Risk of Incident Atrial Fibrillation and Subsequent Use of Oral Anticoagulants in Patients with Dementia.

BACKGROUND: Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes. METHODS: Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group). RESULTS: The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching. CONCLUSION: In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events.

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.

Klotho Modulates Pro-Fibrotic Activities in Human Atrial Fibroblasts through Inhibition of Phospholipase C Signaling and Suppression of Store-Operated Calcium Entry.

BACKGROUND: Atrial fibroblasts activation causes atrial fibrosis, which is one major pathophysiological contributor to atrial fibrillation (AF) genesis. Klotho is a pleiotropic protein with remarkable cardiovascular effects, including anti-inflammatory, anti-oxidative, and anti-apoptotic effects. This study investigated whether Klotho can modulate the activity of human atrial fibroblasts and provides an anti-fibrotic effect. METHODS: Cell migration assay and proliferation assay were used to investigate fibrogenesis activities in single human atrial fibroblasts with or without treatment of Klotho (10 and 100 pM, 48 h). Calcium fluorescence imaging, the whole-cell patch-clamp, and Western blotting were performed in human atrial fibroblasts treated with and without Klotho (100 pM, 48 h) to evaluate the store-operated calcium entry (SOCE), transient receptor potential (TRP) currents, and downstream signaling. RESULTS: High dose of Klotho (100 pM, 48 h) significantly reduced the migration of human atrial fibroblasts without alternating their proliferation; in addition, treatment of Klotho (100 pM, 48 h) also decreased SOCE and TRP currents. In the presence of BI-749327 (a selective canonical TRP 6 channel inhibitor, 1 µM, 48 h), Klotho (100 pM, 48 h) could not inhibit fibroblast migration nor suppress the TRP currents. Klotho-treated fibroblasts (100 pM, 48 h) had lower phosphorylated phospholipase C (PLC) (p-PLCß3 Ser537) expression than the control. The PLC inhibitor, U73122 (1 µM, 48 h), reduced the migration, decreased SOCE and TRP currents, and lowered p-PLCß3 in atrial fibroblasts, similar to Klotho. In the presence of the U73122 (1 µM, 48 h), Klotho (100 pM, 48 h) could not further modulate the migration and collagen synthesis nor suppress the TRP currents in human atrial fibroblasts. CONCLUSIONS: Klotho inhibited pro-fibrotic activities and SOCE by inhibiting the PLC signaling and suppressing the TRP currents, which may provide a novel insight into atrial fibrosis and arrhythmogenesis.

Low voltage zones detected by omnipolar Vmax map accurately identifies the potential atrial substrate and predicts the AF ablation outcome after PV isolation.

INTRODUCTION: The presence of bipolar low-voltage zone (LVZ) is a predictor of AF recurrence after PV isolation (PVI). However, changes of wavefront and bipole directions may cause different electrogram characteristics. We aimed to investigate whether using omnipolar maximum voltage (Vmax) map derived from high density (HD) Grid mapping catheter could assess LVZ and AF ablation outcome accurately. METHODS: Fifty paroxysmal AF patients (27 males, 57.8 ± 9.5 years old) who underwent 3D mapping guided PVI were enrolled. Left atrial voltage mapping during sinus rhythm before ablation was performed. The significant LVZ (<0.5 mV with area > 5 cm2) were defined as sites by omnipolar Vmax, bipolar HD wave map, conventional bipolar electrograms acquired from electrode pairs along to and across to the catheter shaft. The primary end point was the first documented recurrence of any AF during follow-ups. RESULTS: PVI was performed in all patients, and there were 2 patients (4%) who also received additional non-PV triggers ablation. After a follow-up of 11.4 ± 5.4 months, recurrence of AF occurred in 12 patients (24%). The presence of a significant LVZ was less detected by omnipolar Vmax map, compared to HD wave map (24.0% vs. 58.0%, p = 0.001). LVZ detected by omnipolar Vmax map independently predicted the AF recurrence (odds ratio 16.91; 95% CI, 3.17-90.10; p = 0.001). CONCLUSION: LVZ detected by omnipolar Vmax map accurately predicts the AF recurrence following ablation in paroxysmal AF, compared to conventional bipolar and HD wave maps, suggesting the omnipolar Vmax map can precisely define the atrial substrate property.

