Left Atrial Localized Low-Voltage Areas Indicate Whole Left Atrial Electrophysiological Degeneration in Atrial Fibrillation Patients.

BACKGROUND: The efficacy of ablation targeting low-voltage areas (LVAs) is controversial, although LVA presence is well known to be associated with atrial fibrillation (AF) recurrence after ablation. AF substrate may not localize within LVAs.Methods and Results:This observational study enrolled 405 consecutive patients who underwent an initial AF ablation procedure. The left atrial (LA) voltage map was obtained after pulmonary vein isolation. LVAs were defined as areas with voltage <0.5 mV. To estimate whole LA electrophysiological degeneration, mean regional voltage at each of the 6 regions and LA total conduction velocity were measured. LVAs existed in 143 of 405 (35.3%) patients. Patients with LVAs demonstrated lower mean regional voltages throughout all 6 regions compared to those without LVAs (1.3 [1.8, 0.8] vs. 0.6 [1.0, 0.2] mV for the anterior wall, P<0.001). In contrast, LA conduction velocity was lower in patients with LVAs than in those without (0.89 [1.01, 0.74] vs. 0.93 [1.03, 0.87] m/s, P<0.001). Multivariate analysis revealed that low LA total conduction velocity and a higher number of regions with mean voltage reduction were independently associated with AF recurrence, although LVA presence was not. CONCLUSIONS: Patients with localized LA LVAs were characterized by whole LA electrophysiological degeneration as assessed by mean regional voltage and conduction velocity. In addition, whole LA electrophysiological degeneration parameters were well associated with AF recurrence.

Persistent atrial fibrillation ablation in cardiac laminopathy: Electrophysiological findings and clinical outcomes.

BACKGROUND: Little is known about persistent atrial fibrillation (AF) ablation in patients with cardiac laminopathy (CLMNA). OBJECTIVES: We aimed to characterize atrial electrophysiological properties and to assess the long-term outcomes of persistent AF ablation in patients with CLMNA. METHODS: All patients with CLMNA referred in our center for persistent AF ablation were retrospectively included. Left atrial (LA) volume, left atrial appendage (LAA) cycle length, interatrial conduction delay, and LA voltage amplitude were analyzed during the ablation procedure. Sinus rhythm maintenance and LA contractile function were assessed during long-term follow-up. RESULTS: From 2011 to 2020, 8 patients were included. The mean age was 47 ± 14 years, and 3 patients (38%) were women. The LA volume was 205.8 ± 43.7 mL; the LAA AF cycle length was 250.7 ± 85.6 ms; and the interatrial conduction delay was 296.5 ± 110.1 ms. Large low-voltage areas (>50% of the LA surface; <0.5 mV electrogram) were recorded in all 8 patients. Two patients had inadvertent LAA disconnection during ablation. All A waves recorded by pulsed Doppler in sinus rhythm were <30 cm/s before and after AF ablation. Early arrhythmia recurrence was recorded in 7 patients (87%) (time to recurrence 4 ± 4 months; 1.5 procedures per patient). After a mean follow-up of 4.4 ± 3.2 years, 4 patients underwent implantable cardioverter-defibrillator therapy for life-threatening ventricular arrhythmia and 3 patients finally underwent heart transplantation. CONCLUSION: Patients with persistent AF afflicted by CLMNA exhibit severe LA impairment because of large low-voltage areas, prolonged conduction velocity, and reduced contractile function. Ablation procedures have a limited effect with a high recurrence rate.

A new clinical risk score for predicting the prevalence of low-voltage areas in patients undergoing atrial fibrillation ablation.

