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The aim of this study was to fabricate a novel polymer-free everolimus-eluting stent with nanostructure using a femtosecond laser (FSL). The stent were coated with everolimus (EVL) using FSL and electrospinning processes. The surface was rendered hydrophobic, which negatively affected both platelet adhesion (82.1%) and smooth muscle cell response. Animal study was performed using a porcine coronary restenosis model. The study groups were divided into 1) bare metal stent (BMS), 2) poly(L-lactide) (PLA)-based EVL drug eluting stent (DES), 3) commercial EVL-eluting DES, and 4) FSL-EVL-DES. After four weeks of stent implantation, various analyses were performed. Quantitative analysis showed that the amount of in-stent restenosis was higher in the BMS group (BMS; 27.8 ± 2.68%, PLA-based DES; 12.2 ± 0.57%, commercial DES; 9.8 ± 0.28%, and FSL-DES; 9.3 ± 0.25%, n  = 10, p  < 0.05). Specifically, the inflammation score was reduced in the FSL-DES group (1.9 ± 0.39, n  = 10, p  < 0.05). The increment in re-endothelialization in the FSL-DES group was confirmed by immunofluorescence analysis. Taken together, the novel polymer-free EVL-eluting stent fabricated using FSL can be an innovative DES with reduced risk of ISR, thrombosis, and inflammation.

This study was performed to evaluate the effects of a diamond-like carbon (DLC) layer on the biological properties of a pre-treated titanium dioxide (TiO2) coronary stent surface. TiO2 and DLC were coated onto a cobalt-chromium stent surface in consecutive order using the plasma-enhanced chemical vapor deposition method (TiO2/DLC). To investigate the effect of TiO2, a group treated only with DLC was also prepared as a control. The surface characteristics were investigated by SEM, ESCA, AFM, and contact angle analyses. To estimate the effect of surface modification on biological response, endothelial cell migration was carried out. As a result, cracking of the coating layer on the strut curved portion in the DLC group was restored in the TiO2/DLC group. ESCA result showed that the peaks sp2 and sp3 were slightly shifted and higher in the TiO2/DLC group. The surface roughness average was highly increased in the TiO2/DLC group (Ra; 18.033) compared to the BMS (Ra; 9.258) and DLC groups (Ra; 10.144). By the increment of Ra, the surface property became hydrophilic in the TiO2/DLC group (39.8° ± 5.88°) compared to the non-treated (72.7° ± 2.24°) and DLC (78.6° ± 2.24°) groups. Endothelial cell migration was significantly increased in the TiO2/DLC group (68.9 ± 13.52%) compared to the non-treated (5.4 ± 3.14%) and DLC groups (22.3 ± 8.22%). Therefore, the improvement of surface properties and endothelial cell migration in the TiO2/DLC group could improve the physiological response in the human body.Graphic Abstract

Heart failure (HF) remains a major cause of mortality worldwide. While novel approaches, including gene and cell therapies, show promise, efficient delivery methods for such biologics to the heart are critically needed. One emerging strategy is lung-to-heart delivery using nanoparticle (NP)-encapsulated biologics. This study examines the efficiency of delivering a therapeutic peptide conjugated to a cell-penetrating peptide (CPP) to the heart via the lung-to-heart route through intratracheal (IT) injection in mice. The CPP, a tandem repeat of NP2 (dNP2) derived from the human novel LZAP-binding protein (NLBP), facilitates intracellular delivery of the therapeutic payload. The therapeutic peptide, SE, is a decoy peptide designed to inhibit protein phosphatase 1 (PP1)-mediated dephosphorylation of phospholamban (PLN). Our results demonstrated that IT injection of dNP2-SE facilitated efficient delivery to the heart, with peak accumulation at 3 h post-injection. The administration of dNP2-SE significantly ameliorated morphological and functional deterioration of the heart under myocardial infarction. At the molecular level, dNP2-SE effectively prevented PLN dephosphorylation in the heart. Immunoprecipitation experiments further revealed that dNP2-SE binds strongly to PP1 and disrupts its interaction with PLN. Collectively, our findings suggest that lung-to-heart delivery of a CPP-conjugated therapeutic peptide, dNP2-SE, represents a promising approach for the treatment of HF.

