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Abstract Direct cardiac reprogramming represents a novel therapeutic strategy to convert non-cardiac cells such as fibroblasts into cardiomyocytes (CMs). This process involves essential transcription factors, such as Mef2c, Gata4, Tbx5 (MGT), MESP1, and MYOCD (MGTMM). However, the small molecules responsible for inducing immature induced CMs (iCMs) and the signaling mechanisms driving their maturation remain elusive. Our study explored the effects of various small molecules on iCM induction and discovered that the combination of FGF4 and ascorbic acid (FA) enhances CM markers, exhibits organized sarcomere and T-tubule structures, and improves cardiac function. Transcriptome analysis emphasized the importance of ECM-integrin-focal adhesions and the upregulation of the JAK2–STAT3 and TGFB signaling pathways in FA-treated iCMs. Notably, JAK2–STAT3 knockdown affected TGFB signaling and the ECM and downregulated mature CM markers in FA-treated iCMs. Our findings underscore the critical role of the JAK2–STAT3 signaling pathway in activating TGFB signaling and ECM synthesis in directly reprogrammed CMs. Schematic showing FA enhances direct cardiac reprogramming and JAK–STAT3 signaling pathways underlying cardiomyocyte maturation.

Abstract Background Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. Methods From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3–5) and gastrointestinal (GI) bleeding (BARC types 3–5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. Results Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18–8.78). The incidence of major bleeding and GI bleeding (BARC types 3–5) was comparable between PPI users and non-users in the PS-matched cohort. Conclusions In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Background Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on‐treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. Methods and Results The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (22.6 kg/m2). Patients 22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140–1.688]; P=0.001). No differences were shown in major bleeding. Conclusions HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Background Carriers of CYP2C19 loss‐of‐function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. Methods and Results The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel‐based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3‐year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all‐cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3‐year clinical outcomes. Conclusions In older patients, the presence of any CYP2C19 loss‐of‐function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. Registration URL: https://clinicaltrials.gov. Identifier: NCT04734028.

Abstract Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p

Abstract Limited knowledge exists regarding the predictors of mortality after successful weaning of venoarterial extracorporeal membrane oxygenation (ECMO). We aimed to identify predictors of in-hospital mortality in patients with cardiogenic shock (CS) after successful weaning from ECMO. Data were obtained from a multicenter registry of CS. Successful ECMO weaning was defined as survival with minimal mean arterial pressure (> 65 mmHg) for > 24 h after ECMO removal. The primary outcome was in-hospital mortality after successful ECMO weaning. Among 1247 patients with CS, 485 received ECMO, and 262 were successfully weaned from ECMO. In-hospital mortality occurred in 48 patients (18.3%). Survivors at discharge differed significantly from non-survivors in age, cardiovascular comorbidities, cause of CS, left ventricular ejection fraction, and use of adjunctive therapy. Five independent predictors for in-hospital mortality were identified: use of continuous renal replacement therapy (odds ratio 5.429, 95% confidence interval [CI] 2.468–11.940; p

Background/Aims The Genoss DES™ is a novel, biodegradable, polymer-coated, sirolimus-eluting stent with a cobalt-chromium stent platform and thin strut. Although the safety and effectiveness of this stent have been previously investigated, real-world clinical outcomes data are lacking. Therefore, the aim of this prospective, multicenter trial was to evaluate the clinical safety and effectiveness of the Genoss DES™ in all-comer patients undergoing percutaneous coronary intervention. Methods The Genoss DES registry is a prospective, single-arm, observational trial for evaluation of clinical outcomes after Genoss DES™ implantation in all-comer patients undergoing percutaneous coronary intervention from 17 sites in South Korea. The primary endpoint was a device-oriented composite outcome of cardiac death, target vessel-related myocardial infarction (MI), and clinically driven target lesion revascularization (TLR) at 12 months. Results A total of 1,999 patients (66.4 ± 11.1 years of age; 72.8% male) were analyzed. At baseline, 62.8% and 36.7% of patients had hypertension and diabetes, respectively. The implanted stent number, diameter, and length per patient were 1.5 ± 0.8, 3.1 ± 0.5 mm, and 37.0 ± 25.0 mm, respectively. The primary endpoint occurred in 1.8% patients, with a cardiac death rate of 1.1%, target vessel-related MI rate of 0.2%, and clinically driven TLR rate of 0.8%. Conclusions In this real-world registry, the Genoss DES™ demonstrated excellent safety and effectiveness at 12 months among all-comer patients undergoing percutaneous coronary intervention. These findings suggest that the Genoss DES™ may be a viable treatment option for patients with coronary artery disease.

