Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation: An Asian Perspective.

Optimal dosing of direct oral anticoagulants (DOACs) for stroke prevention in "gray area" patients with atrial fibrillation (AF) remains a challenge for clinicians. In Asia, this is concerning in patients who are very elderly, have low body weight, and are at a high risk of bleeding. This review aims to summarize the dose reduction criteria for DOACs, discuss the evidence on dosing of DOACs across Asian regions, and collate opinions from authors across Asia. Nonrecommended dosing of DOACs is common in Asia, primarily due to the fear of bleeding, with the total clinical benefit of higher dosing being overlooked. The ELDERCARE-AF (Edoxaban Low-Dose for Elder Care-Atrial Fibrillation Patients) trial and real-world case studies provide some evidence on the use of low-dose DOACs in gray area patients. Opinions on dose adjustment guidance, concomitant medication adjustments, and therapeutic drug monitoring were collated. Research is needed to fill the evidence gaps on optimal DOAC doses for gray area patients.

Artificial intelligence-enhanced 12-lead electrocardiography for identifying atrial fibrillation during sinus rhythm (AIAFib) trial: protocol for a multicenter retrospective study.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, contributing significantly to morbidity and mortality. In a previous study, we developed a deep neural network for predicting paroxysmal atrial fibrillation (PAF) during sinus rhythm (SR) using digital data from standard 12-lead electrocardiography (ECG). The primary aim of this study is to validate an existing artificial intelligence (AI)-enhanced ECG algorithm for predicting PAF in a multicenter tertiary hospital. The secondary objective is to investigate whether the AI-enhanced ECG is associated with AF-related clinical outcomes. Methods and analysis: We will conduct a retrospective cohort study of more than 50,000 12-lead ECGs from November 1, 2012, to December 31, 2021, at 10 Korean University Hospitals. Data will be collected from patient records, including baseline demographics, comorbidities, laboratory findings, echocardiographic findings, hospitalizations, and related procedural outcomes, such as AF ablation and mortality. De-identification of ECG data through data encryption and anonymization will be conducted and the data will be analyzed using the AI algorithm previously developed for AF prediction. An area under the receiver operating characteristic curve will be created to test and validate the datasets and assess the AI-enabled ECGs acquired during the sinus rhythm to determine whether AF is present. Kaplan-Meier survival functions will be used to estimate the time to hospitalization, AF-related procedure outcomes, and mortality, with log-rank tests to compare patients with low and high risk of AF by AI. Multivariate Cox proportional hazards regression will estimate the effect of AI-enhanced ECG multimorbidity on clinical outcomes after stratifying patients by AF probability by AI. Discussion: This study will advance PAF prediction based on AI-enhanced ECGs. This approach is a novel method for risk stratification and emphasizes shared decision-making for early detection and management of patients with newly diagnosed AF. The results may revolutionize PAF management and unveil the wider potential of AI in predicting and managing cardiovascular diseases. Ethics and dissemination: The study findings will be published in peer-reviewed publications and disseminated at national and international conferences and through social media. This study was approved by the institutional review boards of all participating university hospitals. Data extraction, storage, and management were approved by the data review committees of all institutions. Clinical Trial Registration: [cris.nih.go.kr], identifier (KCT0007881).

E/e' Ratio Predicts the Atrial Pacing-Induced Left Atrial Pressure Response in Patients with Preserved Ejection Fraction.

Background and Objectives: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Materials and Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n = 204, AF group) or supraventricular tachycardia (n = 34, control group) were analyzed (male n = 183, 54 ± 12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e' (≥ 8) than in those with a low E/e' (<8). LAPR at a pacing interval of 400 ms and E/e' were positively correlated (r = 0.373, p < 0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.

Sex-Related Differences in Left Atrial Low-Voltage Areas According to CHA2DS2-VA Scores among Patients with Atrial Fibrillation.

