Case Report: Comprehensive evaluation of ECG phenotypes and genotypes in a family with Brugada syndrome carrying SCN5A-R376H.

Background: Brugada syndrome (BrS) is a channelopathy that can lead to sudden cardiac death in the absence of structural heart disease. Patients with BrS can be asymptomatic or present with symptoms secondary to polymorphic ventricular tachycardia or ventricular fibrillation. Even though BrS can exhibit autosomal dominant inheritance, it is not easy to identify the phenotype and genotype in a family thoroughly. Case: We report the case of a 20-year-old man with variants in SCN5A and RyR2 genes who was resuscitated from sudden cardiac death during sleep due to a ventricular fibrillation. The patient did not have underlying diseases. The routine laboratory results, imaging study, coronary angiogram, and echocardiogram (ECG) were normal. A type 1 BrS pattern was identified in one resting ECG. Furthermore, prominent J wave accentuation with PR interval prolongation was identified during therapeutic hypothermia. Therefore, we were easily able to diagnose BrS. For secondary prevention, the patient underwent implantable cardioverter defibrillator implantation. Before discharge, a genetic study was performed using next-generation sequencing. Genotyping was performed in the first-degree relatives, and ECG evaluations of almost all maternal and paternal family members were conducted. The proband and his mother showed SCN5A-R376H and RyR2-D4038Y variants. However, his mother did not show the BrS phenotype on an ECG. One maternal aunt and uncle showed BrS phenotypes. Conclusion: Genetics alone cannotdiagnose BrS. However, genetics could supply evidence or direction for evaluating ECG phenotypes in family groups. This case report shows how family evaluation using ECGs along with a genetic study can be used in BrS diagnosis.

Left Atrium Volume Measured with Multislice Computed Tomography as a Prognostic Predictor for Atrial Fibrillation Catheter Ablation Outcomes.

Background: Current guidelines consider atrial fibrillation (AF) type as the prognostic factor for a recommendation of catheter ablation. We aimed to determine whether LA and LA appendage (LAA) volumes measured using multislice computed tomography (MSCT) were related to long-term outcomes in AF following radiofrequency catheter ablation (RFCA). Methods: We evaluated 152 consecutive patients with drug-refractory AF (median age, 55.8 ± 9.6 years), including 110 male patients, who underwent RFCA in a single center. All patients underwent MSCT imaging for anatomical assessment. The endpoint of this study was documented AF recurrence after RFCA. Results: The overall procedure success rate was 77.6% (n = 118) during a mean follow-up period of 12.6 months. The LA volume was significantly larger for those who experienced AF recurrence after RFCA than for the patients without recurrent AF after the procedure (153.8 ± 29.9 mL vs. 139.2 ± 34.1 mL, p = 0.025). However, LAA volumes were nearly equivalent between the patients with and without AF recurrence after RFCA (16.2 ± 6.3 mL and 14.7 ± 6.5 mL, respectively; p = 0.235). LA volume ≥ 153.2 mL was the optimal cutoff value for estimating AF recurrence after RFCA, with 94% sensitivity and 66% specificity. LA volume remained an independent predictor of both AF recurrence and permanent AF. Conclusions: LA volume as assessed by MSCT might be helpful for identifying patients likely to achieve successful AF ablation. LA volume ≥ 153.2 mL, but not LAA volume, showed good accuracy in predicting AF recurrence after RFCA.

Modified application of SAMe-TT2R2 scoring system in Asian patients with atrial fibrillation for the selection of oral anticoagulants.