Background Clinical outcome of ischemic cardiogenic shock (CS) requiring extracorporeal membrane oxygenation is highly variable, necessitating appropriate assessment of prognosis. However, a systemic predictive model estimating the mortality of refractory ischemic CS is lacking. The PRECISE (Prediction of In‐Hospital Mortality for Patients With Refractory Ischemic Cardiogenic Shock Requiring Veno‐Arterial Extracorporeal Membrane Oxygenation Support) score was developed to predict the prognosis of refractory ischemic CS due to acute myocardial infarction. Methods and Results Data were obtained from the multicenter CS registry RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) that consists of 322 patients with acute myocardial infarction complicated by refractory ischemic CS requiring extracorporeal membrane oxygenation support. Fifteen parameters were selected to assess in‐hospital mortality. The developed model was validated internally and externally using an independent external cohort (n=138). Among 322 patients, 138 (42.9%) survived postdischarge. Fifteen predictors were included for model development: age, diastolic blood pressure, hypertension, chronic kidney disease, peak lactic acid, serum creatinine, lowest left ventricular ejection fraction, vasoactive inotropic score, shock to extracorporeal membrane oxygenation insertion time, extracorporeal cardiopulmonary resuscitation, use of intra‐aortic balloon pump, continuous renal replacement therapy, mechanical ventilator, successful coronary revascularization, and staged percutaneous coronary intervention. The PRECISE score yielded a high area under the receiver‐operating characteristic curve (0.894 [95% CI, 0.860–0.927]). External validation and calibration resulted in competent sensitivity (area under the receiver‐operating characteristic curve, 0.895 [95% CI, 0.853–0.930]). Conclusions The PRECISE score demonstrated high predictive performance and directly translates into the expected in‐hospital mortality rate. The PRECISE score may be used to support clinical decision‐making in ischemic CS (www.theprecisescore.com). Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Objectives Electrocardiography (ECG)-based diagnosis by experts cannot maintain uniform quality because individual differences may occur. Previous public databases can be used for clinical studies, but there is no common standard that would allow databases to be combined. For this reason, it is difficult to conduct research that derives results by combining databases. Recent commercial ECG machines offer diagnoses similar to those of a physician. Therefore, the purpose of this study was to construct a standardized ECG database using computerized diagnoses. Methods The constructed database was standardized using Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) and Observational Medical Outcomes Partnership– common data model (OMOP-CDM), and data were then categorized into 10 groups based on the Minnesota classification. In addition, to extract high-quality waveforms, poor-quality ECGs were removed, and database bias was minimized by extracting at least 2,000 cases for each group. To check database quality, the difference in baseline displacement according to whether poor ECGs were removed was analyzed, and the usefulness of the database was verified with seven classification models using waveforms. Results The standardized KURIAS-ECG database consists of high-quality ECGs from 13,862 patients, with about 20,000 data points, making it possible to obtain more than 2,000 for each Minnesota classification. An artificial intelligence classification model using the data extracted through SNOMED-CT showed an average accuracy of 88.03%. Conclusions The KURIAS-ECG database contains standardized ECG data extracted from various machines. The proposed protocol should promote cardiovascular disease research using big data and artificial intelligence.

Background: Despite advancements in coronary artery disease (CAD) treatment with drug-eluting stent, its morbidity and mortality remain high. In context, intravascular imaging-guided percutaneous coronary intervention (PCI) is increasingly recommended for better clinical outcomes in patient with CAD. Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), as one of the intravascular imaging methods, is effective in detecting lipid-rich plaques, which is crucial for identifying high-risk or vulnerable plaques employing near-infrared light. High lipid core burden, as identified by NIRS-IVUS, correlates with an increased risk of adverse cardiac events and shows varying degrees of efficacy in plaque management and event prevention. Summary: This article addresses about how NIRS-IVUS can be used to predict event of CAD. The study highlights the crucial role of NIRS-IVUS in predicting future cardiovascular events. Findings indicate that the presence of high lipid core burden is related to increased risks of periprocedural myocardial infarction and reduced coronary flow during PCI. The study also outlines the predictive value of NIRS-IVUS in non-culprit lesions, where plaques with high lipid core burden significantly increase the occurrence of major adverse cardiac events as demonstrated in the PROSPECT II trial. In terms of therapeutic strategies, the study reviews the effectiveness of high-intensity lipid-lowering strategies in stabilizing vulnerable plaques, as evidenced in trials such as the YELLOW and PACMAN AMI trials. Key Messages: NIRS-IVUS emerges as a valuable diagnostic tool in treating CAD. It effectively identifies vulnerable plaques and aids in predicting and preventing future adverse cardiac events. However, to enhance its practicality and promote widespread adoption in clinical settings, further long-term outcome research of NIRS-IVUS-guided PCI is necessary. These efforts can potentially make NIRS-IVUS a more accessible and indispensable tool in cardiovascular disease management.

