Gestational Weight Gain: Is the Role of Genetic Variants a Determinant? A Review.

Excessive or insufficient gestational weight gain (GWG) leads to diverse adverse maternal and neonatal outcomes. There is evidence that pregestational body mass index (pBMI) plays a role in GWG, but no genetic cause has been identified. In this review, we aim to analyze genotype variants associated with GWG. Results: We identified seven genotype variants that may be involved in GWG regulation that were analyzed in studies carried out in Brazil, Romania, the USA, Turkey, Ukraine, and Canada. Some genetic variants were only associated with GWG in certain races or depending on the pBMI. In women who were obese or overweight before gestation, some genetic variants were associated with GWG. Environmental and genetic factors together showed a greater association with GWG than genetic factors alone; for example, type of diet was observed to have a significant influence. Conclusions: We found little scientific evidence of an association between genotype variants in countries with a high prevalence of women of reproductive age who are overweight and obese, such as in Latin America. GWG may be more dependent on environmental factors than genetic variants. We suggest a deeper study of genetic variants, cytokines, and their possible association with GWG, always with the respective control of potential cofounding factors, such as pBMI, diet, and race.

Combined Area of Left and Right Atria May Outperform Atrial Volumes as a Predictor of Recurrences after Ablation in Patients with Persistent Atrial Fibrillation-A Pilot Study.

Background and Objectives: Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. Materials and Methods: This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.1%] persistent AF). Four-chamber cine-sequence was selected to measure LA and RA area, and ventricular end-systolic image phase to obtain atrial 3D volumes. The effect of different variables on event-free survival was investigated using the Cox proportional hazards model. Results: In patients with persistent AF, combined LA and RA area indexed to body surface area (AILA + RA) predicted AF recurrences (HR = 1.08, 95% CI 1.00-1.17, p = 0.048). An AILA + RA cut-off value of 26.7 cm2/m2 had 72% sensitivity and 73% specificity for predicting recurrences in patients with persistent AF. In this group, 65% of patients with AILA + RA > 26.7 cm2/m2 experienced AF recurrence within 2 years of follow-up (median follow-up 11 months), compared to 25% of patients with AILA + RA ≤ 26.7 cm2/m2 (HR 4.28, 95% CI 1.50-12.22; p = 0.007). Indices of LA and RA dilatation did not predict AF recurrences in patients with paroxysmal AF. Atrial 3D volumes did not predict AF recurrences after ablation. Conclusions: In this pilot study, the simple measurement of AILA + RA may predict recurrences after ablation of persistent AF, and may outperform measurements of atrial volumes. In paroxysmal AF, atrial dilatation did not predict recurrences. Further studies on the role of RA and LA remodelling are needed.

Rheology of Pseudomonas fluorescens biofilms: From experiments to predictive DPD mesoscopic modeling.

Bacterial biofilms mechanically behave as viscoelastic media consisting of micron-sized bacteria cross-linked to a self-produced network of extracellular polymeric substances (EPSs) embedded in water. Structural principles for numerical modeling aim at describing mesoscopic viscoelasticity without losing details on the underlying interactions existing in wide regimes of deformation under hydrodynamic stress. Here, we approach the computational challenge to model bacterial biofilms for predictive mechanics in silico under variable stress conditions. Up-to-date models are not entirely satisfactory due to the plethora of parameters required to make them functioning under the effects of stress. As guided by the structural depiction gained in a previous work with Pseudomonas fluorescens [Jara et al., Front. Microbiol. 11, 588884 (2021)], we propose a mechanical modeling by means of Dissipative Particle Dynamics (DPD), which captures the essentials of topological and compositional interactions between bacterial particles and cross-linked EPS-embedding under imposed shear. The P. fluorescens biofilms have been modeled under mechanical stress mimicking shear stresses as undergone in vitro. The predictive capacity for mechanical features in DPD-simulated biofilms has been investigated by varying the externally imposed field of shear strain at variable amplitude and frequency. The parametric map of essential biofilm ingredients has been explored by making the rheological responses to emerge among conservative mesoscopic interactions and frictional dissipation in the underlying microscale. The proposed coarse grained DPD simulation qualitatively catches the rheology of the P. fluorescens biofilm over several decades of dynamic scaling.

Intrinsic structure perspective for MIPS interfaces in two-dimensional systems of active Brownian particles.