Distribution of triggers foci and outcomes of catheter ablation in atrial fibrillation patients in different age groups.

BACKGROUND: Atrial fibrillation (AF) prevalence increases with age. Aging affects the substrate properties of the left atrium (LA) and the outcomes of catheter ablation for treating AF. We investigated the AF trigger distribution and catheter ablation outcomes in patients of different ages with AF. METHODS: 1585 patients with AF (1181 paroxysmal and 404 non- paroxysmal AF) who had undergone catheter ablation were enrolled. The patients were divided into young (20-40 year-old, n = 175), middle-aged (41-64 year-old, n = 1134), and old (≥ 65 year-old, n = 276) groups. Electrophysiological characteristics and AF trigger sites were recorded. RESULT: The incidence of AF with only non-pulmonary vein (non-PV) foci was higher in the young group than in the other groups (8.6% vs. 3.6% vs. 3.3%, p < 0.01). Non-PV foci were more commonly located in the superior vena cava (SVC) in the young group than in the other groups (13.1% vs. 7.8% vs. 6.5%, p = 0.03). The left atrium (LA) mean voltage was higher and the incidence of very late recurrence after AF ablation was lower in the young group than in the other groups. However, the final AF recurrence rate after multiple procedures and complication rates were similar among all the groups at a mean follow-up of 5.6 years. CONCLUSION: The young patients with AF had a higher incidence of only non-PV foci, mostly located in SVC, than the middle-aged and old patients. Our study highlights the importance of identifying the non-PV foci in catheter ablation of young patients with AF.

Comparison of lesion characteristics between conventional and high-power short-duration ablation using contact force-sensing catheter in patients with paroxysmal atrial fibrillation.

BACKGROUND: Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. METHODS: Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25-30 W, force-time integral = 400 g s, n = 40) or with HPSD (power control: 40-50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. RESULTS: 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P < 0.01). In the conventional group, most type A lesions were at the right pulmonary vein (RPV) posterior wall (50.2%) whereas in the HPSD group, most type A lesions were at the RPV anterior wall (44.0%) (P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). CONCLUSION: Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

Renal denervation prevents myocardial structural remodeling and arrhythmogenicity in a chronic kidney disease rabbit model.

BACKGROUND: The electrophysiological (EP) effects and safety of renal artery denervation (RDN) in chronic kidney disease (CKD) are unclear. OBJECTIVE: The purpose of this study was to investigate the arrhythmogenicity of RDN in a rabbit model of CKD. METHODS: Eighteen New Zealand white rabbits were randomized to control (n = 6), CKD (n = 6), and CKD-RDN (n = 6) groups. A 5/6 nephrectomy was selected for the CKD model. RDN was applied in the CKD-RDN group. All rabbits underwent cardiac EP studies for evaluation. Immunohistochemistry, myocardial fibrosis, and renal catecholamine levels were evaluated. RESULTS: The CKD group (34.8% ± 9.2%) had a significantly higher ventricular arrhythmia (VA) inducibility than the control (8.6% ± 3.8%; P <.01) and CKD-RDN (19.5% ± 6.3%; P = .01) groups. In the CKD-RDN group, ventricular fibrosis was significantly decreased compared to the CKD group (7.4% ± 2.0 % vs 10.4% ± 3.7%; P = .02). Sympathetic innervation in the CKD group was significantly increased compared to the control and CKD-RDN groups [left ventricle: 4.1 ± 1.8 vs 0.8 ± 0.5 (102 µm2/mm2), P <.01; 4.1 ± 1.8 vs 0.9± 0.6 (102 µm2/mm2), P <.01; right ventricle: 3.6 ± 1.0 vs 1.0 ± 0.4 (102 µm2/mm2), P <.01; 3.6 ± 1.0 vs 1.0 ± 0.5 (102 µm2/mm2), P <.01]. CONCLUSION: Neuromodulation by RDN demonstrated protective effects with less structural and electrical remodeling, leading to attenuated VAs. In a rabbit model of CKD, RDN plays a therapeutic role by lowering the risk of VA caused by autonomic dysfunction.