Background No large‐scale study has compared the clinical impact of triple antiplatelet therapy (TAPT: aspirin, clopidogrel, and cilostazol) and dual antiplatelet therapy (DAPT) on adverse limb events in patients with diabetes after endovascular therapy (EVT) for peripheral artery disease. Thus, we investigate the effect of cilostazol added to a DAPT on the clinical outcomes after EVT in patients with diabetes using a nationwide, multicenter, real‐world registry. Methods and Results A total of 990 patients with diabetes who underwent EVT were enrolled from the retrospective cohorts of a Korean multicenter EVT registry and were divided according to the antiplatelet regimen (TAPT [n=350; 35.4%] versus DAPT [n=640; 64.6%]). After propensity score matching based on clinical characteristics, a total of 350 pairs were compared for clinical outcomes. The primary end points were major adverse limb events, a composite of major amputation, minor amputation, and reintervention. For the matched study groups, the lesion length was 125.4±102.0 mm, and severe calcification was observed in 47.4%. The technical success rate (96.9% versus 94.0%; P=0.102) and the complication rate (6.9% versus 6.6%; P>0.999) were similar between the TAPT and DAPT groups. At 2‐year follow‐up, the incidence of major adverse limb events (16.6% versus 19.4%; P=0.260) did not differ between the 2 groups. However, the TAPT group showed less minor amputation than the DAPT group (2.0% versus 6.3%; P=0.004). In multivariate analysis, TAPT was an independent predictor of minor amputation (adjusted hazard ratio, 0.354 [95% CI, 0.158–0.794]; P=0.012). Conclusions In patients with diabetes undergoing EVT for peripheral artery disease, TAPT did not decrease the incidence of major adverse limb events but may be associated with a decreased risk of minor amputation.

BackgroundOlder patients who treated by percutaneous coronary intervention (PCI) are at a higher risk of adverse cardiac outcomes. We sought to investigate the clinical impact of bifurcation PCI in older patients from Korea and Italy.MethodsWe selected 5,537 patients who underwent bifurcation PCI from the BIFURCAT (comBined Insights from the Unified RAIN and COBIS bifurcAtion regisTries) database. The primary outcome was a composite of target vessel myocardial infarction, clinically driven target lesion revascularization, and stent thrombosis at two years.ResultsIn patients aged ≥75 years, the mean age was 80.1 ± 4.0 years, 65.2% were men, and 33.7% had diabetes. Older patients more frequently presented with chronic kidney disease (CKD), severe coronary calcification, and left main coronary artery disease (LMCA). During a median follow-up of 2.1 years, older patients showed similar adverse clinical outcomes compared to younger patients (the primary outcome, 5.7% vs. 4.5%; p = 0.21). Advanced age was not an independent predictor of the primary outcome (p = 0.93) in overall patients. Both CKD and LMCA were independent predictors regardless of age group.ConclusionsOlder patients (≥75 years) showed similar clinical outcomes to those of younger patients after bifurcation PCI. Advanced age alone should not deter physicians from performing complex PCIs for bifurcation disease.

