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A limitation of the current guidelines regarding the timing of invasive coronary angiography for patients with non-ST-segment elevation acute coronary syndrome is the randomization time. To date, no study has reported the clinical outcomes of invasive strategy timing on the basis of the time of symptom onset.The aim of this study was to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI).Among 13,104 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health, 5,856 patients with NSTE myocardial infarction were evaluated. The patients were categorized according to symptom-to-catheter (StC) time (48 or ≥48 hours). The primary outcome was 3-year all-cause mortality.Overall, 3,919 patients (66.9%) were classified into the StC time 48 hours group. This group had lower all-cause mortality than the group with StC time ≥48 hours (7.3% vs 13.4%; P 0.001). The lower risk for all-cause mortality in the group with StC time 48 hours group was consistent in all subgroups. Notably, emergency medical service use (HR: 0.31; 95% CI: 0.19-0.52) showed a lower risk for all-cause mortality than no emergency medical service use (HR: 0.54; 95% CI: 0.46-0.65; P value for interaction = 0.008).An early invasive strategy on the basis of StC time was associated with a decreased risk for all-cause mortality in patients with NSTEMI. Because the study was based on a prospective registry, the results should be considered hypothesis generating, highlighting the need for further research. (iCReaT Study No. C110016).

Although aging is a strong and independent predictor of cardiovascular disease, an effective method to evaluate the degree of aging has yet to be reported. Here, we present a straightforward approach to determine aging in a rapid and quantitative manner, using a microfluidic-based electrochemical sensor equipped with a flexible membrane actuator. The flexible membrane in the sensor captures single endothelial cells of various ages (3, 4, and 18 month-old) under different cell capturing pressures (250, 300, and 350 kPa). The sensing electrodes in the sensor measure electrochemical impedance spectra of each cell group in terms of resistance and reactance. An optimal condition showing significant differences in resistance and reactance between different age groups was experimentally determined at a frequency of 1 MHz and a pressure of 350 kPa (p

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).

BackgroundChronic kidney disease (CKD) is a strong risk factor for cardiovascular disease. Electrocardiogram (ECG) is the basic test for screening cardiovascular disease. However, the impact of ECG abnormalities on cardiovascular prognosis in patients with CKD is largely unknown.MethodsA total of 1,295 patients with CKD (stage 3, 4, and 5) who underwent ECG between 2013 and 2015 were selected from the tertiary hospital in Korea. ECG abnormalities were defined using the Minnesota classification. Five-year major adverse cerebrocardiovascular event (MACCE), a composite of death, myocardial infarction (MI) and stroke, was analyzed after excluding 251 patients (n=1,044) with prior MI or stroke.ResultsThe higher the CKD stage, the higher the proportion of patients with a major ECG abnormality. Five-year MACCE incidences were 34%, 23.9%, and 21.7% in patients with major, minor and no ECG abnormalities. MACCE and MI incidences were significantly higher in patients with severe ECG abnormalities (log-rank p < 0.001). Major ECG abnormalities were significantly associated with MACCE (adjusted HR 1.48, 95% CI 1.11-1.97). In particular, atrial fibrillation, atrial premature complex, and QT interval prolongation were identified as important ECG diagnoses. The accuracy of cardiovascular risk stratification was improved when ECG diagnosis was added to the conventional SCORE model (net reclassification index 0.09).ConclusionsMajor ECG abnormality was a significant predictor of cardiovascular events in CKD patients. ECG diagnosis can be useful in evaluating the risk of cardiovascular disease in CKD patients when applied in addition to the conventional risk stratification model.

