Pulmonary Vein Research Articles

Potential Role of Left Atrial Strain to Predict Atrial Fibrillation Recurrence after Catheter Ablation Therapy: A Clinical and Systematic Review.

Pulmonary vein isolation (PVI) with catheter ablation (CA) represents an effective therapy for atrial fibrillation (AF). Unfortunately, it is still not exempt from severe complications. The balance of risks and benefits should be assessed, and a patient-tailored approach is desirable. So far, several clinical and cardiac imaging parameters have been evaluated to investigate pre- and post-procedural features that could help clinicians in the selection of patients at high risk of a poor outcome after CA. This clinical and systematic review analyses the potential role of new LA parameters, such as LA reservoir strain, to predict AF recurrence after CA therapy. Notably, LA reservoir strain gains substantial clinical importance in patients with paroxysmal AF and when a low CHADS2-VASc score is retrieved. LA reservoir strain provides data concerning the risk of AF recurrence after PVI and, thus, in the management of long-term medical therapy in this patient's group.

A case of biatrial tachycardia involving the intercaval bundle with assumed dual loop reentry.

Epicardial connections provided the anatomical substrate for the biatrial reentry circuit. The connections between the right atrium and right pulmonary vein were called "intercaval bundle," and there are few reports of atrial flutter related to this bundle. We present a case of a biatrial tachycardia, involving the intercaval bundle.

Lesion durability found during mandated percutaneous catheter ablation after surgical cryo-ablation for treatment of non-paroxysmal atrial fibrillation

ObjectivesCurrent recommendations support surgical treatment of atrial fibrillation (AF) in patients indicated for cardiac surgery. These procedures are referred to as concomitant and may be carried out using radiofrequency energy or cryo-ablation. This study aimed to assess the electrophysiological findings in patients undergoing concomitant cryo-ablation.MethodsPatients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement were included in the trial if concomitant cryo-ablation was part of the treatment plan according to current guidelines. The patients reported in this study were assigned to undergo staged percutaneous radiofrequency catheter ablation (PRFCA), i.e., hybrid treatment, as a part of the SURHYB trial protocol.ResultsWe analyzed 103 patients who underwent PRFCA 105 ± 35 days after surgery. Left and right pulmonary veins (PVs) were found isolated in 65 (63.1%) and 63 (61.2%) patients, respectively. The LA posterior wall isolation and mitral isthmus conduction block were found in 38 (36.9%) and 18 (20.0%) patients, respectively. Electrical reconnections (gaps) in the left PVs were more often localized superiorly than inferiorly (57.9% vs. 26.3%, P = 0.005) and anteriorly than posteriorly (65.8% vs. 31.6%, P = 0.003). Gaps in the right PVs were more equally distributed anteroposteriorly but dominated in superior segments (72.5% vs. 40.0%, P = 0.003). There was a higher number of gaps on the roof line compared to the inferior line (131 (67.2%) vs. 67 (42.2%), P < 0.001). Compared to epicardial cryo-ablation, endocardial was more effective in creating PVs and LA posterior wall isolation (P < 0.05). Cryo-ablation using nitrous oxide (N20) or argon (Ar) gas as cooling agents was similarly effective (P = NS).ConclusionsThe effectiveness of surgical cryo-ablation in achieving transmural and durable lesions in the left atrium is surprisingly low. Gaps are located predominantly in the superior and anterior portions of the PVs and on the roof line. Endocardial cryo-ablation is more effective than epicardial ablation, irrespective of the cooling agent used.

Minimizing Exposure to Ionizing Radiation in Catheter-Based Treatment of Atrial Fibrillation: Safety and Efficacy

