The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis-a nationwide cohort study.

BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Lower contact force predicts right pulmonary vein carina breakthrough after ablation index-guided pulmonary vein isolation using high-power short-duration.

INTRODUCTION: Carina breakthrough (CB) at the right pulmonary vein (RPV) can occur after circumferential pulmonary vein isolation (PVI) due to epicardial bridging or transient tissue edema. High-power short-duration (HPSD) ablation may increase the incidence of RPV CB. Currently, the surrogate of ablation parameters to predict RPV CB is not well established. This study investigated predictors of RPV CB in patients undergoing ablation index (AI)-guided PVI with HPSD. METHODS: The study included 62 patients with symptomatic atrial fibrillation (AF) who underwent AI-guided PVI using HPSD. Patients were categorized into two groups based on the presence or absence of RPV CB. Lesions adjacent to the RPV carina were assessed, and CB was confirmed through residual voltage, low voltage along the ablation lesions, and activation wavefront propagation. RESULTS: Out of the 62 patients, 21 (33.87%) experienced RPV CB (Group 1), while 41 (66.13%) achieved first-pass RPV isolation (Group 2). Despite similar AI and HPSD, patients with RPV CB had lower contact force (CF) at lesions adjacent to the RPV carina. Receiver operating characteristic (ROC) curve analysis identified CF < 10.5 g as a predictor of RPV CB, with 75.7% sensitivity and 56.2% specificity (area under the curve: 0.714). CONCLUSION: In patients undergoing AI-guided PVI with HPSD, lower CF adjacent to the carina was associated with a higher risk of RPV CB. These findings suggest that maintaining higher CF during ablation in this region may reduce the occurrence of RPV CB.

Feasibility of Auto-Quantified Epicardial Adipose Tissue in Predicting Atrial Fibrillation Recurrence After Catheter Ablation.

BACKGROUND: The aim of this study was to build an auto-segmented artificial intelligence model of the atria and epicardial adipose tissue (EAT) on computed tomography (CT) images, and examine the prognostic significance of auto-quantified left atrium (LA) and EAT volumes for AF.Methods and Results: This retrospective study included 334 patients with AF who were referred for catheter ablation (CA) between 2015 and 2017. Atria and EAT volumes were auto-quantified using a pre-trained 3-dimensional (3D) U-Net model from pre-ablation CT images. After adjusting for factors associated with AF, Cox regression analysis was used to examine predictors of AF recurrence. The mean (±SD) age of patients was 56±11 years; 251 (75%) were men, and 79 (24%) had non-paroxysmal AF. Over 2 years of follow-up, 139 (42%) patients experienced recurrence. Diabetes, non-paroxysmal AF, non-pulmonary vein triggers, mitral line ablation, and larger LA, right atrium, and EAT volume indices were linked to increased hazards of AF recurrence. After multivariate adjustment, non-paroxysmal AF (hazard ratio [HR] 0.6; 95% confidence interval [CI] 0.4-0.8; P=0.003) and larger LA-EAT volume index (HR 1.1; 95% CI 1.0-1.2; P=0.009) remained independent predictors of AF recurrence. CONCLUSIONS: LA-EAT volume measured using the auto-quantified 3D U-Net model is feasible for predicting AF recurrence after CA, regardless of AF type.

Characterization and identification of atrial fibrillation drivers in patients with nonparoxysmal atrial fibrillation using simultaneous amplitude frequency electrogram transform.

INSTRUCTION: We hypothesized that real-time simultaneous amplitude frequency electrogram transform (SAFE-T) during sinus rhythm (SR) is able to identify and characterize the drivers of atrial fibrillation (AF) in nonparoxysmal (NP) AF. METHODS: Twenty-one NPAF patients (85.71% males, mean age 52 years old) underwent substrate mapping during SR (SAFE-T and voltage) and during AF (complex fractionated atrial electrograms [CFAE] and similarity index [SI]). After pulmonary veins isolation, extensive substrate ablation was performed with the endpoint of procedural termination or elimination of all SI sites (>63% similarities). Sites with procedural termination and non-termination sites were tagged for postablation SR analysis using SAFE-T. RESULTS: In 74 CFAE sites identified (average of 3 ± 2 sites per person), 28 (37.84%) were identified as termination sites demonstrating a high SI compared with the non-termination sites (80.11 ± 9.57% vs. 45.96 ± 13.38%, p < .001) during AF. During SR, these termination sites have high SAFE-T values and harbor a highly resonant, localized, repetitive high frequency components superimposed in the low frequency components compared with non-termination sites (5.70 ± 3.04 vs. 1.49 ± 1.66 Hz·mV, p < .001). In the multivariate analysis, the termination sites have higher SAFE-T and SI value (p < .001). CONCLUSION: AF procedural termination sites harbored signal characteristics of repetitive, high frequency component of individualized electrogram during SR, which can be masked by the low frequency fractionated electrogram and are difficult to see from the bipolar electrogram. Thus, SAFE-T mapping is feasible in identifying and characterizing sites of AF drivers.

