclusion In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy. Study registration number This study was registered in the PROSPERO (ID: CRD42021245477).

Data regarding the relationship between malnutrition and clinical outcomes of acute myocardial infarction (AMI) is limited. The study aims to evaluate the clinical impact of malnutrition in AMI patients after percutaneous coronary intervention (PCI).The COREA-AMI registries identified 10,161 AMI patients who underwent PCI from January 2004 to August 2014. Patients with geriatric nutritional risk index (GNRI) scores of82, 82 to92, 92 to98, and ≥98 were categorized as having severe, moderate, mild malnutrition risk, and absence of risk, respectively. Associations of GNRI with Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding, all-cause death, and major cardiovascular events (MACEs; a composite of cardiovascular death, myocardial infarction, or ischemic stroke) were evaluated. Over 50% of AMI patients were malnourished, with 25.0%, 22.7%, and 4.9% having mild, moderate, and severe malnutrition risks, respectively. Over a median 4.9-year follow-up, patients with malnutrition risk had higher risks of BARC 3 or 5 bleeding (adjusted hazard ratios [aHRs], 1.27, 1.55, and 2.02 for mild, moderate, and severe, respectively; p 0.001), all-cause death (aHRs, 1.26, 1.46, and 1.85 for mild, moderate, and severe, respectively; p 0.001), and MACEs (aHRs, 1.14, 1.32, and 1.67 for mild, moderate, and severe, respectively; p 0.001) than patients without risk.Elevated malnutrition risk was common among AMI patients undergoing PCI and was strongly associated with a higher risk of major bleeding, all-cause death, and major ischemic events.

Aims In patients with acute myocardial infarction (MI) and multivessel coronary artery disease, percutaneous coronary intervention (PCI) of non-infarct-related artery reduces death or MI. However, whether selective PCI guided by fractional flow reserve (FFR) is superior to routine PCI guided by angiography alone is unclear. The current trial sought to compare FFR-guided PCI with angiography-guided PCI for non-infarct-related artery lesions among patients with acute MI and multivessel disease. Methods and results Patients with acute MI and multivessel coronary artery disease who had undergone successful PCI of the infarct-related artery were randomly assigned to either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct-related artery lesions. The primary end point was a composite of time to death, MI, or repeat revascularization. A total of 562 patients underwent randomization. Among them, 60.0% underwent immediate PCI for non-infarct-related artery lesions and 40.0% were treated by a staged procedure during the same hospitalization. PCI was performed for non-infarct-related artery in 64.1% in the FFR-guided PCI group and 97.1% in the angiography-guided PCI group, and resulted in significantly fewer stent used in the FFR-guided PCI group (2.2 ± 1.1 vs. 2.5 ± 0.9, P < 0.001). At a median follow-up of 3.5 years (interquartile range: 2.7–4.1 years), the primary end point occurred in 18 patients of 284 patients in the FFR-guided PCI group and in 40 of 278 patients in the angiography-guided PCI group (7.4% vs. 19.7%; hazard ratio, 0.43; 95% confidence interval, 0.25–0.75; P = 0.003). The death occurred in five patients (2.1%) in the FFR-guided PCI group and in 16 patients (8.5%) in the angiography-guided PCI group; MI in seven (2.5%) and 21 (8.9%), respectively; and unplanned revascularization in 10 (4.3%) and 16 (9.0%), respectively. Conclusion In patients with acute MI and multivessel coronary artery disease, a strategy of selective PCI using FFR-guided decision-making was superior to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-infarct-related artery lesions regarding the risk of death, MI, or repeat revascularization.

The role of statins after endovascular abdominal aortic aneurysm repair (EVAR) has not been well established in an Asian context. In this study, the use of statins and their association with long-term health outcomes were evaluated in patients undergoing EVAR using the Korean National Health Insurance Service database. Among the 8893 patients who underwent EVAR from 2008 to 2018, 3386 (38.1%) were on statins prior to the procedure. Patients using statins had a higher prevalence of comorbidities, such as hypertension (88.4% vs. 71.5%), diabetes mellitus (24.5% vs. 14.1%), and heart failure (21.6% vs. 13.1%), compared with non-users (all p < 0.001). After propensity score matching, statin use prior to EVAR was associated with a lower risk of all-cause mortality (HR 0.85, 95% CI 0.78–0.92, p < 0.001) and cardiovascular mortality (HR 0.66, 95% CI 0.51–0.86, p = 0.002). Statin use following EVAR was associated with a lower risk of adverse events, but not significantly so. Patients on statins both preceding and following EVAR had a lower risk of all-cause mortality (HR 0.82, 95% CI 0.73–0.91, p < 0.001) and cardiovascular mortality (HR 0.62, 95% CI 0.44–0.87, p = 0.007), compared with statin non-users. Among Korean patients undergoing EVAR, the persistent use of statins prior to and after the procedure was associated with a lower risk of mortality, compared with non-statin users.

