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.

Sustained beneficial effect of ß-blockers on clinical outcomes after discontinuation in patients with ST elevation myocardial infarction.

Our previous study demonstrated that beneficial effect of ß-blockers on clinical outcomes in patients with ST elevation myocardial infarction (STEMI). In clinical practice, ß-blocker treatment is occasionally discontinued due to their side effect. The purpose of this study is to assess the impact of discontinuation of ß-blockers on long-term clinical outcomes in patients with STEMI. We analyzed the data and clinical outcomes of 901 patients (716 males, 58 ± 13-year-old) STEMI patients who underwent successful primary percutaneous coronary intervention. At discharge of index STEMI, 598 patients were treated with ß-blockers (491 males, 56 ± 12-year-old). After more than 1-month ß-blocker treatment, ß-blockers were stopped in 188 patients for any reason. We classified patients into continuation of ß-blockers (410 patients, 56 ± 12-year-old) and discontinuation of ß-blockers groups (188 patients, 57 ± 11-year-old) according to discontinuation of ß-blockers. Occurrence of major adverse cardiovascular events (MACEs; death, recurrent MI and target vessel revascularization) during up to 10 years of follow-up was evaluated. Mean follow-up month was 56 ± 28 month. In 132 patients (22%), MACEs were occurred. The MACE-free survival rates in the 2 groups were not statistically different (log-rank P = .461). Adjusted hazard ratio (HR) of discontinuation of ß-blockers for MACEs was 1.006 (95% confidence interval (CI) 0.701-1.445, P = .973; all cause of death, HR = 0.942, 95% CI = 0.547-1.622, P = .828; recurrent MI, HR = 0.476, 95% CI = 0.179-1.262, P = .136; target vessel revascularization, HR = 1.417, 95% CI = 0.865-2.321, P = .166). The MACE-free survival and survival rates of the non ß-blockers treatment group was significantly worse than the discontinuation of ß-blockers group (log-rank P = .003 and < 0.001, respectively). This study demonstrated that discontinuation of ß-blockers was not associated with adverse cardiovascular outcomes after STEMI. The beneficial effect of ß-blockers on clinical outcomes may persist in patients with initial ß-blockers treatment at index STEMI.

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.

Edoxaban treatment in atrial fibrillation in routine clinical care: One-year outcomes of the prospective observational ETNA-AF study in South Korean patients.

Background: The real-world outcomes of edoxaban treatment in patients with atrial fibrillation (AF) were analyzed in the ETNA-AF (Edoxaban Treatment in Routine Clinical Practice) study involving data from multiple regional registries. This report addresses effectiveness and safety of edoxaban in the Korean ETNA-AF population. Methods: One-year data from 1887 Korean ETNA-AF participants were analyzed according to edoxaban dose and patient age and compared with results of other ETNA-AF registries. Results: Approximately 70% of patients received the recommended doses of edoxaban (60 mg/30 mg); non-recommended 60 mg and 30 mg doses were prescribed to 9.6% and 19.8% of the patients, respectively. The proportions of reference age (<65 years), youngest-old (65-74 years) and middle-old/oldest-old (≥75 years) groups were 21.4%, 40.2%, and 38.4%, respectively. Incidence of major or clinically relevant nonmajor bleeding was similar within dose (0.57%-1.71%) and age subgroups (1.26%-1.63%). Incidence of net clinical outcome, a composite of stroke, systemic embolic event, major bleeding, and all-cause mortality, was also comparable among dose subgroups (1.14%-3.10%) and age subgroups (2.28%-2.78%). The percentage of Korean patients receiving non-recommended 30 mg (19.8%) was over twice that of the European population (8.4%). However, the clinical outcomes were generally similar among different populations included in the ETNA-AF study. Conclusions: The outcomes in the Korean ETNA-AF population are like those in the global ETNA-AF population, with overall low event rates of stroke, major bleeding and all-cause mortality across age and dose subgroups. Edoxaban can be used effectively and safely in specific populations of Korean AF patients, including the elderly.

Efficacy and Safety of Coadministered Ezetimibe-Rosuvastatin plus Telmisartan in South Korean Patients with Dyslipidemia and Hypertension: A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase III Trial.

