ABSTRACT
Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8+ T cells and the innate-like cytolytic activity of CD8+ T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8+ T cells, a result with implications for acute viral diseases.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cytotoxicity, Immunologic/immunology , Hepatitis A/immunology , Liver Diseases/immunology , Lymphocyte Activation/immunology , Adolescent , Adult , Cytotoxicity Tests, Immunologic , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Fluorescent Antibody Technique , Hepatitis A/complications , Humans , Immunoblotting , Interleukin-15/metabolism , Liver/immunology , Liver/metabolism , Liver/pathology , Liver Diseases/etiology , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Real-Time Polymerase Chain Reaction , Young AdultABSTRACT
BACKGROUND: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. METHODS: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. RESULTS: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively. CONCLUSIONS: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.
Subject(s)
Atrial Fibrillation , Life Style , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Atrial Fibrillation/epidemiology , Biological Specimen Banks , Cohort Studies , Longitudinal Studies , Republic of Korea/epidemiology , Risk Factors , UK Biobank , United Kingdom/epidemiology , White People , East Asian PeopleABSTRACT
BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.
Subject(s)
Anticoagulants , Atrial Fibrillation , Clopidogrel , Drug-Eluting Stents , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Female , Humans , Male , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/therapy , Clopidogrel/administration & dosage , Clopidogrel/therapeutic use , Drug Therapy, Combination , Hemorrhage/chemically induced , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Prospective Studies , Stroke/prevention & control , Stroke/etiology , Time Factors , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
Background: Atrial fibrillation (AF) is an indicator of frailty in old patients. This study aimed to investigate the effect of frailty on the use of oral anticoagulants (OAC) and clinical outcomes in a nationwide cohort of patients with new-onset AF. Methods: This study included 451,368 participants without AF from the Korea National Health Insurance Service-Health Screening cohort between 2002 and 2009. The Hospital Frailty Risk Score was retrospectively calculated for each patient using all available International Classification of Disease 10th revision diagnostic codes. According to the aggregate score, patients were divided into two groups: the participants without frailty ( < 5 points) and the participants with frailty ( ≥ 5 points). The primary outcome was death from any cause, and the secondary outcomes were cardiovascular death, ischemic stroke, major bleeding, and heart failure admission. Results: With up to 7.2 ± 1.5 years of follow-up, 11,953 participants (median age, 67 [interquartile range, 59.5-74.5] years; 7200 [60.2%] males) developed new-onset AF. Among the patients with AF, 3224 (26.9%) had frailty. Frailty was significantly associated with old age, female sex, polypharmacy, and other comorbidities. In patients with AF, frailty was negatively associated with OAC prescription after new-onset AF (p < 0.001). Compared to patients without frailty, patients with frailty had a significantly higher incidence and risk of all-cause death (hazard ratio [HR] 2.88, 95% confidence interval [CI] 2.65-3.14), cardiovascular death (HR 2.42, 95% CI 2.10-2.80), ischemic stroke (HR 2.25, 95% CI 2.02-2.51), major bleeding (HR 2.44, 95% CI 2.17-2.73), and heart failure admission (HR 1.29, 95% CI 1.09-1.52). In subgroup analysis, when compared to the non-OAC group, the risks associated with frailty were significantly lower in the OAC group for all-cause death, cardiovascular death, ischemic stroke, and heart failure admission. Conclusions: Frailty was negatively associated with the use of OAC and was a predictor of poor prognosis owing to the association of frailty with death, thromboembolic events, bleeding, and heart failure admission. However, OAC use was associated with lower risks related to frailty for all-cause death and major adverse cardiovascular events in patients with AF.
