Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study.

BACKGROUND: The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited. OBJECTIVES: We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years. METHODS: Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated. RESULTS: Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively). CONCLUSION: NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Coronary artery bypass graft versus percutaneous coronary intervention in acute heart failure.

OBJECTIVE: Myocardial ischaemia is a leading cause of acute heart failure (AHF). However, optimal revascularisation strategies in AHF are unclear. We aimed to compare two revascularisation strategies, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), in patients with AHF. METHODS: Among 5625 consecutive patients enrolled prospectively in the Korean Acute Heart Failure registry from March 2011 to February 2014, 717 patients who received CABG or PCI during the index hospitalisation for AHF were included in this analysis. We compared adverse outcomes (death, rehospitalisation for HF aggravation or cardiovascular causes, ischaemic stroke and a composite outcome of death and rehospitalisation for HF aggravation or cardiovascular causes) with the use of propensity score matching. RESULTS: For the propensity score-matched cohort with 190 patients, CABG had a lower risk of all-cause mortality than PCI (83 vs 147 deaths per 1000 patient-years; HR 0.57, 95% CI 0.34 to 0.96, p=0.033) during the median follow-up of 4 years. There was also a trend towards lower rates of rehospitalisation due to cardiovascular events or HF aggravation. Subgroup analysis revealed that the adverse outcomes were significantly lower in the CABG group than in PCI group, especially in patients with old age, three-vessel diseases, significant proximal left anterior descending artery disease and those without left main vessel disease or chronic total occlusion. CONCLUSIONS: Compared with PCI, CABG is associated with significant lower all-cause mortality in patients with AHF. Further studies should evaluate proper revascularisation strategies in AHF. CLINICAL TRIAL REGISTRATION: NCT01389843; Results.

Increased risk of atrial fibrillation in patients with inflammatory bowel disease: A nationwide population-based study.

BACKGROUND: Inflammatory bowel disease (IBD), a chronic inflammatory disease of the gastrointestinal tract, could play a role in the pathophysiology of atrial fibrillation (AF). AIM: To investigate the association between IBD and AF development. METHODS: We performed a population-based cohort study using records in the Korean National Health Insurance Services database between 2010 and 2014. A total of 37696 patients with IBD (12349 with Crohn's disease and 25397 with ulcerative colitis) were identified. The incidence rate of newly diagnosed AF in patients with IBD was compared with that in a 3 times larger cohort of 113088 age- and sex-matched controls without IBD. RESULTS: During 4.9 ± 1.3 years of follow-up, 1120 patients newly diagnosed with AF (348 in the IBD group and 772 in controls) were identified. After adjustments using multivariable Cox proportional hazards, patients with IBD were at a 36% [95% confidence interval (CI) 20%-54%] higher risk of AF than controls. The association between IBD and the development of AF was stronger in younger than in older patients. Patients without cardiovascular risk factors showed a higher risk of AF primarily. Additionally, patients receiving immun-omodulators [Hazard ration (HR) 1.46, 95%CI 1.31-1.89], systemic corticosteroids (HR 1.37, 95%CI 1.10-1.71), or biologics agents (HR 2.38, 95%CI 1.51-3.75) were at higher risk of AF than patients without them. CONCLUSION: IBD significantly increased the risk of AF, and the impact of IBD on developing AF was in patients with moderate to severe disease.

Efficacy of the optimal ablation index-targeted strategy for pulmonary vein isolation in patients with atrial fibrillation: the OPTIMUM study results.

