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Abstract Background An idiopathic outflow tract premature ventricular complex (OT-PVC) is a common arrhythmia, and the accuracy of site of origin prediction using the 12-lead electrocardiogram (ECG) algorithm is not high. There are no studies about a systematic strategy that can provide practical help to electrophysiologists in OT-PVC mapping and ablation. This study aims to evaluate the efficacy and safety of the proposed ablation protocol and establish an optimal catheter ablation strategy by simultaneously investigating and synthesizing various indicators observed during the mapping procedure. Methods and design This study (ABOUT-PVC) was designed as a prospective multicenter study to enroll 210 patients from 11 tertiary university hospitals over an estimated 27 months. Patients with idiopathic OT-PVC requiring catheter ablation will receive the procedure through a proposed ablation strategy and will be followed up for at least 12 months. The primary outcome is the acute procedural success rate. The secondary outcomes are clinical success rate, procedure time, complication rate, symptom relief, and changes in echocardiographic parameters. Conclusions The ABOUT-PVC study was designed to investigate the efficacy and safety of the proposed ablation strategy and establish an optimal catheter ablation strategy. We expect this study to overcome the limitations of the ECG prediction algorithms and provide a practical guide to electrophysiologists, increasing the procedure’s success rate and reducing complications and procedure time.

Abstract The application of artificial intelligence (AI) algorithms to 12-lead electrocardiogram (ECG) provides promising age prediction models. We explored whether the gap between the pre-procedural AI-ECG age and chronological age can predict atrial fibrillation (AF) recurrence after catheter ablation. We validated a pre-trained residual network-based model for age prediction on four multinational datasets. Then we estimated AI-ECG age using a pre-procedural sinus rhythm ECG among individuals on anti-arrhythmic drugs who underwent de-novo AF catheter ablation from two independent AF ablation cohorts. We categorized the AI-ECG age gap based on the mean absolute error of the AI-ECG age gap obtained from four model validation datasets; aged-ECG (≥10 years) and normal ECG age (

Abstract Background The impact of delaying atrial fibrillation catheter ablation (AFCA) for antiarrhythmic drug (AAD) management on the disease course remains unclear. This study investigated AFCA rhythm outcomes based on the diagnosis‐to‐ablation time (DAT) and AAD responsiveness in participants with persistent AF (PeAF). Methods We included data from 1038 AAD‐resistant PeAF participants, all of whom had a clear time point for AF diagnosis, especially PeAF at diagnosis time, and had undergone an AFCA for the first time. Participants who experienced recurrences of paroxysmal type on AAD therapy were analyzed as a cohort of AAD‐partial responders; those maintaining PeAF on AAD were AAD‐non‐responders. We determined the DAT cutoff for best discriminating long‐term rhythm outcomes using a maximum log‐likelihood estimation method based on the Cox proportional hazard regression model. Results Of the participants (79.8% male; median age 61), 806 (77.6%) were AAD‐non‐responders. AAD‐non‐responders had a higher body mass index and a larger left atrial diameter than AAD‐partial‐responders. They also had a higher incidence of AF recurrence after AFCA (adjusted hazard ratio 1.75, 95% confidence interval 1.33–2.30; log‐rank p

Abstract Background Hypertrophic cardiomyopathy (HCM) is frequently associated with atrial fibrillation (AF). We compared clinical, echocardiographic, and electrophysiological parameters between HCM subtypes and those without HCM at AF catheter ablation (AFCA) and analyzed post‐AFCA reverse remodeling and AF recurrence based on HCM presence and subtype. Methods Among 5161 consecutive patients who underwent de novo AFCA, we included HCM patients and control patients who were age‐, gender‐, and AF type‐matched. Between AF‐HCM patients and controls, we compared baseline values for left atrium (LA) wall thickness (LAWT), reverse remodeling at 1‐year follow‐up, and procedural outcomes over the course of follow‐up between two groups. Results A total of 122 AF‐HCM patients and 318 control patients were included. AF‐HCM patients had more frequent heart failure and higher LA diameter, E/Em, and LA pressure (all, p

Abstract The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2–12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72–0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84–0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74–0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.

Abstract Background and Objectives Although extra‐pulmonary vein (PV) triggers (ExPVTs) play a role in atrial fibrillation (AF) recurrence after catheter ablation (AFCA), the mechanism is unknown. We explored whether the locations of ExPVTs were associated with low‐voltage scar areas (LVAs). Methods Among 2255 consecutive patients who underwent a de novo AFCA, 1696 (male 72.1%, median 60 years old, paroxysmal 64.7%) were included who underwent isoproterenol provocation and voltage mapping of the left atrium (LA) during their procedures. We investigated the associations between ExPVTs and their mean LA voltage and colocalization of ExPVTs within LVAs (

Abstract Background High‐power short‐duration (HPSD) ablation creates wide, shallow lesions using radiofrequency (RF) heating. It is uncertain if adjusting RF energy based on atrial wall thickness provides extra benefits. We studied the safety and effectiveness of tailored HPSD energy based on left atrial (LA) wall thickness (LAWT) for circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF). Methods We enrolled 212 patients (68.4% male, mean age: 59.5 ± 11.0 years) and randomly assigned them to two groups: LAWT‐guided CPVI (WT, n = 108) and conventional CPVI (control, n = 104). Both groups used an open irrigated‐tip deflectable catheter to apply 50 W for 10 s to the posterior LA, while controls used 60 W for 15 s on other LA regions. RF delivery time in WT was titrated (15 s at LAWT > 2.1 mm, 13 s at 1.4–2.1 mm, and 11 s at .999). The total procedure time, cardioversion rate, and post‐procedural AAD prescription rates did not significantly differ between the groups. Conclusions The LAWT‐guided energy titration strategy did not result in improved procedural safety and efficacy compared to the conventional 50–60 W‐HPSD CPVI in patients with PAF.

Background Increased left atrial pressure (LAP) contributes to dyspnea and heart failure with preserved ejection fraction in patients with atrial fibrillation (AF). The purpose of this study was to investigate the differences in baseline LAP and LAP response to rapid pacing between paroxysmal and persistent AF. Methods and Results This observational study prospectively enrolled 1369 participants who underwent AF catheter ablation, excluding those with reduced left ventricular ejection fraction. H2FPEF score was calculated by echocardiography and baseline characteristics. Patients underwent LAP measurements during AF, sinus rhythm, and heart rates of 90, 100, 110, and 120 beats per minute (bpm), induced by right atrial pacing and isoproterenol. The baseline LAP‐peak in the persistent AF group consistently exceeded that in the paroxysmal AF (PAF) group across each H2FPEF score subgroup (all P

Abstract Although pulmonary vein isolation (PVI) gaps and extrapulmonary vein triggers contribute to recurrence after atrial fibrillation (AF) ablation, their precise mechanisms remain unproven. Our study assessed the impact of PVI gaps on rhythm outcomes using a human AF digital twin. We included 50 patients (76.0% with persistent AF) who underwent catheter ablation with a realistic AF digital twin by integrating computed tomography and electroanatomical mapping. We evaluated the final rhythm status, including AF and atrial tachycardia (AT), across 600 AF episodes, considering factors including PVI level, PVI gap number, and pacing locations. Our findings revealed that antral PVI had a significantly lower ratio of AF at the final rhythm (28% vs. 56%, p = 0.002) than ostial PVI. Increasing PVI gap numbers correlated with an increased ratio of AF at the final rhythm (p