Suspensions of active Brownian particles (ABPs) undergo motility-induced phase separation (MIPS) over a wide range of mean density and activity strength, which implies the spontaneous aggregation of particles due to the persistence of their direction of motion, even in the absence of an explicit attraction. Both similarities and qualitative differences have been obtained when the MIPS is analysed in the same terms as a liquid-gas phase coexistence in an equilibrium attractive system. Negative values of the mechanical surface tension have been reported, from the total forces across the interface, while stable fluctuations of the interfacial line could be interpreted as a positive capillary surface tension; in equilibrium liquid surfaces, these two magnitudes are equal. We present here the analysis of 2D-ABP interfaces in terms of the intrinsic density and force profiles, calculated with the particle distance to the instantaneous interfacial line. Our results provide new insight into the origin of MIPS from the local rectification of the random active force on the particles near the interface. As has been reported, this effect acts as an external potential that produces a pressure gradient across the interface, such that the mechanical surface tension of the MIPS cannot be described as that of equilibrium coexisting phases; however, our analysis shows that most of that effect comes from the tightly caged particles at the dense (inner) side of the MIPS interface, rather than from the free moving particles at the outer side that collide with the dense cluster. Moreover, a clear correlation appears between the decay of the hexatic order parameter at the dense slab and the end of the MIPS as the strength of the active force is lowered. We show that, using the strong active forces required for MIPS, the interfacial structure and properties are very similar for ABPs with purely repulsive interactions (the Weeks-Chandler-Andersen-Lennard-Jones (WCA-LJ) model truncated at its minimum) and when the interaction includes a range of the LJ attractive force.

Collective motion of run-and-tumble repulsive and attractive particles in one-dimensional systems.

Active matter deals with systems whose particles consume energy at the individual level in order to move. To unravel features such as the emergence of collective structures, several models have been suggested, such as the on-lattice model of run-and-tumble particles implemented via the persistent exclusion process (PEP). In our work, we study a one-dimensional system of run-and-tumble repulsive or attractive particles, both on-lattice and off-lattice. Additionally, we implement cluster motility dynamics in the on-lattice case (since in the off-lattice case, cluster motility arises from the individual particle dynamics). While we observe important differences between discrete and continuous dynamics, few common features are of particular importance. Increasing particle density drives aggregation across all different systems explored. For non-attractive particles, the effects of particle activity on aggregation are largely independent of the details of the dynamics. In contrast, once attractive interactions are introduced, the steady-state, which is completely determined by the interplay between these and the particles' activity, becomes highly dependent on the details of the dynamics.

Cardiac magnetic resonance to predict recurrences after ventricular tachycardia ablation: septal involvement, transmural channels, and left ventricular mass.

AIMS: Ventricular tachycardia (VT) substrate-based ablation has an increasing role in patients with structural heart disease-related VT. VT is linked to re-entry in relation to myocardial scarring with areas of conduction block (core scar) and areas of slow conduction [border zone (BZ)]. VT substrate can be analysed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Our study aims to analyse the role of LGE-CMR in identifying predictors of VT recurrence after ablation. METHODS AND RESULTS: We analysed 110 consecutive patients who underwent VT ablation from 2013 to 2018. All patients underwent a preprocedural LGE-CMR, and in 94 patients (85.5%), the CMR was used to aid the ablation. All LGE-CMR images were semi-automatically processed using dedicated software to detect scarring and conducting channels. After a median follow-up of 2.7 ± 1.6 years, the overall VT recurrence was 41.8% with an implantable cardioverter-defibrillator shock reduction from 43.6% to 28.2% before and after ablation, respectively. The amount of BZ (26.6 ± 13.9 vs. 19.6 ± 9.7 g, P = 0.012), the total amount of scarring (37.1 ± 18.2 vs. 29 ± 16.3 g, P = 0,033), and left ventricular (LV) mass (168.3 ± 53.3 vs. 152.3 ± 46.4 g, P < 0.001) were associated with VT recurrence. LGE septal distribution [62.5% vs. 37.8%; hazard ratio (HR) 1.67 (1.02-3.93), P = 0.044], channels with transmural path [66.7% vs. 31.4%, HR 3.25 (1.70-6.23), P < 0.001], and midmural channels [54.3% vs. 27.6%, HR 2.49 (1.21-5.13), P = 0.013] were related with VT recurrence. Multivariate analysis showed that the presence of septal LGE [HR 3.67 (1.60-8.38), P = 0.002], transmural channels [HR 2.32 (1.15-4.72), P = 0.019], and LV mass [HR 1.01 (1.005-1.019), P = 0.002] were independent predictors of VT recurrence. CONCLUSION: Pre-procedural LGE-CMR is a helpful and feasible technique to identify patients with high risk of VT recurrence after ablation. LV mass, septal LGE distribution, and transmural channels were predictive factors of post-ablation VT recurrence.