BACKGROUND/AIMS: The SAMe-TT2R2 score is used for assessing anticoagulation control (AC) quality with warfarin. However, it is hard to apply SAMe-TT2R2 score in Asian patients with atrial fibrillation (AF), because it has not been proven in those populations. This study aimed to validate the SAMe-TT2R2 score in Asian patients with AF and suggest a modified SAMe- TT2R2 score for this population. METHODS: We analyzed 710 Korean patients with AF who were using warfarin. The AC quality was assessed as the mean time in therapeutic range (TTR). Each component of SAMe-TT2R2 score was evaluated for the relationship with AC. Further clinical factors that predict AC were analyzed. Identified factors were re-assorted and constructed as SA2Me-TTR scoring system. RESULTS: Of the components of the SAMe-TT2R2 score, female, age, and rhythm control were associated with AC. Heart failure and renal insufficiency were newly identified factors associated with AC. The modified SA2Me-TTR score was reconstructed with the relevant risk factors (S, female gender, 1 point; A, age < 60 yr, 2 points; Me, medical history of heart failure, 1 point; T, treatment for rhythm control, 1 point; T, history of stroke or transient ischemic attack, 1 point; R, renal insufficiency, 1 point). The modified SA2Me-TTR score demonstrated an excellent relationship with the grading of AC. The modified SA2Me-TTR score ≤ 1 identified patients with good AC (hazard ratio 2.46, 95% CI 1.75-3.47). CONCLUSION: The modified SA2Me-TTR score was useful for guiding oral anticoagulants selection in Asian patients with AF.

Standard-Intensity Versus Low-Intensity Anticoagulation with Warfarin in Asian Patients with Atrial Fibrillation: A Multi-Center, Randomized Controlled Trial.

Anticoagulation with warfarin in Asian patients with atrial fibrillation (AF) often has been decreased as an international normalized ratio (INR) of prothrombin time 1.6-2.6 due to fear of bleeding, although universal criteria recommend an INR of 2.0-3.0. In this randomized, open-label trial, low-intensity anticoagulation (INR 1.6-2.6) was compared with standard-intensity anticoagulation (INR 2.0-3.0) with warfarin. A total 616 patients with AF and at least 1 risk factor for stroke were randomized to low-intensity anticoagulation (n = 308) and standard-intensity anticoagulation (n = 308) groups. The intention-to-treat analysis was performed to determine differences. The baseline characteristics of the two groups were comparable. New-onset stroke occurred in 2 patients (0.44% per year) in the low-intensity group and 5 patients (1.05% per year) in the standard-intensity group (HR 0.42, 95% CI 0.08-2.15). Major bleeding occurred in 4 patients (0.89% per year) in the low-intensity group and 5 patients (1.06% per year) in the standard-intensity group (HR 0.84, 95% CI 0.22-3.11). The rate of the net clinical outcome (composite of stroke, systemic embolism, major bleeding, and death) was 1.33% per year in the low-intensity group compared with 2.12% per year in the standard-intensity group (HR 0.63, 95% CI 0.23-1.72). In Asian patients with AF, clinical outcomes were not different between low-intensity and standard-intensity anticoagulation with warfarin.

Prevalence and Characteristics of Atrial Tachycardia From Noncoronary Aortic Cusp During Atrial Fibrillation Catheter Ablation.

BACKGROUND AND OBJECTIVES: Atrial tachycardias (ATs) from noncoronary aortic cusp (NCC) uncovered after radiofrequency ablation for atrial fibrillation (AF) are rarely reported. This study was conducted to investigate the prevalence and clinical characteristics of NCC ATs detected during AF ablation and compare their characteristics with de novo NCC ATs without AF. METHODS: Consecutive patients who underwent radiofrequency catheter ablation for AF were reviewed from the multicenter AF ablation registry of 11 tertiary hospitals. The clinical and electrophysiological characteristics of NCC AT newly detected during AF ablation were compared with its comparators (de novo NCC AT ablation cases without AF). RESULTS: Among 10,178 AF cases, including 1,301 redo ablation cases, 8 (0.08%) NCC AT cases were discovered after pulmonary vein isolation (PVI; 0.07% in first ablation and 0.15% in redo ablation cases). All ATs were reproducibly inducible spontaneously or with programmed atrial stimulation without isoproterenol infusion. The P-wave morphological features of tachycardia were variable depending on the case, and most cases exhibited 1:1 atrioventricular conduction. AF recurrence rate after PVI and NCC AT successful ablation was 12.5% (1 of 8). Tachycardia cycle length was shorter than that of 17 de novo ATs from NCC (303 versus 378, p=0.012). No AV block occurred during and after successful AT ablation. CONCLUSIONS: Uncommon NCC ATs (0.08% in AF ablation cases) uncovered after PVI, showing different characteristics compared to de-novo NCC ATs, should be suspected irrespective of P-wave morphologies when AT shows broad propagation from the anterior interatrial septum.

