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.

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.

Myocardial Mass Contributes to the Discrepancy Between Anatomic Stenosis Severity Assessed by Intravascular Ultrasound and Fractional Flow Reserve in Intermediate Lesions of the Coronary Artery.

OBJECTIVES: The present study investigated the major contributors to the discrepancy between the minimal lumen area (MLA) and fractional flow reserve (FFR). BACKGROUND: There was considerable discrepancy between MLA or diameter stenosis (DS) and FFR. METHODS: We enrolled 744 patients with intermediate stenoses of the left anterior descending artery (LAD). Summed epicardial coronary artery length distal to the target stenosis was obtained from each longest view of the vessels on the coronary angiograms. Mismatching was defined as a lesion with FFR of >0.80 and MLA smaller than the best cut-off value (BCV) for predicting FFR of ≤0.80. Reverse mismatching was defined as a lesion with FFR of ≤0.80 and MLA larger than the BCV. RESULTS: Summed epicardial coronary artery length was longer at the lesions of proximal LAD than that of middle LAD (380 mm ± 82 mm vs. 341 mm ± 80 mm, P < 0.001). Reverse mismatching was found more frequently in the proximal than middle LAD (28.3% vs. 5.5%, P < 0.001). Independent predictors of FFR ≤ 0.80 were age, male, multi-vessel disease, proximal LAD lesion, MLA, DS, plaque burden at distal reference, lesion length and summed epicardial coronary artery length. Proximal LAD lesion was an independent predictor of reverse mismatching (hazard ratio 3.162, 1.858-5.382, P < 0.001). CONCLUSIONS: Myocardial mass subtended by a lesion is an important factor predicting FFR ≤0.80 and discrepancy between FFR and MLA. Myocardial mass subtended by a lesion should be considered when determining the revascularization therapy by intravascular ultrasound parameters. © 2017 Wiley Periodicals, Inc.

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.

Echocardiographic epicardial fat thickness is a predictor for target vessel revascularization in patients with ST-elevation myocardial infarction.

BACKGROUND: The amount of epicardial adipose tissue (EAT) has been demonstrated to correlate with the severity of coronary artery disease (CAD) and the CAD activity. The aim of this study is to assess the impact of EAT on long term clinical outcomes in patients with ST elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). METHODS: We analyzed the data and clinical outcomes of 761 patients (614 males, 57 ± 12 year-old) with STEMI who underwent successful primary PCI from 2003 to 2009. All patients were divided into two groups: thick EAT group, EAT ≥ 3.5 mm and thin EAT group, EAT < 3.5 mm. The primary end points were all-cause death, recurrent MI, target vessel revascularization (TVR) and major cardiac adverse events (MACEs), composite of all-cause death, recurrent MI and TVR, within 5 years. RESULTS: Median and mean EAT of 761 patients were 3.3 mm and 3.6 ± 1.7 mm, respectively. Mean follow up period was 46 ± 18 months. MACE-free survival rate in the thick EAT group was significantly lower than in the thin EAT group (log-rank P = 0.001). The event-free survival rate of all-cause death of the thick EAT group was significantly lower than that of the thin EAT group (log-rank P = 0.005). The TVR-free survival rate in the thick EAT group was significantly lower than in the thin EAT group (log-rank P = 0.007). The event-free survival rate of recurrent MI were not significantly different between the groups (log-rank P = 0.206). In the Cox's proportional hazard model, the adjusted hazard ratio of thick EAT thickness for TVR was 1.868 (95% confidence interval 1.181-2.953, P = 0.008). CONCLUSION: This study demonstrates that the EAT thickness is related with long term clinical outcome in patients with STEMI. The EAT thickness might provide additional information for future clinical outcome, especially TVR.

ß-Blocker Therapy in the Era of Primary Percutaneous Intervention for ST Elevation Myocardial Infarction.