BackgroundDiabetes mellitus (DM) is a critical risk factor for the pathogenesis and progression of coronary artery disease, with a higher prevalence of complex coronary artery disease, including bifurcation lesions. This study aimed to elucidate the optimal stenting strategy for coronary bifurcation lesions in patients with DM.MethodsA total of 905 patients with DM and bifurcation lesions treated with second-generation drug-eluting stents (DES) from a multicenter retrospective patient cohort were analyzed. The primary outcome was the 5-year incidence of target lesion failure (TLF), which was defined as a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization.ResultsAmong all patients with DM with significant bifurcation lesions, 729 (80.6%) and 176 (19.4%) were treated with one- and two-stent strategies, respectively. TLF incidence differed according to the stenting strategy during the mean follow-up of 42 ± 20 months. Among the stent strategies, T- and V-stents were associated with a higher TLF incidence than one-stent strategy (24.0 vs. 7.3%, p < 0.001), whereas no difference was observed in TLF between the one-stent strategy and crush or culotte technique (7.3 vs. 5.9%, p = 0.645). The T- or V-stent technique was an independent predictor of TLF in multivariate analysis (hazard ratio, 3.592; 95% confidence interval, 2.117–6.095; p < 0.001). Chronic kidney disease, reduced left ventricular ejection fraction, and left main bifurcation were independent predictors of TLF in patients with DM.ConclusionT- or V-stenting in patients with DM resulted in increased cardiovascular events after second-generation DES implantation.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03068494?term=03068494&draw=2&rank=1, identifier: NCT03068494.

The generation of mature and vascularized human pluripotent stem cell-derived cardiac organoids (hPSC-COs) is necessary to ensure the validity of drug screening and disease modeling. This study investigates the effects of cellular aggregate (CA) stemness and self-organization on the generation of mature and vascularized hPSC-COs and elucidates the mechanisms underlying cardiac organoid (CO) maturation and vascularization. COs derived from 2-day-old CAs with high stemness (H-COs) and COs derived from 5-day-old CAs with low stemness (L-COs) were generated in a self-organized microenvironment via Wnt signaling induction. This study finds that H-COs exhibit ventricular, structural, metabolic, and functional cardiomyocyte maturation and vessel networks consisting of endothelial cells, smooth muscle cells, pericytes, and basement membranes compared to L-COs. Transcriptional profiling shows the upregulation of genes associated with cardiac maturation and vessel formation in H-COs compared with the genes in L-COs. Through experiments with LIMK inhibitors, the activation of ROCK-LIMK-pCofilin via ECM–integrin interactions leads to cardiomyocyte maturation and vessel formation in H-COs. Furthermore, the LIMK/Cofilin signaling pathway induces TGFβ/NODAL and PDGF pathway activation for the maturation and vascularization of H-COs. The study demonstrates for the first time that LIMK/Cofilin axis activation plays an important role in the generation of mature and vascularized COs.

Abstract Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08–5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding. Trial registration: NCT02707445 ( https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1 ).

Abstract Background The current guidelines recommend both repeat stenting and drug-coated balloons (DCB) for in-stent restenosis (ISR) lesions, if technically feasible. However, real-world clinical data on the interventional strategies in patients with left main bifurcation (LMB)-ISR have not been elucidated. Methods Seventy-five patients with LMB-ISR, who underwent percutaneous coronary intervention (PCI) between January 2009 and July 2015, were retrospectively reviewed for the present study (repeat drug eluting stent [DES] implantation [n = 51], DCB angioplasty [n = 24]). Results Analysis of the baseline characteristics showed that the patients in the DCB group had a lower incidence of non-ST segment elevation myocardial infarction/ST segment elevation myocardial infarction at the index PCI (8.3% vs. 25.5%; p = 0.12), higher low-density lipoprotein-cholesterol level (92.9 mg/dL vs. 81.7 mg/dL; p = 0.09), and more “stent-in-stent” lesions (25% vs. 7.8%; p = 0.07) than those in the DES group. A smaller post-procedural minimal target lesion lumen diameter was also noted in the DCB group than in the DES group (2.71 mm vs. 2.85 mm; p = 0.03). The cumulative incidence rates of major adverse cardiac events (MACEs) were similar between both groups (median follow-up duration, 868 days; MACE rate, 25% in the DCB group vs. 25.5% in the DES group; p = 0.96). The multivariate Cox regression analysis indicated that the true bifurcation of ISR was an independent risk predictor of MACEs (hazard ratio, 4.62; 95% confidence interval, 1.572–13.561; p

