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.

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.

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.

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.

Benefit of a staged in-hospital revascularization strategy in hemodynamically stable patients with ST-segment elevation myocardial infarction and multivessel disease: Analyses by risk stratification.

AIMS: The proper timing and indication of revascularization for a non-culprit artery in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) without cardiogenic shock remains controversial. METHODS AND RESULTS: This multicenter study included patients with STEMI and MVD without cardiogenic shock. Data were analyzed at 3 years according to the percutaneous coronary intervention (PCI) strategy: immediate multivessel revascularization (MVR) (n = 351), stepwise MVR (n = 510), and culprit-only PCI (n = 1,142). The primary outcome was all-cause mortality. The stepwise MVR group had a lower risk of all-cause death. The results were consistent after multivariate regression, propensity-score matching, inverse probability weighting, and Bayesian proportional hazards modeling. In subgroup analyses stratified by the Global Registry of Acute Coronary Events score, stepwise MVR also lowered the risk of all-cause death compared to culprit-only PCI and immediate MVR in high risk patients but not in patients at low to intermediate risk. CONCLUSIONS: In patients with STEMI and MVD without cardiogenic shock, in-hospital stepwise MVR was associated with a lower risk of all-cause death than culprit-only PCI or immediate MVR, particularly in the high-risk subgroup.

Preclinical Evaluation of a Novel Polymer-free Everolimus-eluting Stent in a Mid-term Porcine Coronary Restenosis Model.

BACKGROUND: Titanium dioxide films exhibit good biocompatibility and may be effective as drug-binding matrices for drug-eluting stents. We conducted a mid-term evaluation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film deposition (TIGEREVOLUTION®) in comparison with a commercial durable polymer everolimus-eluting stent (XIENCE Alpine®) in a porcine coronary restenosis model. METHODS: Twenty-eight coronary arteries from 14 mini-pigs were randomly allocated to TIGEREVOLUTION® stent and XIENCE Alpine® stent groups. The stents were implanted in the coronary artery at a 1.1-1.2:1 stent-to-artery ratio. Eleven stented coronary arteries in each group were finally analyzed using coronary angiography, optical coherence tomography, and histopathologic evaluation 6 months after stenting. RESULTS: Quantitative coronary analysis showed no significant differences in the pre-procedural, post-procedural, and 6-month lumen diameters between the groups. In the volumetric analysis of optical coherence tomography at 6 months, no significant differences were observed in stent volume, lumen volume, and percent area stenosis between the groups. There were no significant differences in injury score, inflammation score, or fibrin score between the groups, although the fibrin score was zero in the TIGEREVOLUTION® stent group (0 vs. 0.07 ± 0.11, P = 0.180). CONCLUSION: Preclinical evaluation, including optical coherence tomographic findings 6 months after stenting, demonstrated that the TIGEREVOLUTION® stent exhibited efficacy and safety comparable with the XIENCE Alpine® stent, supporting the need for further clinical studies on the TIGEREVOLUTION® stent.

Influence of Local Myocardial Infarction on Endothelial Function, Neointimal Progression, and Inflammation in Target and Non-Target Vascular Territories in a Porcine Model of Acute Myocardial Infarction.

BACKGROUND: Patients with acute myocardial infarction (AMI) have worse clinical outcomes than those with stable coronary artery disease despite revascularization. Non-culprit lesions of AMI also involve more adverse cardiovascular events. This study aimed to investigate the influence of AMI on endothelial function, neointimal progression, and inflammation in target and non-target vessels. METHODS: In castrated male pigs, AMI was induced by balloon occlusion and reperfusion into the left anterior descending artery (LAD). Everolimus-eluting stents (EES) were implanted in the LAD and left circumflex (LCX) artery 2 days after AMI induction. In the control group, EES were implanted in the LAD and LCX in a similar fashion without AMI induction. Endothelial function was assessed using acetylcholine infusion before enrollment, after the AMI or sham operation, and at 1 month follow-up. A histological examination was conducted 1 month after stenting. RESULTS: A total of 10 pigs implanted with 20 EES in the LAD and LCX were included. Significant paradoxical vasoconstriction was assessed after acetylcholine challenge in the AMI group compared with the control group. In the histologic analysis, the AMI group showed a larger neointimal area and larger area of stenosis than the control group after EES implantation. Peri-strut inflammation and fibrin formation were significant in the AMI group without differences in injury score. The non-target vessel of the AMI also showed similar findings to the target vessel compared with the control group. CONCLUSION: In the pig model, AMI events induced endothelial dysfunction, inflammation, and neointimal progression in the target and non-target vessels.

