Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04096547.

Regional variations in patient selection and procedural characteristics for cryoballoon ablation of atrial fibrillation in the cryo global registry.

BACKGROUND: Cryoballoon ablation is a well-established anatomical approach for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Although widely adopted, regional variations in standards of care have not been well characterized. METHODS: Patients with AF were enrolled in the Cryo Global Registry (NCT02752737) from May 2016 to Sept 2021 at 128 sites in 37 countries and treated with cryoballoon ablation according to local clinical practice. Baseline patient and procedural characteristics were summarized for 8 regions (Central Asia & Russia, East Asia, Europe, Middle East, North America, South Africa, South America, and Southeast Asia). Serious procedure-related adverse events (SAEs) were evaluated in a subset of patients with ≥ 7 days of follow-up. RESULTS: A total of 3,680 patients undergoing initial PVI for AF were included. Cryoballoon ablation was commonly performed in patients with paroxysmal AF. Mean age ranged from 47 ± 12 years in the Middle East to 64 ± 11 years in East Asia. Mean procedure time was ≤ 95 min in all regions. Average freeze duration ranged from 153 ± 41 s in Southeast Asia to 230 ± 29 s in Central Asia & Russia. Acute procedural success was ≥ 94.7% in all geographies. In 3,126 subjects with ≥ 7 days of follow-up, 122 procedure-related SAEs were reported in 111 patients (3.6%) and remained low in all regions. One procedure-related death was reported during data collection. CONCLUSIONS: Despite regional variations in patient selection and procedural characteristics, PVI using cryoballoon ablation was performed with high acute success and short procedural times around the world. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.

Exercise capacity and risk of incident atrial fibrillation in healthy adults.

BACKGROUND/AIMS: Atrial fibrillation (AF) is a common arrhythmia and is associated with cardiovascular morbidity and mortality. It is important to identify and control the modifiable risk factors of AF. We aimed to examine the association of exercise capacity with the risk of incident AF within 3 years in healthy subjects. METHODS: We evaluated asymptomatic adults who had undergone more than two consecutive health checkups. We included subjects who exhibited normal sinus rhythm on the first health examination and who developed AF on the second or subsequent health examinations. Subjects who underwent cardiopulmonary exercise testing within 3 years before the diagnosis of AF were examined. RESULTS: The study population in the analyses included 428 cases (mean age 58.4 ± 7.6 yr, male 95.6%). There were significant differences in maximal systolic blood pressure (SBP; case 169.4 ± 24.2 vs. control 173.9 ± 22.3 mmHg), peak VO2 (29.5 ± 5.4 vs. 30.4 ± 4.8 mL/kg per minute), and maximal metabolic equivalents (METs; 8.5 ± 1.6 vs. 8.7 ± 1.4) between the two groups. In the multivariable logistic models, adjusted odds ratios were 0.99 for maximal SBP (95% confidence interval [CI] 0.98-0.99), 0.97 for peak VO2 (95% CI 0.95-0.99), and 0.91 for maximal METs (95% CI 0.83-0.98). CONCLUSION: We demonstrated that poorer exercise capacity was associated with the development of AF in a healthy population. A prospective, systematic trial is necessary to confirm that appropriate exercise training will be beneficial in preventing the development of AF in such patients.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Totally Thoracoscopic Ablation in Patients With Recurrent Atrial Fibrillation After Catheter Ablation.

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of totally thoracoscopic ablation (TTA) in patients with recurrent atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA). METHODS: From February 2012 to May 2020, 460 patients who underwent TTA were classified into two groups: CA (presence of RFCA history, n = 74) and nCA groups (absence of RFCA history, n = 386). Inverse probability of treatment weighting (IPTW) analyses were used to adjust for confounders. The primary endpoint was freedom from the composite of AF, typical atrial flutter, atypical atrial flutter and any atrial tachyarrhythmia, lasting more than 30 seconds during the follow-up. All patients were followed up at 3, 6, and 12 months via electrocardiogram and 24-hour Holter monitoring. RESULTS: Bilateral pulmonary vein isolation (PVI) was conducted in all patients and the conduction block tests were confirmed. In the CA group, difficult PVI occasionally occurred due to structural changes, such as pericardial adhesion and fibrosis of the pulmonary venous structure, caused by a previous catheter ablation. Early complications such as stroke and pacemaker insertion were not different between the two groups. The normal sinus rhythm was maintained in 70.1% (317/460) patients after a median follow-up period of 38.1 months. The IPTW-weighted Kaplan-Meier curves revealed that freedom from AF events at 5 years was 68.4% (95% confidence interval, 62.8-74.5) in the nCA group and 31.2% (95% confidence interval, 16.9-57.5) in the CA group (P < 0.001). In IPTW-weighted Cox regression, preoperative left atrial diameter, persistent or long-standing AF, the presence of congestive heart failure and catheter ablation history were associated with AF events. CONCLUSION: Patients in the CA group showed a higher recurrence rate of AF than those in the nCA group, while TTA was safely performed in both the groups.

