2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: Executive Summary.

The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in the Asia-Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The practice guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of the AF Better Care pathway, the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian AF patients with single one stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the "coronavirus disease 2019" pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.

Co-delivery of curcumin and miRNA-144-3p using heart-targeted extracellular vesicles enhances the therapeutic efficacy for myocardial infarction.

Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy.

Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

AIMS: To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). METHODS AND RESULTS: This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. CONCLUSION: In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.

In situ procedure for high-efficiency computational modeling of atrial fibrillation reflecting personal anatomy, fiber orientation, fibrosis, and electrophysiology.

We previously reported the feasibility and efficacy of a simulation-guided clinical catheter ablation of atrial fibrillation (AF) in an in-silico AF model. We developed a highly efficient realistic AF model reflecting the patient endocardial voltage and local conduction and tested its clinical feasibility. We acquired > 500 endocardial bipolar electrograms during right atrial pacing at the beginning of the AF ablation procedures. Based on the clinical bipolar electrograms, we generated simulated voltage maps by applying fibrosis and local activation maps adjusted for the fiber orientation. The software's accuracy (CUVIA2.5) was retrospectively tested in 17 patients and feasibility prospectively in 10 during clinical AF ablation. Results: We found excellent correlations between the clinical and simulated voltage maps (R = 0.933, p < 0.001) and clinical and virtual local conduction (R = 0.958, p < 0.001). The proportion of virtual local fibrosis was 15.4, 22.2, and 36.9% in the paroxysmal AF, persistent AF, and post-pulmonary vein isolation (PVI) states, respectively. The reconstructed virtual bipolar electrogram exhibited a relatively good similarities of morphology to the local clinical bipolar electrogram (R = 0.60 ± 0.08, p < 0.001). Feasibility testing revealed an in situ procedural computing time from the clinical data acquisition to wave-dynamics analyses of 48.2 ± 4.9 min. All virtual analyses were successfully achieved during clinical PVI procedures. We developed a highly efficient, realistic, in situ procedural simulation model reflective of individual anatomy, fiber orientation, fibrosis, and electrophysiology that can be applied during AF ablation.

Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation.

INSTRUCTION: Longer atrial fibrillation (AF) durations have higher recurrence rates after rhythm control. However, there is limited data on the effect of the AF duration on recurrence after atrial fibrillation catheter ablation (AFCA). In the present study, we investigated the rhythm outcome of AFCA according to the AF duration based on the first electrocardiogram (ECG) diagnosis. METHODS AND RESULTS: We included 1005 patients with AF (75% male, 59 ± 11 years old) who underwent AFCA and whose first ECG diagnosis time point was evident. The clinical characteristics and rhythm outcomes were compared based on the AF duration (≤3 years, n = 537; >3 years, n = 468) and AF burden (paroxysmal atrial fibrillation [PAF], n = 387; persistent atrial fibrillation [PeAF], n = 618). Longer AF durations were associated with older age (P = .020), larger left atrial size (P = .009) and a higher number of patients with hypertension (P < .001) or PeAF (P < .001). During 24 ± 22 months of follow-up, the postablation clinical recurrence rate was higher in patients with a longer AF duration (logrank P = .002). The AF recurrence rate was significantly higher in PeAF patients with an AF duration >3 years (logrank P = 0.009), but not in subjects with PAF (logrank P = .939). In a multivariate Cox regression analysis, a longer AF duration was significantly associated with a higher clinical recurrence rate after AFCA in PeAF patients (adjusted hazard ratio, 1.06; range, 1.03-0.10; P = 0.001), but not PAF. CONCLUSION: Although longer AF duration was associated with higher clinical recurrence rates after AFCA, the rate was significant in patients with PeAF lasting >3 years, but not in PAF patients.

Long-term fine particulate matter exposure and cardiovascular mortality in the general population: a nationwide cohort study.

