Sharks give a handle to potent anti-tumor multiparatopic antibodies inducing membrane depletion of PD-L1.

Despite the immense clinical success of the antibody therapeutics that neutralize programmed death receptor ligand 1 (PD-L1) and thus resurrect T cell antitumor activity, the patient response rates remain low. In this issue of Cell Chemical Biology, Ludwig et al. reveal novel topologies of multiparatopic antibodies that mediate potent PD-L1 downregulation.

Trispecific antibodies produced from mAb pairs by controlled Fab-arm exchange.

Bispecific antibodies and antibody fragments are therapeutics of growing importance. They are clinically applied for effector cell engagement, enhanced targeting selectivity, addressing of multiple cellular pathways and active transfer of certain activities into difficult-to-reach compartments. These functionalities could profit from a third antigen specificity.

Targeting non-pulmonary vein triggers in persistent atrial fibrillation: results from a prospective, multicentre, observational registry.

Aims: We evaluated the efficacy of an ablation strategy empirically targeting pulmonary veins (PVs) and posterior wall (PW) and the prevalence and clinical impact of extrapulmonary trigger inducibility and ablation in a large cohort of patients with persistent atrial fibrillation (PerAF).

Methods And Results: A total of 1803 PerAF patients were prospectively enrolled. All patients underwent pulmonary vein antrum isolation (PVAI) extended to the entire PW.

Incidence of Device-Related Thrombosis in Watchman Patients Undergoing a Genotype-Guided Antithrombotic Strategy.

Objectives: This study sought to report the incidence of device-related thrombosis (DRT) and thromboembolic (TE) events when an alternative to clopidogrel is prescribed in loss-of-function (LOF) allele carriers of the cytochrome P450 2C19 (CYP2C19) gene.

Background: LOF polymorphisms of the CYP2C19 gene are associated with reduced hepatic bioactivation of clopidogrel.

Methods: A total of 1,002 Watchman patients were included.

Arrhythmia profile and ablation-outcome in elderly women with atrial fibrillation undergoing first catheter ablation.

Background: This study evaluated the arrhythmia profile and ablation outcome in women with atrial fibrillation (AF) aged ≥75 years.

Methods: A total of 573 consecutive female patients undergoing first AF ablation were classified into group 1: ≥75 years (n = 221) and group 2: < 75 years (n = 352). Isolation of PVs, posterior wall and superior vena cava was performed in all.

Long-Term Outcomes of Left Atrial Appendage Electrical Isolation in Patients With Nonparoxysmal Atrial Fibrillation: A Propensity Score-Matched Analysis.

Background: Left atrial appendage electrical isolation (LAAEI) has been proposed for the treatment of nonparoxysmal atrial fibrillation (AF). The long-term clinical outcomes of this approach remain unclear. The objective of our study was to investigate the incremental benefit and safety of LAAEI in patients undergoing catheter ablation for nonparoxysmal AF.

Use of a Novel Septal Occluder Device for Left Atrial Appendage Closure in Patients With Postsurgical and Postlariat Leaks or Anatomies Unsuitable for Conventional Percutaneous Occlusion.

Background: Interventional therapies aiming at excluding the left atrial appendage (LAA) from systemic circulation have been established as a valid alternative to oral anticoagulation in patients at high thromboembolic risk. However, their efficacy on stroke prophylaxis may be compromised owing to incomplete LAA closure. Additionally, the need for an alternative thromboembolic prevention may remain unmet in patients with contraindications to oral anticoagulation whose appendage anatomy is unsuitable for some conventional devices commercially available.

Is transesophageal echocardiography necessary in patients undergoing ablation of atrial fibrillation on an uninterrupted direct oral anticoagulant regimen? Results from a prospective multicenter registry.

Background: Thromboembolic stroke is a rare but devastating consequence of atrial fibrillation (AF) ablation. Transesophageal echocardiography (TEE) is recommended to rule out left atrial appendage thrombus; however, its use is variable.

Objective: The purpose of this study was to assess whether TEE is mandatory in patients undergoing AF ablation on uninterrupted direct oral anticoagulants (DOACs).

