Wide antral circumferential vs. ostial pulmonary vein isolation using pulsed field ablation—the butterfly effect

BackgroundWide antral circumferential ablation (WACA) in comparison to ostial pulmonary vein (PV) isolation (PVI) has been attributed with improved rhythm outcome. We investigated the feasibility, lesion formation, and rhythm outcome of WACA-PVI in comparison to ostial-PVI using pulsed field ablation (PFA).MethodsSymptomatic atrial fibrillation (AF) patients (69 years, 67% male; 67% paroxysmal AF) were prospectively enrolled into our single-center registry and underwent first-time ostial-PFA or WACA-PFA, N = 15 each. In all patients, eight pulse trains (2 kV/2.5 s, bipolar, biphasic, 4× basket/flower configuration each) were delivered to each PV. In WACA-PFA, two extra pulse trains in a flower configuration were added to the anterior and posterior antrum of the PVs. For comparison of PFA lesion size, pre- and post-ablation left atrial (LA) voltage maps were acquired using a multipolar spiral catheter together with a three-dimensional electroanatomic mapping system.ResultsWACA-PFA resulted in a significant larger lesion formation than ostial-PFA (45.5 vs. 35.1 cm2, p = 0.001) with bilateral overlapping butterfly shape-like lesions and concomitant posterior LA wall isolation in 73% of patients. This was not associated with increased procedure time, sedation dosage, or exposure to radiation. One-year freedom from AF recurrence was numerically higher after WACA-PFA than ostial-PFA (94% vs. 87%) but not statistically significant (p = 0.68). No organized atrial tachycardias (ATs) were observed. Ostial-PFA patients more often underwent re-ablation due to recurrent AF episodes.ConclusionWACA-PFA is feasible and resulted in significantly wider lesion sets than ostial-PFA. Concomitant posterior LA wall isolation occurred as an epiphenomenon in the majority of patients. The WACA approach was associated with neither increased procedure and fluoroscopy times nor statistically significant differences in 1-year rhythm outcome. ATs were absent

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF).

AIMS Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the 'real world' performance of the only approved PFA catheter, including acute effectiveness and safety-in particular, rare oesophageal effects and other unforeseen PFA-related complications. METHODS AND RESULTS This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7-291), full cohort included 1758 patients: mean age 61.6 years (range 19-92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9-100%). Procedure time was 65 min (38-215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). CONCLUSION In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of 'generic' catheter complications (tamponade, stroke) underscores the need for improvement

Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection

IntroductionStreptococcus pneumoniae is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with Streptococcus pneumoniae are incompletely resolved.MethodsWe used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with Streptococcus pneumoniae.ResultsAM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration.DiscussionIn conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with Streptococcus pneumoniae and reveals profound alterations critical for effective antimicrobial immunity

Left Ventricular Wall Motion Analysis to Guide Management of CRT Non-Responders

This doctoral thesis describes a clinical, prospective, single-center pilot study, investigating the feasibility and the outcome of a novel optimization concept for heart failure patients who are not responding to a device-based therapy, so called Cardiac Resynchronization Therapy (CRT)

Effect of concomitant Renal DeNervation and cardiac ablation on Atrial Fibrillation recurrence: RDN+AF study

Background: Renal denervation (RDN) can reduce cardiac sympathetic activity maintained by arterial hypertension (aHT). Its potential antiarrhythmic effect on rhythm outcome in patients with multi-drug resistant aHT undergoing catheter ablation for atrial fibrillation (AF) is unclear. Methods: The RDN+AF study was a prospective, randomized, two-center trial. Patients with paroxysmal or persistent AF and uncontrolled aHT (mean systolic 24-h ambulatory BP > 135 mmHg) despite taking at least three antihypertensive drugs were enrolled. Patients were 1:2 randomized to either RDN+AF ablation or AF-only ablation. Primary endpoint was freedom from any AF episode > 2 min at 12 months assessed by implantable loop recorder (ILR) or 7d-holter electrocardiogram. Secondary endpoints included rhythm outcome at 24 months, blood pressure control, periprocedural complications, and renovascular safety. Results: The study randomized 61 patients (mean age 65 ± 9 years, 53% men). At 12 months, RDN+AF patients tended to have a greater decrease in ambulatory BPs but did not reach statistical significance. No differences in rhythm outcome were observed. Freedom from AF recurrence in the RDN+AF and AF-only group measured 61% versus 53% p = .622 at 12 months and 39% versus 47% p = .927 at 24 months, respectively. Periprocedural complications occurred in 9/61 patients (15%). No patient died. Conclusion: Among patients with multidrug-resistant aHT and paroxysmal or persistent AF, concomitant RDN+AF ablation was not associated with better blood pressure control or rhythm outcome in comparison to AF-only ablation and medical therapy