Pulmonary vein isolation using radiofrequency ablation is the most common method of catheter treatment for atrial fibrillation. Performing this procedure involves the use of X-ray radiation, which at certain stages of the procedure is an indispensable method for navigation and visualization of intracardiac structures. Approaches to minimize X-ray exposure during catheter interventions are attracting increased attention of the electrophysiology community due to the potential risks of adverse effects of ionizing radiation on patients and medical personnel. The aim. To evaluate the effectiveness and safety of performing the pulmonary vein isolation procedure with the intention to minimize X-ray exposure of patients and medical personnel. Materials and methods. Forty-three patients with various forms of atrial fibrillation were selected for the study: 28(65%) with paroxysmal and 15 (35%) with persistent forms. All the patients underwent pulmonary vein isolation usingcatheter radiofrequency ablation with the intention to minimize X-ray exposure at the National Amosov Institute of Cardiovascular Surgery in the period from June 2023 to April 2024. Results. In all 43 patients it was possible to electrically isolate all the veins. Catheter ablation of the cavotricuspidisthmus was performed in 5 (31.2%) patients from group A (“Zero-fluoro”), 7 (33.3%) from group B (“Near Zero-fluoro”) and 3 (50%) from group C (“Non Zero-fluoro”) (p = 0.696). Intraoperative reconnection of the pulmonary veins with the left atrium was observed in 6 (37.5%) patients of group A, 11 (52.3%) of group B, and 4 (66%) of group C (p = 0.429). X-ray time for transseptal puncture did not differ between groups A and B (3.56 ± 2.37 vs. 3.69 ± 2.3 min., p = 0.532), however, X-ray time for pulmonary vein isolation in group A was significantly less than that in group B (0.27 ± 0.13 vs. 1.96 ± 1.21 min., p &lt; 0.001). The total time in the left atrium was not statistically different between these two groups (81.33 ± 22.32 vs. 98.6 ± 29.83 min., p = 0.106). In group C (“Non Zero-fluoro”), the aforementioned parameters were not recorded. Total dose area product (DAP) and total radiation dose, as well as total X-ray time and total procedure time, were significantly lower when using the ionizing exposure minimization approach. DAP and total radiation dose in group A were the lowest (7.29 ± 5.16 Gy/cm2 and 76.62 ± 70.82 mGy, respectively) and significantly differed from those in group C (107.67 ± 97.59 Gy/cm2 and 882.32 ± 868.62 mGy, p &lt; 0.001 and p = 0.001, respectively). No intraoperative complications were observed in the studied sample. Conclusions. Minimizing X-ray exposure using modern navigation systems during pulmonary vein isolation using catheter radiofrequency ablation is not associated with increased intraprocedural complications in patients with paroxysmal and persistent atrial fibrillation. This approach allows you to significantly lower total DAP and the radiation dosewithout increasing the time of performing the pulmonary vein isolation procedure.

Characterization of remodeling processes in the atria of atrioventricular block dogs: Utility as an early-stage atrial fibrillation model

To characterize utility of atrioventricular block (AVB) dogs as atrial fibrillation (AF) model, we studied remodeling processes occurring in their atria in acute (<2 weeks) and chronic (>4 weeks) phases. Fifty beagle dogs were used. Holter electrocardiogram demonstrated that paroxysmal AF occurred immediately after the production of AVB, of which duration tended to be prolonged in chronic phase. Electrophysiological analysis showed that inter-atrial conduction time and duration of burst pacing-induced AF increased in the chronic phase compared with those in the acute phase, but that atrial effective refractory period was hardly altered. Echocardiographic study revealed that diameters of left atrium, right pulmonary vein and inferior vena cava increased similarly in the acute and chronic phases. Histological evaluation indicated that hypertrophy and fibrosis in atrial tissue increased in the chronic phase. Electropharmacological characterization showed that i.v. pilsicainide effectively suppressed burst pacing-induced AF with increasing atrial conduction time and refractoriness of AVB dogs in chronic phase, but that i.v. amiodarone did not exert such electrophysiological effects. Taken together, AVB dogs in chronic phase appear to possess such pathophysiology as developed in the atria of early-stage AF patients, and therefore they can be used to evaluate drug candidates against early-stage AF.

Cryoballoon-Assisted Pulmonary Vein Isolation and Left Atrial Roof Ablation Using a Simplified Sedation Strategy without Esophageal Temperature Monitoring: No Notable Thermal Esophageal Lesions and Low Arrhythmia Recurrence Rates after 2 Years.

Atrial fibrillation (AF) ablation is increasingly effective for managing heart rhythm but poses risks like esophageal fistulas. Minimizing esophageal thermal lesions while simplifying procedures is crucial. This prospective study involved 100 consecutive AF patients undergoing cryoballoon ablation with simplified sedation, without esophageal temperature monitoring. Patients with paroxysmal AF (Group A) received pulmonary vein isolation only, while those with persistent AF (Group B) also had left atrial roof ablation. Gastroesophageal endoscopy was performed post-procedure to detect lesions, and cardiological follow-ups were conducted at 3, 12, and 24 months. The cohort included 69% men, with a median age of 65.5 years. Post-ablation endoscopy was performed in 92 patients; esophageal lesions were found in 1.1% of Group A and none of Group B. GERD was diagnosed in 14% of patients, evenly distributed between groups and not linked to lesion occurrence. Gastric hypomotility was observed in 16% of patients, with no significant difference between groups. At 24 months, arrhythmia-free survival was 88% in Group A and 74% in Group B. Cryoballoon-assisted pulmonary vein isolation, with or without additional left atrial roof ablation and without esophageal temperature monitoring during a simplified sedation strategy, shows low risk of esophageal thermal injury and effective ablation outcomes.