Background Although successful atrial fibrillation (AF) ablation can maintain sinus rhythm and reduce the left atrial (LA) dimension, blunted LA reverse remodeling can be observed in patients with atrial myopathy. We explored the potential mechanisms and long‐term outcomes in patients with blunted LA reverse remodeling after successful AF catheter ablation. Methods and Results We included 1685 patients who underwent baseline and 1‐year follow‐up echocardiograms, had a baseline LA dimension ≥40 mm, and did not have a recurrence of AF within a year. The patients were divided into tertile groups according to the delta value of the change in LA dimension on the preprocedure and 1‐year postprocedure echocardiography. After propensity score matching for age, sex, AF type, and LA dimension, 1272 patients were finally included in the analyses (424 in each group; the least/blunted, moderate, and the most reverse remodeling group). The patients in the T1 group (blunted LA reverse remodeling) were independently associated with higher left ventricular mass index (odds ratio [OR], 1.014 [95% CI, 1.005–1.022], P=0.001), change in ΔH2FPEF score (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder, filling pressure) score (OR, 1.445 [95% CI, 1.121–1.861], P=0.004), ventricular epicardial adipose tissue volume (OR, 1.010 [95% CI, 1.003–1.017], P=0.003), thinner LA wall thickness (OR, 0.461 [95% CI, 0.271–0.785], P=0.004), lower LA voltage (OR, 0.670 [95% CI, 0.499–0.899], P=0.008), and showed higher long‐term AF recurrence (log‐rank P

BackgroundThe comparative efficacy, saftey, and heart rate variability (HRV) parameters after pulmonary vein isolation using cryoballoon (Cryo-PVI), high-power short-duration (HPSD-PVI), and conventional radiofrequency ablation (conventional-PVI) for atrial fibrillation (AF) is unclear.Materials and methodsIn this propensity score-weighted, retrospective analysis of a single-center cohort, we analyzed 3,395 patients (26.2% female, 74.5% paroxysmal AF) who underwent AF catheter ablation without an empirical left atrial ablation. Procedural factors, recurrence rates, complication rates, and the post-procedural HRV parameters were compared across the Cryo-PVI (n = 625), HPSD-PVI (n = 748), and conventional-PVI (n = 2,022) groups.ResultsDespite the shortest procedural time in the Cryo-PVI group (74 min for Cryo-PVI vs. 104 min for HPSD-PVI vs. 153 min for conventional-PVI, p

Heart development and rhythm control are highly Tbx5 dosage-sensitive. TBX5 haploinsufficiency causes congenital conduction disorders, whereas increased expression levels of TBX5 in human heart samples has been associated with atrial fibrillation (AF). We deleted the conserved mouse orthologues of two independent AF-associated genomic regions in the Tbx5 locus, one intronic (RE(int)) and one downstream (RE(down)) of Tbx5. In both lines, we observed a modest (30%) increase of Tbx5 in the postnatal atria. To gain insight into the effects of slight dosage increase in vivo, we investigated the atrial transcriptional, epigenetic and electrophysiological properties of both lines. Increased atrial Tbx5 expression was associated with induction of genes involved in development, ion transport and conduction, with increased susceptibility to atrial arrhythmias, and increased action potential duration of atrial cardiomyocytes. We identified an AF-associated variant in the human RE(int) that increases its transcriptional activity. Expression of the AF-associated transcription factor Prrx1 was induced in Tbx5RE(int)KO cardiomyocytes. We found that some of the transcriptional and functional changes in the atria caused by increased Tbx5 expression were normalized when reducing cardiac Prrx1 expression in Tbx5RE(int)KO mice, indicating an interaction between these two AF genes. We conclude that modest increases in expression of dose-dependent transcription factors, caused by common regulatory variants, significantly impact on the cardiac gene regulatory network and disease susceptibility.

Abstract Background Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation. Methods Three-dimensional heart geometry was constructed from computed tomography images. The finite element method was used to elucidate the electric wave propagation in the heart. The electric excitation and mechanical contraction were coupled with vascular hemodynamics by the lumped parameter model. The model parameters for three-dimensional (3D) heart and vascular mechanics were estimated by matching computed variables with measured physiological parameters. CRT effects were simulated in a patient with HF and left bundle branch block (LBBB). LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV ejection fraction (LVEF), and CRT responsiveness measured from the in silico simulation model were compared with those from clinical observation. A CRT responder was defined as absolute increase in LVEF ≥ 5% or relative increase in LVEF ≥ 15%. Results A 68-year-old female with nonischemic HF and LBBB was retrospectively included. The in silico CRT simulation modeling revealed that changes in LVEDV, LVESV, and LVEF by CRT were from 174 to 173 mL, 116 to 104 mL, and 33 to 40%, respectively. Absolute and relative ΔLVEF were 7% and 18%, respectively, signifying a CRT responder. In clinical observation, echocardiography showed that changes in LVEDV, LVESV, and LVEF by CRT were from 162 to 119 mL, 114 to 69 mL, and 29 to 42%, respectively. Absolute and relative ΔLVESV were 13% and 31%, respectively, also signifying a CRT responder. CRT responsiveness from the in silico CRT simulation model was concordant with that in the clinical observation. Conclusion This in silico CRT simulation method is a feasible technique to screen for CRT non-responders in patients with HF and LBBB.

Abstract We sought to evaluate the clinical implication of LAE based on left atrial anterior–posterior (LA AP) dimension or LA volume index (LAVI) in Korean patients with atrial fibrillation (AF). We enrolled 8159 AF patients from the CODE-AF registry. The primary outcome was rate of stroke or systemic embolism (SSE). The prevalence of mild, moderate, and severe LAE by LA AP dimension was 30.6%, 18.5%, and 21.4%, and by LAVI (available in 5808 patients) was 15.7%, 12.5% and 37.8%, respectively. Compared with no or mild LAE, patients with significant LAE (moderate to severe LAE, n = 3258, 39.9%) were associated with a higher rate of SSE (2.5% vs. 1.4%, P = 0.001). Multivariable analysis suggested presence of significant LAE by LA AP dimension was associated with a higher risk of SSE in the overall population (HR 1.57, 95% CI: 1.14–2.17, P = 0.005) and in patients using anticoagulants (n = 5836, HR 1.79, 95% CI: 1.23–2.63, P = 0.002). Patients with significant LAE by LAVI were also at higher risk of SSE (HR 1.58, 95% CI: 1.09–2.29, P = 0.017). In conclusion, significant LAE by LA dimension or LAVI was present in 39.9% and 50.2% of AF patients, respectively, and was associated with a higher rate of SSE.