An elevated heart rate at admission or discharge is known to be associated with poor cardiovascular outcomes in patients with acute myocardial infarction (AMI). The association between post-discharge average office-visit heart rate and cardiovascular outcomes in patients with AMI has rarely been studied. We analyzed data for 7840 patients from the COREA-AMI registry who had their heart rates measured at least three times after hospital discharge. The office-visit heart rates were averaged and categorized into four groups by quartiles (80 beats per minute). The primary end point was a composite of cardiovascular death, myocardial infarction, and ischemic stroke. During a median of 5.7 years of follow-up, major adverse cardiovascular events (MACE) affected 1357 (17.3%) patients. An average heart rate higher than 80 bpm was associated with an increased incidence of MACE compared to the reference average heart rate of 68–74 bpm. When dichotomized into

Background: Data regarding prognosis and management after nuisance bleeding (NB) is limited. The purpose was to examine the prognostic significance of NB in patients receiving potent dual antiplatelet treatment (DAPT) after acute myocardial infarction and the impact of de-escalation of DAPT on clinical outcomes thereafter. Methods: From the TALOS-AMI trial (Ticagrelor Versus Clopidogrel in Stabilized Patients With Acute Myocardial Infarction)‚ 2583 patients were used to investigate the clinical impact of NB (defined as Bleeding Academic Research Consortium [BARC] 1 bleeding) during 1-month treatment with ticagrelor-based DAPT after acute myocardial infarction. We assessed the associations between NB within 1 month and BARC 2, 3, or 5 bleeding and major adverse cardiovascular event (a composite of cardiovascular death, myocardial infarction, stroke) from 1 to 12 months. We also evaluated the effect of de-escalation to clopidogrel in patients with or without NB. Results: NB occurred in 416 patients (16.7%) after 1 month of ticagrelor-based DAPT. At 1 year, NB was not associated with increase in BARC 2, 3, or 5 bleeding (hazard ratio [HR]‚ 1.29 [95% CI‚ 0.7–2.14]) and major adverse cardiovascular event (HR‚ 1.72 [95% CI‚ 0.87–3.39]). However, patients with NB had an increased risk of BARC 2, 3, or 5 bleeding at 6 months (HR, 1.94 [95% CI, 1.08–3.48]; P =0.026), which diminished over the next 6 months. De-escalation from ticagrelor to clopidogrel reduced the incidence of BARC 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in NB (HR‚ 0.31 [95% CI‚ 0.10–0.92]) and non-NB patients (HR‚ 0.58 [95% CI‚ 0.37–0.90]) without heterogeneity ( P interaction=0.291). There was no increase in major adverse cardiovascular event after DAPT de-escalation, irrespective of NB. Conclusions: NB was frequent in patients with acute myocardial infarction on 1-month ticagrelor-based DAPT and was associated with an early increase of bleeding. DAPT de-escalation after NB may reduce bleeding without increasing ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02018055.

Objectives The aim of this study was to examine the impact of intravascular ultrasound (IVUS)–guided percutaneous coronary intervention (PCI) on long-term clinical outcomes in patients wit...

Summary Background In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction. Methods In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055. Findings From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (pnon-inferiority Interpretation In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events. Funding ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.

The relationship between visit-to-visit blood pressure variability (BPV) and cardiovascular outcomes remains unclear. Our study assessed the prognostic implications of visit-to-visit BPV in patients after acute myocardial infarction (AMI). The present study enrolled 7,375 patients who underwent percutaneous coronary intervention for AMI and at least five measurements of blood pressure after hospital discharge. Visit-to-visit BPV was estimated as variability independent of mean. The primary endpoint was all-cause mortality. The secondary endpoints were major cardiovascular events (the composite of cardiovascular death, myocardial infarction, and ischemic stroke) and hospitalization for heart failure. During a median follow-up of 5.8 years, adjusted risks of all-cause mortality, major cardiovascular events, and hospitalization for heart failure continuously increased as systolic BPV and diastolic BPV increased. Patients in the highest quartile of systolic BPV (versus lowest) had increased risk of all-cause mortality (adjusted hazard ratio (aHR) 1.51 [95% confidence interval (CI) 1.23-1.85]), major cardiovascular events (aHR 1.31 [95% CI 1.1-1.55]), and hospitalization for heart failure (aHR 2.15 [95% CI 1.49-3.1]). Patients in the highest quartile of diastolic BPV was also associated with all-cause mortality (aHR 1.39 [95% CI 1.14-1.7]), major cardiovascular events (aHR 1.29 [95% CI 1.08-1.53]), and hospitalization for heart failure (aHR 2.01[95% CI 1.4-2.87]). Both systolic and diastolic BPV improved the predictive ability of the GRACE (Global Registry of Acute Coronary Events) risk score for both all-cause mortality and major cardiovascular events. Higher visit-to-visit BPV was associated with increased risks of mortality and cardiovascular events in patients after AMI.

