Melosira nummuloides Ethanol Extract Ameliorates Alcohol-Induced Liver Injury by Affecting Metabolic Pathways.

Melosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice. However, MNE administration increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK/AMPK) and PPARα, which was accompanied by a decrease in SREBP-1; this indicates that MNE can inhibit adipogenesis and improve fatty acid oxidation. Moreover, MNE administration upregulated the expression of antioxidant enzymes, including SOD, NAD(P)H quinone dehydrogenase 1, and GPX, and ameliorated alcohol-induced inflammation by repressing the Akt/NFκB/COX-2 pathway. Metabolomic analysis revealed that MNE treatment modulated many lipid metabolites in alcohol-treated HepG2 cells. Our study findings provide evidence for the efficacy and mechanisms of MNE in ameliorating alcohol-induced liver injury.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Characterization of chemoresistant human non-small cell lung cancer cells by metabolic and lipidomic profiling.

INTRODUCTION: Lung cancer is one of the most malignant cancers and the leading cause of cancer-related deaths worldwide, while acquired chemoresistance would represent a major problem in the treatment of non-small cell lung cancer (NSCLC) because of the reduced treatment effect and increased rates of recurrence. METHODS: To establish the chemoresistant NSCLC cells, doxorubicin was treated to A549 cells over 3 months at gradually increasing concentrations from 0.03 to 0.5 µM. Real-time PCR and Western blotting were employed for investigating mRNA and protein expression of the glutathione peroxidase (GPX) protein family and multidrug resistance protein 1 (MRP1) in A549 and A549/CR cells. We also employed gas chromatography mass-spectrometry and nano electrospray ionization mass-spectrometry coupled with multivariate statistical analysis to characterize the unique metabolic and lipidomic profiles of chemoresistant NSCLC cells in order to identify potential therapeutic targets. RESULTS: Reactive oxygen species levels were decreased, and mRNA and protein levels of GPX2 and multidrug resistance protein 1 (MRP1) were increased in A549/CR. We identified 87 metabolites and intact lipid species in A549 and A549/CR. Among these metabolites, lactic acid, glutamic acid, glycine, proline, aspartic acid, succinic acid, and ceramide, alongside the PC to PE ratio, and arachidonic acid-containing phospholipids were suggested as characteristic features of chemoresistant NSCLC cells (A549/CR). CONCLUSIONS: This study reveals characteristic feature differences between drug-resistance NSCLC cells and their parental cells. We suggest potential therapeutic targets in chemoresistant NSCLC. Our results provide new insight into metabolic and lipidomic alterations in chemoresistant NSCLC. This could be used as fundamental information to develop therapeutic strategies for the treatment of chemoresistant NSCLC patients.

Clinical and Genetic Features of Korean Inherited Arrhythmia Probands.

BACKGROUND AND OBJECTIVES: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. METHODS: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. RESULTS: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). CONCLUSIONS: There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial.

Importance: Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking. Objective: To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes. Design, Setting, and Participants: This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021. Interventions and Exposures: Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes. Main Outcomes and Measures: The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up. Results: Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71). Conclusion and Relevance: In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status. Trial Registration: ClinicalTrials.gov Identifier: NCT02044250.

Antioxidant activity of banana flesh and antiproliferative effect on breast and pancreatic cancer cells.

Bananas, one of the most widely consumed fruits worldwide, are a rich source of valuable phytochemicals. In this study, the antioxidant and the anticancer potential of banana flesh was investigated. Of the four kinds of banana flesh extracts, the hexane extract (HE) had the highest total polyphenol content (2.54 ± 0.60 mg GAE/g) and total flavonoid content (1.69 ± 0.34 mg RE/g), followed by the chloroform fraction, total ethanol extract, and ethanol fraction. HE was found to exert a strong radical scavenging activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonicacid) (ABTS•) free radicals. According to the IC50 values in various cancer cell lines, HE was found to possess the greatest cell growth inhibitory potential in human pancreatic cancer PANC-1 cells and human triple-negative breast cancer MDA-MB-231 cells. HE induced apoptosis in PANC-1 and MDA-MB-231 cells, as evidenced by the appearance of condensation of chromatin, proteolytic activation of caspase-3 and 7, and increase in the level of the cleaved form of poly (ADP-ribose) polymerase protein. Gas chromatography mass spectrometry (GC-MS) analysis of HE identified several anticancer compounds including palmitic acid, linoleic acid, oleic acid, campesterol, stigmasterol, and γ-sitosterol, supporting the anticancer potential of HE. Our investigation provides a rationale for the use of banana flesh to minimize the risk of cancer-like diseases.