BACKGROUND: The introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance. METHODS: There were 181 subjects who were randomized to three groups: ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe-rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8. RESULTS: The least-square mean (SE) in MSSBP changes between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe-rosuvastatin 10/20 mg group were -25.81 (2.34) mmHg and -7.66 (2.45) mmHg. There was a significant difference between the two groups (-18.15 (2.83) mmHg, 95% CI -23.75 to -12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were -63.82 (2.87)% and -2.48 (3.12)%. A significant difference was observed between the two groups (-61.34 (3.33)%, 95% CI -67.91 to -54.78, p < 0.0001). No serious adverse events were observed. CONCLUSIONS: Ezetimibe-rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe-rosuvastatin or telmisartan.

Therapeutic implications of galectin-3 in patients with atrial fibrillation.

Atrial fibrosis can present as an arrhythmogenic substrate that is correlated with higher recurrence after catheter ablation for atrial fibrillation. Galectin-3, a beta-galactoside-binding lectin, is highly expressed and secreted from macrophages and is important in inflammation and fibrosis. We assessed the clinical implications of serum galectin-3 in patients with atrial fibrillation. This was a prospective cohort study of consecutive patients who underwent radiofrequency catheter ablation in a tertiary referral center from February 2017 to September 2017. Intracardiac blood sampling, echocardiographic measurements, magnetic resonance imaging with late gadolinium enhancement, electrophysiologic testing, and endocardial voltage mapping were consistently implemented in 75 patients before the ablation. Serum galectin-3 level was higher in patients with diabetes mellitus and was correlated with values that indicated the left atrial size. During a median 14 months of follow-up, atrial tachyarrhythmia recurred in 27% of patients. In multivariable Cox regression analysis, non-paroxysmal atrial fibrillation (hazard ratio 6.8; 95% confidence interval 1.6-28.9) and higher galectin-3 levels (hazard ratio 1.3; 95% confidence interval 1.0-1.7) were associated with increased risk of recurrence. Serum galectin-3 may be a prognostic biomarker for risk stratification in patients with atrial fibrillation planned catheter ablation.

Clinical Events with Edoxaban in South Korean and Taiwanese Atrial Fibrillation Patients in Routine Clinical Practice.

Edoxaban is approved for stroke prevention in nonvalvular atrial fibrillation (AF) patients in numerous countries. Outcome data are sparse on edoxaban treatment in AF patients from routine clinical practice, especially in Asian patients. Global ETNA (Edoxaban in rouTine cliNical prActice) is a noninterventional study that integrates data from patients from multiple regional registries into one database. Here, we report the 1-year clinical events from AF patients receiving edoxaban in South Korea and Taiwan. Clinical events assessed included bleeding, strokes, systemic embolic events, transient ischemic attacks (TIAs), and all-cause and cardiovascular death. Overall, 2677 patients (mean (range) age 72 (66-78) years, male 59.7%, mean CHA2DS2-VASc score ± standard deviation 3.1 ± 1.4) were treated with 60 or 30 mg edoxaban and had 1-year follow-up data. The annualized event rates for major bleeding and clinically relevant non-major (CRNM) bleeding were 0.78% and 0.47%, respectively. Annualized event rates for ischemic stroke and hemorrhagic stroke were 0.90% and 0.19%, respectively. Event rates for major and CRNM bleeding and rates of ischemic stroke and TIA were higher in Taiwanese patients than in Korean patients. Event rates were low and similar to those found in other studies of edoxaban in Korean and Taiwanese AF patients, thus supporting the safety and effectiveness of edoxaban in this population.

Long-term evaluation of sensing variability of a floating atrial dipole in a single­lead defibrillator: The mechanistic basis of long-term stability of amplified atrial electrogram.