Edoxaban-based long-term antithrombotic therapy in patients with atrial fibrillation and stable coronary disease: Rationale and design of the randomized EPIC-CAD trial.

BACKGROUND: Anticoagulants are the standard therapy for patients with atrial fibrillation (AF) and antiplatelet therapy for those with coronary artery disease (CAD). However, compelling clinical evidence is still lacking regarding the long-term maintenance strategy with the combination of anticoagulant and antiplatelet drugs in patients with AF and stable CAD. DESIGN: The EPIC-CAD trial is an investigator-initiated, multicenter, open-label randomized trial comparing the safety and efficacy of 2 antithrombotic strategies in patients with high-risk AF (CHA2DS2-VASc score ≥ 2 points) and stable CAD (≥6 months after revascularization for stable angina or ≥12 months for acute coronary syndrome; or medical therapy alone). Patients (approximately N = 1,038) will be randomly assigned at a 1:1 ratio to (1) monotherapy with edoxaban (a non-vitamin K antagonist oral anticoagulant) or (2) combination therapy with edoxaban plus a single antiplatelet agent. The primary endpoint is the net composite outcome of death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularization, and major or clinically relevant nonmajor bleeding at 1 year after randomization. RESULTS: As of December 2021, approximately 901 patients had been randomly enrolled over 2 years at 18 major cardiac centers across South Korea. The completed enrollment is expected at the mid-term of 2022, and the primary results will be available by 2023. CONCLUSIONS: EPIC-CAD is a large-scale, multicenter, pragmatic design trial, which will provide valuable clinical insight into edoxaban-based long-term antithrombotic therapy in patients with high-risk AF and stable CAD.

Corrigendum to "Covid-19 and the aviation industry: The interrelationship between the spread of the Covid-19 pandemic and the frequency of flights on the EU Market" [Ann. Tour. Res., Volume 91, November 2021, 103298].

[This corrects the article DOI: 10.1016/j.annals.2021.103298.].

Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and non-vitamin K antagonist oral anticoagulant therapy.

BACKGROUND: The use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been increasing. Accordingly, the combined use of antiplatelet agents (APT) and NOAC therapy is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) vs. monotherapy (NOAC only) in patients with AF. METHODS: We retrospectively analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major bleeding and any bleeding events, and the secondary outcomes were stroke/systemic embolic (SE) events and major adverse cardiac events (MACE). RESULTS: Of the 1068 participants, there were 264 (24.7%) patients in the combination therapy group. The prevalence of diabetes (p = 0.017) and history of stroke and transient ischemic attacks (p < 0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6 ± 9.8 months of follow-up, the incidence of any bleeding was significantly higher in the combination therapy group than in the monotherapy group (p < 0.001). The rate of major bleeding, stroke/SE, and MACE between the two groups was similar. The rate of under-dosage NOAC prescriptions was higher in the combination therapy group than in the monotherapy group (p = 0.024). CONCLUSIONS: The combination therapy group had higher incidences of any bleeding events compared to the monotherapy in patients with appropriate dosing. However, there was no difference in stroke/SE, and MACE. The bleeding risk in AF patients taking the combination of NOACs and APT should be carefully evaluated.

Social distancing, trust and post-COVID-19 recovery.