(1) Background: We hypothesized that female sex would have a differential impact on left atrial (LA) low-voltage areas (LVAs) according to CHA2DS2-VA scores. (2) Methods: This study included 553 patients who underwent radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). LVAs were defined as regions with bipolar peak-to-peak voltages of <0.5 mV. The proportion of LVAs was calculated by dividing the total LVA by the LA surface area. (3) Results: There was no sex-related difference in LA LVAs among patients with a CHA2DS2-VA scores ≤ 2. The proportion of LVAs was significantly higher in females among patients with CHA2DS2-VA scores of 3 or 4 (10.1 (4.7−15.1)% vs. 15.8 (9.2−32.1)%; p = 0.027). Female sex was significantly associated with extensive LVAs (LVA proportion ≥ 30%). Females had odd ratios of 27.82 (95% confidence interval (CI) 3.33−756.8, p = 0.01), and 1.53 (95% CI 0.81−2.83, p = 0.184) for extensive LAVs in patients with CHA2DS2-VA scores ≥ 3 and CHA2DS2-VA scores < 3, respectively. In the multiple regression model, female patients with a CHA2DS2-VA ≥3 were significantly associated with a higher proportion of LVAs (ß = 8.52, p = 0.039). (4) Conclusions: Female sex was significantly associated with extensive LVAs, particularly when their CHA2DS2-VA scores were ≥3. This result suggests that female sex has a differential effect on the extent of LVAs based on the presence of additional risk factors.

Combined epicardial and endocardial approach for redo radiofrequency catheter ablation in patients with persistent atrial fibrillation: a randomized clinical trial.

AIMS: An epicardial approach is an effective means to detect and eliminate residual potentials in non-transmural lesions created during prior endocardial ablation. We sought to determine the impact of a combined epicardial and endocardial approach compared with a conventional endocardial approach, on recurrence-free survival after redo ablation. METHODS AND RESULTS: Participants with recurred persistent atrial fibrillation after prior endocardial ablation were randomized (1:1) to undergo treatment with the combined approach (epicardial followed by endocardial ablation) for the treatment group or conventional approach (endocardial ablation only) for the control group. The primary outcome was the time to recurrence of atrial fibrillation or atrial tachycardia following a 90-day blanking period within 12 months after the procedure. The secondary safety outcome was the occurrence of procedure-related complications within 24 h after the procedure. Of 100 randomized participants {median age, 59.0 [(interquartile range (IQR): 53.8-64.3] years, including 16% women, with one prior ablation (IQR: 1-1)}, 93 (93%) completed the trial. Events relevant to the primary outcome occurred in 16 patients in the treatment group and in 21 patients in the control group {Kaplan-Meier estimator percentages, 32 vs. 42%; hazard ratio, 0.71 [95% confidence interval (CI): 0.37-1.37]}. The periprocedural complication rate was lower in the treatment group [2 vs. 16%; odds ratio, 0.11 (95% CI: 0.00-0.87)] with similar achievement of the procedural endpoint in the two groups. CONCLUSION: In the redo procedure for persistent atrial fibrillation, the combined approach had no significant difference of recurrence-free survival and a lower procedural complication rate compared with the conventional approach.

Therapeutic implications of galectin-3 in patients with atrial fibrillation.

Atrial fibrosis can present as an arrhythmogenic substrate that is correlated with higher recurrence after catheter ablation for atrial fibrillation. Galectin-3, a beta-galactoside-binding lectin, is highly expressed and secreted from macrophages and is important in inflammation and fibrosis. We assessed the clinical implications of serum galectin-3 in patients with atrial fibrillation. This was a prospective cohort study of consecutive patients who underwent radiofrequency catheter ablation in a tertiary referral center from February 2017 to September 2017. Intracardiac blood sampling, echocardiographic measurements, magnetic resonance imaging with late gadolinium enhancement, electrophysiologic testing, and endocardial voltage mapping were consistently implemented in 75 patients before the ablation. Serum galectin-3 level was higher in patients with diabetes mellitus and was correlated with values that indicated the left atrial size. During a median 14 months of follow-up, atrial tachyarrhythmia recurred in 27% of patients. In multivariable Cox regression analysis, non-paroxysmal atrial fibrillation (hazard ratio 6.8; 95% confidence interval 1.6-28.9) and higher galectin-3 levels (hazard ratio 1.3; 95% confidence interval 1.0-1.7) were associated with increased risk of recurrence. Serum galectin-3 may be a prognostic biomarker for risk stratification in patients with atrial fibrillation planned catheter ablation.

Association of Depression With Atrial Fibrillation in South Korean Adults.