BACKGROUND: Although eastern Asian countries are exposed to high levels of air pollution, the impact of long-term exposures to fine particulate matter (PM2.5) air pollution on all-cause and cardiovascular mortality is not well identified. We assessed the relationship between long-term PM2.5 exposure and all-cause/cardiovascular mortalities. METHODS: We included 436,933 subjects who received national health examinations from the Korean National Health Insurance Service-based National Sample Cohort. We matched subjects' residential-address areas with hourly-measurements of PM2.5 concentration data. We estimated the risk of mortality with average PM2.5 exposure during the study period using a Cox proportional-hazards model. RESULTS: During 1,683,271 person·years, all-cause and cardiovascular mortalities were observed in 6432 and 1603 subjects (382 and 95 per 100,000 person·years, respectively). An increase in 10 µg/m3 in PM2.5 was associated with increases in all-cause and cardiovascular mortalities by 3.4 % [2.7-4.1] and 4.7 % [3.6-5.8], respectively (each p < 0.001). PM2.5 was linearly and significantly correlated with these all-cause and cardiovascular mortalities above 18 µg/m3 of PM2.5 (p < 0.001), but it was not significant below 18 µg/m3 of PM2.5. To investigate the specific PM2.5 concentration for raising cardiovascular mortality more, we analyzed the sensitivities/specificities for different PM2.5 levels, and 18 µg/m3 showed the highest Youden's index (sensitivity + specificity-1) with c-index of 0.85 (0.84-0.86). PM2.5 effect on all-cause mortality was more profound in subjects with previous myocardial infarction compared to the opposite population. CONCLUSIONS: In the Korean general population exposed to high-air pollution, long-term PM2.5 exposure was linearly associated with increased risk for all-cause and cardiovascular mortality, especially above 18 µg/m3 of PM2.5.

The Electrical Isolation of the Left Atrial Posterior Wall in Catheter Ablation of Persistent Atrial Fibrillation.

OBJECTIVES: This study explored whether complete electrical isolation of the left atrial (LA) posterior wall improves the rhythm outcome of catheter ablation of persistent atrial fibrillation (AF). BACKGROUND: Although the STAR AF2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) proved no additional benefit of empirical extra-pulmonary vein (PV) LA ablation, the long-term recurrence rate after circumferential PV isolation (CPVI) alone remains high. METHODS: We randomly assigned 217 patients with persistent AF (83.1% men, age 58.7 ± 10.8 years, 73.3% long-standing persistent AF) to ablation with CPVI alone (CPVI group) or CPVI with a POsterior wall Box Isolation (POBI group). The endpoint of the POBI group was the elimination of the posterior atrial potentials by roof and posterior inferior lines and touch-up focal ablation. RESULTS: After a mean follow-up of 16.2 ± 8.8 months, the clinical recurrence rate did not significantly differ between the 2 groups (23.8% vs. 26.5%; p = 0.779) in the CPVI and POBI groups. The recurrence rate for atrial tachycardias (16.0% vs. 11.1%; p = 0.913) and cardioversion rates (6.7% vs. 13.7%; p = 0.093) to control clinical recurrences also did not significantly differ between the 2 groups. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drug in 50.5% and 55.9% in the CPVI and POBI groups, respectively (p = 0.522). No significant difference was found in the major complication rates between the 2 groups, but the total ablation time was significantly longer in the POBI group (4,289 ± 1,837 s vs. 5,365 ± 2,358 s; p < 0.001). CONCLUSIONS: In patients with persistent AF, an empirical complete POBI did not improve the rhythm outcome of catheter ablation or influence the type of recurrent atrial arrhythmia. (Comparison of Circumferential Pulmonary Vein Isolation Alone Versus Linear Ablation in Addition to Circumferential Pulmonary Vein Isolation for Catheter Ablation in Persistent Atrial Fibrillation: Prospective Randomized Controlled Trial; NCT02721121).

Improved Population-Based Clinical Outcomes of Patients with Atrial Fibrillation by Compliance with the Simple ABC (Atrial Fibrillation Better Care) Pathway for Integrated Care Management: A Nationwide Cohort Study.