Vitamin D deficiency is related to various cardiovascular diseases, including sudden cardiac arrest (SCA). This study investigated the association of vitamin D level with neurologic outcome and mortality after resuscitation from SCA.We enrolled patients who were successfully resuscitated from out-of-hospital cardiac arrest of presumed cardiac cause in Severance Cardiovascular Hospital as a prospective cohort registry. Baseline blood samples including pH, lactate, and vitamin D were obtained without fluid replacement just after hospital admission. Outcome was assessed by cerebral performance category (CPC) score at 1 month after SCA. Favorable outcome was defined as survival with CPC score of 1 or 2, whereas unfavorable one as death or survival with CPC scores of 3 through 5. Severe vitamin D deficiency was defined as 25(OH)D10 ng/mL.A total of 163 patients were included. Overall 96 (59%) patients had a favorable neurologic outcome, whereas 67 patients (41%) showed unfavorable outcome, including 37 (23%) mortality. Patients with unfavorable outcome were likely to be female and have initial non-shockable rhythm, longer arrest time, severe shock, diabetes, and baseline renal dysfunction. In multivariate analysis, severe vitamin D deficiency was one of the poor prognostic factors of both unfavorable neurologic outcome and mortality after SCA.Vitamin D deficiency is very prevalent and strongly associated with both unfavorable neurologic outcome and mortality in patients resuscitated from SCA.

Background: Drug-eluting stents (DESs) are commonly used in percutaneous coronary intervention (PCI) procedures, however, complications including in-stent restenosis and stent thrombosis are significant challenges. The dual-DES is a stent that elutes two drugs to target various stages of the restenosis reaction. This study investigated the safety and efficacy of dual-DES in clinical practice. Methods: This study included 375 patients who underwent PCI with Cilotax&trade, or DXR&trade, dual-DESs at one of 13 centers in South Korea. The primary endpoint was target lesion failure (TLF) within 1 year. The secondary endpoints were cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis. Results: The rates of TLF in dual-DESs (3.7%) were comparable to those reported in conventional DES. In addition, the DXR&trade, group had a significantly lower rate of TLF than the Cilotax&trade, group. In multivariate analysis, the DXR&trade, group had a lower risk of TLF (adjusted hazard ratio (HR) 0.30, 95%CI 0.09&ndash, 0.92, p = 0.036) and MI (adjusted HR 0.16, 95%CI 0.03&ndash, 0.82, p = 0.027) than the Cilotax&trade, group. Conclusion: Dual-DESs had similar clinical outcomes regarding efficacy and safety as conventional DES. Among the dual-DES, the DXR&trade, stent as a new generation dual-DES had more favorable clinical outcomes than the Cilotax&trade, stent.

Background: Decreased TIMI flow following percutaneous coronary intervention (PCI) is associated with poor clinical outcomes. However, predicting slow TIMI flow after PCI is limited. Herein, we investigated predicting slow TIMI flow based on the lipid core burden (LCB) of target lesion by using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). Methods and Results: This study retrospectively evaluated 636 patients who underwent NIRS-IVUS guided PCI from a single tertiary center registry. Total patients were divided into decreased TIMI flow group (n=90, TIMI 0, 1, and 2) and normal TIMI flow group (n=546, TIMI 3). The extent of LCB in the treatment zone was calculated as the maximal LCB index (maxLCBi) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. In three-month composite events including all-cause death, myocardial infarction, stent thrombosis, and re-intervention, decreased TIMI flow group showed worse clinical outcomes compared to normal TIMI flow group (5.6% vs. 1.5%, log-rank p=0.010). To investigate the correlation between TIMI flow and lipid core burden, a receiver-operating characteristic analysis was performed, and a high LCBi group was defined as maxLCBi 4mm ≥353. Multivariate logistic regression analysis revealed that high LCBi group was strongly associated with decreased TIMI flow (OR 2.223, 95% CI 1.341-3.685, p=0.002). Conclusions: High LCBi measured by NIRS-IVUS could be considered an independent predictor for decreased TIMI flow. Furthermore, a high value for LCBi could lead to worse clinical outcomes.