INTRODUCTION: Although the presence of left atrial low-voltage areas (LVAs) is strongly associated with the recurrence of atrial fibrillation (AF) after ablation, few methods are available to classify the prevalence of LVAs. The purpose of this study was to establish a risk score for predicting the prevalence of LVAs in patients undergoing ablation for AF. METHODS: We enrolled 1004 consecutive patients who underwent initial ablation for AF (age, 68 ± 10 years old; female, 346 (34%); persistent AF, 513 (51%)). LVAs were deemed present when the voltage map after pulmonary vein isolation demonstrated low-voltage areas with a peak-to-peak bipolar voltage of <0.5 mV covering ≥5 cm2 of the left atrium. RESULTS: LVAs were present in 206 (21%) patients. The SPEED score was obtained as the total number of independent predictors as identified on multivariate analysis, namely female sex (odds ratio [OR], 3.4 [95% confidence interval {CI} 2.2-5.2], p < .01), persistent AF (OR, 1.8 [95% CI, 1.1-3.0], p = .02), age ≥ 70 years (OR, 2.3 [95% CI, 1.5-3.4], p < .01), elevated brain natriuretic peptide ≥100 pg/ml or N-terminal probrain natriuretic peptide ≥400 pg/ml (OR, 1.7 [95% CI, 1.02-2.8], p = .04), and diabetes mellitus (OR, 1.8 [95% CI, 1.1-2.8], p = .02). LVAs were more frequent in patients with a higher SPEED score, and prevalence increased with each additional SPEED score point (OR, 2.4 [95% CI, 2.0-2.8], p < .01). CONCLUSION: The SPEED score accurately predicts the prevalence of LVAs in patients undergoing ablation for AF.

Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC. METHODS: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R10, n=37), rivaroxaban 15 mg (R15, n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up. RESULTS: The primary end point was reduced with R10 (179 pmol/L [interquartile range (IQR), 129-273], P<0.0001) and R15 (163 pmol/L [IQR, 112-231], P<0.0001) as compared with DAPT (322 pmol/L [IQR, 218-528]). We observed no significant reduction of the primary end point between R10 and R15 while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127-290) with R10 to 274 ng/mL (IQR, 192-377) with R15, P<0.0001. Thrombin-antithrombin complex and D-dimers were numerically lower with both rivaroxaban doses than with DAPT. These findings were all confirmed at 3 months. The clinical end points were not different between groups. A device thrombosis was noted in 2 patients assigned to DAPT. CONCLUSIONS: Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03273322.

Machine Learning to Classify Intracardiac Electrical Patterns During Atrial Fibrillation: Machine Learning of Atrial Fibrillation.

BACKGROUND: Advances in ablation for atrial fibrillation (AF) continue to be hindered by ambiguities in mapping, even between experts. We hypothesized that convolutional neural networks (CNN) may enable objective analysis of intracardiac activation in AF, which could be applied clinically if CNN classifications could also be explained. METHODS: We performed panoramic recording of bi-atrial electrical signals in AF. We used the Hilbert-transform to produce 175 000 image grids in 35 patients, labeled for rotational activation by experts who showed consistency but with variability (kappa [κ]=0.79). In each patient, ablation terminated AF. A CNN was developed and trained on 100 000 AF image grids, validated on 25 000 grids, then tested on a separate 50 000 grids. RESULTS: In the separate test cohort (50 000 grids), CNN reproducibly classified AF image grids into those with/without rotational sites with 95.0% accuracy (CI, 94.8%-95.2%). This accuracy exceeded that of support vector machines, traditional linear discriminant, and k-nearest neighbor statistical analyses. To probe the CNN, we applied gradient-weighted class activation mapping which revealed that the decision logic closely mimicked rules used by experts (C statistic 0.96). CONCLUSIONS: CNNs improved the classification of intracardiac AF maps compared with other analyses and agreed with expert evaluation. Novel explainability analyses revealed that the CNN operated using a decision logic similar to rules used by experts, even though these rules were not provided in training. We thus describe a scaleable platform for robust comparisons of complex AF data from multiple systems, which may provide immediate clinical utility to guide ablation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02997254. Graphic Abstract: A graphic abstract is available for this article.

Efficacy of an Adjunctive Electrophysiological Test-Guided Left Atrial Posterior Wall Isolation in Persistent Atrial Fibrillation Without a Left Atrial Low-Voltage Area.