Importance: The risk of atrial fibrillation (AF) in people with depression is not fully known. Depression is associated with sympathetic activation and emotional stress, which might increase the risk of new-onset AF. Objective: To assess the incidence of new-onset AF in those with and without depression using data from a nationwide health care database. Design, Setting, and Participants: This cohort study obtained data from the Korean National Health Insurance Service database and enrolled people who underwent a nationwide health checkup in 2009. People younger than 20 years and those with a history of heart valve surgery, previous diagnosis of mitral stenosis, or who were diagnosed with AF between January 1, 2002 and December 31, 2008 were excluded. The risk of new-onset AF (occurring between 2009 and 2018) was compared in people who were and were not diagnosed with depression within a year before the 2009 nationwide health checkup. Data were analyzed between August 1, 2020 and October 31, 2020. Exposure: Previous diagnosis of depression. Main Outcomes and Measures: Cumulative incidence and risk of new-onset AF between 2009 and 2018 in participants with and without depression. Kaplan-Meier analysis was conducted to assess incidence of AF, and Cox proportional hazards regression was used to calculate adjusted and unadjusted hazard ratios (HRs) and 95% CIs. Results: A total of 5 031 222 individuals with a mean (SD) age of 46.99 (14.06) years (2 771 785 men [55.1%]) were included in the analysis; of these individuals, 148 882 (3.0%) had a diagnosis of depression in the year before the 2009 health checkup and 4 882 340 (97%) did not. People with depression vs those without depression were older (aged 56.7 vs 46.7 years) and more likely to be women (96 472 [64.8%] vs 2 162 965 [44.3%]). Prevalence of hypertension, diabetes, dyslipidemia, and heart failure was higher in the depression group. The cumulative incidence of new-onset AF was significantly higher in people with depression vs without depression in the Kaplan-Meier analysis and showed steady divergence throughout 10 years of follow-up (cumulative incidence, 4.44% vs 1.92%; log-rank P < .001). After adjusting for covariates, depression was associated with a 25.1% increased risk of new-onset AF (HR, 1.25; 95% CI, 1.22-1.29; P < .001). People with recurrent episodes of depression showed even higher risk of new-onset AF (HR, 1.32; 95% CI, 1.27-1.37; P < .001). Young age and female sex had significant interactions with depression, which suggests that young people and women with depression may have an increased risk of new-onset AF. Conclusions and Relevance: This study found that depression was associated with a significantly increased cumulative incidence and risk of new-onset AF. Recurrent episodes of depression were associated with even higher risk. These findings suggest the need for adequate screening for AF in people with depression, particularly in younger people and women.

Unipolar and bipolar electrogram characteristics of recurrent cases of idiopathic ventricular arrhythmias undergoing repeat catheter ablation.

INTRODUCTION: Activation mapping guided catheter ablation (CA) of ventricular arrhythmias (VAs) is limited in some cases when it is only relied on bipolar electrogram (EGM). We hypothesized that activation mapping with use of combined bipolar and unipolar EGM facilitates to identify the focal origin of VAs and results in reduction of recurrence rate of CA of VAs. METHODS: We analyzed the data of patients undergoing repeat ablations for idiopathic out-flow tract VAs. The EGM of the 1 st and 2 nd ablations were compared for earliest local activation time (LAT), presence of discrete potentials, and polarity reversal, unipolar potential morphology (QS or non-QS), potential amplitude and activation slope. RESULTS: Thirty-seven patients were included. The Local activation time was significantly earlier in the 2nd ablation as compared to the 1st procedure (36.90 msec vs 31.85 msec, P < 0.01). The incidence of discrete potentials and polarity reversal were similar in both procedures (51% vs 57%, P = 0.8 and 62% in both the occasions, respectively). The unipolar voltage was similar in both occasions (6.94 mV vs 7.22 mV in repeat ablations, P = 0.7). The recurrence rate (5.7%) was significantly lower with routine use of combined unipolar and bipolar EGMs, as compared to the use of bipolar EGM alone (16.7%) CONCLUSIONS: Use of both bipolar and unipolar electrograms helps in better delineation of the sites of earliest activation for effective ablation of VAs. Use of unipolar electrograms in addition to bipolar electrograms is associated with lower long term recurrence rate.

The Impact of Personal Thoracic Impedance on Electrical Cardioversion in Patients with Atrial Arrhythmias.