Insight of electrocardiographic and electrophysiological parameters on the left ventricular function in patients with ventricular arrhythmia from left ventricular summit.

INTRODUCTION: Ventricular arrhythmia (VA) commonly originate from the left ventricular summit (LVS) and results in left ventricular (LV) dysfunction in some patients; however, factors related to LV cardiomyopathy have not been well elucidated. Therefore, this study aimed to investigate the risk factors for LV cardiomyopathy and the outcomes of patients with LVS VA. METHODS: Between 2013 and 2018, a total of 139 patients (60.7% men; mean age 53.2 ± 13.9 years old) underwent catheter ablation for LVS VA in two centers. Detailed patient demographics, electrocardiograms, electrophysiological characteristics, and clinical outcomes were analyzed. LV cardiomyopathy was defined as left ventricular ejection fraction (LVEF) <50%. RESULTS: Acute procedural success was achieved in 92.8% of patients. There were 40 patients (28.8%) with LV cardiomyopathy, and the mean LVEF improved from 37.5 ± 9.3% to 48.5 ± 10.2% after ablation (p < .001). After multivariate analysis, the independent factors of LV dysfunction were wider QRS duration (QRSd) of the VA (odds ratio [OR] 1.02; 95% confidence interval [CI]: 1.00-1.04; p = .046) and the absolute earliest activation time discrepancy (AEAD) between epicardium and endocardium (OR 1.05; 95% CI: 1.00-1.09; p = .048). After ablation, the LV function was completely recovered in 20 patients (50%). The factors for LV dysfunction without recovery included wider premature ventricular complex (PVC) QRSd (OR 1.09; 95% CI: 1.02-1.17; p = .012) and poorer LVEF (OR 0.85; 95% CI: 0.74-0.97; p = .020). CONCLUSION: In patients with VA from the LVS, PVC QRSd and AEAD are factors associated with deteriorating LV systolic function. Catheter ablation can reverse LV remodeling. Narrower QRSd and better LVEF are associated with better recovery of LV function after ablation.

Factors predicting the progression from paroxysmal to persistent atrial fibrillation despite an index catheter ablation.

INTRODUCTION: Despite undergoing an index ablation, some patients progress from paroxysmal atrial fibrillation (PAF) to persistent AF (PersAF), and the mechanism behind this is unclear. The aim of this study was to investigate the predictors of progression to PersAF after catheter ablation in patients with PAF. METHODS: This study included 400 PAF patients who underwent an index ablation between 2015 and 2019. The patients were classified into three groups based on their outcomes: Group 1 (PAF to sinus rhythm, n = 226), Group 2 (PAF to PAF, n = 146), and Group 3 (PAF to PersAF, n = 28). Baseline and procedural characteristics were collected, and predictors for AF recurrence and progression were evaluated. RESULTS: The mean age of the patients was 58.4 ± 11.1 years, with 272 males. After 3 years of follow-up, 7% of the PAF cases recurred and progressed to PersAF despite undergoing an index catheter ablation. In the multivariable analysis, a larger left atrial (LA) diameter and the presence of non-pulmonary vein (PV) triggers during the index procedure independently predicted recurrence. Moreover, a larger LA diameter, the presence of non-PV triggers, and a history of thyroid disease independently predicted AF progression. CONCLUSION: The progression from PAF to PersAF after catheter ablation is associated with a larger LA diameter, history of thyroid disease, and the presence of non-PV triggers. Meticulous preprocedural evaluation, patient selection, and comprehensive provocation tests during catheter ablation are recommended.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients without previous oral anticoagulants or stable under warfarin: a nationwide cohort study.