BACKGROUND: A single­lead implantable cardioverter-defibrillator (ICD) with a floating atrial dipole has been developed to enhance the diagnostic capability of atrial arrhythmias and to facilitate adjudication of arrhythmic events without the additional effort required for atrial lead insertion. However, there have been concerns about the long-term reliability of atrial sensing. METHODS: We enrolled patients with the single-chamber ICD with atrial-sensing electrodes from 4 tertiary university hospitals in Korea. Minimal, maximal, and mean P wave amplitudes were collected at 3-6 months, 6-12 months, and 12-24 months after implantation. The difference between the minimal and maximal sensing amplitudes was calculated as an indicator of the variability of atrial sensing, while the atrial sensing stability was assessed using the mean amplitude. RESULTS: A total of 86 patients were included for analysis. The variability of atrial sensing amplitudes significantly decreased at 12-24 months compared to 3-6 months (p = 0.01), while mean atrial amplitudes were stable throughout the mean follow-up duration of 17.4 months. Nine patients (10.5%) experienced inappropriate ICD therapy mostly due to misclassification of supraventricular tachycardia. CONCLUSIONS: Under the hypothesis that sensing stability can be guaranteed as the variability decreases with time, we suggest that the concern about long-term sensing stability of a floating dipole can be abated with an ICD that has been implanted for over 2 years.

Managing Nonagenarians with Acute Myocardial Infarction: Invasive versus Conservative Treatment.

BACKGROUND: Limited data are available to support an invasive treatment strategy in nonagenarians with acute myocardial infarction (AMI). We aimed to investigate whether percutaneous coronary intervention (PCI) is beneficial in this frail population. METHODS: We retrospectively analyzed 41 nonagenarians with AMI (both ST-segment-elevation and non-ST-segment-elevation MI) between 2006 and 2015 in a single center. We assessed 30-day and one-year mortality rates according to the treatment strategy. RESULTS: Among study subjects, 24 (59%) were treated with PCI (PCI group) and 17 (41%) were treated with conservative management (medical treatment group) per the clinician's discretion. The median follow-up duration was 30 months (0-74 months). Thirty-day mortality was lower in the PCI group than in the medical treatment group (17% vs. 65%; P < 0.001). One-year mortality was also lower in the PCI group than in the medical treatment group (21% vs. 76%; P < 0.001). The PCI group presented a 73% decreased risk of death (adjusted hazard ratio: 0.269; 95% confidence interval: 0.126-0.571; P < 0.001). In the Killip class 1 through 3 subgroups (n = 36), 30-day and one-year mortality were still higher among those in the medical treatment group (13% vs. 54% at 30 days; P < 0.001 and 17% vs. 69% at one year; P < 0.001). Landmark analysis after 30 days revealed no significant difference in the cumulative mortality rate between the two groups, indicating that the mortality difference was mainly determined within the first 30 days after AMI. CONCLUSION: Mortality after AMI was decreased in correlation with the invasive strategy relative to the conservative strategy, even in nonagenarians. Regardless of age, PCI should be considered in AMI patients. However, large-scale randomized controlled trials are needed to support our conclusion.

Usefulness of the trans-stent fractional flow reserve gradient for predicting clinical outcomes.

OBJECTIVES: We evaluated the usefulness of a fractional flow reserve (FFR) gradient across the stent (ΔFFRstent ) for long-term clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). BACKGROUND: The clinical meaning of a trans-stent pressure gradient after DES implantation has not been estimated adequately. METHODS: FFR pull-back and intravascular ultrasound (IVUS) were performed after successful PCI in 135 left anterior descending artery lesions. ΔFFRstent was defined as the FFR gradient across the stent. The ΔFFRstent/length was defined as the ΔFFRstent value divided by the total stent length multiplied by 10. Major adverse cardiac events (MACEs) were the composite of all-cause death, target vessel-related myocardial infarction, and target lesion revascularization. RESULTS: Despite successful PCI, ΔFFRstent > 0 was observed in 98.5% of cases. ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 predicted suboptimal stenting defined as final minimal stent area < 5.5 mm2 . During 2,183 ± 898 days, the MACE-free survival rate was significantly lower in patients with ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 compared to those with lower values (69.6 vs. 93.4%, log-rank p = .031; 72.1 vs. 97.7%, log-rank p = .003, respectively). ΔFFRstent/length ≥ 0.009 (hazard ratio 10.1, p = .032) was an independent predictor of MACE. CONCLUSION: A trans-stent FFR gradient was frequently observed. ΔFFRstent and ΔFFRstent/length are related to long-term outcomes in DES-treated patients.