Abstract Background An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. Methods MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. Results Of the 85 patients [age, 54.0 (41.0–65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65–148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02–1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08–1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. Conclusions The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

BackgroundGreater epicardial adipose tissue (EAT) is related to higher recurrences after atrial fibrillation catheter ablation (AFCA). We investigated the effects of posterior wall box isolation (POBI) in conjunction with circumferential pulmonary vein isolation (CPVI) on rhythm outcomes according to varying EAT volumes among patients with persistent atrial fibrillation (PeAF).Materials and methodsWe included 1,187 patients with PeAF undergoing a de novo AFCA including those receiving CPVI alone (n = 687) and those receiving additional POBI (n = 500). The rhythm outcomes at 2 years post-AFCA were compared in subgroups stratified by the EAT volume using propensity overlap weighting.ResultsA reduced EAT volume was linearly associated with more favorable rhythm outcomes for additional POBI than for CPVI alone (P for interaction = 0.002). Among the patients with smaller EAT volumes (≤116.23 mL, the median value, n = 594), additional POBI was associated with a reduced AF recurrence risk as compared to CPVI only [weighted HR (hazard ratio) 0.74, 95% CI (confidence interval) 0.56–0.99]. In contrast, among the remaining 593 patients with greater EAT volumes (>116.23 mL), No difference was observed in the recurrence risk between the additional POBI and CPVI alone groups (weighted HR 1.13, 95% CI 0.84–1.52). Among 205 patients with repeat ablations, the POBI reconnection rate was more frequent in the large EAT group (77.4%) than in the small EAT group (56.7%, P = 0.034).ConclusionWhile PeAF patients with a smaller EAT volume averted AF recurrence by additional POBI after CPVI, no benefit of the POBI was observed in those with a greater EAT volume.

Abstract Background The relationship between the characteristics of cardiac implantable electronic device (CIED) leads and subclinical cardiac perforations remains unclear. This study aimed to evaluate the incidence of subclinical cardiac perforation among various CIED leads using cardiac computed tomography (CT). Methods A total of 271 consecutive patients with 463 CIED leads, who underwent cardiac CT after CIED implantation, were included in this retrospective observational study. Cardiac CT images were reviewed by one radiologist and two cardiologists. Subclinical perforation was defined as traversal of the lead tip past the outer myocardial layer without symptoms and signs related to cardiac perforation. We compared the subclinical cardiac perforation rates of the available lead types. Results A total of 219, 49, and 3 patients had pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy, respectively. The total subclinical cardiac perforation rate was 5.6%. Subclinical cardiac perforation by screw-in ventricular leads was significantly more frequent than that caused by tined ventricular leads (13.3% vs 3.3%, respectively, p = 0.002). There were no significant differences in the incidence of cardiac perforation between atrial and ventricular leads, screw-in and tined atrial leads, pacing and defibrillator ventricular leads, nor between magnetic resonance (MR)-conditional and MR-unsafe screw-in ventricular leads. Screw-in ventricular leads were significantly associated with subclinical cardiac perforation [odds ratio, 4.554; 95% confidence interval, 1.587–13.065, p = 0.005]. There was no case subclinical cardiac perforation by septal ventricular leads. Conclusions Subclinical cardiac perforation by screw-in ventricular leads is not rare. Septal pacing may be helpful in avoiding cardiac perforation.

Although left atrial (LA) dimension (LAD) is one of the predictors of atrial fibrillation (AF) recurrence after catheter ablation, repetitive recurrences occur in patients without enlarged LAD. We explored the predictive value of pulmonary vein (PV) to LA volume percent ratio (PV/LA%vol) for rhythm outcomes after AF catheter ablation (AFCA). We included 2913 patients (73.5% male, 60.0 [52.0–67.0] years old, 60.6% paroxysmal AF) who underwent AFCA. We evaluated the association between PV/LA%vol and AF recurrence after AFCA and compared the predictive value for AF recurrences according to the LA size with LAD. We additionally investigated the association between PV/LA%vol and PITX2 gene using a genome-wide association study. LAD affected 1-year recurrence only in the highest tertile group (T3, p = 0.046), but PV/LA%vol determined 1-year recurrence in all LAD groups (T1, p = 0.044; T2, p = 0.021; and T3, p = 0.045). During 20.0 (8.0–45.0) months of follow-up, AF recurrence rate was significantly higher in patients with lower PV/LA%vol (Log-rank p = 0.004, HR 0.91 [0.84–1.00], p = 0.044). In the T1 and T2 LAD groups, predicting AF recurrences was better with PV/LA%vol than with LAD (AUC 0.63 vs. 0.51, p < 0.001 at T1; AUC 0.61 vs. 0.50, p = 0.007 at T2). We replicated PITX2-related rs12646447, which was independently associated with PV/LA%vol (β = 0.15 [0–0.30], p = 0.047). In conclusion, smaller PV volumes after LA volume adjustments have genetic background of PITX2 gene and predictive value for poorer rhythm outcomes after AFCA, especially in patients without LA enlargement.

Abstract Aims This study aimed to elucidate the risk for stroke and systemic embolism (SE) in patients with atrial fibrillation and heart failure (HF) according to HF type. Methods and results A total of 10 780 patients with atrial fibrillation were enrolled in a multicentre prospective registry and divided according to HF type: no‐HF, HF with preserved ejection fraction (EF) (HFpEF), HF with mid‐range EF (HFmrEF), and HF with reduced EF (HFrEF). Each group included 237 age‐matched and sex‐matched patients (age, 69.0 ± 10.3 years; men, 69.6%). The baseline characteristics, cumulative incidence, and hazard ratios for stroke/SE and major bleeding were compared across the groups. Patients with HF accounted for 10.3% of the total population; HFpEF, HFmrEF, and HFrEF represented 43.7%, 23.6%, and 32.7% of the patients with HF, respectively. The CHA2DS2‐VASc score was significantly higher in the HFpEF, HFmrEF, and HFrEF groups than in the no‐HF group. The annual stroke/SE incidence rates were 2.8%, 0.7%, 1.1%, and 0.9% in the HFpEF, HFmrEF, HFrEF, and no‐HF groups, respectively. The cumulative incidence of stroke/SE was significantly highest in the HFpEF group at 22.8 ± 10.0 months (P = 0.020). The stroke/SE risk was higher in the HFpEF group than in the HFmrEF and HFrEF groups (hazard ratio, 3.192; 95% confidence interval, 1.039–9.810; P = 0.043). E/e' value was an independent risk factor for stroke/SE. There were no significant differences in the incidence of major bleeding across the groups. Conclusions The stroke/SE risk was the highest in the HFpEF group and comparable between the HFmrEF and HFrEF groups.

A 74-year-old woman presented with incessant wide complex tachycardia that was refractory to cardioversions. Successful radiofrequency catheter ablation was performed on the left ventricular posteromedial papillary muscle. An inaudible steam pop has occurred during the procedure, but we confirmed that there were no complications during the procedure and short-term follow-up of echocardiography. Two months after the procedure, an asymptomatic pseudoaneurysm was identified at the ablation site that had not been observed in the short-term follow-up.

