Effects of radiofrequency catheter ablation for premature ventricular complexes originating from the right ventricular outflow tract on right ventricular function.

INTRODUCTION: This study aimed to elucidate the relationship between premature ventricular complexes (PVCs) and right ventricular (RV) dysfunction, and the effects of radiofrequency catheter ablation (RFCA) on RV function. METHODS: A total of 110 patients (age, 50.8 ± 14.4 years; 30 men) without structural heart disease who had undergone RFCA for RV outflow tract (RVOT) PVCs were retrospectively included. RV function was assessed using fractional area change (FAC) and global longitudinal strain (GLS) before and after RFCA. Clinical data were compared between the RV dysfunction (n = 63) and preserved RV function (n = 47) groups. The relationship between PVC burden and RV function was analyzed. Change in RV function before and after RFCA was compared between patients with successful and failed RFCA. RESULTS: PVC burden was significantly higher in the RV dysfunction group than in the preserved RV function group (p < .001). FAC and GLS were significantly worse in proportion to PVC burden (p < .001 and p < .001, respectively). The risk factor associated with RV dysfunction was PVC burden [odds ratio (95% confidence interval), 1.092 (1.052-1.134); p < .001]. Improvement in FAC (13.0 ± 8.7% and -2.5 ± 5.6%, respectively; p < .001) and GLS (-6.8 ± 5.7% and 2.1 ± 4.2%, respectively; p < .001) was significant in the patients with successful RFCA, compared to the patients in whom RFCA failed. CONCLUSIONS: Frequent RVOT PVCs are associated with RV dysfunction. RV dysfunction is reversible by successful RFCA.

Late recurrence of atrial fibrillation 5 years after catheter ablation: predictors and outcome.

AIMS: Atrial fibrillation (AF) is a chronic progressive disease that continuously recurs even after successful AF catheter ablation (AFCA). We explored the mechanism of long-term recurrence by comparing patient characteristics and redo-ablation findings. METHODS AND RESULTS: Among the 4248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at a single centre, we enrolled 1417 patients [71.7% male, aged 60.0 (52.0-67.0) years, 57.9% paroxysmal AF] who experienced clinical recurrences (CRs), and divided them according to the period of recurrence: within one year (n = 645), 1-2 years (n = 339), 2-5 years (n = 308), and after 5 years (CR>5 yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5 yr, the proportion of paroxysmal AF was higher (P = 0.031); however, the left atrial (LA) volume (quantified by computed tomography, P = 0.003), LA voltage (P = 0.003), frequency of early recurrence (P < 0.001), and use of post-procedure anti-arrhythmic drugs (P < 0.001) were lower. A CR>5 yr was independently associated with a low LA volume [odds ratio (OR) 0.99 (0.98-1.00), P = 0.035], low LA voltage [OR 0.61 (0.38-0.94), P = 0.032], and lower early recurrence [OR 0.40 (0.23-0.67), P < 0.001]. Extra-pulmonary vein triggers during repeat procedures were significantly greater in patients with a CR>5 yr, despite no difference in the de novo protocol (P for trend 0.003). The rhythm outcomes of repeat ablation procedures did not differ according to the timing of the CR (log-rank P = 0.330). CONCLUSIONS: Patients with a later CR exhibited a smaller LA volume, lower LA voltage, and higher extra-pulmonary vein triggers during the repeat procedure, suggesting AF progression.

Electrophysiological significance of the interatrial conduction including cavo-tricuspid isthmus during atrial fibrillation.

