Artificial intelligence-adjudicated spatiotemporal dispersion: A patient-unique fingerprint of persistent atrial fibrillation.

BACKGROUND: Spatiotemporal dispersion-guided ablation is a tailored approach for patients in persistent atrial fibrillation (PsAF). The characterization of dispersion extent and distribution and its association with common clinical descriptors of PsAF patients has not been studied. OBJECTIVES: Artificial intelligence-adjudicated dispersion extent and distribution (AI-DED) was obtained with a machine/deep learning classifier (VX1 Software, Volta Medical) in PsAF patients undergoing ablation. The purpose of this study was to test the hypothesis that AI-DED is unique to each patient and independent of common procedural and clinical parameters. METHODS: In a subanalysis of the Ev-AIFib study (NCT03434964), spatiotemporal dispersion maps were built with VX1 software in 78 consecutive persistent and long-standing PsAF patients. AI-DED was quantified using 2 distinct approaches (visual regional characterization or automated global quantification of AI-DED). RESULTS: AI-DED paired-subregion Euclidean distance measurements between 78 patients (average distance 5.07 ± 0.60; min 2.23; max 9.75) demonstrate that AI-DED is a patient-unique characteristic of PsAF. Importantly, both AF type and AF history do not correlate with AI-DED levels (R2 = 0.006, P = .53; and R2 = 0.03, P = .25, respectively). The most extensive AI-DED levels are not associated with poorer procedural (83%, 81%, and 83% of AF termination in low, medium, and high dispersion groups, respectively; P = .954) and long-term (88%, 75%, and 91% of freedom from AF/atrial tachycardia after multiple procedures; P = .517) outcomes. CONCLUSION: The atrial distribution and extent of multipolar electrogram spatiotemporal dispersion follow a nonrandom, albeit patient-unique, distribution in PsAF patients. AI-DED may represent a procedure-implementable fingerprint of the PsAF substrate.

NEXN Gene in Cardiomyopathies and Sudden Cardiac Deaths: Prevalence, Phenotypic Expression, and Prognosis.

BACKGROUND: Few clinical data are available on NEXN mutation carriers, and the gene's involvement in cardiomyopathies or sudden death has not been fully established. Our objectives were to assess the prevalence of putative pathogenic variants in NEXN and to describe the phenotype and prognosis of patients carrying the variants. METHODS: DNA samples from consecutive patients with cardiomyopathy or sudden cardiac death/sudden infant death syndrome/idiopathic ventricular fibrillation were sequenced with a custom panel of genes. Index cases carrying at least one putative pathogenic variant in the NEXN gene were selected. RESULTS: Of the 9516 index patients sequenced, 31 were carriers of a putative pathogenic variant in NEXN only, including 2 with double variants and 29 with a single variant. Of the 29 unrelated probands with a single variant (16 males; median age at diagnosis, 32.0 [26.0-49.0] years), 21 presented with dilated cardiomyopathy (prevalence, 0.33%), and 3 presented with hypertrophic cardiomyopathy (prevalence, 0.14%). Three patients had idiopathic ventricular fibrillation, and there were 2 cases of sudden infant death syndrome (prevalence, 0.46%). For patients with dilated cardiomyopathy, the median left ventricle ejection fraction was 37.5% (26.25-50.0) at diagnosis and improved with treatment in 13 (61.9%). Over a median follow-up period of 6.0 years, we recorded 3 severe arrhythmic events and 2 severe hemodynamic events. CONCLUSIONS: Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy; in these individuals, the prognosis appeared to be relatively good. However, severe and early onset phenotypes were also observed-especially in patients with double NEXN variants. We also detected NEXN variants in patients with hypertrophic cardiomyopathy and sudden infant death syndrome/idiopathic ventricular fibrillation, although a causal link could not be established.

Right atrial appendage firing in atrial fibrillation.