Coronary artery calcium (CAC), which can be measured in various types of computed tomography (CT) examinations, is a hallmark of coronary artery atherosclerosis. However, despite the clinical value of CAC scores in predicting cardiovascular events, routine measurement of CAC scores is limited due to high cost, radiation exposure, and lack of widespread availability. It would be of great clinical significance if CAC could be predicted by electrocardiograms (ECGs), which are cost-effective and routinely performed during various medical checkups. We aimed to develop binary classification artificial intelligence (AI) models that predict CAC using only ECGs as input. Moreover, we aimed to address the generalizability of our model in different environments by externally validating our model on a dataset from a different institution. Among adult patients, standard 12-lead ECGs were extracted if measured within 60 days before or after the CAC scores, and labeled with the corresponding CAC scores. We constructed deep convolutional neural network models based on residual networks using only the raw waveforms of the ECGs as input, predicting CAC at different levels, namely CAC score ≥100, ≥400 and ≥1,000. Our AI models performed well in predicting CAC in the training and internal validation dataset [area under the receiver operating characteristics curve (AUROC) 0.753 ± 0.009, 0.802 ± 0.027, and 0.835 ± 0.024 for the CAC score ≥100, ≥400, and ≥1,000 model, respectively]. Our models also performed well in the external validation dataset (AUROC 0.718, 0.777 and 0.803 for the CAC score ≥100, ≥400, and ≥1,000 model, respectively), indicating that our model can generalize well to different but plausibly related populations. Model performance in terms of AUROC increased in the order of CAC score ≥100, ≥400, and ≥1,000 model, indicating that higher CAC scores might be associated with more prominent structural changes of the heart detected by the model. With our AI models, a substantial proportion of previously unrecognized CAC can be afforded with a risk stratification of CAC, enabling initiation of prophylactic therapy, and reducing the adverse consequences related to ischemic heart disease.

Abstract Background We aimed to investigate the comparative risk of fracture among patients with atrial fibrillation (AF) treated with warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). Methods Using the Korean National Health Insurance Service database, patients with AF who received a prescription for apixaban, dabigatran, rivaroxaban, or warfarin between 2013 and 2016 were included. Risk of major fractures (osteoporotic hip, vertebral, or pelvic fractures) were compared using inverse probability of treatment weighting. Results There were 70,481 patients identified (41.3% women; mean [SD] age 70.5 [11.3] years); 16,992 apixaban, 22,514 dabigatran, 27,998 rivaroxaban, and 29,390 warfarin users. During a median follow-up of 390 days, 2412 major fractures occurred with weighted incidences per 100 patient-years of 2.56 for apixaban, 2.39 for dabigatran, 2.78 for rivaroxaban, and 3.43 for warfarin. NOAC use was associated with a lower risk for fracture than warfarin use: HR 0.70 (95% confidence interval [CI] 0.57–0.86) for apixaban, HR 0.69 (95% CI 0.60–0.78) for dabigatran, and HR 0.79 (95% CI 0.70–0.90) for rivaroxaban. In head-to-head comparisons between NOACs, there was no significant difference between apixaban and dabigatran. Rivaroxaban was associated with a higher risk for fracture than dabigatran (HR 1.15, 95% CI 1.02–1.31). Conclusion In patients with AF, NOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of NOAC type, except for rivaroxaban. These associations may help inform benefit–risk assessments when choosing between the different anticoagulant types.

Abstract Whether catheter ablation for atrial fibrillation (AF) improves survival and affects other outcomes in real-world heart failure (HF) patients is unclear. This study aimed to evaluate whether ablation reduces death, and other outcomes in real-world AF patients with HF. Among 834,735 patients with AF from 2006 to 2015 in the Korean National Health Insurance Service database, 3173 HF patients underwent AF ablation. Propensity score weighting was used to correct for differences between the groups. During median 54 months follow-up, the risk of all-cause death in ablated patients was less than half of that in patients with medical therapy (2.8 vs. 6.2 per 100 person-years; hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.27–0.65, p

Abstract Background Short QT syndrome is a rare, inherited channelopathy associated with sudden cardiac arrest (SCA) but the characteristics and prognosis of short QT interval (SQTI) in Korean patients remain unclear. This study aimed to determine the clinical characteristics and outcomes of SQTI in a Korean population. Methods Consecutive patients with SQTI from January 1999 to March 2019 in three university hospitals in South Korea were recruited. SQTI was defined as a Bazett’s formula-corrected QT interval (QTc) ≤ 340 ms in serial electrocardiograms. Age- and sex-matched patients with a normal QTc and without overt cardiovascular disease were included in a 1:4 ratio. Clinical and ECG features and outcomes were compared between patients with and without SQTI. Results 34 patients with SQTI [age, 23.5 (21–30.5) years; 31 male] were followed up for 4.8 (2.0–7.8) years. Early repolarization, tall T wave, and U wave were significantly more frequent in patients with SQTI than in those without SQTI. QT dispersion [44.0 (28.0–73.0) vs. 20.0 (12.0–35.0) ms, P

Background/Aims Comparative occurrence of ischemic stroke for rhythm versus rate control strategy in patients with non-valvular atrial fibrillation (NVAF) is still inconclusive. The purpose of this study was to investigate whether the rhythm control strategy is associated with a lower risk of ischemic stroke compared to the rate control strategy in NVAF patients. Methods The CODE-AF registry prospectively enrolled 6,280 consecutive patients who were treated for NVAF at 10 tertiary referral centers in South Korea. Of these, 2,513 NVAF patients (age, 67 ± 10 years; male, 61.8%) were clinically followed up for over 1-year and divided into rate and rhythm control groups. Results Those treated with the rhythm control strategy were younger and had less proportions of underlying disease compared to those treated with the rate control strategy. After the propensity matching analysis, those treated with the rhythm control strategy had similar baseline characteristics including the CHA2DS2-VASC score compared to those treated with the rate control strategy. The rate of oral anticoagulation, all bleeding, and hospitalization were also similarly between the two groups. The incidence rate of ischemic stroke in the rhythm control group was significantly lower than in the rate control group (0.7 vs. 6.9 per 1,000 person-years, p = 0.011). Conclusions The rhythm control strategy demonstrated a beneficial effect to lower the risk of ischemic stroke during a 1-year follow-up compared to the rate control strategy.

Objectives: The aim of this study was to elucidate patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in the natural course of asymptomatic coronavirus disease 2019 (COVID-19). Methods: Consecutive patients with non-severe COVID-19 were included retrospectively. Asymptomatic patients with a normal body temperature and no evidence of pneumonia throughout the disease course were assigned to the asymptomatic group. The reverse transcription PCR (RT-PCR) assay was repeated every two to five days after the first follow-up RT-PCR assay. Negative conversion was defined as two consecutive negative RT-PCR assay results within a 24-h interval. Rebound of the cycle threshold (Ct) value was defined as negative from the single RT-PCR assay and positive from the following assay. Results: Among a total of 396 patients identified (median age 42.5 years (interquartile range (IQR) 25.0–55.0 years), 35.6% male), 68 (17.2%) were assigned to the asymptomatic group and 328 (82.8%) to the symptomatic group. The time until negative conversion was significantly shorter in the asymptomatic group than in the symptomatic group: median 14.5 days (IQR 11.0–21.0 days) and 18.0 days (IQR 15.0–22.0 days), respectively (p = 0.001). Rebound of Ct values was observed in 78 patients (19.7%). Conclusions: Time until negative conversion is shorter in asymptomatic COVID-19 than in symptomatic COVID-19. Rebound of Ct values is not uncommon.

