Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2∼4 and 2∼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

Background/Aims: Left ventricular hypertrophy (LVH) on clinical outcomes in patients with acute myocardial infarction (AMI) is not clear. This study was performed to investigate the effect of abnormal left ventricular geometry on clinical outcomes in Korean patients with AMI. Methods: A total of 852 consecutive patients with AMI were divided into two groups: normal left ventricular geometry (n = 470; 389 males) and LVH (n = 382; 214 males) groups. Major adverse cardiac events (MACEs) were defined as cardiac death, recurrent myocardial infarction, and rehospitalization. Results: During the clinical follow-up period of 21 ± 7.8 months, MACEs developed in 173 patients (20.0%), and the rate was higher in the LVH than normal left ventricular geometry groups (25.5% vs. 16.0%, respectively, p = 0.001). According to Kaplan-Meier survival curves, the MACE-free survival rate was significantly lower in the LVH group than in the left ventricular geometry group (p = 0.008). The rates of MACEs and all-cause mortality differed among the AMI with concentric remodeling, concentric hypertrophy, and eccentric hypertrophy subgroups (11.2% vs. 15.5% vs. 22.1%, respectively, p = 0.046). Eccentric hypertrophy was a predictive factor of MACE according to Cox proportional hazards analysis (hazard ratio 1.804, confidence interval 1.034-3.148, p = 0.038). Conclusions LVH is a predictor of poor outcomes in patients with AMI, and eccentric hypertrophy is associated with a worse prognosis compared with concentric remodeling and concentric hypertrophy. Therefore, Korean patients with AMI and LVH, especially eccentric hypertrophy, require more careful observation and intensive treatment.

BACKGROUND AND OBJECTIVES: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients. METHODS: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death. RESULTS: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6–2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19–0.85), major bleeding (HR, 0.43; 95% CI, 0.23–0.81), primary (HR, 0.50; 95% CI, 0.29–0.84) and secondary (HR, 0.45; 95% CI, 0.28–0.74) net-clinical outcomes, whereas mean INR 2.0–3.0 did not. Simultaneous satisfaction of mean INR 1.6–2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes. CONCLUSIONS Mean INR 1.6–2.6 was better than mean INR 2.0–3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6–2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0–3.0 and TTR ≥70% in Korean patients with non-valvular AF.

Kommerell diverticulum is a rare congenital anomaly of the aortic arch characterized by dilation at the proximal descending aorta, which gives rise to an aberrant subclavian artery. Kommerell diverticulum is usually asymptomatic, but can also be associated with symptoms due to compression of the esophagus or trachea, and can rarely be fatal due to dissection or rupture of the diverticulum. Here, we report a rare case of dysphagia caused by compression of the esophagus by Kommerell diverticulum originating from the right-sided aortic arch.

Background/Aims: Many patients with acute myocardial infarction (AMI) suffer from heart failure due to progressive ischemic left ventricular (LV) remodeling. This study investigated the predictors of ischemic cardiomyopathy (ICMP) in patients with AMI who underwent successful percutaneous intervention. Methods: A total of 547 patients with AMI were divided into two groups: ICMP (n = 66, 67.1 ± 11.9 years, 78.8% males) and non-ICMP (n = 481, 62.5 ± 12.2 years, 70.1% males). Results: On echocardiography, the LVEF was significantly decreased (41.7 ± 10.5 vs. 55.4 ± 10.3%, p < 0.001) but the LV end-diastolic (54.1 ± 7.2 vs. 49.3 ± 5.3 mm, p < 0.001) and systolic (42.1 ± 8.0 vs. 33.5 ± 6.0 mm, p < 0.001) dimensions significantly increased in the ICMP group compared with the non-ICMP group. According to multivariate logistic regression analysis, LVEF < 50% (odds ratio [OR] 8.722, 95% confidence interval [CI] 2.986–25.478, p < 0.001), LV end-diastolic dimension > 55 mm (OR 4.511, 95% CI 1.561–13.038, p = 0.005), and ratio of early mitral inflow velocity to mitral annular early diastolic velocity (E/e’) ≥ 15 (OR 3.270, 95% CI 1.168–9.155, p = 0.024) were independent predictors of ICMP development. Conclusions The present study demonstrates that a larger LV size, lower LV function, and increased E/e’ (≥ 15) were independent predictors of ICMP. Therefore, the development of ICMP should be carefully monitored in AMI patients with these features.