Clinical impact of guideline-based practice and patients' adherence in uncontrolled hypertension.

BACKGROUND: Chronic diseases like hypertension need comprehensive lifetime management. This study assessed clinical and patient-reported outcomes and compared them by treatment patterns and adherence at 6 months among uncontrolled hypertensive patients in Korea. METHODS: This prospective, observational study was conducted at 16 major hospitals where uncontrolled hypertensive patients receiving anti-hypertension medications (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) were enrolled during 2015 to 2016 and studied for the following 6 months. A review of medical records was performed to collect data on treatment patterns to determine the presence of guideline-based practice (GBP). GBP was defined as: (1) maximize first medication before adding second or (2) add second medication before reaching maximum dose of first medication. Patient self-administered questionnaires were utilized to examine medication adherence, treatment satisfaction and quality of life (QoL). RESULTS: A total of 600 patients were included in the study. Overall, 23% of patients were treated based on GBP at 3 months, and the GBP rate increased to 61.4% at 6 months. At baseline and 6 months, 36.7 and 49.2% of patients, respectively, were medication adherent. The proportion of blood pressure-controlled patients reached 65.5% at 6 months. A higher blood pressure control rate was present in patients who were on GBP and also showed adherence than those on GBP, but not adherent, or non-GBP patients (76.8% vs. 70.9% vs. 54.2%, P < 0.001). The same outcomes were found for treatment satisfaction and QoL (P < 0.05). CONCLUSIONS: This study demonstrated the importance of physicians' compliance with GBP and patients' adherence to hypertensive medications. GBP compliance and medication adherence should be taken into account when setting therapeutic strategies for better outcomes in uncontrolled hypertensive patients.

Comparison of multivariate linear regression and a machine learning algorithm developed for prediction of precision warfarin dosing in a Korean population.

BACKGROUND: Personalized warfarin dosing is influenced by various factors including genetic and non-genetic factors. Multiple linear regression (LR) is known as a conventional method to develop predictive models. Recently, machine learning approaches have been extensively implemented for warfarin dosing due to the hypothesis of non-linear association between covariates and stable warfarin dose. OBJECTIVE: To extend the multiple linear regression algorithm for personalized warfarin dosing in a Korean population and compare with a machine learning--based algorithm. METHOD: From this cohort study, we collected information on 650 patients taking warfarin who achieved steady state including demographic information, indications, comorbidities, comedications, habits, and genetic factors. The dataset was randomly split into training set (90%) and test set (10%). The LR and machine learning (gradient boosting machine [GBM]) models were developed on the training set and were evaluated on the test set. RESULT: LR and GBM models were comparable in terms of accuracy of ideal dose (75.38% and 73.85%), correlation (0.77 and 0.73), mean absolute error (0.58 mg/day and 0.64 mg/day), and root mean square error (0.82 mg/day and 0.9 mg/day), respectively. VKORC1 genotype, CYP2C9 genotype, age, and weight were the highest contributors and could obtain 80% of maximum performance in both models. CONCLUSION: This study shows that our LR and GMB models are satisfactory to predict warfarin dose in our dataset. Both models showed similar performance and feature contribution characteristics. LR may be the appropriate model due to its simplicity and interpretability.

Long-Term Left Atrial Function after Device Closure and Surgical Closure in Adult Patients with Atrial Septal Defect.

BACKGROUND: Studies comparing left atrial (LA) function after surgical closure or percutaneous closure in patients with an atrial septal defect (ASD) are lacking. METHODS: Between 1 and 3 years after ASD treatment, we retrospectively analyzed the medical records and transthoracic echocardiographic images of patients who had been diagnosed with an ASD after 20 years of age and who had undergone surgical closure (ASD-S) or percutaneous device closure (ASD-D). We measured LA peak systolic, early diastolic, and late diastolic strain values using 2-dimensional (2D) speckle tracking echocardiography (STE) and calculated reservoir, conduit, and contraction strain. RESULTS: The reservoir strain value of the ASD-D groups was 25.2% ± 7.4%, which was lower compared to the control group (33.6% ± 5.5%) (p = 0.004). The LA conduit strain and the LA contraction values of the ASD-D group were also lower compared to the control group (-13.8% ± 5.8% vs. -20.4% ± 4.7%, p = 0.034; -11.3% ± 4.2% vs. -13.2% ± 2.5%, p = 0.037, respectively). The reservoir, conduit, and contraction strains of the ASD-S group were 27.8% ± 8.8%, -15.3% ± 6.4%, and -12.5% ± 5.8%, respectively, and were not different from those of the control group or the ASD-D group. CONCLUSIONS: The 2D STE is a suitable method for evaluating LA function after ASD closure. Our results demonstrate that 1 year after device closure, the LA reservoir, conduit and contraction function were reduced in ASD-D group compared to healthy controls, while there was no difference between the ASD-S and ASD-D groups.