KEY POINTS: The interatrial conduction, including Bachmann's bundle, the posterior septal conduction, the anterior septal conduction, and the cavo-tricuspid isthmus, contributes to the maintenance mechanisms of atrial fibrillation in a 3D biatrial model. The interatrial conduction ablation including a cavo-tricuspid isthmus ablation significantly affects the wave dynamics of atrial fibrillation (AF) and facilitates the AF termination or atrial tachycardia conversion of the AF after the circumferential pulmonary vein isolation. Additional cavo-tricuspid isthmus ablation after the circumferential pulmonary vein isolation improves long-term rhythm outcome after clinical AF catheter ablation. ABSTRACT: Although it is known that atrial fibrillation (AF) is mainly a left atrial (LA) disease, the role of the right atrium (RA) and interatrial conduction (IAC), including the cavo-tricuspid isthmus (CTI), has not been clearly defined. We tested AF wave dynamics with or without IAC in computational modelling and the rhythm outcome of AF catheter ablation (AFCA) including CTI ablation in clinical cohort data. We evaluated the dominant frequency (DF) in 3D biatrial AF simulations integrated with 3D-computed tomograms obtained from 10 patients. The IAC was implemented at Bachmann's bundle, posterior septum and the CTI. After virtual circumferential PV isolation (CPVI), we disconnected IACs one by one, and observed the wave dynamics. We compared the long-term rhythm outcome after CPVI alone and additional CTI ablation in 846 patients with AFCA. LA-DF was higher than RA-DF in AF (P < 0.001). After CPVI, the DF decreased significantly by additional IAC ablation (P = 0.003), especially in the LA (P = 0.016). The amount of DF reduction (P = 0.020) and rates of AF termination (P < 0.001) or AT conversion (P = 0.021) were significantly higher after IAC ablations including CTI than those without. In clinical AFCA, the AF recurrence rate was significantly lower in patients with additional CTI ablation than CPVI alone during 25 ± 20 months' follow-up (hazard ratio 0.60 [0.46-0.79], P < 0.001, Log rank P < 0.001). IAC contributes to the maintenance mechanism of AF, and IAC including CTI ablation affects AF wave dynamics, facilitating AF termination in 3D biatrial modelling. Additional CTI ablation after CPVI improves the long-term rhythm outcome in clinical AFCA, potentially in a paroxysmal type with accompanying atrial flutter, or atrial dimension close to normal.

A mesh-type flexible tip catheter vs a contact force catheter for catheter ablation of atrial fibrillation: A prospective nonrandomized 1:1 matched study.

INTRODUCTION: Mesh-type flexible tip (MFT) catheters allow clinicians to safely generate large radiofrequency lesions during catheter ablation of atrial fibrillation (AF), while contact force (CF) catheters provide better catheter-tissue contact. We compared the clinical outcomes of catheter ablation of AF using MFT and CF catheters in a prospective, nonrandomized manner. METHODS: We prospectively assigned 217 patients with AF (paroxysmal AF 73.5%; male 69.1%; 59.9 ± 10.7 years old) at a 1:1 ratio to ablation with MFT catheters (FlexAbility) or CF catheters (TactiCath). The primary endpoint was AF recurrence after a single procedure; the secondary endpoint was a response to antiarrhythmic drugs. RESULTS: After a mean follow-up of 22.3 ± 4.4 months, the clinical recurrence rate did not significantly differ between the two study groups (29.7% vs 30.2%; P = .941) (log-rank P = .838). The recurrence rate for atrial tachycardias (30.3% vs 9.7%; P = .035) and cardioversion rates (8.1% vs 1.9%; P = .024) were higher in the MFT group than CF group. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drugs in 57.7% of the MFT group and 40.6% of the CF group (P = .010). No significant difference was found in the major complication rates between the two groups (0.9% vs 5.7%), although the ablation time was significantly longer in the MFT group (4192.1 ± 1080.2 vs 3583.8 ± 977.2 seconds; P < .001). CONCLUSION: MFT and CF catheters had similar effectiveness in achieving AF rhythm control during catheter ablation, and there was no significant difference between the two catheters with regard to overall safety.

A mendelian randomization analysis: The causal association between serum uric acid and atrial fibrillation.