Comparison of Clinical Outcomes Between Ticagrelor and Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction　- Results From the Korea Acute Myocardial Infarction Registry-National Institutes of Health.

BACKGROUND: There is little information regarding comparison of ticagrelor and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI). We sought to compare clinical outcomes between ticagrelor and prasugrel in STEMI.Methods and Results:A total of 1,440 patients with STEMI who underwent successful primary percutaneous coronary intervention were analyzed; the data were obtained from the Korea Acute Myocardial Infarction Registry-National Institutes of Health. Of the patients, 963 received ticagrelor, and 477 received prasugrel. The primary study endpoint was 12-month major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). MACE occurred in 91 patients (6.3%) over the 1-year follow-up, and there were no differences in the incidence of MACE (hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.76-1.91, P=0.438) between the 2 groups. Analysis by propensity score matching (429 pairs) did not significantly affect the results. The incidence of in-hospital major bleeding events was still comparable between the 2 groups (2.4% vs. 2.5%, odds ratio 0.75, 95% CI 0.30-1.86, P=0.532), and there was no significant difference in the incidence of MACE (5.4% vs. 5.8%, HR 0.98, 95% CI 0.56-1.74, P=0.951) after matching. CONCLUSIONS: Ticagrelor and prasugrel showed similar efficacy and safety profiles for treating STEMI in this Korean multicenter registry.

Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in Korean patients with atrial fibrillation.

AIMS: We aim to determine the optimal dose of dabigatran in Korean patients with atrial fibrillation (AF). METHODS AND RESULTS: We analysed 1834 patients with non-valvular AF, classified into a warfarin group (n = 990), dabigatran 150 mg group (D150, n = 294), and 110 mg group (D110, n = 550). The D110 group was further classified into patients concordant (co-D110, n = 367) and patients discordant (di-D110, n = 183) with guidelines to dose reduction. Propensity-matched 1-year clinical outcomes were then compared. Efficacy outcomes were defined as thromboembolism composed of new-onset stroke or systemic embolism. Safety outcomes were major bleeding. Both D150 and D110 had comparable efficacies as warfarin. However, only D110 significantly lowered the risk of major bleeding [hazard ratio (HR) 0.19, 95% confidence interval (CI) 0.07-0.55, P = 0.002]. In a subgroup analysis according to guideline-concordant indications for dose reduction, both co-D110 and di-D110 displayed a comparable efficacy as warfarin. Both co-D110 (HR 0.22, 95% CI 0.06-0.76, P = 0.017) and di-D110 (HR 0.11, 95% CI 0.02-0.81, P = 0.030) significantly lowered incidences of major bleeding. There were no differences in the efficacy and safety between di-D110 and D150, and net clinical outcomes were similar. CONCLUSION: Although D150 and D110 had a comparable efficacy, only D110 lowered the risk of major bleeding in Korean AF patients compared with warfarin. Even the guideline-discordant use of dabigatran 110 mg demonstrated a similar efficacy and safety compared with D150. However, further prospective randomized trials are needed in order to comprehensively evaluate whether D150 or D110 is the optimal dosage in Asian patients with AF.

Tpeak-Tend interval during therapeutic hypothermia can predict upcoming ventricular fibrillation in subjects with aborted arrhythmic sudden cardiac death: 3-years follow-up results.

