Background: Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (ACM) are inherited cardiac diseases that may predispose to ventricular arrhythmia. Although overlapping features between BrS and ACM have been demonstrated previously, it remains to be determined whether genetic testing for ACM-related genes is needed in BrS probands.MethodBased on a single-center, retrospective registry of BrS, we aimed to verify genetic profiles of BrS using a next-generation sequencing panel, and further analyzed genetic testing of ACM-related variants in Brugada phenotypes. Results: Among a total of 119 Brugada phenotypes, 114 patients (95.8%) were male and the mean age of onset was 43.6 years. Genetic variants were identified in 25 of the 42 patients who underwent genetic testing. Fifteen patients had BrS-related genotypes, including SCN5A in 6 patients, and non-SCN5A genes in 9 patients (SCN10A, HCN4, SCN3B, and KCNE3). Nineteen patients underwent additional genetic testing with cardiomyopathy panel, which revealed ACM-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) present in 6 patients (31.5%). None of the patients had structural or electrocardiographic features that fulfilled the diagnostic criteria for ACM. Conclusions In clinical setting, ACM-related genes were identified in a significant proportion of Brugada phenotypes, supporting the argument that genetic testing of ACM overlapping is needed. Follow-up imaging studies should be considered to monitor if the disease progresses to ACM.

Background: An idiopathic outflow tract premature ventricular complex (OT-PVC) is a common arrhythmia, and the accuracy of site of origin prediction using the 12-lead electrocardiogram (ECG) algorithm is not high. There are no studies about a systematic strategy that can provide practical help to electrophysiologists in OT-PVC mapping and ablation. This study aims to evaluate the efficacy and safety of the proposed ablation protocol and establish an optimal catheter ablation strategy by simultaneously investigating and synthesizing various indicators observed during the mapping procedure. Methods: and designThis study (ABOUT-PVC) was designed as a prospective multicenter study to enroll 210 patients from 11 tertiary university hospitals over an estimated 27 months. Patients with idiopathic OT-PVC requiring catheter ablation will receive the procedure through a proposed ablation strategy and will be followed up for at least 12 months. The primary outcome is the acute procedural success rate. The secondary outcomes are clinical success rate, procedure time, complication rate, symptom relief, and changes in echocardiographic parameters. Conclusions The ABOUT-PVC study was designed to investigate the efficacy and safety of the proposed ablation strategy and establish an optimal catheter ablation strategy. We expect this study to overcome the limitations of the ECG prediction algorithms and provide a practical guide to electrophysiologists, increasing the procedure’s success rate and reducing complications and procedure time.

Background: In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. Methods: This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. Results: A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21–1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54–19.03), and composite outcomes (adjusted HR, 1.13;95% CI, 0.47–2.69) between the HDRR and LDRR groups. Conclusion This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients.

Background: It has become important to identify and manage risk factors for subclinical atrial fibrillation (AF) with an increase in its detection rate. Thus, this research aimed to investigate whether alcohol consumption contrib‑ utes to the development of subclinical AF. Methods: This prospective study enrolled 467 patients without AF from a multicenter pacemaker registry. The incidence of subclinical AF (episodes of atrial rate > 220 beats per minute without symptoms) was compared between alcohol-drinking and non-drinking groups. Results: During followup (median 18 months), the incidence and risk of long-duration atrial high-rate episodes (AHRE) ≥ 24 h were increased in the alcohol group compared to the non-alcohol group [5.47 vs. 2.10 per 100 personyears, adjusted hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.14–7.04; P = 0.03]. After propensity score match‑ ing, the incidence and risk of long-duration AHRE were higher in the alcohol group (6.97 vs. 1.27 per 100 personyears, adjusted HR, 7.84; 95% CI, 1.21–50.93; P = 0.03). The mean burden of long-duration subclinical AF was higher in the alcohol group than in the non-alcohol group (0.18 vs. 1.61% during follow-up, P = 0.08). Conclusion Alcohol consumption was associated with an increased risk of subclinical AF. Long-duration AHRE inci‑ dence and AHRE burden were higher in alcohol drinkers than in non-drinkers.