BACKGROUND: Electrical remodeling precedes structural remodeling. In adjunctive left atrial (LA) low-voltage area (LVA) ablation to pulmonary vein isolation of atrial fibrillation (AF), LA areas without LVA have not been targeted for ablation. We studied the effect of adjunctive LA posterior wall isolation (PWI) on persistent AF without LA-LVA according to electrophysiological testing (EP test). METHODS: We examined consecutive patients with persistent AF with (n=33) and without (n=111) LA-LVA. Patients without LA-LVA were randomly assigned to EP test-guided (n=57) and control (n=54) groups. In the EP test-guided group, an adjunctive PWI was performed in those with positive results (PWI subgroup; n=24), but not in those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, effective refractory period>20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia (AT) during measurements. LVA ablation was performed in the patients with LA-LVA. RESULTS: During the follow-up period (62±33 weeks), the EP test-guided group had significantly lower recurrence rates (19%,11/57 versus 41%, 22/54, P=0.012) and higher Kaplan-Meier AF/AT-free survival curve rates than the control group (P=0.01). No significant differences in the recurrence and AF/AT-free survival curve rates between the PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analyses identified EP test-guided ablation as a factor reducing the recurrence rate. The recurrence rates in the LA-LVA ablation group and EP test-guided group were similar. CONCLUSIONS: This pilot study proposed that an EP test-guided adjunctive PWI of persistent AF without LA-LVA potentially reduced AF/AT recurrences. The results suggest that there is an AF substrate in the LA with altered electrophysiological function even when there is no LA-LVA. Graphic Abstract: A graphic abstract is available for this article.

Additional Low-Voltage-Area Ablation in Patients With Paroxysmal Atrial Fibrillation: Results of the Randomized Controlled VOLCANO Trial.

Background The efficacy of low-voltage-area (LVA) ablation has not been well determined. This study aimed to investigate the efficacy of LVA ablation in addition to pulmonary vein isolation on rhythm outcomes in patients with paroxysmal atrial fibrillation (AF). Methods and Results VOLCANO (Catheter Ablation Targeting Low-Voltage Areas After Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation Patients) trial included paroxysmal AF patients undergoing initial AF ablation. Of 398 patients in whom a left atrial voltage map was obtained after pulmonary vein isolation, 336 (85%) had no LVA (group A). The remaining 62 (15%) patients with LVAs were randomly allocated to undergo LVA ablation (group B, n=30) or not (group C, n=32) in a 1:1 fashion. Primary end point was 1-year AF-recurrence-free survival rate. No adverse events related to LVA ablation occurred. Procedural (124±40 versus 95±33 minutes, P=0.003) and fluoroscopic times (29±11 versus 24±8 minutes, P=0.034) were longer in group B than group C. Patients with LVAs demonstrated lower AF-recurrence-free survival rates (88%) than those without LVA (B, 57%, P<0.0001; C, 53%, P<0.0001). However, LVA ablation in addition to pulmonary vein isolation did not impact AF-recurrence-free survival rate (group B versus C, P=0.67). Conclusions The presence of LVA was a strong predictor of AF recurrence after pulmonary vein isolation in patients with paroxysmal AF. However, LVA ablation had no beneficial impact on 1-year rhythm outcomes. Registration URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023403.

Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation.

BACKGROUND: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. METHODS: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. RESULTS: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. CONCLUSION: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker.

Computed tomography-derived left atrial volume index, sex, and age to predict the presence and the extent of left atrial low-voltage zones in patients with atrial fibrillation: The ZAQ score.