NET burden in left atrial blood is associated with biomarkers of thrombosis and cardiac injury in patients with enlarged left atria.

Emerging data suggest an association between left atrial (LA) enlargement, thrombus formation, and ischemic stroke. However, it is unknown what may mediate such clot formation in LA dysfunction. Neutrophils promote large vessel occlusion and microthrombosis via neutrophil extracellular trap (NET) release, thus lying at the interface of inflammation, thrombosis, and fibrosis. We conducted a prospective all-comers cohort study in patients undergoing catheterization procedures with atrial transseptal access (MitraClip, MC; left atrial appendage closure, LAAC; pulmonary vein ablation, PVA; patent foramen ovale closure, PFO). We measured NETs, cytokines, thrombotic factors, and cardiac injury markers in paired blood samples collected from peripheral blood and within the left atrium. We correlated these biomarkers with echocardiographic measures of LA structure and function (including left atrial volume index, LAVI). Data were analyzed by procedure type, and stratified by LAVI or atrial fibrillation (AF) status. We enrolled 70 patients (mean age 64years, 53% women). NETs, but not other markers, were elevated in LA compared to peripheral blood samples. Most thrombotic, inflammatory, and cardiac damage markers were elevated in LAs from MC or LAAC compared to PFO patients. Overall, NET biomarkers positively correlated with VWF, LAVI, and markers of cardiac injury and negatively with ADAMTS13 activity. LA enlargement and the presence of AF similarly stratified patients based on thromboinflammation measurements, but this was not limited to AF at the time of sample collection. Elevated NETs and VWF in patients with enlarged LA or AF suggest enhanced thromboinflammation within the LA.

Assessing the risk of reoperation for mild pulmonary vein obstruction post-TAPVC repair: a retrospective cohort study.

This study investigates the impact of mild pulmonary vein obstruction, detected via echocardiography before hospital discharge, on the likelihood of reoperation in patients who have undergone repair for Total Anomalous Pulmonary Venous Connection (TAPVC). Utilizing a single-center, retrospective cohort approach, we analyzed 38 cases from October 2017 to December 2023, excluding patients with functionally univentricular circulations or atrial isomerism. Our primary outcome was the necessity for reoperation within one year due to anatomical issues related to the initial TAPVC repair. Mild obstruction was defined as a pulmonary vein flow velocity ≥1.2 m/s. Our findings revealed that 31.6% of patients exhibited pre-discharge mild obstruction. During the median follow-up of 10 months, reoperations were notably higher in the mild obstruction group compared to the normal group, with a significant association between pre-discharge mild obstruction and increased risk of reoperation. Specifically, in the fully adjusted model, mild obstruction was linked to a 13.9-fold increased risk of reoperation. Our results suggest that a pre-discharge echocardiography Doppler velocity threshold of 1.2 m/s could serve as a critical predictor for reoperation, emphasizing the need for targeted follow-up strategies for at-risk patients.

Long-Term Changes in Atrial Arrhythmia Burden After Renal Denervation Combined With Pulmonary Vein Isolation: SYMPLICITY-AF

BackgroundThe autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood. ObjectivesThe purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI). MethodsThis study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline. ResultsA total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by −17.8 ± 12.8 mm Hg and −13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups. ConclusionsIn patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.

Pulmonary Vein Intervention for Severe Pulmonary Vein Stenosis After Atrial Fibrillation Ablation - A Retrospective Cohort Study.