PURPOSE: The ablation index (AI) is a recently developed marker for ablation lesion quality that incorporates contact force (CF), time, and power in a weighted formula. There is a paucity of information on whether AI-guided pulmonary vein isolation (PVI) could improve the outcome in patients with atrial fibrillation (AF). We evaluated the optimal AI threshold for avoiding acute pulmonary vein reconnection (PVR), and to compare the efficacy of optimal AI-targeted PVI with that of conventional CF-guided PVI. METHODS: Seventy patients with AF (paroxysmal, 67%) were enrolled. In a phase 1 study, the patients underwent conventional CF-guided PVI (CON group), and the optimal AI threshold for avoiding acute PVR was identified. In phase 2, the patients underwent AI-guided PVI (OAI group). We compared the acute PVR rate between the CON group and the OAI group to demonstrate the efficacy of AI-guided PVI. RESULTS: In phase 1 (n = 38), acute PVR was observed in 57 of 532 (10.7%) segments. AI values of ≥ 450 at the anterior/roof segments and of ≥ 350 at the posterior/inferior/carina segments were identified as the optimal AI thresholds for avoiding acute PVR. In the phase 2 study targeting those AI values, the OAI group (n = 32) showed a significantly lower acute PVR rate than the CON group (4.2% vs. 10.7%, p < 0.001). The OAI group showed a higher minimum AI and smaller variations in AI values than the CON group. CONCLUSIONS: Optimal AI-targeted PVI is feasible and could improve the acute outcome in patients with AF. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03389074.

Anatomic Conformation of Renal Sympathetic Nerve Fibers in Living Human Tissues.

Renal denervation using radiofrequency catheter ablation is known to eliminate the renal sympathetic nerve and to lower blood pressure in patients with resistant hypertension. We sought to investigate the detailed anatomic conformation of the peri-renal arterial sympathetic nerve fibers with living human specimens. Peri-renal arterial tissue was harvested from patients undergoing elective radical or simple nephrectomy. Digital images of each section from the distal arterial bifurcation to the proximal margin were obtained and analyzed after immunohistochemical staining with anti-tyrosine hydroxylase antibodies. A total of 3,075 nerve fibers were identified from 84 sections of peri-renal arterial tissue from 28 patients (mean age 62.5 ± 10.2 years, male 68%). Overall, 16% of nerve fibers were located at distances greater than 3 mm from the endoluminal surface of the renal artery. The median distance from the arterial lumen to the nerve fibers of the proximal, middle, and distal renal arterial segments was 1.51 mm, 1.48 mm, and 1.52 mm, respectively. The median diameter of the nerve fibers was 65 µm, and there was no significant difference between the segments. A substantial proportion of the sympathetic nerve fibers were located deeper in the peri-arterial soft tissue than in the lesion depth created by the conventional catheter-based renal sympathetic denervation system.

Temporal trends in prevalence and antithrombotic treatment among Asians with atrial fibrillation undergoing percutaneous coronary intervention: A nationwide Korean population-based study.

BACKGROUND: We investigated the recent 10-year trends in the number of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in relation to prescription patterns of antithrombotic therapy. METHODS: We analyzed the annual prevalence of PCI and patterns of antithrombotic therapy after PCI, including antiplatelets and oral anticoagulants (vitamin K antagonists and non-vitamin K antagonist oral anticoagulants [NOACs]), in patients with AF between 2006 and 2015 by using the Korean National Health Insurance Service database. Independent factors associated with triple therapy (oral anticoagulant plus dual antiplatelet) prescription were assessed using multivariable logistic regression analysis. RESULTS: The number of patients with AF undergoing PCI increased gradually from 2006 (n = 2,140) to 2015 (n = 3,631) (ptrend<0.001). In 2006, only 22.7% of patients received triple therapy after PCI although 96.2% of them were indicated for anticoagulation (CHA2DS2-VASc score ≥2). The prescription rate of triple therapy increased to 38.3% in 2015 (ptrend<0.001), which was mainly attributed to a recent increment of NOAC-based triple therapy from 2013 (17.5% in 2015). Previous ischemic stroke or systemic embolism, old age, hypertension, and congestive heart failure were significantly associated with a higher triple therapy prescription rate, whereas previous myocardial infarction, PCI, and peripheral arterial disease were associated with triple therapy underuse. CONCLUSIONS: From 2006 to 2015, the number of patients with AF undergoing PCI and the prescription rate of triple therapy increased gradually with a recent increment of NOAC-based antithrombotic therapy from 2013. Previous myocardial infarction, peripheral artery disease, and PCI were associated with underuse of triple therapy.