Non-Invasive Risk Assessment and Prediction of Mortality in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Objectives: Heart rate turbulence (HRT) and T-wave alternans (TWA), non-invasive markers of cardiac autonomic dysfunction, and ventricular repolarization abnormality, reportedly, predict the risk of cardiovascular death after myocardial infarction. We investigated whether pre-operative assessment of HRT and/or TWA could predict long-term mortality following coronary artery bypass graft (CABG) surgery. Methods: From May 2010 to December 2017, patients undergoing elective CABG and receiving 24 h ambulatory electrocardiogram monitoring 1 to 5 days prior to CABG surgery were prospectively enrolled. Pre-operative HRT and TWA were measured using a 24 h ambulatory electrocardiogram. The relative risk of cardiac or overall death was assessed according to abnormalities of HRT, TWA, or left ventricular ejection fraction (LV EF). Results: During the mean follow-up period of 4.6 ± 3.9 years, 40 adjudicated overall (5.9%/yr) and 5 cardiac deaths (0.9%/yr) occurred in 146 enrolled patients (64.9 ± 9.3 years; 108 males). Patients with abnormal HRT exhibited significantly higher relative risks of cardiac death (adjusted hazard ratio [HR] 24.9, 95% confidence interval [CI] 1.46-427) and all-cause death (adjusted HR 5.77, 95% CI 2.34-14.2) compared to those with normal HRT. Moreover, abnormal HRT plus abnormal TWA and LV EF < 50% was associated with a greater elevation in cardiac and overall mortality risk. The predictive role of abnormal HRT with/without abnormal TWA for all-cause death was likely more prominent in patients with mildly reduced (35 to 50%) or preserved (≥50%) LV EF. Abnormal HRT plus abnormal TWA and LV EF < 50% showed high negative predictive value in cardiac and overall mortality risk. Conclusions: Assessment of pre-operative HRT and/or TWA predicted mortality risk in patients undergoing elective CABG. Combined analysis of HRT, TWA, and LVEF enhanced the prognostic power. In particular, the predictive value of HRT was enhanced in patients with preserved or mid-range LV EF.

A Comparative Study of Thoracoscopic Left Atrial Appendage Clipping vs Stapled Resection.

BACKGROUND: The left atrial appendage (LAA) is the predominant site of thrombus formation in atrial fibrillation (AF), which is associated with ischemic stroke. This study comparatively evaluated the complete LAA closure rates between LAA clipping and stapled resections. METHODS: The study included 333 patients who underwent thoracoscopic operation with both preoperative and postoperative computed tomographic scans. Propensity score matching (4:1 ratio) was applied, matching 90 LAA clipping patients with 206 stapled resection patients. The primary end point was complete LAA closure, defined as a residual LAA depth of <1 cm on computed tomographic images obtained 1 year postoperatively. RESULTS: No 30-day death was observed. Complete LAA closure was achieved in 85.9% (286 of 333) of patients. After propensity score matching, the clipping group demonstrated a significantly higher complete LAA closure rate than the stapled resection group (95.6% vs 83.0%, P = .003). The residual LAA stump depth was also shorter in the clipping group compared with the stapled resection group (2.9 vs 5.3 mm, P = .001). Two patients with a residual LAA stump exhibited an association with ischemic stroke during follow-up. CONCLUSIONS: The clipping group demonstrated a higher rate of complete LAA closure compared with the stapled resection group. Close monitoring of patients with residual LAA stumps is essential. Further research with larger cohorts is needed to elucidate impact of the residual LAA stump on thromboembolic events.

Clinical and Genetic Features of Korean Inherited Arrhythmia Probands.

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

Association of right bundle branch block or intraventricular conduction delay with recurrence of atrial fibrillation after catheter ablation.