Recently, the number of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) has reduced, whereas increased mortality was reported. A plausible explanation for increased mortality was prehospital delay because of patients' reticence of their symptoms.The purpose of this study was to investigate the association between prehospital delay and clinical outcomes in patients with NSTEMI METHODS: Among 13,104 patients from the Korea-Acute-Myocardial-Infarction-Registry-National Institutes of Health, the authors evaluated 6,544 patients with NSTEMI. Study patients were categorized into 2 groups according to symptom-to-door (StD) time (24 or ≥24 hours). The primary outcome was 3-year all-cause mortality, and the secondary outcome was 3-year composite of all-cause mortality, recurrent MI, and hospitalization for heart failure.Overall, 1,827 (27.9%) patients were classified into the StD time ≥24 hours group. The StD time ≥24 hours group had higher all-cause mortality (17.0% vs 10.5%; P 0.001) and incidence of secondary outcomes (23.3% vs 15.7%; P 0.001) than the StD time 24 hours group. The higher all-cause mortality in the StD time ≥24 hours group was observed consistently in the subgroup analysis regarding age, sex, atypical chest pain, dyspnea, Q-wave in electrocardiogram, use of emergency medical services, hypertension, diabetes mellitus, chronic kidney disease, left ventricle dysfunction, TIMI (Thrombolysis In Myocardial Infarction) flow, and the GRACE risk score. In the multivariable analysis, independent predictors of prehospital delay were the elderly, women, nonspecific symptoms such as atypical chest pain or dyspnea, diabetes, and no use of emergency medical services.Prehospital delay is associated with an increased risk of 3-year all-cause mortality in patients with NSTEMI. (iCReaT Study No. C110016).

Decreased thrombolysis in myocardial infarction (TIMI) flow is associated with poor clinical outcomes. However, its predictors are not fully known. A combination of near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) could be used to detect lesions at high risk of slow TIMI flow. This study evaluated 636 consecutive patients undergoing target-lesion NIRS-IVUS imaging prior to percutaneous coronary intervention (PCI). The maximal lipid core burden index over 4-mm segments (maxLCBI4mm) per target vessel was calculated. The primary endpoint was the association between maxLCBI4mm and post-interventional TIMI flow. A high lipid core burden index (LCBI) cut-off point was determined using receiver-operating characteristic analysis. Decreased TIMI flow (TIMI less than 3) occurred in 90 patients and normal TIMI flow in 546 patients. The decreased TIMI flow group showed significantly higher incidence of cardiovascular events (5.6% vs. 1.5%, log-rank p = 0.010) in three months of composite events including cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization. In multivariable analysis, a high LCBI (≥354) was independently associated with slow TIMI flow (OR, 2.59 (95% CI, 1.33–5.04), p = 0.005). High LCBI measured using NIRS-IVUS imaging was an independent predictor of decreased post-PCI TIMI flow. Performing PCI for high-LCBI lesions may necessitate adjunctive measures to prevent suboptimal post-PCI reperfusion.

Atherectomy as a pretreatment has the potential to improve the outcomes of drug-coated balloon (DCB) treatment by reducing and modifying atherosclerotic plaques. The present study investigated the outcomes of atherectomy plus DCB (A+DCB) compared with DCB alone for the treatment of femoropopliteal artery disease.A total of 311 patients (348 limbs) underwent endovascular therapy using DCB for native femoropopliteal artery lesions at two endovascular centers. Of these, 82 limbs were treated with A+DCB and 266 limbs with DCB alone. After propensity score matching based on clinical and lesion characteristics, a total of 82 pairs was compared for immediate and mid-term outcomes.For the matched study groups, the lesion length was 172.7±111.2 mm, and severe calcification was observed in 43.3%. The technical success rate was higher in the A+DCB group than in the DCB group (80.5% vs. 62.2%, p=0.015). However, the A+DCB group showed more procedure-related minor complications (37.0% vs. 13.4%, p=0.047). At 2-year follow-up, primary clinical patency (73.8% vs. 82.6%, p=0.158) and the target lesion revascularization (TLR)-free survival (84.3% vs. 88.2%, p=0.261) did not differ between the two groups. In Cox proportional hazard analysis, atherectomy showed no significant impact on the outcome of DCB treatments.The pretreatment with atherectomy improved technical success of DCB treatment; however, it was associated with increased minor complications. In this study, A+DCB showed no clinical benefit in terms of TLR-free survival or clinical patency compared with DCB treatment alone.