Background Potent P2Y12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS. Methods The EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting). Results A total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56–2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups. Conclusions Dual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI. Trial registration: KCT0002356, registered June 13, 2017.

Aims In patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), the risk of ischaemic complications is highest in the early phase (during the first 30 days), while most bleeding events occur predominantly during the maintenance phase of treatment (after the first 30 days). Data on the de-escalation of dual antiplatelet therapy by switching from ticagrelor to clopidogrel in stabilised AMI patients are limited. The aim of this study is to investigate the efficacy and safety of switching from ticagrelor to clopidogrel in AMI patients with no adverse event during the first month after the index PCI with newer-generation DES. Methods and results TALOS-AMI is a multicentre, randomised, open-label study enrolling 2,590 AMI patients with no adverse events during the first month after the index PCI. One month after the index PCI, eligible patients are randomly assigned either to 1) aspirin 100 mg plus clopidogrel 75 mg daily, or to 2) aspirin 100 mg plus ticagrelor 90 mg twice daily, in a 1:1 ratio. The primary endpoint is a composite of cardiovascular death, MI, stroke, and bleeding type 2, 3 or 5 according to the Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months after the index PCI. Conclusions The TALOS-AMI trial is the first large-scale, multicentre, randomised study exploring the efficacy and safety of the de-escalation of antiplatelet therapy by switching from ticagrelor to clopidogrel in stabilised AMI patients undergoing PCI.

BACKGROUND Systemic effects of long-term narrowband ultraviolet B (NB-UVB) phototherapy have not been well studied in vitiligo patients. An 11-year nationwide population-based retrospective cohort study was conducted using the Korean National Health Insurance claims database (2007-2017). OBJECTIVES To investigate the effects of long-term NB-UVB phototherapy on the risk of cardiovascular and cerebrovascular events in vitiligo patients. METHODS This study included vitiligo patients with ≥100 phototherapy sessions (phototherapy group, n = 3229) and

Current stem cell-based therapy for cardiac repair and regeneration after myocardial infarction (MI) is not readily translatable into clinical scenarios due to the low retention and survival of the transplanted cells. Here, we evaluated a simple and feasible design of gelatin-hydroxyphenyl propionic acid (GH) hydrogel as an in situ cross-linkable and injectable cell delivery platform for cardiac tissue regeneration. The GH hydrogel exhibited improved cell retention and survival in vitro and in vivo when encapsulating mouse bone marrow-derived mesenchymal stem cells (MSCs) that were used as promising therapeutic candidates for stem cell therapy. Moreover, we demonstrated that MSC-encapsulating GH hydrogels led to a significant improvement in cardiac functional metrics, such as the fractional shortening (FS), ejection fraction (EF), and end-systolic volume (ESV). Similarly, MSC-encapsulating GH hydrogels induced favorable effects in the cardiac structures of the infarcted heart, producing less fibrosis and thicker infarcted walls. These results suggest that GH hydrogels can be used as an instructive cell delivery platform to provide a suitable microenvironment for transplanted cells; therefore, their in vivo applications combined with MSCs may provide great potential for repair and regeneration of injured cardiac tissues after MI.

Background: Atrial fibrillation (AF) has been identified as a major risk factor for mortality after acute coronary syndrome (ACS). However, the long-term risk of ischemic stroke associated with new-onset atrial fibrillation (NOAF) in ACS remains controversial, and its gender-specific association is unknown. Methods: We analyzed the data of 10,137 ACS survivors included in a multicenter, prospective registry for Korean patients with acute myocardial infarction (AMI) between January 2004 and August 2014. Subjects were categorized into three groups (non-AF vs. NOAF vs. previous AF) based on medical history and electrocardiographic evidence of AF, either at admission or during hospitalization. Results: Among the total study population (72.3% men), 370 patients (3.6%) had NOAF and 130 (1.3%) had previous AF. During a median follow-up of 61 months (interquartile range, 38.8 to 89.3 months), 245 (2.4%) patients (218 (2.3%) non-AF vs. 15 (4.1%) NOAF vs. 12 (9.2%) previous AF, p &lt, 0.001) experienced ischemic stroke. After adjustment for confounding variables, both NOAF (adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.09–3.24, p = 0.024) and previous AF (adjusted HR 4.00, 95% CI 2.03–7.87, p &lt, 0.001), along with older age, diabetes, current smoker, and previous stroke were independent risk factors of ischemic stroke. In the gender-stratified analysis, men with previous AF but not NOAF had a significantly higher risk of ischemic stroke (adjusted HR 4.14, 95% CI 1.79–9.55, p = 0.001) than those without AF. In women, NOAF (adjusted HR 2.54, 95% CI 1.21–5.35, p = 0.014) as well as previous AF (adjusted HR 3.72, 95% CI 1.16–11.96, p = 0.028) was a strong predictor of ischemic stroke, and the predictive value was comparable to that of previous AF among patients with a CHA2DS2-VASc score ≥ 2. Conclusions: Both NOAF and previous AF were associated with ischemic stroke after AMI, but the impact of NOAF as a risk factor of ischemic stroke was significant only in women.