AIMS: Prolonged Tpeak-Tend interval has been shown to be markers of arrhythmogenesis in various cardiac disorders. However, its dynamicity is one of the obstacles to predict fatal ventricular arrhythmia. This study investigated whether Tpeak-Tend interval during therapeutic hypothermia (TH) is associated with ventricular fibrillation (VF) inducibility and clinical arrhythmia in subjects with aborted arrhythmic sudden cardiac death (SCD). METHODS AND RESULTS: The study group included 31 patients (24 males, age 39.1 ± 17.6 years) presenting with arrhythmic SCD in whom Tpeak-Tend interval and J-wave amplitude were measured in electrocardiogram (ECG) of the earliest medical contact and during TH; these patients underwent programmed ventricular stimulation. The summation of J-wave amplitude and QTc interval increased during TH. However, it was not associated with VF inducibility. Patients with inducible VF showed a small Tpeak-Tend interval dispersion in the baseline 12-lead ECG (68.8 ± 24.7 vs. 94.0 ± 55.6 ms, P = 0.044) and a marked increase of the dispersion during the TH (36.2 ± 51.2 vs. -6.1 ± 45.5 ms, P = 0.039). Twenty-four patients underwent implantable cardioverter defibrillator (ICD) implantation. Among them, the patients with long QTc, Tpeak-Tend, and precordial Tpeak-Tend during the TH developed VF more frequently (QTc, 511.9 ± 53.71 ms vs. 566.5 ± 56.08 ms, P = 0.038; Tpeak-Tend interval, 145.6 ± 38.4 ms vs. 185.7 ± 49.95 ms, P = 0.048; precordial Tpeak-Tend interval, 139.3 ± 35.11 ms vs. 185.7 ± 49.95 ms, P = 0.018). The initial VF inducibility was not related with the VF development in follow-up. CONCLUSION: In patients with aborted arrhythmic SCD, long Tpeak-Tend interval and QTc interval during TH could predict VF development in their follow-up.

Impact of Postprocedural TIMI Flow on Long-Term Clinical Outcomes in Patients with Acute Myocardial Infarction.

This study aimed to evaluate the clinical prognostic implications of postprocedural Thrombolysis in Myocardial Infarction (TIMI) flow in acute myocardial infarction patients. A total of 2796 ST-elevation myocardial infarction (STEMI) and 1720 non ST-elevation myocardial infarction (NSTEMI) patients treated in 8 hospitals affiliated with the Catholic University of Korea and Chonnam National University Hospital were analyzed. The study populations were divided according to the final TIMI flow. The primary outcome were the major adverse cardiac events (MACE), defined as a composite of cardiac deaths (CD), nonfatal myocardial infarctions (MI), and target lesion revascularization (TLR). Over a median follow-up of 3.3 years (minimum 2 to maximum 5 years), MACE and CD occurred more frequently in STEMI patients with TIMI ≤ 2 group than those with TIMI 3 (MACE: adjusted hazard ratio [aHR], 1.962; 95% confidence interval [CI] 1.513 to 2.546, P < 0.001, CD: aHR, 3.154, CI 2.308 to 4.309, P < 0.001). However, there was no significant difference between the two subgroups in NSTEMI (aHR, 0.932; 95% CI 0.586 to 1.484, P = 0.087). In STEMI patients, good postprocedural TIMI flow after PCI was associated with favorable clinical outcomes. And the effect of poor TIMI flow in STEMI was on death, not the components of MACE. Meanwhile, postprocedural TIMI flow had no effect on long-term outcomes in NSTEMI patients.

Effect of stents coated with a combination of sirolimus and alpha-lipoic acid in a porcine coronary restenosis model.