Chlorogenic acid, an ester of caffeic acid and quinic acid, is found in foods such as eggplant and peaches. Its role in heart disease remains poorly understood. This study investigated whether chlorogenic acid affects cardiac hypertrophy and fibrosis in animal and cellular models of isoproterenol-induced cardiac hypertrophy. Treatment of isoproterenol-stimulated cardiomyocytes with chlorogenic acid reduced cell size and the expression levels of cardiac hypertrophy-related genes. In the animal model, isoproterenol was delivered via an osmotic minipump for 2 weeks to induce cardiac hypertrophy, and chlorogenic acid was intraperitoneally administered for the same duration. Echocardiographic analysis showed that chlorogenic acid significantly reduced wall thickness in mice. Picrosirius red staining, quantitative reverse transcription polymerase chain reaction, and Western blot analysis revealed that cardiac fibrosis was attenuated by chlorogenic acid. Chlorogenic acid treatment downregulated galectin 3 ( Lgals3 ), a fibrosis-associated gene that had been upregulated by isoproterenol stimulation. Galectin 3 knockdown ameliorated isoproterenol-induced cardiac hypertrophy and reduced the expression levels of COL1A1 and ADAMTS8; galectin 3 overexpression increased cardiomyocyte size and upregulated COL1A1 and ADAMTS8 expression levels. These findings suggest that chlorogenic acid could serve as a novel treatment for cardiac hypertrophy and fibrosis via downregulation of galectin 3.

Dyslipidemia is an important risk factor for acute myocardial infarction. However, real-world data on its prevalence and lipid management trends for Korean patients with acute myocardial infarction are limited. This study aimed to determine the 10-year temporal trends in dyslipidemia prevalence and lipid management in this patient population. The study used a merged database of two nationwide observational cohorts (2011-2020) that included 26,751 participants. The primary endpoints were the achievement rates of the (1) absolute low-density lipoprotein cholesterol (LDL-C) target of <70 mg/dL (<1.8 mmol/L), (2) relative LDL-C target reduction of >50% from the baseline, (3) absolute or relative LDL-C target (American target), and (4) both absolute and relative LDL-C targets (European target). The dyslipidemia prevalence increased from 11.1% to 17.1%, whereas the statin prescription rate increased from 92.9% to 97.0% from 2011 to 2020. The rate of high-intensity statin use increased from 12.80% in 2012 to 69.30% in 2020. The rate of ezetimibe use increased from 4.50% in 2016 to 22.50% in 2020. The high-intensity statin and ezetimibe prescription rates (0.20% to 9.30% from 2016 to 2020) increased gradually. The absolute and relative LDL-C target achievement rates increased from 41.4% and 20.8% in 2012 to 62.5% and 39.5% in 2019, respectively. The American (45.7% in 2012 to 68.6% in 2019) and European (16.5% in 2012 to 33.8% in 2019) target achievement rates also increased. The adoption of lipid management guidelines in clinical practice has improved. However, continued efforts are needed to reduce the risk of recurrent ischemic events.

The optimal timing of complete revascularisation for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. We aimed to assess whether immediate complete revascularisation was non-inferior to staged complete revascularisation during the index admission. We conducted an open-label, randomised, non-inferiority trial at 14 hospitals in South Korea. Patients aged 19 years or older with STEMI and multivessel disease who had undergone percutaneous coronary intervention (PCI) for a culprit lesion were randomly assigned 1:1 to immediate complete revascularisation (PCI for non-culprit lesions during the index procedure) or staged complete revascularisation (non-culprit PCI on another day during the index admission). Web-based, permuted-block randomisation (using mixed block sizes of two or four) was implemented at each participating centre to allocate patients. Non-culprit lesions with 50–69% stenosis were evaluated by fractional flow reserve. Study participants and study investigators were aware of treatment allocation, but members of the independent clinical committee reviewing primary and secondary endpoints were masked to treatment allocation. The primary endpoint was a composite of death from any cause, non-fatal myocardial infarction, or any unplanned revascularisation at 1 year in the intention-to-treat population, and the non-inferiority margin was set at a hazard ratio (HR) of 1·42; if the upper boundary of the one-sided 97·5% CI of the HR was less than 1·42, immediate complete revascularisation would be considered non-inferior to staged complete revascularisation. Reported adverse events consisted of procedural complications, other complications during admission, and in-hospital clinical events occurring during the index admission. This trial is registered with the Clinical Research Information Service (KCT0004457) and ClinicalTrials.gov (NCT04626882). Long-term follow-up is ongoing. Between Dec 30, 2019, and Jan 15, 2024, 994 patients were enrolled and randomly assigned to immediate revascularisation (n=498; immediate group) or staged revascularisation (n=496; staged group). The primary endpoint occurred at 1 year in 65 patients (13%) in the immediate group and 53 patients (11%) in the staged group (HR 1·24 [95% CI 0·86–1·79]; pnon-inferiority=0·24). Rates of stroke, major bleeding, and contrast-induced nephropathy did not differ significantly between the two groups. Cardiogenic shock during the index hospitalisation occurred in 18 (4%) of 498 patients in the immediate group and nine (2%) of 496 patients in the staged complete revascularisation group. Among patients with STEMI and multivessel disease, immediate complete revascularisation was not shown to be non-inferior to staged complete revascularisation during the index admission in terms of incidence of a composite of death from any cause, non-fatal myocardial infarction, or any unplanned revascularisation at 1 year. This finding might inform future clinical guidelines on the role and optimal use of immediate complete revascularisation during the index admission. Boston Scientific.