Proximity to the descending aorta predicts regional fibrosis in the adjacent left atrial wall: aetiopathogenic and prognostic implications.

AIMS: Left atrial (LA) fibrosis is present in patients with atrial fibrillation (AF) and can be visualized by magnetic resonance imaging with late gadolinium enhancement (LGE-MRI). Previous studies have shown that LA fibrosis is not randomly distributed, being more frequent in the area adjacent to the descending aorta (DAo). The objective of this study is to analyse the relationship between fibrosis in the atrial area adjacent to the DAo and the distance to it, as well as the prognostic implications of this fibrosis. METHODS AND RESULTS: Magnetic resonance imaging with late gadolinium enhancement was obtained in 108 patients before AF ablation to analyse the extent of LA fibrosis and the distance DAo-to-LA. A high-density electroanatomic map was performed in a subgroup of 16 patients to exclude the possibility of an MRI artifact. Recurrences after ablation were analysed at 1 year of follow-up. The extent of atrial fibrosis in the area adjacent to the DAo was inversely correlated with the distance DAo-to-LA (r = -0.34, P < 0.001). This area had the greatest intensity of LGE [image intensity ratio (IIR) 1.14 ± 0.15 vs. 0.99 ± 0.16; P < 0.001] and also the lowest voltage (1.07 ± 0.86 vs. 1.54 ± 1.07 mV; P < 0.001) and conduction velocity (0.65 ± 0.06 vs. 0.96 ± 0.57 mm/ms; P < 0.001). The extent of this regional fibrosis predicted recurrence after AF ablation [hazard ratio (HR) 1.02, 95% CI 1.01-1.03; P = 0.01], however total fibrosis did not (HR = 1.01, 95% CI 0.97-1.06, P = 0.54). CONCLUSIONS: Atrial fibrosis was predominantly located in the area adjacent to the DAo, and increased with the proximity between the two structures. Furthermore, this regional fibrosis better predicted recurrence after AF ablation than total atrial fibrosis.

Accuracy of left atrial fibrosis detection with cardiac magnetic resonance: correlation of late gadolinium enhancement with endocardial voltage and conduction velocity.

AIMS: Myocardial fibrosis is a hallmark of atrial fibrillation (AF) and its characterization could be used to guide ablation procedures. Late gadolinium enhanced-magnetic resonance imaging (LGE-MRI) detects areas of atrial fibrosis. However, its accuracy remains controversial. We aimed to analyse the accuracy of LGE-MRI to identify left atrial (LA) arrhythmogenic substrate by analysing voltage and conduction velocity at the areas of LGE. METHODS AND RESULTS: Late gadolinium enhanced-magnetic resonance imaging was performed before ablation in 16 patients. Atrial wall intensity was normalized to blood pool and classified as healthy, interstitial fibrosis, and dense scar tissue depending of the resulting image intensity ratio. Bipolar voltage and local conduction velocity were measured in LA with high-density electroanatomic maps recorded in sinus rhythm and subsequently projected into the LGE-MRI. A semi-automatic, point-by-point correlation was made between LGE-MRI and electroanatomical mapping. Mean bipolar voltage and local velocity progressively decreased from healthy to interstitial fibrosis to scar. There was a significant negative correlation between LGE with voltage (r = -0.39, P < 0.001) and conduction velocity (r = -0.25, P < 0.001). In patients showing dilated atria (LA diameter ≥45 mm) the conduction velocity predictive capacity of LGE-MRI was weaker (r = -0.40 ± 0.09 vs. -0.20 ± 0.13, P = 0.02). CONCLUSIONS: Areas with higher LGE show lower voltage and slower conduction in sinus rhythm. The enhancement intensity correlates with bipolar voltage and conduction velocity in a point-by-point analysis. The performance of LGE-MRI in assessing local velocity might be reduced in patients with dilated atria (LA diameter ≥45).

Optimized single-point left ventricular pacing leads to improved resynchronization compared with multipoint pacing.