Background: The role of atrial fibrillation (AF) drivers located at the left atrium, superior vena cava, crista terminalis and coronary sinus (CS) is well established. While these regions are classically targeted during catheter ablation, the role of right atrial appendage (RAA) drivers has been incompletely investigated. Objective: To determine the prevalence and electrophysiological characteristics of AF driver's arising from the RAA. Materials and methods: We conducted a retrospective analysis of clinical and procedural data of 317 consecutive patients who underwent an AF ablation procedure after bi-atrial mapping (multipolar catheter). We selected patients who presented with a per-procedural RAA firing (RAAF). RAAF was defined as the recording of a sustained RAA EGM with a cycle length shorter than 120 ms or 120 < RAAF CL ≤ 130 ms and ratio RAA CL/CS CL ≤ 0.75. Results: Right atrial/atrium appendage firing was found in 22 patients. The prevalence was estimated at 7% (95% CI, 4-10). These patients were mostly men (72%), median age: 66 yo ± 8 without structural heart disease (77%). RAAFs were predominantly found in paroxysmal AF patients (63%, 32%, and 5% for paroxysmal, short standing and long-standing AF, respectively, p > 0.05). RAAF median cycle length was 117 ms ± 7 while CS cycle length was 180 ms ± 10 (p < 0.01). Conclusion: In 317 consecutive AF ablation patients (22 patients, 7%) the presence of a high-voltage short-cycle-length right atrial appendage driver (RAAF) may conclusively be associated with AF termination. This case series exemplifies the not-so-uncommon role of the RAA in the perpetuation of AF.

Artificial intelligence software standardizes electrogram-based ablation outcome for persistent atrial fibrillation.

INTRODUCTION: Multiple groups have reported on the usefulness of ablating in atrial regions exhibiting abnormal electrograms during atrial fibrillation (AF). Still, previous studies have suggested that ablation outcomes are highly operator- and center-dependent. This study sought to evaluate a novel machine learning software algorithm named VX1 (Volta Medical), trained to adjudicate multipolar electrogram dispersion. METHODS: This study was a prospective, multicentric, nonrandomized study conducted to assess the feasibility of generating VX1 dispersion maps. In 85 patients, 8 centers, and 17 operators, we compared the acute and long-term outcomes after ablation in regions exhibiting dispersion between primary and satellite centers. We also compared outcomes to a control group in which dispersion-guided ablation was performed visually by trained operators. RESULTS: The study population included 29% of long-standing persistent AF. AF termination occurred in 92% and 83% of the patients in primary and satellite centers, respectively, p = 0.31. The average rate of freedom from documented AF, with or without antiarrhythmic drugs (AADs), was 86% after a single procedure, and 89% after an average of 1.3 procedures per patient (p = 0.4). The rate of freedom from any documented atrial arrhythmia, with or without AADs, was 54% and 73% after a single or an average of 1.3 procedures per patient, respectively (p < 0.001). No statistically significant differences between outcomes of the primary versus satellite centers were observed for one (p = 0.8) or multiple procedures (p = 0.4), or between outcomes of the entire study population versus the control group (p > 0.2). Interestingly, intraprocedural AF termination and type of recurrent arrhythmia (i.e., AF vs. AT) appear to be predictors of the subsequent clinical course. CONCLUSION: VX1, an expertise-based artificial intelligence software solution, allowed for robust center-to-center standardization of acute and long-term ablation outcomes after electrogram-based ablation.

Localized Atrial Tachycardia and Dispersion Regions in Atrial Fibrillation: Evidence of Spatial Concordance.

INTRODUCTION: During atrial fibrillation (AF) ablation, it is generally considered that atrial tachycardia (AT) episodes are a consequence of ablation. Objective: To investigate the spatial relationship between localized AT episodes and dispersion/ablation regions during persistent AF ablation procedures. Methods: We analyzed 72 consecutive patients who presented for an index persistent AF ablation procedure guided by the presence of spatiotemporal dispersion of multipolar electrograms. We characterized spontaneous or post-ablation ATs' mechanism and location in regard to dispersion regions and ablation lesions. RESULTS: In 72 consecutive patients admitted for persistent AF ablation, 128 ATs occurred in 62 patients (1.9 ± 1.1/patient). Seventeen ATs were recorded before any ablation. In a total of 100 ATs with elucidated mechanism, there were 58 localized sources and 42 macro-reentries. A large number of localized ATs arose from regions exhibiting dispersion during AF (n = 49, 84%). Importantly, these ATs' locations were generally remote from the closest ablation lesion (n = 42, 72%). CONCLUSIONS: In patients undergoing a persistent AF ablation procedure guided by the presence of spatiotemporal dispersion of multipolar electrograms, localized ATs originate within dispersion regions but remotely from the closest ablation lesion. These results suggest that ATs represent a stabilized manifestation of co-existing AF drivers rather than ablation-induced arrhythmias.