AIMS: Investigations on non-VKA oral anticoagulants (NOACs) for atrial fibrillation (AF) patients without taking any oral anticoagulants (OACs) or staying well on warfarin were limited. We aimed to investigate the associations between stroke prevention strategies and clinical outcomes among AF patients who were previously well without taking any OACs or stayed well on warfarin for years. METHODS AND RESULTS: The retrospective analysis included a total of 54 803 AF patients who did not experience an ischaemic stroke or intra-cranial haemorrhage (ICH) for years after AF was diagnosed. Among these patients, 32 917 patients who did not receive OACs were defined as the 'original non-OAC cohort' (group 1), and 8007 patients who continuously received warfarin were defined as the 'original warfarin cohort' (group 2). In group 1, compared to non-OAC, warfarin showed no significant difference in ischaemic stroke (aHR 0.979, 95%CI 0.863-1.110, P = 0.137) while those initiated NOACs were associated with lower risk (aHR 0.867, 95%CI 0.786-0.956, P = 0.043). When compared to warfarin, the composite of 'ischaemic stroke or ICH' and 'ischaemic stroke or major bleeding' was significantly lower in the NOAC initiator with an aHR of 0.927 (95%CI 0.865-0.994; P = 0.042) and 0.912 (95%CI 0.837-0.994; P < 0.001), respectively. In group 2, when compared to warfarin, those shifted to NOACs were associated with a lower risk of ischaemic stroke (aHR 0.886, 95%CI 0.790-0.993, P = 0.002) and major bleeding (aHR 0.849, 95%CI 0.756-0.953, P < 0.001). CONCLUSIONS: The NOACs should be considered for AF patients who were previously well without taking OACs and those who were free of ischaemic stroke and ICH under warfarin for years.

Comparison of Long-Term Clinical Outcomes Between Segmental and Circumferential Pulmonary Vein Isolation in Patients Undergoing Repeat Atrial Fibrillation Ablation.

BACKGROUND: Circumferential pulmonary vein isolation (CPVI) has supplanted segmental PVI (SPVI) as standard procedure for atrial fibrillation (AF). However, there is limited evidence examining the efficacy of these strategies in redo ablations. In this study, we investigated the difference in recurrence rates between SPVI and CPVI in redo ablations for PV reconnection.Methods and Results: This study retrospectively enrolled 543 patients who had undergone AF ablation between 2015 and 2017. Among them, 167 patients (30.8%, including 128 male patients and 100 patients with paroxysmal AF) underwent redo ablation for recurrent AF. Excluding 26 patients without PV reconnection, 141 patients [90 patients of SPVI (Group 1) and 51 patients of CPVI (Group 2)] were included. The AF-free survival rates were 53.3% and 56.9% in Group 1 and Group 2, respectively (P=0.700). The atrial flutter (AFL)-free survival rates were 90% and 100% in Group 1 and Group 2, respectively (P=0.036). The ablation time was similar between groups, and there no major complications were observed. CONCLUSIONS: For redo AF ablation procedures, SPVI and CPVI showed similar outcomes, except for a higher AFL recurrence rate for SPVI after long-term follow-up (>2 years). This may be due to a higher probability of residual PV gaps causing reentrant AFL.

Fractal complexity alternations in paroxysmal atrial fibrillation patients with and without recurrence after pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. METHODS: Twenty-five drug-refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1-3, and 6-12 months after PVI. After 8.2 ± 2.5 months of follow-ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non-recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). RESULTS: The non-recurrence group, but not the recurrence group, had decreased high-frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1-3 months after PVI and increased DFAslope2 6-12 months after PVI. The non-recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1-3 and 6-12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. CONCLUSIONS: Significantly reduced vagal tone 1-3 months after PVI, increased long-term fractal complexity 6-12 months after PVI, and decreased sympathetic tone as well as short-term fractal complexity 1-3 and 6-12 months after PVI led to a better AF-free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.

Shared decision making for anticoagulation reduces anxiety and improves adherence in patients with atrial fibrillation.