BACKGROUND: An integrated care approach might be of benefit for clinical outcomes of patients with atrial fibrillation (AF). This study evaluated whether compliance with the Atrial fibrillation Better Care (ABC) pathway for integrated care management ("A" Avoid stroke; "B" Better symptom management; "C" Cardiovascular risk and Comorbidity optimization) would improve population-based clinical outcomes in a nationwide AF cohort. METHODS AND RESULTS: From the Korea National Health Insurance Service database, a total of 204,842 nonvalvular AF patients were enrolled between January 1, 2005 and December 31, 2015. Patients that fulfilled all criteria of the ABC pathway were defined as the "ABC" group, and those who did not were the "Non-ABC" group.Over a mean follow-up of 6.2 ± 3.5 years, the ABC pathway compliant group had lower rates of all-cause death (0.80 vs. 2.72 per 100 person-years, p < 0.001) and the composite outcome of "death, ischemic stroke, major bleeding, and myocardial infarction" (2.34 vs. 5.92 per 100 person-years, p < 0.001) compared with the Non-ABC compliant group. Adjusted Cox multivariable regression showed that the ABC group had a significantly lower risk of all-cause death (adjusted hazard ratio [HR] 0.82; 95% confidence interval [CI], 0.78-0.86) and the composite outcome (adjusted HR 0.86; 95% CI, 0.83-0.89). With the increasing numbers of ABC pathway criteria fulfilled, the risk of all-cause death and composite outcome were progressively lowered. CONCLUSION: In the first study of a nationwide population cohort, we show that compliance with the simple ABC pathway is associated with improved clinically relevant outcomes of patients with AF. Given the high health care burden associated with AF, such a streamlined holistic approach to AF management should be implemented, to improve the care of such patients.

Multiple factors influence the morphology of the bipolar electrogram: An in silico modeling study.

Although bipolar electrograms (Bi-egms) are commonly used for catheter mapping and ablation of cardiac arrhythmias, the accuracy and reproducibility of Bi-egms have not been evaluated. We aimed to clarify the influence of the catheter orientation (CO), catheter contact angle (CA), local conduction velocity (CV), scar size, and catheter type on the Bi-egm morphology using an in silico 3-dimensional realistic model of atrial fibrillation. We constructed a 3-dimensional, realistic, in silico left atrial model with activation wave propagation including bipolar catheter models. Bi-egms were obtained by computing the extracellular potentials from the distal and proximal electrodes. The amplitude and width were measured on virtual Bi-egms obtained under different conditions created by changing the CO according to the wave direction, catheter-atrial wall CA, local CV, size of the non-conductive area, and catheter type. Bipolar voltages were also compared between virtual and clinically acquired Bi-egms. Bi-egm amplitudes were lower for a perpendicular than parallel CO relative to the wave direction (p<0.001), lower for a 90° than 0° CA (p<0.001), and lower for a CV of 0.13m/s than 0.48m/s (p<0.001). Larger sized non-conductive areas were associated with a decreased bipolar amplitude (p<0.001) and increased bipolar width (p<0.001). Among three commercially available catheters (Orion, Pentaray, and Thermocool), those with more narrowly spaced and smaller electrodes produced higher voltages on the virtual Bi-egms (p<0.001). Multiple factors including the CO, CA, CV, and catheter design significantly influence the Bi-egm morphology. Universal voltage cut-off values may not be appropriate for bipolar voltage-guided substrate mapping.

Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation.

PURPOSE: Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs. MATERIALS AND METHODS: In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations. RESULTS: We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA2DS2-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use. CONCLUSION: In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.

Impact of Renal Function on Outcomes With Edoxaban in Real-World Patients With Atrial Fibrillation.

Background and Purpose- Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods- In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results- The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels ( P for interaction=0.023). Conclusions- In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population.