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

BACKGROUND: Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access. OBJECTIVES: This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR. METHODS: Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed. RESULTS: Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers. CONCLUSIONS: n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.

AF Ablation Guided by Spatiotemporal Electrogram Dispersion Without Pulmonary Vein Isolation: A Wholly Patient-Tailored Approach.

BACKGROUND: The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. OBJECTIVES: The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. METHODS: The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. RESULTS: Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p < 0.001). Compared with the validation set, radiofrequency times (49 ± 21 min vs. 85 ± 34.5 min; p = 0.001) and procedure times (168 ± 42 min vs. 230 ± 67 min; p < 0.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver. CONCLUSIONS: The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949).

Electrogram Fractionation-Guided Ablation in the Left Atrium Decreases the Frequency of Activation in the Pulmonary Veins and Leads to Atrial Fibrillation Termination: Pulmonary Vein Modulation Rather Than Isolation.

OBJECTIVES: This study sought to evaluate the impact of a complex fractionated atrial electrogram (CFAE)-guided ablation strategy on atrial fibrillation (AF) dynamics in patients with persistent AF. BACKGROUND: It is still unclear whether complete pulmonary vein isolation (PVI) is required or if the ablation of well-delineated pulmonary vein (PV) subregions could achieve similar outcomes in persistent AF. METHODS: CFAE-guided ablations were performed in 76 patients (65.2 ± 10 years of age) with persistent AF. In 47 patients, we measured mean PVs and left atrial appendage (LAA) cycle length (CL) values (PV-CL and LAA-CL), before ablation and before AF termination. We defined "active" PVs as PV-CL ≤ LAA-CL, "rapid fires" as PV-CL ≤80% of LAA-CL, and "PV-LAA CL gradient" as a significant CL difference between the 2 regions. RESULTS: AF termination (sinus rhythm [SR] or atrial tachycardia [AT] conversion) occurred in 92% and SR conversion in 75%. The radiofrequency time for AF termination and total radiofrequency time were 26 ± 25 min and 61.1 ± 21.6 min, respectively. Thirty of 47 patients had active PV (with 19 PV "rapid fires"). Ablation significantly increased median CL, both at PVs and LAA from 188 ms (interquartile range [IQR]: 161 to 210 ms) to 227.5 ms (IQR: 200 to 256 ms) (p < 0.0001) and from 197 ms (IQR: 168 to 220 ms) to 224 ms (IQR: 193 to 250 ms) (p < 0001), respectively. After ablation, PV-LAA CL gradients were withdrawn and all PV "rapid fires" were extinguished (without PVI). After 17.2 ± 10 months of follow-up and 1.61 ± 0.75 procedures, 86.3% and 73% of the patients were free from AF and from any arrhythmia (AF/AT), respectively. CONCLUSIONS: CFAE-guided ablation leads to a large decrease in PV frequency of activation, preceding AF termination. A PV modulation approach, rather than complete PVI, may be preferable for persistent AF.

Active or passive pulmonary vein in atrial fibrillation: is pulmonary vein isolation always essential?