BACKGROUND: Treatment with oral anticoagulants (OACs) could prevent stroke in atrial fibrillation (AF), but side effects developed due to OACs may cause patients anxiety during decision making. This study aimed to investigate whether shared decision making (SDM) reduces anxiety and improves adherence to stroke prevention measures in patients with AF. METHODS: A one-group pretest-posttest design using a questionnaire survey was applied at the outpatient cardiology clinic between July 2019 until September 2020. A Patient Decision Aid (PDA) tool was used for the completion of the questionnaire survey after health education and counseling. Ten questions were included for patients' recognition of SDM, and a 5-point scoring method was used, where "very much" was scored as 5 points, and "totally not" was scored as 1 point. RESULTS: Fifty-two patients with AF were enrolled. In terms of patients' recognition of SDM, points of more than 4.17 out of 5 were noted, indicating recognition above the level of "very much." The patients' anxiety scores before SDM were 3.56 (1.2), with a decrease of 0.64 points (p < 0.001) to 2.92 (1.3) after SDM. After SDM, the number of patients who decided to take OAC increased from 76.9% to 88.5%, and the 15.4% answering "unclear" decreased to 1.9% (p = 0.006). The patients' anxiety levels after SDM were associated with gender (p = 0.025). CONCLUSIONS: The approach using SDM enhanced our understanding of the pros and cons of OAC treatment and, in patients with AF, decreased anxiety about therapeutic decisions and increased willingness to accept treatment options.

Comparison of efficacy of pulmonary vein isolation between cryoballoon ablation and high-power short-duration ablation.

BACKGROUND: High-power short-duration (HPSD) and cryoballoon ablation (CBA) has been used for pulmonary vein isolation (PVI). OBJECTIVE: We aimed to compare the efficacy of PVI between CBA and HPSD ablation in patients with paroxysmal atrial fibrillation (PAF). METHODS: We retrospectively analyzed 251 consecutive PAF patients from January 2018 to July 2020. Of them, 124 patients (mean age 57.2 ± 10.1 year) received HPSD and 127 patients (mean age 59.6 ± 9.4 year) received CBA. In HPSD group, the radiofrequency energy was set as 50 W/10 s at anterior wall and 40 W/10 s at posterior wall. In CBA group, 28 mm s generation cryoballoon was used for PVI according the guidelines. RESULTS: There was no significant difference in baseline characteristics between these 2 groups. The time to achieve PVI was significantly shorter in cryoballoon ablation group than in HPSD group (20.6 ± 1.7 min vs 51.8 ± 36.3, P = 0.001). The 6-month overall recurrence for atrial tachyarrhythmias was not significantly different between the two groups (HPSD:14.50% vs CBA:11.0%, P = 0.40). There were different types of recurrent atrial tachyarrhythmia between these 2 groups. Recurrence as atrial flutter was significantly more common in CBA group compared to HPSD group (57.1% vs 12.5%, P = 0.04). CONCLUSION: In PAF patients, CBA and HPSD had a favourable and comparable outcome. The recurrence pattern was different between CBA and HPSD groups.

Application of Ensite™ LiveView function for identification of scar-related ventricular tachycardia isthmus.

INTRODUCTION: Dynamic display of real-time wavefront activation pattern may facilitate the recognition of reentrant circuits, particularly the diastolic path of ventricular tachycardia (VT). OBJECTIVE: We aimed to evaluate the feasibility of LiveView Dynamic Display for mapping the critical isthmus of scar-related reentrant VT. METHODS: Patients with mappable scar-related reentrant VT were selected. The characteristics of the underlying substrates and VT circuits were assessed using HD grid multielectrode catheter. The VT isthmuses were identified based on the activation map, entrainment, and ablation results. The accuracy of the LiveView findings in detecting potential VT isthmus was assessed. RESULTS: We studied 18 scar-related reentrant VTs in 10 patients (median age: 59.5 years, 100% male) including 6 and 4 patients with ischemic and nonischemic cardiomyopathy, respectively. The median VT cycle length was 426 ms (interquartile range: 386-466 ms). Among 590 regional mapping displays, 92.0% of the VT isthmus sites were identified by LiveView Dynamic Display. The accuracy of LiveView for isthmus identification was 84%, with positive and negative predictive values of 54.8% and 97.8%, respectively. The area with abnormal electrograms was negatively correlated with the accuracy of LiveView Dynamic Display (r = -.506, p = .027). The median time interval to identify a VT isthmus using LiveView was significantly shorter than that using conventional activation maps (50.5 [29.8-120] vs. 219 [157.5-400.8] s, p = .015). CONCLUSION: This study demonstrated the feasibility of LiveView Dynamic Display in identifying the critical isthmus of scar-related VT with modest accuracy.