Abstract Background Sca-1+ cardiac stem cells and their limited proliferative potential were major limiting factors for use in various studies. Methods Therefore, the effects of sphere genetically engineered cardiac stem cells (S-GECS) inserted with telomerase reverse transcriptase (TERT) were investigated to examine cardiomyocyte survival under hypoxic conditions. GECS was obtained from hTERT-immortalized Sca-1+ cardiac stem cell (CSC) lines, and S-GECS were generated using poly-HEMA. Results The optimal conditions for S-GECS was determined to be 1052 GECS cells/mm2 and a 48 h culture period to produce spheroids. Compared to adherent-GECS (A-GECS) and S-GECS showed significantly higher mRNA expression of SDF-1α and CXCR4. S-GECS conditioned medium (CM) significantly reduced the proportion of early and late apoptotic cardiomyoblasts during CoCl2-induced hypoxic injury; however, gene silencing via CXCR4 siRNA deteriorated the protective effects of S-GECS against hypoxic injury. As downstream pathways of SDF-1α/CXCR4, the Erk and Akt signaling pathways were stimulated in the presence of S-GECS CM. S-GECS transplantation into a rat acute myocardial infarction model improved cardiac function and reduced the fibrotic area. These cardioprotective effects were confirmed to be related with the SDF-1α/CXCR4 pathway. Conclusions Our findings suggest that paracrine factors secreted from transplanted cells may protect host cardiomyoblasts in the infarcted myocardium, contributing to beneficial left ventricle (LV) remodeling after acute myocardial infarction (AMI).

Abstract Background Statin therapy reduces the risk of cardiovascular events across a broad spectrum of patients; however, it increases the risk of new-onset diabetes (NOD). Although the highest dose pitavastatin is considered to not be associated with NOD, there are limited data regarding the impact of long-term highest dose pitavastatin use on the development of NOD in patients at high risk of developing diabetes. Therefore, we prospectively compared the differences in the development of NOD between the lowest and the highest dose of pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up. Methods This post hoc analysis of a prospective, single-blinded, randomized study compared the risk of NOD between the highest dose of pitavastatin (4 mg) and the lowest dose of pitavastatin (1 mg) over a 3-year follow-up in patients with acute coronary syndrome. Among 1044 patients of the original study, 667 patients at high risk of developing type 2 diabetes mellitus were in the subgroup analysis. The primary endpoint was a comparison of the differences in the cumulative incidence of NOD in the pitavastatin 1 mg and 4 mg groups during a 3-year follow-up. Results With propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups. Incidence of NOD was similar between the pitavastatin 1 mg and 4 mg groups [12 of 289 patients (4.2%) and 8 of 289 patients (2.8%), respectively; p = 0.36]. In a prespecified analysis, there were no significant differences in NOD events according to sex, age, diagnosis, body mass index, glucose intolerance, or dyslipidemia. Conclusions Administration of highest-dose pitavastatin did not increase the risk of NOD in patients at high risk of developing diabetes during the 3-year follow-up. Moreover, various risk factors for NOD such as metabolic syndrome components, glucose intolerance, dyslipidemia, obesity, or hypertension did not affect the development of NOD during pitavastatin administration. Thus, the highest dose pitavastatin can be safely used in patients with metabolic syndrome who are at high risk of developing diabetes. Trial registration Clinical Trial registration information. URL: https://clinicaltrials.gov/ct2/show/NCT02545231. Unique identifier: NCT02545231

Abstract Background There have been limited data on the impact of hyperuricemia on long-term clinical outcomes after percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). Methods From January 2009 to July 2015, 317 patients who underwent repeat PCI for ISR were divided into two groups: patients with normal serum uric acid (UA) levels (normal UA group) and patients with higher serum UA levels (higher UA group). The higher UA group included patients with serum UA levels > 6.8 mg/dL or patients who were taking anti-hyperuricemic medication. Results During a median follow-up period of 1088 days, the cumulative incidence rates of major adverse event (MAE), including a composite of all-cause death, non-fatal myocardial infarction, and any revascularization, were similar between the two groups (higher UA 36.4% vs. normal UA 29.9%, p = 0.389, log-rank p = 0.367). Follow-up angiographic data showed similar outcomes of late lumen loss (0.8 ± 0.9 mm vs. 0.8 ± 1.1 mm, p = 0.895) and binary restenosis rate (28.1% vs. 34.7%, p = 0.622). Multivariate Cox regression analysis indicated higher levels of low-density lipoprotein cholesterol (hazard ratio [HR] 1.011, 95% confidence interval [CI] 1.003–1.019, p = 0.006) and lower left ventricular ejection fraction (HR 0.972, 95% CI 0.948–0.996, p = 0.022), but not UA levels, to be the independent risk predictors of MAE. Conclusion Hyperuricemia is not associated with poor clinical outcomes after repeat PCI for ISR lesions.