OBJECTIVES: With the present therapeutic advances in the era of primary percutaneous coronary intervention (PCI), the role of ß-blockers in ST elevation acute myocardial infarction (STEMI) has remained contentious. METHODS: We analyzed the data and clinical outcomes of 901 STEMI patients who had undergone primary PCI. We classified the patients into ß-blocker (n = 598) and non-ß-blocker groups (n = 303). RESULTS: The cumulative incidence of all-cause death was 10.0% in the ß-blocker group and 25.4% in the non-ß-blocker group (p < 0.001). The incidence of major adverse cardiac events (MACE) was 22.1% in the ß-blocker group and 34.3% in the non-ß-blocker group (p < 0.001). The relative hazard ratio (HR) of ß-blockers for all-cause death and MACE with low left ventricle ejection fraction (LVEF; <50%) was 0.55 [95% confidence interval (CI) 0.35-0.86, p = 0.009] and 0.75 (95% CI 0.51-1.09, p = 0.125), respectively. In patients with normal LVEF (≥50%), the relative HR of ß-blockers for death and MACE were 0.50 (95% CI 0.29-0.88, p = 0.016) and 0.75 (95% CI 0.51-1.12, p = 0.162), respectively. After propensity score matching of the difference of the baseline characteristics, the Kaplan-Meier survival curve demonstrated lower mortality in the ß-blocker group than in the non-ß-blocker group with both low LVEF and normal LVEF (p = 0.02 and p = 0.001, respectively). CONCLUSIONS: ß-Blockers have beneficial clinical outcomes in the era of primary PCI for STEMI, regardless of the LVEF. © 2015 S. Karger AG, Basel.

Left ventricular hypertrophy on long-term cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: Left ventricular hypertrophy (LVH) had been associated with increased adverse cardiovascular events in hypertensive patients. Prognostic significance of LVH in patients with ST-elevation myocardial infarction (STEMI) is not established. This study aimed to investigate prognostic impact of LVH on the patients with STEMI. METHODS: We analyzed the data and clinical outcomes of 30-day survivors with STEMI who underwent successful coronary intervention from 2003 to 2009. Definition of LVH was LV mass index (LVMI) >115 g/m(2) in male and >95 g/m(2) in female. Patients were classified into a LVH group and a non-LVH group. Occurrence of major adverse cardiovascular events (MACE; death, recurrent MI, target vessel revascularization (TVR)) within 5 years was evaluated. RESULTS: We enrolled 418 patients and mean follow-up duration was 43 ± 17 months. Two hundred and fourteen patients (51%) had LVH. The survival of the patients with LVH was significantly worse than the patients without LVH (log-rank p = 0.024). In a multivariate regression model, the presence of LVH was independently associated with increased risk for all-cause mortality (OR, 2.37; 95% CI, 1.096-5.123, p = 0.028). When the end points were analyzed based on LVH severity, all-cause mortality was significantly correlated with LVH severity (p = 0.011). The severe LVH was independently associated with increased risk for all-cause mortality (OR, 5.110; 95% CI, 1.454-17.9, p = 0.001). CONCLUSION: LVH was associated with increased rate of adverse clinical outcomes in 30-day survivors after STEMI, who underwent successful coronary intervention.

Clinical Implication of Heart Rate Variability in Obstructive Sleep Apnea Syndrome Patients.

UNLABELLED: Obstructive sleep apnea syndrome (OSAS) is a common disease with the prevalence of approximately 10% in general population, and this disease entity is considered to be highly related with the development of cerebrovascular and cardiovascular diseases. In the pathogenesis of cardiovascular disease, maintaining the homeostasis of autonomic nervous system (ANS) is critical. To evaluate the homeostasis of ANS, heart rate variability (HRV) is commonly used. The object of this study was to evaluate the homeostasis of ANS using the parameters of HRV and to elucidate the correlation between the parameters and apnea-hypopnea index (AHI). METHODS: Retrospective review of 806 patients was performed and 164 patients who were diagnosed as having OSAS by in-room polysomnography and met the criteria of age, sex, and body mass index were enrolled. The calculation of HRV parameters was executed using echocardiographic data from polysomnography. RESULTS: Between the control group (N = 81, AHI < 5) and OSAS patient group (N = 83, AHI > 15), standard deviation of NN (SDNN) intervals, SDNN index, HRV triangular index, very low frequency (VLF), low frequency (LF), 5-minute total power (TP), and low-frequency to high-frequency (LF/HF) ratio showed significant differences. In the correlation analysis between AHI and HRV parameters, only LF/HF ratio was proven to be significant. CONCLUSIONS: Elucidating the imbalance of ANS in OSAS patients was feasible by HRV and its parameters.