Current guidelines for the management of acute myocardial infarction (AMI) recommend potent P2Y12 inhibitors rather than clopidogrel to prevent ischemic events. However, their ischemic benefits are offset by an increased major bleeding risk. We compared the efficacy and safety of triple antiplatelet therapy with cilostazol in the first month after AMI. This study investigated 16,643 AMI patients who received percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in nationwide, real-world, multicenter registries in Korea. Patients were divided into DAPT (aspirin and clopidogrel, n = 11,285), Triple (aspirin, clopidogrel and cilostazol, n = 2547), and Potent (aspirin and ticagrelor/prasugrel, n = 2811) groups. The primary outcomes were net adverse clinical events (NACE), a composite of death from any cause, myocardial infarction (MI), stroke, and TIMI major bleeding one month after AMI. After adjusting for covariates, there were no statistically significant differences in the risk of death from any cause, MI, or stroke between the three groups. However, the risk of TIMI major bleeding was significantly greater in the Potent group than in the DAPT and Triple groups (p < 0.001). Accordingly, NACE was significantly higher in the DAPT (HR 1.265; 95% CI 1.006–1.591, p = 0.044) and Potent groups (HR 1.515; 95% CI 1.142–2.011, p = 0.004) than in the Triple group. Triple antiplatelet therapy with cilostazol was associated with an improved net clinical outcome in the first month after AMI without increasing the risk of bleeding compared to potent or standard P2Y12 inhibitor-based DAPT.

The current study aimed to investigate the association between serum UA levels and the mortality rate of AMI patients. We analyzed 5888 patients with successfully revascularized AMI (mean age: 64.0 ± 12.7 years). The subjects were divided into the high UA group (uric acid >6.5 mg/dL for males, >5.8 mg/dL for females) or the normal UA group based on initial serum UA level measured at admission. The primary outcome was all-cause mortality. A total of 4141 (70.3%) and 1747 (29.7%) patients were classified into the normal UA group and high UA groups, respectively. Over a median follow-up of 5.02 (3.07, 7.55) years, 929 (21.5%) and 532 (34.1%) patients died in each group. Cox regression analysis identified high UA levels as an independent predictor of all-cause mortality (unadjusted hazard ratio (HR) 1.69 [95% CI 1.52–1.88]; p < 0.001, adjusted HR 1.18 [95% CI: 1.05–1.32]; p = 0.005). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences. The predictive accuracies of conventional clinical factor discrimination and reclassification were significantly improved upon the addition of hyperuricemia (C-index 0.788 [95% CI 0.775–0.801]; p = 0.005, IDI 0.004 [95% CI 0.002–0.006]; p < 0.001, NRI 0.263 [95% CI 0.208–0.318]; p < 0.001).

Current treatments for acute myocardial infarction (AMI) have dramatically improved clinical outcomes during the first year after AMI. Less is known, however, about the subsequent risks of recurrent cardiovascular events and mortality in patients who survive 1 year after AMI. The purpose of the present study is to evaluate long-term clinical outcomes in 1-year AMI survivors who were implanted with newer-generation drug-eluting stents (DESs) since 2010. The COREA-AMI (CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI) registry consecutively enrolled AMI patients who underwent percutaneous coronary intervention (PCI), and patients who received newer-generation DESs since 2010 were analyzed. The primary endpoint was major adverse cardiovascular events (MACEs), and secondary endpoint was all-cause mortality. Of 6242 AMI patients, 5397 were alive 1 year after the index procedure. The cumulative incidence of MACEs and all-cause death 1 to 7 years after AMI were 28.4% (annually 4–6%) and 20.2% (annually 3–4%), respectively. Multivariate analysis showed that uncontrolled systolic blood pressure (SBP) and serum low-density lipoprotein cholesterol (LDL-C) concentration, as well as traditional risk factors, were associated with MACEs and all-cause death. Recurrent non-fatal myocardial infarction, ischemic stroke, and bleeding events within 1 year were significantly associated with all-cause death. The risks of adverse cardiovascular events and death remain high in AMI patients more than 1 year after the index PCI with newer-generation DESs. Traditional risk factors, uncontrolled SBP and LDL-C, and non-fatal adverse events within 1 year after the index procedure strongly influence long-term clinical outcomes.