BACKGROUND: The role of pulmonary veins (PVs) in persistent atrial fibrillation (AF) perpetuation appears less important than in paroxysmal AF. Electrogram-based substrate ablation is not widely performed as a stand-alone strategy. OBJECTIVE: To evaluate PV activity in AF perpetuation and efficacy of our patient-tailored ablation strategy (electrogram-based substrate ablation with or without pulmonary vein isolation [PVI]). METHODS: One hundred twenty-one patients with paroxysmal (n = 19; 15.7%), persistent (n = 77; 63.6%), or long-standing persistent (n = 25; 20.7%) AF underwent electrogram-based substrate ablation with AF termination end point: sinus rhythm or atrial tachycardia conversion. Before ablation, we classified PVs as "passive" if silent PV or if PV cycle length is greater than left atrial appendage cycle length. No PVI was performed in such cases. RESULTS: Passive PVs were observed in 52 of 121 patients (paroxysmal AF = 0%, persistent AF = 40%, and long-standing persistent AF = 76%; P < .0001]). Substrate ablation terminated AF in 95.6% (sinus rhythm conversion in 80.2%). Compared with patients with active PVs, patients with passive PVs had longer AF sustained duration (19.1 ± 29.7 months vs 4.9 ± 11.1 months; P < .0001), larger left atrial diameter (46.9 ± 7.3 mm vs 41.9 ± 6.0 mm; P = .0014), lower left ventricular ejection fraction (45.4% ± 13.5% vs 55.1% ± 9.4%; P < .0001), and more often structural heart disease (57% vs 33%; P = .02). After a follow-up of 20.39 ± 11.23 months (1.6 procedures per patient), 82% were arrhythmia free with this strategy. CONCLUSIONS: PV activity during AF decreases with AF chronicity, left atrial dilatation, and left ventricular ejection fraction. Our patient-tailored ablation strategy without systematic PVI provides good results.

Automated Detection of Complex Fractionated Atrial Electrograms In Substrate-Based Atrial Fibrillation Ablation: Better Discrimination with a New Setting of CARTO® Algorithm.

Background and purpose: Up until recently complex fractionated atrial electrogram (CFAE) ablation has been considered as time consuming and its achievement as challenging, especially for non experimented operators. Moreover, results of substrate ablation based on CFAE detection in atrial fibrillation (AF) are very disparate, mainly because of the operator's subjective electrogram visual analysis and the difficult distinction between CFAEs really involved in AF perpetuation from other CFAE. Automatic detection provided by 3D mapping system (CARTO® algorithm) can be helpful but is not selective enough, drawing too wide CFAE areas. We sought to demonstrate a better selectivity of a new CFAE algorithm setting in order to better discriminate CFAEs really involved in AF perpetuation from other CFAE. Methods and subjects: A population of 32 patients (60.4±12.7 years) with paroxysmal (n=3) AF (PAF), persistent (n=16) AF (PeAF) or long-standing persistent (n=13) AF (LSPeAF), and AF history =56±65 months, underwent CFAE ablation based on visual analysis. Before ablation, left atrium CFAE mapping was performed on CARTO® shortest complex interval (SCI) algorithm and reanalyzed after ablation with the two different settings: nominal (SCI 60-120ms/0.05-0.15mV) vs. customized setting (SCI 30-40ms/0,04-0.15mV). CFAE areas automatically detected by both settings (CFAE-CARTO® areas) were respectively measured. The decision to ablate CFAE was only based upon the operator's electrogram visual analysis taken as reference because of high AF termination rate (93.7%) due to operator's CFAE selection experience. These ablation points drawn reference-CFAE areas involved in AF perpetuation (ablation point=60mm2) allowing to compare the selectivity of the two previous automatic maps. Results: With the customized CARTO® SCI setting, we observed a significant reduction of CFAE areas detected by CARTO® (CFAE-CARTO® areas) and of the ablated CFAE surface inside non-CFAE CARTO® areas, (30.6±20.5cm2 vs. 68.8±24.5cm2, p<0.0001, and 1.86±1.82% vs. 3±3%, p=0.003). Furthermore the proportion of ablated areas/detected CFAE-CARTO® areas were higher with customized setting (38.2±19.6% vs. 20.4±17.5%, p=0.008). Conclusions: This new customized CFAE algorithm setting is significantly more selective than the nominal one and allows an automated detection of CFAE really involved in AF perpetuation truer to an efficient experienced operator's electrogram visual analysis.

Bifurcation angioplasty using drug eluting stents of post-AF ablation severe pulmonary vein stenosis.