Adherence to triple-component antihypertensive regimens is higher with single-pill than equivalent two-pill regimens: A randomized controlled trial.

Using a single-pill combination (SPC) for hypertension (HTN) treatment resulted in better adherence and persistence than a free-equivalent combination in previous observational studies. The aim of this study is to confirm superior adherence with a triple-component SPC compared with an equivalent two-pill regimen in a randomized controlled trial (RCT) using a medication event monitoring system (MEMS). This is a multicenter, open-label, RCT. Subjects were persons with HTN whose clinic blood pressure was not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with a dual combination. Eligible patients were randomized to either the triple-component SPC (olmesartan/amlodipine/hydrochlorothiazide 20/5/12.5 mg) group or the equivalent two-pill (olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) group and maintained for 12 weeks. Primary outcomes were the difference in percentage of doses taken (PDT) and percentage of days with the prescribed dose taken correctly (PDTc) between the single- and two-pill therapy groups, calculated from MEMS data. From 8 hospitals, 145 patients with HTN were randomized. The single-pill group had significantly higher PDT and PDTc than the two-pill group: median (25-75 percentile) PDT 95.1 (86.7-100.0) versus 92.1 (73.0-97.3); and PDTc 91.0 (79.4-96.5) versus 88.6 (69.2-96.3%), P = 0.04 for both by the Wilcoxon rank sum test. The single-pill combination of the triple-component antihypertensive regimen showed better adherence than the equivalent two-pill therapy. Reducing pill burden by means of a single-pill combination is an effective strategy for enhancing adherence to multiple-agent antihypertensive therapy. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Previous studies suggested that the use of a single-pill combination (SPC) in hypertension (HTN) treatment produced better adherence and persistence than a free-equivalent combination. However, supportive data are confined to dual-component SPC and came from observational studies using medication possession ratio as an outcome. WHAT QUESTION DID THIS STUDY ADDRESS? The objective of this study is to investigate whether a triple-component SPC improved medication adherence over an equivalent two-pill combination therapy in a randomized controlled trial using medication event monitoring systems. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Medication adherence in the SPC group was superior to that of two-pill group, confirming previous findings from observational studies. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This finding strongly supports the current HTN treatment guideline to prefer SPC with a higher level of evidence.

Adherence to dabigatran and the influence of dabigatran-induced gastrointestinal discomfort in the real-world practice.

BACKGROUND: Dabigatran-induced gastrointestinal discomfort (DGID) is an important factor influencing the adherence to dabigatran. We investigated the incidence and risk factors of DGID and its impact on the adherence and persistence to dabigatran. METHODS: We prospectively enrolled the patients prescribed with dabigatran in 10 tertiary hospitals of the South Korea. The adherence was assessed using the percentage of the prescribed doses of the medication presumably taken by the patient (PDT by pill count). We evaluated the relationship between DGID and the baseline GI symptoms or the previous GI disease history using a questionnaire. RESULTS: A total of 474 patients (mean age 67.8 ± 9.3 years, male 68.6%, and mean CHA2DS2-VASc score 2.2 ± 1.2) were enrolled. The adherence assessed by the PDT was 93.5 ± 5.5% at 1-month and 96.4 ± 8.4% at 6-months among the persistent patients. During the 6-month follow-up, 82 (18.1%) patients discontinued dabigatran, and the most common reason for dabigatran discontinuation was DGID (49, 59.8%). Sixty-eight (14.3%) patients experienced DGID, and there was no difference in the clinical factors between those with or without DGID. Among the patients who experienced DGID, 42 discontinued dabigatran (61.8%). In a multivariate analysis, DGID was the only predictor of dabigatran discontinuation and a low adherence. CONCLUSION: Overall adherence of dabigatran was excellent, but those with DGID showed low adherence and persistence. Furthermore, it was challenging to predict DGID by clinical parameters. Therefore, it is recommended to follow the patients closely to check for DGID when prescribing dabigatran.

A prospective cohort study on effects of gemigliptin on cardiovascular outcomes in patients with type 2 diabetes (OPTIMUS study).