Relationship between intravascular ultrasound parameters and fractional flow reserve in intermediate coronary artery stenosis of left anterior descending artery: intravascular ultrasound volumetric analysis.

OBJECTIVES: The objective of this study was to assess the relationship between intravascular ultrasound (IVUS) parameters, including volumetric analysis, and fractional flow reserve (FFR). BACKGROUND: Although it is known that coronary atherosclerosis burden measured by IVUS volumetric analysis is related with clinical outcomes, its relationship with functional significance remains unknown. METHODS: Both IVUS and FFR were performed in 206 cases of intermediate stenosis of the left anterior descending artery (LAD). Myocardial ischemia was assessed by FFR and maximal hyperemia was induced by continuous intracoronary adenosine infusion. FFR < 0.80 was considered as significant inducible myocardial ischemia. We performed standard IVUS parameter measurements and volumetric analyses. IVUS parameter comparison was performed in the presence (n = 90) or absence (n =116) of significant myocardial ischemia. RESULTS: Lesions with minimal lumen area (MLA) ≥ 4.0 mm2 had FFR ≥ 0.80 in 91.4% of cases, while 50.9% of lesions with MLA < 4.0 mm2 had FFR < 0.80. The independent predictors of FFR < 0.80 were IVUS lesion length (odds ratio [OR]: 1.1, 95% confidence interval [CI] = 1.06­1.18, P < 0.001) and MLA significance according to the lesion location (OR: 7.01, 95% CI = 3.09­15.92, P = 0.001). FFR correlated with plaque volume (r = −0.345, P < 0.001) and percent atheroma volume (PAV) (r = −0.398, P < 0.001). Lesions with significant ischemia (FFR < 0.80) as compared to those with FFR > 0.80 were associated with larger plaque volume (181.8 ± 82.3 vs. 125.9 ± 77.9 mm3, P < 0.001) and PAV (58.9 ± 5.6 vs. 53.8 ± 7.9%, P < 0.001). CONCLUSIONS: IVUS parameters representing severity and extent of atheromatous plaque correlated with functional significance in LAD lesions with intermediate stenosis.

The pattern of Tpeak-Tend and QT interval, and J wave during therapeutic hypothermia.

BACKGROUND AND PURPOSE: The electrocardiogram manifestations of hypothermia include J waves and prolongation of QT intervals. This study described changes in repolarization patterns during therapeutic hypothermia (TH). METHODS: We measured the QTc and the interval from the peak to the end of the T wave (TpTe) from the V4 and V6 leads in 20 patients with TH. The TpTe was also expressed as a ratio to the duration of QT ([TpTe/QT]×100%), and to the corrected value for heart rate (TpTe/√RR). RESULTS: The QTc became prolonged in all patients during TH. While the TpTe/√RR did not change, the ([TpTe/QTe]×100%] decreased significantly during TH. The J wave developed during TH in seven patients. With one patient, ventricular fibrillation occurred preceded by an abnormal J wave and prolonged TpTe during TH. CONCLUSIONS: QTc prolongation without TpTe increase or abnormal J wave may not be arrhythmogenic during TH.

Noncoronary ST elevation and polymorphic ventricular tachycardia during left-sided accessory pathway ablation.

INTRODUCTION: An early repolarization (ER) pattern on electrocardiogram (ECG) sometimes has the risk of polymorphic ventricular tachycardia (PVT) or ventricular fibrillation (VF). An abnormal ER pattern can develop in various experimental or clinical situations. We experienced 4 cases of abnormal ER pattern with or without PVT during the radiofrequency (RF) ablation of the left accessory pathway. METHODS AND RESULTS: An electrophysiologic study and RF ablation were performed in 4 patients. Four patients had atrioventricular reentrant tachycardia. During RF ablation of the left accessory pathway, severe chest pain developed and was followed by abnormal J-point elevation. During the ongoing chest pain and J-point elevation, coronary angiograms showed normal findings. The chest pain and J-point elevation were followed by PVT or VF that was unresponsive to defibrillation. The PVT was spontaneously terminated and repeated. After 0.5 mg atropin was given, chest pain and ECG change disappeared. CONCLUSION: The mechanisms of ER syndrome during RF ablation might be increased vagal tone due to chest pain or direct vagal stimulation.