Background The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2‐[1’H‐indole‐3’‐carbonyl]‐thiazole‐4‐carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T‐cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE‐treated mice exhibited significantly improved systolic function ( P P + (forkhead box protein P3‐positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post‐MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.

Background and aim Regulatory T cells (Tregs) play an important role in cardiovascular complications with the immune response. However, the role of Tregs in high fat diet (HFD)-induced myocardial fibrosis has not been fully elucidated to date. Therefore, we investigated whether HFD suppresses Tregs activation in the myocardium of spontaneously hypertensive rats (SHRs), which aggregates myocardial fibrosis. Methods and results Eight-week-old male SHRs were fed to either HFD or control diet (CHO) groups for 12 weeks. We measured Tregs (CD4+FoxP3+) in the heart and mediastinal lymph nodes (LNs). The flow cytometry analysis confirmed that SHR-HFD exhibited a decreased Tregs compared to that of SHR-CHO in the heart and mediastinal LNs. Furthermore, the CD4 and FoxP3 antigens were used in the immunofluorescence microscopy of Tregs in the heart tissues. In the heart, dual staining for the Treg population was increased more in SHR-CHO than it was in SHR-HFD rats. In line with these findings, SHR-HFD significantly exacerbated myocardial fibrosis. Conclusion We found that diet-induced obesity typically showed an exacerbated myocardial fibrosis and down-regulation of Tregs pathway in the heart and mediastinal LNs. Therefore, we suggest that the up-regulation of Tregs may be a promising therapeutic approach to preventing obesity induced heart failure.

No data exist whether statins have robust anti-inflammatory effects of atherosclerotic plaques primarily during the early treatment period or continuously throughout use. This prospective three time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) study of the carotid artery assessed anti-inflammatory effects of statin during the early treatment period (initiation to 3 months) and late treatment period (3 months to 1 year) and their correlation with lipid and inflammatory profile changes during a year of therapy. Nine statin-naive stable angina patients with inflammatory carotid plaques received 20 mg/day atorvastatin after undergoing initial 18F-FDG PET/CT scanning of carotid arteries and ascending thoracic aorta, and then completed serial 18F-FDG PET/CT imaging at 3 and 12 months whose data were analyzed. The primary outcome was the inter-scan percent change in target-to-background ratio (ΔTBR) within the index vessel. At 3 months of atorvastatin treatment, mean serum low-density lipoprotein cholesterol (LDL-C) level decreased by 36.4% to 40 mg/dL (p = 0.041), with both maintained with no further reduction up to 1 year (p = 0.516 and 0.715, respectively) while mean serum high sensitivity C-reactive protein level only numerically decreased (p = 0.093). The index vessel ΔTBR showed continuous plaque inflammation reduction over 1 year, by 4.4% (p = 0.015) from the initiation to 3rd months and 6.2% (p = 0.009) from 3rd months to 1 year, respectively, without correlation with lipid profile changes. The ΔTBR of the bilateral carotid arteries and ascending aorta also continuously decreased from 3 months to 1 year. Three time point 18F-FDG PET/CT imaging demonstrates that statin’s anti-inflammatory effect continues throughout its use up to 1 year, even though yielding stable below-target plasma LDL-C levels at 3 months.

Background Chronic total occlusion (CTO) is a challenging entity in coronary interventions. With improvements in technology and techniques, success rates for percutaneous coronary intervention (PCI) of CTO continue to improve. However, the clinical benefits of PCI remain unclear. The aim of the study was to determine the effectiveness of successful PCI on clinical outcomes using drug-eluting stents in patients with CTO. Methods From 2004 to 2010, we analyzed 898 patients with at least one CTO who underwent successful PCI (n = 424, 448 lesions) or only medical treatment (n = 474, 519 lesions) from a multicenter registry. The primary outcome was all-cause death. Results During a median of 2.2 years, incidence rate of all-cause death after successful PCI was lower than that after medical treatment (10.6% and 17.5%, p = 0.004). However, the multivariate Cox proportional hazards model showed that successful PCI was not associated with improvement in mortality compared to medical treatment [adjusted hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.57–1.24, p = 0.38]. Comparable results were obtained after propensity-score matching. Subgroup analysis of propensity-score matched population demonstrated that patients with age under 65 years benefited from successful PCI (HR 0.25, 95% CI 0.08–0.75, p for interaction = 0.005). Conclusions In patients considered for CTO intervention, medical treatment appears to be associated with a similar mortality compared to successful PCI. Successful CTO PCI might be associated with survival benefit in younger patients compared to medical treatment.