Background and Objectives: Direct current cardioversion (DCCV) is a safe and useful treatment for atrial tachyarrhythmias. In the past, the energy delivered in DCCV was decided upon empirically, based only on the type of tachyarrhythmia. This conventional method does not consider individual factors and may lead to unnecessary electrical damage. Materials and Methods: We performed DCCV in patients with atrial tachyarrhythmias. The impedance and electrical current at the moment of shock were measured. The human thoracic impedance between both defibrillator patches and the electric current that was used were measured. Results: A total of 683 DCCVs were performed on 466 atrial tachyarrhythmia patients. The average impedance was 64 ± 11 Ω and the average successful current was 23 ± 6 mA. The magnitude of the electrical current that was successful depended upon the human impedance (linear regression, B = -0.266, p < 0.001) and the left atrial diameter (B = 0.092, p < 0.001). Impedance was directly proportional to body mass index (BMI) (B = 1.598, p < 0.001) and was higher in females than in males (77 ± 15 Ω vs. 63 ± 11 Ω, p < 0.001). Notably, the high-impedance (>70 Ω) group had a higher BMI (27 ± 4 kg/m2 vs. 25 ± 3 kg/m2, p < 0.001) and a higher proportion of females (37% vs. 9%, p < 0.001) than the low-impedance group (<70 Ω). However, thoracic impedance was not an independent predictor for successful DCCV. Conclusions: Human thoracic impedance was one of the factors that impacted the level of electrical current required for successful DCCV in patients with atrial arrhythmias. In the future, it will be helpful to consider individual predictors, such as BMI and gender, to minimize electrical damage during DCCV.

Non-genetic risk factors for atrial fibrillation are equally important in both young and old age: A nationwide population-based study.

AIMS: There are several non-genetic risk factors for new-onset atrial fibrillation, including age, sex, obesity, hypertension, diabetes, and alcohol consumption. However, whether these non-genetic risk factors have equal significance among different age groups is not known. We performed a nationwide population-based analysis to compare the clinical significance of non-genetic risk factors for new-onset atrial fibrillation in various age groups. METHODS AND RESULTS: A total of 9,797,409 people without a prior diagnosis of atrial fibrillation who underwent a national health check-up in 2009 were included. During 80,130,090 person-years of follow-up, a total of 196,136 people were diagnosed with new-onset atrial fibrillation. The impact of non-genetic risk factors on new-onset atrial fibrillation was examined in different age groups. Obesity, male sex, heavy alcohol consumption, smoking, hypertension, diabetes and chronic kidney disease were associated with an increased risk of new-onset atrial fibrillation. With minor variations, these risk factors were consistently associated with the risk of new-onset atrial fibrillation among various age groups. Using these risk factors, we created a scoring system to predict future risk of new-onset atrial fibrillation in different age groups. In receiver operating characteristic curve analysis, the predictive value of these risk factors ranged between 0.556 and 0.603, and no significant trends were observed. CONCLUSIONS: Non-genetic risk factors for new-onset atrial fibrillation may have a similar impact on different age groups. Except for sex, these non-genetic risk factors can be modifiable. Therefore, efforts to control non-genetic risk factors might have relevance for both the young and old.

A novel predictive model for late recurrence after catheter ablation for atrial fibrillation using left appendage volume measured by cardiac computed tomography.

Larger left atrial appendage (LAA) volume is associated with a higher risk of late recurrence (LR) in patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). However, it is unclear whether LAA volume predicts LR, independent of established risk factors. We sought to evaluate the value of LAA volume in predicting LR after RFCA for AF and to develop a score prediction model including LAA volume for these patients. We retrospectively studied 992 patients who underwent RFCA for AF and cardiac computed tomography before RFCA at a single center. At 3 years after RFCA, 362 patients (36.5 %) experienced recurrence. The multivariate Cox regression model showed that age ≥ 75 years (10 points), non-paroxysmal AF (9 points), diabetes mellitus (4 points), left atrial volume index (1 point per 10 ml/m2 rounded to the nearest integer), and the second (4.7 to < 7 ml/m2; 4 points) and third (≥ 7 ml/m2; 5 points) tertiles of the LAA volume index were independent risk factors LR. The above-mentioned risk factors were included in the integrated score model, and the C-index of the proposed score model was 0.715 (95 % confidence interval [CI] 0.679-0.752). LAA volume is an independent predictor of LR and the predictive model including LAA volume showed good discrimination power. These findings provide evidence for the inclusion of LAA volume in the risk stratification for AF recurrence in patients undergoing RFCA for AF.

Impact of carotid atherosclerosis in CHA2DS2-VASc-based risk score on predicting ischemic stroke in patients with atrial fibrillation.