With the tourism and hospitality sector reopening post-lockdown of COVID-19, the recovery of customers' purchase intentions is essential to reboot the sector. This study aims to examine the relationship between social distancing measures and purchase intentions in the UK's restaurant and hotel sectors using a propensity score weighting experimental design method. The findings suggest that the impact of social distancing measures on purchase intentions is mediated by the trust in the targeted restaurant and hotel. Risk tolerance significantly moderates the influence of social distancing measures on trust; (non-) cash promotions have an insignificant impact on purchase intentions. The introduction of the propensity score weighting scheme addresses the endogeneity caused by the sampling bias in non-probability sampling experiment studies.

Algorithm for diagnosing hypertension using out-of-office blood pressure measurements.

The authors developed and validated a diagnostic algorithm using the optimal upper and lower cut-off values of office and home BP at which ambulatory BP measurements need to be applied. Patients presenting with high BP (≥140/90 mm Hg) at the outpatient clinic were referred to measure office, home, and ambulatory BP. Office and home BP were divided into hypertension, intermediate (requiring diagnosis using ambulatory BP), and normotension zones. The upper and lower BP cut-off levels of intermediate zone were determined corresponding to a level of 95% specificity and 95% sensitivity for detecting daytime ambulatory hypertension by using the receiver operator characteristic curve. A diagnostic algorithm using three methods, OBP-ABP: office BP measurement and subsequent ambulatory BP measurements if office BP is intermediate zone; OBP-HBP-ABP: office BP, subsequent home BP measurement if office BP is within intermediate zone and subsequent ambulatory BP measurement if home BP is within intermediate zone; and HBP-ABP: home BP measurement and subsequent ambulatory BP measurements if home BP is within intermediate zone, were developed and validated. In the development population (n = 256), the developed algorithm yielded better diagnostic accuracies than 75.8% (95%CI 70.1-80.9) for office BP alone and 76.2% (95%CI 70.5-81.3) for home BP alone as follows: 96.5% (95%CI: 93.4-98.4) for OBP-ABP, 93.4% (95%CI: 89.6-96.1) for OBP-HBP-ABP, and 94.9% (95%CI: 91.5-97.3%) for HBP-ABP.  In the validation population (n = 399), the developed algorithm showed similarly improved diagnostic accuracy. The developed algorithm applying ambulatory BP measurement to the intermediate zone of office and home BP improves the diagnostic accuracy for hypertension.

COVID-19 and the aviation industry: The interrelationship between the spread of the COVID-19 pandemic and the frequency of flights on the EU market.

This study aims to investigate the contribution of aviation related travel restrictions to control the spread of COVID-19 in Europe by using quasi-experiment approaches including the regression discontinuity design and a two-stage spatial Durbin model with an instrumental variable. The study provides concrete evidence that the severe curtailing of flights had a spontaneous impact in controlling the spread of COVID-19. The counterfactual analysis encapsulated the spillover effects deduced that a 1% decrease in flight frequency can decrease the number of confirmed cases by 0.908%. The study also reveals that during the lockdown, the aviation industry cancelled over 795,000 flights, which resulted in averting an additional six million people being from being infected and saving 101,309 lives.

Corrigendum: Comparison of Mobile Application-Based ECG Consultation by Collective Intelligence and ECG Interpretation by Conventional System in a Tertiary-Level Hospital.

This corrects the article on p. 351 in vol. 51, PMID: 33821585.

Comparison of Mobile Application-Based ECG Consultation by Collective Intelligence and ECG Interpretation by Conventional System in a Tertiary-Level Hospital.