Impact of new-onset diabetes on clinical outcomes after ST segment-elevated myocardial infarction.

Objective. Patients with diabetes have higher mortality rate than patients without diabetes after ST-segment elevated myocardial infarction (STEMI). Prognosis of patients with new onset diabetes (NOD) after STEMI remains unclear. The aim of this study was to evaluate the prognosis of patients with NOD compared to that of patients without NOD after STEMI. Design. This study was a retrospective observational study. We enrolled 901 STEMI patients. Patients were divided into diabetic and non-diabetic groups at index admission. Non-diabetic group was divided into NOD and non-NOD groups. Kaplan-Meier analysis and Cox's proportional hazard regression models were used to compare major adverse cardiac events (MACE) free survival rate and hazard ratio for MACE between NOD and non-NOD groups. Results. Mean follow-up period was 59 ± 28 months. Diabetes group had higher MACE than non-diabetes group (p = .038). However, MACE was not different between NOD and non-NOD groups (p = 1.000). After 1:2 propensity score matching, incidence of MACE was not different between the two groups. In Kaplan-Meier survival curves, MACE-free survival rates were not statistically different between NOD and non-NOD groups either (p = .244). Adjusted hazard ratios of NOD for MACE, all-cause of death, recurrent myocardial infarction, and target vessel revascularization were 0.697 (95% confidence interval [CI]: 0.362-1.345, p = .282), 0.625 (95% CI: 0.179-2.183, p = .461), 0.794 (95% CI: 0.223-2.835, p = .723), and 0.506 (95% CI: 0.196-1.303, p = .158), respectively. Conclusion. This retrospective observational study with a limited statistical power did not show a different prognosis in patients with and without NOD.

Lipid-Core Plaque Assessed by Near-Infrared Spectroscopy and Procedure Related Microvascular Injury.

BACKGROUND AND OBJECTIVES: Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction. We assessed the lipid-core plaque using near-infrared spectroscopy (NIRS) and microvascular dysfunction invasively with the index of microcirculatory resistance (IMR) and evaluated their relationship. METHODS: This study is pilot retrospective observational study. We analyzed 39 patients who performed NIRS before and after PCI, while fractional flow reserve, thermo-dilution coronary flow reserve (CFR) and IMR were measured after PCI. The maximum value of lipid core burden index (LCBI) for any of the 4-mm segments at the culprit lesion (culprit LCBI4mm) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit LCBI4mm ≥500. RESULTS: Mean pre-PCI LCBI was 333±196 and mean post-PCI IMR was 20±14 U. Post-PCI IMR was higher (15.6±7.3 vs. 42.6±17.6 U, p<0.001) and post-PCI CFR was lower (3.7±2.2 vs. 2.1±1.0, p=0.029) in the high LCBI group. Pre-PCI LCBI was positively correlated with post-PCI IMR (ρ=0.358, p=0.025) and negatively correlated with post-PCI CFR (ρ=-0.494, p=0.001). The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high LCBI group (9.4% vs. 85.7%, p<0.001). However, there were no significant differences in the incidences of creatine Kinase-MB (9.4% vs. 14.3%, p=0.563) and troponin-I elevation (12.5% vs. 14.3%, p=1.000). CONCLUSIONS: A large lipid-core plaque at the 'culprit' lesion is observed higher incidence of post-PCI microvascular dysfunction after PCI. Prospective study with adequate subject numbers will be needed.

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.

Visit-to-visit systolic blood pressure variability in patients with ST-elevation myocardial infarction predicts long-term cardiovascular outcomes.