Fluoroless Atrial Fibrillation Catheter Ablation: Technique and Clinical Outcomes.

Fluoroscopy continues to be considered an indispensable part of atrial fibrillation (AF) ablation worldwide. Deleterious effects of radiation exposure to patients, physicians, and catheter laboratory personnel are gaining increased consideration. Safety and efficacy of a fluoroless approach for AF ablation is comparable with outcomes achieved with fluoroscopy use.

Beyond Pulmonary Vein Isolation in Nonparoxysmal Atrial Fibrillation: Posterior Wall, Vein of Marshall, Coronary Sinus, Superior Vena Cava, and Left Atrial Appendage.

The optimal ablation strategy for non-paroxysmal atrial fibrillation remains controversial. Non-PV triggers have been shown to have a major arrhythmogenic role in these patients. Common sources of non-PV triggers are: posterior wall, left atrial appendage, superior vena cava, coronary sinus, vein of Marshall, interatrial septum, crista terminalis/Eustachian ridge, and mitral and tricuspid valve annuli.

Clinical and economic impact of multipoint left ventricular pacing: A comparative analysis from the Italian registry on multipoint pacing in cardiac resynchronization therapy (IRON-MPP).

Introduction: Early evidence suggests that multipoint left ventricular pacing (MPP) may improve response to cardiac resynchronization therapy (CRT). It is unknown whether this benefit is sustained and cost-effective. We used real-world data to evaluate long-term impact of MPP-ON clinical status, heart failure hospitalizations (HFH) and costs.

First Experience of Transcatheter Leak Occlusion With Detachable Coils Following Left Atrial Appendage Closure.

Objectives: The aim of this study was to assess the feasibility and efficacy of transcatheter leak closure with detachable coils in patients with incomplete left atrial appendage (LAA) closure.

Background: Incomplete LAA closure is common after interventional therapies targeting the LAA, potentially hindering effective thromboembolic prevention. Detachable coils have found a wide range of applications for transcatheter vascular occlusion and embolization procedures.

Impact of multipoint pacing on projected battery longevity in cardiac resynchronization therapy. An IRON-MPP study sub-analysis.

Background: Multipoint pacing (MPP) may improve clinical outcomes in patients with cardiac resynchronization therapy defibrillators (CRT-D), but its impact on battery longevity in a real-world population has not been investigated in large trials.

Objective: Compare projected battery longevity in CRT-D patients with and without MPP during long-term follow-up.

Methods: The Italian registry on multipoint left ventricular pacing (IRON-MPP) is a prospective, multicenter registry of patients implanted with MPP-capable CRT-D devices.

Stroke Risk in Patients With Atrial Fibrillation Undergoing Electrical Isolation of the Left Atrial Appendage.

Background: Loss of contractility leading to stasis of blood flow following left atrial appendage electrical isolation (LAAEI) could lead to thrombus formation.

Objectives: This study evaluated the incidence of thromboembolic events (TE) in post-LAAEI cases "on" and "off" oral anticoagulation (OAC).

Methods: A total of 1,854 consecutive post-LAAEI patients with follow-up transesophageal echocardiography (TEE) performed in sinus rhythm at 6 months to assess left atrial appendage (LAA) function were included in this analysis.

Impact of weight loss on ablation outcome in obese patients with longstanding persistent atrial fibrillation.

Aims: This study investigated the impact of weight loss in longstanding persistent (LSPAF) patients undergoing catheter ablation (CA).

Methods: Ninety consecutive obese LSPAF patients were approached; 58 volunteered to try weight loss interventions for up to 1 year (group 1), while 32 patients declined weight loss interventions and were included as a control (group 2). Both groups remained on antiarrhythmic drugs.

Differential Association of Exercise Intensity With Risk of Atrial Fibrillation in Men and Women: Evidence from a Meta-Analysis.

Background: Despite widespread interest and extensive research, the association between different levels of physical activity (PA) and risk of atrial fibrillation (AF) is still not clearly defined. Therefore, we systematically evaluated and summarized the evidences regarding association of different intensity of PA with the risk of AF in this meta-analysis.

Methods And Results: An extensive literature search was performed on databases for studies showing association of exercise with AF risk.