BACKGROUND: Most data on the clinical epidemiology of atrial fibrillation (AF) are reported from Western populations, and data for Asians are limited. We aimed to investigate the 10-year trends of the prevalence and incidence of non-valvular AF and provide prevalence projections till 2060 in Korea. We also investigated the annual risks of adverse outcomes among patients with AF. METHODS: Using the Korean National Health Insurance Service database involving the entire Korean population, a total of 679,416 adults with newly diagnosed AF were identified from 2006 to 2015. The incidence and prevalence of AF and risk of adverse outcomes following AF onset were assessed. RESULTS: The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015. The trend of its incidence was flat with a 10-year overall incidence of 1.77 per 1,000 person-years. The prevalence of AF is expected to reach 5.81% (2,290,591 patients with AF) in 2060. For a decade, the risk of all-cause mortality following AF declined by 30% (adjusted hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.68-0.72), heart failure by 52% (adjusted HR: 0.48, 95% CI: 0.44-0.51), and ischemic stroke by 9% (adjusted HR: 0.91, 95% CI: 0.88-0.93). CONCLUSIONS: The burden of AF among Asian patients is increasing. Although the overall risks of cardiovascular events and death following AF onset have decreased over a decade, the event rates are still high. Optimized management of any associated comorbidities should be part of the holistic management approach for patients with AF.

A stepwise approach to conduit puncture for electrophysiological procedures in patients with Fontan circulation.

Aims: In patients with Fontan circulation, the conduit may be punctured for electrophysiological procedures. We evaluated the feasibility and safety of a stepwise approach to conduit puncture in adults who have undergone Fontan operation. Methods and results: We included 13 consecutive patients with lateral tunnel or extracardiac conduit Fontan circulation [median age (interquartile range), 24.0 (16.0-25.0) years; seven men] who had undergone electrophysiological procedures. We performed a stepwise approach to conduit puncture: 1st, Brockenbrough needle; 2nd, Brockenbrough needle with snare; 3rd, extra-steep Brockenbrough needle with/without snare; 4th radiofrequency transseptal needle with/without snare; 5th, wiring through the puncture; 6th, conduit dilation with angioplasty balloon; 7th, non-compliant or cutting balloon; and 8th, Inoue dilator. In 12 patients, conduit puncture was successful. In two, one, and two patients with a lateral tunnel made of the pericardium or right atrial wall, conduit puncture was performed by steps 1st, 2nd, and 4th, respectively. In one, three, two, and one patient with the Goretex lateral tunnel or extracardiac conduit, conduit puncture was performed by steps 1st, 6th, 7th, and 8th, respectively. Puncture time was significantly longer in patients with Goretex conduits than with pericardial conduits [62.0 (50.0-120.0) and 11.5 (10.0-14.8) min, respectively; P < 0.001]. A snare was necessary in patients with angles ≤ 35° between the conduit wall and vertical line. Conclusion: A stepwise conduit puncture approach is feasible and safe in patients with lateral tunnel and extracardiac conduit Fontan circulation. Goretex conduit puncture was more difficult than pericardial conduit puncture.

Real-world Data and Recommended Dosage of Non-vitamin K Oral Anticoagulants for Korean Patients.

Regulatory approvals of non-vitamin K antagonist oral anticoagulants (NOACs) have been based on large randomized phase III trials evaluating dabigatran, rivaroxaban, apixaban, or edoxaban relative to warfarin for atrial fibrillation (AF). The results of the trials showed that all NOACs were at least non-inferior to warfarin in the prevention of stroke/thromboembolism and showed lower rates of intracranial bleeding than those associated with warfarin. However, the trials were designed differently, varied in the inclusion/exclusion criteria, and used either one dose or a low/high dose of the NOAC drug. Some of these differences have challenged the ability to directly compare various NOACs, and comparative data on effectiveness and intracranial bleeding are sparse in "real-world" patients. Real-world data complement data from large randomized phase III trials by providing new aspects of the "real-world" absolute risks of ischemic and hemorrhagic stroke associated with NOACs vs. warfarin. Moreover, "real-world" fragile patients might have been included (e.g., patients with increased risk of bleeding, liver disease, and chronic kidney disease), although these patients would be less represented in trials. This paper introduces recently published real-world data of NOACs and further suggests the recommended dosage of NOACs for Korean patients.