BACKGROUND: Observational studies have shown that high levels of serum uric acid (UA) were associated with atrial fibrillation (AF). However, the causal effect of urate on the risk of AF is still unknown. To clarify the potential causal association between UA and AF, we performed a Mendelian randomization (MR) analysis using genetic instrumental variables (IVs). MATERIALS AND METHODS: From the Korean GWAS dataset of 633 patients with AF (mean age 50.6 ± 7.8 years, 80.9% male, Yonsei AF Ablation cohort) who underwent radiofrequency catheter ablation and the data from 3533 controls (from the Korea Genome Epidemiology Study), we selected 9 SNPs, with a P value less than .05, associated with an increased UA serum level. Additionally, we calculated the weighted genetic risk score (wGRS) using the selected 9 SNPs, to use it as an instrumental variable. A Mendelian randomization analysis was calculated by a 2-stage estimator method. RESULTS: The conventional association between the serum UA and AF was significant (P = .001) after adjusting for potential confounding factors. The SNP rs1165196 on SLC17A1 (F-statistics = 208.34, 0.18 mg/mL per allele change, P < .001) and wGRS (F-statistics = 222.26, 0.20 mg/mL per 1SD change, P < .001) were significantly associated with an increase in the UA level. The MR analysis was causally associated with rs1165196 (estimated odds ratio (OR), 0.21, 95% confidence interval (CI), 0.06-0.75, P = .017), but not wGRS (estimated OR, 1.07, 95% CI, 0.57-2.01, P = .832). CONCLUSION: The serum UA level was independently associated with the AF risk.

Trends and Outcome of Catheter Ablation of Atrial Fibrillation Over 9 Years　- Focus on Empirical Extra-Pulmonary Vein Ablation.

BACKGROUND: The Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II (STAR-AF2) emphasized the importance of circumferential pulmonary vein isolation (CPVI) during AF ablation. Methods and Results: This study involved 2,297 consecutive patients (mean age, 58±11 years; 73.1% male, 70.1% paroxysmal AF) undergoing AF ablation from 2009 to 2017. We investigated the ablation lesion set, ablation time, catheter type, and clinical outcomes. Over the 9 years, the extra-pulmonary vein (PV) left atrial (LA) ablation rate (76.8% to 19.4%, P<0.001 for trend) and ablation time (P<0.001 for trend) decreased dramatically, whereas the 1-year recurrence rates decreased (21.8% to 14.1%, P=0.04 for trend). In persistent AF patients, the extra-PV LA ablation rate (91.4% to 55.3%, P<0.001) and ablation time (P<0.001) decreased after the STAR-AF2 report, but the 1-year recurrence rates remained similar (22.1% to 17.9%, P=0.281). A mesh-type flexible tip (MFT) catheter with a moderately increased radiofrequency power was used since 2012, and the MFT catheter was independently associated with a lower clinical recurrence compared to other irrigated-tip catheters (HR, 0.670; 95% CI: 0.559-0.803, P<0.001; log rank P=0.002) without increasing the procedure-related complications (OR, 1.434; 95% CI: 0.937-2.194, P=0.097). CONCLUSIONS: Over the 9 years the extra-PV LA ablation and 1-year recurrence rates in the AF ablation cohort decreased, in part due to improved catheter technology.

Cardiac Vein Accessibility According to Heart Diseases and Sex: Implications for Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an important therapy in patients with heart failure (HF) and dyssynchrony. We performed the present study to elucidate clinical factors associated with cardiac vein accessibility. METHODS: In 255 consecutive patients (age, 48.7 ± 19.4 years; male, 126), cardiac venography was performed during CRT implantation or an electrophysiological study. We measured the diameters and the proximal branching angles of the lateral cardiac and posterior ventricular veins. Easy accessibility of the cardiac vein was defined as a lumen diameter ≥1.6 mm with an angle of ≥90°. We compared baseline characteristics between patients with and without easily accessible cardiac veins. We compared cardiac vein accessibility between patients with and without HF, including ischemic and nonischemic HF, and between males and females. RESULTS: In 189 (74.1%) patients, the cardiac veins were easily accessible. The cardiac veins were more easily accessible in patients with HF (n = 75) compared with patients without HF (n = 180; 89.3% and 67.8%, respectively; P < 0.001). The cardiac veins were more easily accessible in patients with nonischemic HF (n = 56) compared with patients with ischemic HF (n = 19; 96.4% and 68.4%, respectively; P = 0.003). The cardiac veins were more easily accessible in females compared with males (79.8% and 68.3%, respectively; P = 0.035). CONCLUSIONS: Accessing the cardiac veins for CRT implantation was difficult in ∼10% of patients with HF. Cardiac vein accessibility was high in patients with nonischemic HF and in females.