Pulmonary vein (PV) stenosis (PVS) is a serious complication of atrial fibrillation (AF) ablation. The objective of this study was to describe interventional treatments for PVS after AF ablation and long-term outcomes in Japanese patients. This multicenter retrospective observational study enrolled 30 patients (26 [87%] male; median age 55 years) with 56 severe PVS lesions from 43 PV interventional procedures. Twenty-seven (90%) patients had symptomatic PVS and 19 (63%) had a history of a single AF ablation. Of the 56 lesions, 41 (73%) were de novo lesions and 15 (27%) were retreated. Thirty-three (59%) lesions were treated with bare metal stents, 14 (25%) were treated with plain balloons, and 9 (16%) were treated with drug-coated balloons. All lesions were successfully treated without any systemic embolic event. Over a median follow-up of 584 days (interquartile range 265-1,165 days), restenosis rates at 1 and 2 years were 35% and 47%, respectively. Multivariate Cox regression analysis revealed devices <7 mm in diameter (hazard ratio [HR] 2.52; 95% confidence interval [CI] 1.04-6.0; P=0.040) and totally occluded lesions (HR 3.33; 95% CI 1.21-9.15; P=0.020) were independent risk factors for restenosis. All PVS lesions were successfully enlarged by the PV intervention; however, restenosis developed in approximately half the lesions within 2 years.

Appropriate Selection of Substrate Ablation for Persistent Atrial Fibrillation Using Intraprocedural Assessment.

It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers.Methods and Results: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70). Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

Utility of noninvasive electrocardiographic imaging in the localization of nonpulmonary vein triggers of atrial fibrillation determined by pacing common trigger sites.

Identifying the origin of nonpulmonary vein atrial fibrillation (AF) triggers (NPVTs) after pulmonary vein isolation (PVI) can be challenging. We aimed to determine if noninvasive electrocardiographic imaging (ECGi) could localize pacing from common NPVT sites. ECGi combines measured body surface potentials with heart-torso geometry acquired from computed tomography (CT) to generate an activation map. In 12 patients with AF undergoing first time ablation, the ECGi vest was fitted for preprocedural CT scan and worn during the procedure. After PVI, we performed steady-state pacing from 15 typical anatomic NPVT sites at a cycle length of 700-800 ms. We co-registered the invasive anatomic map with the CT-based ECGi epicardial activation map to compare ECGi predicted to true pacing origin. In the study cohort (67% male, 58% persistent AF, and 67% with left atrial dilation), 148 (82%) pacing sites had both capture and adequate anatomy acquired from the three-dimensional mapping system to co-register with ECGi activation map. Median distance between true pacing sites and point of earliest epicardial activation derived from the ECGi maps for all sites was 17 mm (interquartile range, 10-22 mm). Assuming paced sites treated as regions with a radius of 2.5 cm, the earliest activation site on ECGi map falls within the region with 94% accuracy. ECGi can approximate the origin of paced beats from common NPVT sites to within a median distance of 17 mm. A rapidly identified region may then be the focus of more detailed catheter-based mapping techniques to facilitate successful localization and ablation of NPVTs.

Efficacy and safety of a novel hexaspline pulsed field ablation system in patients with paroxysmal atrial fibrillation: the PLEASE-AF study.

Pulsed field ablation (PFA) is an emerging non-thermal ablative modality demonstrating considerable promise for catheter ablation of atrial fibrillation (AF). However, these PFA trials have almost universally included only Caucasian populations, with little data on its effect on other races/ethnicities. The PLEASE-AF trial sought to study the 12-month efficacy and the safety of a multi-electrode hexaspline PFA catheter in treating a predominantly Asian/Chinese population of patients with drug-refractory paroxysmal AF. Patients underwent pulmonary vein (PV) isolation (PVI) by delivering different pulse intensities at the PV ostium (1800 V) and atrium (2000 V). Acute success was defined as no PV potentials and entrance/exit conduction block of all PVs after a 20-min waiting period. Follow-up at 3, 6, and 12 months included 12-lead electrocardiogram and 24-h Holter examinations. The primary efficacy endpoint was 12-month freedom from any atrial arrhythmias lasting at least 30 s. The cohort included 143 patients from 12 hospitals treated by 28 operators: age 60.2 ± 10.0 years, 65.7% male, Asian/Chinese 100%, and left atrial diameter 36.6 ± 4.9 mm. All PVs (565/565, 100%) were successfully isolated. The total procedure, catheter dwell, total PFA application, and total fluoroscopy times were 123.5 ± 38.8 min, 63.0 ± 30.7 min, 169.7 ± 34.6 s, and 27.3 ± 10.1 min, respectively. The primary endpoint was observed in 124 of 143 patients (86.7%). One patient (0.7%) developed a small pericardial effusion 1-month post-procedure, not requiring intervention. The novel hexaspline PFA catheter demonstrated universal acute PVI with an excellent safety profile and promising 12-month freedom from recurrent atrial arrhythmias in an Asian/Chinese population with paroxysmal AF. ClinicalTrials.gov Identifier: NCT05114954.