BACKGROUND: Multipoint pacing (MPP) in cardiac resynchronization therapy (CRT) activates the left ventricle from two locations, thereby shortening the QRS duration and enabling better resynchronization; however, compared with conventional CRT, MPP reduces battery longevity. On the other hand, electrocardiogram-based optimization using the fusion-optimized intervals (FOI) method achieves more significant reverse remodeling than nominal CRT programming. Our study aimed to determine whether MPP could attain better resynchronization than single-point pacing (SPP) optimized by FOI. METHODS: This prospective study included 32 consecutive patients who successfully received CRT devices with MPP capabilities. After implantation, the QRS duration was measured during intrinsic rhythm and with three pacing configurations: MPP, SPP-FOI, and MPP-FOI. In 14 patients, biventricular activation times (by electrocardiographic imaging, ECGI) were obtained during intrinsic rhythm and for each pacing configuration to validate the findings. Device battery longevity was estimated at the 45-day follow-up. RESULTS: The SPP-FOI method achieved greater QRS shortening than MPP (-56 ± 16 vs. -42 ± 17 ms, p < .001). Adding MPP to the best FOI programming did not result in further shortening (MPP-FOI: -58 ± 14 ms, p = .69). Although biventricular activation times did not differ significantly among the three pacing configurations, only the two FOI configurations achieved significant shortening compared with intrinsic rhythm. The estimated battery longevity was longer with SPP than with MPP (8.1 ± 2.3 vs. 6.3 ± 2.0 years, p = .03). CONCLUSIONS: SPP optimized by FOI resulted in better resynchronization and longer battery duration than MPP.

Characterization of MIPS in a suspension of repulsive active Brownian particles through dynamical features.

We study a two-dimensional system composed by Active Brownian Particles (ABPs), focusing on the onset of Motility Induced Phase Separation (MIPS), by means of molecular dynamics simulations. For a pure hard-disk system with no translational diffusion, the phase diagram would be completely determined by their density and Péclet number. In our model, two additional effects are present: translational noise and the overlap of particles; we study the effects of both in the phase space. As we show, the second effect can be mitigated if we use, instead of the standard Weeks-Chandler-Andersen potential, a stiffer potential: the pseudo-hard sphere potential. Moreover, in determining the boundary of our phase space, we explore different approaches to detect MIPS and conclude that observing dynamical features, via the non-Gaussian parameter, is more efficient than observing structural ones, such as through the local density distribution function. We also demonstrate that the Vogel-Fulcher equation successfully reproduces the decay of the diffusion as a function of density, with the exception of very high densities. Thus, in this regard, the ABP system behaves similar to a fragile glass.

Impact of cryoballoon applications on lesion gaps detected by magnetic resonance after pulmonary vein isolation.

INTRODUCTION: Ablation with second-generation cryoballoon technology evolves as an effective and safe alternative to radiofrequency for atrial fibrillation ablation procedures. Nevertheless, the optimal freezing strategy remains unknown. Our objective was to identify the procedural cryoablation parameters predicting successful peri-pulmonary vein (PV) lesions by directly analyzing Postablation gaps in late-gadolinium-enhanced cardiac magnetic resonance (LGE-CMR). METHODS AND RESULTS: Forty-nine consecutive patients (196 PVs) undergoing ablation with second-generation cryoballoon at our center were included. The number and duration of cryoballoon application to achieve PV isolation were left to operator discretion. Gap number and length were quantified in all patients with a LGE-CMR performed 3 months postablation. Application time (420 ± 217 seconds), number of applications (2.1 ± 1.2), application time after electrical isolation (311 ± 194 seconds) and minimum temperature (-45.8 ± 6.5°C) were similar in the 4 PVs. Gaps were observed in 148 PVs (76%), averaging 1.3 ± 1 gaps per vein. Gaps were longer and more frequent in the right PVs (91% vs 59% in left PVs, P < .001). Neither the number, total duration of applications, nor postisolation application time predicted relative length or number of gaps. CONCLUSIONS: After successful PV isolation was achieved in patients undergoing cryoablation, increasing the number of applications, the total application time or application time postisolation did not result in a reduction in the number or the relative length of gaps.

Trapping flocking particles with asymmetric obstacles.