Does Additional Electrogram-Guided Ablation After Linear Ablation Reduce Recurrence After Catheter Ablation for Longstanding Persistent Atrial Fibrillation? A Prospective Randomized Study.

BACKGROUND: Although circumferential pulmonary vein isolation (CPVI) catheter ablation may not be sufficient for long-standing persistent atrial fibrillation (L-PeAF), it is not clear which ablation strategy is beneficial in addition to CPVI. We sought to investigate whether additional complex fractionated atrial electrogram (CFAE)-guided ablation improves clinical outcomes in L-PeAF patients who exhibit continuous atrial fibrillation (AF) after CPVI and linear ablation (Line). METHODS AND RESULTS: This study enrolled 137 L-PeAF patients (71.4% male, 61.6±10.9 years old) who underwent radiofrequency catheter ablation. We conducted CPVI+Line based on the Dallas lesion set (posterior box+anterior line) after baseline CFAE mapping in all patients. If AF was defragmented (terminated or changed to atrial tachycardia), the procedure was stopped (AF-Defrag group, n=29). If AF was maintained after CPVI+Line, we mapped the CFAE again and randomly assigned the patient to the CPVI+Line group (n=54) or the additional CFAE ablation group (CPVI+Line+CFAE group, n=54). L-PeAF was defragmented during CPVI+Line in 21.2% of patients (29/137, AF-Defrag group). The mean CFAE cycle length was prolonged (P<0.001), and CFAE area (CFAE cycle length <120 milliseconds) was reduced (P<0.001) after CPVI+Line in the remaining patients. Procedure time was longer in the CPVI+Line+CFAE group than the CPVI+Line group (P=0.023), but procedure-related complication rates did not vary. During 22.3±13.2 months of follow-up, the clinical recurrence rates were 17.2% in the AF-Defrag group, 18.5% in the CPVI+Line group, and 32.1% in the CPVI+Line+CFAE group (log rank, P=0.166). CONCLUSIONS: Although CPVI+Line reduces and localizes CFAE area, additional CFAE ablation after CPVI+Line does not improve the clinical outcomes of catheter ablation in patients with L-PeAF.

Pulmonary vein reconnection predicts good clinical outcome after second catheter ablation for atrial fibrillation.

AIMS: Although electrically reconnected pulmonary veins (PV) are the main mechanism of atrial fibrillation (AF) recurrence, PV isolation (PVI) is well-preserved in certain patients who undergo a repeat procedure. We explored the association between PV reconnection and clinical outcomes after a second ablation. METHODS AND RESULTS: This observational cohort study included 143 patients (79.0% male, 56.1 ± 10.0 years old, 65.0% paroxysmal AF) who underwent a second procedure. Pulmonary vein isolation was well-maintained in 52 patients (PVP- group, 36.4%), although the remaining 91 patients showed PV reconnection (PVP+ group). After confirming PVI, we mapped non-PV triggers and conducted trigger ablation or additional linear ablation at redo-procedures. The proportion of females was higher (P = 0.030), and redo-ablation timing after the de novo procedure was later (P = 0.039) in the PVP- group than in the PVP+ group. Additional linear ablations were more likely to be performed in the PVP- group (90.4 vs. 61.5%, P < 0.001). During the 18.4 ± 10.2 month follow-up after the redo-ablation, the PVP+ group showed a lower clinical recurrence rate than the PVP- group (log-rank P = 0.011). The number of reconnected PVs was independently associated with a lower recurrence of AF after the redo-ablation in the total study population (HR 0.56, 95% CI 0.34-0.95, P = 0.032), particularly for patients with paroxysmal AF (HR 0.41, 95% CI 0.19-0.87, P = 0.021). CONCLUSION: Among patients who underwent redo-AF ablation, those with more PV reconnections showed better clinical outcomes than those with fewer PV reconnections. The mechanism of AF recurrence might be different in patients with lower numbers of PV reconnections during redo-procedures.