Although it has been demonstrated that visceral adipose tissue content and serum levels of adiponectin are associated with metabolic syndrome, their predictive potential for the development of metabolic syndrome remains to be elucidated.We studied 1,130 participants of the Seoul Metabolic Syndrome cohort. A total of 337 subjects without metabolic syndrome underwent the follow-up evaluation and finally analyzed. Visceral fat area (VFA) was measured using dual bioelectrical impedance analysis. We compared the 1-year incidence rate of metabolic syndrome among four different groups: Group 1 (high adiponectin level and low VFA), Group 2 (low adiponectin level and low VFA), Group 3 (high adiponectin level and high VFA) and Group 4 (low adiponectin level and high VFA).Median follow-up duration was 17 months. Cut-off points of adiponectin level and VFA for metabolic syndrome were 7.34 ng/ml and 84 cm2 for men, and 12.55 and 58 cm2 ng/ml for women, respectively. The incidence of metabolic syndrome was the highest in Group 4 (Group 1; 16.47%, Group 2; 22.08%, Group 3; 25%, and Group 4; 46.15%, p

Background: Coronary spasm cause transient LV dysfunction and consequently may increase BNP by chance. However, the correlation between coronary spasm and BNP has not been verified. We investigated the association between coronary spasm and BNP and pulse wave velocity (PWV) in patients with preserved LV function. Methods: A patients with chest pain who have ejection fraction >50% underwent both diagnostic coronary angiography with acetylcholine provocation and NT-proBNP measurement simultaneously were enrolled for the study. PWV were done in all patients. Significant coronary artery spasm was defined as focal (>70%) or diffuse severe transient luminal narrowing (>90%) with/without chest pain or ST-T change of ECG. Results: Among total 1,342 patients, 793 patients with heart failure, arrhythmia, CAD or VHD were excluded and 549 patients were enrolled. Thirty five percent (192/549) of enrolled subjects showed positive result at acetylcholine provocation test. Baseline characteristics were well balanced between the spasm group and control group. In the univariate analysis, the BNP levels of spasm group were lower than control group (146±363pg/mL vs. 197±532pg/mL, P=0.050). But in the multivariate analysis, there was no significant difference of BNP between two groups. Also there is no difference of PWV value between the groups. Conclusion: There is no significant relationship between BNP, PWV and vasospastic angina. These finding suggest that vasospastic angina with normal left ventricular systolic function is not associated with BNP or PWV.

The article discusses the results of a survey conducted by the Study Group on Generating Recommendations to Encourage Environmentally-Responsible Networking (SG-GREEN) within the PICES organization. The survey aimed to gather information on members' interest in changing the way they meet, purchasing carbon credits, participating in beach clean-ups, and other environmental activities. The survey found that there was overwhelming interest in changing the way business is conducted within the organization. The article also includes information on respondents' demographics, their opinions on attending annual meetings, carbon offsets, and ocean preservation activities. The article concludes by mentioning the efforts of partner organizations in addressing these issues and emphasizes the importance of continuing the discussion on climate mitigation activities. [Extracted from the article]

An air-sea interaction field campaign was conducted in September of 2017 within the warm and cold eddy region of the western Northwest Pacific (WNP) (17.5°-20.5°N, 127.5°E-133.5°E). Both near-surface oceanic and atmospheric conditions in addition to ocean heat content (OHC) were examined to better understand the mechanisms governing high heat flux magnitudes responsible for rapidly intensifying tropical cyclones. Observations from this experiment indicate that the latent heat flux (LHF) under modest wind conditions reached 400Wm-2 within the vicinity of a warm eddy, with OHC higher than 100 kJ cm-2 of warm eddy region being 2~3 times as large as that of cold eddy region. These high OHC and a resultant high LHF in the warm eddy, comparable to the magnitude of LHF in the North Equatorial Current, may explain the mechanism of why tropical cyclones over a warm eddy in eddy-rich zones often rapidly intensify in the WNP. A month later typhoon Lan rapidly intensified into a super typhoon, while passing over the boundary region of warm and cold eddies during the observation period. Results from this study illustrate that both the wind-normalized LHF and the difference (Qs-Qa) between the specific humidity at air (Qa) and at the sea surface (Qs), closely correlate with OHC patterns, which suggests that the ocean looks likely to control the spatial pattern of LHF. Overall, both the ocean and weather conditions govern the pattern of specific humidity difference between the air-sea interface, with large OHC over the warm eddy controlling higher Qs and the pattern of Qa depending on the pattern of wind direction. Qa as a factor impacting LHF magnitude is strongly linked to wind direction in the experimental area, that is, the drier northwesterly flow and southeasterly moist wind, resulting in the enhanced contrast of specific humidity at cold eddy region. [ABSTRACT FROM AUTHOR]