ABSTRACT
Background: Polypharmacy is commonly observed in atrial fibrillation (AF) and is associated with poorer clinical outcomes. Our study aimed to elucidate the polypharmacy prevalence, its associated risk factors, and its relationship with adverse clinical outcomes using a 'real-world' database. Methods: This study included 451,368 subjects without prior history of AF (median age, 54 [interquartile range, 48.0-63.0] years; 207,748 [46.0%] female) from the Korea National Health Insurance Service-Health Screening (NHIS-HealS) database between 2002 and 2013. All concomitant medications prescribed were collected, and the intake of five or more concomitant drugs was defined as polypharmacy. During the follow-up, all-cause death, major bleeding events, transient ischemic attack (TIA) or ischemic stroke, and admission due to worsened heart failure were recorded. Results: Based on up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, there were 12,241 cases of new-onset AF identified. Among patients with new-onset AF (40.0% females, median age 63.0 [54.0-70.0] years), the polypharmacy prevalence was 30.9% (3784). For newly diagnosed AF, factors, such as advanced age (with each increase of 10 years, odds ratios (OR) 1.32, 95% confidence interval (CI) 1.26-1.40), hypertension (OR 4.00, 95% CI 3.62-4.43), diabetes mellitus (OR 3.25, 95% CI 2.86-3.70), chronic obstructive pulmonary disease (COPD) (OR 3.00, 95% CI 2.51-3.57), TIA/ischemic stroke (OR 2.36, 95% CI 2.03-2.73), dementia history (OR 2.30, 95% CI 1.06-4.98), end-stage renal disease (ESRD) or chronic kidney disease (CKD) (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26), were found to be independently correlated with the incidence of polypharmacy. Polypharmacy significantly increased the incidence and risk of major bleeding (adjusted hazard ratio (aHR) 1.26, 95% CI 1.12-1.41). The study observed a statistically significant increase in the incidence of all-cause mortality, however, the risk for all-cause mortality elevated but did not show significance (aHR 1.11, 95% CI 0.99-1.24). The risk of stroke and admission for heart failure did not change with polypharmacy. Conclusions: In our investigation using data from a nationwide database, polypharmacy was widespread in new-onset AF population and was related to major bleeding events. However, polypharmacy does not serve as an independent risk factor for adverse outcomes, with exception of major bleeding event. For AF patients, ensuring tailored medication for comorbidities as well as reducing polypharmacy are essential considerations.
ABSTRACT
INTRODUCTION: This study aimed to elucidate the relationship between premature ventricular complexes (PVCs) and right ventricular (RV) dysfunction, and the effects of radiofrequency catheter ablation (RFCA) on RV function. METHODS: A total of 110 patients (age, 50.8 ± 14.4 years; 30 men) without structural heart disease who had undergone RFCA for RV outflow tract (RVOT) PVCs were retrospectively included. RV function was assessed using fractional area change (FAC) and global longitudinal strain (GLS) before and after RFCA. Clinical data were compared between the RV dysfunction (n = 63) and preserved RV function (n = 47) groups. The relationship between PVC burden and RV function was analyzed. Change in RV function before and after RFCA was compared between patients with successful and failed RFCA. RESULTS: PVC burden was significantly higher in the RV dysfunction group than in the preserved RV function group (p < .001). FAC and GLS were significantly worse in proportion to PVC burden (p < .001 and p < .001, respectively). The risk factor associated with RV dysfunction was PVC burden [odds ratio (95% confidence interval), 1.092 (1.052-1.134); p < .001]. Improvement in FAC (13.0 ± 8.7% and -2.5 ± 5.6%, respectively; p < .001) and GLS (-6.8 ± 5.7% and 2.1 ± 4.2%, respectively; p < .001) was significant in the patients with successful RFCA, compared to the patients in whom RFCA failed. CONCLUSIONS: Frequent RVOT PVCs are associated with RV dysfunction. RV dysfunction is reversible by successful RFCA.