IntroductionAlthough the dominant frequency (DF) localizes the reentrant drivers and the maximal slope of the action potential duration (APD) restitution curve (Smax) reflects the tendency of the wave-break, their interaction has never been studied. We hypothesized that DF ablation has different effects on atrial fibrillation (AF) depending on Smax.MethodsWe studied the DF and Smax in 25 realistic human persistent AF model samples (68% male, 60 ± 10 years old). Virtual AF was induced by ramp pacing measuring Smax, followed by spatiotemporal DF evaluation for 34 s. We assessed the DF ablation effect depending on Smax in both computational modeling and a previous clinical trial, CUVIA-AF (170 patients with persistent AF, 70.6% male, 60 ± 11 years old).ResultsMean DF had an inverse relationship with Smax regardless of AF acquisition timing (p < 0.001). Virtual DF ablations increased the defragmentation rate compared to pulmonary vein isolation (PVI) alone (p = 0.015), especially at Smax

BackgroundAtrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively).MethodsEchocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61–80 bpm, 81–110 bpm, and >110 bpm.ResultsA total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61–80 bpm group: hazard ratio, 0.66; 95% CI, 0.46–0.94; p = 0.021; 81–110 bpm group: hazard ratio, 0.60; 95% CI, 0.40–0.90; p = 0.013). Especially, HFpEF patients with HR 81–110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011).ConclusionIn patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.

BackgroundHere we aimed to analyze changes in the outcomes of atrial fibrillation (AF) catheter ablation (AFCA) during the coronavirus disease 2019 (COVID-19) pandemic and examine the relationship between rhythm outcomes and the stringency of government social distancing measures.MethodsWe included 453 patients who underwent de novo AFCA between May 2018 and October 2019 (pre-COVID-19 era) and 601 between November 2019 and April 2021 (COVID-19 era). The primary outcome was late recurrence, defined as any episode of AF or atrial tachycardia documented after a 3-month blanking period. A multivariable Cox regression analysis was performed to estimate the relative hazards of AF recurrence in the two eras.ResultsIn the study population (24.3% women; median age, 60 years), 660 (62.6%) patients had paroxysmal AF. Among those with paroxysmal AF, the late recurrence rate was significantly lower in the COVID-19 era than in the pre-COVID-19 era [9.4% vs. 17.0%, respectively, log-rank P = 0.004; adjusted hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.35–0.90] during a median follow-up of 11 months. In patients with persistent AF, the late recurrence rate did not significantly differ between the pre-COVID-19 and COVID-19 era groups (18.9% vs. 21.5%, respectively; log-rank P = 0.523; adjusted HR 0.84, 95% CI 0.47–1.53) during the median follow-up of 11 months.ConclusionA decrease in AF recurrence after catheter ablation was observed in patients with paroxysmal AF during the COVID-19 outbreak, whereas no change was observed in those with persistent AF.

Background The purpose of the RAFAS (Risk and Benefits of Urgent Rhythm Control of Atrial Fibrillation in Patients With Acute Stroke) trial was to explore the risks and benefits of early rhythm control in patients with newly documented atrial fibrillation (AF) during an acute ischemic stroke (IS). Method and Results An open‐label, randomized, multicenter trial design was used. If AF was diagnosed, the patients in the early rhythm control group started rhythm control within 2 months after the occurrence of an IS, unlikely the usual care. The primary end points were recurrent IS within 3 and 12 months. The secondary end points were a composite of all deaths, unplanned hospitalizations from any cause, and adverse arrhythmia events. Patients (n=300) with AF and an acute IS (63.0% men, aged 69.6±8.5 years; 51.2% with paroxysmal AF) were randomized 2:1 to early rhythm control (n=194) or usual care (n=106). A total of 273 patients excluding those lost to follow‐up (n=27) were analyzed. The IS recurrences did not differ between the groups within 3 months of the index stroke (2 [1.1%] versus 4 [4.2%]; hazard ratio [HR], 0.257 [log‐rank P=0.091]) but were significantly lower in the early rhythm control group at 12 months (3 [1.7%] versus 6 [6.3%]; HR, 0.251 [log‐rank P=0.034]). Although the rates of overall mortality, any cause of hospitalizations (25 [14.0%] versus 16 [16.8%]; HR, 0.808 [log‐rank P=0.504]), and arrhythmia‐related adverse events (5 [2.8%] versus 1 [1.1%]; HR, 2.565 [log‐rank P=0.372]) did not differ, the proportion of sustained AF was lower in the early rhythm control group than the usual care group (60 [34.1%] versus 59 [62.8%], P

BackgroundIschemic strokes (ISs) can appear even in non-gender-related CHA2DS2-VA scores 0~1 patients with atrial fibrillation (AF). We explored the determinants associated with IS development among the patients with non-gender-related CHA2DS2-VA score 0~1 AF.Methods and ResultsIn this single-center retrospective registry data for AF catheter ablation (AFCA), we included 1,353 patients with AF (24.7% female, median age 56 years, and paroxysmal AF 72.6%) who had non-gender-related CHA2DS2-VA score 0~1, normal left ventricular (LV) systolic function, and available H2FPEF score. Among those patients, 113 experienced IS despite a non-gender-related CHA2DS2-VA score of 0~1. All included patients underwent AFCA, and we evaluated the associated factors with IS in non-gender-related CHA2DS2-VA score 0~1 AF. Patients with ISs in this study had a lower estimated glomerular filtration rate (eGFR) (p < 0.001) and LV ejection fraction (LVEF; p = 0.017), larger LA diameter (p < 0.001), reduced LA appendage peak velocity (p < 0.001), and a higher baseline H2FPEF score (p = 0.018) relative to those without ISs. Age [odds ratio (OR) 1.11 (1.07–1.17), p < 0.001, Model 1] and H2FPEF score as continuous [OR 1.31 (1.03–1.67), p = 0.028, Model 2] variable were independently associated with ISs by multivariate analysis. Moreover, the eGFR was independently associated with IS at low CHA2DS2-VA scores in both Models 1 and 2. AF recurrence was significantly higher in patients with IS (log-rank p < 0.001) but not in those with high H2FPEF scores (log-rank p = 0.079), respectively.ConclusionsAmong the patients with normal LVEF and non-gender-related CHA2DS2-VA score 0~1 AF, the high H2FPEF score, and increasing age were independently associated with IS development (ClinicalTrials.gov Identifier: NCT02138695).

