Novel Computational Analysis of Left Atrial Anatomy Improves Prediction of Atrial Fibrillation Recurrence after Ablation

The left atrium (LA) can change in size and shape due to atrial fibrillation (AF)-induced remodeling. These alterations can be linked to poorer outcomes of AF ablation. In this study, we propose a novel comprehensive computational analysis of LA anatomy to identify what features of LA shape can optimally predict post-ablation AF recurrence. To this end, we construct smooth 3D geometrical models from the segmentation of the LA blood pool captured in pre-procedural MR images. We first apply this methodology to characterize the LA anatomy of 144 AF patients and build a statistical shape model that includes the most salient variations in shape across this cohort. We then perform a discriminant analysis to optimally distinguish between recurrent and non-recurrent patients. From this analysis, we propose a new shape metric called vertical asymmetry, which measures the imbalance of size along the anterior to posterior direction between the superior and inferior left atrial hemispheres. Vertical asymmetry was found, in combination with LA sphericity, to be the best predictor of post-ablation recurrence at both 12 and 24 months (area under the ROC curve: 0.71 and 0.68, respectively) outperforming other shape markers and any of their combinations. We also found that model-derived shape metrics, such as the anterior-posterior radius, were better predictors than equivalent metrics taken directly from MRI or echocardiography, suggesting that the proposed approach leads to a reduction of the impact of data artifacts and noise. This novel methodology contributes to an improved characterization of LA organ remodeling and the reported findings have the potential to improve patient selection and risk stratification for catheter ablations in AF

Improving the effect of incubation and oxidative stress on thawed spermatozoa from red deer by using different antioxidant treatments

P. 856-870Antioxidants could improve sperm media, extending the viability of spermatozoa and protecting their DNA. The protective ability of lipoic acid, melatonin, Trolox and crocin was tested on red deer spermatozoa incubated at 37°C. Cryopreserved spermatozoa were thawed and incubated with 1 mM or 0.1 mM of each antioxidant, with or without oxidative stress (100 μM Fe2+). Motility (CASA), viability, mitochondrial membrane potential and acrosomal status were assessed. Lipoperoxidation (malondialdehyde production), intracellular reactive oxygen species (ROS) and DNA status (TUNEL) were checked at 4 h. Incubation alone increased ROS and decreased motility. Oxidative stress intensified these effects, increasing lipoperoxidation and DNA damage. Lipoic acid had little protective effect, whereas 1 mM melatonin showed limited protection. Trolox lowered ROS and lipoperoxidation both in oxidised and non-oxidised samples. In oxidised samples, Trolox prevented DNA and acrosomal damage, and ameliorated motility. Crocin at 1 mM showed similar results to Trolox, but noticeably stimulated motility and had no effect on lipoperoxidation. In a second experiment, a broader range of crocin and melatonin concentrations were tested, confirming the effects of crocin (positive effects noticeable at 0.5–0.75 mM), but showing an increase in lipoperoxidation at 2 mM. Melatonin was increasingly effective at 2.5 and 5 mM (ROS, lipoperoxidation and DNA status). Crocin seems a promising new antioxidant, but its particular effects on sperm physiology must be further studied, especially the consequences of motility stimulation and confirming its effect on lipoperoxidation. Melatonin might be useful at relatively high concentrations, compared to Trolox.S

Functional mapping to reveal slow conduction and substrate progression in atrial fibrillation