Introduction: Understanding the underlying dynamics of regional sea-level rise (SLR), which often deviates from global trends, is crucial for mitigating and adapting to the impacts of severe climate change. This study investigated the causes of high regional SLR rates (> 6.0 mm yr-1) around the frontal region near Ulleung Island in the southwestern East/Japan Sea (EJS). Despite exhibiting rates higher than the global average (3.1 mm yr-1) from 1993 to 2020, the reasons for these higher rates in this region have not been clearly elucidated. Methods: We aimed to clarify the quantitative effect of the long-term variations of the Ulleung Warm Eddy (UWE) on the high SLR rates near Ulleung Island based on satellite altimetry and ship-based hydrographic data. Results: During this period, the temperature within the UWE increased, particularly at the temperature-homogeneous layer of approximately 200 m, the lower boundary of the UWE deepened, and the eddy duration per year increased, resulting in high SLR rates within the eddy owing to the steric height rise. The long-term variations in the internal temperature and vertical thickness of the UWE had significantly comparable impacts on SLR rates, with the duration being less influential. The SLR rates by integrating all long-term variations in the UWE (7.6 mm yr-1) quantitatively explained the high long-term SLR rates at Ulleung Island (7.0 mm yr-1). Discussion: The increasing temperature within the UWE was attributed to the rising temperature of water flowing through the southwestern strait (Korean Strait) in late fall, and the deepening lower boundary and the increasing duration of the UWE resulted from the increased horizontal temperature gradients near the front, leading to enhanced baroclinic instability in the subsurface layers. Our findings suggest that long-term variations in mesoscale eddies can significantly influence the regional SLR rates, deviating substantially from the global average in the frontal region. [ABSTRACT FROM AUTHOR]

In this study, we investigate the record-breaking intensification and abrupt weakening of the East Korea Warm Current (EKWC) in the summer of 2021. We analyzed the ocean data assimilation products resolving this event to examine the association between the abrupt changes in the EKWC and various oceanic/atmospheric factors. The results indicate that during the summer of 2021, the EKWC extended northward beyond its climatology, reaching up to 40°N with the maximum speed of 1.16 m s-1 on August 1. In mid-August, the EKWC underwent a rapid weakening, returning to its climatological level. We could attribute the temporal variability in the anomalous EKWC in 2021 to the distinct temporal variability in the dynamic height anomalies between coastal and offshore regions. The offshore variability in the dynamic height anomaly, which is related to warm eddy variability, led to an anomalously increased EKWC velocity (up to 0.59 m s-1) during the EKWC peak velocity period in 2021. However, anomalous coastal downwelling induced by a weak northerly wind anomaly decelerated the EKWC by -0.06 m s-1 in the same period. In mid-August, a typhoon-related northerly wind induced a sudden rise in the coastal dynamic height anomaly, resulting in a rapid weakening of the EKWC. Our findings suggest that changes in geostrophic current related to warm eddies and typhoons have substantially contributed to the temporal variability in the EKWC, improving our understanding of the temporal variability in the western boundary currents. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the mean pulse rate (PR) and mean blood pressure (BP) between patients with obstructive sleep apnea (OSA) and those with simple snoring (SS) during a 24-hour period, and to investigate the correlation between apnea-hypopnea index (AHI), PR, and BP in sleep-related breathing disorder (SRBD) patients with and without hypertension, diabetes mellitus (DM), and cardiovascular diseases (CVDs). Methods: Ninety SRBD patients underwent full-night polysomnography, and ambulatory BP and PR were monitored for 24 hours. Participants were classified into OSA (AHI = 5) and control (SS) (AHI < 5) groups, and BP and PR were compared. Participants were also divided into groups with and without hypertension, CVDs, or DM to analyze the correlation between AHI, BP, and PR in each group. Results: Mean PRs during the daytime period and during the whole 24-hour period in the OSA group were significantly higher than those in the SS group after controlling for potential confounders. No significant difference was observed in mean BP between the groups. Partial correlation analysis after controlling for confounders showed significant correlation between AHI and PR during daytime and the 24-hour period in participants without hypertension, DM, or CVDs, but not in participants with these conditions. Conclusion: The significant differences and correlations only in PR (not in BP) found in this study suggest that PR could be an early marker for SRBD in individuals without comorbidities, and that an increased sympathetic tone could be responsible for future occurrence of CVD. [ABSTRACT FROM AUTHOR]