IntroductionWe developed a prediction model for atrial fibrillation (AF) progression and tested whether machine learning (ML) could reproduce the prediction power in an independent cohort using pre-procedural non-invasive variables alone.MethodsCohort 1 included 1,214 patients and cohort 2, 658, and all underwent AF catheter ablation (AFCA). AF progression to permanent AF was defined as sustained AF despite repeat AFCA or cardioversion under antiarrhythmic drugs. We developed a risk stratification model for AF progression (STAAR score) and stratified cohort 1 into three groups. We also developed an ML-prediction model to classify three STAAR risk groups without invasive parameters and validated the risk score in cohort 2.ResultsThe STAAR score consisted of a stroke (2 points, p = 0.003), persistent AF (1 point, p = 0.049), left atrial (LA) dimension ≥43 mm (1 point, p = 0.010), LA voltage

Background: The ZFHX3 gene (16q22) is the second most highly associated gene with atrial fibrillation (AF) and is related to inflammation and fibrosis. We hypothesized that ZFHX3 is associated with extra-pulmonary vein (PV) triggers, left atrial (LA) structural remodeling, and poor rhythm outcomes of AF catheter ablation (AFCA).Methods: We included 1,782 patients who underwent a de novo AFCA (73.5% male, 59.4 ± 10.8 years old, 65.9% paroxysmal AF) and genome-wide association study and divided them into discovery (n = 891) and replication cohorts (n = 891). All included patients underwent isoproterenol provocation tests and LA voltage mapping. We analyzed the ZFHX3, extra-PV trigger-related factors, and rhythm outcomes.Result: Among 14 single-nucleotide polymorphisms (SNPs) of ZFHX3, rs13336412, rs61208973, rs2106259, rs12927436, and rs1858801 were associated with extra-PV triggers. In the overall patient group, extra-PV triggers were independently associated with the ZFHX3 polygenic risk score (PRS) (OR 1.65 [1.22–2.22], p = 0.001, model 1) and a low LA voltage (OR 0.74 [0.56–0.97], p = 0.029, model 2). During 49.9 ± 40.3 months of follow-up, clinical recurrence of AF was significantly higher in patients with extra-PV triggers (Log-rank p < 0.001, HR 1.89 [1.49–2.39], p < 0.001, model 1), large LA dimensions (Log-rank p < 0.001, HR 1.03 [1.01–1.05], p = 0.002, model 2), and low LA voltages (Log-rank p < 0.001, HR 0.73 [0.61–0.86], p < 0.001, model 2) but not the ZFHX3 PRS (Log-rank p = 0.819).Conclusion: The extra-PV triggers had significant associations with both ZFHX3 genetic polymorphisms and acquired LA remodeling. Although extra-PV triggers were an independent predictor of AF recurrence after AFCA, the studied AF risk SNPs intronic in ZFHX3 were not associated with AF recurrence.

Background/Aims The current study aimed to elucidate a time-course change in left atrial volume after cardiac resynchronization therapy (CRT) and to verify factors associated with left atrial volume reduction (LAVR) and its prognostic implications. Methods The records of 97 patients were retrospectively reviewed after CRT. Echocardiographic data were analyzed at baseline before CRT, at early follow-up (FU) (≤ 1 year, median 6 months), and at late FU (median 30 months). Left ventricular volume response (LVVR) was defined as 15% reduction in left ventricular (LV) end-systolic volume (ESV). LAVR was classified into two groups by the median value at early FU: LAVR (≥ 7.5%) and no LAVR (< 7.5%). Results LV ESV index continuously decreased from baseline to early FU and from early FU to late FU (106.1 ± 47.4 mL/m2 vs. 87.6 ± 51.6 mL/m2 vs. 72.5 ± 57.1 mL/m2). LA volume index decreased from baseline to early FU, but there were no reductions thereafter (51.8 ± 21.9 mL/m2 vs. 45.1 ± 19.6 mL/m2 vs. 44.9 ± 23.0 mL/m2). The only echocardiographic factor associated with LAVR was change in E velocity (odds ratio [OR], 1.04; p = 0.002). Early LAVR (OR, 10.05; p = 0.002) was an independent predictor for late LVVR. Conclusions LAVR was related to reduction in E velocity, suggesting its relation with optimization of LV filling pressure. Early LAVR was a predictor for LVVR to CRT in long-term FU.

Abstract Background Although myocardial thickness is an important variable for therapeutic catheter ablation of cardiac arrhythmias, quantification of wall thickness has been overlooked. We developed a software (AMBER) that measures 3D-myocardial thickness using a cardiac computed tomogram (CT) image, verified its accuracy, and tested its clinical feasibility. Methods We generated 3D-thickness maps by calculating wall thickness (WT) from the CT images of 120 patients’ hearts and a 3D-phantom model (PhM). The initial vector field of the Laplace equation was oriented to calculate WT with the field lines derived from the 3D mesh. We demonstrate the robustness of the Laplace WT algorithm by comparing with the real thickness of 3D-PhM, echocardiographically measured left ventricular (LV) WT, and regional left atrial (LA) WT reported from previous studies. We conducted a pilot case of catheter ablation for atrial fibrillation (AF) utilizing real-time LAWT map-guided radiofrequency (RF) energy titration. Results AMBER 3D-WT had excellent correlations with the real thickness of the PhM (R = 0.968, p

Background/Aims Atrial arrhythmia (AA) occasionally occurs after lung transplantation (LT); however, risk factors for AA and their impact on clinical outcomes are inconsistent. We aimed to investigate the incidence, predisposing factors, and clinical outcomes of AA after LT. Methods We retrospectively evaluated 153 consecutive patients who underwent LT between January 2010 and August 2016. An AA episode was defined as a documented atrial fibrillation (AF), atrial flutter, or atrial tachycardia on 12-lead electrocardiography or episodes lasting ≥ 30 seconds on telemetry monitoring. Results The mean follow-up time was 22.0 ± 19.1 months. Postoperative AA occurred in 46 patients (30.1%) after LT. Patients with postoperative AA were older, had larger body surface area, and had an increased incidence of paroxysmal AF prior to transplantation, idiopathic pulmonary fibrosis, and postoperative tracheostomy than patients without AA. Preoperative right atrial pressure (RAP) (odds ratio [OR], 1.19; p = 0.005) and longer periods of mechanical ventilation (OR, 1.03; p = 0.008) were found to be independent risk factors for AA after surgery. Development of AA was a significant predictor of long-term overall mortality (hazard ratio, 2.75; p = 0.017). Conclusions Patients with elevated preoperative RAP and long-term ventilator care had a higher risk of AA after LT. Further, AA after LT was associated with poor long-term survival.

Abstract Background and objectives A prolonged QTc interval is associated with an increased risk of a stroke or atrial fibrillation (AF). However, its direct causal relationship with AF associated a stroke has not been proven yet. To examine whether QTc interval is causally linked with risk of stroke in AF patients, we used the Mendelian randomization analysis. Subjects and methods Among 2742 patients (73.6% male; 58.2 ± 11.0 years old; 69.5% with paroxysmal AF) who underwent AF catheter ablation, we analyzed 1766 patients who had preablation sinus rhythm electrocardiograms off antiarrhythmic drugs after excluding amiodarone users. Among them, 1213 subjects had genome-wide association study dataset analyzable for the Mendelian randomization. We explored the mechanistic relationships between QTc interval (ms) and the risk of a stroke by analyzing the Mendelian randomization (1213 subjects) after reviewing 35 genetic polymorphisms associated with the QTc in 31 European descent studies. Results Among the patients in the higher quartile with a higher QTc, CHA2DS2-VASc score (p