Asymmetric obstacles can be exploited to direct the motion and induce sorting of run-and-tumble particles. In this work, we show that flocking particles which follow the Vicsek model aligning rules experience collective trapping in the presence of a wall of funnels made of chevrons, concentrating at the opposite side of the wall of funnels to run-and-tumble particles. Flocking particles can be completely trapped or exhibit a dynamical trapping behaviour; these two regimes open the door to the design of a system with two perpendicular flows of active particles. This systematic study broadens our understanding of the emergence of collective motion of microorganisms in confined environments and directs the design of new microfluidic devices able to control these collective behaviours.

Phase behaviour and dynamical features of a two-dimensional binary mixture of active/passive spherical particles.

In this work we have characterized the phase behaviour and the dynamics of bidimensional mixtures of active and passive Brownian particles. We have evaluated state diagrams at several concentrations of the passive components finding that, while passive agents tend to hinder phase separation, active agents force crystal-like structures on passive colloids. In order to study how passive particles affect the dynamics of the mixture, we have computed the long-time diffusion coefficient of each species, concluding that active particles induce activity and super-diffusive behaviour on passive ones. Interestingly, at the density at which the system enters a MIPS state the active particles' diffusivity shows an inflection point and the passive particles' one goes through a maximum, due to the change in the dynamics of the active components, as shown in the displacement's probability distribution function.

Magnetic resonance-guided re-ablation for atrial fibrillation is associated with a lower recurrence rate: a case-control study.

AIMS: Our aim was to analyse whether using delayed enhancement cardiac magnetic resonance imaging (DE-CMR) to localize veno-atrial gaps in atrial fibrillation (AF) redo ablation procedures improves outcomes during follow-up. METHODS AND RESULTS: We conducted a case-control study with 35 consecutive patients undergoing a DE-CMR-guided Repeat-pulmonary vein isolation (Re-PVI) procedure. Those with more extensive ablations (e.g. roof lines, box) were excluded. Patients were matched for age, sex, AF pattern, and left atrial dimension with 35 patients who had undergone a conventional Re-PVI procedure guided with a three dimensional (3D)-navigation system. Procedural characteristics were recorded, and patients were followed for 24 months in a specialized outpatient clinic. The primary endpoint was freedom from recurrent AF, atrial tachycardia, or flutter. The duration of CMR-guided procedures was shorter compared to the conventional group (161 ± 52 vs. 195 ± 72 min, respectively, P = 0.049), with no significant differences in fluoroscopy or total radiofrequency time. At the 2-year follow-up, more patients in the DE-CMR-guided group remained free from recurrences compared with the conventional group (70% vs. 39%, respectively, P = 0.007). In univariate Cox-regression analyses, AF pattern [persistent AF, hazard ratio (HR) 2.66 (1.27-5.46), P = 0.006] and the use of DE-CMR [HR 0.36 (0.17-0.79), P = 0.009] predicted recurrences during follow-up; both factors remained independent predictors in multivariate analyses. CONCLUSION: The substrate characterization provided by DE-CMR facilitates the identification of anatomical veno-atrial gaps and associates with shorter procedures and better clinical outcomes in repeated AF ablation procedures.

Ventricular scar channel entrances identified by new wideband cardiac magnetic resonance sequence to guide ventricular tachycardia ablation in patients with cardiac defibrillators.

AIMS: Ventricular tachycardia (VT) substrate-based ablation has become a standard procedure. Electroanatomical mapping (EAM) detects scar tissue heterogeneity and define conduction channels (CCs) that are the ablation target. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is able to depict CCs and increase ablation success. Most patients undergoing VT ablation have an implantable cardioverter-defibrillator (ICD) that can cause image artefacts in LGE-CMR. Recently wideband (WB) LGE-CMR sequence has demonstrated to decrease these artefacts. The aim of this study is to analyse accuracy of WB-LGE-CMR in identifying the CC entrances. METHODS AND RESULTS: Thirteen consecutive ICD-patients who underwent VT ablation after WB-LGE-CMR were included. Number and location of CC entrances in three-dimensional EAM and in WB-LGE-CMR reconstruction were compared. Concordance was compared with a historical cohort matched by cardiomyopathy, scar location, and age (26 patients) with LGE-CMR prior to ICD and VT ablation. In WB-CMR group, 101 and 93 CC entrances were identified in EAM and WB-LGE-CMR, respectively. In historical cohort, 179 CC entrances were identified in both EAM and LGE-CMR. The EAM/CMR concordance was 85.1% and 92.2% in the WB and historical group, respectively (P = 0.66). There were no differences in false-positive rate (CC entrances detected in CMR and absent in EAM: 7.5% vs 7.8% in WB vs. conventional CMR, P = 0.92) nor in false-negative rate (CC entrances present in EAM not detected in CMR: 14.9% vs.7.8% in WB vs. conventional CMR, P = 0.23). Epicardial CCs was predictor of poor CMR/EAM concordance (OR 2.15, P = 0.031). CONCLUSION: Use of WB-LGE-CMR sequence in ICD-patients allows adequate VT substrate characterization to guide VT ablation with similar accuracy than conventional LGE-CMR in patients without an ICD.