Prognosis of high sinus heart rate after catheter ablation for atrial fibrillation.

AIMS: Although atrial fibrillation (AF) catheter ablation increases sinus heart rate (HR), its mechanism and prognosis have not yet been clearly elucidated. We hypothesize that post-AF ablation high sinus HR (PA-HSR) is associated with a better clinical outcome of AF ablation without adverse cardiac effects. METHODS AND RESULTS: We studied 991 AF patients (75% male, 58 ± 11 years old, 70% paroxysmal AF) with HR variability (HRV) at 3 months and 1 year after catheter ablation, and pre- and post-1-year echocardiograms. Post-AF ablation high sinus HR was defined as an average HR greater than 2 SD (≥92 bpm) as measured by 24 h Holter. (1) Average HR increased significantly (P< 0.001), and PA-HSR was observed in 28 patients (2.8%) 3 months after AF ablation. At 1 year after catheter ablation, 21% were taking ß-blockers and 36% maintained an average HR of ≥92 bpm. (2) Post-AF ablation high sinus HR was independently associated with pre-procedural high average HR (OR 1.097; 95% CI 1.029-1.169, P= 0.005), high left atrium (LA) electrogram voltage (OR 3.545; 95% CI 1.183-10.618, P= 0.024), and reduced root mean square of differences between successive NN intervals (rMSSD) at 3 months HRV (OR 0.959; 95% CI 0.919-0.999, P= 0.047). (3) At 1 year echocardiography, size reduction of LA (P= 0.055) or LV (P= 0.372) and the improvement in ejection fraction (P= 0.529) were not significantly different between patients with PA-HSR and those without. (4) Throughout 27 ± 17 months of follow-up, patients with PA-HSR showed significantly lower clinical recurrence than those without (log rank, P= 0.020). CONCLUSION: Post-AF ablation high sinus HR was observed in patients with smaller LA size and higher LA electrogram voltage and significant vagal modulation without adverse cardiac effects. Post-AF ablation high sinus HR was associated with a significantly lower clinical recurrence of AF after catheter ablation.

Challenging Achievement of Bidirectional Block After Linear Ablation Affects the Rhythm Outcome in Patients With Persistent Atrial Fibrillation.

BACKGROUND: It is not clear whether bidirectional block (BDB) of linear ablations reduces atrial fibrillation (AF) recurrence after radiofrequency catheter ablation. We hypothesized that BDB of linear ablation has prognostic significance after radiofrequency catheter ablation for persistent AF. METHODS AND RESULTS: Among 1793 consecutive patients in the Yonsei AF ablation cohort, this observational cohort study included 398 patients with persistent AF (75.6% male; age, 59.8±10.3 years) who underwent catheter ablation with a consistent ablation protocol of the Dallas lesion set: circumferential pulmonary vein isolation; cavotricuspid isthmus ablation (CTI); roof line (RL); posterior-inferior line (PIL); and anterior line (AL). BDB rates of de novo ablation lines were 100% in circumferential pulmonary vein isolation, 100% in CTI, 84.7% in RL, 44.7% in PIL, and 63.6% in AL. During 29.0±18.4 months of follow-up, 31.7% (126/398) of the patients showed clinical recurrence. Left atrial posterior wall (LAPW) isolation (BDBs of RL and PIL) was independently associated with lower clinical AF/atrial tachycardia recurrence (hazard ratio, 0.68; 95% CI, 0.47-0.98; P=0.041; log-rank, P=0.017), whereas BDBs of RL or AL were not (log-rank, P=0.178 for RL; P=0.764 for AL). Among 52 patients who underwent repeat procedures (23.0±16.1 months after de novo procedure), the BDB maintenance rates for CTI, RL, PIL, and AL were 94.2% (49 of 52), 63.5% (33 of 47), 62.1% (18 of 29), and 61.8% (21 of 34), respectively. CONCLUSIONS: Although PIL crosses the esophageal contact area, LAPW isolation is important for better clinical outcome in catheter ablation with a linear ablation strategy for patients with persistent AF.