The Effects of Radiofrequency Catheter Ablation for Atrial Fibrillation on Right Ventricular Function.

BACKGROUND AND OBJECTIVE: The effects of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) on right ventricular (RV) function are not well known. METHODS: Patients who underwent RFCA for AF and underwent pre- and post-procedural echocardiography were enrolled consecutively. Fractional area change (FAC), RV free-wall longitudinal strain (RVFWSL), and RV 4-chamber strain including the ventricular septum (RV4CSL) were measured. Changes in FAC, RVFWSL, and RV4CSL before and after RFCA were compared among paroxysmal AF (PAF), persistent AF (PeAF), and long-standing persistent AF (LSPeAF) groups. RESULTS: A total of 164 participants (74 PAF, 47 PeAF, and 43 LSPeAF; age, 60.8 ± 9.8 years; men, 74.4%) was enrolled. The patients with PeAF and LSPeAF had worse RV4CSL (p<0.001) and RVFWSL (p<0.001) than those with PAF and reference values. Improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared with the PAF and LSPeAF groups (ΔRV4CSL, 8.4% [5.1, 11.6] in PeAF vs. 1.0% [-1.0, 4.1] in PAF, 1.9% [-0.2, 4.4] in LSPeAF, p<0.001; ΔRVFWSL, 9.0% [6.9, 11.5] in PeAF vs. 0.9% [-1.4, 4.9] in PAF, 1.0% [-1.0, 3.6] in LSPeAF, p<0.001). In patients without recurrence, improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared to the LSPeAF group. CONCLUSIONS: RV systolic function is more impaired in patients with PeAF and LSPeAF than in those with PAF. RV systolic function is more improved after RFCA in patients with PeAF than in those with PAF or LSPeAF.

Clinical Characteristics and Rhythm Outcomes in Patients With Atrial Myopathy After Successful Catheter Ablation of Atrial Fibrillation.

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<0.001) than other groups. CONCLUSIONS: Blunted LA reverse remodeling after AF catheter ablation, which is suggestive of atrial myopathy, was independently associated with a larger ventricular epicardial adipose tissue volume and worsening of H2FPEF score. Blunted LA reverse remodeling after AF catheter ablation was also an independent predictor for higher recurrences of AF post-1-year AF catheter ablation.

Anti- and pro-fibrillatory effects of pulmonary vein isolation gaps in human atrial fibrillation digital twins.

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 < 0.001). Extra-PV induction yielded a higher ratio of AF at the final rhythm than internal PV induction (77.5% vs. 59.0%, p < 0.001). In conclusion, our human AF digital twin model helped assess AF maintenance mechanisms. Clinical trial registration: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695.

Sex difference in atrial fibrillation recurrence after catheter ablation and antiarrhythmic drugs.

OBJECTIVE: The risk of recurrence after atrial fibrillation (AF) catheter ablation (AFCA) is higher in women than in men. However, it is unknown whether a sex difference exists in antiarrhythmic drug (AAD) responsiveness among patients with recurrence. METHODS: Among 2999 consecutive patients (26.5% women, 58.3±10.9 years old, 68.1% paroxysmal AF) who underwent de novo AFCA, we compared and evaluated the sex differences in rhythm outcome in 1094 patients with recurrence and in 788 patients who subsequently underwent rhythm control with AAD. RESULTS: During a follow-up of 48.2±34.9 months, 1094 patients (36.5%) had AF recurrence after AFCA, and 508 of 788 patients (64.5%) had AF recurrence under AAD. Although the rhythm outcome of a de novo AFCA was worse (log-rank p=0.041, HR 1.28, 95% CI 1.02 to 1.59), p=0.031) in women, AAD response after postprocedural recurrences was better in women than in men (log-rank p=0.003, HR 0.75, 95% CI 0.59 to 0.95, p=0.022), especially in women older than 60 years old (log-rank p=0.003). In 249 patients who underwent repeat procedure after AAD use, the pulmonary vein (PV) reconnection rate (62.7% vs 76.8%, p=0.048) was lower in women than in men but not the existence of extra-PV trigger (37.8% vs 25.4%, p=0.169). CONCLUSIONS: Although women showed worse rhythm outcomes than men after AFCA, the post-AFCA AAD response was better in elderly women than in men. TRIAL REGISTRATION NUMBER: NCT02138695.