Subject(s)
Catheter Ablation , Ventricular Dysfunction, Right , Ventricular Premature Complexes , Male , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Ventricular Function, Right , Treatment Outcome , Heart Ventricles/diagnostic imaging , Heart Ventricles/surgery , Ventricular Premature Complexes/diagnosis , Ventricular Premature Complexes/surgery , Ventricular Premature Complexes/complications , Catheter Ablation/adverse effects , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/surgeryABSTRACT
Background: Physiological conduction system pacing has attracted attention to overcome the dyssynchrony problems of conventional right ventricular pacing (RVP). Left bundle branch area pacing (LBBAP), which complements short combing of His bundle pacing (HBP), has emerged and has proven its efficiency and safety. In addition, initial experiences of LBBAP were mainly using lumen-less pacing lead, and the feasibility of stylet-driven pacing lead (SDL) was also established. The purpose of this study is to evaluate the learning curve for LBBAP using SDL. Methods: The study enrolled 265 patients who underwent LBBAP or RVP performed by operators without previous LBBAP experience at Yonsei University Severance Hospital in Korea between December 2020 and October 2021. LBBAP was performed using SDL with an extendable helix. The learning curve was evaluated by analyzing fluoroscopy and procedure times. And, before and after reaching the learning curve, we evaluated how much the time required for the LBBAP differed from the time required for the RVP. Results: LBBAP was successful in 50 of 50 (100.0%) patients left bundle branch pacing was successful in 49 of 50 (98.0%). In 50 patients who underwent LBBAP, mean fluoroscopy and procedural times were 15.1 ± 13.5 minutes and 59.9 ± 24.8 minutes, respectively. The plateau of fluoroscopy time reached in the 25th case and the plateau of procedure time reached in the 24th case. Conclusion: During the initial experience with LBBAP, fluoroscopy and procedural times improved with increasing operator experience. For operators who were experienced in cardiac pacemaker implantation, the steepest part of the learning curve was over the first 24-25 cases. It is shorter than the previously reported learning curves of HBP.
Subject(s)
Bundle of His , Learning Curve , Humans , Cardiac Pacing, Artificial/methods , Electrocardiography/methods , Treatment OutcomeABSTRACT
AIMS: Atrial fibrillation (AF) is a chronic progressive disease that continuously recurs even after successful AF catheter ablation (AFCA). We explored the mechanism of long-term recurrence by comparing patient characteristics and redo-ablation findings. METHODS AND RESULTS: Among the 4248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at a single centre, we enrolled 1417 patients [71.7% male, aged 60.0 (52.0-67.0) years, 57.9% paroxysmal AF] who experienced clinical recurrences (CRs), and divided them according to the period of recurrence: within one year (n = 645), 1-2 years (n = 339), 2-5 years (n = 308), and after 5 years (CR>5â yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5â yr, the proportion of paroxysmal AF was higher (P = 0.031); however, the left atrial (LA) volume (quantified by computed tomography, P = 0.003), LA voltage (P = 0.003), frequency of early recurrence (P < 0.001), and use of post-procedure anti-arrhythmic drugs (P < 0.001) were lower. A CR>5â yr was independently associated with a low LA volume [odds ratio (OR) 0.99 (0.98-1.00), P = 0.035], low LA voltage [OR 0.61 (0.38-0.94), P = 0.032], and lower early recurrence [OR 0.40 (0.23-0.67), P < 0.001]. Extra-pulmonary vein triggers during repeat procedures were significantly greater in patients with a CR>5â yr, despite no difference in the de novo protocol (P for trend 0.003). The rhythm outcomes of repeat ablation procedures did not differ according to the timing of the CR (log-rank P = 0.330). CONCLUSIONS: Patients with a later CR exhibited a smaller LA volume, lower LA voltage, and higher extra-pulmonary vein triggers during the repeat procedure, suggesting AF progression.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Male , Female , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Atrial Fibrillation/etiology , Treatment Outcome , Heart Atria , Tomography, X-Ray Computed , Chronic Disease , Catheter Ablation/adverse effects , Catheter Ablation/methods , Recurrence , Pulmonary Veins/surgeryABSTRACT
BACKGROUND: Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA2DS2-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial). OBJECTIVE: To investigate whether the results can be generalized to patients with low stroke risk. DESIGN: Population-based cohort study. SETTING: Nationwide claims database of the Korean National Health Insurance Service. PARTICIPANTS: 54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis. MEASUREMENTS: The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA2DS2-VASc score, approximately 0 to 1) using propensity overlap weighting. RESULTS: In total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA2DS2-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16 659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA2DS2-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility. LIMITATION: Residual confounding. CONCLUSION: In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility. PRIMARY FUNDING SOURCE: The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea.