Risk prediction for 30-day heart failure-specific readmission or death after discharge: Data from the Korean Acute Heart Failure (KorAHF) registry.

BACKGROUND: Identifying patients with acute heart failure (HF) at high risk for readmission or death after hospital discharge will enable the optimization of treatment and management. The objective of this study was to develop a risk score for 30-day HF-specific readmission or death in Korea. METHODS: We analyzed the data from the Korean Acute Heart Failure (KorAHF) registry to develop a risk score. The model was derived from a multiple logistic regression analysis using a stepwise variable selection method. We also proposed a point-based risk score to predict the risk of 30-day HF-specific readmission or death by simply summing the scores assigned to each risk variable. Model performance was assessed using an area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow goodness-of-fit test, the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) index to evaluate discrimination, calibration, and reclassification, respectively. RESULTS: Data from 4566 patients aged ≥40 years were included in the analysis. Among them, 446 (9.8%) had 30-day HF-specific readmission or death. The final model included 12 independent variables (age, New York Heart Association functional class, clinical history of hypertension, HF admission, chronic obstructive pulmonary disease, etiology of cardiomyopathy, systolic blood pressure, left ventricular ejection fraction, serum sodium, brain natriuretic peptide, N-terminal prohormone of brain natriuretic peptide at discharge, and prescription of ß-blockers and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists at discharge). The point risk score showed moderate discrimination (AUC of 0.710; 95% confidence interval, 0.685-0.735) and good calibration (χ2=8.540, p=0.3826). CONCLUSIONS: The risk score for the prediction of the risk of 30-day HF-specific readmission or death after hospital discharge was developed using 12 predictors. It can be utilized to guide appropriate interventions or care strategies for patients with HF.

Ankylosing spondylitis: A novel risk factor for atrial fibrillation - A nationwide population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, associated with a number of cardiovascular diseases. We sought to investigate whether AS increases the risk of atrial fibrillation (AF) in a nationwide population-based study. METHODS: A total of 14,129 patients newly diagnosed with AS (mean age 41.8 ±â€¯15.3 years, 72% male) were recruited from the Korean National Health Insurance Service database between 2010 and 2014 and followed up for new onset AF. Age- and sex-matched non-AS subjects (1:5, n = 70,645) were selected and compared with the AS patients. RESULTS: During a mean follow-up of 3.5 years, AF was newly diagnosed in 486 patients (114 patients of the AS group). The AS patients developed AF more frequently than the non-AS subjects (2.32 vs. 1.51 per 1000 person-years). In multivariate Cox regression analysis, AS was an independent risk factor for AF (Hazard ratio [HR] 1.28, 95% confidence interval [1.03-1.58]). The AS with tumor necrosis factor inhibitor (TNFi) therapy group showed higher risk for AF (HR 1.60 [1.02-2.39]). In younger patients of the AS group (patients <40 years old), the risk for AF was three times higher than patients at same age in the non-AS group. AS was an independent risk factor for AF in men, but not in women (HR 1.53 [1.18-1.95]; HR 1.42 [0.94-2.08], respectively). CONCLUSIONS: AS was an independent risk factor for AF, especially in those under 40 years of age and those administered TNFi. It would be reasonable to screen for AF and stroke prevention in these high-risk patients.

Comparison of Characteristics and 3-Year Outcomes in Patients With Acute Heart Failure With Preserved, Mid-Range, and Reduced Ejection Fraction.