This study was performed to evaluate the long-term cardiovascular safety of gemigliptin in patients with type 2 diabetes mellitus (T2DM). After screening, eligible patients with T2DM were enrolled, received gemigliptin, and were followed up for a median of 2.50 years. The primary outcome was a composite of confirmed cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke (3-point major adverse cardiovascular event [MACE]). The key secondary outcomes were incidence of all-cause mortality and any other cardiovascular events. A total of 5179 patients were included in the study and 5113 were treated with gemigliptin. Overall, the primary outcome occurred in 26 patients within 12 months (estimated incidence by Cox proportional hazard model 0.49%, 95% CI 0.29-0.69%) and in 54 patients within 54 months (estimated incidence from Cox proportional hazard model 1.35%, 95% CI 0.92-1.77%). During the study period, the incidence rates of each component of the primary composite outcome were 0.04% (0.2 events per 1000 person-years) for cardiovascular death, 0.51% (2.2 events per 1000 person-years) for nonfatal myocardial infarction, and 0.61% (2.5 events per 1000 person-years) for nonfatal ischemic stroke. The incidence of all-cause mortality was 0.82% (3.2 events per 1000 person-years) and the incidences of other cardiovascular events were all less than 0.3%. In conclusion, T2DM patients who received gemigliptin exhibited a low incidence of the primary composite MACE and all-cause mortality. Therefore, the use of gemigliptin is expected to be safe without an increase in cardiovascular risk.Trial registration: The study was registered at ClinicalTrials.gov (identifier: NCT02290301).

Status of international normalized ratio control and treatment patterns in patients with nonvalvular atrial fibrillation taking vitamin K antagonist with or without antiplatelet therapy: Results from KORAFII registry.

BACKGROUND: Studies have shown that the concomitant use of a vitamin K antagonist (VKA) and an antiplatelet (APL) drug increased the bleeding risk and was less effective at preventing ischemic events. This study aimed to investigate the control status of international normalized ratio (INR) and the discontinuation rate of a VKA in patients taking VKA plus an APL drug compared with those taking a VKA alone. METHODS: Data were extracted from the KORean Atrial Fibrillation Investigation II registry, a multicenter noninterventional prospective observational study. Nonvalvular atrial fibrillation (NVAF) patients with CHADS 2 scores ≥ 1 who newly started (within 3 months) a VKA were enrolled and followed up for 1 year. RESULTS: A total of 866 NVAF patients (mean age, 67.7 years; 60.3% men) without a bleeding history were divided into the VKA+APL (n = 229) and VKA alone (n = 637) groups. During follow-up, mean INR level was lower in the VKA+APL group than in the VKA alone group (1.7 ± 0.8 vs 1.9 ± 0.9, P = 0.0005). INR levels were poorly controlled in both groups (66.1% and 64.7%, respectively). Patients in the VKA+APL group more frequently discontinued VKA than patients in the VKA alone group (28.8% vs 24.2%, P = 0.045). Major causes of VKA discontinuation were uncontrolled INR level and patient dissatisfaction or concerns. CONCLUSIONS: The conditions of NVAF patients were inadequately controlled with VKA with or without an APL. These findings suggest that other antithrombotic treatment options are warranted in NVAF patients to achieve INR control.

Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

Supraventricular tachyarrhythmias in patients with a persistent left superior vena cava.

Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed. Of 6662 adult SVA patients who underwent an EP study or catheter ablation of SVA during the 10-year study period, 18 patients had PLSVC (mean age 47.6 ± 14.8 years, 10 men). The proportion of PLSVC in adult SVA patients was 0.27% (18/6662). SVA type and procedural outcomes of radiofrequency (RF) catheter ablation in these patients were investigated and the results were as follows: successful slow pathway modification in six of seven patients with atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation of accessory pathway in three of four patients with atrioventricular reentrant tachycardia, and successful ablation of atrial tachycardia (cavotricuspid isthmus-dependent in two, septal macroreentry in one, focal from the PLSVC in one) in three of four patients. In one patient with junctional tachycardia, catheter ablation failed. In two patients with atrial fibrillation, catheter ablation was successful. Conclusion: Among adult SVA patients who underwent an EP study or RF catheter ablation during the 10-year study period, 0.27% had PLSVC. The most common type of SVA was AVNRT. The success rate of catheter ablation was 82% in SVA patients with PLSVC. There were no procedure-related complications.

Erratum: Diagnostic Performance of Intravascular Ultrasound-Derived Minimal Lumen Area to Predict Functionally Significant Non-Left Main Coronary Artery Disease: a Meta-Analysis.

[This corrects the article on p. 622 in vol. 46, PMID: 27721852.].

Local Atrial/Ventricular Ratio as an Adjuvant Marker for Catheter Ablation of Atrioventricular Accessory Pathways.