Abstract Background and objectives Atrial fibrillation is a known risk factor for cryptogenic stroke and therefore requires early detection and prompt management. We investigated predictors of stroke recurrence in patients with cryptogenic stroke and concomitant non-sustained atrial tachycardia but not atrial fibrillation. Subjects and methods We investigated 390 patients (219 men, mean age 67 ± 12 years) diagnosed with stroke and non-sustained atrial tachycardia on 24-h Holter monitoring and recorded the total number of atrial premature contractions identified by the Holter monitor. Multiple atrial premature contractions were defined as atrial premature contractions > 34 beats/day. We analyzed the rates of 5-year freedom from stroke recurrence or atrial fibrillation and investigated independent predictors of stroke recurrence and undiagnosed atrial fibrillation. Results The mean follow-up period was 35 ± 21 months, and the overall stroke recurrence rate was 9.0%. Kaplan–Meier survival analysis revealed that the rate of freedom from stroke recurrence was significantly lower in patients with multiple atrial premature contractions. Also, the patients with multiple atrial premature contractions had higher cumulative incidence rate of new-onset AF (p = 0.019). Multivariate analysis showed that multiple atrial premature contractions (hazard ratio 2.49, 95% confidence interval 1.05–5.88, p = 0.038), cigarette smoking status (hazard ratio 2.66, 95% confidence interval 1.15–6.17, p = 0.022), and the left atrial volume index (hazard ratio 1.05, 95% confidence interval 1.01–1.09, p = 0.020) were significantly associated with stroke recurrence in patients with cryptogenic stroke. However, these factors were not statistically significant predictors of future onset of atrial fibrillation. Conclusions Multiple atrial premature contractions were significantly correlated with an increased left atrial volume index, which could predict future onset of atrial fibrillation and stroke recurrence. This study showed that multiple atrial premature contractions predict stroke recurrence in patients with cryptogenic stroke without atrial fibrillation.

Abstract Purpose Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. This study investigated anticoagulation patterns and outcomes in patients with chronic kidney disease (CKD). Materials and methods In a prospective observational registry (CODE-AF), 3445 patients with non-valvular AF including 1129 with CKD (estimated glomerular filtration rate ≤ 60 mL min−1 1.73 m−2) were identified between June 1, 2016, and July 3, 2017. Results Compared with patients with no-CKD, patients with CKD more frequently had a high stroke risk (94.9% vs. 67.0%, p

Abstract Background Symptom burden is an important factor in determining the treatment of atrial fibrillation (AF). AF is frequently accompanied by heart failure (HF). This study investigated the characteristics of AF symptoms with concomitant HF. Methods A total of 4885 patients with AF were consecutively enrolled through a prospective observational registry (the Comparison Study of Drugs for Symptom Control and Complication Prevention of Atrial Fibrillation [CODE-AF] registry). Clinically diagnosed HF was divided into three categories (preserved, mid-range, and reduced ejection fraction [EF]). Symptom severity was assessed using the European Heart Rhythm Association (EHRA) classification. Results The presence of AF-related symptoms was comparable irrespective of concomitant HF. Patients with HF with reduced EF demonstrated severe (EHRA classes 3 and 4) and atypical symptoms. HF with preserved EF was also associated with atypical symptoms. Female sex and AF type were associated with the presence of symptoms in AF without HF, and non-maintenance of sinus rhythm and increased left atrial pressure (E/e′ ≥ 15) were factors related to the presence of symptoms in AF with HF. Conclusion AF with concomitant HF presented with more severe and atypical symptoms than AF without HF. Maintaining the sinus rhythm and reducing the E/e’ ratio are important factors for reducing symptoms in AF with concomitant HF.

Background/Aims Efforts to reduce stroke in patients with atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines; however, the high early discontinuation rate of vitamin K antagonists (VKAs) is a limitation. Although non-VKA OACs (NOACs) are more convenient to administer than warfarin, their lack of monitoring may predispose patients to nonpersistence. We compared the persistence of NOAC and VKA treatment for AF in real-world practice. Methods In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 7,013 patients with nonvalvular AF (mean age 67.2 ± 10.9 years, women 36.4%) were consecutively enrolled between June 2016 and June 2017 from 10 tertiary hospitals in Korea. This study included 3,381 patients who started OAC 30 days before enrollment (maintenance group) and 572 patients who newly started OAC (new-starter group). The persistence rate of OAC was evaluated. Results In the maintenance group, persistence to OAC declined during 6 months, to 88.3% for VKA and 95.5% for NOAC (p < 0.0001). However, the persistence rate was not different among NOACs. In the new-starter group, persistence to OAC declined during 6 months, to 78.9% for VKA and 92.1% for NOAC (p < 0.0001). The persistence rate was lower for rivaroxaban (83.7%) than apixaban (94.6%) and edoxaban (94.1%, p < 0.001). In the new-starter group, diabetes, valve disease, and cancer were related to nonpersistence of OAC. Conclusions Nonpersistence was significantly lower with NOAC than VKA in both the maintenance and new-starter groups. In only the new-starter group, apixaban or edoxaban showed higher persistence rates than rivaroxaban.

Background: Clinical recurrence after atrial fibrillation catheter ablation (AFCA) still remains high in patients with persistent AF (PeAF). We investigated whether an extra-pulmonary vein (PV) ablation targeting the dominant frequency (DF) extracted from electroanatomical map–integrated AF computational modeling improves the AFCA rhythm outcome in patients with PeAF.Methods: In this open-label, randomized, multi-center, controlled trial, 170 patients with PeAF were randomized at a 1:1 ratio to the computational modeling-guided virtual DF (V-DF) ablation and empirical PV isolation (E-PVI) groups. We generated a virtual dominant frequency (DF) map based on the atrial substrate map obtained during the clinical AF ablation procedure using computational modeling. This simulation was possible within the time of the PVI procedure. V-DF group underwent extra-PV V-DF ablation in addition to PVI, but DF information was not notified to the operators from the core lab in the E-PVI group.Results: After a mean follow-up period of 16.3 ± 5.3 months, the clinical recurrence rate was significantly lower in the V-DF than with E-PVI group (P = 0.018, log-rank). Recurrences appearing as atrial tachycardias (P = 0.145) and the cardioversion rates (P = 0.362) did not significantly differ between the groups. At the final follow-up, sinus rhythm was maintained without any AADs in 74.7% in the V-DF group and 48.2% in the E-PVI group (P < 0.001). No significant difference was found in the major complication rates (P = 0.489) or total procedure time (P = 0.513) between the groups. The V-DF ablation was independently associated with a reduced AF recurrence after AFCA [hazard ratio: 0.51 (95% confidence interval: 0.30–0.88); P = 0.016].Conclusions: The computational modeling-guided V-DF ablation improved the rhythm outcome of AFCA in patients with PeAF.Clinical Trial Registration: Clinical Research Information Service, CRIS identifier: KCT0003613.