We present intensive observational data of surface chlorophyll-a bloom episodes occurring over several days in the summers of 2011, 2012, and 2013, accompanying the equatorward advection of low sea-surface salinity (SSS) water near the east coast of Korea. Time-series analysis of meteorological and oceanographic (physical and biochemical) parameter data, such as chlorophyll fluorescence (CF) from surface mooring, ocean color (chlorophyll a and total suspended sediment), sea surface height (satellite-derived), and serial hydrographic data (from in-situ measurements) were used to investigate the relationship between surface bloom events and changes in seawater characteristics and currents. In the summers of the three years, a total of 10 bloom events (E01-E10) were identified where the surface CF was significantly (> 2 μg/l) enhanced over a relatively long (> 1 day) period. The bloom events in the summers of 2011 and 2012 accompanied low or decreasing SSS for several days to a week after heavy rainfalls at upstream stations and equatorward currents. Unlike the typical 8 of the 10 events (80 %), E07 was potentially derived from the onshore advection of high CF offshore water of southern origin into the coastal zone near the mooring, whereas E10 is likely prevailed by offshore advection of high CF plume water trapped by the coastal area. Contrasting with many coastal systems, these findings indicate that event-scale productivity near the east coast of Korea in summer is not controlled by local blooms triggered by either nutrients or light availability, but by the equatorward and cross-shore advections of high CF plume water. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) not only eliminate unwanted molecular components, but also carry molecular cargo essential for specific intercellular communication mechanisms. As the molecular characteristics and biogenetical mechanisms of heterogeneous EVs are different, many studies have attempted to purify and characterize EVs. In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. However, several unresolved issues and challenges remain despite these promising results, including source variability before the isolation of exosomes from body fluids, the contamination of proteins during isolation, and methodological issues related to the purification of exosomes. This paper reviews the general characteristics of EVs, particularly microvesicles and exosomes, along with their physiological roles and contribution to the pathogenesis of major diseases, several widely used methods to isolate exosomes, and challenges in the development of disease biomarkers using the molecular contents of EVs isolated from body fluids. [ABSTRACT FROM AUTHOR]

Background: Arterial stiffness has been suggested as a valuable predictor of coronary artery stenosis (CAS). However, little data are available on aortic stiffness and CAS in patients who have previously undergone percutaneous coronary artery intervention (PCI). The aim of this study was to investigate the association of arterial stiffness to CAS in patients with a history of PCI and those without a history of PCI.Methods: We retrospectively studied 1093 consecutive patients who had undergone coronary angiography (CAG). Arterial stiffness was determined by brachial-ankle pulse wave velocity (baPWV) measured prior to CAG.Results: In patients without a history of PCI, baPWV significantly increased in patients with CAS compared to that in patients without CAS (p < 0.001). However, among patients with a history of PCI, there was no significant difference in baPWV. Multivariate logistic regression analysis demonstrated that baPWV was an independent risk predictor for CAS in patients without a history of PCI, but not in those with a history of PCI (OR 1.106, 95% CI 1.039-1.177, p = 0.002). In CAS patients without a history of PCI, increased baPWV was significantly associated with multiple cardiovascular risk factors, multivessel involvement, and anatomical severity.Conclusions: Prediction of CAS by baPWV is significantly attenuated in patients with a history of PCI. [ABSTRACT FROM AUTHOR]

In this work, a silicon-based micro-probe array was fabricated using multi-step deep reactive ion etching (DRIE) and reactive ion etching (RIE) processes. The micro-probe structure was implemented using a micromachining technique through a combination of two anisotropic DRIE and two isotropic RIE processes with a single etch mask. The cone-shaped tip height and tapered tip-end angle were experimentally varied with respect to the first DRIE depth. As the first DRIE depth was decreased, the micro-probe tip height increased and the sharpness consequently improved. The conductive layer was exposed only at the tip ends of the micro-probe to form a conical ultra-micro electrode, and it was characterised via cyclic voltammetry measurements. [ABSTRACT FROM AUTHOR]