Subject(s)
Anti-Arrhythmia Agents , Atrial Fibrillation , Aged , Humans , Middle Aged , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Cohort Studies , Propensity Score , Risk Assessment/methods , Risk Factors , Stroke/prevention & control , Clinical Trials as TopicABSTRACT
BACKGROUND: Frail patients with atrial fibrillation (AF) are less likely to receive anticoagulation than nonfrail patients with AF despite frailty being associated with poorer clinical outcomes including stroke. Using a population-based cohort, we sought to assess the effectiveness and safety of oral anticoagulants (OACs) in frail patients with AF. METHODS: This retrospective cohort study analyzed 83 635 patients aged at least 65 years with AF and frailty (≥5 Hospital Frailty Risk Score) between January 1, 2013 and December 31, 2016 from the Korean National Health Insurance Service database. To account for the differences between patients receiving OAC or not and across different OAC regimens, propensity score-weighting was used. Net adverse clinical event, defined as the first event of ischemic stroke, major bleeding, or cardiovascular death, was compared. In addition, each individual outcome was examined separately. RESULTS: In the study population (57.1% women; mean age, 78.5±7.2 years), a total of 14 968 net adverse clinical event, 3718 ischemic stroke, 5536 major bleeding, and 6188 cardiovascular death occurred. In comparison with no OAC use, OAC use was associated with lower risks of net adverse clinical event (hazard ratio, 0.78 [95% CI, 0.75-0.82]), ischemic stroke (hazard ratio, 0.91 [95% CI, 0.86-0.97]), and cardiovascular death (hazard ratio, 0.52 [95% CI, 0.49-0.55]), but no difference was observed for major bleeding (hazard ratio, 1.02 [95% CI, 0.95-1.10]). Compared with warfarin, all four individual direct OAC were associated with decreased risks of net adverse clinical event, ischemic stroke, major bleeding, and cardiovascular death. The associations for OAC use (compared to no OAC use) or direct OAC use (compared to warfarin) with favorable outcomes were more prominent in individuals with a higher CHA2DS2-VASc score of at least 3. CONCLUSIONS: Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin.
Subject(s)
Atrial Fibrillation , Frailty , Ischemic Stroke , Stroke , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Female , Frail Elderly , Frailty/chemically induced , Frailty/complications , Frailty/drug therapy , Hemorrhage/chemically induced , Hemorrhage/complications , Hemorrhage/epidemiology , Humans , Male , Retrospective Studies , Risk Assessment , Risk Factors , Stroke/drug therapy , Warfarin/adverse effectsABSTRACT
Background: Regular exercise improves the functional ability and quality of life of patients with heart failure (HF). However, studies on the results of intensity of exercise in the older population are scarce, especially in the Asian population. Method and Results: A total of 8982 older people (age ≥ 65 years) with HF were selected from the Korean National Health Insurance Service-Senior database (2005-2012). Participants were stratified according to the levels of physical activity per week as follows: (1) inactive group; (2) insufficiently active group: 1-499 metabolic equivalent task minutes (MET-min)/week; (3) active group: 500-999 MET-min/week; and (4) highly active group: ≥ 1000 MET-min/week. During a median follow-up period of 3.2 years, the incidence and risk of mortality were reduced in the insufficiently active (6.7 vs. 4.2 per 100 person-years, adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94; p < 0.001), active (3.8 per 100 person-years; HR, 0.81; 95% CI, 0.70-0.95; p = 0.010), and highly active (2.4 per 100 person-years; HR, 0.52; 95% CI, 0.41-0.67; p < 0.001) groups compared to inactive patients. Conclusions: In older Asians with HF, increased physical activity reduced the risk of all-cause mortality. The mortality-reducing benefit started at a lower physical activity compared to the World Health Organization guideline (500-999 MET-min/week), and the risk decreased with more physical activity.
ABSTRACT
BACKGROUND: Atrial fibrillation (AF) increases the risk of dementia, and catheter ablation of AF may be associated with a lower risk of dementia. We investigated the association of a rhythm-control strategy for AF with the risk of dementia, compared with a rate-control strategy. METHODS: This population-based cohort study included 41,135 patients with AF on anticoagulation who were newly treated with rhythm-control (anti-arrhythmic drugs or ablation) or rate-control strategies between 1 January 2005 and 31 December 2015 from the Korean National Health Insurance Service database. The primary outcome was all-cause dementia, which was compared using propensity score overlap weighting. RESULTS: In the study population (46.7% female; median age: 68 years), a total of 4,039 patients were diagnosed with dementia during a median follow-up of 51.7 months. Rhythm control, compared with rate control, was associated with decreased dementia risk (weighted incidence rate: 21.2 versus 25.2 per 1,000 person-years; subdistribution hazard ratio [sHR] 0.86, 95% confidence interval [CI] 0.80-0.93). The associations between rhythm control and decreased dementia risk were consistently observed even after censoring for incident stroke (sHR 0.89, 95% CI 0.82-0.97) and were more pronounced in relatively younger patients and those with lower CHA2DS2-VASc scores. Among dementia subtypes, rhythm control was associated with a lower risk of Alzheimer's disease (sHR 0.86, 95% CI 0.79-0.95). CONCLUSIONS: Among anticoagulated patients with AF, rhythm control was associated with a lower risk of dementia, compared with rate control. Initiating rhythm control in AF patients with fewer stroke risk factors might help prevent subsequent dementia.