BACKGROUND: Pulmonary vein isolation is the cornerstone of catheter ablation in patients with atrial fibrillation (AF). However, with advanced left atrial (LA) structural changes, additional targeted catheter ablation of low-voltage zones (LVZs) has produced favorable results. Therefore, with the advent of single-shot techniques, it would be helpful to predict the presence of LVZs before an ablation procedure. OBJECTIVE: We hypothesized that computed tomography (CT)-derived left atrial volume index (LAVI), in combination with other objective parameters, could be used to develop a score able to predict the presence of LVZs. METHODS: In a large cohort of patients undergoing their first AF ablations, comprehensive echocardiographic evaluations and cardiac CT were performed. During the electrophysiological studies, LA geometry and electroanatomic voltage maps were created. LVZs were defined as areas ≥1 cm2 with bipolar peak-to-peak voltage amplitudes ≤0.5 mV. RESULTS: In a derivation cohort of 374 patients, predictors of LVZs were identified by regression analysis and used to build the Zentralklinik Bad Berka and University of L'Aquila (ZAQ) score (age ≥65 years; female sex; and CT-LAVI ≥57 mL/m2 ). The ZAQ score of 2 points accurately identified the presence and the extent of LVZs (area under the curve [AUC], 0.809; 95% confidence interval [CI], 0.758-0.861; P < .001 and 3 [interquartile range, IQR, 1.5-4.5] vs 7 cm2 [IQR 4-9]; P = .001). In a validation cohort of 103 patients, the predictive value of the score was confirmed (AUC, 0.793; 95% CI, 0.709-0.878; P < .001 and 4 [IQR, 2-7] vs 11.5 cm2 [IQR, 8-16.5]; P = .001). CONCLUSIONS: The ZAQ score identifies LVZs and may be useful for planning the ablation strategy ahead of time.

Association between left atrial reverse remodeling and maintenance of sinus rhythm after catheter ablation of persistent atrial fibrillation.

The success rate of catheter ablation of persistent atrial fibrillation (AF) is not satisfactory, for reasons that are unclear. The purpose of this study was to examine the relationship between left atrial reverse remodeling after ablation and recurrence of AF in patients with persistent AF. One hundred and thirty-two patients with persistent AF were enrolled. Extensive encircling pulmonary vein isolation plus ablation of complex fractionated atrial electrograms was performed. Bepridil or amiodarone was prescribed for 3 months after ablation. All patients were studied by serial echocardiography and 24-h ambulatory electrocardiogram at baseline, for the day after ablation, and at 1-, 3-, and 6-month intervals after ablation. Recurrence of AF was observed in 42 patients at 2-year follow-up. The duration of AF (median 12 (IQR 6-37) vs 8 (IQR 5-17) months, p < 0.05), and early recurrence of AF (69 vs 26%, p < 0.05) after ablation were significantly different between the patients with AF recurrence and those without. The left atrial dimensions at 3 months (40 ± 6 vs 44 ± 6 mm, p < 0.001) and 6 months (40 ± 6 vs 44 ± 6 mm, p < 0.001) were significantly smaller than those just after ablation in the patients without AF recurrence. A 5% reduction from baseline in the left atrial dimension at 6 months after ablation was associated with freedom from late AF recurrence (p < 0.05). Left atrial reverse remodeling after ablation of persistent AF was associated with freedom from late recurrence of AF.

Endocardial contact mapping of the left atrial appendage in persistent atrial fibrillation.

INTRODUCTION: Isolation of the left atrial appendage (LAA) is often performed in persistent atrial fibrillation (AF). Propagation patterns in the LAA during AF remain to be elucidated. We sought to characterize propagation patterns in the LAA during AF in persistent AF. METHODS: Persistent AF patients undergoing catheter ablation were studied. Pulmonary vein isolation (PVI) was performed during continuous AF. If AF was not terminated by PVI, bi-atrial mapping was performed using a multi-electrode catheter during AF. Maps were collected at each site for 30 seconds and analyzed offline with a novel software, CARTOFINDER. This software made automatic determinations of whether activation was focal or rotational. The left atrium (LA) was divided into five regions, of which the LAA was one, and the right atrium (RA) into three. RESULTS: Eighty patients were studied (62 ± 10 years, 65 males). On average, 9.6 ± 2.2 and 4.1 ± 1.2 maps were created in the LA and RA, respectively. The LAA was mapped in 70 patients, resulting in 85 maps. In the LAA, activation was identified as focal more often than rotational (64 [91%] vs 10 [14%] patients, P < .001), seven patients displayed both. The number of focal activation events was greatest in the LAA (28.5 events/30 seconds [interquartile range, 15-54]) of the eight atrial regions. During focal activation, sites designated as earliest activation frequently covered a wide area, rather than being localized to a discrete site (5.4 ± 3.1 electrodes). CONCLUSIONS: The results of this study suggest that focal activation is a major mechanism underlying the arrhythmogenicity of the LAA in persistent AF.