BACKGROUND: The clinical characteristics and outcomes of acute heart failure (AHF) according to left ventricular ejection fraction (LVEF) have not been fully elucidated, especially for patients with mid-range LVEF. We performed a comprehensive comparison of the epidemiology, patterns of in-hospital management, and clinical outcomes in AHF patients with different LVEF categories. Methods and Results: The Korean Acute Heart Failure (KorAHF) registry is a prospective multicenter cohort of hospitalized AHF patients in Korea. A total of 5,374 patients enrolled in the KorAHF registry were classified according to LVEF based on the 2016 ESC guidelines. More than half of the HF patients (58%) had reduced EF (HFrEF), 16% had mid-range EF (HFmrEF), and 25% had preserved EF (HFpEF). The HFmrEF patients showed intermediate epidemiological profiles between HFrEF and HFpEF and had a propensity to present as de-novo HF with ischemic etiology. Patients with lower LVEF had worse short-term outcomes, and the all-cause in-hospital mortality, including urgent heart transplantation, of HFrEF, HFmrEF, and HFpEF was 7.1%, 3.6%, and 3.0%, respectively. Overall, discharged AHF patients showed poor 3-year all-cause death up to 38%, which was comparable between LVEF subgroups (P=0.623). CONCLUSIONS: Each LVEF subgroup of AHF patients was a heterogeneous population with diverse characteristics, which have a significant effect on the clinical outcomes. This finding suggested that focused phenotyping of AHF patients could help identify the optimal management strategy and develop novel effective therapies.

Association of metabolic syndrome and chronic kidney disease with atrial fibrillation: A nationwide population-based study in Korea.

AIMS: Metabolic syndrome (MetS) and chronic kidney disease (CKD) are significant risk factors for incident atrial fibrillation (AF). Few studies have reported the synergistic effect of MetS and CKD on development of AF. We investigated the individual and synergistic effects of MetS and CKD on the risk of incident AF. METHODS: We studied a retrospective cohort comprising 22,886,663 Koreans whose data was obtained from the national health claims database established by the Korean National Health Insurance Service between 2008 and 2013. Patients were classified into a MetS and a CKD group and followed-up until 2016 for new-onset AF. A Cox proportional hazards model assessed the independent and synergistic effect of MetS and CKD on the risk of incident AF. RESULTS: The prevalence of MetS and CKD in these patients was 27.4% and 5.4%, respectively. During a mean follow-up of 5.4 years, AF developed in 225,529 patients (1% of the total cohort). The adjusted hazard ratio (HR) for incident AF was 1.38 (95% confidence interval [CI] 1.36-1.39) for MetS, and 1.35 (95% CI 1.34-1.37) for CKD. Patients with MetS and CKD showed a higher risk of AF (HR 1.75, 95% CI 1.73-1.78) than that observed in those without MetS and CKD. CONCLUSIONS: The combination of MetS and CKD showed a high risk of development of AF in a large-scale nationwide cohort. Further studies are warranted to determine whether pharmacological and/or lifestyle interventions can control/manage these modifiable risk factors to reduce the risk of development of AF.

Mortality and causes of death in patients with atrial fibrillation: A nationwide population-based study.

BACKGROUND: Patients with atrial fibrillation are known to have a high risk of mortality. There is a paucity of population-based studies about the impact of atrial fibrillation on the mortality risk stratified by age, sex, and detailed causes of death. METHODS: A total of 15,411 patients with atrial fibrillation from the Korean National Health Insurance Service-National Sample Cohort were enrolled, and causes of death were identified according to codes of the 10th revision of the International Classification of Diseases. RESULTS: From 2002 to 2013, a total of 4,479 (29%) deaths were confirmed, and the crude mortality rate for all-cause death was 63.3 per 1,000 patient-years. Patients with atrial fibrillation had a 3.7-fold increased risk of all-cause death compared with the general population. The standardized mortality ratio for all-cause death was the highest in young patients and decreased with increasing age (standardized mortality ratio 21.93, 95% confidence interval 7.60-26.26 in patients aged <20 years; standardized mortality ratio 2.77, 95% confidence interval 2.63-2.91 in patients aged ≥80 years). Women with atrial fibrillation exhibited a greater excess mortality risk than men (standardized mortality ratio 3.81, 95% confidence interval 3.65-3.98 in women; standardized mortality ratio 3.35, 95% confidence interval 3.21-3.48 in men). Cardiovascular disease was the leading cause of death (38.5%), and cerebral infarction was the most common specific disease. Patients with atrial fibrillation had an about 5 times increased risk of death due to cardiovascular disease compared with the general population. CONCLUSIONS: Patients with atrial fibrillation had a 4 times increased risk of mortality compared with the general population. However, the impact of atrial fibrillation on mortality decreased with age and in men. Cerebral infarction was the most common cause of death, and more attention should be paid to reducing the risk of stroke.