Subject(s)
Atrial Fibrillation , Dementia , Stroke , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Cohort Studies , Dementia/diagnosis , Dementia/epidemiology , Dementia/prevention & control , Female , Humans , Incidence , Male , Risk Assessment , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Stroke/prevention & controlABSTRACT
BACKGROUND: We aimed to evaluate the long-term risk of ischemic stroke/systemic embolism of hyperthyroidism-related AF. METHODS: This retrospective population-based cohort study included records of 1,034,099 atrial fibrillation patients between 2005 and 2016 from the Korean National Health Insurance Service database. After exclusion, we identified 615,724 oral anticoagulation-naïve patients aged ≥18 years with new-onset non-valvular atrial fibrillation, of whom 20,773 had hyperthyroidism-related atrial fibrillation. After 3:1 propensity score matching, ischemic stroke and systemic embolism occurrences were compared between hyperthyroidism-related and non-hyperthyroidism-related ("nonthyroidal") atrial fibrillation patients. RESULTS: After exclusion, we identified 615,724 oral anticoagulation-naïve AF patients of whom 20,773 had hyperthyroidism-related AF. Median follow-up duration was 5.9 years. Hyperthyroidism-related AF patients had significantly higher risks of ischemic stroke and systemic embolism than nonthyroidal AF patients (1.83 vs 1.62 per 100-person year, hazard ratio[HR], 1.13; 95% confidence interval[CI], 1.07 to 1.19; P < 0.001). This risk was 36% higher in hyperthyroidism-related than in nonthyroidal AF patients within 1 year of atrial fibrillation diagnosis (3.65 vs 2.67 per 100-person year, HR, 1.36; 95% CI, 1.24 - 1.50; P < 0.001). This difference was also observed in the CHA2DS2-VASc score subgroup analysis. The risk of ischemic stroke and systemic embolism significantly decreased in patients treated for hyperthyroidism (HR, 0.64; 95% CI, 0.58 to 0.70; P < 0.001). CONCLUSIONS: Hyperthyroidism-related AF patients have high risks of ischemic stroke and systemic embolism like nonthyroidal AF, especially when initially diagnosed. This risk is reduced by treating hyperthyroidism.
Subject(s)
Atrial Fibrillation , Embolism , Hyperthyroidism , Ischemic Stroke , Adolescent , Adult , Atrial Fibrillation/etiology , Cohort Studies , Embolism/epidemiology , Humans , Hyperthyroidism/complications , Ischemic Stroke/epidemiology , Risk AssessmentABSTRACT
BACKGROUND: Sinoatrial node dysfunction and atrial fibrillation (AF) frequently coexist and interact with each other, often to initiate and perpetuate each other. OBJECTIVE: To determine the effect of AF on the incidence and risk of sick sinus syndrome (SSS). METHODS: The association of incident AF with the development of incident SSS was assessed from 2004 to 2014 in 302 229 SSS- and pacemaker-free subjects aged ≥60 years in the Korea National Health Insurance Service-Senior cohort. RESULTS: During an observation period of 1 854 800 person-years, incident AF was observed in a total of 12 797 subjects (0.69%/year). The incidence of SSS was 3.4 and 0.2 per 1000 person-years in the propensity score-matched incident AF and no-AF groups, respectively. After adjustment, the significantly increased risk of SSS was observed in the incident AF group, with a hazard ratio (HR) of 13.4 (95% confidence interval [CI]: 8.4-21.4). This finding was consistently observed after censoring for heart failure (HR: 16.0; 95% CI: 9.2-28.0) or heart failure/myocardial infarction (HR: 16.6; 95% CI: 9.3-29.7). Incident AF also was associated with an increased risk of pacemaker implantation related with both SSS (HR: 21.8; 95% CI: 8.7-18.4) and atrioventricular (AV) block (HR: 9.5; 95% CI: 4.9-18.4). These results were consistent regardless of sex and comorbidities. CONCLUSION: Incident AF was associated with more than 10 times increased risk of SSS in an elderly population regardless of comorbidities. The risk of pacemaker implantations related with both sinus node dysfunction and AV block was increased in the elderly population with incident AF.