BACKGROUND/AIMS: Vascular disease is an established risk factor for stroke in patients with atrial fibrillation (AF), which is included in CHA2DS2-VASc score. However, the role of carotid atherosclerosis remains to be determined. METHODS: Three hundred-ten patients with AF who underwent carotid sonography were enrolled. RESULTS: During a median follow-up of 31 months, 18 events (5.8%) of stroke were identified. Patients with stroke had higher carotid intima-media thickness (CIMT) (1.16 ± 0.33 mm vs. 0.98 ± 0.25 mm, p = 0.017). CIMT was significantly increased according to the CHA2DS2-VASc score (p < 0.001) and it was correlated with left ventricular mass index and early diastolic mitral annular velocity (e'), a ratio of early transmitral flow velocity to e' (E/e') and pulmonary artery systolic pressure (all p < 0.05). Cox regression using multivariate models showed that carotid plaque was associated with the risk of stroke (hazard ratio, 3.748; 95% confidence interval [CI], 1.107 to 12.688; p = 0.034). C-statistics increased from 0.648 (95% CI, 0.538 to 0.757) to 0.716 (95% CI, 0.628 to 0.804) in the CHA2DS2-VASc score model after the addition of CIMT and carotid plaque as a vascular component (p = 0.013). CONCLUSION: Increased CIMT and presence of carotid plaque are associated with a high risk of ischemic stroke, and CIMT is related to myocardial remodeling and diastolic dysfunction, suggesting that carotid atherosclerosis can improve risk prediction of stroke in patients with AF, when included under vascular disease in the CHA2DS2-VASc scoring system.

Right bundle branch block-type wide QRS complex tachycardia with a reversed R/S complex in lead V6: Development and validation of electrocardiographic differentiation criteria.

BACKGROUND: Differentiation of supraventricular tachycardia (SVT) with a right bundle branch block (RBBB) pattern from ventricular tachycardia (VT) is difficult, particularly when the R/S ratio in lead V6 is below 1.0. OBJECTIVE: We sought to investigate the electrocardiographic criteria for distinguishing between these arrhythmias. METHODS: We investigated electrocardiographic parameters from 111 consecutive patients who had RBBB pattern wide QRS complex tachycardia with a reversed R/S ratio in lead V6 (72 VTs, 39 SVTs). Diagnostic criteria from the previous algorithms were compared with our new criterion, the RS/QRS ratio, which was defined as the ratio of the interval from the onset of the QRS complex to the nadir of the S wave, divided by the QRS width in lead V6. The RS/QRS ratio was further tested in a prospective population (31 fascicular VTs, 29 SVTs). RESULTS: The diagnostic accuracy of previous criteria (Brugada algorithm, Vereckei algorithm, and R-wave peak time criterion) was only modest. However, the RS/QRS ratio in lead V6 was significantly lower in SVT than in VT (0.36 ± 0.04 vs 0.50 ± 0.08; P < .001). A cutoff value of the RS/QRS ratio >0.41 differentiated VT from SVT with a high diagnostic accuracy (sensitivity 97.2%; specificity 89.7%). When tested in a prospective population with fascicular VT, the diagnostic accuracy of the criteria was maintained (sensitivity 90.3%; specificity 86.2%). CONCLUSION: The RS/QRS ratio >0.41 in lead V6 is a simple and reliable index for distinguishing VT from SVT in RBBB pattern wide QRS complex tachycardia with a reversed R/S complex in lead V6. This criterion was particularly useful for the differential diagnosis of fascicular VT from RBBB pattern SVT.

Incidence and etiology of sudden cardiac arrest in Koreans: A cohort from the national health insurance service database.

The incidence of sudden cardiac arrest (SCA) in Asians is lower than that seen in Western populations, but there are few available data on the incidence and associated cardiac etiology of SCA in Asians. From 2002 to 2013, patients with SCA were analyzed using a cohort from the South Korean National Health Insurance Service (NHIS) coded database. Sudden unexplained death syndrome (SUDS) was defined as cryptogenic arrest, excluding that of non-cardiac origin, coronary artery disease (CAD), cardiomyopathy (CM), and valvular heart disease. During the 12-year study period, 5,973 patients (0.53%) from the total cohort of 1,125,691 had a cardiac arrest code. The overall incidence of arrest was 48.7 per 100,000 person-years (95% CI 16.6-18.0). The incidence of primary SCA excluding those of non-cardiac origin was 16.1 per 100,000 person-years (95% CI 15.4-16.8). It was higher in males than in females (18.1 vs. 14.1 per 100,000 person-years). CAD was the most common cause of SCA (59.4%), and followed by CM (13.9%). SUDS accounted for 14.7% of SCA events. The risk of SCA had increased gradually from over 25 years old. Heart failure, atrial fibrillation and hypertension are major factors associated with SCA incidence. Our findings outline epidemiologic data for SCA and the proportion of associated cardiac etiology leads SCA in a large population.