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.

ALDH2 deficiency induces atrial fibrillation through dysregulated cardiac sodium channel and mitochondrial bioenergetics: A multi-omics analysis.

Point mutation in alcohol dehydrogenase 2 (ALDH2), ALDH2*2 results in decreased catalytic enzyme activity and has been found to be associated with different human pathologies. Whether ALDH2*2 would induce cardiac remodeling and increase the attack of atrial fibrillation (AF) remains poorly understood. The present study evaluated the effect of ALDH2*2 mutation on AF susceptibility and unravelled the underlying mechanisms using a multi-omics approach including whole-genome gene expression and proteomics analysis. The in-vivo electrophysiological study showed an increase in the incidence and reduction in the threshold of AF for the mutant mice heterozygous for ALDH2*2 as compared to the wild type littermates. The microarray analysis revealed a reduction in the retinoic acid signals which was accompanied by a downstream reduction in the expression of voltage-gated Na+ channels (SCN5A). The treatment of an antagonist for retinoic acid receptor resulted in a decrease in SCN5A transcript levels. The integrated analysis of the transcriptome and proteome data showed a dysregulation of fatty acid ß-oxidation, adenosine triphosphate synthesis via electron transport chain, and activated oxidative responses in the mitochondria. Oral administration of Coenzyme Q10, an essential co-factor known to meliorate mitochondrial oxidative stress and preserve bioenergetics, conferred a protection against AF attack in the mutant ALDH2*2 mice. The multi-omics approach showed the unique pathophysiology mechanisms of concurrent dysregulated SCN5A channel and mitochondrial bioenergetics in AF. This inspired the development of a personalized therapeutic agent, Coenzyme Q10, to protect against AF attack in humans characterized by ALDH2*2 genotype.

Identification of critical isthmus using coherent mapping in patients with scar-related atrial tachycardia.

INTRODUCTION: Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS: Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval < 20 ms), CV < 0.3 m/s and local fractionated electrograms were evaluated. RESULTS: Twenty-six complex ATs were mapped (mean: 1.3 ± 0.7 maps/pt; 4 focal, 22 isthmus-dependent). Coherent mapping was better in identifying CI/breakout sites where ablation terminated the tachycardia (96.2% vs 69.2%; P = .010) and identified significantly more CI (mean/chamber 2.0 ± 1.1 vs 1.0 ± 0.7; P < .001) with narrower width (19.8 ± 10.5 vs 43.0 ± 23.9 mm; P < .001) than conventional mapping. Ablation at origin and CI sites was successful in 25 (96.2%) with long-term recurrence in 25%. CONCLUSIONS: Coherent mapping with conduction velocity vectors derived from adjacent mapping sites significantly improved the identification of CI sites in scar-related ATs with isthmus-dependent re-entry better than conventional mapping. It may be used in conjunction with conventional mapping strategies to facilitate recognition of slow conduction areas and critical sites that are important targets of ablation.

Low-Dose Rivaroxaban and Risks of Adverse Events in Patients With Atrial Fibrillation.