The aim of this study was to evaluate antiproliferative sirolimus- and antioxidative alpha-lipoic acid (ALA)-eluting stents using biodegradable polymer [poly-L-lactic acid (PLA)] in a porcine coronary overstretch restenosis model. Forty coronary arteries of 20 pigs were randomized into four groups in which the coronary arteries had a bare metal stent (BMS, n = 10), ALA-eluting stent with PLA (AES, n = 10), sirolimus-eluting stent with PLA (SES, n = 10), or sirolimus- and ALA-eluting stent with PLA (SAS, n = 10). A histopathological analysis was performed 28 days after the stenting. The ALA and sirolimus released slowly over 30 days. There were no significant differences between groups in the injury or inflammation score; however, there were significant differences in the percent area of stenosis (56.2 ± 11.78% in BMS vs. 51.5 ± 12.20% in AES vs. 34.7 ± 7.23% in SES vs. 28.7 ± 7.30% in SAS, P < 0.0001) and fibrin score [1.0 (range 1.0-1.0) in BMS vs. 1.0 (range 1.0-1.0) in AES vs. 2.0 (range 2.0-2.0) in SES vs. 2.0 (range 2.0-2.0) in SAS, P < 0.0001] between the four groups. The percent area of stenosis based on micro-computed tomography corresponded with the restenosis rates based on histopathological stenosis in different proportions in the four groups (54.8 ± 7.88% in BMS vs. 50.4 ± 14.87% in AES vs. 34.5 ± 7.22% in SES vs. 28.9 ± 7.22% in SAS, P < 0.05). SAS showed a better neointimal inhibitory effect than BMS, AES, and SES at 1 month after stenting in a porcine coronary restenosis model. Therefore, SAS with PLA can be a useful drug combination for coronary stent coating to suppress neointimal hyperplasia.

The factors associated with sexual recovery in male patients with acute myocardial infarction under phase II cardiac rehabilitation.

AIMS AND OBJECTIVES: The aim of the study was to assess the prognostic factors of short-term sexual recovery in patients with acute myocardial infarction after phase II cardiac rehabilitation for six weeks. BACKGROUND: It is often observed that patients who have suffered acute myocardial infarction and have sufficient aerobic capacity for sexual activity do not recover sexual activity. Until now, few studies have investigated factors associated with recovery of sexual activity. DESIGN: Observational study. METHODS: Among 627 male patients with acute myocardial infarction who were referred for cardiac rehabilitation from October 2010-September 2014, 72 were finally analysed. Subjects who met all the following criteria were included: (1) completed a questionnaire about sexual activity before and after phase II cardiac rehabilitation; (2) showed usual sexual activity before onset of acute myocardial infarction and (3) revealed decreased sexual activity at baseline of cardiac rehabilitation compared to preacute myocardial infarction status despite ≥5 maximal metabolic equivalents. Information on sociodemographic characteristics and cardiopulmonary function obtained before cardiac rehabilitation was used for the analysis. RESULTS: (1) Twenty-five of the 72 subjects (34·7%) had improved sexual activity after six weeks of cardiac rehabilitation, but 47 (65·3%) continued the status of no-recovery sexual activity after cardiac rehabilitation. (2) Age, body mass index and use of statins were significantly different between subjects who recovered and those who did not. (3) No differences in other clinical characteristics and cardiopulmonary functions were detected between the two groups. (4) Age and body mass index were significant factors associated with recovery of sexual activity. CONCLUSIONS: Age and body mass index were significant factors associated with recovery of sexual activity in acute myocardial infarction patients. Aerobic capacity at baseline of cardiac rehabilitation was not an independent factor to predict the recovery of sexual activity. RELEVANCE TO CLINICAL PRACTICE: These results should be considered when educating patients under phase II cardiac rehabilitation on their return to normal sexual activity.

Comparison of non-vitamin K antagonist oral anticoagulants and warfarin on clinical outcomes in atrial fibrillation patients with renal dysfunction.