Elevated visit-to-visit blood pressure variability (BPV), independent of mean BP, has been associated with cardiovascular events. However, its impact after ST-elevation myocardial infarction (STEMI) has not been established. This study aimed to investigate the prognostic impact of BPV on patients after STEMI. We analyzed the data and clinical outcomes of STEMI survivors who underwent successful primary coronary intervention from 2003 to 2009. BP was measured at discharge and at 1, 3, 6, 12, 24, and 36 months, and we calculated BPV as the intra-individual standard deviations (SDs) of systolic BP (SBP) across these measurements. We classified the patients as high and low-BPV group, and evaluated the outcomes: occurrence of major adverse cardiovascular events (MACEs), death, recurrent myocardial infarction, and target vessel revascularization within 60 months. We enrolled 343 patients, and mean follow-up duration was 68 ± 34 months (median: 76 months). Mean and median SBP SDs were 13.2 and 12.3 mmHg, and patients were divided into one of the two groups based on the median (high-BPV group = SD ≥ 12.3 mmHg; low-BPV group = SD < 12.3 mmHg). The MACE-free survival in the high-BPV group was significantly worse than that in low-BPV group (log-rank p = 0.035). For the high-BPV group, the risk of a MACE significantly increased by 57% (95% confidence interval: 1.03-2.39; p = 0.038). Visit-to-visit systolic BPV was associated with increased rates of adverse clinical outcomes in patients after STEMI. Careful assessment of BP and attempts to reduce BPV might be also important in STEMI survivors.

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.

Importance of prognostic value of neutrophil to lymphocyte ratio in patients with ST-elevation myocardial infarction.

The ratio between the absolute number of neutrophils and the number of lymphocytes (NLR) has recently emerged as a potential new biomarker predicting worse clinical conditions ranging from infectious disease to cardiovascular disease. Prognostic significance of NLR in patients with ST-elevation myocardial infarction (STEMI) is not established. This study aimed to investigate prognostic impact of NLR in patients with STEMI.We analyzed the data and clinical outcomes of 30-day survivors with STEMI who received successful coronary intervention from 2006 to 2010. NLR was computed from the absolute values of neutrophils and lymphocytes from the complete blood count at admission. Occurrence of major adverse cardiovascular events (MACEs; death, recurrent MI, target vessel revascularization (TVR)) at 5 years was evaluated.We enrolled 326 patients and mean follow-up duration was 68 ±â€Š36 months. The mean NLR was 4.7 ±â€Š5.2. Among all patients, all-cause mortality occurred in 46 patients (14%). Initial NLR was higher in patients who experienced all-cause mortality (6.39 ±â€Š8.9 vs 4.2 ±â€Š3.1, P = .004). In a multivariate regression model, the higher NLR was independently associated with increased risk for all-cause mortality (Hazard ratio, 1.085; 95% confidence interval, 1.002-1.174, P = .044).Increased NLR was associated increased rate of all-cause mortality in 30-day survivors after index STEMI, who received successful coronary intervention.

Comparison of efficacy and safety between two different irbesartan, generic vs branded, in the treatment of Korean patients with mild-to-moderate hypertension: an 8-week, multicenter, randomized, open-label, Phase IV clinical study.

PURPOSE: This study aimed to compare the efficacy and safety of generic and branded irbesartan for 8 weeks in patients with mild-to-moderate essential hypertension. PATIENTS AND METHODS: We screened 221 patients with mild-to-moderate hypertension. After exclusion per study criteria, 177 subjects were randomized to receive 150 mg generic irbesartan (n=91) or branded irbesartan (n=86) as the intention to treat set. The primary efficacy endpoint of this study was the change in mean sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks between the generic and branded irbesartan groups. The secondary efficacy endpoints were the change in mean SiDBP at Week 4 from baseline and the change in mean sitting systolic blood pressure (SiSBP) at Weeks 4 and 8 from baseline in both groups. All safety issues were evaluated. RESULTS: At Week 8, the generic and branded irbesartan groups showed significantly reduced SiDBP (-10.3±8.0, -10.7±7.7 mmHg, all P<0.0001) compared with baseline values, and the mean between-group difference in SiDBP change after 8 weeks of treatment was -0.4±1.2 mmHg, showing the non-inferiority of generic irbesartan vs branded irbesartan. Furthermore, secondary efficacy, which was the mean change of SiDBP from baseline at 4 weeks, was comparable between the two groups (-9.4±8.1 vs -9.9±7.4 mmHg, P=0.69). There were no between-group differences in mean changes of SiSBP after 4 or 8 weeks of treatment (P=0.78, P=0.97, respectively), or in the incidence of adverse effects (16.7 vs 24.4%, P=0.20). CONCLUSION: Generic irbesartan treatment in patients with mild-to-moderate essential hypertension has shown effective antihypertensive effects comparable with the branded irbesartan treatment, with similar incidence of adverse effects.