•This detailed time-point outcome assessment, which accounts for the number of patients at risk during specific periods, could be a step toward developing an advanced risk prediction model for time-course personalized medicine.•Patients with ST-elevation myocardial infarction (STEMI) initially had a significantly higher mortality rate than those with non-STEMI; however, this trend was inverted since the second week.•The higher mortality rate in patients with STEMI versus non-STEMI was inverted since the second week for male patients but only since the tenth week for female patients.•Several baseline variables, including Killip class, systolic blood pressure, total cholesterol, and STEMI diagnosis, had significantly different effects on deaths over time after acute myocardial infarction. Limited data exist regarding time-point risk stratification models after acute coronary syndrome. This study aimed to investigate time-point mortality rates in patients with acute myocardial infarction, focusing on comparison by type of myocardial infarction, in a real-world cohort. A total of 12,836 patients from a nationwide Korean registry were analyzed. Mortality rates at yearly, monthly, and weekly time points after admission were calculated by dividing the number of deaths during a specific period by the number of patients at risk in the same period for ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) groups. In the first week after admission, patients with STEMI had a significantly higher mortality rate than patients with NSTEMI (4.62% vs 1.79%, p <0.001). However, this trend was inverted since the second week. The higher mortality rate in patients with STEMI versus NSTEMI was inverted since the second week for male patients but only since the tenth week for female patients. Temporal assessment of correlates of mortality revealed that several baseline variables, including Killip class, systolic blood pressure, total cholesterol, and STEMI diagnosis, had significantly different effects on deaths over time. In conclusion, temporal assessment of time-point outcomes from the Korean registry revealed that an initially higher mortality rate in patients with STEMI versus NSTEMI was inverted in the second week. This outcome assessment could be a step toward developing an advanced risk prediction model for time-course personalized medicine. Further studies are needed to clarify this issue.

The clinical benefit of percutaneous coronary intervention (PCI) is controversial in stable early latecomers with ST-segment elevation myocardial infarction (STEMI). We evaluated the efficacy of PCI in 2,344 stable patients with STEMI presenting 12 to 72 hours after symptom onset. Patients who had impaired hemodynamics or who had undergone fibrinolysis or immediate or urgent PCI were excluded. The patients were divided into the PCI group (n = 1,889) and medical treatment group (n = 455). The 12-month clinical outcome was compared between the 2 groups. After adjustment using propensity score stratification, the PCI group had lower mortality (3.1% vs 10.1%; hazard ratio 0.31; 95% confidence interval 0.20 to 0.47; p <0.001) and a lower incidence of composite death/myocardial infarction (3.8% vs 11.2%; hazard ratio 0.36; 95% confidence interval 0.25 to 0.53; p <0.001) at 12 months. The benefit of PCI was consistent across all subgroups, including patients presenting without chest pain. In conclusion, in stable patients with STEMI presenting 12 to 72 hours after symptom onset, PCI was associated with significant improvement in the 12-month clinical outcome.

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. 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. 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. URL: https://www.clinicaltrials.gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457.

Recently, interventional cardiologists have been increasingly interested in snuffbox approach for coronary angiography (CAG) and percutaneous coronary intervention (PCI). However, there is lack of data regarding distal radial artery (RA) diameter according to gender. Therefore, the aim herein was to investigate gender differences in the diameter of distal RA diameter. Left snuffbox approach was done in 117 patients who had planned CAG or PCI for suspected myocardial ischemia between 1 December 2017 and 28 February 2018 at the Chonnam National University Hospital, Gwangju, Korea. Left RA angiography was achieved from 101 patients. Among 101 individuals, 69 (68.3%) men and 32 (31.7%) women were enrolled. There was no significant difference in systolic and diastolic blood pressure, body mass index, left ventricular systolic function, or patients with acute coronary syndrome in either group. The average diameter of distal RA was 2.57 mm in all patients. Women had a significantly smaller diameter of distal RA than men (2.40 mm vs. 2.65 mm, p = 0.016). Nevertheless, CAG via snuffbox approach by 6 Fr sheath was successfully performed in all 117 patients. Regarding success rate of the distal RA approach, women had a lower success rate (32/38) compared with men (72/79), but not significantly (84.2% vs. 91.1%, p = 0.264). Females has a significantly smaller distal RA diameter compared to males. Moreover, the success rate of the distal RA approach tends to be higher in men than in women.