Cryoballoon vs. radiofrequency lesions as detected by late-enhancement cardiac magnetic resonance after ablation of paroxysmal atrial fibrillation: a case-control study.

AIMS: Cryoballoon (CB) ablation has emerged as a reliable modality to isolate pulmonary veins (PVs) in atrial fibrillation. Ablation lesions and the long-term effects of energy delivery can be assessed by delayed-enhancement cardiac magnetic resonance (DE-CMR). The aim of the study was to compare the number, extension, and localization of gaps in CB and radiofrequency (RF) techniques in pulmonary vein isolation (PVI). METHODS AND RESULTS: Consecutive patients submitted to PVI with CB in whom DE-CMR images were available (n = 30) were matched (1:1) to patients who underwent PVI with RF (n = 30), considering age, sex, hypertension, and diabetes. Delayed-enhancement cardiac magnetic resonance was obtained at 3 months post-procedure, and images were processed to assess the mean number of gaps around PV ostia, their localization, and the normalized gap length (NGL), calculated as the difference between total gap length and total PV perimeter. Patients were followed up for 12 months. The CB and RF procedures did not differ in the mean number of gaps per patient (4.40 vs. 5.13 gaps, respectively; P = 0.21) nor NGL (0.35 vs. 0.32, P = 0.59). For both techniques, a higher mean number of gaps were detected in right vs. left PVs (3.18 vs. 1.58, respectively; P = 0.01). The incidence of recurrences did not differ between techniques (odds ratio 1.87, 95% confidence interval 0.66-4.97; P = 0.29). CONCLUSION: Location and extension of ablation gaps in PVI did not differ between CB and RF groups in DE-CMR image analysis.

Partial Characterization of Protease Inhibitors of Ulva ohnoi and Their Effect on Digestive Proteases of Marine Fish.

This piece of research evaluates the presence of protease inhibitors in the macroalga Ulva ohnoi and provides an initial overview of their mode of action. The ability of Ulva protease inhibitors to inhibit digestive proteases of three marine fish species, as well as their capacity to hamper the hydrolysis of a reference protein by those fish proteases, were assessed. In addition, thermal stability and the mode of inhibition on trypsin and chymotrypsin were also studied. Dose-response inhibition curves and in vitro protein hydrolysis assays revealed a noticeable inhibition of fish enzymes when Ulva concentration increased in the assay. The thermal treatment of Ulva reduced markedly the inhibitory effect on fish digestive protease. Finally, Lineweaver-Burk plots indicated that trypsin and chymotrypsin inhibition consisted of a mixed-type inhibition mechanism in which the inhibitory effect depends on Ulva concentration. Overall, the results confirmed the presence of protease inhibitors in Ulva, though heat treatment was enough for inactivating these compounds.

Diagnosis-to-ablation time in atrial fibrillation: A modifiable factor relevant to clinical outcome.

INTRODUCTION: Recurrences after atrial fibrillation (AF) ablation are still common. Among the reported clinical and imaging predictors of recurrences, diagnosis-to-ablation time (DAT) has been defined as a predictor of ablation outcome in single-center studies. We aimed to validate DAT in a multicenter real-life cohort. METHODS: This was a multicenter study including consecutive patients undergoing first paroxysmal and persistent AF ablation with radiofrequency or cryoballoon catheters during 2013. Cox proportional hazard regression models were performed to identify predictors of recurrence. RESULTS: In total, 309 patients were included across nine centers (71% men, 57 ± 10 years old, 46% with hypertension, and 66% with CHA2 DS2 -VASc ≤ 1). Most patients had paroxysmal AF (67%) and underwent radiofrequency ablation (68%) with a median DAT of 51 (43) months. Patients with DAT ≤ 1 year (16.6%) were less likely to have repeat procedures (4% vs 18%; P = .017). The adjusted proportional hazards Cox model identified hypertension (P = .005), heart failure (P = .011), nonparoxysmal AF (P = .038), DAT > 1 year (P = .007), and LA diameter (P = .026) as independent predictors for AF recurrence. DAT > 1 year was the only modifiable factor independently associated with recurrence (HR 4.2 [95% CI, 1.5-11.9]) CONCLUSION: Diagnosis-to-ablation time is a modifiable factor independently associated with recurrent arrhythmia and repeat ablation after first AF ablation. An early intervention strategy during the first year from AF diagnosis might improve outcomes.