Intravascular ultrasound characteristics in patients with intermediate coronary lesions and borderline fractional flow reserve measurements.

Revascularization of borderline fractional flow reserve (FFR) is controversial and the morphologic characteristics of borderline FFR lesions are not well known. The objective of this study was to determine the intravascular ultrasound (IVUS) characteristics in intermediate coronary lesions with borderline FFR in patients with intermediate coronary artery stenosis (40%-70% diameter stenosis).Both IVUS and FFR were performed in a total of 228 left anterior descending arteries. We divided them into 3 groups by FFR value: ischemic (n = 46, FFR < 0.75), borderline (n = 71, FFR 0.75 to ≤0.80), and non-ischemic (n = 111, FFR > 0.80). We compared the IVUS parameters, including minimum lumen area, lesion length, plaque burden, and volumetric analysis among the 3 groups.In the IVUS analysis, the minimum lumen area was smaller (2.5 ±â€Š0.6 vs. 2.7 ±â€Š0.7 vs. 3.4 ±â€Š1.2 mm, P < .001); lesion length was longer (23.6 ±â€Š8.4 vs. 23.6 ±â€Š7.4 vs. 17.4 ±â€Š6.8 mm, P < .001); plaque burden was larger (76.1 ±â€Š9.6 vs. 73.9 ±â€Š7.5 vs. 69.8 ±â€Š9.5%, P < .001); plaque volume was larger (173.0 ±â€Š78.3 vs. 167.7 ±â€Š75.0 vs. 129.5 ±â€Š79.1 mm, P < .01); and percent atheroma volume was larger (57.9 ±â€Š7.5 vs. 57.6 ±â€Š6.6 vs. 53.9 ±â€Š8.0%, P < .01) in the ischemic and borderline groups compared with the non-ischemic group, respectively. However, post-hoc analyses showed there were no significant differences between the ischemic and borderline group for all IVUS parameters.There were no differences in IVUS characteristics between borderline and functionally significant FFR, but the amount of atheromatous plaque was more severe in these 2 groups than in the non-ischemic group.

Efficacy and Safety of Ezetimibe and Rosuvastatin Combination Therapy Versus Those of Rosuvastatin Monotherapy in Patients With Primary Hypercholesterolemia.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia. METHODS: This multicenter, randomized, double-blind study comprised a main study and an extension study. In the main study, the efficacy and safety of a combination of rosuvastatin (5, 10, and 20 mg) with ezetimibe (10 mg) were compared with those of rosuvastatin (5, 10, and 20 mg) alone. The subjects who achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the main study and agreed to a further study were enrolled for the extension study. In the extension study, ezetimibe 10 mg was also administered to subjects who had received rosuvastatin (5, 10, and 20 mg) alone in the main study, and the same treatment was continued for subjects who had received a combination of rosuvastatin with ezetimibe in the main study. FINDINGS: At the end of the main study (week 8), LDL-C levels were significantly lower in subjects receiving combination therapy than in those receiving rosuvastatin monotherapy. Other lipid profiles also significantly improved in the combination therapy group. These improvements continued in the extension study. The combination therapy of rosuvastatin and ezetimibe was generally well tolerated. At the end of the main study, more subjects achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the combination therapy group than in the monotherapy group. The increased dosage of rosuvastatin was also well tolerated in the combination treatment. IMPLICATIONS: Combination therapy of ezetimibe 10 mg with varying doses of rosuvastatin that are commonly used in the clinical field improved the lipid profile and allowed more subjects to reach the LDL-C goal in primary hypercholesterolemia compared with rosuvastatin monotherapy. In addition, the efficacy of the combination therapy was maintained for the extended period. Additional beneficial changes were also achieved with combination therapy even in patients who responded well to rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT03288038.