Long-term mortality and cardiovascular outcomes in patients with atrial flutter after catheter ablation.

AIMS: For patients with typical and atypical atrial flutter (AFL) but without history of atrial fibrillation (AF), the long-term cardiovascular (CV) outcomes after catheter ablation for AFL remain unclear. We compared the long-term all-cause mortality and CV outcomes in patients with AFL receiving catheter ablation compared with the results with medical therapy. METHODS AND RESULTS: Atrial flutter patients receiving catheter ablation for typical AFL were identified using the Health Insurance Database, and constituted the 'AFL ablation group'. Patients with typical and atypical AFL but without ablation (AFL without ablation group) were propensity matched to the AFL ablation group. Patients with prior AF diagnosis were excluded. Primary outcomes included all-cause and CV mortality, heart failure (HF) hospitalization, and stroke. The multivariable cox hazards regression model was used to evaluate the hazard ratio (HR) for study outcomes. A total of 3784 AFL patients (1892 patients in each group) was studied. Their mean follow-up durations were 7.85 ± 2.57 years (AFL without ablation group) and 8.31 ± 4.53 years (AFL ablation group). Atrial flutter with ablation patients had lower risks of all-cause mortality (HR: 0.68, P < 0.001), CV deaths (HR: 0.78, P = 0.001), HF hospitalization (HR: 0.84, P = 0.01), and stroke (HR: 0.80, P = 0.01). CONCLUSIONS: Catheter ablation for AFL in patients without prior AF was associated with lower risks of all-cause mortality and CV events compared with AFL patients without ablation during long-term follow-ups.

10-Year Outcomes of Patients With Non-Paroxysmal Atrial Fibrillation Undergoing Catheter Ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is commonly performed in patients with non-paroxysmal atrial fibrillation (AF), but because very long-term follow-up results of RFCA are limited, we investigated the 10-year RFCA outcomes of non-paroxysmal AF.Methods and Results: We retrospectively enrolled 100 patients (89 men, mean age 53.5±8.4years) with drug-refractory symptomatic non-paroxysmal AF who underwent 3D electroanatomic-guided RFCA. Procedural characteristics at index procedures and clinical outcomes were investigated. In the index procedures, all patients had pulmonary vein isolation, 56 (56.0%), 48 (48.0%), and 32 (32.0%) underwent additional linear, complex fractionated atrial electrogram (CFAE) and non-pulmonary vein (NPV) foci ablations, respectively. After 124.1±31.7 months, 16 (16%) patients remained in sinus rhythm after just 1 procedure (3 with antiarrhythmic drugs [AAD]) and after multiple (2.1±1.3) procedures in 53 (53.0%) patients (22 with AAD). Left atrial (LA) diameter (hazard ratio HR 1.061; 95% confidence interval (CI) 1.020 to 1.103; P=0.003), presence of NPV triggers (HR 1.634; 95% CI 1.019 to 2.623; P=0.042) and undergoing CFAE ablation (HR 2.003; 95% CI 1.262 to 3.180; P=0.003) in the index procedure were independent predictors for recurrent atrial tachyarrhythmia. CONCLUSIONS: The 10-year outcomes of single RFCA in non-paroxysmal AF were unsatisfactory. Enlarged LA, presence of NPV triggers, and undergoing CFAE ablation in the index procedure independently predicted single-procedure recurrence. Multiple procedures are required to achieve adequate rhythm control.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with advanced chronic kidney and liver diseases.