Reproducibility and accuracy of late gadolinium enhancement cardiac magnetic resonance measurements for the detection of left atrial fibrosis in patients undergoing atrial fibrillation ablation procedures.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) may define left atrial (LA) anatomy and structural remodelling, and facilitate atrial fibrillation (AF) ablation. We aimed to assess the intra- and inter-observer reproducibility and agreement of LGE-CMR parameters with direct application to AF ablation techniques. METHODS AND RESULTS: One experienced and one non-experienced observer performed complete LGE-CMR data analysis twice, on different days, in 40 randomly selected LGE-CMR examinations [20 performed before ablation (pre-ablation) and 20 performed 3 months after ablation (post-ablation)]. Four additional observers (two experienced and two non-experienced) performed complete LGE-CMR data analysis in a subgroup of 30 patients (15 pre-ablation and 15 post-ablation). All LGE-CMR were performed in sinus rhythm. Intra- and inter-observer reproducibility of LA volume, LA area, and sphericity index (SI) was high: coefficient of variation <10% and intraclass correlation coefficient >0.71. Geometric congruency of repeated reconstruction of LA shape was high: maximal error <5 mm for intra-observer and <8 mm for inter-observer. The precision of scar location increased with extent of scar, and was high (Dice coefficient >0.75) when the scar area was >5 cm2 for a single observer and >15 cm2 for multiple observers. Non-experienced observers performed equally well to experienced observers. CONCLUSION: Late gadolinium enhancement cardiac magnetic resonance measurements of LA area, volume, and SI were reproducible, and geometric congruency of LA shape was high. Location of scar was precise for scar areas >5 cm2 for single observers and >15 cm2 for multiple observers, regardless of the observers' experience. These results may serve as a reference for future studies on the role for substrate-based AF ablation procedures.

Analysis of late reconnections after pulmonary vein isolation: Impact of interlesion contiguity and ablation index.

BACKGROUND: Interlesion distance and ablation index (AI) have been proposed as parameters of radiofrequency (RF) lesion durability. This study analyzes the relationship between RF parameters of automatically acquired lesion tags and late reconnections in repeat pulmonary vein isolation (PVI) procedures. METHODS: One hundred fifty-seven patients underwent contact force (CF)-guided PVI with automatic acquisition of RF lesions. During follow-up, 21 patients underwent a repeat PVI procedure. The relationship between RF parameters (power, CF, impedance drop, and AI) of the initial PVI procedure and reconnections observed at repeat PVI was analyzed. Visual gap was defined as the existence of a discontinuity between two RF lesions automatically acquired in the initial PVI procedure. Regional values of AI associated with lesion durability were identified. RESULTS: Twenty-one patients were included. Three hundred thirty-six segments and 2507 RF lesions were analyzed. The median interval between the initial and repeat PVI procedures was 17 (11-24) months. All patients showed ≥1 reconnected segment. Sixty-three segments (18.7%) were reconnected. Reconnected segments showed visual gaps more frequently than non-reconnected segments (66.6% vs 17.6%; P < .001; negative predictive value 91.4%). The mean distance of visual gaps was 8 ± 2.8 mm. No differences were observed in power (31.4 ± 4.7 W vs 31 ± 4.1 W; P = .573), CF (14.4 ± 5.3 g vs 15.4 ± 5.4 g; P = .315), and impedance drop (6.9 ± 5.2 ohms vs 6.5 ± 3.8 ohms; P = .576) between reconnected and non-reconnected segments. Among segments without visual gap, the minimum AI value was significantly higher in the non-reconnected segments (325 ± 96.1 vs 204.7 ± 78.5; P < .001). No reconnections were observed in segments without visual gap and minimum AI ≥ 330/220 in anterior/posterior wall, respectively. CONCLUSIONS: Contiguity between automatically acquired RF lesions and minimum AI value are the main determinants of long-term PVI durability.