This study aimed to investigate the relationship between a complex percutaneous coronary intervention (C-PCI) and long-term clinical outcomes in the AMI cohort. A total of 10,329 patients were categorized into the C-PCI and non-C-PCI groups. The primary ischemic endpoint was a composite of major adverse cardiac events (MACEs, cardiac death, myocardial infarction, stent thrombosis and revascularization). The primary bleeding endpoint was the risk of overt bleeding (BARC 2, 3 or 5). The median follow-up duration was 4.9 (2.97, 7.16) years. The risks of MACEs and bleeding were significantly higher in the C-PCI group (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.60 to 1.85; p < 0.001; and HR: 1.32; 95% CI: 1.17 to 1.50; p < 0.001, respectively). After propensity score matching, compared to the non-C-PCI group, the adjusted MACE rate in C-PCI remained significantly higher (p < 0.001), but no significant interaction (p = 0.273) was observed for bleeding. Significant differences in overt bleeding were observed only within the first three months (p = 0.024). The MACEs were consistently higher in the C-PCI group with or without severe comorbid conditions (p < 0.001 for both). Patients with AMI who undergo C-PCI experience worse long-term ischemic outcomes after successful PCI, regardless of the presence of severe comorbidities.

Background The available data are not sufficient to understand the clinical impact of statin intensity in elderly patients who undergo percutaneous coronary intervention (PCI) due to acute myocardial infarction (AMI). Methods Using the COREA-AMI registry, we sought to compare the clinical impact of high- versus low-to-moderate-intensity statin in younger ( Results In younger patients, high-intensity statin showed the better clinical outcomes than low-to-moderate-intensity statin (TVF: 79 [5.4%] vs. 329 [6.8%], adjusted hazard ratio [aHR] 0.76; 95% confidence interval [CI] 0.59–0.99; P = 0.038). However, in elderly patients, the incidence rates of the adverse clinical outcomes were similar between two statin-intensity groups (TVF: 38 [11.4%] vs. 131 [10.6%], aHR 1.1; 95% CI 0.76–1.59; P = 0.63). Conclusions In this AMI cohort underwent PCI, high-intensity statin showed the better 1-year clinical outcomes than low-to-moderate-intensity statin in younger patients. Meanwhile, the incidence rates of adverse clinical events between high- and low-to-moderate-intensity statin were not statistically different in elderly patients. Further randomized study with large elderly population is warranted.

Severe cardiac damage following myocardial infarction (MI) causes excessive inflammation, which sustains tissue damage and often induces adverse cardiac remodeling toward cardiac function impairment and heart failure. Timely resolution of post-MI inflammation may prevent cardiac remodeling and development of heart failure. Cell therapy approaches for MI are time-consuming and costly, and have shown marginal efficacy in clinical trials. Here, nanoparticles targeting the immune system to attenuate excessive inflammation in infarcted myocardium are presented. Liposomal nanoparticles loaded with MI antigens and rapamycin (L-Ag/R) enable effective induction of tolerogenic dendritic cells presenting the antigens and subsequent induction of antigen-specific regulatory T cells (Tregs). Impressively, intradermal injection of L-Ag/R into acute MI mice attenuates inflammation in the myocardium by inducing Tregs and an inflammatory-to-reparative macrophage polarization, inhibits adverse cardiac remodeling, and improves cardiac function. Nanoparticle-mediated blocking of excessive inflammation in infarcted myocardium may be an effective intervention to prevent the development of post-MI heart failure.

The quantitative flow ratio (QFR) is a novel angiography-based computational method assessing functional ischemia caused by coronary stenosis. This study aimed to evaluate the diagnostic performance of quantitative flow ratio (QFR) in patients with angina and acute myocardial infarction (AMI) and to identify the conditions with low diagnostic performance. We assessed the QFR for 1077 vessels under fractional flow ratio (FFR) evaluation in 915 patients with angina and AMI. The diagnostic accuracies of the QFR for identifying an FFR ≤ 0.8 were 95.98% (95% confidence interval [CI] 94.52 to 97.14%) for the angina group and 92.42% (95% CI 86.51 to 96.31%) for the AMI group. The diagnostic accuracy of the QFR in the borderline FFR zones (> 0.75, ≤ 0.85) (91.23% [95% CI 88.25 to 93.66%]) was significantly lower than that in others (difference: 4.32; p = 0.001). The condition accompanying both AMI and the borderline FFR zone showed the lowest QFR diagnostic accuracy in our data (83.93% [95% CI 71.67 to 92.38]). The diagnostic accuracy was reduced for tandem lesions (p = 0.04, not correcting for multiple testing). Our study found that the QFR method yielded a high overall diagnostic performance in real-world patients. However, low diagnostic accuracy has been observed in borderline FFR zones with AMI, and the hybrid FFR approach needs to be considered.