Arnebiae Radix prevents atrial fibrillation in rats by ameliorating atrial remodeling and cardiac function.

ETHNOPHARMACOLOGICAL RELEVANCE: Arnebiae Radix, a common herbal medicine in China, is often utilized to treat blood-heat syndrome and has been reported to exert an effect on the heart. AIM OF THE STUDY: The combination of acetylcholine (Ach) and CaCl2 has been widely used to induce atrial fibrillation (AF) in animals. However, whether Arnebiae Radix displays any preventive action on Ach-CaCl2 induced AF in rats remains uncertain. In our study, we attempted to investigate the protective effects of Arnebiae Radix on Ach-CaCl2 induced AF compared to amiodarone, which was employed as the positive control. MATERIALS AND METHODS: To establish the AF model, SD rats were treated with a mixture of 0.1 mL/100 g Ach-CaCl2 (60 µg/mL Ach and 10 mg/mL CaCl2) by tail vein injection for 7 days. Rats were also given a gavage of Arnebiae Radix (0.18 g/mL) one week before or concurrently with the establishment of the AF model. At the end of the experimental period, the induction, duration and timing of AF were monitored using electrocardiogram recordings. Left atrial tissues were stained to observe the level of fibrosis. Electrophysiological measurements were used to examine atrial size and function. RESULTS: In Ach-CaCl2-induced AF rats, Arnebiae Radix decreased AF induction, duration and susceptibility to AF. In addition, Arnebiae Radix significantly reduced atrial fibrosis and inhibited atrial enlargement induced by Ach-CaCl2. Moreover, there was an apparent improvement in cardiac function in the Arnebiae Radix-treated group. CONCLUSIONS: Our findings indicate that Arnebiae Radix treatment can attenuate Ach-CaCl2-induced atrial injury and serve as an effective therapeutic strategy for the treatment of AF in the future.

Invited review: hypertension and atrial fibrillation: epidemiology, pathophysiology, and implications for management.

Hypertension affects around half of the adult population worldwide, being one of the most common cardiovascular disorders. On a population basis, high blood pressure is considered to be the major independent risk factor for atrial fibrillation (AF). The incidence of both diseases has increased significantly in the recent decades and it is expected to continuously surge in the following years. Due to close relation between the both diseases and their frequent coexistence, hypertension and AF become major health priorities. The multidirectional linking between raised blood pressure and AF is based on complex associations including structural, hemodynamic, neuroendocrine, and autonomic mechanisms. Hypertension provokes excessive fibroblasts proliferation and increased collagen accumulation. It also stimulates cardiomyocytes apoptosis and inflammation, leading to diffused fibrosis and left ventricular hypertrophy development. This is mainly driven by renin-angiotensin-aldosterone system (RAAS) activation, and autonomic dysregulation. Moreover, exposure on long-term stretch due to hypertension causes arterial stiffness with subsequent systolic and diastolic function loss resulting in further heart muscle remodeling. All these pathological changes combined seem influence on myocardial electrical activity, triggering AF development. Given the prevalence and frequent lack of symptoms of both disorders, opportunistic arrhythmia screening in hypertensive patients is needed. In all individuals with established diagnosis of AF, adequate anticoagulation has to be considered for stroke prevention. Blood pressure control is also an essential component of a holistic approach to AF care.

Left atrial voltage mapping with a direction-independent grid catheter: Comparison with a conventional circular mapping catheter.