BACKGROUND: The association between bundle branch block (BBB) and recurrence of atrial fibrillation (AF) after catheter ablation is unclear. The aim of this study was to determine whether AF combined with BBB is associated with AF recurrence after catheter ablation. METHODS: A total of 477 consecutive AF patients who underwent catheter ablation were included. The AF patients were divided into three groups according to BBB: AF without BBB (n = 427), AF with right bundle branch block (AF with RBBB) (n = 16), and AF with intraventricular conduction delay (AF with IVCD) (n = 34). RESULTS: Of the 477 AF patients (mean age 57 years, 81% men, median CHA2 DS2 -VASc score of 1), 16 (3.4%) patients had RBBB, and 34 (7.1%) patients had IVCD. During a mean follow-up of 15.2 ± 6.7 months, 119 patients (24.9%) had recurrence of AF. Of these, 111 (26%) patients were in the AF without BBB group, with 2 (12.5%) and 6 (17.6%) patients in the RBBB and IVCD groups, respectively. The Kaplan-Meier estimate of the rate of recurrent AF was not significantly different among the three groups (p = .39). Multivariable analysis showed that persistent AF (HR 1.7, 95% CI 1.15-2.50, p = .007), chronic kidney disease (HR 2.94, 95% CI 1.20-7.17, p = .01), and left atrial diameter (HR 1.04, 95% CI 1.009-1.082, p = .01) were significantly associated with AF recurrence. CONCLUSION: AF with BBB was not significantly associated with the recurrence of AF after catheter ablation in middle-aged patients with low-risk cardiovascular profile.

Comparison of propofol vs. remimazolam on emergence profiles after general anesthesia: A randomized clinical trial.

STUDY OBJECTIVE: The emergence profiles in patients undergoing total intravenous anesthesia with either propofol or remimazolam with flumazenil reversal were compared. DESIGN: A prospective, double-blind, randomized trial. SETTING: An operating room and a post-anesthesia care unit (PACU). PATIENTS: Adult patients (n = 100) having American Society of Anesthesiologists (ASA) physical status of I-III undergoing general anesthesia were enrolled and randomly assigned to the propofol or the remimazolam group. INTERVENTIONS: The propofol group received target-controlled infusion of propofol, and the remimazolam group received continuous infusion of remimazolam. Continuous infusion of remifentanil was used in both groups. For emergence, flumazenil was used in increments of 0.2 mg in the remimazolam group. MEASUREMENTS: The primary outcome was the time required for the patient to obey verbal commands. The secondary outcomes included the time to bispectral index (BIS) over 80, the time to laryngeal mask airway (LMA) removal, the Richmond Agitation-Sedation Scale (RASS) scores in the PACU, and adverse events throughout the study period. MAIN RESULTS: The time taken to obey verbal commands was significantly longer in the propofol group than the remimazolam group (14 [9, 19]) vs. 5 [3, 7]) minutes, P < 0.001; median difference -9, 95% confidence interval -11 to -6). The times to BIS over 80 and to LMA removal were also significantly longer in the propofol group. In addition, the RASS score upon arrival to the PACU differed significantly between the two groups (P = 0.006). Re-sedation in the PACU was observed in 11 (22%) of the patients in the remimazolam group. CONCLUSIONS: Remimazolam-based total intravenous anesthesia with flumazenil reversal may be effective in reducing emergence time, but a significant incidence of re-sedation was observed in the PACU. Further studies are needed to determine adequate dose and timing of routine flumazenil use and minimize the risk of re-sedation.

Long-term outcome of thoracoscopic ablation and radiofrequency catheter ablation for persistent atrial fibrillation as a de novo procedure.

AIMS: Limited data are available regarding the efficacy of thoracoscopic ablation as the first procedure for persistent atrial fibrillation (AF). We sought to compare the long-term efficacy of thoracoscopic ablation vs. radiofrequency (RF) catheter ablation as the first procedure for persistent AF. METHODS AND RESULTS: Between February 2011 and December 2020, 575 patients who underwent ablation for persistent AF were studied. Among them, thoracoscopic ablation was performed in 281 patients, RF catheter ablation in 228, and hybrid ablation in 66. Rhythm, clinical, and safety outcomes during 7-year follow-up were compared. The patients who underwent thoracoscopic ablation were older, had a higher prevalence of stroke, and had a larger left atrial volume than those who underwent RF catheter ablation. In the propensity score-matched population (n = 306), incidences of atrial tachyarrhythmia recurrence were 51.4% in the thoracoscopic ablation group and 62.5% in the RF catheter ablation group [adjusted hazard ratio (HR) 0.869, 95% confidence interval (CI) 0.618-1.223, P = 0.420]. Stroke and total procedural adverse events were not significantly different between thoracoscopic and RF catheter ablation (2.7 vs. 2.5%, P = 0.603, and 7.1 vs. 4.8%, P = 0.374, respectively). The hybrid ablation group showed similar rhythm outcomes compared with both the thoracoscopic and the RF catheter ablation groups. At the redo procedure, pulmonary vein gaps were more frequently observed in the RF catheter ablation group (32.6%) than in the thoracoscopic ablation group (7.9%) and in the hybrid ablation group (8.8%) (P < 0.001). CONCLUSION: As a first procedure in persistent AF, thoracoscopic ablation and RF catheter ablation showed comparable efficacy, clinical, and safety outcomes during long-term follow-up.

Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.

The mechanism of premature ventricular complexes (PVC) occurring in the ventricular outflow tract (OT) is related to an intracellular calcium overload and delayed afterdepolarizations that lead to triggered activity. The guidelines recommend using beta-blockers and flecainide for idiopathic PVCs, but they also acknowledge the limited evidence supporting this recommendation. We conducted a multicenter, randomized, open-label pilot study comparing the effect of carvedilol and flecainide on OT PVC, which are widely used to treat this arrhythmia. Patients with a 24 h Holter recording a PVC burden ≥ 5%, which showed positive R waves in leads II, III, and aVF, and without structural heart disease were enrolled. They were randomly assigned to the carvedilol or flecainide group, and the maximum tolerated dose was administered for 12 weeks. A total of 103 participants completed the protocol: 51 with carvedilol and 52 with flecainide. After 12 weeks of treatment, the mean PVC burden significantly decreased in both groups: 20.3 ± 11.5 to 14.6 ± 10.8% with carvedilol (p < 0.0001) and 17.1 ± 9.9 to 6.6 ± 9.9% with flecainide (p < 0.0001). Both carvedilol and flecainide effectively suppressed OT PVCs in patients without structural heart disease, with flecainide showing a superior efficacy compared to carvedilol.

The higher recurrence rate after catheter ablation in younger patients with atrial fibrillation suggesting different pathophysiology.

BACKGROUND: Young atrial fibrillation (AF) patients have been underrepresented in studies of radiofrequency catheter ablation (RFCA) and the outcome of RFCA has not been widely addressed. We investigated age-related differences in clinical features, the recurrence of atrial tachyarrhythmia, and its predictors of patients who underwent RFCA for AF. METHODS: This is a multicenter prospective study of 2799 patients who underwent RFCA for AF in 2017-2020. The patients were divided into two groups - group A (age < 60 years, n = 1269) and group B (age ≥ 60 years, n = 1530) - and a recurrence of any atrial tachyarrhythmia 1 year after RFCA following a 90-day blanking period was compared. RESULTS: The mean age was 51.6 ± 6.7 and 66.8 ± 5.2 years for groups A and B, respectively. Higher body mass index, smaller left atrium, and more prevalent cardiomyopathy and obstructive sleep apnea were observed in group A. Overall, 1-year atrial tachyarrhythmia-free survival was 85.6% and lower in young patients (83.1% in group A vs. 87.7% in group B, log-rank p < 0.01): adjusted hazard ratio (aHR) of recurrence (95% confidence interval (CI)), 1.45 (1.13-1.86) for group A compared to group B (p < 0.01). The association between younger age and higher recurrence was continuously observed in patients under 60 years. Any non-PV ablation was associated with a lower recurrence of atrial tachyarrhythmia in group B (aHR 0.68 (0.47-0.96), p < 0.05), but not in group A. CONCLUSIONS: AF patients younger than 60 years had a higher 1-year AF recurrence after RFCA. Young AF patients might have distinctive pathophysiology of AF requiring more integrated management.

Comparison of Early Complications of Oral Anticoagulants after Totally Thoracoscopic Ablation: Warfarin versus Non-vitamin K Antagonist Oral Anticoagulants.