The early and late ischemic and bleeding clinical outcomes according to baseline platelet count after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) remain unclear. Overall, 10,667 patients from the Cardiovascular Risk and identification of potential high-risk population in AMI (COREA-AMI) I and II registries were classified according to the following universal criteria on baseline platelet counts: (1) moderate to severe thrombocytopenia (platelet &lt, 100 K/&mu, L, n = 101), (2) mild thrombocytopenia (platelet = 100~149 K/&mu, L, n = 631), (3) normal reference (platelet = 150~450 K/&mu, L, n = 9832), and (4) thrombocytosis (platelet &gt, 450 K/&mu, L, n = 103). The primary endpoint was the occurrence of major adverse cardiovascular events (MACE). The secondary outcome was Bleeding Academic Research Consortium (BARC) 2, 3, and 5 bleeding. After adjusting for confounders, the moderate to severe thrombocytopenia (HR, 2.03, 95% CI, 1.49&ndash, 2.78), p &lt, 0.001), mild thrombocytopenia (HR, 1.15, 95% CI, 1.01&ndash, 1.34, p = 0.045), and thrombocytosis groups (HR, 1.47, 95% CI, 1.07&ndash, 2.03, p = 0.019) showed higher 5-year MACE rates than the normal reference. In BARC 2, 3, and 5 bleeding outcomes, the bleedings rates were higher than the normal range in the moderate to severe thrombocytopenia (HR, 2.18, 95% CI, 1.36&ndash, 3.49, p = 0.001) and mild thrombocytopenia (HR, 1.41, 95% CI, 1.12&ndash, 1.78, p = 0.004) groups. Patients with AMI had higher 5-year MACE rates after PCI if they had lower- or higher-than-normal platelet counts. Thrombocytopenia revealed higher early and late bleeding rates whereas thrombocytosis showed long-term bleeding trends, although these trends were not statistically significant.

Limited data exist on the temporal trend of major bleeding and its prediction by the Academic Research Consortium-High Bleeding Risk (ARC-HBR) criteria in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). We investigated 10-year trends of major bleeding and predictive ability of the ARC-HBR criteria in AMI patients. In a multicenter registry of 10,291 AMI patients undergoing PCI between 2004 and 2014 the incidence of Bleeding Academic Research Consortium (BARC) 3 and 5 bleeding was assessed, and, outcomes in ARC-defined HBR patients with AMI were compared with those in non-HBR. The primary outcome was BARC 3 and 5 bleeding at 1 year. Secondary outcomes included all-cause mortality and composite of cardiovascular death, myocardial infarction, or ischemic stroke. The annual incidence of BARC 3 and 5 bleeding in the AMI population has increased over the years (1.8% to 5.8%; p < 0.001). At 1 year, ARC-defined HBR (n = 3371, 32.8%) had significantly higher incidence of BARC 3 and 5 bleeding (9.8% vs. 2.9%; p < 0.001), all-cause mortality (22.8% vs. 4.3%; p < 0.001) and composite of ischemic events (22.6% vs. 5.8%; p < 0.001) compared to non-HBR. During the past decade, the incidence of major bleeding in the AMI population has increased. The ARC-HBR criteria provided reliable predictions for major bleeding, mortality, and ischemic events in AMI patients.

Aminoacyl-tRNA synthetase-interacting multifunctional protein 3 (AIMP3), a tumor suppressor, mediates a progeroid phenotype in mice by downregulating lamin A. We investigated whether AIMP3 induces laminopathy and senescence of human aortic smooth muscle cells (HASMCs) and is associated with vascular aging in mice and humans in line with decreased lamin A expression. Cellular senescence was evaluated after transfecting HASMCs with AIMP3. Molecular analyses of genes encoding AIMP3, lamin A, chemokine (C-C motif) ligand 2 (CCL2), and C-C chemokine receptor type 2 (CCR2) and histological comparisons of aortas were performed with mice at various ages (7 weeks, 5 months, 12 months, 24 months, and 32 months), AIMP3-transgenic mice, and human femoral arteries of cadavers. AIMP3-transfected HASMCs exhibited increased AIMP3 and senescence marker p16 protein expression and decreased lamin A protein expression in accordance with their disrupted nuclear morphology in histological analyses. AIMP3-transgenic mice displayed increased AIMP3 protein expression and decreased lamin A protein expression in aortas together with typical aging pathologies. Similar changes were observed in wild-type aging (24-month-old) mice but not in wild-type young (7-week-old) mice. In humans, AIMP3 and lamin A protein expression was higher and lower, respectively, in femoral arteries of elderly individuals than in those of their younger counterparts. This study found that AIMP3 overexpression in vitro decreased lamin A expression and induced nuclear laminopathy and cellular senescence. Similar findings were made in the vasculature of aging mice and elderly humans.