Ablation of drivers in patients with persistent atrial fibrillation refractory to pulmonary vein antral isolation: Target characteristics and 3-year outcomes.

Ablation of drivers in patients with persistent atrial fibrillation refractory to pulmonary vein antral isolation: Target characteristics and 3-year outcomes.

Venous retrograde approach for endovascular angioplasty in chronic total pulmonary vein occlusion -a case report

IntroductionFibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc.Case presentationAn aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent.ConclusionsThis report may provide new management ideas for the interventional treatment of PV occlusion.

A validation study of the accuracy of the atrial pace map assessed with intracardiac pattern matching: Potential utility of non-pulmonary vein mapping.

Identification of infrequent nonpulmonary vein trigger premature atrial contractions (PACs) is challenging. We hypothesized that pace mapping (PM) assessed by correlation scores calculated by an intracardiac pattern matching (ICPM) module was useful for locating PAC origins, and conducted a validation study to assess the accuracy of ICPM-guided PM. Analyzed were 30 patients with atrial fibrillation. After pulmonary vein isolation, atrial pacing was performed at one or two of four sites on the anterior and posterior aspects of the left atrium (LA, n=10/10), LA septum (n=10), and lateral RA (n=10), which was arbitrarily determined as PAC. The intracardiac activation obtained from each pacing was set as an ICPM reference consisting of six CS unipolar electrograms (CS group) or six CS unipolar electrograms and four RA electrograms (CS-RA group). The PM was performed at 193±107 sites for each reference pacing site. All reference pacing sites corresponded to sites where the maximal ICPM correlation score was obtained. Sites with a correlation score ≥98% were rarely obtained in the CS-RA than CS group (33%vs. 55%, P=.04), but those ≥95% were similarly obtained between the two groups (93%vs. 88%, P=.71), and those ≥90% were obtained in all. The surface areas with correlation scores ≥98% (0[0,10] vs. 10[0,35] mm2, P=.02), ≥95% (10[10,30] vs. 50[10,180] mm2, P=.002) and ≥90% (60[30,100] vs. 170[100,560] mm2, P=.0002) were smaller in the CS-RA than CS group. ICPM-guided PM was useful for identifying the reference pacing sites. Combined use of RA and CS electrograms may improve the mapping quality.

Utility of visualization and quantification of surgical techniques using motion analysis software for thoracoscopic surgery.

In this era of endoscopic surgery, feedback from recorded surgical videos is useful and efficient; therefore, effective methods of obtaining this feedback are needed. We analyzed surgical videos using motion analysis software and verified the usefulness of visualizing and objectively evaluating surgical procedures. We measured the grasping and traction angles of the vascular sheath when using forceps and the trajectory of the forceps tip for the upper pulmonary vein during right upper lobectomy during video-assisted thoracoscopic surgery performed by three trainers and trainees. Compared with the trainers, the trainees exhibited insufficient traction of the vascular sheath, performed many slow and unnecessary manipulations, and sometimes performed sudden and fast movements. By visualizing the surgical procedures, the trainee will be better able to identify dangerous or futile movements. It may also make it easier to objectively recognize improvements in one's technique. Motion analysis software could allow for efficient surgical education and self-learning.

Real-world evidence demonstrates an appropriate atrial fibrillation population for hybrid convergent approach versus stand-alone cryoballoon ablation: A long-term safety and efficacy study.