Temporal trends of the prevalence and incidence of atrial fibrillation and stroke among Asian patients with hypertrophic cardiomyopathy: A nationwide population-based study.

BACKGROUND: Atrial fibrillation (AF) and stroke are common in hypertrophic cardiomyopathy (HCM). We aimed to determine the prevalence and incidence of AF and stroke in patients with HCM during a 10-year period. METHODS: Using the Korean National Health Insurance Services database, we identified patients diagnosed with HCM from the entire Korean population between 2005 and 2015. The annual prevalence and incidence of AF and stroke in HCM patients were estimated. RESULTS: The prevalence of AF in HCM patients has gradually increased to 1.6-fold from 13.4% in 2005 to 20.9% in 2015. The incidence of AF ranged from 4.1 to 5.5%, a similar trend was observed for each year in HCM patients. The prevalence of stroke in HCM patients was approximately 10%, while that in HCM patients with AF was about 20%. During 8741 person-years, AF-related stroke occurred in 257 subjects among 2309 HCM patients with new-onset AF. The overall incidence rate of AF-associated stroke was 2.94 per 100 person-years. In subgroup analysis, the incidence rate of AF-associated stroke was 1.49 per 100 person-years in the under 45 year-old group and 1.48 per 100 person-years in the group with CHA2DS2-VASc score of 0 or 1 point in HCM patients. CONCLUSIONS: The prevalence of AF in HCM patients gradually increased over 10 years. The annual risk of AF-associated stroke in HCM was over 1% even in younger patients and those with CHA2DS2-VASc score of 0 or 1 point, which provide evidence to support the prevention of stroke in HCM patients with AF.

A Terahertz CMOS V-Shaped Patch Antenna with Defected Ground Structure.

In this paper, a V-shaped patch antenna with defected ground structure is proposed at terahertz to overcome the limited performance of a standard complementary metal-oxide semiconductor (CMOS) patch antenna consisting of several metal layers and very thin interdielectric layers. The proposed V-shaped patch with slots allows the increased radiation resistance and broadband performance. In addition, the patch resonating at different frequency from the V-shaped patch is stacked on the top to broaden the impedance-matching bandwidth. More importantly, the slots are formed in the ground plane, which is called the defected ground structure, to further increase the radiation resistance and thus improve the bandwidth and efficiency. It is verified from electromagnetic simulations that the leakage waves from the defected ground can enhance the antenna directivity and gain by coherently interfering with the topside radiation. The proposed on-chip antenna is fabricated using a standard 65 nm CMOS process. The on-wafer measurement shows very wide bandwidth in input reflection coefficient (<-10 dB), greater than 28.7% from 240 to >320 GHz. The measured peak gain was as high as 5.48 dBi at 295 GHz. To the best of the authors' knowledge, these results belong to the best performance among the terahertz CMOS on-chip antennas without using additional components or processes such as dielectric resonators, lens, or substrate thinning.

Reverse J-Curve Relationship Between On-Treatment Blood Pressure and Mortality in Patients With Heart Failure.