Background and Purpose- In the daily practice, low-dose nonvitamin K antagonist oral anticoagulants are commonly used among Asian patients with atrial fibrillation (AF). The aim of the present study was to compare the risks of ischemic stroke, intracranial hemorrhage, and net clinical benefit of Asian patients with AF treated with off-label low-dose and on-label dosing rivaroxaban. Methods- A total of 2214 patients with AF aged ≥20 years treated with rivaroxaban at a tertiary medical center in Taiwan were studied. Patients were categorized into 2 groups: (1) on-label dose (n=1630): ROCKET-AF or J-ROCKET dosage criteria; and (2) off-label low-dose (10 mg/d for patients with an estimated glomerulus filtration rate >50 mL/min, n=584). The risks of ischemic stroke and intracranial hemorrhage were compared between 2 groups. Results- Compared with the on-label dose group, off-label low-dose rivaroxaban was associated with an increased risk of ischemic stroke with an adjusted hazard ratio of 2.75; 95% CI =1.62-4.69; P<0.001). The risk intracranial hemorrhage did not differ significantly between the on-label and off-label low-dosing groups (adjusted hazard ratio =0.62; 95% CI =0.32-1.20; P=0.213). Compared with off-label low-dose group, on-label dosing rivaroxaban was associated with a positive net clinical benefit in different weighted models. The results were consistent among the propensity-matched cohort. Conclusions- Off-label low-dosing rivaroxaban should be avoided for Asian patients with AF giving the higher risk of ischemic stroke without risk reduction in intracranial hemorrhage compared with on-label dosing.

Ultra-rapid high-density mapping system with the phase singularity technique is feasible in identifying rotors and focal sources and predicting AF termination.

INTRODUCTION: Phase singularity (PS) mapping provides additional insight into the AF mechanism and is accurate in identifying rotors. The study aimed to evaluate the feasibility of PS mapping in identifying AF rotors using data obtained from an automatic ultra-rapid high-resolution mapping system with a high-density mini-basket catheter. METHODS: Twenty-three pigs underwent rapid right atrial (RA) pacing (RAP 480 bpm) for 5 weeks before the experiment. During AF, RA endocardial automatic continuous mappings with a mini-basket catheter were generated using an automatic ultra-rapid mapping system. Both fractionation mapping and waveform similarity measurements using a PS mapping algorithm were applied on the same recording signals to localize substrates maintaining AF. RESULTS: Seventeen (74%) pigs developed sustained AF after RAP. Three were excluded because of periprocedural ventricular arrhythmia and corrupted digital data. RA fractionation maps were acquired with 6.17 ± 4.29 minutes mean acquisition time, 13768 ± 12698 acquisition points mapped during AF from 581 ± 387 beats. Fractionation mapping identified extensively distributed (66.7%) RA complex fractionated atrial electrogram (CFAE), whereas the nonlinear analysis identified high similarity index (SI > 0.7) parts in limited areas (23.7%). There was an average of 1.67 ± 0.87 SI sites with 0.43 ± 0.76 rotor/focal source/chamber. AF termination occurred in 11/16 (68.75%) AF events in 14 pigs during ablation targeting max CFAE. There was a higher incidence of rotor/focal source at AF termination sites compared with non-AF termination sites (54.5% vs 0%, P = 0.011). CONCLUSIONS: The data obtained from ultra-rapid high-density automatic mapping is feasible and effective in identifying AF rotors/focal sources using PS technique, and those critical substrates were closely related to AF procedural termination.

Comparison of phase mapping and electrogram-based driver mapping for catheter ablation in atrial fibrillation.