Safety and Feasibility of Catheter Ablation Procedures in Patients with Bleeding Disorders

Aims/Objectives: Patients with bleeding disorders are a rare and complex population in catheter ablation (CA) procedures. The most common types of bleeding disorders are von Willebrand disease (VWD) and hemophilia A (HA). Patients with VWD or HA tend to have a higher risk of bleeding complications compared to other patients. There is a lack of data concerning peri- and postinterventional coagulation treatment. We sought to assess the optimal management of patients with VWD and HA referred for catheter ablation procedures. Methods and Results: In this study, we analyzed patients with VWD or HA undergoing CA procedures at two centers in Germany and Switzerland between 2016 and 2021. Clotting factors were administered in conjunction with hemostaseological recommendations. CA was performed as per the institutional standard. During the procedure, unfractionated heparin (UFH) was given intravenously with respect to the activated clotting time (ACT). Primary endpoints included the feasibility of the procedure, bleeding complications, and thromboembolic events during the procedure. Secondary endpoints included bleeding complications and thromboembolic events up to one year after catheter ablation. A total of seven patients (three VWD Type I, one VWD Type IIa, three HA) underwent 10 catheter ablation procedures (pulmonary vein isolation (PVI): two × radiofrequency (RF), one × laser balloon (LB), one × cryoballoon (CB); PVI + cavotricuspid isthmus (CTI): one × RF; PVI + left atrial appendage isolation (LAAI): one × RF; Premature ventricular contraction (PVC): three × RF; Atrioventricular nodal reentrant tachycardia (AVNRT): one × RF). VWD patients received 2000–3000 IE Wilate i.v. 30 to 45 min prior to ablation. Patients with HA received 2000–3000 IE factor VIII before the procedure. All patients undergoing PVI received UFH (cumulative dose 9000–18,000 IE) with a target ACT of >300 s. All patients after PVI were started on oral anticoagulation (OAC) 12 h after ablation. Two patients received aspirin (acetylsalicylic acid; ASA) for 4 weeks after the ablation of left-sided PVCs. No anticoagulation was prescribed after slow pathway modulation in a case with AVNRT. No bleeding complications or thromboembolic events were reported. During a follow-up of one year, one case of gastrointestinal bleeding occurred following OAC withdrawal after LAA occlusion. Conclusions: After the substitution of clotting factors, catheter ablation in patients with VWD and HA seems to be safe and feasible

Safety and Feasibility of Catheter Ablation Procedures in Patients with Bleeding Disorders

AIMS/OBJECTIVES Patients with bleeding disorders are a rare and complex population in catheter ablation (CA) procedures. The most common types of bleeding disorders are von Willebrand disease (VWD) and hemophilia A (HA). Patients with VWD or HA tend to have a higher risk of bleeding complications compared to other patients. There is a lack of data concerning peri- and postinterventional coagulation treatment. We sought to assess the optimal management of patients with VWD and HA referred for catheter ablation procedures. METHODS AND RESULTS In this study, we analyzed patients with VWD or HA undergoing CA procedures at two centers in Germany and Switzerland between 2016 and 2021. Clotting factors were administered in conjunction with hemostaseological recommendations. CA was performed as per the institutional standard. During the procedure, unfractionated heparin (UFH) was given intravenously with respect to the activated clotting time (ACT). Primary endpoints included the feasibility of the procedure, bleeding complications, and thromboembolic events during the procedure. Secondary endpoints included bleeding complications and thromboembolic events up to one year after catheter ablation. A total of seven patients (three VWD Type I, one VWD Type IIa, three HA) underwent 10 catheter ablation procedures (pulmonary vein isolation (PVI): two × radiofrequency (RF), one × laser balloon (LB), one × cryoballoon (CB); PVI + cavotricuspid isthmus (CTI): one × RF; PVI + left atrial appendage isolation (LAAI): one × RF; Premature ventricular contraction (PVC): three × RF; Atrioventricular nodal reentrant tachycardia (AVNRT): one × RF). VWD patients received 2000-3000 IE Wilate i.v. 30 to 45 min prior to ablation. Patients with HA received 2000-3000 IE factor VIII before the procedure. All patients undergoing PVI received UFH (cumulative dose 9000-18,000 IE) with a target ACT of >300 s. All patients after PVI were started on oral anticoagulation (OAC) 12 h after ablation. Two patients received aspirin (acetylsalicylic acid; ASA) for 4 weeks after the ablation of left-sided PVCs. No anticoagulation was prescribed after slow pathway modulation in a case with AVNRT. No bleeding complications or thromboembolic events were reported. During a follow-up of one year, one case of gastrointestinal bleeding occurred following OAC withdrawal after LAA occlusion. CONCLUSIONS After the substitution of clotting factors, catheter ablation in patients with VWD and HA seems to be safe and feasible