Comparison of pulmonary vein isolation using cryoballoon, high-power short-duration, and conventional radiofrequency ablation for atrial fibrillation: a propensity score-weighted study.

Background: The 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 methods: In 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. Results: Despite 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 < 0.001), the major complication (p = 0.906) and clinical recurrence rates were similar across the three ablation groups (weighted log-rank, p = 0.824). However, the Cryo-PVI group was associated with a significantly lower risk of recurrent AF in patients with paroxysmal AF [weighted hazard ratio (WHR) 0.57, 95% confidence interval (CI) 0.37-0.86], whereas it was associated with a higher risk of recurrent AF in patients with persistent AF (WHR 1.41, 95% CI 1.06-1.89, p for interaction of <0.001) compared with the conventional-PVI group. In the subgroup analysis for the HRV, the Cryo-PVI group had the highest low-frequency-to-high-frequency ratio at 1-year post-procedure, whereas the HPSD-PVI group had the lowest low-frequency-to-high-frequency ratio at 1-year post-procedure (p < 0.001). Conclusions: The Cryo-PVI group had better rhythm outcomes in patients with paroxysmal AF but worse rhythm outcomes in patients with persistent AF and a higher long-term post-procedural sympathetic nervous activity and sympatho-vagal balance compared with the conventional-PVI group.

Artificial Intelligence-Enabled ECG Algorithm for the Prediction of Coronary Artery Calcification.

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.

Anti-atrial Fibrillation Effects of Pulmonary Vein Isolation With or Without Ablation Gaps: A Computational Modeling Study.

Background: Although pulmonary vein isolation (PVI) gaps contribute to recurrence after atrial fibrillation (AF) catheter ablation, the mechanism is unclear. We used realistic computational human AF modeling to explore the AF wave-dynamic changes of PVI with gaps (PVI-gaps). Methods: We included 40 patients (80% male, 61.0 ± 9.8 years old, 92.5% persistent AF) who underwent AF catheter ablation to develop our realistic computational AF model. We compared the effects of a complete PVI (CPVI) and PVI-gap (2-mm × 4) on the AF wave-dynamics by evaluating the dominant frequency (DF), spatial change of DF, maximal slope of the action potential duration restitution curve (Smax), and AF defragmentation rate (termination or change to atrial tachycardia), and tested the effects of additional virtual interventions and flecainide on ongoing AF with PVI-gaps. Results: Compared with the baseline AF, CPVIs significantly reduced extra-PV DFs (p < 0.001), but PVI-gaps did not. COV-DFs were greater after CPVIs than PVI-gaps (p < 0.001). Neither CPVIs nor PVI-gaps changed the mean Smax. CPVIs resulted in higher AF defragmentation rates (80%) than PVI-gaps (12.5%, p < 0.001). In ongoing AF after PVI-gaps, the AF defragmentation rates after a wave-breaking gap ablation, extra-PV DF ablation, or flecainide were 60.0, 34.3, and 25.7%, respectively (p = 0.010). Conclusion: CPVIs effectively reduced the DF, increased its spatial heterogeneity in extra-PV areas, and offered better anti-AF effects than extra-PV DF ablation or additional flecainide in PVI-gap conditions.

Corrigendum: Computational modeling for antiarrhythmic drugs for atrial fibrillation according to genotype.

[This corrects the article DOI: 10.3389/fphys.2021.650449.].

Corrigendum: Association of ZFHX3 genetic polymorphisms and extrapulmonary vein triggers in patients with atrial fibrillation who underwent catheter ablation.

[This corrects the article DOI: 10.3389/fphys.2021.807545.].

Ablation and antiarrhythmic drug effects on PITX2 +/- deficient atrial fibrillation: A computational modeling study.