BACKGROUND Vitamin D deficiency is associated with various cardiovascular diseases, including sudden cardiac arrest (SCA). Profound cardiogenic shock is associated with morbidity and mortality in patients with SCA. This study investigated the association of vitamin D deficiency with profound cardiogenic shock in patients resuscitated from SCA. PATIENTS AND METHODS We enrolled patients who were successfully resuscitated from out-of-hospital cardiac arrests of a presumed cardiac cause. Profound cardiogenic shock was defined as refractory hypotension requiring high-dose vasopressor infusion (norepinephrine >0.5 mcg/kg/min) despite adequate intravascular volume replacement. Vitamin D levels were measured as plasma 25(OH)D concentrations and severe vitamin D deficiency was defined as 25(OH)D

The generation of mature ventricular cardiomyocytes (CMs) resembling adult CMs from human pluripotent stem cells (hPSCs) is necessary for disease modeling and drug discovery. To investigate the effect of self-organizing capacity on the generation of mature cardiac organoids (COs), we generated cardiac mesoderm cell-derived COs (CMC-COs) and CM-derived COs (CM-COs) and evaluated COs. CMC-COs exhibited more organized sarcomere structures and mitochondria, well-arranged t-tubule structures, and evenly distributed intercalated discs. Increased expressions of ventricular CM, cardiac metabolic, t-tubule formation, K+ ion channel, and junctional markers were confirmed in CMC-COs. Mature ventricular-like function such as faster motion vector speed, decreased beats per min, increased peak-to-peak duration, and prolonged APD50 and APD90 were observed in CMC-COs. Transcriptional profiling revealed that extracellular matrix-integrin, focal adhesion, and LEFTY-PITX2 signaling pathways are upregulated in CMC-COs. LEFTY knockdown affected ECM-integrin-FA signaling pathways in CMC-COs. Here, we found that high self-organizing capacity of CMCs is critical for the generation of mature and ventricular COs. We also demonstrated that LEFTY-PITX2 signaling plays key roles for CM maturation and specification into ventricular-like CM subtype in CMC-COs. CMC-COs are an attractive resource for disease modeling and drug discovery.

Background Uncertainty remains regarding the associations of angiographic optimization and intravascular ultrasound (IVUS) optimization after new-generation drug-eluting stent (DES) implantation. Methods From four randomized trials comparing outcomes between IVUS and angiography-guidance for long or chronic total occlusion (CTO) lesions, 1396 patients who underwent IVUS-guided new-generation DES implantation were enrolled. Of these, 1112 patients (80%) met angiographic optimization criteria (postprocedural diameter stenosis, ≤20%) and were further classified into the matched (same results for angiographic optimization and IVUS optimization) and the mismatched group (opposite results for angiographic optimization and IVUS optimization) according to the meeting of IVUS optimization criteria (minimal stent area, ≥5.5 mm2 or ≥80% of mean reference lumen area). The major adverse clinical events (MACE) were compared. Results Of 1112 patients with angiographic optimization, 675 patients met the IVUS optimization criteria (61%; matched), but 437 patients (39%; mismatched) failed to meet IVUS optimization criteria (false-positive rate = 76%). On multivariate analyses, age >60 years, reference vessel diameter ≤2.7 mm, left circumflex artery and lesion length ≥33 mm were significant predictors for the mismatched. When comparing the 12-month MACE rates, the mismatched group (6.8%) showed a significantly higher rate than the matched group (1.5%; hazard ratio = 2.62; 95% confidence interval = 1.20-5.72; P = 0.012), mainly driven by a higher target-vessel revascularization rate (6.4 vs 1.4%; P = 0.021). Conclusion Despite meeting angiographic optimization criteria in long or CTO lesions, more than one-third of the patients with IVUS-guided new-generation DES implantation failed to meet the IVUS optimization criteria and had worse clinical outcomes. Therefore, IVUS optimization should be considered for patients who had predictors of mismatch.

