Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A.

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.

Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

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.

Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial.

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.

Effects of radiofrequency catheter ablation for premature ventricular complexes originating from the right ventricular outflow tract on right ventricular function.

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.

Learning Curve Analyses for Left Bundle Branch Area Pacing with Conventional Stylet-Driven Pacing Leads.

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.

Late recurrence of atrial fibrillation 5 years after catheter ablation: predictors and outcome.

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>5 yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5 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>5 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>5 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.

Early Rhythm Control Therapy for Atrial Fibrillation in Low-Risk Patients : A Nationwide Propensity Score-Weighted Study.

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.

Effectiveness and Safety of Anticoagulation Therapy in Frail Patients With Atrial Fibrillation.

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.

Association of rhythm control with incident dementia among patients with atrial fibrillation: a nationwide population-based cohort study.

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.

Increased risk of ischemic stroke and systemic embolism in hyperthyroidism-related atrial fibrillation: A nationwide cohort study.

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.

Risk of sick sinus syndrome in patients diagnosed with atrial fibrillation: A population-based cohort.

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.

Ethnic similarities in genetic polymorphisms associated with atrial fibrillation: Far East Asian vs European populations.

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.

Atrial fibrillation and the risk of ischaemic strokes or intracranial haemorrhages: comparisons of the catheter ablation, medical therapy, and non-atrial fibrillation population.

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.

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry.

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.

Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

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.

Frailty and the Effect of Catheter Ablation in the Elderly Population With Atrial Fibrillation　- A Real-World Analysis.

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.Methods and Results: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.

Clinical Outcomes of Implantable Cardioverter-Defibrillator in Pediatric Patients　- A Korean Multicenter Study.

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.Methods and Results: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.

Long-term prognosis of short QT interval in Korean patients: a multicenter retrospective cohort study.

BACKGROUND: Short QT syndrome is a rare, inherited channelopathy associated with sudden cardiac arrest (SCA) but the characteristics and prognosis of short QT interval (SQTI) in Korean patients remain unclear. This study aimed to determine the clinical characteristics and outcomes of SQTI in a Korean population. METHODS: Consecutive patients with SQTI from January 1999 to March 2019 in three university hospitals in South Korea were recruited. SQTI was defined as a Bazett's formula-corrected QT interval (QTc) ≤ 340 ms in serial electrocardiograms. Age- and sex-matched patients with a normal QTc and without overt cardiovascular disease were included in a 1:4 ratio. Clinical and ECG features and outcomes were compared between patients with and without SQTI. RESULTS: 34 patients with SQTI [age, 23.5 (21-30.5) years; 31 male] were followed up for 4.8 (2.0-7.8) years. Early repolarization, tall T wave, and U wave were significantly more frequent in patients with SQTI than in those without SQTI. QT dispersion [44.0 (28.0-73.0) vs. 20.0 (12.0-35.0) ms, P < 0.001] was significantly wider and heart rate [52.0 (47.0-58.0) vs. 70.0 (62.3-84.0)/min, P < 0.001] was significantly slower in patients with SQTI than in those without. Atrial fibrillation (AF, 11.8% vs. 2.2%, P = 0.030) and ventricular arrhythmia (VA)/SCA (8.7% vs. 0%, P = 0.007) were significantly more frequent in patients with SQTI than in those without. SQTI was significantly associated with AF [odds ratio, 5.911; 95% confidence interval, 1.257-27.808; P = 0.025] and VA/SCA. CONCLUSIONS: In this subset of Korean population, SQTI was associated with AF and VA/SCA.

Subclinical cardiac perforation by cardiac implantable electronic device leads detected by cardiac computed tomography.

BACKGROUND: The relationship between the characteristics of cardiac implantable electronic device (CIED) leads and subclinical cardiac perforations remains unclear. This study aimed to evaluate the incidence of subclinical cardiac perforation among various CIED leads using cardiac computed tomography (CT). METHODS: A total of 271 consecutive patients with 463 CIED leads, who underwent cardiac CT after CIED implantation, were included in this retrospective observational study. Cardiac CT images were reviewed by one radiologist and two cardiologists. Subclinical perforation was defined as traversal of the lead tip past the outer myocardial layer without symptoms and signs related to cardiac perforation. We compared the subclinical cardiac perforation rates of the available lead types. RESULTS: A total of 219, 49, and 3 patients had pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy, respectively. The total subclinical cardiac perforation rate was 5.6%. Subclinical cardiac perforation by screw-in ventricular leads was significantly more frequent than that caused by tined ventricular leads (13.3% vs 3.3%, respectively, p = 0.002). There were no significant differences in the incidence of cardiac perforation between atrial and ventricular leads, screw-in and tined atrial leads, pacing and defibrillator ventricular leads, nor between magnetic resonance (MR)-conditional and MR-unsafe screw-in ventricular leads. Screw-in ventricular leads were significantly associated with subclinical cardiac perforation [odds ratio, 4.554; 95% confidence interval, 1.587-13.065, p = 0.005]. There was no case subclinical cardiac perforation by septal ventricular leads. CONCLUSIONS: Subclinical cardiac perforation by screw-in ventricular leads is not rare. Septal pacing may be helpful in avoiding cardiac perforation.

Usefulness of cardiac magnetic resonance images for prediction of sudden cardiac arrest in patients with mitral valve prolapse: a multicenter retrospective cohort study.

BACKGROUND: An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. METHODS: MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. RESULTS: Of the 85 patients [age, 54.0 (41.0-65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65-148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02-1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08-1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. CONCLUSIONS: The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.