A 53-year-old man with long-standing persistent AF underwent multiple ablation procedures. A presentation with hemoptysis led to a left pulmonary artery wedge angiography and thoracic computed tomography (CT) scan, which revealed a tight bifurcation stenosis of the left superior pulmonary vein (LSPV). This was treated by angioplasty with drug-eluting stents to avoid restenosis by bare-metal stent implantation in small diameter PVs as already described. After predilatation, two 4 × 32-mm and a 3 × 20-mm Taxus® Liberté stents (Boston Scientific, Natick, MA, USA) were deployed across upper and lower LSPV branches and the ostio-antral segment. Twenty-two month follow-up CT angiography showed patent stents in the LSPV, without in-stent restenosis (no arrhythmia or hemoptysis at 24-month follow-up).

Correlation between AF substrate ablation difficulty and left atrial fibrosis quantified by delayed-enhancement cardiac magnetic resonance.

BACKGROUND: Studies have shown that the presence of left atrial (LA) fibrosis can be assessed by LA delayed-enhancement cardiac magnetic resonance (LA DE-CMR) and may be predictive of outcome after ablation for atrial fibrillation (AF). We sought to test the hypothesis that the amount of LA fibrosis evaluated by DE-CMR correlates with the difficulty of complex fractionated atrial electrograms (CFAE) ablation. METHODS: Twenty-two consecutive patients (86.4% nonparoxysmal AF) underwent substrate CFAE radiofrequency (RF) ablation (±Pulmonary veins isolation) with AF termination as the endpoint. LA DE-CMR was performed prior to ablation. A global index of DE was defined by an average of six LA segmental scores based on a four-grade scale (no enhancement to maximum enhancement). Time between first RF application and AF termination, and RF duration until AF termination, was recorded. CFAE area/total LA surface was also measured on CARTO maps (Biosense Webster, Diamond Bar, CA, USA). These measures served to evaluate ablation difficulty, and were correlated with CMR images by double-blinded analysis. RESULTS: Ablation restored sinus rhythm in 20 of 22 patients (91%), with a time to terminate AF of 140 ± 91 minutes. There was a significant correlation between the global averaged DE-CMR fibrosis grade and the electrophysiological substrate indexes such as "time to terminate AF" (Rho = 0.70, P = 0.0003), "RF duration until AF termination" (Rho = 0.65, P = 0.001), and a trend toward correlation with "CFAE area/LA surface" (Rho = 0.47, P = 0.03). CONCLUSIONS: LA DE-CMR can predict increased difficulty of CFAE ablation in AF. This tool may be beneficial in both selection of patients and ablation strategy.

The dynamic air bronchogram. A lung ultrasound sign of alveolar consolidation ruling out atelectasis.

BACKGROUND: The objective of this study was to identify the relationship between a dynamic lung artifact, the dynamic air bronchogram, within alveolar consolidation and the diagnosis of pneumonia vs resorptive atelectasis. METHODS: This prospective study was undertaken within the medical ICU of a university-affiliated teaching hospital. The sample comprised 52 patients with proven pneumonia (pneumonia group) and 16 patients with proven resorptive atelectasis (atelectasis group). All patients had alveolar consolidation with air bronchograms on lung ultrasound, were mechanically ventilated, and received fibroscopy and bacteriological tests. The air bronchogram dynamic was analyzed within the ultrasound area of consolidation. RESULTS: The air bronchograms in the pneumonia group yielded the dynamic air bronchogram in 32 patients and a static air bronchogram in 20. In the atelectasis group, air bronchograms yielded a dynamic air bronchogram in 1 out of 16 patients. With regard to pneumonia vs resorptive atelectasis in patients with ultrasound-visible alveolar consolidation with air bronchograms, the dynamic air bronchogram had a specificity of 94% and a positive predictive value of 97%. The sensitivity was 61%, and the negative predictive value 43%. CONCLUSIONS: In patients with alveolar consolidation displaying air bronchograms on an ultrasound, the dynamic air bronchogram indicated pneumonia, distinguishing it from resorptive atelectasis. Static air bronchograms were seen in most resorptive atelectases and one third of cases of pneumonia. This finding increases the understanding of the pathophysiology of lung diseases within the clinical context and decreases the need for fibroscopy in practice.