INTRODUCTION: A recently introduced grid mapping catheter (GMC) is designed for better electrode-tissue contact and can collect bipolar signals both along and across the splines, which may allow more efficient voltage map generation independent of propagation direction. We compared the GMC with a conventional circular mapping catheter (CMC) for left atrial (LA) voltage mapping. METHODS: This study included 20 consecutive patients undergoing repeat ablation for recurrent atrial fibrillation who had demonstrated LA low-voltage areas (LVAs, <0.10 mV). Following pulmonary vein isolation, LA voltage mapping was performed twice, once using the GMC and once using the CMC. RESULTS: Voltage mapping was more efficient using the GMC than the CMC in terms of mapping time (459 [404, 543] vs 602 [496, 814] seconds; P = .014) and the number of mapping points (2446 [2099, 3104] vs 1841 [1494, 2314]; P = .002). The incidence of catheter-induced ectopies was lower (44 [28, 62] vs 114 [74, 188]; P < .0001) using the GMC. The GMC utilizing all bipoles detected LVAs in 85% of patients with LVAs detected by CMC. LVA measurements were significantly smaller on maps generated by the GMC using bipoles along or across the splines than those measured with the CMC (11.1 [4.6, 17.2] or 9.7 [2.5, 16.0] vs 16.4 [6.8, 26.8] cm2 ; P = .008 and P = .001, respectively), and were even smaller when using all bipoles (7.9 [1.1, 13.5] cm2 , P = .0001). CONCLUSION: The GMC allowed a more efficient mapping procedure and enabled more selective identification of LVAs with smaller LVA size.

Significance of inducibility of atrial fibrillation after pulmonary vein isolation in patients with healthy left atrium substrate.

BACKGROUND: The significance of the inducibility of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF remains disputable and polarizing. Therefore, we investigated the prognostic value of the inducibility of AF on long-term outcome after PVI in patients without low-voltage left atrial (LA) substrate. METHODS: Two hundred forty-five patients (mean age 59+/-9years, 72% male) without LA low-voltage areas (defined as electrogram amplitudes <0.5 mV) undergoing first PVI procedure were included in the study. Following successful PVI, inducibility was assessed by burst pacing from coronary sinus with a cycle length (CL) of 300, 250, and 200 ms or the shortest CL resulting in 1:1 atrial capture. During the follow-up period of up to 3 years, the rhythm outcome was monitored by serial 7-days Holter electrocardiogram. RESULTS: AF was induced in 38 patients (16%). Atypical atrial flutter was observed in six patients (2%), while typical flutter in three cases (1%). Within the first 3 months, early recurrence was diagnosed in 39 patients (16%), while late recurrence was detected in 58 patients (24%) after a mean AF free survival of 28 ± 1 months. While there was no impact on early recurrence, AF inducibility affected long-term recurrence (31 ± 1 vs 23 ± 3 months; P = .001). In multivariate analysis, AF inducibility (hazard ratio [HR] 2.14; 95% confidence interval [CI], 1.03-4.45; P = .041) and persistent type of AF (HR 2.17; 95%CI, 1.06-4.47; P = .034) were associated with late AF recurrence. CONCLUSION: In patients without low-voltage substrate undergoing PVI, AF inducibility is a significant predictor of long-term outcome. The pathomechanisms of this phenomenon must be further studied to be addressed by additional treatment.

Association between prolonged P wave duration and left atrial scarring in patients with paroxysmal atrial fibrillation.

BACKGROUND: We evaluated the association of P wave duration (PWD) with left atrial scar (LAS) in patients with paroxysmal atrial fibrillation (PAF). METHODS: Consecutive patients with PAF undergoing their first catheter ablation were screened and only those in sinus rhythm at baseline were included in the analysis. A standard 12-lead electrocardiogram (ECG) was performed in all and three-dimensional voltage mapping of the left atrium was generated for identification of low-voltage areas (≤0.2 mV) before the procedure. RESULTS: In total, 411 patients with PAF were included in this study of which 181 had LASs (scar group), while 230 had no scar (nonscar group). In the scar group, patients were older (65.5 ± 8.8 vs 59.7 ± 11.7 years; P < .001), the proportion of female was higher (47.5% vs 37.4%; P = .04) and left atrial (LA) diameter (4.1 ± 0.6 vs 3.9 ± 0.6 cm; P < .001) was larger compared with the nonscar group. There was no significant difference in terms of hypertension, sleep apnea, and diabetes between the two groups. When comparing ECG characteristics between the two groups, PWD was significantly longer in the scar group (122.9 ± 18.5 and 116.9 ± 28.0 ms; P = .01). A multivariate analysis was performed, after adjustment of age, sex, LA diameter, PWD ≥ 120 ms was found to be an independent predictor of LA scarring (OR: 1.69, p-value: 0.02). CONCLUSION: In the current series, prolonged PWD was found to be independently associated with LA scarring in PAF, even after adjustment for age, sex, and LA diameter.