Introduction: Atrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 (PITX2) gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablation, additional high dominant frequency (DF) site ablation, and antiarrhythmic drug (AAD) effects according to the patient genotype (wild-type and PITX2 +/- deficient) using computational modeling. Methods: We included 25 patients with AF (68% men, 59.8 ± 9.8 years of age, 32% paroxysmal AF) who underwent AF catheter ablation to develop a realistic computational AF model. The ion currents for baseline AF and the amiodarone, dronedarone, and flecainide AADs according to the patient genotype (wild type and PITX2 +/- deficient) were defined by relevant publications. We tested the virtual CPVI (V-CPVI) with and without DF ablation (±DFA) and three virtual AADs (V-AADs, amiodarone, dronedarone, and flecainide) and evaluated the AF defragmentation rates (AF termination or changes to regular atrial tachycardia (AT), DF, and maximal slope of the action potential duration restitution curves (Smax), which indicates the vulnerability of wave-breaks. Results: At the baseline AF, mean DF (p = 0.003), and Smax (p < 0.001) were significantly lower in PITX2 +/- deficient patients than wild-type patients. In the overall AF episodes, V-CPVI (±DFA) resulted in a higher AF defragmentation relative to V-AADs (65 vs. 42%, p < 0.001) without changing the DF or Smax. Although a PITX2 +/- deficiency did not affect the AF defragmentation rate after the V-CPVI (±DFA), V-AADs had a higher AF defragmentation rate (p = 0.014), lower DF (p < 0.001), and lower Smax (p = 0.001) in PITX2 +/- deficient AF than in wild-type patients. In the clinical setting, the PITX2 +/- genetic risk score did not affect the AF ablation rhythm outcome (Log-rank p = 0.273). Conclusion: Consistent with previous clinical studies, the V-CPVI had effective anti-AF effects regardless of the PITX2 genotype, whereas V-AADs exhibited more significant defragmentation or wave-dynamic change in the PITX2 +/- deficient patients.

Corrigendum: Spatial changes in the atrial fibrillation wave-dynamics after using antiarrhythmic drugs: A computational modeling study.

[This corrects the article DOI: 10.3389/fphys.2021.733543.].

Restitution Slope Affects the Outcome of Dominant Frequency Ablation in Persistent Atrial Fibrillation: CUVIA-AF2 Post-Hoc Analysis Based on Computational Modeling Study.

Introduction: Although 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. Methods: We 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). Results: Mean 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 <1 (61.5 vs. 7.7%, p = 0.011). In post-DF ablation defragmentation episodes, DF was significantly higher (p = 0.002), and Smax was lower (p = 0.003) than in episodes without defragmentation. In the post-hoc analysis of CUVIA-AF2, we replicated the inverse relationship between Smax and DF (r = -0.47, p < 0.001), and we observed better rhythm outcomes of clinical DF ablations in addition to a PVI than of empirical PVI at Smax <1 [hazard ratio 0.45, 95% CI (0.22-0.89), p = 0.022; log-rank p = 0.021] but not at ≥ 1 (log-rank p = 0.177). Conclusion: We found an inverse relationship between DF and Smax and the outcome of DF ablation after PVI was superior at the condition with Smax <1 in both in-silico and clinical trials.

Machine Learning-Predicted Progression to Permanent Atrial Fibrillation After Catheter Ablation.

INTRODUCTION: We 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. METHODS: Cohort 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. RESULTS: The 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 <1.109 mV (2 points, p = 0.004), and PR interval ≥196 ms (1 point, p = 0.001), based on multivariate Cox analyses, and it had a good discriminative power for progression to permanent AF [area under curve (AUC) 0.796, 95% confidence interval (CI): 0.753-0.838]. The ML prediction model calculated the risk for AF progression without invasive variables and achieved excellent risk stratification: AUC 0.935 for low-risk groups (score = 0), AUC 0.855 for intermediate-risk groups (score 1-3), and AUC 0.965 for high-risk groups (score ≥ 4) in cohort 1. The ML model successfully predicted the high-risk group for AF progression in cohort 2 (log-rank p < 0.001). CONCLUSIONS: The ML-prediction model successfully classified the high-risk patients who will progress to permanent AF after AFCA without invasive variables but has a limited discrimination power for the intermediate-risk group.