Although lowering low-density lipoprotein cholesterol (LDL-C) levels following acute myocardial infarction (MI) is the cornerstone of secondary prevention, the attainment of recommended LDL-C goals remains suboptimal in real-world practice. We sought to investigate recurrent adverse events in post-MI patients. From the Korea Acute Myocardial Infarction-National Institutes of Health registry, a total of 5049 patients with both measurements of plasma LDL-C levels at index admission and at the one-year follow-up visit were identified. Patients who achieved an LDL-C reduction ≥ 50% from the index MI and an LDL-C level ≤ 70 mg/dL at follow-up were classified as target LDL-C achievers. The primary endpoint was a two-year major adverse cardiac and cerebrovascular event (MACCE), including cardiovascular mortality, recurrent MI, and ischemic stroke. Among the 5049 patients, 1114 (22.1%) patients achieved the target LDL-C level. During a median follow-up of 2.1 years, target LDL-C achievers showed a significantly lower incidence (2.2% vs. 3.5%, log-rank p = 0.022) and a reduced adjusted hazard of MACCE (0.63; p = 0.041). In patients with acute MI, achieving a target LDL-C level was associated with a lower incidence and a reduced hazard of recurrent clinical events. These results highlight the need to improve current practices for managing LDL-C levels in real-world settings.

Background Machine learning approaches using intravascular optical coherence tomography (OCT) to predict fractional flow reserve (FFR) have not been previously investigated. The objective of the study was to evaluate a machine learning method to estimate FFR based on intravascular OCT images in intermediate coronary lesions. Methods Data from both OCT- and wire-based FFR methods were obtained for lesions of the left anterior descending artery in 125 patients. Based on the total number of lesions, training and testing groups were partitioned at a ratio of 5:1. For the training group, 36 features, including 16 clinical and lesion characteristics, and 21 OCT features, were used to model machine learning-FFR. machine learning-FFR values were then derived for the testing group and compared with wire-based FFR values in terms of a diagnosis of ischemia (FFR Results Clinical and lesion characteristics and OCT features between the training and testing groups were similar. During the machine learning modeling of the training group, six important features of machine learning-FFR were identified: minimal luminal area, percentage of the stenotic area, lesion length, proximal luminal area, pre-procedural platelet count, and hypertension. machine learning-FFR values showed a good correlation (r=0.853, P Conclusions The OCT-based machine learning-FFR method can be used to simultaneously acquire information on both image and functional modalities using one invasive procedure, suggesting that it may be used to optimize treatments for intermediate coronary artery stenosis, as well as save time and cost. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Funded by the Korean government (MSIT) (no. 2017R1A2B2003191)

Machine learning approaches using intravascular optical coherence tomography (OCT) to predict fractional flow reserve (FFR) have not been investigated. Both OCT and FFR data were obtained for left anterior descending artery lesions in 125 patients. Training and testing groups were partitioned in the ratio of 5:1. The OCT-based machine learning-FFR was derived for the testing group and compared with wire-based FFR in terms of ischemia diagnosis (FFR ≤ 0.8). The OCT-based machine learning-FFR showed good correlation (r = 0.853, P

Elderly patients treated with percutaneous coronary intervention (PCI) have a higher risk of both ischemic and bleeding complications than younger patients. However, few studies have reported how genetic information of elderly patients treated with PCI affects clinical outcomes. We investigated the impact of genetic variants on clinical outcomes in elderly patients. Correlations between single-nucleotide polymorphisms (CYP2C19 and P2Y12 receptor gene G52T polymorphism) and clinical outcomes were analyzed in 811 elderly patients (≥75 years of age) from a prospective multicenter registry. The primary endpoint was a composite of myocardial infarction and death. Secondary endpoints were an individual event of death, cardiac death, myocardial infarction, stent thrombosis, target lesion revascularization, stroke, and major bleeding (Bleeding Academic Research Consortium ≥3). Regarding CYP2C19, patients with poor metabolizers had a significantly higher risk for the primary endpoint (hazard ratio [HR] 2.43; 95% confidence interval [95% CI] 1.12-5.24; p=0.024) and secondary endpoints (death and cardiac death). Regarding P2Y12 G52T, the TT group had a significantly higher occurrence of major bleeding than the other groups (HR 3.87; 95% CI 1.41-10.68; p=0.009). In conclusion, poor metabolizers of CYP2C19 and TT groups of P2Y12 G52T may be significant predictors of poor clinical outcomes in elderly patients.