INTRODUCTION: Adjunctive driver-guided ablation in addition to pulmonary vein isolation has been proposed as a strategy to improve procedural success and outcomes for various populations with atrial fibrillation (AF). First, this study aimed to evaluate the different mapping techniques for driver/rotor identification and second to evaluate the benefits of driver/rotor-guided ablation in patients with paroxysmal and persistent AF (PerAF). METHODS: We searched the electronic database in PubMed using the keywords "atrial fibrillation," "rotor," "rotational driver," "atrial fibrillation source," and "drivers" for both randomized controlled trials and observational controlled trials. Clinical studies reporting efficacy or safety outcomes of driver-guided ablation for paroxysmal AF or (PerAF) were identified. We performed subgroup analyses comparing different driver mapping methods in patients with PerAF. The odds ratios (ORs) with random effects were analyzed. RESULTS: Out of 175 published articles, seven met the inclusion criteria, of which two were randomized controlled trials, one was quasiexperimental study, and four observational studies (three case-controlled studies and one cross-sectional study). Overall, adjunctive driver-guided ablation was associated with higher rates of acute AF termination (OR: 4.62, 95% confidence interval [CI]: 2.12-10.08; P < 0.001), lower recurrence of any atrial arrhythmia (OR: 0.44, 95% CI: 0.30-0.065; P < 0.001), and comparable complication incidence. CONCLUSIONS: Adjunctive driver-guided catheter ablation suggested an increased freedom from AF/AT relative to conventional strategies, irrespective of the mapping techniques. Furthermore, phase mapping appears to be superior to electrogram-based driver mapping in PerAF ablation.

High-resolution mapping of pulmonary vein potentials improved the successful pulmonary vein isolation using small electrodes and inter-electrode spacing catheter.

BACKGROUND: Intracardiac electrogram recording is influenced by the electrode size and inter-electrode spacing. Smaller electrodes with a closer inter-electrode spacing may improve the mapping resolution and outcome. METHODS: Substrate mapping of the left atrium and residual pulmonary vein (PV) potentials during sinus rhythm was sequentially performed using a 3.5-mm electrode tip catheter and a 1-mm electrode multielectrode catheter in 33 patients (Group 1) that underwent repeat atrial fibrillation (AF) procedures. PV gap identification and electrophysiological characteristics were compared. Arrhythmia freedom was compared with a propensity matched (1:2) control group (66 patients, Group 2) undergoing repeat AF procedures guided by wide inter-electrode spacing catheter. RESULTS: In the Group 1 patients, the total area of residual PV potentials measured using the 1-mm catheter was larger than that measured by the 3.5-mm catheter. Overall 1.97 ±â€¯0.59 (1-3) and 1.49 ±â€¯0.62 (1-3) PVs were identified by the 1-mm electrode and 3.5 mm catheters, respectively (P = 0.02). The gaps not identified by the 3.5 mm catheter had a smaller width and lower voltage. Radiofrequency catheter ablation in the areas with residual PV potentials identified by the 1-mm catheter resulted in complete electrical isolation of the PVs. Arrhythmia freedom at one year of follow-up was achieved in 26 of 33 (78.8%) patients in Group 1, which was significantly higher than the matched control group (33/66 [50%], P < 0.05). CONCLUSION: In the patients with a previous PV isolation, mapping with small, closely spaced electrodes can increase the detection rate of residual PV potentials and improve the outcome.

Cigarette smoking causes a worse long-term outcome in persistent atrial fibrillation following catheter ablation.

INTRODUCTION: Cigarette smoking contributes to the development of atrial fibrosis via nicotine. The impact of smoking on ablation results in persistent atrial fibrillation (AF) is unknown. We aimed to investigate the triggers and long-term outcome between smokers and nonsmokers in the patients with persistent AF after catheter ablation. METHODS: This study included 201 (177 males, 53 ± 10 years old) patients who received index catheter ablation, including pulmonary vein isolation (PVI) and complex fractionated atrial electrograms (CFAEs) ablation for persistent AF, retrospectively. Electrophysiological characteristics at the index procedure and long-term outcome were investigated to determine the differences between smokers and nonsmokers. RESULTS: Baseline characteristics were similar between two groups. Pulmonary vein (PV) triggers were found in all patients in the two groups. There was a higher incidence of nonpulmonary vein (NPV) triggers in smokers than in nonsmokers (61% vs. 31%, P < 0.05). There were no differences of the long-term ablation outcomes between smokers and nonsmokers in Kaplan-Meier analysis. Smokers with PV plus right atrial NPV (RA-NPV) triggers had a higher incidence of recurrence (log-rank P < 0.05) than those without RA-NPV triggers, but not in nonsmokers, after a mean follow-up of 31 ± 25 months. CONCLUSIONS: Smoking increases the incidence of NPV triggers in patients with persistent AF. Smokers who have RA-NPV triggers during index procedure do have a worse outcome after catheter ablation, indicating the harmful effects of nicotine to right atrium.