Pulmonary vein isolation durability after very high-power short-duration ablation utilizing a very-close protocol – The FAST AND FURIOUS redo study

Background: Very high-power short-duration (vHP-SD) radiofrequency (RF) ablation of atrial fibrillation (AF) treatment by pulmonary vein isolation (PVI) aims for safer, more effective and faster procedures. Although acute efficacy and safety for PVI was recently shown data on chronic PVI durability is limited. Here chronic PVI durability was evaluated during repeat electrophysiological procedures in patients after initial vHP-SD and conventional RF based PVI. Methods: A total of 25 consecutive patients with repeat left atrial procedures after initial vHP-SD based PVI were included in this study. Twenty-five patients with previous conventional RF based PVI and repeat left atrial procedures served as control (control group). Results: For index procedures the median RF time was 328 (277, 392) seconds (vHP-SD) and 1470 (1310, 1742) seconds (control); p < 0.001, the median procedure time was 55 (53, 68) minutes (vHP-SD) and 110 (94, 119) (control); p < 0.001). First pass isolation rate was 84 % (vHP-SD) and 88 % (control, p = 0.888). No differences for severe adverse events (vHP-SD: 1/25, 4 % vs. control: 0/25, 0 %; p = 0.676 were detected.Chronic durability of all PVs was assessed in vHP-SD: 16/25 (64 %) and control: 8/25 (32 %) patients (p = 0.023) and vHP-SD: 81 % and control: 62 % of PVs were found to be isolated (p = 0.003). For right PVs vHP-SD: 84 % vs. control: 60 % of PVs (p < 0.001) and for left PVs vHP-SD: 78 % vs. control: 64 % (p = 0.123) were found to be isolated. Conclusions: PVI solely utilizing vHP-SD via a very close-protocol provides fast, safe and effective acute PVI. High rates of chronically isolated pulmonary veins have been detected

mHTT Seeding Activity:A Marker of Disease Progression and Neurotoxicity in Models of Huntington's Disease

Self-propagating, amyloidogenic mutant huntingtin (mHTT) aggregates may drive progression of Huntington's disease (HD). Here, we report the development of a FRET-based mHTT aggregate seeding (FRASE) assay that enables the quantification of mHTT seeding activity (HSA) in complex biosamples from HD patients and disease models. Application of the FRASE assay revealed HSA in brain homogenates of presymptomatic HD transgenic and knockin mice and its progressive increase with phenotypic changes, suggesting that HSA quantitatively tracks disease progression. Biochemical investigations of mouse brain homogenates demonstrated that small, rather than large, mHTT structures are responsible for the HSA measured in FRASE assays. Finally, we assessed the neurotoxicity of mHTT seeds in an inducible Drosophila model transgenic for HTTex1. We found a strong correlation between the HSA measured in adult neurons and the increased mortality of transgenic HD flies, indicating that FRASE assays detect disease-relevant, neurotoxic, mHTT structures with severe phenotypic consequences in vivo. Ast et al. present the development of a FRET-based aggregate seeding (FRASE) assay that facilitates the detection and quantification of mHTT seeding activity (HSA) in complex biosamples. They show that HSA is detectable in brains of presymptomatic Huntington's disease (HD) mice and correlates with disease progression and neurotoxicity in HD transgenic flies