OBJECTIVES: This study aimed to assess the relationship between on-treatment blood pressure (BP) and clinical outcomes of patients with heart failure (HF). BACKGROUND: Lower BP has been reported to be related to increased mortality in various cardiovascular diseases. The optimal BP level for patients already experiencing HF is contentious. METHODS: The Korean Acute Heart Failure registry prospectively enrolled a total of 5,625 consecutive patients hospitalized for acute HF in 10 tertiary university hospitals in Korea between March 2011 and February 2014. Clinical profiles including BP were collected at admission, discharge, and during outpatient follow-up. Mean on-treatment BP was calculated from BP at discharge and at each follow-up visit. We evaluated the effects of mean on-treatment BP on the clinical outcomes of patients. RESULTS: Patients were followed up for a median 2.2 years. One-year mortality after discharge was 18.2%. The relationship between on-treatment BP and all-cause mortality followed a reversed J-curve relationship. A nonlinear, multivariable Cox proportional hazard model identified a nadir of systolic and diastolic BPs of 132.4/74.2 mm Hg in patients, for whom the mortality rate was lowest (p < 0.0001). The relationship with increased mortality above and below the reference BP was more definitive for diastolic BP and for HF with a preserved ejection fraction. CONCLUSIONS: Systolic and diastolic BPs <130/70 mm Hg at discharge and during follow-up was associated with worse survival in HF patients. These data suggest that the lowest BP possible might not be an optimal target for HF patients. Further studies should establish a proper BP goal in HF patients. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843).

Clinical Characteristics and Outcome of Acute Heart Failure in Korea: Results from the Korean Acute Heart Failure Registry (KorAHF).

BACKGROUND AND OBJECTIVES: The burden of heart failure has increased in Korea. This registry aims to evaluate demographics, clinical characteristics, management, and long-term outcomes in patients hospitalized for acute heart failure (AHF). SUBJECTS AND METHODS: We prospectively enrolled a total of 5625 consecutive subjects hospitalized for AHF in one of 10 tertiary university hospitals from March 2011 to February 2014. Descriptive statistics were used to determine the baseline characteristics of the study population and to compare them with those from other registries. RESULTS: The mean age was 68.5±14.5 years, 53.2% were male, and 52.2% had de novo heart failure. The mean systolic and diastolic blood pressures were 131.2±30.3 mmHg and 78.6±18.8 mmHg at admission, respectively. The left ventricular ejection fraction was ≤40% in 60.5% of patients. Ischemia was the most frequent etiology (37.6%) and aggravating factor (26.3%). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists were prescribed in 68.8%, 52.2%, and 46.6% of the patients at discharge, respectively. Compared with the previous registry performed in Korea a decade ago, extracorporeal membrane oxygenation (ECMO) and heart transplantation have been performed more frequently (ECMO 0.8% vs. 2.8%, heart transplantation 0.3% vs. 1.2%), and in-hospital mortality decreased from 7.6% to 4.8%. However, the total cost of hospital care increased by 40%, and one-year follow-up mortality remained high. CONCLUSION: While the quality of acute clinical care and AHF-related outcomes have improved over the last decade, the long-term prognosis of heart failure is still poor in Korea. Therefore, additional research is needed to improve long-term outcomes and implement cost-effective care.

Atrial fibrillation risk in metabolically healthy obesity: A nationwide population-based study.