BACKGROUND AND OBJECTIVES: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients.METHODS: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death.RESULTS: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6–2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19–0.85), major bleeding (HR, 0.43; 95% CI, 0.23–0.81), primary (HR, 0.50; 95% CI, 0.29–0.84) and secondary (HR, 0.45; 95% CI, 0.28–0.74) net-clinical outcomes, whereas mean INR 2.0–3.0 did not. Simultaneous satisfaction of mean INR 1.6–2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes.CONCLUSIONS: Mean INR 1.6–2.6 was better than mean INR 2.0–3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6–2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0–3.0 and TTR ≥70% in Korean patients with non-valvular AF.
Atrial Fibrillation ; Follow-Up Studies ; Hemorrhage ; Humans ; International Normalized Ratio ; Prothrombin Time ; Risk Reduction Behavior ; Stroke ; Thromboembolism ; Warfarin

Background/Aims: Left ventricular hypertrophy (LVH) on clinical outcomes in patients with acute myocardial infarction (AMI) is not clear. This study was performed to investigate the effect of abnormal left ventricular geometry on clinical outcomes in Korean patients with AMI. Methods: A total of 852 consecutive patients with AMI were divided into two groups: normal left ventricular geometry (n = 470; 389 males) and LVH (n = 382; 214 males) groups. Major adverse cardiac events (MACEs) were defined as cardiac death, recurrent myocardial infarction, and rehospitalization. Results: During the clinical follow-up period of 21 ± 7.8 months, MACEs developed in 173 patients (20.0%), and the rate was higher in the LVH than normal left ventricular geometry groups (25.5% vs. 16.0%, respectively, p = 0.001). According to Kaplan-Meier survival curves, the MACE-free survival rate was significantly lower in the LVH group than in the left ventricular geometry group (p = 0.008). The rates of MACEs and all-cause mortality differed among the AMI with concentric remodeling, concentric hypertrophy, and eccentric hypertrophy subgroups (11.2% vs. 15.5% vs. 22.1%, respectively, p = 0.046). Eccentric hypertrophy was a predictive factor of MACE according to Cox proportional hazards analysis (hazard ratio 1.804, confidence interval 1.034-3.148, p = 0.038). Conclusions LVH is a predictor of poor outcomes in patients with AMI, and eccentric hypertrophy is associated with a worse prognosis compared with concentric remodeling and concentric hypertrophy. Therefore, Korean patients with AMI and LVH, especially eccentric hypertrophy, require more careful observation and intensive treatment.

BACKGROUND AND OBJECTIVES: Although current guidelines recommend early initiation of statin in patients with acute myocardial infarction (AMI), there is no consensus for optimal timing of statin initiation. METHODS: A total of 3,921 statin-naïve patients undergoing percutaneous coronary intervention were analyzed, and divided into 3 groups according to statin initiation time: group 1 (statin initiation <24 hours after admission), group 2 (24–48 hours) and group 3 (≥48 hours). We also made 3 stratified models to reduce bias: model 1 (<24 hours vs. ≥24 hours), model 2 (<48 hours vs. ≥48 hours) and model 3 (<24 hours vs. 24–48 hours). The endpoint was major adverse cardiac events (MACE; composite of cardiac death, myocardial infarction and target-vessel revascularization) during median 3.8 years. RESULTS: During follow-up, incidence of MACE was lower in early statin group in both model 1 (14.3% vs. 18.4%, hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66–0.91; p=0.002) and model 2 (14.6% vs. 19.7%, HR, 0.81; 95% CI, 0.67–0.97; p=0.022). After propensity-score matching, results remained unaltered. Statin initiation <24 hours reduced MACE compared to statin initiation ≥24 hours in model 1. Statin initiation <48 hours also reduced MACE compared to statin initiation later in model 2. However, there was no difference in incidence of MACE between statin initiation <24 hours and 24–48 hours) in model 3. CONCLUSIONS: Early statin therapy within 48 hours after admission in statin-naïve patients with AMI reduced long-term clinical outcomes compared with statin initiation later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02385682
Bias (Epidemiology) ; Consensus ; Death ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare coronary artery anomaly and double right coronary artery (RCA) is a very rare coronary anomaly. Because patients with ALCAPA usually die within 1 year of being born due to myocardial infarction (MI) and heart failure, ALPACA is very rarely seen in adults. Here, we report an extremely rare asymptomatic case of MI, presumably caused by ALCAPA and double RCA, and provide a review of the literature. This is the first reported case of coronary artery anomaly that had both ALCAPA and double RCA.
Adult ; Bland White Garland Syndrome ; Camelids, New World ; Coronary Vessel Anomalies ; Coronary Vessels ; Heart Failure ; Humans ; Myocardial Infarction ; Pulmonary Artery

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare coronary artery anomaly and double right coronary artery (RCA) is a very rare coronary anomaly. Because patients with ALCAPA usually die within 1 year of being born due to myocardial infarction (MI) and heart failure, ALPACA is very rarely seen in adults. Here, we report an extremely rare asymptomatic case of MI, presumably caused by ALCAPA and double RCA, and provide a review of the literature. This is the first reported case of coronary artery anomaly that had both ALCAPA and double RCA.