BACKGROUND AND OBJECTIVES: A mobile application (app)-based electrocardiogram (ECG) consultation system (InterMD Co., Ltd., Seoul, Korea) using the collective intelligence (CI) and the availability of large-scale digitized ECG data would extend the utility of ECGs beyond their current limitations, while at the same time preserving interpretability that remains critical to medical decision-making. METHODS: We developed a new mobile app-based ECG consultation system by CI for general practitioners. We compared the responses of ECG reading between the mobile app-based CI system and the conventional system in a tertiary referring hospital. RESULTS: We analyzed 376 consecutive ECGs between December 2017 and May 2019. Of these, 159 ECGs (42.3%) were interpreted by CI through the mobile app-based ECG consultation system and 217 ECGs (57.7%) were analyzed by cardiologists in the conventional systems based on electronic medical record data in a tertiary hospital. All ECG readings were confirmed by an electrophysiologist (EP). The time to an initial response by the CI system was faster than that of the conventional system (6.6 hours vs. 35.8 hours, p<0.0001). The number of responses of each ECG in CI system outnumbered those of the conventional system in the tertiary hospital (3.1 vs. 1.2, p<0.0001). The consensus of the ECG readings with EP was similar in both systems (98.6% vs. 100%, p=0.158). CONCLUSIONS: The mobile app-based ECG consultation system by CI is as reliable method as the conventional referral system. It would expand the app of the 12-lead ECG with the collaboration of physicians in clinics and hospitals without time and space constraints.

The shape of the left lateral ridge as a predictor of long-term outcome of catheter ablation for atrial fibrillation based on clinical and experimental data.

BACKGROUND: The left lateral ridge (LLR) is an important structure for ablation of atrial fibrillation (AF). This study assessed how the LLR shape is associated with the long-term outcomes of AF ablation and investigated the relationship with radiofrequency (RF) lesion formation. METHODS AND RESULTS: Clinical study - we assessed multi-detector computed tomography (MDCT) images in 247 patients who underwent AF ablation. Patients were classified into two groups according to the shape of the LLR: Narrow LLR group (n = 116; 47%) and Wide LLR group (n = 131; 53%). After a follow-up period 475 ± 245 days, the AF-free rate was significantly higher in the wide LLR than Narrow LLR group (83.2% vs. 62.9%, p = 0.0004). A multivariate analysis showed that the shape of the LLR was an independent predictor of AF recurrence after ablation (hazard ratio 2.58; 95% confidential interval = 1.48-4.51, p = 0.001). Experimental study - Two types of the ridge models were made with porcine atrial tissues: "Narrow ridge(4.2 ± 0.9 mm)" and "Wide ridge(9.7 ± 1.8 mm)" RF ablation was performed on each ridge model using a contact force (CF)-sensing catheter. The mean CF and the RF lesion volume of the narrow ridge were significantly less than those of the wide ridge model (5.42 ± 3.13 g vs. 10.37 ± 3.98 g, p = 0.001; 19.8 ± 9.9 mm3 vs. 44.2 ± 13.6 mm3, p < 0.001, respectively). CONCLUSIONS: AF recurrence after ablation was more frequent in patients with a narrow LLR. LLR shape as assessed using MDCT is associated with long-term outcomes after AF ablation. CF and lesion formation data using the porcine atrial tissue model support our clinical results.

Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis.

BACKGROUND: Patients with mitral stenosis and atrial fibrillation (AF) require anticoagulation for stroke prevention. Thus far, all studies on direct oral anticoagulants (DOACs) have excluded patients with moderate to severe mitral stenosis. OBJECTIVES: The aim of this study was to validate the efficacy of DOACs in patients with mitral stenosis. METHODS: The study population was enrolled from the Health Insurance Review and Assessment Service (HIRA) database in the Republic of Korea, and it included patients who were diagnosed with mitral stenosis and AF and either were prescribed DOACs for off-label use or received conventional treatment with warfarin. The primary efficacy endpoint was ischemic strokes or systemic embolisms, and the safety outcome was intracranial hemorrhage. RESULTS: A total of 2,230 patients (mean age 69.7 ± 10.5 years; 682 [30.6%] males) were included in the present study. Thromboembolic events occurred at a rate of 2.22%/year in the DOAC group, and 4.19%/year in the warfarin group (adjusted hazard ratio for DOAC: 0.28; 95% confidence interval: 0.18 to 0.45). Intracranial hemorrhage occurred in 0.49% of the DOAC group and 0.93% of the warfarin group (adjusted hazard ratio for DOAC: 0.53; 95% confidence interval: 0.22 to 1.26). CONCLUSIONS: In patients with AF accompanied with mitral stenosis, DOAC use is promising and hypothesis generating in preventing thromboembolism. Our results need to be replicated in a randomized trial.