Heterogeneous distribution of substrates between the endocardium and epicardium promotes ventricular fibrillation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Aims: Whether the distribution of scar in arrhythmogenic right ventricular cardiomyopathy (ARVC) plays a role in predicting different types of ventricular arrhythmias is unknown. This study aimed to investigate the prognostic value of scar distribution in patients with ARVC. Methods and results: We studied 80 consecutive ARVC patients (46 men, mean age 47 ± 15 years) who underwent an electrophysiological study with ablation. Thirty-four patients receive both endocardial and epicardial mapping. Abnormal endocardial substrates and epicardial substrates were characterized. Three groups were defined according to the epicardial and endocardial scar gradient (<10%: transmural, 10-20%: intermediate, >20%: horizontal, as groups 1, 2, and 3, respectively). Sinus rhythm electrograms underwent a Hilbert-Huang spectral analysis and were displayed as 3D Simultaneous Amplitude Frequency Electrogram Transformation (SAFE-T) maps, which represented the arrhythmogenic potentials. The baseline characteristics were similar between the three groups. Group 3 patients had a higher incidence of fatal ventricular arrhythmias requiring defibrillation and cardiac arrest during the initial presentation despite having fewer premature ventricular complexes. A larger area of arrhythmogenic potentials in the epicardium was observed in patients with horizontal scar. The epicardial-endocardial scar gradient was independently associated with the occurrence of fatal ventricular arrhythmias after a multivariate adjustment. The total, ventricular tachycardia, and VF recurrent rates were higher in Group 3 during 38 ± 21 months of follow-up. Conclusion: For ARVC, the epicardial substrate that extended in the horizontal plane rather than transmurally provided the arrhythmogenic substrate for a fatal ventricular arrhythmia circuit.

Novel electrophysiological criteria for septal ventricular outflow tract tachycardias requiring a sequential bilateral ablation.

BACKGROUND: Septal ventricular outflow tract ventricular arrhythmias (OT-VAs) are defined as septal origin VAs from the right ventricular or left ventricular OT. Patients with septal OT-VAs may require a sequential bilateral OT ablation. This study aimed to evaluate the electrophysiological characteristics and ablation outcome in patients with septal OT-VAs. METHODS: We retrospectively analyzed the electrocardiography and electrophysiological parameters in 96 patients (mean age 49 ± 15 years, 49 male) undergoing bilateral activation mapping before catheter ablation of idiopathic septal OT-VAs. The patients were categorized into three groups based on the successful ablation sites, including the right ventricular outflow tract (RVOT), RVOT/left ventricular outflow tract (LVOT), and LVOT. RESULTS: Mapping in the three groups demonstrated a gradually decreasing and increasing trend in the earliest activation time obtained from the RVOT and LVOT, respectively. The absolute earliest activation time discrepancy (AEAD) of ≤18 milliseconds could predict the requirement for a sequential bilateral ablation with a sensitivity and specificity of 100.0% and 93.7%, respectively. The small AEAD (≤21 milliseconds) was associated with a higher recurrence rate in patients receiving a successful unilateral ablation, while patients with a longer distance between the bilateral OT earliest activation sites (DEA > 26 mm) increased future recurrences after an initially successful sequential bilateral ablation. CONCLUSIONS: The application of bilateral OT-VA activation mapping and the measurement of the AEAD and DEA provided not only pivotal information for the ablation strategy, but also prognostic implications for recurrences in patients with septal OT-VAs.