BACKGROUND AND OBJECTIVES: The earliest atrial (A)/ventricular (V) activation potential, or accessory pathway (AP) potential are commonly used as ablation targets for atrioventricular (AV) APs. However, these targets are sometimes ambiguous. SUBJECTS AND METHODS: We reviewed 119 catheter ablation cases in 112 patients diagnosed with orthodromic atrioventricular reentrant tachycardia (AVRT) or Wolff-Parkinson-White (WPW) syndrome. Local A/V amplitude potentials with the earliest activation or AP potential were measured shortly before achieving antegrade AP conduction block, ventriculoatrial block during right ventricle (RV) pacing, or AVRT termination with no AP conduction. RESULTS: APs were located in the left lateral (55.5%), left posterior (17.6%), left posteroseptal (10.1%), midseptal (1.7%), right posteroseptal (7.6%), right posterior (1.7%), and right lateral (5.9%) regions. The mean earliest activation time was 16.7±15.5 ms, mean A/V potential was 1.1±0.9/1.0±0.9 mV, and mean A/V ratio was 1.7±2.0. There was no statistically significant difference between the activation methods (antegrade vs. RV pacing vs. orthodromic AVRT) or AP locations (left vs. right atrium). However, when the local A/V ratio was divided into 3 groups (≤0.6, 1.0±0.3, and ≥1.4), the antegrade approach resulted in an A/V ratio greater than 1.0±0.3 (86.7%, p=0.007), and the orthodromic AVRT state resulted in a ratio of less than 1.0±0.3 (87.5%, p<0.001). CONCLUSION: The mean local A/V potential and ratio did not differ by activation method or AP location. However, a different A/V ratio based on activation method (≥1.0±0.3, antegrade approach; and ≤1.0±0.3, orthodromic AVRT state) could be a good adjuvant marker for targeting AV APs.

Combined Use of Neutrophil to Lymphocyte Ratio and C-Reactive Protein Level to Predict Clinical Outcomes in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: Both neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) are biomarkers associated with poor prognosis of patients with acute myocardial infarction (AMI). However, the combined usefulness of NLR and CRP in predicting adverse outcomes has not been investigated. SUBJECTS AND METHODS: We analyzed 381 consecutive AMI patients who underwent percutaneous coronary intervention (PCI) from January 2012 to January 2014. The endpoints were all-cause mortality, recurrent myocardial infarction (MI), stent thrombosis, repeat revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE) at 2-year follow-up. Included patients were divided into 4 groups according to the optimal cut-off values for NLR and CRP on receiver operating characteristic analysis predicting mortality. RESULTS: Patients with both high NLR (>6.30) and high CRP (>0.76) had significantly greater risk of all-cause death and MACCE at 24 months, with no significant increase in the risk of recurrent MI, stent thrombosis, or stroke compared with patients with either low NLR or low CRP, as well as those with low NLR and low CRP. Kaplan-Meier analysis revealed significantly lower survival in patients with high NLR-CRP. On Cox multivariate analysis, high NLR-CRP (hazard ratio 23.172, 95% confidence interval 6.575 to 81.671, p<0.001) was an independent predictor of all-cause death. CONCLUSION: Elevated levels of both NLR and CRP are associated with increased risk of long-term mortality in AMI patients who have undergone PCI.

Extension of catheter ablation and outcome for ventricular tachycardia or premature ventricular contractions from the right ventricular outflow tract.

Objective We aimed to determine whether the extension of ablation could influence the ablation outcome for ventricular tachycardia (VT)/premature ventricular contractions (PVCs) from the right ventricular outflow tract (RVOT). Methods and results The radiofrequency catheter ablation results of 33 VT/6 frequent PVCs from the RVOT were analysed. The ablation extension was divided into 3 categories from the final successful ablation point with the earliest activation: (I) focal ablation (15 cases); ablation at 1 or 2 points; (II) focal with extended ablation (12 cases); focal and surrounding area ablation (maximum ≤1 cm) after elimination of clinical VT/PVCs; and (III) broad ablation (12 cases); continued broad ablation (maximum >1 cm) after elimination of clinical VT/PVCs. Acute termination was defined as the complete elimination and non-inducibility of clinical VT/PVCs during the procedure. For the mean follow-up of 12.8 months, the recurrence rate was not significantly different among the groups (P = 0.49). The mean procedure time was longer in group II, but ablation times and complication rates were not different among the groups. When acute termination was achieved, the overall recurrence rate was 7.6%. However, when confirming absence of the clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure, the recurrence rate was 2.7%. Conclusions Ablation extension did not affect ablation outcome of VT/PVCs from the RVOT. Confirmation of absence of clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure could guarantee long-term success.