Utility of acute arrhythmia termination as an ablation endpoint for induced atrial tachyarrhythmia after complete pulmonary vein isolation during catheter ablation for persistent atrial fibrillation.

PURPOSE: The presence of inducible atrial tachyarrhythmia after pulmonary vein isolation (PVI) during radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (AF) may indicate the necessity of further substrate modification, but the optimal ablation endpoint is unknown. We sought to assess the impact of procedural termination of inducible atrial tachyarrhythmia after PVI in comparison with continued atrial tachyarrhythmia after PVI. METHODS: Among patients who underwent RFCA for persistent AF, we enrolled 93 patients who were in sinus rhythm after PVI and had inducible atrial tachyarrhythmia and 157 patients with continued atrial tachyarrhythmia after PVI. The impact of acute arrhythmia termination during further substrate modification on recurrence was compared between the two groups. RESULTS: Acute termination was achieved in 51 (54.8%) patients in the induced arrhythmia group and 61 (38.9%) in the continued arrhythmia group. During a mean 35.8 months, acute termination did not significantly reduce arrhythmia recurrence in the induced arrhythmia group (HR 0.712, 95% CI 0.400-1.266, p = 0.247), while it was associated with improved outcome in the continued arrhythmia group (HR 0.590, 95% CI 0.355-0.979, p = 0.038). Acute termination of either induced atrial tachycardia (AT) or induced AF was not associated with improved procedure outcome. Among the continued arrhythmia group, the benefit of acute termination was statistically significant in AT (HR 0.329, 95% CI 0.108-0.997, p = 0.039), but not in AF (HR 0.704, 95% CI 0.396-1.253, p = 0.233) after PVI. CONCLUSIONS: Acute termination of induced rhythm is not a reliable ablation endpoint during substrate modification in patients with inducible arrhythmia after PVI.

Complications of Cardiac Perforation and Lead Dislodgement with an MRI-Conditional Pacing Lead: a Korean Multi-Center Experience.

Medtronic CapSureFix MRI 5086 pacing lead (5086; Medtronic, Inc., Minneapolis, MN, USA) has been reported to be associated with increased cardiac perforation and lead dislodgement. This study aimed to compare the incidence of cardiac perforation and lead dislodgement within 30 days after pacemaker implantation between 5086 MRI lead and previous Medtronic CapSureFix Novus 5076 non-MRI pacing lead. This was a nationwide, multicenter retrospective study in which we compared the incidence of adverse events between 277 patients implanted with 5086 lead and 205 patients implanted with 5076 lead between March 2009 and September 2014. Cardiac perforation within 30 days of pacemaker implantation occurred in 4 patients (1.4%) with the 5086 lead and in no patient with the 5076 lead (P = 0.084). Lead dislodgement occurred in 8 patients (2.9%) with the 5086 lead and in 5 patients (2.4%) with the 5076 lead (P = 0.764). On multivariate logistic regression analysis, age was significantly associated with cardiac perforation. Congestive heart failure and implantation of right atrial (RA) lead at RA free wall or septum were significant factors for the incidence of lead dislodgement and lead revision. The incidence of cardiac perforation and lead dislodgement were not statistically different between the patients with 5086 lead and the patients with 5076 lead. However, careful attention for cardiac perforation may be needed when using the 5086 MRI lead, especially in elderly patients.