BACKGROUND: Metabolically healthy obese (MHO) individuals are reported to have a marginal increase in cardiovascular risk; however, their atrial fibrillation (AF) risk is unclear. We aimed to assess AF risk in MHO individuals and identify whether AF development is associated with obesity or influenced by metabolic comorbidities. METHODS: A retrospective cohort of 389,321 individuals (age, 45.6±14.5years; male, 52.1%) was extracted from the Korean National Health Insurance sample database between 2004 and 2006 and followed-up for new-onset AF until 2013. Subjects with diabetes mellitus, hypertension, and/or dyslipidemia were classified as "metabolically unhealthy." The cohort was stratified into four groups according to obesity and metabolic healthiness: metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), MHO, and metabolically unhealthy obese (MUO). RESULTS: AF was newly diagnosed in 5106 (1.3%) individuals during a mean follow-up of 7.5±1.5years. The AF incidence rates for the MHNO, MUNO, MHO, and MUO groups were 0.76, 2.66, 1.10, and 2.88 per 1000 person-years, respectively. Compared with the MHNO group, the MHO group had increased AF risk (adjusted hazard ratio, 1.30; 95% CI, 1.14-1.48) on multivariate analysis. One fourth of the MHO cohort became metabolically unhealthy, contributing to increased AF risk. Obesity was an independent risk factor for AF, and increased AF risk by 20%. Metabolic unhealthiness increased AF risk by around 40%, and of its components, hypertension contributed the most. CONCLUSIONS: MHO individuals are at increased risk for AF development, and obesity was independently associated with elevated AF risk.

Fabrication of biofunctional stents with endothelial progenitor cell specificity for vascular re-endothelialization.

Endothelial progenitor cells (EPCs) have been identified as a crucial factor for re-endothelialization after stenting, resulting in the prevention of stent thrombosis and neointimal hyperplasia. Because EPCs can be introduced by antibody-antigen interactions, the suitable choice of antibody and the biocompatible surface modification technology including antibody immobilization are essential for developing an EPC-capturing stent. In this study, we fabricated a biofunctional stent with EPC specificity by grafting a hydrophilic polymer and consecutively immobilizing the antibody against vascular endothelial cadherin (VE-cadherin) which is one of the specific EPC surface markers. The surface of a stainless steel stent was sequentially modified by acid-treatment, silanization and covalent attachment of polymers not only to improve biocompatibility but also to introduce functional groups on the stent surface. The surface-modified stent immobilized anti-VE-cadherin antibodies, and the EPCs were remarkably captured whereas THP-1s, human acute monocytic leukemia cells, were not adsorbed on the stent. Furthermore, we confirmed that the recruited EPCs developed the endothelial cell layers on the antibody-conjugated stent. These positive in vitro results will encourage the extensive application of biofunctional surface modification technology for a variety of medical devices.

Comparison of endothelialization and neointimal formation with stents coated with antibodies against CD34 and vascular endothelial-cadherin.

Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC). Therefore, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation more than anti-CD34 antibody-coated stents (CD34 stents) through the superior ability to capture the late EPC. The stainless steel stents were coated with anti-human VE-cadherin antibodies or anti-human CD34 antibodies under the same condition. In vitro, VE-cad stents showed higher number of adhering EPC (823.6 ± 182.2 versus 379.2 ± 137.2 cells per HPF, p < 0.001). VE-cad stents also demonstrated better specific capturing of cells with endothelial lineage markers than CD34 stents did in flow cytometric analysis. VE-cad stents showed more effective re-endothelialization after 1 h, 24 h, and 3 days in vivo. At 42 days, VE-cad stents demonstrated significantly smaller neointima area (0.92 ± 0.38 versus 1.24 ± 0.41 mm(2), p = 0.002) and significantly lower PCNA positive cells in neointima (1684.8 ± 658.8/mm(2) versus 2681.7 ± 375.1/mm(2), p = 0.008), compared with CD34 stents. In conclusion, VE-cad stents captured EPC and endothelial cells more selectively in vitro, accelerated re-endothelialization over stents, and reduced neointimal formation in vivo, compared with CD34 stents.

Recurrent syncope triggered by temporal lobe epilepsy: ictal bradycardia syndrome.

Ictal asystole is potentially lethal, and known to originate from the involvement of limbic autonomic regions. Appropriate treatment must include an antiepileptic drug and the implantation of a pacemaker. We report the case of a 54-year-old male with recurrent syncope secondary to ictal asystole triggered by temporal lobe epilepsy. This was confirmed by combined Holter and video-electroencephalogram monitoring.