AIMS: We aimed to compare the efficacy and safety between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in atrial fibrillation (AF) patients according to renal dysfunction. METHODS AND RESULTS: We analysed 1319 patients who had been taken oral anticoagulants. They were classified into patients taking NOACs (n = 326) and warfarin (n = 993). Renal dysfunction was defined as the estimated glomerular filtration rate <60 mL/min by using the Chronic Kidney Disease Epidemiology Collaboration equation. The composite clinical outcomes were defined as the composite of death, hospitalization, and new-onset strokes. Safety outcomes were composed of major and minor bleeding. Subgroup analyses for clinical and safety outcomes were performed according to renal dysfunction during median 596 (506-612) follow-up days. The prevalence of renal dysfunction was similar between the two groups. The incidences of death, hospitalization, and strokes were not different between the two groups. However, the incidences of major bleeding was significantly higher in patients taking warfarin. In the subgroup analysis with renal dysfunction, the use of NOACs significantly improved the composite clinical outcomes (adjusted hazard ratio, HR, 0.30, 95% confidence interval, CI, 0.11-0.77, interaction P = 0.018) and major bleeding (adjusted HR 0.18, 95% CI 0.07-0.45, interaction P = 0.199) even after the covariate adjustment. However, in patients without renal dysfunction, there were no differences in the incidences of the composite clinical outcomes between the two groups. CONCLUSIONS: The benefit of NOACs was more prominent in AF patients with renal dysfunction than without renal dysfunction. These results suggest that NOACs as the first choice oral anticoagulant in AF patients with renal dysfunction.

Red cell distribution width as a novel predictor for clinical outcomes in patients with paroxysmal atrial fibrillation.

AIMS: Elevated red cell distribution width (RDW) has been known to be associated with adverse long-term outcomes in patients with cardiovascular diseases. We aimed to evaluate relationship between RDW values and clinical outcomes in patients with paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: We analysed 567 patients who were newly diagnosed as paroxysmal AF. Clinical outcomes were analysed after median 4.8 (3.4-6.9) years follow-up. The composite clinical outcomes were defined as the composite of death, hospitalization due to heart failure, and new-onset stroke. Bleeding events were composed of major and minor bleeding. The relationship of RDW with clinical outcomes was assessed using continuous or categorical variables as quartiles: <12.8, 12.8-13.2, 13.3-13.8, and ≥13.9%. Patients with the highest RDW quartile were the oldest and had more frequent history of heart failure. CHA2DS2-VASc score was increased along with increasing RDW quartiles (1.75 ± 1.48 vs. 1.77 ± 1.63 vs. 1.87 ± 1.61 vs. 2.33 ± 1.65, P = 0.008). Incidence of new-onset stroke (log-rank P = 0.032), the composite clinical outcomes (log-rank P = 0.014), and bleeding events (log-rank P = 0.001) were increased as increasing RDW quartiles. Multivariate analysis identified that RDW was a significant predictor for new-onset stroke [adjusted hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.06-1.65, P = 0.015], the composite clinical outcomes (adjusted HR 1.21, 95% CI 1.03-1.41, P = 0.017), and bleeding events (adjusted HR 1.36, 95% CI 1.13-1.64, P = 0.001). CONCLUSIONS: RDW can be a new, useful, novel predictor of clinical and safety outcomes in patients with paroxysmal AF.

Effect of a novel peptide, WKYMVm- and sirolimus-coated stent on re-endothelialization and anti-restenosis.