Comparison of 3-year clinical outcomes between classic crush and modified mini-crush technique in coronary bifurcation lesions.

OBJECTIVES: We aimed to compare long-term clinical outcomes between modified mini-crush (modi-MC) technique with classic crush (crush) technique for treatment of bifurcation lesions. BACKGROUND: The modi-MC technique showed excellent procedural success and favorable 9-month clinical outcomes. METHODS: From January 2005 to November 2009, we enrolled patients with de novo bifurcation lesions treated with modi-MC (n = 112 lesions in 111 patients) and crush technique (n = 69 lesions in 67 patients). Primary endpoint was rate of major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target lesion revascularization (TLR) at 3 years. RESULTS: There was no significant difference in baseline characteristics. The modi-MC technique showed a significantly higher success rate of final kissing balloon inflation (84.1 vs. 98.2%, P = 0.001). After 3 years, MACE rate was significantly lower in the modi-MC group (25.4 vs. 12.6%, P = 0.030). The incidence of all-cause death was 7.5 vs. 2.7% (P = 0.087), MI was 4.5 vs. 1.8% (P = 0.290), TLR was 17.4 vs. 8.9% (P = 0.093) and stent thrombosis was 3.0 vs. 1.8% (P = 0.632) in the crush and modi-MC groups, respectively. CONCLUSIONS: The modified mini-crush technique showed more favorable 3-year clinical outcomes compared to the classic crush technique.

Echocardiographically measured epicardial fat predicts restenosis after coronary stenting.

OBJECTIVE: Epicardial adipose tissue (EAT), deposited around subepicardial coronary vessels, may contribute directly to perivascular inflammation and smooth muscle cell proliferation. This study assessed the relationship between EAT and in-stent restenosis. METHODS: Four hundred and seven patients had received successful coronary intervention. EAT thickness was measured by echocardiography. Angiographic follow-up was obtained between 6 months and 2 years. Restenosis was defined as target lesion revascularization (TLR). EAT thickness of patients was compared by TLR controlling for additional well-known predictors of restenosis. The TLR-free survival analysis according to EAT thickness was estimated using the Kaplan-Meier method and the differences between groups were assessed by the log-rank test. RESULTS: Median EAT thickness was significantly increased in patients undergoing TLR compared with those without restenosis (3.7 vs. 3.0 mm, p = 0.001). EAT thickness was one of the independent factors associated with restenosis (Odds ratio = 1.19, 95% confidence interval = 1.01-1.33, p = 0.007). The TLR-free survival of patients with thick EAT was significantly worse than patients with thin EAT (log-rank p = 0.001). CONCLUSIONS: EAT thickness is related with restenosis and may provide additional information for future restenosis.

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.

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.

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.

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.

The Relationship between coronary artery calcification as assessed by multi-detector computed tomography and arterial stiffness.

Pulse wave analysis and intima-media thickness (IMT) of carotid artery are the non-invasive indicators of subclinical atherosclerosis. Coronary artery calcification (CAC) score measured by multi-detector computed tomography (MDCT) is well known as a predictor of coronary heart disease (CHD). We investigated the association between coronary calcification assessed by MDCT and extracoronary atherosclerosis measured by pulse wave analysis and IMT of carotid artery. Arterial stiffness and carotid IMT were measured consecutively in 133 patients who underwent their first coronary MDCT angiography due to chest pain. Patients were divided into three groups according to the CAC score (group 1, score = 0, n = 62; group 2, 0 < score < 400, n = 58; group 3, score ≥ 400, n = 13). The classification of CAC score was associated with age, prevalence of hypertension and dyslipidemia, systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity, percentage of brachial mean artery pressure, upstroke time (UT), augmentation index, and carotid IMT. In a multivariate analysis, age (P = .048), hypertension (P = .007), dyslipidemia (P = .24), and mean ankle UT (P = .038) were independent variables for the classification of CAC score. The UT of pulse wave was significantly associated with the CAC score. The increased UT of pulse wave might provide incremental risk prediction in addition to that defined by conventional CHD risk assessment.