Advanced chronic kidney disease (CKD) or chronic liver disease (CLD) is frequent in patients with atrial fibrillation (AF) because of their common risk factors. Chronic kidney disease and CLD superimposed on AF are associated with increased risks of thrombosis and bleeding, which further complicates the use of oral anticoagulants (OACs). Because currently approved non-vitamin K antagonist oral anticoagulants (NOACs) undergo certain degrees of metabolism and clearance in the liver and kidney, increased exposure to medications and risk of bleeding are major concerns with the use of NOACs in patients with advanced CKD and CLD. Besides, these patients were mostly excluded from landmark trials of NOACs and related cohort studies are also limited. Therefore, the optimal strategy for the use of NOACs in this population remains unclear. This review would go through current evidence regarding the safety and efficacy of NOACs in AF patients with advanced CKD and CLD and provide a comprehensive discussion for clinical practices.

Decreased Expression of Plakophilin-2 and αT-Catenin in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Markers for Diagnosis.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disease of the heart muscle. Clinical challenges remain, however, in identifying patients with ARVC in the early or concealed stages with subtle clinical manifestations. Therefore, we wanted to identify potential targets by immunohistochemical (IHC) analysis in comparison with controls. Pathogenic mutations were identified in 11 of 37 autopsied patients with ARVC. As observed from IHC analysis of the RV, expression of αT-catenin and plakophilin-2 is significantly decreased in autopsied patients with ARVC as compared to controls, and the decreased expression is consistent in patients with and without pathogenic mutations. Furthermore, ARVC specimens demonstrated a reduced localization of αT-catenin, desmocollin-2, desmoglein-2, desmoplakin, and plakophilin-2 on intercalated discs. These findings have been validated by comparing RV specimens obtained via endomyocardial biopsy between patients with ARVC and those without. The pathogenic mutation was present in 3 of 5 clinical patients with ARVC. In HL-1 myocytes, siRNA was used to knockdown CTNNA3, and western blotting analysis demonstrated that the decline in αT-catenin expression was accompanied by a significant decline in the expression of plakophilin-2. The aforementioned effect was directed towards protein degradation rather than mRNA stability. Plakophilin-2 expression decreases concurrently with the decline in CTNNA3 expression. Therefore, the expression of αT-catenin and plakophilin-2 could be potential surrogates for the diagnosis of ARVC.

Nonlinear Heart Rate Dynamics Before and After Paroxysmal Atrial Fibrillation Events.

Background: Heart rate complexity, derived from nonlinear heart rate variability (HRV), has been shown to help predict the outcomes of various diseases. Changes in heart rate complexity before and after paroxysmal atrial fibrillation (PAF) events are unclear. Objectives: To evaluate changes in heart rate complexity through nonlinear HRV before and after PAF events. Methods: We enrolled 65 patients (72 ± 12.34 years old, 31 females) with 99 PAF events who received 24-hour Holter recording, and analyzed nonlinear HRV variables including Poincaré plot analysis, sample entropy (SampEn), and multiscale entropy (MSE). HRV analyses were applied to a 20-minute window before the onset and after the termination of PAF events. HRV parameters were evaluated and compared based on eight different 5-minute time segments, as we divided each 20-minute window into four segments of 5 minutes each. Results: SampEn and MSE1~5 significantly decreased before the onset of PAF events, whereas SampEn, MSE1~5 and MSE6~20 significantly increased after the termination of PAF events. SD1 and SD2, which are nonlinear HRV parameters calculated via Poincaré plot analysis, did not significantly change before the PAF events, however they both decreased significantly after termination. Conclusions: Heart rate complexity significantly decreased before the initiation and increased after the termination of PAF events, which indicates the crucial role of nonlinear heart rate dynamics in the initiation and termination of PAF.

Risks of Ventricular Tachyarrhythmia and Mortality in Patients with Amyloidosis - A Long-Term Cohort Study.