Background: Extra-pulmonary vein triggers can play a significant role in atrial fibrillation recurrence after catheter ablation. We explored the characteristics of the extra-pulmonary vein (PV) triggers in de novo and repeat atrial fibrillation (AF) catheter ablation (AFCA).Methods: We included 2,118 patients who underwent a de novo AFCA (women 27.6%, 59.2 ± 10.9 years old, paroxysmal AF 65.9%) and 227 of them conducted repeat procedures. All included patients underwent isoproterenol provocation tests at the end of the procedure, and then we analyzed extra-PV triggers-related factors.Results: Extra-PV triggers were documented in 11.7% of patients undergoing de novo AFCA (1.22 ± 0.46 foci per patient) and 28.6% undergoing repeat AFCA (1.49 ± 0.73 foci per patient). Older age and higher LA volume index in de novo procedures and women, diabetes, and higher parasympathetic nerve activity (heart rate variability) in repeat-AFCA were independently associated with the existence of extra-PV triggers. The septum (19.9%), coronary sinus (14.7%), and superior vena cava (11.2%) were common extra-PV foci. Among 46 patients who were newly found to have mappable extra-PV triggers upon repeat procedures, 15 (32.6%) matched with the previous focal or empirical extra-PV ablation sites. The rate of AF recurrence was significantly higher in patients with extra-PV triggers than in those without after de novo (HR 1.91, 95% CI 1.54–2.38, p < 0.001) and repeat procedures (HR 2.68, 95% CI 1.63–4.42, p < 0.001).Conclusions: Extra-PV triggers were commonly found in AF patients with significant remodeling and previous empirical extra-PV ablation. The existence of extra-PV triggers was independently associated with poorer rhythm outcomes after the de novo and repeat AFCA.

Introduction: Whereas, high-power short-duration (HPSD) radiofrequency (RF) ablation is generally used in atrial fibrillation (AF) catheter ablation (CA), its efficacy, safety, and influence on autonomic function have not been well established in a large population. This study compared HPSD-AFCA and conventional power (ConvP)-AFCA in propensity score matched-population.Methods: In 3,045 consecutive patients who underwent AFCA, this study included 1,260 patients (73.9% male, 59 ± 10 years old, 58.2% paroxysmal type) after propensity score matching: 315 in 50~60W HPSD group vs. 945 in the ConvP group. This study investigated the procedural factors, complication rate, rhythm status, and 3-month heart rate variability (HRV) between the two groups and subgroups.Results: Procedure time was considerably short in the HPSD group (135 min in HPSD vs. 181 min in ConvP, p < 0.001) compared to ConvP group, but there was no significant difference in the complication rate (2.9% in HPSD vs. 3.7% in ConvP, p = 0.477) and the 3-month HRV between the two groups. At the one-year follow-up, there was no significant difference in rhythm outcomes between the two groups (Overall, Log-rank p = 0.885; anti-arrhythmic drug free, Log-rank p = 0.673). These efficacy and safety outcomes were consistently similar irrespective of the AF type or ablation lesion set. The Cox regression analysis showed that the left atrium volume index estimated by computed tomography (HR 1.01 [1.00–1.02]), p = 0.003) and extra-pulmonary vein triggers (HR 1.59 [1.03–2.44], p = 0.036) were independently associated with one-year clinical recurrence, whereas the HPSD ablation was not (HR 1.03 [0.73–1.44], p = 0.887).Conclusion: HPSD-AFCA notably reduced the procedure time with similar rhythm outcomes, complication rate, and influence on autonomic function as ConvP-AFCA, irrespective of the AF type or ablation lesion set.

Background: Little is known about the prognostic value of nutritional status among patients undergoing atrial fibrillation (AF) catheter ablation (AFCA). We compared the risk of procedure-related complications and long-term rhythm outcomes of AFCA according to nutritional status.Methods: We included 3,239 patients undergoing de novo AFCA in 2009-2020. Nutritional status was assessed using the controlling nutritional status (CONUT) score. The association between malnutrition and the risk of AFCA complications or long-term rhythm outcomes was evaluated. We validated the effects of malnutrition using an external cohort of 360 patients undergoing AFCA in 2013-2016.Results: In the study population (26.8% women, median age: 58 years), 1,005 (31.0%) had malnutrition (CONUT scores ≥ 2); 991 (30.6%) had mild (CONUT 2–4) and 14 (0.4%) had moderate-to-severe (CONUT ≥ 5) malnutrition. The overall complication rates after AFCA were 3.3% for normal nutrition, 4.2% for mild malnutrition, and 21.4% for moderate-to-severe malnutrition. Moderate-to-severe malnutrition [odds ratio (OR) 6.456, 95% confidence interval (CI) 1.637-25.463, compared with normal nutrition], older age (OR 1.020 per 1-year increase, 95% CI 1.001-1.039), female sex (OR 1.915, 95% CI 1.302-2.817), and higher systolic blood pressure (OR 1.013 per 1-mmHg increase, 95% CI 1.000-1.026) were independent predictors for the occurrence of complications. In the validation cohort, malnutrition (CONUT ≥ 2) was associated with a 2.87-fold higher risk of AFCA complications (95% CI 1.174-7.033). The association between malnutrition and a higher risk of AFCA complications was consistently observed regardless of body mass index and sex. Malnutrition did not affect rhythm outcomes during the median follow-up of 40 months (clinical recurrence: 37.0% in normal nutrition vs. 36.5% in malnutrition).Conclusion: Malnutrition, which is common in patients undergoing AFCA, was associated with a substantially higher risk for complications after AFCA.

Catheter ablation is the most effective rhythm control method for patients with atrial fibrillation (AF); however, it inevitably causes atrial tissue damage. We previously reported that AF catheter ablation (AFCA) increases left atrial (LA) pressure without changes in symptom scores. We hypothesized that extensive LA ablation increased the risk of stiff LA physiology. We included 1,720 patients (69.1% male, 60.0 [53.0–68.0] years old, 66.2% with paroxysmal AF) who underwent de novo AFCA and echocardiography before and 1-year after the procedure. Stiff LA physiology was defined, when the amount of the estimated pulmonary arterial pressure increase between the pre-procedural and the 1-year post-procedural follow-up echocardiography was >10 mmHg and when right ventricular systolic pressure (RVSP) was >35 mmHg at 1-year follow-up echocardiography. The failed rhythm control within 1 year was defined as recurrent AF despite using anti-arrhythmic drugs or cardioversion within a year of AFCA. We explored the incidence and risk factors for stiff LA physiology and the rhythm outcome of AFCA. Among the 1,720 patients, 64 (3.7%) had stiff LA physiology 1 year after AFCA. Stiff LA physiology was independently associated with diabetes (odds ratio [OR], 2.36 [95% CI, 1.14–4.87], p = 0.020), the ratio of the peak mitral flow velocity of the early rapid filling to the early diastolic velocity of the mitral annulus (E/Em; OR, 1.04 [95% CI, 1.00–1.10], p = 0.049), LA pulse pressure (Model 2: OR, 1.05 [95% CI, 1.00–1.11], p = 0.049), low LA voltage (OR, 0.36 [95% CI, 0.18–0.74], p = 0.005), empirical extra-pulmonary vein (PV) LA ablation (OR, 2.60 [95% CI, 1.17–5.74], p = 0.018), and radiofrequency (RF) ablation duration (Model 2: OR, 1.02 [95% CI, 1.01–1.03], p = 0.003). Although the incidence of post-AFCA stiff LA physiology was 3.7% and most of the cases were subclinical, the empirical extra-PV ablation was associated with this undesirable condition. In addition, patients who had low mean LA voltage before AFCA could be susceptible to stiff LA physiology.