Detecting Regional Myocardial Abnormalities in Patients With Wolff-Parkinson-White Syndrome With the Use of ECG-Gated Cardiac MDCT.

OBJECTIVE: Myocardial dyskinesia caused by the accessory pathway and related reversible heart failure have been well documented in echocardiographic studies of pediatric patients with Wolff-Parkinson-White (WPW) syndrome. However, the long-term effects of dyskinesia on the myocardium of adult patients have not been studied in depth. The goal of the present study was to evaluate regional myocardial abnormalities on cardiac CT examinations of adult patients with WPW syndrome. MATERIALS AND METHODS: Of 74 patients with WPW syndrome who underwent cardiac CT from January 2006 through December 2013, 58 patients (mean [± SD] age, 52.2 ± 12.7 years), 36 (62.1%) of whom were men, were included in the study after the presence of combined cardiac disease was excluded. Two observers blindly evaluated myocardial thickness and attenuation on cardiac CT scans. On the basis of CT findings, patients were classified as having either normal or abnormal findings. We compared the two groups for other clinical findings, including observations from ECG, echocardiography, and electrophysiologic study. RESULTS: Of the 58 patients studied, 16 patients (27.6%) were found to have myocardial abnormalities (i.e., abnormal wall thinning with or without low attenuation). All abnormal findings corresponded with the location of the accessory pathway. Patients with abnormal findings had statistically significantly decreased left ventricular function, compared with patients with normal findings (p < 0.001). The frequency of regional wall motion abnormality was statistically significantly higher in patients with abnormal findings (p = 0.043). However, echocardiography documented structurally normal hearts in all patients. CONCLUSION: A relatively high frequency (27.6%) of regional myocardial abnormalities was observed on the cardiac CT examinations of adult patients with WPW syndrome. These abnormal findings might reflect the long-term effects of dyskinesia, suggesting irreversible myocardial injury that ultimately causes left ventricular dysfunction.

Low P-wave amplitude (<0.1 mV) in lead I is associated with displaced inter-atrial conduction and clinical recurrence of paroxysmal atrial fibrillation after radiofrequency catheter ablation.

AIMS: We hypothesized that P-wave amplitude in lead I is related to left atrial (LA) remodelling and inter-atrial conduction pattern, and has a predictive value for recurrence after radiofrequency catheter ablation (RFCA) among patients with paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: A total of 525 consecutive patients with PAF (76% male, 56 ± 12 years old) who underwent RFCA were included. We compared pre-procedural sinus rhythm electrocardiograms without antiarrhythmic drug effect with LA volume (CT), LA voltage (NavX), the earliest activation site (EAS) conduction pattern of LA, and clinical recurrence rate. P-wave amplitude in lead I was significantly lower in patients with recurrence than in those that remained in sinus rhythm (P < 0.001) during 21 ± 10-month follow-up. P-wave amplitude in lead I was linearly correlated with LA voltage (ß = 2.52, 95% CI 0.606-4.425, P = 0.010), LA conduction velocity (ß = 1.91, 95% CI 0.941-2.876, P < 0.001), and low septal displacement of EAS (ß = -1.67, 95% CI -2.352 to -0.996, P < 0.001). P-wave amplitudes <0.1 mV in lead I were independently associated with clinical recurrence of AF on multivariate Cox regression analysis (adjusted HR 2.163, 95% CI 1.307-3.581, P = 0.003). The integrated area under the curves was 0.705 (95% CI 0.655-0.755). CONCLUSION: Low P-wave amplitude (<0.1 mV) in lead I is related to LA remodelling and displaced inter-atrial conduction pattern to low septum, and independently predicts clinical recurrence after RFCA in patients with PAF.