The drug-eluting stent still has limitations such as thrombosis and inflammation. These limitations often occur in the absence of endothelialization. This study investigated the effects of WKYMVm- and sirolimus-coated stents on re-endothelialization and anti-restenosis. The WKYMVm peptide, specially synthesized for homing endothelial colony-forming cells, was coated onto a bare-metal stent with hyaluronic acid through a simple dip-coating method (designated HA-Pep). Thereafter, sirolimus was consecutively coated to onto the HA-Pep (designated Pep/SRL). The cellular response to stents by human umbilical-vein endothelial cells and vascular smooth-muscle cells was examined by XTT assay. Stents were implanted into rabbit iliac arteries, isolated 6 weeks post-implantation, and then subjected to histological analysis. The peptide was well attached to the surface of the stents and the sirolimus coating made the surface smooth. The release pattern for sirolimus was similar to that of commercial sirolimus-coated stents (57.2% within 7 days, with further release for up to 28 days). Endothelial-cell proliferation was enhanced in the HA-Pep group after 7 days of culture (38.2 ± 7.62%, compared with controls). On the other hand, the proliferation of smooth-muscle cells was inhibited in the Pep/SRL group after 7 days of culture (40.7 ± 6.71%, compared with controls). In an animal study, the restenosis rates for the Pep/SRL group (13.5 ± 4.50%) and commercial drug-eluting stents (Xience Prime™; 9.2 ± 7.20%) were lower than those for bare-metal stents (25.2 ± 4.52%) and HA-Pep stents (26.9 ± 3.88%). CD31 staining was incomplete for the bare-metal and Xience Prime™ groups. On the other hand, CD31 staining showed a consecutive linear pattern in the HA-Pep and Pep/SRL groups, suggesting that WKYMVm promotes endothelialization. These results indicate that the WKYMVm coating could promote endothelial healing, and consecutive coatings of WKYMVm and sirolimus onto bare-metal stents have a potential role in re-endothelialization and neointimal suppression.

Reliable femoral chronic total occlusion model using a thin biodegradable polymer coated copper stent in a porcine model.

Chronic total occlusions (CTOs) are common in patients with peripheral arterial disease (PAD). This study aimed to examine the feasibility and reliability of a CTO induced by a thin biodegradable polymer (polyglycolic acid) coated copper stent in a porcine femoral artery. Novel thin biodegradable polymer coated copper stents (9 mm long) were crimped on an angioplasty balloon (4.5 mm diameter × 12 mm length) and inserted into the femoral artery. Histopathologic analysis was performed 35 days after stenting. In five of six stented femoral arteries, severe in-stent restenosis and total occlusion with collateral circulation were observed without adverse effects such as acute stent thrombosis, leg necrosis, or death at 5 weeks. Fibrous tissue deposition, small vascular channels, calcification, and inflammatory cells were observed in hematoxylin-eosin, Carstair's, and von Kossa tissue stains; these characteristics were similar to pathological findings associated with CTOs in humans. The neointima volume measured by micro-computed tomography was 93.9 ± 4.04 % in the stented femoral arteries. CTOs were reliably induced by novel thin biodegradable polymer coated copper stents in porcine femoral arteries. Successful induction of CTOs may provide a practical understanding of their formation and application of an interventional device for CTO treatment.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

New strategy for detection of subclinical coronary atherosclerosis in asymptomatic patients with type 2 diabetes based on cardiac multi-detector computed tomography and treadmill test.

BACKGROUND: The current screening strategy for subclinical coronary atherosclerosis in asymptomatic diabetic patients is not sufficient in real clinical practice. A new strategy was investigated that uses cardiac multi-detector computed tomography (MDCT) and a treadmill test (TMT). METHODS AND RESULTS: A total of 445 self-referred asymptomatic diabetic patients underwent cardiac MDCT. The treatment plan was determined according to the new strategy that uses MDCT and TMT. All patients underwent clinical follow-up and cardiac events were investigated. The incidence of subclinical atherosclerosis was 49.4%. The group without plaque underwent clinical follow-up without treatment and did not experience any cardiac events in 675.1 person-years of follow-up. Among patients with subclinical atherosclerosis without significant stenosis (n=136) who received medical treatment only, 11 patients experienced cardiac events over 326.4 person-years. The patients with significant stenosis (n=84) underwent TMT. Patients with positive TMT (n=14) underwent coronary angiograms and revascularization therapy was performed in all of them over 39.2 person-years. Patients with negative TMT (n=70) underwent medical treatment, and 27 of them experienced cardiac events. The incidence of cardiac death was 0% during 3 years of follow-up. CONCLUSIONS: The new strategy for detecting subclinical atherosclerosis on MDCT combined with TMT may be a useful method for minimizing the mortality rate from cardiovascular disease in asymptomatic diabetic patients.