Aims: The aim of our study was to analyse the response to short-coupled atrial extrastimuli to identify areas of hidden slow conduction (HSC) and their relationship with the atrial fibrillation (AF) phenotype. Methods and results: Twenty consecutive patients with paroxysmal AF and persistent AF (10:10) underwent the first pulmonary vein isolation procedure. Triple short-coupled extrastimuli were delivered in sinus rhythm (SR), and the evoked response was analysed: sites exhibiting double or highly fragmented electrograms (EGM) were defined as positive for HSC (HSC+). The delta of the duration of the bipolar EGM was analysed, and bipolar EGM duration maps were built. High-density maps were acquired using a multipolar catheter during AF, SR, and paced rhythm. Spatial co-localization of HSC+ and complex fractionated atrial EGMs (CFAE) during AF was evaluated. Persistent AF showed a higher number and percentage of HSC+ than paroxysmal AF (13.9% vs. 3.3%, P < 0.001). The delta of EGM duration was 53 ± 22ms for HSC+ compared with 13 ± 11 (10)ms in sites with negative HSC (HSC-) (P < 0.001). The number and density of HSC+ were lower than CFAE during AF (19 vs. 56 per map, P < 0.001). The reproducibility and distribution of HSC+ in repeated maps were superior to CFAE (P = 0.19 vs. P < 0.001). Sites with negative and positive responses showed a similar bipolar voltage in the preceding sinus beat (1.65 ± 1.34 and 1.48 ± 1.47mV, P = 0.12). Conclusion: Functional mapping identifies more discrete and reproducible abnormal substrates than mapping during AF. The HSC+ sites in response to triple extrastimuli are more frequent in persistent AF than in paroxysmal AF

Benefit of left atrial roof linear ablation in paroxysmal atrial fibrillation: a prospective, randomized study

Background Isolation of the pulmonary veins (PVs) for the treatment of atrial fibrillation (AF) is often supplemented with linear lesions within the left atrium (LA). However, there are conflicting data on the effects of creating a roof line (RL) joining the superior PVs in paroxysmal atrial fibrillation (PAF). Methods and Results A cohort of 120 patients with drug-refractory PAF referred for ablation were prospectively randomized into 2 strategies: (1) PV isolation in combination with RL ablation (LA roof ablation [LARA]-1: 59 patients) or (2) PV isolation (LARA-2: 61 patients). Follow-up was performed at 1, 3, and 6 months after the procedure and every 6 months thereafter. After a 3-month blanking period, recurrence was defined as the ocurrence of any atrial tachyarrhythmia lasting ≥30 seconds. PV isolation was achieved in 89% and complete RL block in 81%. RF duration, fluoroscopy, and procedural times were slightly, but not significantly, longer in the LARA-1 group. After 15±10 months, there was no difference in the arrhythmia-free survival after a single AF ablation procedure (LARA-1: 59% vs. LARA-2: 56% at 12 months; log rank P=0.77). The achievement of complete RL block did not influence the results. The incidence of LA macroreentrant tachycardias was 5.1% in the LARA-1 group (n=3) versus 8.2% in the LARA-2 (n=5) (P=ns). Univariate analysis only identified AF duration as a covariate associated with arrhythmia recurrence (hazard ratio, 1.01 [95% confidence interval, 1.002 to 1.012]; P<0.01). Conclusion The linear block at the LA roof is not associated with an improved clinical outcome compared with PV isolation alone

Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study

A history of a parts per thousand yen2000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk

Left atrial geometry and outcome of atrial fibrillation ablation: results from the multicentre LAGO-AF study

Aims: Left atrial (LA) remodelling is a key determinant of atrial fibrillation (AF) ablation outcome. Optimal methods to assess this process are scarce. LA sphericity is a shape-based parameter shown to be independently associated to procedural success. In a multicentre study, we aimed to test the feasibility of assessing LA sphericity and evaluate its capability to predict procedural outcomes. Methods and results: This study included consecutive patients undergoing first AF ablation during 2013. A 3D model of the LA chamber, excluding pulmonary veins and LA appendage, was used to quantify LA volume (LAV) and LA sphericity (≥82.1% was considered spherical LA). In total, 243 patients were included across 9 centres (71% men, aged 56 ± 10 years, 44% with hypertension and 76% CHA2DS2-VASc ≤ 1). Most patients had paroxysmal AF (66%) and underwent radiofrequency ablation (60%). Mean LA diameter (LAD), LAV, and LA sphericity were 42 ± 6 mm, 100 ± 33 mL, and 82.6 ± 3.5%, respectively. Adjusted Cox models identified paroxysmal AF [hazard ratio (HR 0.54, P = 0.032)] and LA sphericity (HR 1.87, P = 0.035) as independent predictors for AF recurrence. A combined clinical-imaging score [Left Atrial Geometry and Outcome (LAGO)] including five items (AF phenotype, structural heart disease, CHA2DS2-VASc ≤ 1, LAD, and LA sphericity) classified patients at low (≤2 points) and high risk (≥3 points) of procedural failure (35% vs. 82% recurrence at 3-year follow-up, respectively; HR 3.10, P < 0.001). Conclusion: In this multicentre, real-life cohort, LA sphericity and AF phenotype were the strongest predictors of AF ablation outcome after adjustment for covariates. The LAGO score was easy to implement, identified high risk of procedural failure, and could help select optimal candidates. Clinical Trial Registration Information: NCT02373982 (http://clinicaltrials.gov/ct2/show/NCT02373982)

Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation : A multicentre, randomized, controlled trial (SARA study)

BackgroundCatheter ablation (CA) is a highly effective therapy for the treatment of paroxysmal atrial fibrillation (AF) when compared with antiarrhythmic drug therapy (ADT). No randomized studies have compared the two strategies in persistent AF. The present randomized trial aimed to compare the effectiveness of CA vs. ADT in treating persistent AF.Methods and resultsPatients with persistent AF were randomly assigned to CA or ADT (excluding patients with long-standing persistent AF). Primary endpoint at 12-month follow-up was defined as any episode of AF or atrial flutter lasting >24 h that occurred after a 3-month blanking period. Secondary endpoints were any atrial tachyarrhythmia lasting >30 s, hospitalization, and electrical cardioversion. In total, 146 patients were included (aged 55 ± 9 years, 77% male). The ADT group received class Ic (43.8%) or class III drugs (56.3%). In an intention-to-treat analysis, 69 of 98 patients (70.4%) in the CA group and 21 of 48 patients (43.7%) in the ADT group were free of the primary endpoint (P = 0.002), implying an absolute risk difference of 26.6% (95% CI 10.0-43.3) in favour of CA. The proportion of patients free of any recurrence (>30 s) was higher in the CA group than in the ADT group (60.2 vs. 29.2%; P < 0.001) and cardioversion was less frequent (34.7 vs. 50%, respectively; P = 0.018).ConclusionCatheter ablation is superior to medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up.Clinical Trial Registration InformationNCT00863213 (http://clinicaltrials.gov/ct2/show/NCT00863213)

Personalized assessment of the cumulative complication risk of the atrial fibrillation ablation track: The AF-TRACK calculator

Atrial fibrillation (AF) ablation strategy is associated with a non-negligible risk of complications and often requires repeat procedures (AF ablation track), implying repetitive exposure to procedural risk.The purpose of this study was to develop and validate a model to estimate individualized cumulative risk of complications in patients undergoing the AF ablation track (Atrial Fibrillation TRAck Complication risK [AF-TRACK] calculator).The model was derived from a multicenter cohort including 3762 AF ablation procedures in 2943 patients. A first regression model was fitted to predict the propensity for repeat ablation. The AF-TRACK calculator computed the risk of AF ablation track complications, considering the propensity for repeat ablation. Internal (cross-validation) and external (independent cohort) validation were assessed for discrimination capacity (area under the curve [AUC]) and goodness of fit (Hosmer-Lemeshow [HL] test).Complications (N = 111) occurred in 3.7% of patients (2.9% of procedures). Predictors included female sex, heart failure, sleep apnea syndrome, and repeat procedures. The model showed fair discrimination capacity to predict complications (AUC 0.61 [0.55-0.67]) and likelihood of repeat procedure (AUC 0.62 [0.60-0.64]), with good calibration (HL χ2 12.5; P = .13). The model maintained adequate discrimination capacity (AUC 0.67 [0.57-0.77]) and calibration (HL χ2 5.6; P = .23) in the external validation cohort. The validated model was used to create the Web-based AF-TRACK calculator.The proposed risk model provides individualized estimates of the cumulative risk of complications of undergoing the AF ablation track. The AF-TRACK calculator is a validated, easy-to-use, Web-based clinical tool to calibrate the risk-to-benefit ratio of this treatment strategy.© 2022 Heart Rhythm Society. Published by Elsevier Inc