Background and objectives Atrial fibrillation is a known risk factor for cryptogenic stroke and therefore requires early detection and prompt management. We investigated predictors of stroke recurrence in patients with cryptogenic stroke and concomitant non-sustained atrial tachycardia but not atrial fibrillation. Subjects and methods We investigated 390 patients (219 men, mean age 67 ± 12 years) diagnosed with stroke and non-sustained atrial tachycardia on 24-h Holter monitoring and recorded the total number of atrial premature contractions identified by the Holter monitor. Multiple atrial premature contractions were defined as atrial premature contractions > 34 beats/day. We analyzed the rates of 5-year freedom from stroke recurrence or atrial fibrillation and investigated independent predictors of stroke recurrence and undiagnosed atrial fibrillation. Results The mean follow-up period was 35 ± 21 months, and the overall stroke recurrence rate was 9.0%. Kaplan–Meier survival analysis revealed that the rate of freedom from stroke recurrence was significantly lower in patients with multiple atrial premature contractions. Also, the patients with multiple atrial premature contractions had higher cumulative incidence rate of new-onset AF (p = 0.019). Multivariate analysis showed that multiple atrial premature contractions (hazard ratio 2.49, 95% confidence interval 1.05–5.88, p = 0.038), cigarette smoking status (hazard ratio 2.66, 95% confidence interval 1.15–6.17, p = 0.022), and the left atrial volume index (hazard ratio 1.05, 95% confidence interval 1.01–1.09, p = 0.020) were significantly associated with stroke recurrence in patients with cryptogenic stroke. However, these factors were not statistically significant predictors of future onset of atrial fibrillation. Conclusions Multiple atrial premature contractions were significantly correlated with an increased left atrial volume index, which could predict future onset of atrial fibrillation and stroke recurrence. This study showed that multiple atrial premature contractions predict stroke recurrence in patients with cryptogenic stroke without atrial fibrillation.

Background The influence of intensive glucose control in diabetic patients on the macrovascular outcomes is controversial. Thus, this study aimed to elucidate the effect of preprocedural hemoglobin A1c (HbA1c) on clinical outcomes after endovascular therapy for lower extremity artery disease (LEAD) in diabetic patients. Methods Diabetic patients were enrolled from the retrospective cohorts of a Korean multicenter endovascular therapy registry and were divided according to the HbA1c level during index admission into the optimal ( Results Of the 1103 patients enrolled (897 men, mean age 68.2 ± 8.9 years), 432 (39.2%) were classified into the optimal glycemic control group and 671 (60.8%) into the suboptimal glycemic control group. In-hospital events and immediate procedural complications were not different between the two groups. The suboptimal group showed a trend towards a higher incidence of MALE than the optimal group (log-rank p = 0.072). Although no significant differences were found between the two groups in terms of overall survival or amputation, the risk of reintervention was significantly higher in the suboptimal group (log-rank p = 0.048). In the multivariate Cox regression model, suboptimal glycemic control was one of the independent predictors for reintervention. When our data were analyzed according to the initial presentation, suboptimal preprocedural HbA1c significantly increased the incidence of MALE compared with optimal preprocedural HbA1c only in patients with intermittent claudication. Conclusion In diabetic patients undergoing endovascular therapy for LEAD, suboptimal preprocedural HbA1c is associated with an increased risk of adverse limb events, especially in patients with intermittent claudication. Further prospective research will be required to validate the role of more intensive glycemic control on the reduction of adverse limb events in diabetic patients undergoing endovascular therapy for LEAD.

Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors.From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention).Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p0.001), end-stage renal disease (ESRD; HR, 2.340; p0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471; p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3-4 years.In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes.ClinicalTrials.gov Identifier: NCT02748226.

A novel tissue engineering strategy using 3D bio-print technology has become a promising therapeutic method for acute myocardial infarction (AMI) in an animal model. However, the application of 3D bio-printed tissue remains limited due to poor graft survival. Therefore, it is a scientific priority to enhance graft survival by precisely adjusting the 3D environment of encapsulated cells. In this study, novel transplantable 3D cardiac mesh (cMesh) tissue with a porous mesh structure was presented using human cardiomyocytes, human cardiac fibroblasts, and gelatin-methacryloyl-collagen hydrogel. Cardiomyocytes and cardiac fibroblasts were well spreaded. The cardiomyocytes were connected with a gap junction channel in bio-printed cMesh and a 3D cardiac patch with an aggregated structure. Porous cMesh demonstrated structural advantages by increased phosphorylation of mTOR, AKT, and ERK signals associated with cell survival. Transplanted cMesh in rats with AMI improved long-term graft survival, vessel formation, and stabilization, reduced fibrosis, increased left ventricle thickness, and enhanced cardiac function. Our results suggest that porous cMesh provides structural advantages and a positive therapeutic effect in an AMI animal model.

Background: No large-scale study has compared the clinical and angiographic predictors of cardiovascular events in patients with left main bifurcation (LMB) and non-LMB stenting after second-generation DES implantation. Herein, we investigated differential clinical and angiographic factors for predicting outcomes in LMB versus non-LMB stenting. Methods: A total of 2648 patients with bifurcation lesions treated with second-generation DESs from the retrospective patient cohort were divided into an LMB group (n = 935) and a non-LMB group (n = 1713). The primary outcome was the 7-year incidence of target lesion failure (TLF), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: The incidence of TLF was 9.8%. Those in the LMB group were associated with a higher risk of TLF (14.2% versus 7.5%, p &lt, 0.001) than those in the non-LMB group. Regarding the LMB group, independent predictors of TLF were chronic kidney disease (CKD), reduced left ventricular ejection fraction (LVEF), and two-stenting. Regarding the non-LMB group, CKD, reduced LVEF, old age, diabetes, and small diameter of the main vessel stent were independent predictors of TLF. Conclusions: The two-stent strategy could potentially increase TLF for the LMB lesions, and achieving the maximal diameter of the main vessel stent could result in better clinical outcomes for non-LMB lesions.

An EoN (electrochemical impedance spectroscopy-on-a-needle) with bipolar interdigitated electrodes fabricated at the end of a curved surface of a hypodermic needle has been introduced to electrically discriminate biotissues. A flexible photomask and photoresist spray coating were employed in the photolithography process to fabricate fine electrode patterns on the round surface of the needle, which was insulated with parylene C. The electrodes were coated again with parylene C to enhance biocompatibility and durability. A repeatability test using a PBS (phosphate buffered saline) solution with known properties was carried out ten times; the maximum standard deviation was approximately 7% in electrical impedance. To analyze the EoN as an electrical circuit, equivalent modeling was introduced for the design of EIS (electrochemical impedance spectroscopy) devices with a target performance. In order to evaluate the discrimination capability of the EoN, the electrical depth profiling was conducted for three-layered (fat-muscle-fat) porcine tissues over a frequency range of 100 Hz–1 MHz as the needle sequentially penetrated the biotissues. The discrimination index (DI), defined as the ratio of the mean difference and the square root of sum of two variances, was introduced to find the optimal frequency at which the largest DI occurred for two boundaries of three-layered tissues. To improve the DI, the measured electrical impedance of three-layered porcine tissue was compensated by excluding the unwanted measurement error induced by the connection lines inserted in the biotissues. As a result, the discrimination index was considerably increased by 9.3 times in real (Z′) part of impedance and 3 times in imaginary (Z′′) part of impedance. We believe that the proposed EoN can be utilized to find the exact location of specific tissues and to discriminate between normal and abnormal lesion tissues prior to biopsy.