Background: The prognostic significance of resting heart rate and its therapeutic target in atrial fibrillation (AF) is uncertain. We sought to investigate the relationship between resting heart rate and cardiovascular outcomes in patients with non-paroxysmal AF (non-PAF). Methods: In this propensity score-weighted, multi-center prospective cohort study, 3217 patients with non-PAF were analyzed. Patients were categorized according to the baseline resting heart rate and cardiovascular outcomes were accessed for a median follow-up of 30 months. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and myocardial infarction/critical limb ischemia. Results: Freedom from primary outcome was longest among patients with resting heart rate 80–99 beats per minute (bpm) whereas shortest among those with ≤ 59 bpm (weighted log rank, p = 0.008). Compared with heart rate ≥ 100 bpm, resting heart rate 80–99 and 60–79 bpm was associated with reduced risk of primary outcome (weighted hazard ratio [WHR] 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.008 and WHR 0.58, 95% CI 0.37–0.92, p = 0.021 for heart rate 80–99 and 60–79 bpm, respectively). Using weighted restricted cubic spline curves, there was a U-shaped association between the resting heart rate and primary outcome with reduced risk of primary outcome in heart rate range of 68–99 bpm. This association was maintained regardless of atrioventricular node (AVN) blocker use or persistent/permanent AF (p for interaction 0.767 for AVN blocker use and 0.720 for AF type). Conclusion Resting heart rate was associated with cardiovascular outcomes in patients with non-PAF and those with resting heart rate between 68 and 99 bpm had lower risk of adverse cardiovascular events regardless of AVN blocker use or persistent/permanent AF.

Purpose: Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. Materials and Methods: Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m2 ) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. Results: During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). Conclusion Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC.ClinicalTrials.gov (NCT02786095)

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Background and Objectives: In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. Methods: This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA 2 DS 2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. Results: Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25 the and 75 the percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25–0.91, p=0.025) than men. Conclusions In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events.

Neurofibromatosis type 1 is the most common tumor predisposition syndrome inherited in an autosomal dominant (100% penetrance) fashion with a wide variety of expressivity. From the perspective of plastic surgery, the most significant clinical symptoms, including disfiguration, peripheral neurologic symptoms, and skeletal abnormalities, are caused by various tumors originating from the affected nerves. Surgical removal is the standard of care for these tumors. However, the outcome is frequently unsatisfactory, facilitating the search for additional therapeutic adjuvants. Current trials of molecularly targeted therapies are promising.Abbreviations: CALMs, café-au-lait macules; CNs, cutaneous neurofibromas; FDG, 18F-fluoro-deoxy-glucose; MAPK, mitogen-activated protein kinase; MPNSTs, malignant peripheral nerve sheath tumors; MRI, magnetic resonance imaging; NF1, neurofibromatosis type 1; NIH, National Institutes of Health; PET, positron emission tomography; PN, plexiform neurofibromas; TME, tumor microenvironment

Background and Objectives: Recurrence rates after radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients are not low especially in non-paroxysmal AF. The diameter of left atrium (LA) has been widely used to predict the recurrence after RFCA for decades. However, LA diameter represents structural remodeling of LA and does not reflect electrical remodeling. We aimed to determine the predictive value of electrical remodeling of LA which is represented by the amount of low voltage zone (LVZ). Methods: We performed a retrospective cohort analysis of AF patients who underwent de novo RFCA in a single-center. Results: A total of 3,120 AF patients with de novo RFCA were analyzed. Among these patients, 537 patients underwent an electroanatomic mapping with bipolar voltage measurement of LA.The diameter of LA and flow velocity of LA appendage (LAA) differed significantly according to quartile group of LVZ area and percentage: patients with high LVZ had large LA diameter and low LAA flow velocity (p<0.001). Freedom from late recurrence (LR) was significantly lower in patients with high LVZ area and percentage (p<0.001). The diameter and surface area of LA had area under curve (AUC) of 0.592 and 0.593, respectively (p=0.002 for both). The predictive value of LVZ area (AUC, 0.676) and percentage (AUC, 0.671) were both superior compared with LA diameter (p=0.011 and 0.027 for each comparison). Conclusions In conclusion, LVZ can predict freedom from LR after RFCA in AF patients. Predictive value was higher in parameters reflecting electrical rather than structural remodeling of LA.