Background: The presence of ventricular tachycardia (VT) is associated with higher mortality. The annual incidence of VT after a diagnosis of amyloidosis and the associated cardiovascular (CV) outcomes have not been well assessed in a large cohort. Methods: A total of 12,139 amyloidosis patients were identified from the Taiwan National Health Insurance Research Database. Non-amyloidosis group was matched 1:1 for age, gender, hypertension, and diabetes mellitus (DM) to the amyloidosis group using a propensity score. Analysis of the risk of CV outcomes was conducted. We also analyzed the incidence of cardiac amyloidosis (CA). Results: The incidence rates of amyloidosis and CA were 6.54 and 0.61 per 100,000 person-years, respectively. Multivariable analysis revealed that the risk of VT was higher in both the amyloidosis [hazard ratio (HR): 7.90; 95% confidence interval (CI): 4.49-13.9] and CA (HR: 153.3, 95% CI: 54.3-432.7) groups. In the amyloidosis group, the risk of heart failure (HF)-related hospitalization, CV death, and all-cause death was also higher. Amyloidosis was associated with a higher CV mortality rate following VT (HR: 1.50; 95% CI: 1.07-2.12). The onset of a new VT event in patients with amyloidosis was associated with HF, DM, chronic liver disease, and anti-arrhythmic drug use. Conclusions: In this nationwide cohort study, the incidence rates of amyloidosis and CA were 6.54 and 0.61 per 100,000 person-years, respectively. The long-term risks of VT and CV mortality were higher in the patients with amyloidosis and CA. The patients with amyloidosis had a poorer prognosis following VT events, highlighting the importance of continuous monitoring in these patients.

The isthmus characteristics of scar-related macroreentrant atrial tachycardia in patients with and without cardiac surgery.

INTRODUCTION: Identifying the critical isthmus (CI) in scar-related macroreentrant atrial tachycardia (AT) is challenging, especially for patients with cardiac surgery. We aimed to investigate the electrophysiological characteristics of scar-related macroreentrant ATs in patients with and without cardiac surgery. METHODS: A prospective study of 31 patients (mean age 59.4 ± 9.81 years old) with scar-related macroreentrant ATs were enrolled for investigation of substrate properties. Patients were categorized into the nonsurgery (n = 18) and surgery group (n = 13). The CIs were defined by concealed entrainment, conduction velocity less than 0.3 m/s, and the presence of local fractionated electrograms. RESULTS: Among the 31 patients, a total of 65 reentrant circuits and 76 CIs were identified on the coherent map. The scar in the surgical group is larger than the nonsurgical group (18.81 ± 9.22 vs. 10.23 ± 5.34%, p = .016). The CIs in surgical group have longer CI length (15.27 ± 4.89 vs. 11.20 ± 2.96 mm, p = .004), slower conduction velocity (0.46 ± 0.19 vs. 0.69 ± 0.14 m/s, p < .001), and longer total activation time (45.34 ± 9.04 vs. 38.24 ± 8.41%, p = .016) than those in the nonsurgical group. After ablation, 93.54% of patients remained in sinus rhythm during a follow-up of 182 ± 19 days. CONCLUSION: The characteristics of the isthmus in macroreentrant AT are diverse, especially for surgical scar-related AT. The identification of CIs can facilitate the successful ablation of scar-related ATs.

Spatiotemporal differences in precordial electrocardiographic amplitude before and after flecainide provocation are associated with a history of unstable ventricular arrhythmia in Brugada syndrome.

INTRODUCTION: A drug provocation test (DPT) is important for the diagnosis of Brugada syndrome (BrS). The link, however, between dynamic changes of electrocardiography (ECG) features after DPT and unstable ventricular arrhythmia (VA) in BrS remains unknown. METHODS: Between 2014 and 2019, we assessed 27 patients with BrS (median age: 37.0 [interquartile range, IQR: 22.0-51.0] years; 25 men), including 9 (33.3%) with a history of unstable VA and 18 (66.7%) without. All patients in the study presented with Brugada-like ECG features before DPT. The ECG parameters and dynamic changes (∆) in 12-lead ECGs recorded from the second, third, and fourth intercostal spaces (ICS) before and at 1, 6, 12, 18, and 24 h after DPT (oral flecainide 400 mg) were analyzed. RESULTS: The total amplitude of V1 at the third ICS 18 and 24 h after DPT was significantly lower in patients with a history of unstable VA than in those without. Patients with BrS and unstable VAs had a significantly larger ∆ amplitude of V1 at the second ICS 12 h after DPT than in those without unstable VAs (0.28 [0.18-0.41] mV vs. 0.08 [0.01-0.15] mV, p = .01). A multivariate analysis revealed that the amplitude of V1 at the third ICS 18 and 24 h after DPT and the ∆ amplitude of V1 at the second ICS 12 h after DPT were associated with a history of unstable VA. CONCLUSION: Nonuniform changes and spatiotemporal differences in precordial ECG features after DPT were observed in patients with BrS and these may be surrogate markers for risk stratification.