Background: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Totally thoracoscopic ablation (TTA) is a surgical treatment showing a high success rate as a hybrid procedure with radiofrequency catheter ablation to control AF. This study compared the early complications of warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) in patients who underwent TTA. Methods: This single-center retrospective cohort study enrolled patients who underwent planned TTA for AF from February 2012 to October 2020. All patients received postoperative anticoagulation, either with warfarin or a NOAC (apixaban, rivaroxaban, dabigatran, or edoxaban). Propensity score matching was performed for both groups. Early complications were assessed at 12 weeks after TTA and were divided into efficacy and safety outcomes. Both efficacy and safety outcomes were compared in the propensity score-matched groups. Results: Early complications involving efficacy outcomes, such as stroke and transient ischemic attack, were seen in 5 patients in the warfarin group and none in the NOAC group. Although the 2 groups differed in the incidence of efficacy outcomes, it was not statistically significant. In safety outcomes, 11 patients in the warfarin group and 24 patients in the NOAC group had complications, but likewise, the between-group difference was not statistically significant. Conclusion: Among patients who underwent TTA, those who received NOACs had a lower incidence of thromboembolic complications than those who received warfarin; however, both groups showed a similar bleeding complication rate. Using a NOAC after TTA does not reduce efficacy and safety when compared to warfarin.

Impact of first-line cryoablation for atrial fibrillation on healthcare utilization, arrhythmia disease burden and efficacy outcomes: real-world evidence from the Cryo Global Registry.

BACKGROUND: Cryoballoon ablation (CBA) is an effective first-line treatment for symptomatic atrial fibrillation (AF), as recently demonstrated by three randomized trials. This sub-analysis of the Cryo Global Registry aims to examine current clinical practices of first-line CBA. METHODS: AF patients treated with first-line CBA were compared to CBA in antiarrhythmic drug (AAD)-refractory patients at 12 months. Efficacy was examined using time-to-first atrial arrhythmia recurrence following a 90-day blanking period. Healthcare utilization was evaluated by repeat ablations and hospitalizations. Disease burden was examined by assessing quality of life (QOL) and patients' reporting of symptoms. RESULTS: Of 1394 patients, 433 (31.1%) were treated with first-line CBA, which was more frequent in high-volume centers. Serious procedure-related adverse event rates were similar. Efficacy at 12 months was higher in the first-line group (87.8 vs. 81.6%, HRunadj 0.64 (95% CI 0.47-0.88); p < 0.01) regardless of the centers' CBA experience; when controlling for baseline characteristics, the difference was not significant (HRadj 0.87 (95% CI 0.56-1.37); p = 0.55). No difference was observed in repeat ablations and hospitalizations between cohorts. First-line patients experienced a larger mean reduction in symptoms and were prescribed AADs at a lower rate at 12-month follow-up (9.7 vs. 29.9%). QOL improved in both cohorts from baseline to 12 months with no significant difference between groups (p = 0.29). CONCLUSIONS: In this global real-world experience, first-line CBA in patients with symptomatic AF is effective, with a larger symptom reduction compared with CBA after AAD failure and without a difference in healthcare utilization at mid-term follow-up. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.

New Oral Anticoagulant Versus Vitamin K Antagonists for Thoracoscopic Ablation in Patients With Persistent Atrial Fibrillation: A Randomized Controlled Trial.

Anticoagulation could not be currently stopped even after successful thoracoscopic ablation of atrial fibrillation for at least 2 months. The aim of this study is to compare the safety and efficacy outcomes between a new oral anticoagulant and warfarin after thoracoscopic ablation. This trial was a single-center, prospective, randomized controlled study comparing edoxaban and warfarin in patients undergoing thoracoscopic ablation of atrial fibrillation. This study enrolled 60 patients randomly assigned into 2 groups. The primary endpoint was efficacy outcomes, including stroke and systemic thromboembolic events. The secondary endpoint was safety outcomes including major bleeding and pericarditis. The patients were evaluated at discharge, 2 weeks, 3 months, and 6 months postoperatively. No stroke and thromboembolic events were noted in both treatment groups during the follow-up period. During the 6 months follow-up period, 4 (13%) of 30 patients in the edoxaban group experienced minor bleeding events, whereas none were noted in the warfarin group. Five anticoagulation-related events (bleeding, and prolongation of international normalized ratio), including pericarditis, were noted in both the edoxaban and warfarin groups. No statistically significant difference existed between the 2 groups. In conclusion, this study showed the comparable results of edoxaban to warfarin during the window period of post-thoracoscopic ablation of atrial fibrillation. Moreover, anticoagulation-related events were rather affected by patient factors and not by the anticoagulant type.