Subject(s)
Atrial Fibrillation , Atrioventricular Block , Pacemaker, Artificial , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Cohort Studies , Humans , Sick Sinus Syndrome/diagnosis , Sick Sinus Syndrome/epidemiology , Sick Sinus Syndrome/therapyABSTRACT
BACKGROUND: In European ancestry, 111 genetic loci were identified as associated with atrial fibrillation (AF). We explored the reproducibility of those single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) meta-analysis of Far East Asian populations. METHODS: We performed a meta-analysis of the Korean AF network and Japanese AF data sets (9118 cases and 33 467 controls) by an inverse-variance fixed-effects model. We compared the results with 111 previously reported SNPs proven in Europeans after excluding 36 missing loci and a locus with a minor allelic frequency (MAF) < 0.01 in the European population. RESULTS: Among remaining 74 loci, 29 loci were replicated at a P < .05, and 17 of those loci were newly found in the Far East Asian population: 3 loci with a P < 5×10-8 (METTL11B at 1q24, KCNN2 at 5q22 and LRMDA at 10q22), 4 loci at the threshold of the Bonferroni correction of P = 4.5 × 10-4 ~ 5×10-8 (KIF3C at 2p23, REEP3, NRBF2 at 10q21, SIRT1, MYPN at 10q21 and CFL2 at 14q13) and 10 SNPs with a P = .05 ~ 4.5 × 10-4 . Among 18 AF loci with a MAF< 0.01 in the Far East Asian populations, 2 loci (GATA4 at 8q23 and SGCG at 13q12) were replicated after a fine mapping. Twenty-seven AF loci, including a locus, which had a sufficient sample size to get a power of over 80% (with a type 1 error α = 4.5 × 10-4 ), were not replicated in the Far East Asian populations. CONCLUSIONS: We newly replicated 19 AF-associated genetic loci in the European descent among the Far East Asian populations. It highlights the extensive sharing of AF genetic risks across Far East Asian populations.
Subject(s)
Asian People/genetics , Atrial Fibrillation/genetics , White People/genetics , Adult , Aged , Asia, Eastern , Female , Genetic Predisposition to Disease , Humans , Japan , Korea , Male , Middle Aged , Polymorphism, Genetic , Polymorphism, Single NucleotideABSTRACT
AIMS: Although atrial fibrillation (AF) catheter ablation (AFCA) is an effective rhythm control strategy, there is limited data on whether ischaemic stroke (IS) or intracranial haemorrhage (ICH) decreases after AFCA compared with medical therapy or non-AF population. We explored the IS and ICH risk after AFCA or medical therapy in the AF population and matched non-AF population. METHODS AND RESULTS: We compared 1629 patients with AFCA (Yonsei AF ablation cohort), 3258 with medical therapy [Korean National Health Insurance (NHIS) database], and 3258 non-AF subjects (NHIS database) following a 1:2:2 propensity score matching. All AFCA patients underwent regular rhythm follow-ups for 51 ± 29 months. Among the AFCA group, the incidence rate ratio (IRR) of ISs was significantly higher in patients with sustained AF recurrences after the last ablation (0.87%) than in those remaining in sinus rhythm (0.24%, P = 0.017; log rank P = 0.003). The IRR of ISs was significantly higher in the medical therapy (1.09%) than AFCA (0.30%, P < 0.001, log rank P < 0.001 vs. medical therapy) or non-AF groups (0.34%, P < 0.001, log rank P < 0.001 vs. medical therapy; P = 0.673, log rank P = 0.874 vs. AFCA). The IRR of ICHs was 0.17% in the medical therapy, 0.06% in the AFCA (P = 0.023, log rank P = 0.042 vs. medical therapy), and 0.12% in the non-AF group (P = 0.226, log rank P = 0.241 vs. medical therapy; P = 0.172, log rank P = 0.193 vs. AFCA). CONCLUSION: Post-procedural AF control influences the risk of ISs. Atrial fibrillation catheter ablation significantly reduces the risk of both ISs and ICHs to the extent of the non-AF population compared to the medical therapy.