Association of left atrial pressure with late gadolinium enhancement extent in patient who underwent catheter ablation for atrial fibrillation.

Atrial remodeling with fibrosis has been well-described in patients with atrial fibrillation (AF). We hypothesized that the left atrial (LA)-late gadolinium enhancement (LGE) extent on cardiac magnetic resonance (CMR) imaging is associated with LA pressure and can be a marker for suitable candidates for non-paroxysmal AF ablation. A total of 173 AF patients with an LA-LGE area on CMR imaging were enrolled. The clinical parameters, including invasively measured LA pressure, were compared between the patients with extensive LA-LGE (E-LGE, LGE extent ≥ 20%, n = 78) and those with small LA-LGE (S-LGE, LGE extent < 20%, n = 95). The E-LGE group had higher peak LA pressures than the S-LGE group (23 versus 19 mmHg, p < 0.001). The E-LGE group had more patients with non-paroxysmal AF (non-PAF) (51% vs. 34%), heart failure (9% vs. 0%), and higher NT pro-B-type natriuretic peptide (472 vs. 265 pg/ml) (all p < 0.05). LA pressure ≥ 21 mmHg was an independent predictor of E-LGE (OR = 2.218; p = 0.019). In the paroxysmal AF (PAF) subgroup, freedom from atrial arrhythmia after catheter ablation was not different (81% vs 86%, log-rank p = 0.529). However, in the non-PAF subgroup, it was significantly higher in the S-LGE group than in the E-LGE group (81% vs 55%, log-rank p = 0.014). Increased LA pressure was related to the LA-LGE extent. LA-LGE was a good predictor of outcome after catheter ablation, but only in patients with non-PAF.

Slit-based irrigation catheters can reduce procedure-related ischemic stroke in atrial fibrillation patients undergoing radiofrequency catheter ablation.

Open irrigation ablation catheters are now the standard in radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Among various irrigation catheters, laser-cut slit-based irrigation system (Cool Flex and FlexAbility) has a unique design to cool the catheter tip more efficiently. We aimed to assess the safety of slit-based irrigation catheters regarding prevention of procedure-related ischemic complication in AF patients undergoing RFCA. The analysis was performed with Korea University Medicine Anam Hospital RFCA registry. Procedure-related ischemic complication was defined as ischemic stroke or transient ischemic attack (TIA) occurring within 30 days after RFCA. Patients were divided into 3 groups: non-irrigation, hole-based irrigation, and slit-based irrigation catheter groups. A total of 3,120 AF patients underwent first RFCA. Non-irrigation, non-slit-based irrigation, and slit-based irrigation catheters were used in 290, 1,539, and 1,291 patients, respectively. As compared with non-irrigation and non-slit-based irrigation catheter groups, slit-based irrigation catheter group had significantly older age, higher prevalence of non-paroxysmal AF, large left atrial size, and decreased left atrial appendage flow velocity. The CHA2DS2-VASc score was not different among the 3 groups. Procedure-related ischemic complication occurred in 17 patients (0.54%) with 16 ischemic strokes and 1 TIA event: 5/290 (1.72%), 11/1,539 (0.71%), and 1/1,291 (0.08%) events in non-irrigation, non-slit-based irrigation, and slit-based irrigation catheter groups, respectively (p = 0.001). Slit-based irrigation catheter was superior in direct comparison with non-slit-based irrigation catheter (0.71% vs. 0.08%; p = 0.009). Slit-based irrigation catheters were highly effective in preventing procedure-related ischemic complications.

Atrial Substrate Underlies the Recurrence after Catheter Ablation in Patients with Atrial Fibrillation.