Extent and spatial distribution of left atrial arrhythmogenic sites, late gadolinium enhancement at magnetic resonance imaging, and low-voltage areas in patients with persistent atrial fibrillation: comparison of imaging vs. electrical parameters of fibrosis and arrhythmogenesis.

AIMS: Atrial fibrosis contributes to arrhythmogenesis in atrial fibrillation and can be detected by MRI or electrophysiological mapping. The current study compares the spatial correlation between delayed enhancement (DE) areas to low-voltage areas (LVAs) and to arrhythmogenic areas with spatio-temporal dispersion (ST-Disp) or continuous activity (CA) in atrial fibrillation (AF). METHODS AND RESULTS: Sixteen patients with persistent AF (nine long-standing) underwent DE-magnetic resonance imaging (1.25 mm × 1.25 mm × 2.5 mm) prior to pulmonary vein isolation. Left atrial (LA) voltage mapping was acquired in AF and the regional activation patterns of 7680 AF wavelets were analysed. Sites with ST-Disp or CA were characterized (voltage, duration) and their spatial relationship to DE areas and LVAs <0.5 mV was assessed. Delayed enhancement areas and LVAs covered 55% and 24% (P < 0.01) of total LA surface, respectively. Delayed enhancement area was present at 61% of LVAs, whereas low voltage was present at 28% of DE areas. Most DE areas (72%) overlapped with atrial high-voltage areas (>0.5 mV). Spatio-temporal dispersion and CA more frequently co-localized with LVAs than with DE areas (78% vs. 63%, P = 0.02). Regional bipolar voltage of ST-Disp vs. CA was 0.64 ± 0.47 mV vs. 0.58 ± 0.51 mV. All 28 ST-Disp and 56 CA areas contained electrograms with prolonged duration (115 ± 14 ms) displaying low voltage (0.34 ± 0.11 mV). CONCLUSION: A small portion of DE areas and LVAs harbour the arrhythmogenic areas displaying ST-Disp or CA. Most arrhythmogenic activities co-localized with LVAs, while there was less co-localization with DE areas. There is an important mismatch between DE areas and LVAs which needs to be considered when used as target for catheter ablation.

Evaluation of a new algorithm for tracking activation during atrial fibrillation using multipolar catheters in humans.

BACKGROUND: Conventional mapping techniques during atrial fibrillation (AF) are difficult to apply because of cycle length irregularity. Mapping studies are usually restricted to short durations of AF in limited regions because of the laborious manual annotation of local activation time (LAT). The purpose of this study was to test an automated algorithm to map activation during AF, with comparable accuracy to manual annotation. METHODS: Left atrial (LA) mapping was performed using a 20-pole double loop catheter (AFocusII) in 30-second data segments from 16 patients. The new algorithm (RETRO-Mapping) was designed to detect wavefront propagation between electrodes, and display activating wavefronts on a two-dimensional representation of the catheter. Activation patterns were validated against their bipolar electrograms and with isochronal maps. The mapping protocol was approved by the research ethics committee (13/LO1169 and 14/LO1367). RESULTS: During AF, uniform wavefront activation direction (mean ± SD, degrees) from manually constructed isochronal maps was comparable to RETRO-Propagation Map (RETRO-PM) and RETRO-Automated Direction (RETRO-AD): 1 ± 6.9 for RETRO-PM; and 2 ± 6.6 for RETRO-AD. There was no significant difference in activation direction assigned to 1373 uniform wavefronts during AF when comparing RETRO-PM with RETRO-AD (Bland-Altman mean difference: -0.1 degrees; limits of agreement: -8.0 to 8.3; 95% CI -0.4 to 0.2; (r = 0.01) R2 = < 0.005; P = .77). CONCLUSION: We have developed and validated a new technique to map activation during AF. This technique shows comparable accuracy to that of conventional isochronal mapping with careful manual adjustment of LAT.