OBJECTIVE We investigated the efficacy of coronary computed tomography angiography (CCTA) in predicting the long-term risks in asymptomatic patients with type 2 diabetes and compared it with traditional risk factors. RESEARCH DESIGN AND METHODS We analyzed 933 patients with asymptomatic type 2 diabetes who underwent CCTA. Stenosis was considered obstructive (≥50%) in each coronary artery segment using CCTA. The extent and severity scores for coronary artery disease (CAD) were evaluated. The primary end point was major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization during a mean follow-up period of 5.5 ± 2.1 years. RESULTS Ninety-four patients with MACE exhibited obstructive CAD with a greater extent and higher severity scores (P < 0.001 for all). After adjusting for confounding risk factors, obstructive CAD remained an independent predictor of MACE (hazard ratio 3.11 [95% CI 2.00–4.86]; P < 0.001]). The performance of a risk prediction model based on C-statistics was significantly improved (C-index 0.788 [95% CI 0.747–0.829]; P = 0.0349) upon the addition of a finding of obstructive CAD using CCTA to traditional risk factors, including age, male, hypertension, hyperlipidemia, smoking, estimated glomerular filtration rate, and HbA1c. Both integrated discrimination improvement (IDI) and net reclassification improvement (NRI) analyses further supported this finding (IDI 0.046 [95% CI 0.020–0.072], P < 0.001, and NRI 0.55 [95% CI 0.343–0.757], P < 0.001). In contrast, the risk prediction power of the coronary artery calcium score remained unimproved (C-index 0.740, P = 0.547). CONCLUSIONS Based on our data, the addition of CCTA-detected obstructive CAD to models that include traditional risk factors improves the predictions of MACE in asymptomatic patients with type 2 diabetes.

Background Myocardial infarction with nonobstructive coronary arteries ( MINOCA ) is a heterogeneous disease entity. Its prognosis and predictor of mortality remain unclear. This study aimed to compare the prognosis between MINOCA and myocardial infarction with obstructive coronary artery disease and identify factors related to all‐cause death in MINOCA using a nation‐wide, multicenter, and prospective registry. Methods and Results Among 13 104 consecutive patients enrolled, patients without previous history of significant coronary artery disease who underwent coronary angiography were selected. The primary outcome was 2‐year all‐cause death. Secondary outcomes were cardiac death, noncardiac death, reinfarction, and repeat revascularization. Patients with MINOCA (n=396) and myocardial infarction with obstructive coronary artery disease (n=10 871) showed similar incidence of all‐cause death (9.1% versus 8.8%; hazard ratio [ HR ], 1.04; 95% CI, 0.74–1.45; P =0.83). Risks of cardiac death, noncardiac death, and reinfarction were not significantly different between the 2 groups ( HR , 0.82; 95% CI , 0.53–1.28; P =0.38; HR , 1.55; 95% CI , 0.93–2.56; P =0.09; HR , 1.23; 95% CI , 0.65–2.31; P =0.38, respectively). MINOCA patients had lower incidence of repeat revascularization (1.3% versus 7.2%; HR , 0.17; 95% CI , 0.07–0.41; P MINOCA were found, including the nonuse of renin‐angiotensin system blockers ( HR , 2.63; 95% CI , 1.08–6.25; P =0.033) and statins ( HR , 2.17; 95% CI , 1.04–4.54; P =0.039). Conclusions Patients with MINOCA and those with myocardial infarction with obstructive coronary artery disease had comparable clinical outcomes. Use of renin‐angiotensin system blockers and statins was associated with lower mortality in patients with MINOCA .

Background: Ticagrelor is an intriguing antiplatelet agent with a potentially beneficial impact on endothelial dysfunction and confers a mortality benefit beyond 1 month after acute coronary syndrome (ACS). However, little data exist on whether ticagrelor improves endothelial dysfunction in stable patients who survive the acute period and receive guideline-directed medical therapy. Methods and Results: This study is a prospective, randomized, parallel, open-labeled study that enrolled 30-day survivors of non-ST-segment elevation ACS (NSTE-ACS). Forty patients with NSTE-ACS were randomly assigned to ticagrelor or clopidogrel groups. The primary end point was the change in the percentage brachial artery flow-mediated dilation (baFMD) from baseline. Baseline characteristics were not different between the 2 groups. The median time from the stent implantation to screening was 269 days. After 30 days of study medication administration, the change in the percentage baFMD value was similar between the ticagrelor and clopidogrel groups (−0.08 [1.42] vs 0.30 [1.69], P = .66). There was no difference in the change in high-sensitive C-reactive protein (−0.61 [1.48] vs −0.01 [0.57], P = .28); however, the change in platelet inhibition significantly differed (P2Y12 reaction units, −140.5 [49.5] vs −3.9 [51.4], P < .001). Conclusions: This dual time point baFMD study demonstrated that treatment with ticagrelor was not superior to clopidogrel for improving endothelial dysfunction in stabilized patients with NSTE-ACS.