Subject(s)
Atrial Fibrillation , Brain Ischemia , Catheter Ablation , Ischemic Stroke , Stroke , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/surgery , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Brain Ischemia/prevention & control , Catheter Ablation/adverse effects , Humans , Intracranial Hemorrhages/diagnosis , Intracranial Hemorrhages/epidemiology , Recurrence , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Stroke/etiology , Treatment OutcomeABSTRACT
AIMS: To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). METHODS AND RESULTS: This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. CONCLUSION: In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.
Subject(s)
Atrial Fibrillation , Dementia , Stroke , Administration, Oral , Aged , Anticoagulants/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Cohort Studies , Dabigatran/therapeutic use , Dementia/epidemiology , Female , Humans , Male , Pyridones/therapeutic use , Rivaroxaban/adverse effectsABSTRACT
AIMS: The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population. METHODS AND RESULTS: A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption-abstainer-rare, light (<100 g/week), moderate (100-200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06-1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68-1.13) and moderate (aHR 0.91, 95% CI 0.63-1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom ß-blocker were not prescribed. CONCLUSION: Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.
Subject(s)
Atrial Fibrillation , Brain Ischemia , Pharmaceutical Preparations , Stroke , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Anticoagulants , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Humans , Registries , Risk Assessment , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Stroke/prevention & controlABSTRACT
BACKGROUND: It is unclear whether catheter ablation is beneficial for frail elderly patients with atrial fibrillation (AF). This study evaluated the effect of ablation on outcomes in frail elderly patients with AF.MethodsâandâResults:From the Korean National Health Insurance Service database, 194,928 newly diagnosed AF patients were treated with ablation or medical therapy (rhythm or rate control) between 2005 and 2015. Among these patients, the study included 1,818 (ablation; n=119) frail and 1,907 (ablation; n=230) non-frail elderly (≥75 years) patients. Propensity score matching was used to correct for differences between groups. During 28 months (median) follow up, the risk of all-cause death, composite outcome (all-cause death, heart failure admission, stroke/systemic embolism, and sudden cardiac arrest), and each outcome did not change after ablation in frail elderly patients. However, in non-frail elderly patients, ablation was associated with a lower risk of all-cause death (3.5 and 6.2 per 100 person-years; hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.30-0.79; P=0.004), and composite outcome (6.9 and 11.2 per 100 person-years; HR 0.54; 95% CI 0.38-0.75; P<0.001). CONCLUSIONS: Ablation may be associated with a lower risk of death and composite outcome in non-frail elderly, but the beneficial effect of ablation was not significant in frail elderly patients with AF. The effect of frailty on the outcome of ablation should be evaluated in further studies.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Frailty , Aged , Atrial Fibrillation/surgery , Frail Elderly , Humans , Risk Factors , Stroke , Treatment OutcomeABSTRACT
BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is important for the prevention of sudden cardiac death, but data on clinical outcomes of ICD therapy in Asian pediatric patients are scarce. The aim of this Korean multicenter study was to evaluate the current state and elucidate the clinical outcomes of ICD therapy in children.MethodsâandâResults:Data from 5 pediatric cardiology centers were retrospectively collected from 2007 to 2019. Altogether, 99 patients were enrolled (mean age 13.9±4.1 years). The most common underlying disease was a primary electrical disease (56%). An ICD was implanted for primary prevention in 19%. Appropriate shock occurred in 44% of patients at a median of 1.6 years after implantation. There was no significant difference in the appropriate shock rate between patients with primary and secondary prevention indications (32% vs. 48%, respectively). A total of 33 patients (33%) experienced inappropriate shock, which was associated with primary electrical disease and follow-up duration on multivariate analysis. 17% of patients had ICD-related complications. CONCLUSIONS: The utilization rate of ICD for primary prevention was still low in the pediatric population in Korea, but there was a substantial rate of appropriate shock in these patients. Efforts to increase ICD usage to save the lives of high-risk patients and reduce the incidence of inappropriate shock are required.