Prediction of recurrences after catheter ablation of atrial fibrillation (AF) remains challenging. We sought to investigate the long-term outcomes after AF catheter ablation. A total of 2221 consecutive patients who underwent catheter ablation for symptomatic AF were included in this study (mean age 55 ± 11 years, 20.3% women, and 59.0% paroxysmal AF). Extensive ablation, in addition to circumferential pulmonary vein isolation, was more often accomplished in patients with non-paroxysmal AF than in those with paroxysmal AF (87.4% vs. 25.3%, p < 0.001). During a median follow-up of 54 months, sinus rhythm (SR) was maintained in 67.1% after index procedure. After redo procedures in 418 patients, 83.3% exhibited SR maintenance. Recurrence rates were similar for single and multiple procedures (17.4% vs. 16.7%, p = 0.765). Subanalysis showed that the extent of late gadolinium enhancement (LGE), as assessed by cardiac magnetic resonance, is greater in patients with recurrence than in those without recurrence (36.2 ± 23.9% vs. 21.8 ± 13.7%, p < 0.001). Cox-regression analysis revealed that non-paroxysmal AF (hazard ratio (HR) 2.238, 95% confidence interval (CI) 1.905-2.629, p < 0.001), overweight (HR 1.314, 95% CI 1.107-1.559, p = 0.020), left atrium dimension ≥ 45 mm (HR 1.284, 95% CI 1.085-1.518, p = 0.004), AF duration (HR 1.020 per year, 95% CI 1.006-1.034, p = 0.004), and LGE ≥ 25% (HR 1.726, 95% CI 1.330-2.239, p < 0.001) are significantly associated with AF recurrence after catheter ablation. This study showed that repeated catheter ablation improves the clinical outcomes of patients with non-paroxysmal AF, suggesting that AF substrate based on LGE may underpin the mechanism of recurrence after catheter ablation.

Management of Atrio-esophageal Fistula Induced by Radiofrequency Catheter Ablation in Atrial Fibrillation Patients: a Case Series.

Atrio-esophageal fistula (AEF) is one of the most devastating complication of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) and surgical repair is strongly recommended. However, optimal surgical approach remains to be elucidated. We retrospectively reviewed AEF cases that occurred after RFCA in a single center and evaluated the clinical results of different surgical approach. Surgical or endoscopic repair was attempted in five AF patients who underwent RFCA. Atrio-esophageal fistula and mediastinal infection was not controlled in the patient who underwent endoscopic repair eventually died. Lethal cerebral air embolism occurred two days after surgery in a patient who underwent esophageal repair only. Primary surgical repair of both the left atrium (LA) and esophagus was performed in the remaining three patients. Among these three patients, two underwent external LA repair and the remaining had internal LA repair via open-heart surgery. External repair of the LA was unsuccessful and one patient dies and another had to undergo second operation with internal repair of the LA. The patient who underwent internal LA repair during the first operation survived without additional surgery. Furthermore, we applied veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with artificial induction of ventricular fibrillation in this patient to prevent air and septic embolism and she had no neurologic sequelae. In summary, surgical correction can be considered preferentially to correct AEF. Open-heart surgical repair of LA from the internal side seems to be an acceptable surgical method. Application of VA-ECMO with artificial induction of ventricular fibrillation might be effective to prevent air and septic embolism.

Molecular Signatures of Sinus Node Dysfunction Induce Structural Remodeling in the Right Atrial Tissue.

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-ß (TGF-ß) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-ß-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

Effectiveness and Safety of Off-label Dosing of Non-vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients.

Non-vitamin K antagonist anticoagulants (NOACs) have been used to prevent thromboembolism in patients with atrial fibrillation (AF) and shown favorable clinical outcomes compared with warfarin. However, off-label use of NOACs is frequent in practice, and its clinical results are inconsistent. Furthermore, the quality of anticoagulation available with warfarin is often suboptimal and even inaccurate in real-world data. We have therefore compared the effectiveness and safety of off-label use of NOACs with those of warfarin whose anticoagulant intensity was accurately estimated. We retrospectively analyzed data from 2,659 and 3,733 AF patients at a tertiary referral center who were prescribed warfarin and NOACs, respectively, between 2013 and 2018. NOACs were used at off-label doses in 27% of the NOAC patients. After adjusting for significant covariates, underdosed NOAC (off-label use of the reduced dose) was associated with a 2.5-times increased risk of thromboembolism compared with warfarin, and overdosed NOAC (off-label use of the standard dose) showed no significant difference in either thromboembolism or major bleeding compared with warfarin. Well-controlled warfarin (TTR ≥ 60%) reduced both thromboembolism and bleeding events. In conclusion, the effectiveness of NOACs was decreased by off-label use of the reduced dose.