A hybrid convergent approach (endocardial and epicardial ablation) demonstrated superior effectiveness in a recent randomized study for long-standing persistent atrial fibrillation (LSPAF). Yet, there is a lack of real-world, long-term evidence as to which patients are best candidates for a hybrid convergent approach compared to standard endocardial cryoballoon pulmonary vein isolation (CB PVI). This single-center, retrospective analysis spanning from 2010 to 2015 compared two distinctly different atrial fibrillation (AF) cohorts; one treated with stand-alone cryoablation and one treated with a hybrid convergent approach. Baseline characteristics described candidates for each approach. The following criteria were utilized to determine CB PVI candidacy: (1) paroxysmal AF (PAF) (stage 3A) with failed class I/III antiarrhythmic drug (AAD) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD unwilling to undergo hybrid procedure. Selection criteria for the hybrid procedure included: (1) PAF refractory to both class I/III AAD and prior CB PVI (stage 3D) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD agreeable to hybrid procedure. Prior sternotomy was excluded. Serial electrocardiograms and continuous monitoring evaluated primary efficacy outcome of time-to-first recurrence of atrial arrhythmia after a 90-day blanking period. Secondary outcomes were procedure-related complications and AAD use (at discharge, 12, and 36 months). Kaplan-Meier methods evaluated arrhythmia recurrence. Of 276 patients, 197 (64.2 ± 10.6 years old; 66.5% male; 74.1% 3A-PAF; 18.3% 3B/3D-persistent AF; 1.0% 3C-LSPAF; 6.6% undetermined) underwent CB PVI and 79 (61.4 ± 8.1 years old; 83.5% male; 41.8% 3D-PAF; 45.5% 3B/3D-persistent AF; 12.7% 3C/3D-LSPAF) underwent hybrid procedure. Arrhythmia freedom through 36 months was 55.2% for CB PVI and 50.4% for hybrid (p = .32). Class I AAD utilization at discharge occurred in 38 (19.3%) patients in the CB PVI group and 5 (6.3%) patients in the hybrid group (p = .01). CB PVI class I AAD utilization at 12 months occurred in 14 (9.0) patients versus 0 patients for hybrid convergent (p = .004). Patients with one or more adverse event were as follows: two (1.0%) in the CB PVI group (both transient phrenic nerve palsy) and three (3.7%) in the hybrid group (two with significant bleeding and one with wound infection) (p = .14). This study demonstrated that patients with more complex forms of AF (3D-PAF or 3B/3C/3D-persistent/LSPAF) could be well managed with a convergent approach. In a real-world evaluation, outcomes match safety and efficacy thresholds achieved for patients with earlier, less complex AF etiologies treated by CB PVI alone.

Identification of endothelial and mesenchymal FOXF1 enhancers involved in alveolar capillary dysplasia

Mutations in the FOXF1 gene, a key transcriptional regulator of pulmonary vascular development, cause Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins, a lethal lung disease affecting newborns and infants. Identification of new FOXF1 upstream regulatory elements is critical to explain why frequent non-coding FOXF1 deletions are linked to the disease. Herein, we use multiome single-nuclei RNA and ATAC sequencing of mouse and human patient lungs to identify four conserved endothelial and mesenchymal FOXF1 enhancers. We demonstrate that endothelial FOXF1 enhancers are autoactivated, whereas mesenchymal FOXF1 enhancers are regulated by EBF1 and GLI1. The cell-specificity of FOXF1 enhancers is validated by disrupting these enhancers in mouse embryonic stem cells using CRISPR/Cpf1 genome editing followed by lineage-tracing of mutant embryonic stem cells in mouse embryos using blastocyst complementation. This study resolves an important clinical question why frequent non-coding FOXF1 deletions that interfere with endothelial and mesenchymal enhancers can lead to the disease.

Pulmonary Vein Morphology in Patients Undergoing Catheter Ablation of Atrial Fibrillation.

Variations in the anatomy of pulmonary veins can influence selection of approaches of atrial fibrillation catheter ablation. Therefore, preprocedural evaluation and knowledge of pulmonary veins anatomy is crucial for proper mapping and the successful ablation of atrial fibrillation. The aim of this observational study was to assess CT angiography scans and perform detailed analysis of pulmonary veins morphology in patients scheduled for catheter ablation of atrial fibrillation. CT angiography was performed in 771 individuals (223 females, 548 males, mean age 58.4 ± 10.7years). Pulmonary veins anatomy was evaluated using 3D models. The patterns used for evaluation included typical anatomy with four separate pulmonary veins, a common left ostium, and various types of accessory veins either alone or in combination with common left ostia. An anatomical variant with common left ostium was observed as the most prevalent anatomy (44%). The typical variant was observed in 34.8% of patients. Accessory pulmonary veins were observed predominantly on the right side. The prevalence of anatomical variants did not differ between sexes with the exception of the unclassifiable category U (4.4% vs. 9%, p < 0.05). Our study shows that a considerable number of atypical anatomies is present in patients undergoing AF catheter ablation. This knowledge may influence the choice of instrumentation. The data could be possibly helpful also in development of new ablation techniques.