Outcomes of On-Label Reduced-Dose Edoxaban in Patients With Atrial Fibrillation: The LEDIOS Registry.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are effective in preventing thromboembolisms and reduce the risk of bleeding compared with warfarin. There are few reports on the outcomes of on-label reduced-dose NOACs. The aim of this study was to assess the safety and efficacy of on-label reduced-dose edoxaban in patients with atrial fibrillation (AF). METHODS: This study is a multi-center, prospective, non-interventional study to evaluate the safety and efficacy of on-label reduced-dose edoxaban in patients with AF. We evaluated outcomes of major bleeding, stroke or systemic embolism, all-cause death, and composite clinical outcomes. RESULTS: A total of 2,448 patients (mean age 75.0 ± 8.3 years, 801 [32.7%] males) was included in the present study. The mean CHA2DS2-VASc score was 3.7 ± 1.5. Major bleeding events occurred at a rate of 1.34%/yr. The event rate of strokes and systemic embolisms was 1.13%/yr. The overall net clinical outcomes occurred at a rate of 3.19%/yr. There were no significant differences according to the number of dose reduction criteria, renal dysfunction, or body weight. Higher HAS-BLED score and higher combination of CHA2DS2-VASc and HAS-BLED score was associated with an increased risk of composite clinical outcomes compared to the lower score groups. CONCLUSIONS: This study was the largest prospective real-world study to investigate the safety and efficacy of on-label low-dose edoxaban in an Asian population. Reduced-dose edoxaban can be used safely in patients with severe renal dysfunction or extremely low body weight. Our observation suggests that physicians should consider bleeding risk even in a low-dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03554837.

Cryoballoon Catheter Ablation in Korean Patients With Paroxysmal and Persistent Atrial Fibrillation: One Year Outcome From the Cryo Global Registry.

BACKGROUND AND OBJECTIVES: Cryoballoon catheter ablation for the treatment of patients with symptomatic atrial fibrillation (AF) has been adopted globally, but there are limited multicenter reports of 12-month outcomes in the Korean patient population. This analysis evaluated the clinical performance and safety of cryoballoon ablation (CBA) according to standard-of-care practices in Korea. METHODS: This evaluation of Korean patients with AF was conducted within the larger Cryo Global Registry, which is a prospective, multicenter, post-market registry. Freedom from a ≥30-second recurrence of atrial arrhythmias (after a 90-day blanking period until 12 months) and procedural safety were examined in subjects treated with CBA at 3 Korean centers. RESULTS: Overall, 299 patients with AF (60±11 years old, 24.7% female, 50.5% paroxysmal AF) underwent CBA using the Arctic Front Advance cryoballoon. Of those, 298 were followed-up for at least 12 months. Mean procedure-, left atrial dwell- and fluoroscopy time was 76±21 minutes, 56±23 minutes, and 27±23 minutes, respectively. Freedom from AF recurrence at 12 months was 83.9% (95% confidence interval [CI], 76.9-88.9%) in the paroxysmal and 61.6% (95% CI, 53.1-69.0%) in the persistent AF cohort. Rhythm monitoring was performed on average 4.7±1.4 times during the follow-up period. Serious device- or procedure-related adverse events occurred in 2 patients (0.7%). The 12-month Kaplan-Meier estimate of freedom from repeat ablation and cardiovascular-related hospitalization was 93.8% (95% CI, 90.4-96.1%) and 89.7% (95% CI, 85.6-92.7%), respectively. CONCLUSIONS: CBA is an efficient, effective, and safe procedure for the treatment of AF patients when used according to real-world practices in Korea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02752737.

Genetic Analysis of Cardiac Syncope-Related Genes in Korean Patients with Recurrent Neurally Mediated Syncope.

Neurally mediated syncope (NMS) is a common clinical problem. The underlying genetic factors of NMS remain controversial. We hypothesized that cardiac syncope-related genes may contribute to NMS in patients with previous frequent syncopal episodes and/or a family history of syncope. A total of 54 consecutive patients diagnosed with NMS were prospectively enrolled between 2013 and 2016. Inclusion criteria were more than five syncopal episodes with a family history of syncope (n = 17) or more than five syncopal episodes with no family history of syncope (n = 37). Ninety-eight cardiac syncope-related genes (channelopathy: 43 genes, cardiomyopathy: 50 genes, primary pulmonary hypertension: 5 genes) were screened by exome sequencing. All identified variants were classified according to the standards and guidelines by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Of the 54 patients, 17 patients (31.5%) had a family history of syncope. Two patients (3.7%) had pathogenic and likely pathogenic variants (PV/LPV) in cardiac syncope-related genes TTN and MYH7. We investigated genetic variation in patients with frequent NMS with a positive family history of syncope in Korea. PV/LPVs in genes related to cardiomyopathy were associated with recurrent NMS in Korean patients. Closer follow-up of these patients might be needed.